Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.

PubMed

Holubar, Marisa; Stavroulakis, Maria Christina; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina

2017-01-01

Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect. Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.

Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis

PubMed Central

Maldonado, Yvonne; Ioannidis, John P. A.; Contopoulos-Ioannidis, Despina

2017-01-01

Background Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. Methods We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. Results We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect. Conclusions Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution. PMID:28249046

[Cost-effectiveness and cost-benefit analysis on strategy for preventing mother-to-child transmission of hepatitis B virus].

PubMed

Cai, Y L; Zhang, S X; Yang, P C; Lin, Y

2016-06-01

Through cost-benefit analysis (CBA), cost-effectiveness analysis (CEA) and quantitative optimization analysis to understand the economic benefit and outcomes of strategy regarding preventing mother-to-child transmission (PMTCT) on hepatitis B virus. Based on the principle of Hepatitis B immunization decision analytic-Markov model, strategies on PMTCT and universal vaccination were compared. Related parameters of Shenzhen were introduced to the model, a birth cohort was set up as the study population in 2013. The net present value (NPV), benefit-cost ratio (BCR), incremental cost-effectiveness ratio (ICER) were calculated and the differences between CBA and CEA were compared. A decision tree was built as the decision analysis model for hepatitis B immunization. Three kinds of Markov models were used to simulate the outcomes after the implementation of vaccination program. The PMTCT strategy of Shenzhen showed a net-gain as 38 097.51 Yuan/per person in 2013, with BCR as 14.37. The universal vaccination strategy showed a net-gain as 37 083.03 Yuan/per person, with BCR as 12.07. Data showed that the PMTCT strategy was better than the universal vaccination one and would end with gaining more economic benefit. When comparing with the universal vaccination program, the PMTCT strategy would save 85 100.00 Yuan more on QALY gains for every person. The PMTCT strategy seemed more cost-effective compared with the one under universal vaccination program. In the CBA and CEA hepatitis B immunization programs, the immunization coverage rate and costs of hepatitis B related diseases were the most important influencing factors. Outcomes of joint-changes of all the parameters in CEA showed that PMTCT strategy was a more cost-effective. The PMTCT strategy gained more economic benefit and effects on health. However, the cost of PMTCT strategy was more than the universal vaccination program, thus it is important to pay attention to the process of PMTCT strategy and the universal vaccination program. CBA seemed suitable for strategy optimization while CEA was better for strategy evaluation. Hopefully, programs as combination of the above said two methods would facilitate the process of economic evaluation.

A Systematic Review and Methodological Evaluation of Published Cost-Effectiveness Analyses of Aromatase Inhibitors versus Tamoxifen in Early Stage Breast Cancer

PubMed Central

John-Baptiste, Ava A.; Wu, Wei; Rochon, Paula; Anderson, Geoffrey M.; Bell, Chaim M.

2013-01-01

Background A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. Methods We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. Results We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. Conclusion Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these CEA analyses may be suboptimal for guiding policy. PMID:23671612

A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

PubMed

John-Baptiste, Ava A; Wu, Wei; Rochon, Paula; Anderson, Geoffrey M; Bell, Chaim M

2013-01-01

A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these CEA analyses may be suboptimal for guiding policy.

Cost-effectiveness analysis and efficient use of the pharmaceutical budget: the key role of clinical pharmacologists

PubMed Central

Edlin, Richard; Round, Jeff; Hulme, Claire; McCabe, Christopher

2010-01-01

The purpose of this paper is to provide information about cost-effectiveness analysis and the roles of clinical pharmacologists generally in providing efficient health care. The paper highlights the potential consequences of ‘off-label prescribing’ and ‘indication creep’ behaviour given slower growth (or potential cuts) in the NHS budget. This paper highlights the key roles of clinical pharmacologists in delivering an efficient health care system when resources are allocated using cost-effectiveness analyses. It describes what cost-effectiveness analysis (CEA) is and how incremental cost-effectiveness ratios (ICERs) are used to identify efficient options. After outlining the theoretical framework within which using CEA can promote the efficient allocation of the health care budget, it considers the place of disinvestment within achieving efficient resource allocation. Clinical pharmacologists are argued to be critical to providing improved population health under CEA-based resource allocation processes because of their roles in implementation and disinvestment. Given that the challenges facing the United Kingdom National Health Service (NHS) are likely to increase, this paper sets out the stark choices facing clinical pharmacologists. PMID:20716234

Cost-effectiveness analysis and efficient use of the pharmaceutical budget: the key role of clinical pharmacologists.

PubMed

Edlin, Richard; Round, Jeff; Hulme, Claire; McCabe, Christopher

2010-09-01

The purpose of this paper is to provide information about cost-effectiveness analysis and the roles of clinical pharmacologists generally in providing efficient health care. The paper highlights the potential consequences of 'off-label prescribing' and 'indication creep' behaviour given slower growth (or potential cuts) in the NHS budget. This paper highlights the key roles of clinical pharmacologists in delivering an efficient health care system when resources are allocated using cost-effectiveness analyses. It describes what cost-effectiveness analysis (CEA) is and how incremental cost-effectiveness ratios (ICERs) are used to identify efficient options. After outlining the theoretical framework within which using CEA can promote the efficient allocation of the health care budget, it considers the place of disinvestment within achieving efficient resource allocation. Clinical pharmacologists are argued to be critical to providing improved population health under CEA-based resource allocation processes because of their roles in implementation and disinvestment. Given that the challenges facing the United Kingdom National Health Service (NHS) are likely to increase, this paper sets out the stark choices facing clinical pharmacologists.

Principles of cost-effective resource allocation in health care organizations.

PubMed

Weinstein, M C

1990-01-01

Cost-effectiveness analysis (CEA) is a method of economic evaluation that can be used to assess the efficiency with which health care technologies use limited resources to produce health outputs. However, inconsistencies in the way that such ratios are constructed often lead to misleading conclusions when CEAs are compared. Some of these inconsistencies, such as failure to discount or to calculate incremental ratios correctly, reflect analytical errors that, if corrected, would resolve the inconsistencies. Others reflect fundamental differences in the viewpoint of the analysis. The perspectives of different decision-making entities can properly lead to different items in the numerator and denominator of the cost-effectiveness (C/E) ratio. Producers and consumers of CEA need to be more conscious of the perspectives of analysis, so that C/E comparisons from a given perspective are based upon a common understanding of the elements that are properly included.

Good research practices for measuring drug costs in cost effectiveness analyses: issues and recommendations: the ISPOR Drug Cost Task Force report--Part I.

PubMed

Hay, Joel W; Smeeding, Jim; Carroll, Norman V; Drummond, Michael; Garrison, Louis P; Mansley, Edward C; Mullins, C Daniel; Mycka, Jack M; Seal, Brian; Shi, Lizheng

2010-01-01

The assignment of prices or costs to pharmaceuticals can be crucial to results and conclusions that are derived from pharmacoeconomic cost effectiveness analyses (CEAs). Although numerous pharmacoeconomic practice guidelines are available in the literature and have been promulgated in many countries, these guidelines are either vague or silent about how drug costs should be established or measured. This is particularly problematic in pharmacoeconomic studies performed from the "societal" perspective, because typically the measured cost of a brand name pharmaceutical is not a true economic cost but also includes transfer payments from some members of society (patients and third party payers) to other members of society (pharmaceutical manufacturer stockholders) in large part as a reward for biomedical innovation. Moreover, there are numerous and complex institutional factors that influence how drug costs should be measured from other CEA perspectives, both internationally and within the domestic US context. The objective of this report is to provide guidance and recommendations on how drug costs should be measured for CEAs performed from a number of key analytic perspectives. ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (Drug Cost Task Force [DCTF]) was appointed with the advice and consent of the ISPOR Board of Directors. Members were experienced developers or users of CEA models, worked in academia, industry, and as advisors to governments, and came from several countries. Because how drug costs should be measured for CEAs depend on the perspectives, five Task Force subgroups were created to develop drug cost standards from the societal, managed care, US government, industry, and international perspective. The ISPOR Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (DCTF) subgroups met to develop core assumptions and an outline before preparing six draft reports. They solicited comments on the outline and drafts from a core group of 174 external reviewers and more broadly from the membership of ISPOR at two ISPOR meetings and via the ISPOR web site. Drug cost measurements should be fully transparent and reflect the net payment most relevant to the user's perspective. The Task Force recommends that for CEAs of brand name drugs performed from a societal perspective, either 1) CEA analysts use a cost that more accurately reflects true societal drug costs (e.g., 20-60% of average sales price), or when that is too unrealistic to be meaningful for decision-makers, 2) refer to their analyses as from a "limited societal perspective." CEAs performed from a payer perspective should use drug prices actually paid by the relevant payer net of all rebates, copays, or other adjustments. When such price adjustments are confidential, the analyst should apply a typical or average discount that preserves this confidentiality. Drug transaction prices not only ration current use of medication but also ration future biomedical research and development. CEA researchers should tailor the appropriate measure of drug costs to the analytic perspective, maintain clarity and transparency on drug cost measurement, and report the sensitivity of CEA results to reasonable drug cost measurement alternatives.

The impact of economic evaluation on quality management in spine surgery

PubMed Central

2009-01-01

Health care expenditures are substantially increasing within the last two decades prompting the imperative need for economic evaluations in health care. Historically, economic evaluations in health care have been carried out by four approaches: (1) the human-capital approach (HCA), (2) cost-effectiveness analysis (CEA), (3) cost-utility analysis (CUA) and (4) cost-benefit analysis (CBA). While the HCA cannot be recommended because of methodological shortcomings, CEA and CUA have been used frequently in healthcare. In CEA, costs are measured in monetary terms and health effects are measured in a non-monetary unit, e.g. number of successfully treated patients. In an attempt to develop an effectiveness measure that incorporates effects on both quantity and quality of life, so-called Quality Adjusted Life Years (QUALYs) were introduced. Contingent valuation surveys are used in cost-benefit analyses (CBA) to elicit the consumer’s monetary valuations for program benefits by applying the willingness-to-pay approach. A distinguished feature of CBA is that costs and benefits are expressed in the same units of value, i.e. money. Only recently, economic evaluations have started to explore various spinal interventions particularly the very expensive fusion operations. While most of the studies used CEA or CUA approaches, CBAs are still rare. Most studies fail to show that sophisticated spinal interventions are more cost-effective than conventional treatments. In spite of the lack of therapeutic or cost-effectiveness for most spinal surgeries, there is rapidly growing spinal implant market demonstrating market imperfection and information asymmetry. A change can only be anticipated when physicians start to focus on the improvement of health care quality as documented by outcome research and economic evaluations of cost-effectiveness and net benefits. PMID:19337760

The impact of economic evaluation on quality management in spine surgery.

PubMed

Boos, Norbert

2009-08-01

Health care expenditures are substantially increasing within the last two decades prompting the imperative need for economic evaluations in health care. Historically, economic evaluations in health care have been carried out by four approaches: (1) the human-capital approach (HCA), (2) cost-effectiveness analysis (CEA), (3) cost-utility analysis (CUA) and (4) cost-benefit analysis (CBA). While the HCA cannot be recommended because of methodological shortcomings, CEA and CUA have been used frequently in healthcare. In CEA, costs are measured in monetary terms and health effects are measured in a non-monetary unit, e.g. number of successfully treated patients. In an attempt to develop an effectiveness measure that incorporates effects on both quantity and quality of life, so-called Quality Adjusted Life Years (QUALYs) were introduced. Contingent valuation surveys are used in cost-benefit analyses (CBA) to elicit the consumer's monetary valuations for program benefits by applying the willingness-to-pay approach. A distinguished feature of CBA is that costs and benefits are expressed in the same units of value, i.e. money. Only recently, economic evaluations have started to explore various spinal interventions particularly the very expensive fusion operations. While most of the studies used CEA or CUA approaches, CBAs are still rare. Most studies fail to show that sophisticated spinal interventions are more cost-effective than conventional treatments. In spite of the lack of therapeutic or cost-effectiveness for most spinal surgeries, there is rapidly growing spinal implant market demonstrating market imperfection and information asymmetry. A change can only be anticipated when physicians start to focus on the improvement of health care quality as documented by outcome research and economic evaluations of cost-effectiveness and net benefits.

A systematic review on the quality, validity and usefulness of current cost-effectiveness studies for treatments of neovascular age-related macular degeneration.

PubMed

Elshout, Mari; Webers, Carroll A B; van der Reis, Margriet I; Schouten, Jan S A G

2018-06-04

Ophthalmologists increasingly depend on new drugs to advance their treatment options. These options are limited by restraints on reimbursements for new and expensive drugs. These restraints are put in place through health policy decisions based on cost-effectiveness analyses (CEA). Cost-effectiveness analyses need to be valid and of good quality to support correct decisions to create new treatment opportunities. In this study, we report the quality, validity and usefulness of CEAs for therapies for nAMD. A systematic review in PubMed, EMBASE and Cochrane was performed to include CEAs. Quality and validity assessment was based on current general quality criteria and on elements that are specific to the field of ophthalmology. Forty-eight CEAs were included in the review. Forty-four CEAs did not meet four basic model quality and validity criteria specific to CEAs in the field of ophthalmology (both eyes analysed instead of one; a time horizon extending beyond 4 years; extrapolating VA and treatment intervals beyond trial data realistically; and including the costs of low-vision). Four CEAs aligned with the quality and validity criteria. In two of these CEAs bevacizumab as-needed (PRN) was more cost-effective than bevacizumab monthly; aflibercept (VIEW); or ranibizumab monthly or PRN. In two CEAs, ranibizumab (PRN or treat and extent) was dominant over aflibercept. In two other CEAs, aflibercept was either more cost-effective or dominant over ranibizumab monthly or PRN. Two of the CEAs of sufficient quality and validity show that bevacizumab PRN is the most cost-effective treatment. Comparing ranibizumab and aflibercept, either treatment can be more cost-effective depending on the assumptions used for drug prices and treatment frequencies. The majority of the published CEAs are of insufficient quality and validity. They wrongly inform decision-makers at the cost of opportunities for ophthalmologists to treat patients. As such, they may negatively influence overall patient outcomes and societal costs. For future ophthalmic treatments, CEAs need to be improved and only published when they are of sufficient quality and validity. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

STAR--people-powered prioritization: a 21st-century solution to allocation headaches.

PubMed

Airoldi, Mara; Morton, Alec; Smith, Jenifer A E; Bevan, Gwyn

2014-11-01

The aim of cost effectiveness analysis (CEA) is to inform the allocation of scarce resources. CEA is routinely used in assessing the cost-effectiveness of specific health technologies by agencies such as the National Institute for Health and Clinical Excellence (NICE) in England and Wales. But there is extensive evidence that because of barriers of accessibility and acceptability, CEA has not been used by local health planners in their annual task of allocating fixed budgets to a wide range of types of health care. This paper argues that these planners can use Socio Technical Allocation of Resources (STAR) for that task. STAR builds on the principles of CEA and the practice of program budgeting and marginal analysis. STAR uses requisite models to assess the cost-effectiveness of all interventions considered for resource reallocation by explicitly applying the theory of health economics to evidence of scale, costs, and benefits, with deliberation facilitated through an interactive social process of engaging key stakeholders. In that social process, the stakeholders generate missing estimates of scale, costs, and benefits of the interventions; develop visual models of their relative cost-effectiveness; and interpret the results. We demonstrate the feasibility of STAR by showing how it was used by a local health planning agency of the English National Health Service, the Isle of Wight Primary Care Trust, to allocate a fixed budget in 2008 and 2009. © The Author(s) 2014.

Scaling-up essential neuropsychiatric services in Ethiopia: a cost-effectiveness analysis

PubMed Central

Strand, Kirsten Bjerkreim; Chisholm, Dan; Fekadu, Abebaw; Johansson, Kjell Arne

2016-01-01

Introduction There is an immense need for scaling-up neuropsychiatric care in low-income countries. Contextualized cost-effectiveness analyses (CEAs) provide relevant information for local policies. The aim of this study is to perform a contextualized CEA of neuropsychiatric interventions in Ethiopia and to illustrate expected population health and budget impacts across neuropsychiatric disorders. Methods A mathematical population model (PopMod) was used to estimate intervention costs and effectiveness. Existing variables from a previous WHO-CHOICE regional CEA model were substantially revised. Treatments for depression, schizophrenia, bipolar disorder and epilepsy were analysed. The best available local data on epidemiology, intervention efficacy, current and target coverage, resource prices and salaries were used. Data were obtained from expert opinion, local hospital information systems, the Ministry of Health and literature reviews. Results Treatment of epilepsy with a first generation antiepileptic drug is the most cost-effective treatment (US$ 321 per DALY adverted). Treatments for depression have mid-range values compared with other interventions (US$ 457–1026 per DALY adverted). Treatments for schizophrenia and bipolar disorders are least cost-effective (US$ 1168–3739 per DALY adverted). Conclusion This analysis gives the Ethiopian government a comprehensive overview of the expected costs, effectiveness and cost-effectiveness of introducing basic neuropsychiatric interventions. PMID:26491060

Economic evaluation of Avonex (interferon beta-Ia) in patients following a single demyelinating event.

PubMed

Iskedjian, Michael; Walker, John H; Gray, Trevor; Vicente, Colin; Einarson, Thomas R; Gehshan, Adel

2005-10-01

Interferon beta-Ia (Avonex) 30 microg, intramuscular (i.m.), once weekly is efficacious in delaying clinically definite multiple sclerosis (CDMS) following a single demyelinating event (SDE). This study determined the cost effectiveness of Avonex compared to current treatment in delaying the onset of CDMS. A cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) were performed from Ministry of Health (MoH) and societal perspectives. For CEA, the outcome of interest was time spent in the pre-CDMS state, termed monosymptomatic life years (MLY) gained. For CUA, the outcome was quality-adjusted monosymptomatic life years (QAMLY) gained. A Markov model was developed with transitional probabilities and utilities derived from the literature. Costs were reported in 2002 Canadian dollars. Costs and outcomes were discounted at 5%. The time horizon was 12 years for the CEA, and 15 years for the CUA. All uncertainties were tested via univariate and multivariate sensitivity analyses. In the CEA, the incremental cost of Avonex per ILYgained was $53110 and $44789 from MoH and societal perspectives, respectively. In the CUA, the incremental cost of Avonex per QAMLY gained was $227586 and $189286 from MoH and societal perspectives, respectively. Both models were sensitive to the probability of progressing to CDMS and the analytical time horizon. The CUA was sensitive to the utilities value. Avonex may be considered as a reasonably cost-effective approach to treatment of patients experiencing an SDE In addition, the overall incremental cost-effectiveness profile of Avonex improves if treatment is initiated in pre-CDMS rather than waiting until CDMS.

Cost-effectiveness analysis in minimally invasive spine surgery.

PubMed

Al-Khouja, Lutfi T; Baron, Eli M; Johnson, J Patrick; Kim, Terrence T; Drazin, Doniel

2014-06-01

Medical care has been evolving with the increased influence of a value-based health care system. As a result, more emphasis is being placed on ensuring cost-effectiveness and utility in the services provided to patients. This study looks at this development in respect to minimally invasive spine surgery (MISS) costs. A literature review using PubMed, the Cost-Effectiveness Analysis (CEA) Registry, and the National Health Service Economic Evaluation Database (NHS EED) was performed. Papers were included in the study if they reported costs associated with minimally invasive spine surgery (MISS). If there was no mention of cost, CEA, cost-utility analysis (CUA), quality-adjusted life year (QALY), quality, or outcomes mentioned, then the article was excluded. Fourteen studies reporting costs associated with MISS in 12,425 patients (3675 undergoing minimally invasive procedures and 8750 undergoing open procedures) were identified through PubMed, the CEA Registry, and NHS EED. The percent cost difference between minimally invasive and open approaches ranged from 2.54% to 33.68%-all indicating cost saving with a minimally invasive surgical approach. Average length of stay (LOS) for minimally invasive surgery ranged from 0.93 days to 5.1 days compared with 1.53 days to 12 days for an open approach. All studies reporting EBL reported lower volume loss in an MISS approach (range 10-392.5 ml) than in an open approach (range 55-535.5 ml). There are currently an insufficient number of studies published reporting the costs of MISS. Of the studies published, none have followed a standardized method of reporting and analyzing cost data. Preliminary findings analyzing the 14 studies showed both cost saving and better outcomes in MISS compared with an open approach. However, more Level I CEA/CUA studies including cost/QALY evaluations with specifics of the techniques utilized need to be reported in a standardized manner to make more accurate conclusions on the cost effectiveness of minimally invasive spine surgery.

Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea.

PubMed

Jeong, Y J; Kim, H; Baik, S J; Kim, T M; Yang, S J; Lee, S-H; Cho, J-H; Lee, H; Yim, H W; Choi, I Y; Yoon, K-H; Kim, H-S

2017-06-01

There are a few Korean studies on the economics of statins based on reduction in low-density lipoprotein cholesterol (LDL-C) data from other countries. This study aimed to analyse and compare the cost-effectiveness of statins according to the baseline LDL-C level in Korea. Between January 2009 and December 2015, the data of patients who were prescribed statins for the first time were extracted from electronic medical records. We performed a cost-effectiveness analysis (CEA) based on the LDL-C reduction rate (CEA-RR) and target achievement rate. Among high-intensity statins, the CEA-RR value of rosuvastatin (20 mg) was significantly lower than that of atorvastatin (40 mg) at all baseline LDL-C levels, except levels of 160-189 mg/dL. Additionally, at baseline LDL-C levels of 130-159 mg/dL, the CEA-RR value of rosuvastatin (20 mg) was three times lower than that of atorvastatin (40 mg) (9·1 ± 2·5 $/% vs. 31·7 ± 15·0 $/%, P < 0·001). Among moderate-to-low-intensity statins, rosuvastatin (5 mg) showed the lowest CEA-RR value (4·0 ± 0·6 $/%), and the value significantly increased for pitavastatin (2 mg) (8·0 ± 0·6 $/%), atorvastatin (10 mg) (9·5 ± 0·5 $/%), simvastatin (10·8 ± 1·1 $/%) and pravastatin (40 mg) (11·5 ± 0·9 $/%) in order (P < 0·0001). On changing from atorvastatin (10 mg) to atorvastatin (20 mg), the additional yearly cost was 16·0 and additional CEA-RR value was 2·74 $/%. On the other hand, on changing from atorvastatin (10 mg) to rosuvastatin (10 mg), the additional yearly cost was -16·3 and additional CEA-RR value was -1·8 $/%. We successfully compared the cost-effectiveness of statins according to the baseline LDL-C level in Korea. It is expected that our findings will help clinical decision-making with regard to statin prescription, and this will help reduce national medical expenditure. © 2017 John Wiley & Sons Ltd.

Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective

PubMed Central

Hunter, Rachael M.; Shemilt, Ian; Serra-Sastre, Victoria

2017-01-01

Background Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. Methods and findings Network meta-analysis (NMA) was used to examine which trials’ data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks’ trastuzumab is cost-saving and leads to more QALYs than 12 months’, i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant-disease-free survival and overall survival, and safer in terms of fewer adverse cardiac events. Conclusions Our CEA results suggest that 9-week trastuzumab dominates 12-month trastuzumab in cost-effectiveness terms at conventional thresholds of willingness to pay for a QALY, and the 9-week regimen is also suggested to be as clinically effective as the 12-month regimen according to the NMA and Bucher analyses. This finding agrees with the results of the E2198 head-to-head study that compared 10 weeks’ with 14 months’ trastuzumab and found no significant difference. Appropriate trial design and reporting is critical if results are to be synthesisable with existing evidence, as selection bias can lead to recruitment of a different patient population from existing trials. Our analysis was not based on head-to-head trials’ data, so the results should be viewed with caution. Short-duration trials would benefit from recruiting larger numbers of participants to reduce uncertainty in the synthesised results. PMID:28248984

Multi-arm Cost-Effectiveness Analysis (CEA) comparing different durations of adjuvant trastuzumab in early breast cancer, from the English NHS payer perspective.

PubMed

Clarke, Caroline S; Hunter, Rachael M; Shemilt, Ian; Serra-Sastre, Victoria

2017-01-01

Trastuzumab improves survival in HER2+ breast cancer patients, with some evidence of adverse cardiac side effects. Current recommendations are to give adjuvant trastuzumab for one year or until recurrence, although trastuzumab treatment for only 9 or 10 weeks has shown similar survival rates to 12-month treatment. We present here a multi-arm joint analysis examining the relative cost-effectiveness of different durations of adjuvant trastuzumab. Network meta-analysis (NMA) was used to examine which trials' data to include in the cost-effectiveness analysis (CEA). A network using FinHer (9 weeks vs. zero) and BCIRG006 (12 months vs. zero) trials offered the only jointly randomisable network so these trials were used in the CEA. The 3-arm CEA compared costs and quality-adjusted life-years (QALYs) associated with zero, 9-week and 12-month adjuvant trastuzumab durations in early breast cancer, using a decision tree followed by a Markov model that extrapolated the results to a lifetime time horizon. Pairwise incremental cost-effectiveness ratios (ICERs) were also calculated for each pair of regimens and used in budget impact analysis, and the Bucher method was used to check face validity of the findings. Addition of the PHARE trial (6 months vs. 12 months) to the network, in order to create a 4-arm CEA including the 6-month regimen, was not possible as late randomisation in this trial resulted in recruitment of a different patient population as evidenced by the NMA findings. The CEA results suggest that 9 weeks' trastuzumab is cost-saving and leads to more QALYs than 12 months', i.e. the former dominates the latter. The cost-effectiveness acceptability frontier (CEAF) favours zero trastuzumab at willingness-to-pay levels below £2,500/QALY and treatment for 9 weeks above this threshold. The combination of the NMA and Bucher investigations suggests that the 9-week duration is as efficacious as the 12-month duration for distant-disease-free survival and overall survival, and safer in terms of fewer adverse cardiac events. Our CEA results suggest that 9-week trastuzumab dominates 12-month trastuzumab in cost-effectiveness terms at conventional thresholds of willingness to pay for a QALY, and the 9-week regimen is also suggested to be as clinically effective as the 12-month regimen according to the NMA and Bucher analyses. This finding agrees with the results of the E2198 head-to-head study that compared 10 weeks' with 14 months' trastuzumab and found no significant difference. Appropriate trial design and reporting is critical if results are to be synthesisable with existing evidence, as selection bias can lead to recruitment of a different patient population from existing trials. Our analysis was not based on head-to-head trials' data, so the results should be viewed with caution. Short-duration trials would benefit from recruiting larger numbers of participants to reduce uncertainty in the synthesised results.

Recommendations of the Panel on Cost-effectiveness in Health and Medicine.

PubMed

Weinstein, M C; Siegel, J E; Gold, M R; Kamlet, M S; Russell, L B

1996-10-16

To develop consensus-based recommendations for the conduct of cost-effectiveness analysis (CEA). This article, the second in a 3-part series, describes the basis for recommendations constituting the reference case analysis, the set of practices developed to guide CEAs that inform societal resource allocation decisions, and the content of these recommendations. The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS). The panel reviewed the theoretical foundations of CEA, current practices, and alternative methods used in analyses. Recommendations were developed on the basis of theory where possible, but tempered by ethical and pragmatic considerations, as well as the needs of users. The panel developed recommendations through 2 1/2 years of discussions. Comments on preliminary drafts prepared by panel working groups were solicited from federal government methodologists, health agency officials, and academic methodologists. The panel's methodological recommendations address (1) components belonging in the numerator and denominator of a cost-effectiveness (C/E) ratio; (2) measuring resource use in the numerator of a C/E ratio; (3) valuing health consequences in the denominator of a C/E ratio; (4) estimating effectiveness of interventions; (5) incorporating time preference and discounting; and (6) handling uncertainty. Recommendations are subject to the ¿rule of reason,¿ balancing the burden engendered by a practice with its importance to a study. If researchers follow a standard set of methods in CEA, the quality and comparability of studies, and their ultimate utility, can be much improved.

Universal access to HIV treatment in developing countries: going beyond the misinterpretations of the 'cost-effectiveness' algorithm.

PubMed

Moatti, Jean Paul; Marlink, Richard; Luchini, Stephane; Kazatchkine, Michel

2008-07-01

Economic cost-effectiveness analysis (CEA) has been proposed as the appropriate tool to set priorities for resource allocation among available health interventions. Controversy remains about the way CEA should be used in the field of HIV/AIDS. This paper reviews the general literature in health economics and public economics about the use of CEA for priority setting in public health, in order better to inform current debates about resource allocation in the fight against HIV/AIDS. Theoretical and practical limitations of CEA do not raise major problems when it is applied to compare alternatives for treating the same medical condition or public health problem. Using CEA to set priorities among different health interventions by ranking them from the lowest to the highest values of their cost per life-year saved is appropriate only under the very restrictive and unrealistic assumptions that all interventions compared are discrete and finite alternatives that cannot vary in terms of size and scale. In order for CEA to inform resource allocation compared across programmes to fight the AIDS epidemic, a pragmatic interpretation of this economic approach, like that proposed by the Commission on Macroeconomics and Health, is better suited. Interventions, like a number of preventive strategies and first-line antiretroviral treatments for HIV, whose marginal costs per additional life-year saved are less than three times the gross domestic product per capita, should be considered cost-effective. Because of their empirical and theoretical limitations, results of CEA should only be one element in priority setting among interventions for HIV/AIDS, which should also be informed by explicit debates about societal and ethical preferences.

Cost-effectiveness of tiotropium versus salmeterol: the POET-COPD trial.

PubMed

Hoogendoorn, Martine; Al, Maiwenn J; Beeh, Kai-Michael; Bowles, David; Graf von der Schulenburg, J Matthias; Lungershausen, Juliane; Monz, Brigitta U; Schmidt, Hendrik; Vogelmeier, Claus; Rutten-van Mölken, Maureen P M H

2013-03-01

The aim of this study was to perform a 1-yr trial-based cost-effectiveness analysis (CEA) of tiotropium versus salmeterol followed by a 5-yr model-based CEA. The within-trial CEA, including 7,250 patients with moderate to very severe chronic obstructive pulmonary disease (COPD), was performed alongside the 1-yr international randomised controlled Prevention of Exacerbations with Tiotropium (POET)-COPD trial comparing tiotropium with salmeterol regarding the effect on exacerbations. Main end-points of the trial-based analysis were costs, number of exacerbations and exacerbation days. The model-based analysis was conducted to extrapolate results to 5 yrs and to calculate quality-adjusted life years (QALYs). 1-yr costs per patient from the German statutory health insurance (SHI) perspective and the societal perspective were €126 (95% uncertainty interval (UI) €55-195) and €170 (95% UI €77-260) higher for tiotropium, respectively. The annual number of exacerbations was 0.064 (95% UI 0.010-0.118) lower for tiotropium, leading to a reduction in exacerbation-related costs of €87 (95% UI €19-157). The incremental cost-effectiveness ratio was €1,961 per exacerbation avoided from the SHI perspective and €2,647 from the societal perspective. In the model-based analyses, the 5-yr costs per QALY were €3,488 from the SHI perspective and €8,141 from the societal perspective. Tiotropium reduced exacerbations and exacerbation-related costs, but increased total costs. Tiotropium can be considered cost-effective as the resulting cost-effectiveness ratios were below commonly accepted willingness-to-pay thresholds.

Cost-effectiveness analysis in melanoma detection: A transition model applied to dermoscopy.

PubMed

Tromme, Isabelle; Legrand, Catherine; Devleesschauwer, Brecht; Leiter, Ulrike; Suciu, Stefan; Eggermont, Alexander; Sacré, Laurine; Baurain, Jean-François; Thomas, Luc; Beutels, Philippe; Speybroeck, Niko

2016-11-01

The main aim of this study is to demonstrate how our melanoma disease model (MDM) can be used for cost-effectiveness analyses (CEAs) in the melanoma detection field. In particular, we used the data of two cohorts of Belgian melanoma patients to investigate the cost-effectiveness of dermoscopy. A MDM, previously constructed to calculate the melanoma burden, was slightly modified to be suitable for CEAs. Two cohorts of patients entered into the model to calculate morbidity, mortality and costs. These cohorts were constituted by melanoma patients diagnosed by dermatologists adequately, or not adequately, trained in dermoscopy. Effectiveness and costs were calculated for each cohort and compared. Effectiveness was expressed in quality-adjusted life years (QALYs), a composite measure depending on melanoma-related morbidity and mortality. Costs included costs of treatment and follow-up as well as costs of detection in non-melanoma patients and costs of excision and pathology of benign lesions excised to rule out melanoma. The result of our analysis concluded that melanoma diagnosis by dermatologists adequately trained in dermoscopy resulted in both a gain of QALYs (less morbidity and/or mortality) and a reduction in costs. This study demonstrates how our MDM can be used in CEAs in the melanoma detection field. The model and the methodology suggested in this paper were applied to two cohorts of Belgian melanoma patients. Their analysis concluded that adequate dermoscopy training is cost-effective. The results should be confirmed by a large-scale randomised study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Scaling-up essential neuropsychiatric services in Ethiopia: a cost-effectiveness analysis.

PubMed

Strand, Kirsten Bjerkreim; Chisholm, Dan; Fekadu, Abebaw; Johansson, Kjell Arne

2016-05-01

There is an immense need for scaling-up neuropsychiatric care in low-income countries. Contextualized cost-effectiveness analyses (CEAs) provide relevant information for local policies. The aim of this study is to perform a contextualized CEA of neuropsychiatric interventions in Ethiopia and to illustrate expected population health and budget impacts across neuropsychiatric disorders. A mathematical population model (PopMod) was used to estimate intervention costs and effectiveness. Existing variables from a previous WHO-CHOICE regional CEA model were substantially revised. Treatments for depression, schizophrenia, bipolar disorder and epilepsy were analysed. The best available local data on epidemiology, intervention efficacy, current and target coverage, resource prices and salaries were used. Data were obtained from expert opinion, local hospital information systems, the Ministry of Health and literature reviews. Treatment of epilepsy with a first generation antiepileptic drug is the most cost-effective treatment (US$ 321 per DALY adverted). Treatments for depression have mid-range values compared with other interventions (US$ 457-1026 per DALY adverted). Treatments for schizophrenia and bipolar disorders are least cost-effective (US$ 1168-3739 per DALY adverted). This analysis gives the Ethiopian government a comprehensive overview of the expected costs, effectiveness and cost-effectiveness of introducing basic neuropsychiatric interventions. © The Author 2015. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses

PubMed Central

Soares, Marta O.; Palmer, Stephen; Ades, Anthony E.; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M.

2015-01-01

Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. PMID:25712447

Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.

PubMed

Welton, Nicky J; Soares, Marta O; Palmer, Stephen; Ades, Anthony E; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M

2015-07-01

Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. © The Author(s) 2015.

When is critical care medicine cost-effective? A systematic review of the cost-effectiveness literature.

PubMed

Talmor, Daniel; Shapiro, Nathan; Greenberg, Dan; Stone, Patricia W; Neumann, Peter J

2006-11-01

Receiving care in an intensive care unit can greatly influence patients' survival and quality of life. Such treatments can, however, be extremely resource intensive. Therefore, it is increasingly important to understand the costs and consequences associated with interventions aimed at reducing mortality and morbidity of critically ill patients. Cost-effectiveness analyses (CEAs) have become increasingly common to aid decisions about the allocation of scarce healthcare resources. To identify published original CEAs presenting cost/quality-adjusted life year or cost/life-year ratios for treatments used in intensive care units, to summarize the results in an accessible format, and to identify areas in critical care medicine that merit further economic evaluation. We conducted a systematic search of the English-language literature for original CEAs of critical care interventions published from 1993 through 2003. We collected data on the target population, therapy or program, study results, analytic methods employed, and the cost-effectiveness ratios presented. We identified 19 CEAs published through 2003 with 48 cost-effectiveness ratios pertaining to treatment of severe sepsis, acute respiratory failure, and general critical care interventions. These ratios ranged from cost saving to 958,423 US dollars/quality-adjusted life year and from 1,150 to 575,054 US dollars/life year gained. Many studies reported favorable cost-effectiveness profiles (i.e., below 50,000 US dollars/life year or quality-adjusted life year). Specific interventions such as activated protein C for patients with severe sepsis have been shown to provide good value for money. However, overall there is a paucity of CEA literature on the management of the critically ill, and further high-quality CEA is needed. In particular, research should focus on costly interventions such as 24-hr intensivist availability, early goal-directed therapy, and renal replacement therapy. Recent guidelines for the conduct of CEAs in critical care may increase the number and improve the quality of future CEAs.

Comparing the cost-per-QALYs gained and cost-per-DALYs averted literatures.

PubMed

Neumann, Peter J; Anderson, Jordan E; Panzer, Ari D; Pope, Elle F; D'Cruz, Brittany N; Kim, David D; Cohen, Joshua T

2018-01-18

Background : We examined the similarities and differences between studies using two common metrics used in cost-effectiveness analyses (CEAs): cost per quality-adjusted life years (QALYs) gained and cost per disability-adjusted life year (DALY) averted. Methods : We used the Tufts Medical Center CEA Registry, which contains English-language cost-per-QALY gained studies, and  Global Cost-Effectiveness Analysis (GHCEA) Registry, which contains cost-per-DALY averted studies. We examined study characteristics including intervention type, sponsor, country, and primary disease, and also analysed the number of CEAs versus disease burden estimates for major diseases and conditions across three geographic regions. Results : We identified 6,438 cost-per-QALY and 543 cost-per-DALY studies published through 2016 and observed rapid growth in publication rates for both literatures. Cost-per-QALY studies were most likely to examine pharmaceuticals and interventions in high-income countries. Cost-per-DALY studies predominantly focused on infectious disease interventions and interventions in low and lower-middle income countries. We found discrepancies in the number of published CEAs for certain diseases and conditions in certain regions, suggesting "under-studied" areas (e.g., cardiovascular disease in Southeast Asia, East Asia, and Oceania and "overstudied" areas (e.g., HIV in Sub Saharan Africa) relative to disease burden in those regions. Conclusions : The number of cost-per QALY and cost-per-DALY analyses has grown rapidly with applications to diverse interventions and diseases.  Discrepancies between the number of published studies and disease burden suggest funding opportunities for future cost-effectiveness research.

Computed Tomography Screening for Lung Cancer in the National Lung Screening Trial

PubMed Central

Black, William C.

2016-01-01

The National Lung Screening Trial (NLST) demonstrated that screening with low-dose CT versus chest radiography reduced lung cancer mortality by 16% to 20%. More recently, a cost-effectiveness analysis (CEA) of CT screening for lung cancer versus no screening in the NLST was performed. The CEA conformed to the reference-case recommendations of the US Panel on Cost-Effectiveness in Health and Medicine, including the use of the societal perspective and an annual discount rate of 3%. The CEA was based on several important assumptions. In this paper, I review the methods and assumptions used to obtain the base case estimate of $81,000 per quality-adjusted life-year gained. In addition, I show how this estimate varied widely among different subsets and when some of the base case assumptions were changed and speculate on the cost-effectiveness of CT screening for lung cancer outside the NLST. PMID:25635704

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

PubMed

Vilain, Katherine R; Magnuson, Elizabeth A; Li, Haiyan; Clark, Wayne M; Begg, Richard J; Sam, Albert D; Sternbergh, W Charles; Weaver, Fred A; Gray, William A; Voeks, Jenifer H; Brott, Thomas G; Cohen, David J

2012-09-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.

Costs and Cost-Effectiveness of Carotid Stenting versus Endarterectomy for Patients at Standard Surgical Risk: Results from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

PubMed Central

Vilain, Katherine R.; Magnuson, Elizabeth A.; Li, Haiyan; Clark, Wayne M.; Begg, Richard J.; Sam, Albert D.; Sternbergh, W. Charles; Weaver, Fred A.; Gray, William A.; Voeks, Jenifer H.; Brott, Thomas G.; Cohen, David J.

2012-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite endpoint between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction (MI) was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for healthcare policy and treatment guidelines. Methods We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health utility scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Results Although initial procedural costs were $1025/patient higher with CAS, post-procedure costs and physician costs were lower, such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15,055 versus $14,816; mean difference $239/patient, 95% CI for difference, −$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50,000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Conclusions Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. PMID:22821614

A strategic plan for integrating cost-effectiveness analysis into the US healthcare system.

PubMed

Neumann, Peter J; Palmer, Jennifer A; Daniels, Norman; Quigley, Karen; Gold, Marthe R; Chao, Schumarry

2008-04-01

The Panel on Integrating Cost-Effectiveness Considerations into Health Policy Decisions, composed of medical and pharmacy directors at public and private health plans, was convened to (1) explore the views of health plan purchasers about cost-effectiveness analysis (CEA) and (2) to develop a strategic plan for policymakers to address obstacles and to integrate CEA into health policy decisions, drawing on stakeholders as part of the solution. Panelists expressed strong support for a greater role for CEA in US health policy decisions, although they also highlighted barriers in the current system and challenges involved in moving forward. The strategic plan involves a series of activities to advance the use of CEA in the United States, including research and demonstration projects to illustrate potential gains from using the technique and ongoing consensus- building steps (eg, workshops, conferences, town meetings) involving a broad coalition of stakeholders. Funding and leadership from policymakers and nonprofit foundations will be needed, as well as the active engagement of legislators and business and consumer groups. Panelists emphasized the importance of the Medicare program taking a lead role, and the need for new "infrastructure," in the form of either a new institute for conducting research or increased funding for existing institutions.

Systematic review of incremental non-vaccine cost estimates used in cost-effectiveness analysis on the introduction of rotavirus and pneumococcal vaccines.

PubMed

De la Hoz-Restrepo, Fernando; Castañeda-Orjuela, Carlos; Paternina, Angel; Alvis-Guzman, Nelson

2013-07-02

To review the approaches used in the cost-effectiveness analysis (CEAs) literature to estimate the cost of expanded program on immunization (EPI) activities, other than vaccine purchase, for rotavirus and pneumococcal vaccines. A systematic review in PubMed and NHS EED databases of rotavirus and pneumococcal vaccines CEAs was done. Selected articles were read and information on how EPI costs were calculated was extracted. EPI costing approaches were classified according to the method or assumption used for estimation. Seventy-nine studies that evaluated cost effectiveness of rotavirus (n=43) or pneumococcal (n=36) vaccines were identified. In general, there are few details on how EPI costs other than vaccine procurement were estimated. While 30 studies used some measurement of that cost, only one study on pneumococcal vaccine used a primary cost evaluation (bottom-up costing analysis) and one study used a costing tool. Twenty-seven studies (17 on rotavirus and 10 on pneumococcal vaccine) assumed the non-vaccine costs. Five studies made no reference to additional costs. Fourteen studies (9 rotavirus and 5 pneumococcal) did not consider any additional EPI cost beyond vaccine procurement. For rotavirus studies, the median for non-vaccine cost per dose was US$0.74 in developing countries and US$6.39 in developed countries. For pneumococcal vaccines, the median for non-vaccine cost per dose was US$1.27 in developing countries and US$8.71 in developed countries. Many pneumococcal (52.8%) and rotavirus (60.4%) cost-effectiveness analyses did not consider additional EPI costs or used poorly supported assumptions. Ignoring EPI costs in addition to those for vaccine procurement in CEA analysis of new vaccines may lead to significant errors in the estimations of ICERs since several factors like personnel, cold chain, or social mobilization can be substantially affected by the introduction of new vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Missing data in trial-based cost-effectiveness analysis: An incomplete journey.

PubMed

Leurent, Baptiste; Gomes, Manuel; Carpenter, James R

2018-06-01

Cost-effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial-based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty-two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost-effectiveness data was 63% (interquartile range: 47%-81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing-at-random assumption. Further improvements are needed to address missing data in cost-effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing-at-random assumption. © 2018 The Authors Health Economics published by John Wiley & Sons Ltd.

Cost-effectiveness analysis of malaria interventions using disability adjusted life years: a systematic review.

PubMed

Gunda, Resign; Chimbari, Moses John

2017-01-01

Malaria continues to be a public health problem despite past and on-going control efforts. For sustenance of control efforts to achieve the malaria elimination goal, it is important that the most cost-effective interventions are employed. This paper reviews studies on cost-effectiveness of malaria interventions using disability-adjusted life years. A review of literature was conducted through a literature search of international peer-reviewed journals as well as grey literature. Searches were conducted through Medline (PubMed), EMBASE and Google Scholar search engines. The searches included articles published in English for the period from 1996 to 2016. The inclusion criteria for the study were type of malaria intervention, year of publication and cost-effectiveness ratio in terms of cost per DALY averted. We included 40 studies which specifically used the DALY metric in cost-effectiveness analysis (CEA) of malaria interventions. The majority of the reviewed studies (75%) were done using data from African settings with the majority of the interventions (60.0%) targeting all age categories. Interventions included case treatment, prophylaxis, vector control, insecticide treated nets, early detection, environmental management, diagnosis and educational programmes. Sulfadoxine-pyrimethamine was the most common drug of choice in malaria prophylaxis, while artemisinin-based combination therapies were the most common drugs for case treatment. Based on guidelines for CEA, most interventions proved cost-effective in terms of cost per DALYs averted for each intervention. The DALY metric is a useful tool for determining the cost-effectiveness of malaria interventions. This paper demonstrates the importance of CEA in informing decisions made by policy makers.

HPV testing for cervical cancer screening appears more cost-effective than Papanicolau cytology in Mexico.

PubMed

Flores, Yvonne N; Bishai, David M; Lorincz, Attila; Shah, Keerti V; Lazcano-Ponce, Eduardo; Hernández, Mauricio; Granados-García, Víctor; Pérez, Ruth; Salmerón, Jorge

2011-02-01

To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico. A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico. Screening women between the ages of 30-80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone. This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program.

HPV testing for cervical cancer screening appears more cost-effective than Papanicolau cytology in Mexico

PubMed Central

Bishai, David M.; Lőrincz, Attila; Shah, Keerti V.; Lazcano-Ponce, Eduardo; Hernández, Mauricio; Granados-García, Víctor; Pérez, Ruth; Salmerón, Jorge

2010-01-01

Objective To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico. Methods A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico. Results Screening women between the ages of 30–80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone. Conclusions This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program. PMID:21170578

The influence of time horizon on results of cost-effectiveness analyses.

PubMed

Kim, David D; Wilkinson, Colby L; Pope, Elle F; Chambers, James D; Cohen, Joshua T; Neumann, Peter J

2017-12-01

Debates persist on the appropriate time horizon from a payer's perspective and how the time horizon in cost-effectiveness analysis (CEA) influences the value assessment. We systematically reviewed the Tufts Medical Center CEA Registry and identified US-based studies that used a payer perspective from 2005-2014. We classified the identified CEAs as short-term (time horizon ≤ 5 years) and long-term (> 5 years), and examined associations between study characteristics and the specified time horizon. We also developed case studies with selected interventions to further explore the relationship between time horizon and projected costs, benefits, and incremental cost-effectiveness ratios (ICER). Among 782 identified studies that met our inclusion criteria, 552 studies (71%) utilized a long-term time horizon while 198 studies (25%) used a short-term horizon. Among studies that employed multiple time horizons, the extension of the time horizon yielded more favorable ICERs in 19 cases and less favorable ICERs in 4 cases. Case studies showed the use of a longer time horizon also yielded more favorable ICERs. The assumed time horizon in CEAs can substantially influence the value assessment of medical interventions. To capture all consequences, we encourage the use of time horizons that extend sufficiently into the future.

Cost-Effectiveness of Guided Self-Help Treatment for Recurrent Binge Eating

ERIC Educational Resources Information Center

Lynch, Frances L.; Striegel-Moore, Ruth H.; Dickerson, John F.; Perrin, Nancy; DeBar, Lynn; Wilson, G. Terence; Kraemer, Helena C.

2010-01-01

Objective: Adoption of effective treatments for recurrent binge-eating disorders depends on the balance of costs and benefits. Using data from a recent randomized controlled trial, we conducted an incremental cost-effectiveness analysis (CEA) of a cognitive-behavioral therapy guided self-help intervention (CBT-GSH) to treat recurrent binge eating…

An Evaluation of Clinical Economics and Cases of Cost-effectiveness.

PubMed

Takura, Tomoyuki

2018-05-01

In order to maintain and develop a universal health insurance system, it is crucial to utilize limited medical resources effectively. In this context, considerations are underway to introduce health technology assessments (HTAs), such as cost-effectiveness analyses (CEAs), into the medical treatment fee system. CEAs, which is the general term for these methods, are classified into four categories, such as cost-effectiveness analyses based on performance indicators, and in the comparison of health technologies, the incremental cost-effectiveness ratio (ICER) is also applied. When I comprehensively consider several Japanese studies based on these concepts, I find that, in the results of the analysis of the economic performance of healthcare systems, Japan shows the most promising trend in the world. In addition, there is research indicating the superior cost-effectiveness of Rituximab against refractory nephrotic syndrome, and it is expected that health economics will be actively applied to the valuation of technical innovations such as drug discovery.

Endogenous patient responses and the consistency principle in cost-effectiveness analysis.

PubMed

Liu, Liqun; Rettenmaier, Andrew J; Saving, Thomas R

2012-01-01

In addition to incurring direct treatment costs and generating direct health benefits that improve longevity and/or health-related quality of life, medical interventions often have further or "unrelated" financial and health impacts, raising the issue of what costs and effects should be included in calculating the cost-effectiveness ratio of an intervention. The "consistency principle" in medical cost-effectiveness analysis (CEA) requires that one include both the cost and the utility benefit of a change (in medical expenditures, consumption, or leisure) caused by an intervention or neither of them. By distinguishing between exogenous changes directly brought about by an intervention and endogenous patient responses to the exogenous changes, and within a lifetime utility maximization framework, this article addresses 2 questions related to the consistency principle: 1) how to choose among alternative internally consistent exclusion/inclusion rules, and 2) what to do with survival consumption costs and earnings. It finds that, for an endogenous change, excluding or including both the cost and the utility benefit of the change does not alter cost-effectiveness results. Further, in agreement with the consistency principle, welfare maximization implies that consumption costs and earnings during the extended life directly caused by an intervention should be included in CEA.

Good research practices for measuring drug costs in cost-effectiveness analyses: a societal perspective: the ISPOR Drug Cost Task Force report--Part II.

PubMed

Garrison, Louis P; Mansley, Edward C; Abbott, Thomas A; Bresnahan, Brian W; Hay, Joel W; Smeeding, James

2010-01-01

Major guidelines regarding the application of cost-effectiveness analysis (CEA) have recommended the common and widespread use of the "societal perspective" for purposes of consistency and comparability. The objective of this Task Force subgroup report (one of six reports from the International Society for Pharmacoeconomics and Outcomes Research [ISPOR] Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis [Drug Cost Task Force (DCTF)]) was to review the definition of this perspective, assess its specific application in measuring drug costs, identify any limitations in theory or practice, and make recommendations regarding potential improvements. Key articles, books, and reports in the methodological literature were reviewed, summarized, and integrated into a draft review and report. This draft report was posted for review and comment by ISPOR membership. Numerous comments and suggestions were received, and the report was revised in response to them. The societal perspective can be defined by three conditions: 1) the inclusion of time costs, 2) the use of opportunity costs, and 3) the use of community preferences. In practice, very few, if any, published CEAs have met all of these conditions, though many claim to have taken a societal perspective. Branded drug costs have typically used actual acquisition cost rather than the much lower social opportunity costs that would reflect only short-run manufacturing and distribution costs. This practice is understandable, pragmatic, and useful to current decision-makers. Nevertheless, this use of CEA focuses on static rather than dynamic efficacy and overlooks the related incentives for innovation. Our key recommendation is that current CEA practice acknowledge and embrace this limitation by adopting a new standard for the reference case as one of a "limited societal" or "health systems" perspective, using acquisition drug prices while including indirect costs and community preferences. The field of pharmacoeconomics also needs to acknowledge the limitations of this perspective when it comes to important questions of research and development costs, and incentives for innovation.

Cost-effectiveness analysis of risk-reduction measures to reach water safety targets.

PubMed

Lindhe, Andreas; Rosén, Lars; Norberg, Tommy; Bergstedt, Olof; Pettersson, Thomas J R

2011-01-01

Identifying the most suitable risk-reduction measures in drinking water systems requires a thorough analysis of possible alternatives. In addition to the effects on the risk level, also the economic aspects of the risk-reduction alternatives are commonly considered important. Drinking water supplies are complex systems and to avoid sub-optimisation of risk-reduction measures, the entire system from source to tap needs to be considered. There is a lack of methods for quantification of water supply risk reduction in an economic context for entire drinking water systems. The aim of this paper is to present a novel approach for risk assessment in combination with economic analysis to evaluate risk-reduction measures based on a source-to-tap approach. The approach combines a probabilistic and dynamic fault tree method with cost-effectiveness analysis (CEA). The developed approach comprises the following main parts: (1) quantification of risk reduction of alternatives using a probabilistic fault tree model of the entire system; (2) combination of the modelling results with CEA; and (3) evaluation of the alternatives with respect to the risk reduction, the probability of not reaching water safety targets and the cost-effectiveness. The fault tree method and CEA enable comparison of risk-reduction measures in the same quantitative unit and consider costs and uncertainties. The approach provides a structured and thorough analysis of risk-reduction measures that facilitates transparency and long-term planning of drinking water systems in order to avoid sub-optimisation of available resources for risk reduction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Generalized cost-effectiveness analysis for national-level priority-setting in the health sector

PubMed Central

Hutubessy, Raymond; Chisholm, Dan; Edejer, Tessa Tan-Torres

2003-01-01

Cost-effectiveness analysis (CEA) is potentially an important aid to public health decision-making but, with some notable exceptions, its use and impact at the level of individual countries is limited. A number of potential reasons may account for this, among them technical shortcomings associated with the generation of current economic evidence, political expediency, social preferences and systemic barriers to implementation. As a form of sectoral CEA, Generalized CEA sets out to overcome a number of these barriers to the appropriate use of cost-effectiveness information at the regional and country level. Its application via WHO-CHOICE provides a new economic evidence base, as well as underlying methodological developments, concerning the cost-effectiveness of a range of health interventions for leading causes of, and risk factors for, disease. The estimated sub-regional costs and effects of different interventions provided by WHO-CHOICE can readily be tailored to the specific context of individual countries, for example by adjustment to the quantity and unit prices of intervention inputs (costs) or the coverage, efficacy and adherence rates of interventions (effectiveness). The potential usefulness of this information for health policy and planning is in assessing if current intervention strategies represent an efficient use of scarce resources, and which of the potential additional interventions that are not yet implemented, or not implemented fully, should be given priority on the grounds of cost-effectiveness. Health policy-makers and programme managers can use results from WHO-CHOICE as a valuable input into the planning and prioritization of services at national level, as well as a starting point for additional analyses of the trade-off between the efficiency of interventions in producing health and their impact on other key outcomes such as reducing inequalities and improving the health of the poor. PMID:14687420

Generalized cost-effectiveness analysis for national-level priority-setting in the health sector.

PubMed

Hutubessy, Raymond; Chisholm, Dan; Edejer, Tessa Tan-Torres

2003-12-19

Cost-effectiveness analysis (CEA) is potentially an important aid to public health decision-making but, with some notable exceptions, its use and impact at the level of individual countries is limited. A number of potential reasons may account for this, among them technical shortcomings associated with the generation of current economic evidence, political expediency, social preferences and systemic barriers to implementation. As a form of sectoral CEA, Generalized CEA sets out to overcome a number of these barriers to the appropriate use of cost-effectiveness information at the regional and country level. Its application via WHO-CHOICE provides a new economic evidence base, as well as underlying methodological developments, concerning the cost-effectiveness of a range of health interventions for leading causes of, and risk factors for, disease.The estimated sub-regional costs and effects of different interventions provided by WHO-CHOICE can readily be tailored to the specific context of individual countries, for example by adjustment to the quantity and unit prices of intervention inputs (costs) or the coverage, efficacy and adherence rates of interventions (effectiveness). The potential usefulness of this information for health policy and planning is in assessing if current intervention strategies represent an efficient use of scarce resources, and which of the potential additional interventions that are not yet implemented, or not implemented fully, should be given priority on the grounds of cost-effectiveness.Health policy-makers and programme managers can use results from WHO-CHOICE as a valuable input into the planning and prioritization of services at national level, as well as a starting point for additional analyses of the trade-off between the efficiency of interventions in producing health and their impact on other key outcomes such as reducing inequalities and improving the health of the poor.

Use of number needed to treat in cost-effectiveness analyses.

PubMed

Garg, Vishvas; Shen, Xian; Cheng, Yan; Nawarskas, James J; Raisch, Dennis W

2013-03-01

To review the use of number needed to treat (NNT) and/or number needed to harm (NNH) values to determine their relevance in helping clinicians evaluate cost-effectiveness analyses (CEAs). PubMed and EconLit were searched from 1966 to September 2012. Reviews, editorials, non-English-language articles, and articles that did not report NNT/NNH or cost-effectiveness ratios were excluded. CEA studies reporting cost per life-year gained, per quality-adjusted life-year (QALY), or other cost per effectiveness measure were included. Full texts of all included articles were reviewed for study information, including type of journal, impact factor of the journal, focus of study, data source, publication year, how NNT/NNH values were reported, and outcome measures. A total of 188 studies were initially identified, with 69 meeting our inclusion criteria. Most were published in clinician-practice-focused journals (78.3%) while 5.8% were in policy-focused journals, and 15.9% in health-economics-focused journals. The majority (72.4%) of the articles were published in high-impact journals (impact factor >3.0). Many articles focused on either disease treatment (40.5%) or disease prevention (40.5%). Forty-eight percent reported NNT as a part of the CEA ratio per event. Most (53.6%) articles used data from literature reviews, while 24.6% used data from randomized clinical trials, and 20.3% used data from observational studies. In addition, 10% of the studies implemented modeling to perform CEA. CEA studies sometimes include NNT ratios. Although it has several limitations, clinicians often use NNT for decision-making, so including NNT information alongside CEA findings may help clinicians better understand and apply CEA results. Further research is needed to assess how NNT/NNH might meaningfully be incorporated into CEA publications.

Cost-effectiveness analyses in orthopaedic sports medicine: a systematic review.

PubMed

Nwachukwu, Benedict U; Schairer, William W; Bernstein, Jaime L; Dodwell, Emily R; Marx, Robert G; Allen, Answorth A

2015-06-01

As increasing attention is paid to the cost of health care delivered in the United States (US), cost-effectiveness analyses (CEAs) are gaining in popularity. Reviews of the CEA literature have been performed in other areas of medicine, including some subspecialties within orthopaedics. Demonstrating the value of medical procedures is of utmost importance, yet very little is known about the overall quality and findings of CEAs in sports medicine. To identify and summarize CEA studies in orthopaedic sports medicine and to grade the quality of the available literature. Systematic review. A systematic review of the literature was performed to compile findings and grade the methodological quality of US-based CEA studies in sports medicine. The Quality of Health Economic Studies (QHES) instrument and the checklist by the US Panel on Cost-effectiveness in Health and Medicine were used to assess study quality. One-sided Fisher exact testing was performed to analyze the predictors of high-quality CEAs. Twelve studies met inclusion criteria. Five studies examined anterior cruciate ligament reconstruction, 3 studies examined rotator cuff repair, 2 examined autologous chondrocyte implantation, 1 study examined hip arthroscopic surgery, and 1 study examined the operative management of shoulder dislocations. Based on study findings, operative intervention in sports medicine is highly cost-effective. The quality of published evidence is good, with a mean quality score of 81.8 (range, 70-94). There is a trend toward higher quality in more recent publications. No significant predictor of high-quality evidence was found. The CEA literature in sports medicine is good; however, there is a paucity of studies, and the available evidence is focused on a few procedures. More work needs to be conducted to quantify the cost-effectiveness of different techniques and procedures within sports medicine. The QHES tool may be useful for the evaluation of future CEAs. © 2014 The Author(s).

Assessing value-for-money in maternal and newborn health.

PubMed

Banke-Thomas, Aduragbemi; Madaj, Barbara; Kumar, Shubha; Ameh, Charles; van den Broek, Nynke

2017-01-01

Responding to increasing demands to demonstrate value-for-money (VfM) for maternal and newborn health interventions, and in the absence of VfM analysis in peer-reviewed literature, this paper reviews VfM components and methods, critiques their applicability, strengths and weakness and proposes how VfM assessments can be improved. VfM comprises four components: economy, efficiency, effectiveness and cost-effectiveness. Both 'economy' and 'efficiency' can be assessed with detailed cost analysis utilising costs obtained from programme accounting data or generic cost databases. Before-and-after studies, case-control studies or randomised controlled trials can be used to assess 'effectiveness'. To assess 'cost-effectiveness', cost-effectiveness analysis (CEA), cost-utility analysis (CUA), cost-benefit analysis (CBA) or social return on investment (SROI) analysis are applicable. Generally, costs can be obtained from programme accounting data or existing generic cost databases. As such 'economy' and 'efficiency' are relatively easy to assess. However, 'effectiveness' and 'cost-effectiveness' which require establishment of the counterfactual are more difficult to ascertain. Either a combination of CEA or CUA with tools for assessing other VfM components, or the independent use of CBA or SROI are alternative approaches proposed to strengthen VfM assessments. Cross-cutting themes such as equity, sustainability, scalability and cultural acceptability should also be assessed, as they provide critical contextual information for interpreting VfM assessments. To select an assessment approach, consideration should be given to the purpose, data availability, stakeholders requiring the findings and perspectives of programme beneficiaries. Implementers and researchers should work together to improve the quality of assessments. Standardisation around definitions, methodology and effectiveness measures to be assessed would help.

Improving data collection processes for routine evaluation of treatment cost-effectiveness.

PubMed

Monto, Sari; Penttilä, Riku; Kärri, Timo; Puolakka, Kari; Valpas, Antti; Talonpoika, Anna-Maria

2016-04-01

The healthcare system in Finland has begun routine collection of health-related quality of life (HRQoL) information for patients in hospitals to support more systematic cost-effectiveness analysis (CEA). This article describes the systematic collection of HRQoL survey data, and addresses challenges in the implementation of patient surveys and acquisition of cost data in the case hospital. Challenges include problems with incomplete data and undefined management processes. In order to support CEA of hospital treatments, improvements are sought from the process management literature and in the observation of healthcare professionals. The article has been written from an information system and process management perspective, concluding that process ownership, automation of data collection and better staff training are keys to generating more reliable data.

An Evaluation of Clinical Economics and Cases of Cost-effectiveness

PubMed Central

Takura, Tomoyuki

2017-01-01

In order to maintain and develop a universal health insurance system, it is crucial to utilize limited medical resources effectively. In this context, considerations are underway to introduce health technology assessments (HTAs), such as cost-effectiveness analyses (CEAs), into the medical treatment fee system. CEAs, which is the general term for these methods, are classified into four categories, such as cost-effectiveness analyses based on performance indicators, and in the comparison of health technologies, the incremental cost-effectiveness ratio (ICER) is also applied. When I comprehensively consider several Japanese studies based on these concepts, I find that, in the results of the analysis of the economic performance of healthcare systems, Japan shows the most promising trend in the world. In addition, there is research indicating the superior cost-effectiveness of Rituximab against refractory nephrotic syndrome, and it is expected that health economics will be actively applied to the valuation of technical innovations such as drug discovery. PMID:29279514

A cost-effectiveness analysis of school-based suicide prevention programmes.

PubMed

Ahern, Susan; Burke, Lee-Ann; McElroy, Brendan; Corcoran, Paul; McMahon, Elaine M; Keeley, Helen; Carli, Vladimir; Wasserman, Camilla; Hoven, Christina W; Sarchiapone, Marco; Apter, Alan; Balazs, Judit; Banzer, Raphaela; Bobes, Julio; Brunner, Romuald; Cosman, Doina; Haring, Christian; Kaess, Michael; Kahn, Jean-Pierre; Kereszteny, Agnes; Postuvan, Vita; Sáiz, Pilar A; Varnik, Peeter; Wasserman, Danuta

2018-02-14

Suicide is one of the leading causes of death among young people globally. In light of emerging evidence supporting the effectiveness of school-based suicide prevention programmes, an analysis of cost-effectiveness is required. We aimed to conduct a full cost-effectiveness analysis (CEA) of the large pan-European school-based RCT, Saving and Empowering Young Lives in Europe (SEYLE). The health outcomes of interest were suicide attempt and severe suicidal ideation with suicide plans. Adopting a payer's perspective, three suicide prevention interventions were modelled with a Control over a 12-month time period. Incremental cost-effectiveness ratios (ICERs) indicate that the Youth Aware of Mental Health (YAM) programme has the lowest incremental cost per 1% point reduction in incident for both outcomes and per quality adjusted life year (QALY) gained versus the Control. The ICERs reported for YAM were €34.83 and €45.42 per 1% point reduction in incident suicide attempt and incident severe suicidal ideation, respectively, and a cost per QALY gained of €47,017 for suicide attempt and €48,216 for severe suicidal ideation. Cost-effectiveness acceptability curves were used to examine uncertainty in the QALY analysis, where cost-effectiveness probabilities were calculated using net monetary benefit analysis incorporating a two-stage bootstrapping technique. For suicide attempt, the probability that YAM was cost-effective at a willingness to pay of €47,000 was 39%. For severe suicidal ideation, the probability that YAM was cost-effective at a willingness to pay of €48,000 was 43%. This CEA supports YAM as the most cost-effective of the SEYLE interventions in preventing both a suicide attempt and severe suicidal ideation.Trial registration number DRKS00000214.

Algorithm-guided treatment of depression reduces treatment costs--results from the randomized controlled German Algorithm Project (GAPII).

PubMed

Ricken, Roland; Wiethoff, Katja; Reinhold, Thomas; Schietsch, Kathrin; Stamm, Thomas; Kiermeir, Julia; Neu, Peter; Heinz, Andreas; Bauer, Michael; Adli, Mazda

2011-11-01

The German Algorithm Project, Phase 2 (GAP2) revealed that a standardized stepwise treatment regimen (SSTR) results in better treatment outcomes than treatment as usual (TAU) in depressed inpatients. The objective of this study was a health economic evaluation of SSTR based on a cost effectiveness analysis (CEA). GAP2 was a randomized controlled study with 148 patients. In an intention to treat (ITT) analysis direct treatment costs for study duration (SD) and total time in hospital (TTH; enrolment to discharge) were calculated based on daily hospital charges followed by a CEA to calculate cost expenditure per remitted patient. Treatment costs in SSTR compared to TAU were significantly lower for SD (SSTR: 10 830 € ± 8 632 €, TAU: 15 202 € ± 12 483 €; p = 0.026) and did not differ significantly for TTH (SSTR: 21 561 € ± 16 162 €; TAU: 18 248 € ± 13 454; p = 0.208). CEA revealed that the costs per remission in SSTR were significantly lower for SD (SSTR: 20 035 € ± 15 970 €; SSTR: 38 793 € ± 31 853 €; p<0.0001) and TTH (SSTR: 31 285 € ± 23 451 €; TAU: 38 581 € ± 28 449 €, p = 0.041). Indirect costs were not assessed. Different dropout rates in TAU and SSTR complicated interpretation of data. An SSTR-based algorithm results in a superior cost effectiveness at no significant extra costs. Implementation of treatment algorithms in inpatient-care may help reduce treatment costs. Copyright © 2011 Elsevier B.V. All rights reserved.

Coauthorship and Institutional Collaborations on Cost-Effectiveness Analyses: A Systematic Network Analysis

PubMed Central

Catalá-López, Ferrán; Alonso-Arroyo, Adolfo; Aleixandre-Benavent, Rafael; Ridao, Manuel; Bolaños, Máxima; García-Altés, Anna; Sanfélix-Gimeno, Gabriel; Peiró, Salvador

2012-01-01

Background Cost-Effectiveness Analysis (CEA) has been promoted as an important research methodology for determining the efficiency of healthcare technology and guiding medical decision-making. Our aim was to characterize the collaborative patterns of CEA conducted over the past two decades in Spain. Methods and Findings A systematic analysis was carried out with the information obtained through an updated comprehensive literature review and from reports of health technology assessment agencies. We identified CEAs with outcomes expressed as a time-based summary measure of population health (e.g. quality-adjusted life-years or disability-adjusted life-years), conducted in Spain and published between 1989 and 2011. Networks of coauthorship and institutional collaboration were produced using PAJEK software. One-hundred and thirty-one papers were analyzed, in which 526 authors and 230 institutions participated. The overall signatures per paper index was 5.4. Six major groups (one with 14 members, three with 7 members and two with 6 members) were identified. The most prolific authors were generally affiliated with the private-for-profit sector (e.g. consulting firms and the pharmaceutical industry). The private-for-profit sector mantains profuse collaborative networks including public hospitals and academia. Collaboration within the public sector (e.g. healthcare administration and primary care) was weak and fragmented. Conclusions This empirical analysis reflects critical practices among collaborative networks that contributed substantially to the production of CEA, raises challenges for redesigning future policies and provides a framework for similar analyses in other regions. PMID:22666435

The impact of structural uncertainty on cost-effectiveness models for adjuvant endocrine breast cancer treatments: the need for disease-specific model standardization and improved guidance.

PubMed

Frederix, Gerardus W J; van Hasselt, Johan G C; Schellens, Jan H M; Hövels, Anke M; Raaijmakers, Jan A M; Huitema, Alwin D R; Severens, Johan L

2014-01-01

Structural uncertainty relates to differences in model structure and parameterization. For many published health economic analyses in oncology, substantial differences in model structure exist, leading to differences in analysis outcomes and potentially impacting decision-making processes. The objectives of this analysis were (1) to identify differences in model structure and parameterization for cost-effectiveness analyses (CEAs) comparing tamoxifen and anastrazole for adjuvant breast cancer (ABC) treatment; and (2) to quantify the impact of these differences on analysis outcome metrics. The analysis consisted of four steps: (1) review of the literature for identification of eligible CEAs; (2) definition and implementation of a base model structure, which included the core structural components for all identified CEAs; (3) definition and implementation of changes or additions in the base model structure or parameterization; and (4) quantification of the impact of changes in model structure or parameterizations on the analysis outcome metrics life-years gained (LYG), incremental costs (IC) and the incremental cost-effectiveness ratio (ICER). Eleven CEA analyses comparing anastrazole and tamoxifen as ABC treatment were identified. The base model consisted of the following health states: (1) on treatment; (2) off treatment; (3) local recurrence; (4) metastatic disease; (5) death due to breast cancer; and (6) death due to other causes. The base model estimates of anastrazole versus tamoxifen for the LYG, IC and ICER were 0.263 years, €3,647 and €13,868/LYG, respectively. In the published models that were evaluated, differences in model structure included the addition of different recurrence health states, and associated transition rates were identified. Differences in parameterization were related to the incidences of recurrence, local recurrence to metastatic disease, and metastatic disease to death. The separate impact of these model components on the LYG ranged from 0.207 to 0.356 years, while incremental costs ranged from €3,490 to €3,714 and ICERs ranged from €9,804/LYG to €17,966/LYG. When we re-analyzed the published CEAs in our framework by including their respective model properties, the LYG ranged from 0.207 to 0.383 years, IC ranged from €3,556 to €3,731 and ICERs ranged from €9,683/LYG to €17,570/LYG. Differences in model structure and parameterization lead to substantial differences in analysis outcome metrics. This analysis supports the need for more guidance regarding structural uncertainty and the use of standardized disease-specific models for health economic analyses of adjuvant endocrine breast cancer therapies. The developed approach in the current analysis could potentially serve as a template for further evaluations of structural uncertainty and development of disease-specific models.

Smoke Alarm Giveaway and Installation Programs

PubMed Central

Liu, Ying; Mack, Karin A.; Diekman, Shane T.

2015-01-01

Background The burden of residential fire injury and death is substantial. Targeted smoke alarm giveaway and installation programs are popular interventions used to reduce residential fire mortality and morbidity. Purpose To evaluate the cost effectiveness and cost benefit of implementing a giveaway or installation program in a small hypothetic community with a high risk of fire death and injury through a decision-analysis model. Methods Model inputs included program costs; program effectiveness (life-years and quality-adjusted life-years saved); and monetized program benefits (medical cost, productivity, property loss and quality-of-life losses averted) and were identified through structured reviews of existing literature (done in 2011) and supplemented by expert opinion. Future costs and effectiveness were discounted at a rate of 3% per year. All costs were expressed in 2011 U.S. dollars. Results Cost-effectiveness analysis (CEA) resulted in anaverage cost-effectiveness ratio (ACER) of $51,404 per quality-adjusted life-years (QALYs) saved and $45,630 per QALY for the giveaway and installation programs, respectively. Cost–benefit analysis (CBA) showed that both programs were associated with a positive net benefit with a benefit–cost ratio of 2.1 and 2.3, respectively. Smoke alarm functional rate, baseline prevalence of functional alarms, and baseline home fire death rate were among the most influential factors for the CEA and CBA results. Conclusions Both giveaway and installation programs have an average cost-effectiveness ratio similar to or lower than the median cost-effectiveness ratio reported for other interventionsto reduce fatal injuries in homes. Although more effort is required, installation programs result in lower cost per outcome achieved compared with giveaways. PMID:22992356

Seeing the NICE side of cost-effectiveness analysis: a qualitative investigation of the use of CEA in NICE technology appraisals.

PubMed

Bryan, Stirling; Williams, Iestyn; McIver, Shirley

2007-02-01

Resource scarcity is the raison d'être for the discipline of economics. Thus, the primary purpose of economic analysis is to help decision-makers when addressing problems arising due to the scarcity problem. The research reported here was concerned with how cost-effectiveness information is used by the National Institute for Health & Clinical Excellence (NICE) in national technology coverage decisions in the UK, and how its impact might be increased. The research followed a qualitative case study methodology with semi-structured interviews, supported by observation and analysis of secondary sources. Our research highlights that the technology appraisal function of NICE represents an important progression for the UK health economics community: new cost-effectiveness work is commissioned for each technology and that work directly informs national health policy. However, accountability in policy decisions necessitates that the information upon which decisions are based (including cost-effectiveness analysis, CEA) is accessible. This was found to be a serious problem and represents one of the main ongoing challenges. Other issues highlighted include perceived weaknesses in analysis methods and the poor alignment between the health maximisation objectives assumed in economic analyses and the range of other objectives facing decision-makers in reality. Copyright (c) 2006 John Wiley & Sons, Ltd.

Cost-effectiveness analyses and their role in improving healthcare strategies.

PubMed

Rodriguez, Maria I; Caughey, Aaron B

2013-12-01

In this era of healthcare reform, attention is focused on increasing the quality of care and access to services, while simultaneously reducing the cost. Economic evaluations can play an important role in translating research to evidence-based practice and policy. Cost-effectiveness analysis (CEA) and its utility for clinical and policy decision making among U.S. obstetricians and gynecologists is reviewed. Three case examples demonstrating the value of this methodology in decision making are considered. A discussion of the methodologic principles of CEA, the advantages, and the limitations of the methodology are presented. CEA can play an important role in evidence-based decision making, with value for clinicians and policy makers alike. These studies are of particular interest in the field of obstetrics and gynecology, in which uncertainty from epidemiologic or clinical trials exists, or multiple perspectives need to be considered (maternal, neonatal, and societal). As with all research, it is essential that economic evaluations are conducted according to established methodologic standards. Interpretation and application of results should occur with a clear understanding of both the value and the limitations of economic evaluations.

Accounting for equity considerations in cost-effectiveness analysis: a systematic review of rotavirus vaccine in low- and middle-income countries.

PubMed

Boujaoude, Marie-Anne; Mirelman, Andrew J; Dalziel, Kim; Carvalho, Natalie

2018-01-01

Cost-effectiveness analysis (CEA) is frequently used as an input for guiding priority setting in health. However, CEA seldom incorporates information about trade-offs between total health gains and equity impacts of interventions. This study investigates to what extent equity considerations have been taken into account in CEA in low- and middle-income countries (LMICs), using rotavirus vaccination as a case study. Specific equity-related indicators for vaccination were first mapped to the Guidance on Priority Setting in Health Care (GPS-Health) checklist criteria. Economic evaluations of rotavirus vaccine in LMICs identified via a systematic review of the literature were assessed to explore the extent to which equity was considered in the research objectives and analysis, and whether it was reflected in the evaluation results. The mapping process resulted in 18 unique indicators. Under the 'disease and intervention' criteria, severity of illness was incorporated in 75% of the articles, age distribution of the disease in 70%, and presence of comorbidities in 5%. For the 'social groups' criteria, relative coverage reflecting wealth-based coverage inequality was taken into account in 30% of the articles, geographic location in 27%, household income level in 8%, and sex at birth in 5%. For the criteria of 'protection against the financial and social effects of ill health', age weighting was incorporated in 43% of the articles, societal perspective in 58%, caregiver's loss of productivity in 45%, and financial risk protection in 5%. Overall, some articles incorporated the indicators in their model inputs (20%) while the majority (80%) presented results (costs, health outcomes, or incremental cost-effectiveness ratios) differentiated according to the indicators. Critically, less than a fifth (17%) of articles incorporating indicators did so due to an explicit study objective related to capturing equity considerations. Most indicators were increasingly incorporated over time, with a notable exception of age-weighting of DALYs. Integrating equity criteria in CEA can help policy-makers better understand the distributional impact of health interventions. This study illustrates how equity considerations are currently being incorporated within CEA of rotavirus vaccination and highlights the components of equity that have been used in studies in LMICs. Areas for further improvement are identified.

Examining the cost-effectiveness of cancer screening promotion.

PubMed

Andersen, M Robyn; Urban, Nicole; Ramsey, Scott; Briss, Peter A

2004-09-01

Cost-effectiveness analyses (CEAs) can help to quantify the contribution of the promotion of a screening program to increased participation in screening. The cost-effectiveness (C/E) of screening promotion depends in large part on the endpoints of interest. At the most fundamental level, the C/E of a strategy for promoting screening would focus on the attendance rate, or cost per person screened, and the C/E would be influenced by the costs of promotion, as well as by the size and responsiveness of the target population. In addition, the costs of screening promotion (measured as the cost per additional participant in screening) can be included in a CEA estimate of the screening technology. In this case, depending on the efficacy of the screening test and the costs and influence of the promotion, the C/E of screening may improve or become poorer. In the current study, the authors reviewed the literature on the C/E of cancer screening promotion. The following lessons were learned regarding the C/E of screening and its promotion: 1) high-quality information on the C/E of screening is increasingly available; 2) cost-effective promotion of screening is dependent on cost-effective screening strategies; 3) quality-of-life effects may be important in assessing the overall C/E of screening programs; 4) research efforts aimed at identifying cost-effective approaches to screening promotion are useful but sparse; 5) C/E studies should be better incorporated into well designed effectiveness research efforts; 6) variations in C/E according to intervention characteristics, population characteristics, and context should be evaluated in greater depth; 7) the long-term effects of screening promotion are critical to assessing C/E; 8) the effects of promotion on costs of screening must be better understood; and 9) CEA must be interpreted in light of other information. The authors showed that CEA can be a valuable tool for understanding the merits of health promotion interventions and that CEA is particularly valuable in identifying screening strategies that might be promoted most cost-effectively.

Assessing value-for-money in maternal and newborn health

PubMed Central

Madaj, Barbara; Kumar, Shubha

2017-01-01

Responding to increasing demands to demonstrate value-for-money (VfM) for maternal and newborn health interventions, and in the absence of VfM analysis in peer-reviewed literature, this paper reviews VfM components and methods, critiques their applicability, strengths and weakness and proposes how VfM assessments can be improved. VfM comprises four components: economy, efficiency, effectiveness and cost-effectiveness. Both ‘economy’ and ‘efficiency’ can be assessed with detailed cost analysis utilising costs obtained from programme accounting data or generic cost databases. Before-and-after studies, case–control studies or randomised controlled trials can be used to assess ‘effectiveness’. To assess ‘cost-effectiveness’, cost-effectiveness analysis (CEA), cost-utility analysis (CUA), cost-benefit analysis (CBA) or social return on investment (SROI) analysis are applicable. Generally, costs can be obtained from programme accounting data or existing generic cost databases. As such ‘economy’ and ‘efficiency’ are relatively easy to assess. However, ‘effectiveness’ and ‘cost-effectiveness’ which require establishment of the counterfactual are more difficult to ascertain. Either a combination of CEA or CUA with tools for assessing other VfM components, or the independent use of CBA or SROI are alternative approaches proposed to strengthen VfM assessments. Cross-cutting themes such as equity, sustainability, scalability and cultural acceptability should also be assessed, as they provide critical contextual information for interpreting VfM assessments. To select an assessment approach, consideration should be given to the purpose, data availability, stakeholders requiring the findings and perspectives of programme beneficiaries. Implementers and researchers should work together to improve the quality of assessments. Standardisation around definitions, methodology and effectiveness measures to be assessed would help. PMID:29081998

Health economics evaluation of a gastric cancer early detection and treatment program in China.

PubMed

Li, Dan; Yuan, Yuan; Sun, Li-Ping; Fang, Xue; Zhou, Bao-Sen

2014-01-01

To use health economics methodology to assess the screening program on gastric cancer in Zhuanghe, China, so as to provide the basis for health decision on expanding the program of early detection and treatment. The expense of an early detection and treatment program for gastric cancer in patients found by screening, and also costs of traditional treatment in a hospital of Zhuanghe were assessed. Three major techniques of medical economics, namely cost-effective analysis (CEA), cost-benefit analysis (CBA) and cost-utility analysis (CUA), were used to assess the screening program. RESULTS from CEA showed that investing every 25, 235 Yuan on screening program in Zhuanghe area, one gastric cancer patient could be saved. Data from CUA showed that it was cost 1, 370 Yuan per QALY saved. RESULTS from CBA showed that: the total cost was 1,945,206 Yuan with a benefit as 8,669,709 Yuan and an CBR of 4.46. The early detection and treatment program of gastric cancer appears economic and society-beneficial. We suggest that it should be carry out in more high risk areas for gastric cancer.

Smoke alarm giveaway and installation programs: an economic evaluation.

PubMed

Liu, Ying; Mack, Karin A; Diekman, Shane T

2012-10-01

The burden of residential fire injury and death is substantial. Targeted smoke alarm giveaway and installation programs are popular interventions used to reduce residential fire mortality and morbidity. To evaluate the cost effectiveness and cost benefit of implementing a giveaway or installation program in a small hypothetic community with a high risk of fire death and injury through a decision-analysis model. Model inputs included program costs; program effectiveness (life-years and quality-adjusted life-years saved); and monetized program benefits (medical cost, productivity, property loss and quality-of-life losses averted) and were identified through structured reviews of existing literature (done in 2011) and supplemented by expert opinion. Future costs and effectiveness were discounted at a rate of 3% per year. All costs were expressed in 2011 U.S. dollars. Cost-effectiveness analysis (CEA) resulted in an average cost-effectiveness ratio (ACER) of $51,404 per quality-adjusted life-years (QALYs) saved and $45,630 per QALY for the giveaway and installation programs, respectively. Cost-benefit analysis (CBA) showed that both programs were associated with a positive net benefit with a benefit-cost ratio of 2.1 and 2.3, respectively. Smoke alarm functional rate, baseline prevalence of functional alarms, and baseline home fire death rate were among the most influential factors for the CEA and CBA results. Both giveaway and installation programs have an average cost-effectiveness ratio similar to or lower than the median cost-effectiveness ratio reported for other interventions to reduce fatal injuries in homes. Although more effort is required, installation programs result in lower cost per outcome achieved compared with giveaways. Published by Elsevier Inc.

Incorporating external evidence in trial-based cost-effectiveness analyses: the use of resampling methods

PubMed Central

2014-01-01

Background Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence. Methods We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions. Results In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods. Conclusions The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes. PMID:24888356

Incorporating external evidence in trial-based cost-effectiveness analyses: the use of resampling methods.

PubMed

Sadatsafavi, Mohsen; Marra, Carlo; Aaron, Shawn; Bryan, Stirling

2014-06-03

Cost-effectiveness analyses (CEAs) that use patient-specific data from a randomized controlled trial (RCT) are popular, yet such CEAs are criticized because they neglect to incorporate evidence external to the trial. A popular method for quantifying uncertainty in a RCT-based CEA is the bootstrap. The objective of the present study was to further expand the bootstrap method of RCT-based CEA for the incorporation of external evidence. We utilize the Bayesian interpretation of the bootstrap and derive the distribution for the cost and effectiveness outcomes after observing the current RCT data and the external evidence. We propose simple modifications of the bootstrap for sampling from such posterior distributions. In a proof-of-concept case study, we use data from a clinical trial and incorporate external evidence on the effect size of treatments to illustrate the method in action. Compared to the parametric models of evidence synthesis, the proposed approach requires fewer distributional assumptions, does not require explicit modeling of the relation between external evidence and outcomes of interest, and is generally easier to implement. A drawback of this approach is potential computational inefficiency compared to the parametric Bayesian methods. The bootstrap method of RCT-based CEA can be extended to incorporate external evidence, while preserving its appealing features such as no requirement for parametric modeling of cost and effectiveness outcomes.

Bayesian hierarchical models for cost-effectiveness analyses that use data from cluster randomized trials.

PubMed

Grieve, Richard; Nixon, Richard; Thompson, Simon G

2010-01-01

Cost-effectiveness analyses (CEA) may be undertaken alongside cluster randomized trials (CRTs) where randomization is at the level of the cluster (for example, the hospital or primary care provider) rather than the individual. Costs (and outcomes) within clusters may be correlated so that the assumption made by standard bivariate regression models, that observations are independent, is incorrect. This study develops a flexible modeling framework to acknowledge the clustering in CEA that use CRTs. The authors extend previous Bayesian bivariate models for CEA of multicenter trials to recognize the specific form of clustering in CRTs. They develop new Bayesian hierarchical models (BHMs) that allow mean costs and outcomes, and also variances, to differ across clusters. They illustrate how each model can be applied using data from a large (1732 cases, 70 primary care providers) CRT evaluating alternative interventions for reducing postnatal depression. The analyses compare cost-effectiveness estimates from BHMs with standard bivariate regression models that ignore the data hierarchy. The BHMs show high levels of cost heterogeneity across clusters (intracluster correlation coefficient, 0.17). Compared with standard regression models, the BHMs yield substantially increased uncertainty surrounding the cost-effectiveness estimates, and altered point estimates. The authors conclude that ignoring clustering can lead to incorrect inferences. The BHMs that they present offer a flexible modeling framework that can be applied more generally to CEA that use CRTs.

Tamoxifen for breast cancer risk reduction: impact of alternative approaches to quality-of-life adjustment on cost-effectiveness analysis.

PubMed

Melnikow, Joy; Birch, Stephen; Slee, Christina; McCarthy, Theodore J; Helms, L Jay; Kuppermann, Miriam

2008-09-01

In cost-effectiveness analysis (CEA), the effects of health-care interventions on multiple health dimensions typically require consideration of both quantity and quality of life. To explore the impact of alternative approaches to quality-of-life adjustment using patient preferences (utilities) on the outcome of a CEA on use of tamoxifen for breast cancer risk reduction. A state transition Markov model tracked hypothetical cohorts of women who did or did not take 5 years of tamoxifen for breast cancer risk reduction. Incremental quality-adjusted effectiveness and cost-effectiveness ratios (ICERs) for models including and excluding a utility adjustment for menopausal symptoms were compared with each other and to a global utility model. Two hundred fifty-five women aged 50 and over with estimated 5-year breast cancer risk >or=1.67% participated in utility assessment interviews. Standard gamble utilities were assessed for specified tamoxifen-related health outcomes, current health, and for a global assessment of possible outcomes of tamoxifen use. Inclusion of a utility for menopausal symptoms in the outcome-specific models substantially increased the ICER; at the threshold 5-year breast cancer risk of 1.67%, tamoxifen was dominated. When a global utility for tamoxifen was used in place of outcome-specific utilities, tamoxifen was dominated under all circumstances. CEAs may be profoundly affected by the types of outcomes considered for quality-of-life adjustment and how these outcomes are grouped for utility assessment. Comparisons of ICERs across analyses must consider effects of different approaches to using utilities for quality-of-life adjustment.

Cost and cost-effectiveness studies in urologic oncology using large administrative databases.

PubMed

Wang, Ye; Mossanen, Matthew; Chang, Steven L

2018-04-01

Urologic cancers are not only among the most common types of cancers, but also among the most expensive cancers to treat in the United States. This study aimed to review the use of CEAs and other cost analyses in urologic oncology using large databases to better understand the value of management strategies of these cancers. A literature review on CEAs and other cost analyses in urologic oncology using large databases. The options for and costs of diagnosing, treating, and following patients with urologic cancers can be expected to rise in the coming years. There are numerous opportunities in each urologic cancer to use CEAs to both lower costs and provide high-quality services. Improved cancer care must balance the integration of novelty with ensuring reasonable costs to patients and the health care system. With the increasing focus cost containment, appreciating the value of competing strategies in caring for our patients is pivotal. Leveraging methods such as CEAs and harnessing large databases may help evaluate the merit of established or emerging strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

Cost-effectiveness analysis in relation to budgetary constraints and reallocative restrictions.

PubMed

Adang, Eddy; Voordijk, Leo; Jan van der Wilt, Gert; Ament, André

2005-10-01

Present cost-effectiveness analyses (CEAs) provide not all information necessary for decision-making. One of the factors that hamper decision-making is the difficulty in reallocating resources to new technologies. In a CEA, the incremental costs and incremental benefits of a new technology are calculated. In this article we focus on the incremental cost side. The underlying assumption in socio-economic evaluation is that resources from the substituted alternatives can be used to finance the new technology. In practice, however, not all resources are becoming available to introduce the alternative. The budgets in health care are rather fixed and shifting from one alternative to another or from one sector to another is often impossible. Even within a budget, the personnel and material resources are usually not entirely usable for the new technology, and sometimes not at all. Therefore, the present CEA outcomes might overestimate the cost-effectiveness in practice, which might influence implementation of a new technology. To optimise the usefulness of economic evaluation for health care decision-making by correcting the incremental costs of a new technology for the possible limitations in reallocating resources and adjusting budgets in health care. Case Research. Literature, data from two completed CEAs and interviews with decision makers in the hospital setting. Case 1: The combined outpatient and home-treatment of psoriasis--In a CEA it was calculated that the new technology lead to much lower cost, given the same effects. The direct costs of this technology comprise personnel, material and capacity costs. Personnel and capacity are inflexible with regard to reallocation, at least in the short term. Considering these reallocative restrictions results show that the cost-savings of the combined treatment are in the short run significantly smaller than in the long run: 694 versus 6.058, respectively. Therefore, the anticipated savings, estimated are not realistic for decision makers with a short time horizon. The short-term savings amount to only 11% of the anticipated savings in the long run. Nevertheless, the combined treatment remains a cost-effective treatment. Analysing the budgetary constraints resulted in the finding that the substitution of the in-hospital treatment by the combined treatment has taken place without negative financial consequences for the hospital. Case 2: The ground bound mobile medical team--Economic arguments to implement the ground bound mobile medical team (MMT) are undecided. With respect to the budgetary constraints we find that the budget for the trauma centre is conditional upon the deployment of the ground bound MMT. Moreover, the cost of the ground bound MMT is a relatively small part of the budget for the trauma centre and therefore no hurdle to implement. On the basis of these findings we conclude that limitations in reallocating resources and adjusting budgets in health care may hamper the usefulness of economic evaluation for decision-making. Researching the extent of these limitations provides, together with the CEA, better information on which the decision whether a new technology should be implemented and what the expected welfare gains from such an implementation might be can be made. For this a set of checklists is developed.

Cost-effectiveness of antibiotic treatment strategies for community-acquired pneumonia: results from a cluster randomized cross-over trial.

PubMed

van Werkhoven, Cornelis H; Postma, Douwe F; Mangen, Marie-Josee J; Oosterheert, Jan Jelrik; Bonten, Marc J M

2017-01-10

To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy. Costs and effects were estimated using data from a cluster-randomized cross-over trial of antibiotic treatment strategies, primarily from the reduced third payer perspective (i.e. hospital admission costs). Cost-minimization analysis (CMA) and cost-effectiveness analysis (CEA) were performed using linear mixed models. CMA results were expressed as difference in costs per patient. CEA results were expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per prevented death. A total of 2,283 patients were included. Crude average costs within 90 days from the reduced third payer perspective were €4,294, €4,392, and €4,002 per patient for the beta-lactam monotherapy, beta-lactam/macrolide combination, and fluoroquinolone monotherapy strategy, respectively. CMA results were €106 (95% CI €-697 to €754) for the beta-lactam/macrolide combination strategy and €-278 (95%CI €-991 to €396) for the fluoroquinolone monotherapy strategy, both compared to the beta-lactam monotherapy strategy. The ICER was not statistically significantly different between the strategies. Other perspectives yielded similar results. There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy, beta-lactam/macrolide combination therapy, or fluoroquinolone monotherapy. The trial was registered with ClinicalTrials.gov, number NCT01660204 , on May 2nd, 2012.

Hispanic ethnicity is associated with increased costs after carotid endarterectomy and carotid stenting in the United States.

PubMed

Propper, Brandon; Black, James H; Schneider, Eric B; Lum, Ying Wei; Malas, Mahmoud B; Arnold, Margaret W; Abularrage, Christopher J

2013-09-01

We have previously demonstrated an adverse impact of black race and Hispanic ethnicity on the outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS). The current study was undertaken to examine the influence of race and ethnicity on the cost of CEA and CAS. The Nationwide Inpatient Sample (2005-2009) was queried using ICD-9 codes for CEA and CAS in patients with carotid artery stenosis. The primary outcome was total hospital charges. Multivariate analysis was performed using a generalized linear model adjusting for age, sex, race, comorbidities (Charlson index), high-risk status, procedure type, symptomatic status, year, insurance type, and surgeon and hospital operative volumes and characteristics. Hispanic and black patients were more likely to have a symptomatic presentation, and were more likely to undergo either CEA or CAS by low-volume surgeons at low-volume hospitals (P < 0.05, all). They were also less likely to have private insurance or Medicare (P < 0.001). Overall, CEA was less expensive than CAS over the 4-y study period ($29,502 ± $104 versus $46,713 ± $409, P < 0.001). Total hospital charges after CEA were increased in both blacks ($39,562 ± $843) and Hispanics ($45,325 ± $735) compared with whites on univariate analysis ($28,403 ± $101, P < 0.001). After CAS, total hospital charges were similarly increased in both blacks ($51,770 ± $2085) and Hispanics ($63,637 ± $2766) compared with whites on univariate analysis ($45,550 ± $412, P < 0.001). On multivariable analysis, however, only Hispanic ethnicity remained independently associated with increased charges after both CEA (exponentiated coefficient 1.18; 95% CI [1.15-1.20]; P < 0.001) and CAS (exponentiated coefficient 1.17; 95% CI [1.09-1.24]; P < 0.001). Hispanic ethnicity was independently associated with increased hospital charges after both CEA and CAS. The increased charges seen in black patients were explained, in part, by decreased surgeon operative volume and increased postoperative complications. Further efforts are warranted to contain costs in minorities undergoing carotid revascularization. Copyright © 2013 Elsevier Inc. All rights reserved.

Cost-effective strategy to mitigate transportation disruptions in supply chain

NASA Astrophysics Data System (ADS)

Albertzeth, G.; Pujawan, I. N.

2018-04-01

Supply chain disruptions have gained significant attention by scholars. But, even though transportation plays a central role in supply chain, only few studies address transportation disruptions. This research demonstrates a real case of an order delivery process from a focal company (FC) to a single distributor, where transportation disruptions stochastically occurs. Considering the possibility of sales loss during the disruption duration, we proposed a redundant stock, flexible route, and combined flexibility-redundancy (ReFlex) as mitigation strategies and a base case as a risk acceptance strategy. The objective is to find out the best strategy that promotes cost-effectiveness against transportation disruptions. To fulfill this objective, we use simulation modeling and cost-effectiveness analysis (CEA) as our research method. We simulate the delivery process of 5 brands using each strategy to produce two different responses: loss of sales percentage and the incurred costs. Next, using these responses, we evaluate and compare the cost-effectiveness ratio of each strategy using CEA. We found that redundant stock gave the best effectiveness on all brands, ReFlex as the second best, while flexible route gave the least effectiveness. Finally, we recommend which strategy should be applied based on the decision maker willingness to pay.

Economic Evaluation of Teledentistry in Cleft Lip and Palate Patients.

PubMed

Teoh, Jonathan; Hsueh, Arthur; Mariño, Rodrigo; Manton, David; Hallett, Kerrod

2018-06-01

To assess the use of Teledentistry (TD) in delivering specialist dental services at the Royal Children's Hospital (RCH) for rural and regional patients and to conduct an economic evaluation by building a decision model to estimate the costs and effectiveness of Teledental consultations compared with standard consultations at the RCH. A model-based analysis was conducted to determine the potential costs of implementing TD at the RCH. The outcome measure was timely consultations (whether the patient presented within an appropriate time according to the recommended schedule). Dental records at the RCH of those who presented for orthodontic or pediatric dental consultations were assessed. A cost-effectiveness analysis (CEA), comparing TD with the traditional method of consultation, was conducted. One-way sensitivity analysis was performed to test the robustness of the results. Results and Materials: A total of 367 TD appropriate consultations were identified, of which 241 were timely (65.7%). The mean cost of a RCH consultation was A$431.29, with the mean TD consult costing A$294.35. This represents a cost saving of A$136.95 per appointment. The CEA found TD to be a dominant option, with cost savings of A$3,160.81 for every additional timely consult. The model indicated that 36.7 days of clinic time may be freed up at the RCH to treat other patients and expand capacity. These results were robust when performing one-way sensitivity analysis. When taking a societal perspective, the implementation of TD is likely to be a cost-effective alternative compared with the standard practice of face-to-face consultation at the RCH.

Better Informing Decision Making with Multiple Outcomes Cost-Effectiveness Analysis under Uncertainty in Cost-Disutility Space

PubMed Central

McCaffrey, Nikki; Agar, Meera; Harlum, Janeane; Karnon, Jonathon; Currow, David; Eckermann, Simon

2015-01-01

Introduction Comparing multiple, diverse outcomes with cost-effectiveness analysis (CEA) is important, yet challenging in areas like palliative care where domains are unamenable to integration with survival. Generic multi-attribute utility values exclude important domains and non-health outcomes, while partial analyses—where outcomes are considered separately, with their joint relationship under uncertainty ignored—lead to incorrect inference regarding preferred strategies. Objective The objective of this paper is to consider whether such decision making can be better informed with alternative presentation and summary measures, extending methods previously shown to have advantages in multiple strategy comparison. Methods Multiple outcomes CEA of a home-based palliative care model (PEACH) relative to usual care is undertaken in cost disutility (CDU) space and compared with analysis on the cost-effectiveness plane. Summary measures developed for comparing strategies across potential threshold values for multiple outcomes include: expected net loss (ENL) planes quantifying differences in expected net benefit; the ENL contour identifying preferred strategies minimising ENL and their expected value of perfect information; and cost-effectiveness acceptability planes showing probability of strategies minimising ENL. Results Conventional analysis suggests PEACH is cost-effective when the threshold value per additional day at home ( 1) exceeds $1,068 or dominated by usual care when only the proportion of home deaths is considered. In contrast, neither alternative dominate in CDU space where cost and outcomes are jointly considered, with the optimal strategy depending on threshold values. For example, PEACH minimises ENL when 1=$2,000 and 2=$2,000 (threshold value for dying at home), with a 51.6% chance of PEACH being cost-effective. Conclusion Comparison in CDU space and associated summary measures have distinct advantages to multiple domain comparisons, aiding transparent and robust joint comparison of costs and multiple effects under uncertainty across potential threshold values for effect, better informing net benefit assessment and related reimbursement and research decisions. PMID:25751629

The cost effectiveness of radon mitigation in existing German dwellings--a decision theoretic analysis.

PubMed

Haucke, Florian

2010-11-01

Radon is a naturally occurring inert radioactive gas found in soils and rocks that can accumulate in dwellings, and is associated with an increased risk of lung cancer. This study aims to analyze the cost effectiveness of different intervention strategies to reduce radon concentrations in existing German dwellings. The cost effectiveness analysis (CEA) was conducted as a scenario analysis, where each scenario represents a specific regulatory regime. A decision theoretic model was developed, which reflects accepted recommendations for radon screening and mitigation and uses most up-to-date data on radon distribution and relative risks. The model was programmed to account for compliance with respect to the single steps of radon intervention, as well as data on the sensitivity/specificity of radon tests. A societal perspective was adopted to calculate costs and effects. All scenarios were calculated for different action levels. Cost effectiveness was measured in costs per averted case of lung cancer, costs per life year gained and costs per quality adjusted life year (QALY) gained. Univariate and multivariate deterministic and probabilistic sensitivity analyses (SA) were performed. Probabilistic sensitivity analyses were based on Monte Carlo simulations with 5000 model runs. The results show that legal regulations with mandatory screening and mitigation for indoor radon levels >100 Bq/m(3) are most cost effective. Incremental cost effectiveness compared to the no mitigation base case is 25,181 euro (95% CI: 7371 euro-90,593 euro) per QALY gained. Other intervention strategies focussing primarily on the personal responsibility for screening and/or mitigative actions show considerably worse cost effectiveness ratios. However, targeting radon intervention to radon-prone areas is significantly more cost effective. Most of the uncertainty that surrounds the results can be ascribed to the relative risk of radon exposure. It can be concluded that in the light of international experience a legal regulation requiring radon screening and, if necessary, mitigation is justifiable under the terms of CEA. Copyright 2010 Elsevier Ltd. All rights reserved.

Developing appropriate methods for cost-effectiveness analysis of cluster randomized trials.

PubMed

Gomes, Manuel; Ng, Edmond S-W; Grieve, Richard; Nixon, Richard; Carpenter, James; Thompson, Simon G

2012-01-01

Cost-effectiveness analyses (CEAs) may use data from cluster randomized trials (CRTs), where the unit of randomization is the cluster, not the individual. However, most studies use analytical methods that ignore clustering. This article compares alternative statistical methods for accommodating clustering in CEAs of CRTs. Our simulation study compared the performance of statistical methods for CEAs of CRTs with 2 treatment arms. The study considered a method that ignored clustering--seemingly unrelated regression (SUR) without a robust standard error (SE)--and 4 methods that recognized clustering--SUR and generalized estimating equations (GEEs), both with robust SE, a "2-stage" nonparametric bootstrap (TSB) with shrinkage correction, and a multilevel model (MLM). The base case assumed CRTs with moderate numbers of balanced clusters (20 per arm) and normally distributed costs. Other scenarios included CRTs with few clusters, imbalanced cluster sizes, and skewed costs. Performance was reported as bias, root mean squared error (rMSE), and confidence interval (CI) coverage for estimating incremental net benefits (INBs). We also compared the methods in a case study. Each method reported low levels of bias. Without the robust SE, SUR gave poor CI coverage (base case: 0.89 v. nominal level: 0.95). The MLM and TSB performed well in each scenario (CI coverage, 0.92-0.95). With few clusters, the GEE and SUR (with robust SE) had coverage below 0.90. In the case study, the mean INBs were similar across all methods, but ignoring clustering underestimated statistical uncertainty and the value of further research. MLMs and the TSB are appropriate analytical methods for CEAs of CRTs with the characteristics described. SUR and GEE are not recommended for studies with few clusters.

Developing Appropriate Methods for Cost-Effectiveness Analysis of Cluster Randomized Trials

PubMed Central

Gomes, Manuel; Ng, Edmond S.-W.; Nixon, Richard; Carpenter, James; Thompson, Simon G.

2012-01-01

Aim. Cost-effectiveness analyses (CEAs) may use data from cluster randomized trials (CRTs), where the unit of randomization is the cluster, not the individual. However, most studies use analytical methods that ignore clustering. This article compares alternative statistical methods for accommodating clustering in CEAs of CRTs. Methods. Our simulation study compared the performance of statistical methods for CEAs of CRTs with 2 treatment arms. The study considered a method that ignored clustering—seemingly unrelated regression (SUR) without a robust standard error (SE)—and 4 methods that recognized clustering—SUR and generalized estimating equations (GEEs), both with robust SE, a “2-stage” nonparametric bootstrap (TSB) with shrinkage correction, and a multilevel model (MLM). The base case assumed CRTs with moderate numbers of balanced clusters (20 per arm) and normally distributed costs. Other scenarios included CRTs with few clusters, imbalanced cluster sizes, and skewed costs. Performance was reported as bias, root mean squared error (rMSE), and confidence interval (CI) coverage for estimating incremental net benefits (INBs). We also compared the methods in a case study. Results. Each method reported low levels of bias. Without the robust SE, SUR gave poor CI coverage (base case: 0.89 v. nominal level: 0.95). The MLM and TSB performed well in each scenario (CI coverage, 0.92–0.95). With few clusters, the GEE and SUR (with robust SE) had coverage below 0.90. In the case study, the mean INBs were similar across all methods, but ignoring clustering underestimated statistical uncertainty and the value of further research. Conclusions. MLMs and the TSB are appropriate analytical methods for CEAs of CRTs with the characteristics described. SUR and GEE are not recommended for studies with few clusters. PMID:22016450

Valuation of Drug Abuse: A Review of Current Methodologies and Implications for Policy Making

ERIC Educational Resources Information Center

Schori, Maayan

2011-01-01

This article reviews the use of several valuation methods as they relate to drug abuse and places them within the context of U.S. policy. First, cost-of-illness (COI) studies are reviewed and their limitations discussed. Second, three additional economic methods of valuing drug abuse are reviewed, including cost-effectiveness analysis (CEA),…

Cost-Effectiveness Analysis of Universal Influenza Vaccination: Application of Susceptible-Infectious-Complication-Recovery Model.

PubMed

Yang, Kuen-Cheh; Hung, Hui-Fang; Chen, Meng-Kan; Chen, Li-Sheng; Fann, Jean Ching-Yuan; Chiu, Sherry Yueh-Hsia; Yen, Amy-Ming Fang; Huang, Kuo-Chin; Chen, Hsiu-Hsi; Wang, Sen-Te

2018-06-12

Despite the fact that vaccination is an effective primary prevention strategy for containing influenza outbreak, health policymakers show great concern over enormous costs involved in universal immunization particularly when resources are limited. We conducted a two-arm cost-effectiveness analysis (CEA) that takes into account the aspect of herd immunity, using a study cohort that was composed of 100,000 residents with the make-up of demographic characteristics identical to those of the underlying population in Taipei County, Taiwan, during the epidemic influenza season of 2001-2002. The parameters embedded in the dynamic process of infection were estimated by the application of the newly proposed susceptible-infection-complication-recovery model to the empirical data in order to compute the number of deaths and complications averted due to universal vaccination compared to non-vaccination. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curve (CEAC) given maximum amount of willingness-to-pay (WTP) were calculated to delineate the results of the two-arm CEA. Incremental costs involved in the vaccinated group as opposed to the unvaccinated group was $1,195 for reducing one additional complication and $805 for averting one additional death, allowing for herd immunity. The corresponding figures were higher for the results without considering herd immunity. Given the ceiling ratio of willingness-to-pay (WTP) equal to $10,000 (approximately two-thirds of the GDP), the probability of being cost-effective for vaccination was 100% and 96.7% for averting death and complications, respectively. Universal vaccination against seasonal influenza was very cost-effective particularly when herd immunity is considered. The probability of being cost-effective was almost certain given the maximum amount of WTP within two-thirds of the GDP. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regression analysis on the variation in efficiency frontiers for prevention stage of HIV/AIDS.

PubMed

Kamae, Maki S; Kamae, Isao; Cohen, Joshua T; Neumann, Peter J

2011-01-01

To investigate how the cost effectiveness of preventing HIV/AIDS varies across possible efficiency frontiers (EFs) by taking into account potentially relevant external factors, such as prevention stage, and how the EFs can be characterized using regression analysis given uncertainty of the QALY-cost estimates. We reviewed cost-effectiveness estimates for the prevention and treatment of HIV/AIDS published from 2002-2007 and catalogued in the Tufts Medical Center Cost-Effectiveness Analysis (CEA) Registry. We constructed efficiency frontier (EF) curves by plotting QALYs against costs, using methods used by the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany. We stratified the QALY-cost ratios by prevention stage, country of study, and payer perspective, and estimated EF equations using log and square-root models. A total of 53 QALY-cost ratios were identified for HIV/AIDS in the Tufts CEA Registry. Plotted ratios stratified by prevention stage were visually grouped into a cluster consisting of primary/secondary prevention measures and a cluster consisting of tertiary measures. Correlation coefficients for each cluster were statistically significant. For each cluster, we derived two EF equations - one based on the log model, and one based on the square-root model. Our findings indicate that stratification of HIV/AIDS interventions by prevention stage can yield distinct EFs, and that the correlation and regression analyses are useful for parametrically characterizing EF equations. Our study has certain limitations, such as the small number of included articles and the potential for study populations to be non-representative of countries of interest. Nonetheless, our approach could help develop a deeper appreciation of cost effectiveness beyond the deterministic approach developed by IQWiG.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

PubMed

Kim, Chong H; Simmons, Sierra C; Williams, Lance A; Staley, Elizabeth M; Zheng, X Long; Pham, Huy P

2017-11-01

The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center. © 2017 AABB.

Presenting evidence and summary measures to best inform societal decisions when comparing multiple strategies.

PubMed

Eckermann, Simon; Willan, Andrew R

2011-07-01

Multiple strategy comparisons in health technology assessment (HTA) are becoming increasingly important, with multiple alternative therapeutic actions, combinations of therapies and diagnostic and genetic testing alternatives. Comparison under uncertainty of incremental cost, effects and cost effectiveness across more than two strategies is conceptually and practically very different from that for two strategies, where all evidence can be summarized in a single bivariate distribution on the incremental cost-effectiveness plane. Alternative methods for comparing multiple strategies in HTA have been developed in (i) presenting cost and effects on the cost-disutility plane and (ii) summarizing evidence with multiple strategy cost-effectiveness acceptability (CEA) and expected net loss (ENL) curves and frontiers. However, critical questions remain for the analyst and decision maker of how these techniques can be best employed across multiple strategies to (i) inform clinical and cost inference in presenting evidence, and (ii) summarize evidence of cost effectiveness to inform societal reimbursement decisions where preferences may be risk neutral or somewhat risk averse under the Arrow-Lind theorem. We critically consider how evidence across multiple strategies can be best presented and summarized to inform inference and societal reimbursement decisions, given currently available methods. In the process, we make a number of important original findings. First, in presenting evidence for multiple strategies, the joint distribution of costs and effects on the cost-disutility plane with associated flexible comparators varying across replicates for cost and effect axes ensure full cost and effect inference. Such inference is usually confounded on the cost-effectiveness plane with comparison relative to a fixed origin and axes. Second, in summarizing evidence for risk-neutral societal decision making, ENL curves and frontiers are shown to have advantages over the CEA frontier in directly presenting differences in expected net benefit (ENB). The CEA frontier, while identifying strategies that maximize ENB, only presents their probability of maximizing net benefit (NB) and, hence, fails to explain why strategies maximize ENB at any given threshold value. Third, in summarizing evidence for somewhat risk-averse societal decision making, trade-offs between the strategy maximizing ENB and other potentially optimal strategies with higher probability of maximizing NB should be presented over discrete threshold values where they arise. However, the probabilities informing these trade-offs and associated discrete threshold value regions should be derived from bilateral CEA curves to prevent confounding by other strategies inherent in multiple strategy CEA curves. Based on these findings, a series of recommendations are made for best presenting and summarizing cost-effectiveness evidence for reimbursement decisions when comparing multiple strategies, which are contrasted with advice for comparing two strategies. Implications for joint research and reimbursement decisions are also discussed.

Cost-Effectiveness Analysis (CEA) of Four Interventions for Adolescents with a Substance Use Disorder

PubMed Central

French, Michael T.; Zavala, Silvana K.; McCollister, Kathryn E.; Waldron, Holly B.; Turner, Charles W.; Ozechowski, Timothy J.

2008-01-01

Alcohol, tobacco, and illicit drug use among adolescents in the U.S. continues to be a serious public health challenge. A variety of outpatient treatments for adolescent substance use disorders have been developed and evaluated. Although no specific treatment modality is effective in all settings, a number of promising adolescent interventions have emerged. As policy makers try to prioritize which programs to fund with limited public resources, the need for systematic economic evaluations of these programs is critical. The present study attempted a cost-effectiveness analysis (CEA) of four interventions, including family-based, individual, and group cognitive behavioral approaches, for adolescents with a substance use disorder. The results indicated that treatment costs varied substantially across the four interventions. Moreover, family therapy showed significantly better substance use outcome compared to group treatment at the 4-month assessment, but group treatment was similar to the other interventions for substance use outcome at the 7-month assessment and for delinquency outcome at both the 4-month and 7-month assessments. These findings over a relatively short follow-up period suggest that the least expensive intervention (group) was the most cost effective. However, this study encountered numerous data and methodological challenges in trying to supplement a completed clinical trial with an economic evaluation. These challenges are explained and recommendations are proposed to guide future economic evaluations in this area. PMID:17600651

A health economic outcome evaluation of an internet-based mobile-supported stress management intervention for employees.

PubMed

Ebert, David Daniel; Kählke, Fanny; Buntrock, Claudia; Berking, Matthias; Smit, Filip; Heber, Elena; Baumeister, Harald; Funk, Burkhardt; Riper, Heleen; Lehr, Dirk

2018-03-01

Objective This study aimed to estimate and evaluate the cost-effectiveness and cost-benefit of a guided internet- and mobile-supported occupational stress-management intervention (iSMI) for employees from the employer's perspective alongside a randomized controlled trial. Methods A sample of 264 employees with elevated symptoms of perceived stress (Perceived Stress Scale, PSS-10 ≥22) was randomly assigned either to the iSMI or a waitlist control (WLC) group with unrestricted access to treatment as usual. The iSMI consisted of seven sessions of problem-solving and emotion-regulation techniques and one booster session. Self-report data on symptoms of perceived stress and economic data were assessed at baseline, and at six months following randomization. A cost-benefit analysis (CBA) and a cost-effectiveness analysis (CEA) with symptom-free status as the main outcome from the employer's perspective was carried out. Statistical uncertainty was estimated using bootstrapping (N=5000). Results The CBA yielded a net-benefit of EUR181 [95% confidence interval (CI) -6043-1042] per participant within the first six months following randomization. CEA showed that at a willingness-to-pay ceiling of EUR0, EUR1000, EUR2000 for one additional symptom free employee yielded a 67%, 90%, and 98% probability, respectively, of the intervention being cost-effective compared to the WLC. Conclusion The iSMI was cost-effective when compared to WLC and even lead to cost savings within the first six months after randomization. Offering stress-management interventions can present good value for money in occupational healthcare.

Using Real-World Data in Health Technology Assessment (HTA) Practice: A Comparative Study of Five HTA Agencies.

PubMed

Makady, Amr; van Veelen, Ard; Jonsson, Páll; Moseley, Owen; D'Andon, Anne; de Boer, Anthonius; Hillege, Hans; Klungel, Olaf; Goettsch, Wim

2018-03-01

Reimbursement decisions are conventionally based on evidence from randomised controlled trials (RCTs), which often have high internal validity but low external validity. Real-world data (RWD) may provide complimentary evidence for relative effectiveness assessments (REAs) and cost-effectiveness assessments (CEAs). This study examines whether RWD is incorporated in health technology assessment (HTA) of melanoma drugs by European HTA agencies, as well as differences in RWD use between agencies and across time. HTA reports published between 1 January 2011 and 31 December 2016 were retrieved from websites of agencies representing five jurisdictions: England [National Institute for Health and Care Excellence (NICE)], Scotland [Scottish Medicines Consortium (SMC)], France [Haute Autorité de santé (HAS)], Germany [Institute for Quality and Efficacy in Healthcare (IQWiG)] and The Netherlands [Zorginstituut Nederland (ZIN)]. A standardized data extraction form was used to extract information on RWD inclusion for both REAs and CEAs. Overall, 52 reports were retrieved, all of which contained REAs; CEAs were present in 25 of the reports. RWD was included in 28 of the 52 REAs (54%), mainly to estimate melanoma prevalence, and in 22 of the 25 (88%) CEAs, mainly to extrapolate long-term effectiveness and/or identify drug-related costs. Differences emerged between agencies regarding RWD use in REAs; the ZIN and IQWiG cited RWD for evidence on prevalence, whereas the NICE, SMC and HAS additionally cited RWD use for drug effectiveness. No visible trend for RWD use in REAs and CEAs over time was observed. In general, RWD inclusion was higher in CEAs than REAs, and was mostly used to estimate melanoma prevalence in REAs or to predict long-term effectiveness in CEAs. Differences emerged between agencies' use of RWD; however, no visible trends for RWD use over time were observed.

Economic Evaluation of a Problem Solving Intervention to Prevent Recurrent Sickness Absence in Workers with Common Mental Disorders

PubMed Central

Arends, Iris; Bültmann, Ute; van Rhenen, Willem; Groen, Henk; van der Klink, Jac J. L.

2013-01-01

Objectives Workers with common mental disorders (CMDs) frequently experience recurrent sickness absence but scientifically evaluated interventions to prevent recurrences are lacking. The objectives of this study are to evaluate the cost-effectiveness and cost-benefit of a problem solving intervention aimed at preventing recurrent sickness absence in workers with CMDs compared to care as usual. Methods An economic evaluation was conducted alongside a cluster-randomised controlled trial with 12 months follow-up. Treatment providers were randomised to either a 2-day training in the SHARP-at work intervention, i.e. a problem solving intervention, or care as usual. Effect outcomes were the incidence of recurrent sickness absence and time to recurrent sickness absence. Self-reported health care utilisation was measured by questionnaires. A cost-effectiveness analysis (CEA) from the societal perspective and a cost-benefit analysis (CBA) from the employer’s perspective were conducted. Results The CEA showed that the SHARP-at work intervention was more effective but also more expensive than care as usual. The CBA revealed that employer’s occupational health care costs were significantly higher in the intervention group compared to care as usual. Overall, the SHARP-at work intervention showed no economic benefit compared to care as usual. Conclusions As implementation of the SHARP-at work intervention might require additional investments, health care policy makers need to decide if these investments are worthwhile considering the results that can be accomplished in reducing recurrent sickness absence. PMID:23951270

Lean systems approaches to health technology assessment: a patient-focused alternative to cost-effectiveness analysis.

PubMed

Bridges, John F P

2006-12-01

Many countries now use health technology assessment (HTA) to review new and emerging technologies, especially with regard to reimbursement, pricing and/or clinical guidelines. One of the common, but not universal, features of these systems is the use of economic evaluation, normally cost-effectiveness analysis (CEA), to confirm that new technologies offer value for money. Many have criticised these systems as primarily being concerned with cost containment, rather than advancing the interests of patients or innovators. This paper calls into question the underlying principles of CEA by arguing that value in the healthcare system may in fact be unconstrained. It is suggested that 'lean management principles' can be used not only to trim waste from the health system, but as a method of creating real incentives for innovation and value creation. Following the lean paradigm, this value must be defined purely from the patients' perspective, and the entire health system needs to work towards the creation of such value. This paper offers as a practical example a lean approach to HTA, arguing that such an approach would lead to better incentives for innovation in health, as well as more patient-friendly outcomes in the long run.

The value of innovation under value-based pricing.

PubMed

Moreno, Santiago G; Ray, Joshua A

2016-01-01

The role of cost-effectiveness analysis (CEA) in incentivizing innovation is controversial. Critics of CEA argue that its use for pricing purposes disregards the 'value of innovation' reflected in new drug development, whereas supporters of CEA highlight that the value of innovation is already accounted for. Our objective in this article is to outline the limitations of the conventional CEA approach, while proposing an alternative method of evaluation that captures the value of innovation more accurately. The adoption of a new drug benefits present and future patients (with cost implications) for as long as the drug is part of clinical practice. Incidence patients and off-patent prices are identified as two key missing features preventing the conventional CEA approach from capturing 1) benefit to future patients and 2) future savings from off-patent prices. The proposed CEA approach incorporates these two features to derive the total lifetime value of an innovative drug (i.e., the value of innovation). The conventional CEA approach tends to underestimate the value of innovative drugs by disregarding the benefit to future patients and savings from off-patent prices. As a result, innovative drugs are underpriced, only allowing manufacturers to capture approximately 15% of the total value of innovation during the patent protection period. In addition to including the incidence population and off-patent price, the alternative approach proposes pricing new drugs by first negotiating the share of value of innovation to be appropriated by the manufacturer (>15%?) and payer (<85%?), in order to then identify the drug price that satisfies this condition. We argue for a modification to the conventional CEA approach that integrates the total lifetime value of innovative drugs into CEA, by taking into account off-patent pricing and future patients. The proposed approach derives a price that allows manufacturers to capture an agreed share of this value, thereby incentivizing innovation, while supporting health-care systems to pursue dynamic allocative efficiency. However, the long-term sustainability of health-care systems must be assessed before this proposal is adopted by policy makers.

The value of innovation under value-based pricing

PubMed Central

Moreno, Santiago G.; Ray, Joshua A.

2016-01-01

Objective The role of cost-effectiveness analysis (CEA) in incentivizing innovation is controversial. Critics of CEA argue that its use for pricing purposes disregards the ‘value of innovation’ reflected in new drug development, whereas supporters of CEA highlight that the value of innovation is already accounted for. Our objective in this article is to outline the limitations of the conventional CEA approach, while proposing an alternative method of evaluation that captures the value of innovation more accurately. Method The adoption of a new drug benefits present and future patients (with cost implications) for as long as the drug is part of clinical practice. Incidence patients and off-patent prices are identified as two key missing features preventing the conventional CEA approach from capturing 1) benefit to future patients and 2) future savings from off-patent prices. The proposed CEA approach incorporates these two features to derive the total lifetime value of an innovative drug (i.e., the value of innovation). Results The conventional CEA approach tends to underestimate the value of innovative drugs by disregarding the benefit to future patients and savings from off-patent prices. As a result, innovative drugs are underpriced, only allowing manufacturers to capture approximately 15% of the total value of innovation during the patent protection period. In addition to including the incidence population and off-patent price, the alternative approach proposes pricing new drugs by first negotiating the share of value of innovation to be appropriated by the manufacturer (>15%?) and payer (<85%?), in order to then identify the drug price that satisfies this condition. Conclusion We argue for a modification to the conventional CEA approach that integrates the total lifetime value of innovative drugs into CEA, by taking into account off-patent pricing and future patients. The proposed approach derives a price that allows manufacturers to capture an agreed share of this value, thereby incentivizing innovation, while supporting health-care systems to pursue dynamic allocative efficiency. However, the long-term sustainability of health-care systems must be assessed before this proposal is adopted by policy makers. PMID:27123192

Defining Elements of Value in Health Care-A Health Economics Approach: An ISPOR Special Task Force Report [3].

PubMed

Lakdawalla, Darius N; Doshi, Jalpa A; Garrison, Louis P; Phelps, Charles E; Basu, Anirban; Danzon, Patricia M

2018-02-01

The third section of our Special Task Force report identifies and defines a series of elements that warrant consideration in value assessments of medical technologies. We aim to broaden the view of what constitutes value in health care and to spur new research on incorporating additional elements of value into cost-effectiveness analysis (CEA). Twelve potential elements of value are considered. Four of them-quality-adjusted life-years, net costs, productivity, and adherence-improving factors-are conventionally included or considered in value assessments. Eight others, which would be more novel in economic assessments, are defined and discussed: reduction in uncertainty, fear of contagion, insurance value, severity of disease, value of hope, real option value, equity, and scientific spillovers. Most of these are theoretically well understood and available for inclusion in value assessments. The two exceptions are equity and scientific spillover effects, which require more theoretical development and consensus. A number of regulatory authorities around the globe have shown interest in some of these novel elements. Augmenting CEA to consider these additional elements would result in a more comprehensive CEA in line with the "impact inventory" of the Second Panel on Cost-Effectiveness in Health and Medicine. Possible approaches for valuation and inclusion of these elements include integrating them as part of a net monetary benefit calculation, including elements as attributes in health state descriptions, or using them as criteria in a multicriteria decision analysis. Further research is needed on how best to measure and include them in decision making. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Epidemiology and economic impact of health care-associated infections and cost-effectiveness of infection control measures at a Thai university hospital.

PubMed

Rattanaumpawan, Pinyo; Thamlikitkul, Visanu

2017-02-01

Data on clinical and economic impact of health care-associated infections (HAIs) from resource limited countries are limited. We aimed to determine epidemiology and economic impact of HAIs and cost-effectiveness of infection prevention and control measures in a resource-limited setting. A retrospective cohort study was conducted among hospitalized patients at Siriraj Hospital, Thailand. Results from the cohort were subsequently used to conduct cost-effective analysis (CEA) to compare the comprehensive implementation of individualized bundling infection control measures (IBICMs) with regular infection control care. From February-May 2013, there were 515 hospitalizations (497 patients) with 7,848 hospitalization days. Cumulative incidence of HAIs was 23.30%, and the incidence rate of HAIs was 18.66 ± 44.19 per 1,000 hospitalization days. Hospital mortality among those with and without HAIs was 33.33% and 20.00%, respectively (P < .001). The adjusted cost attributable to HAIs was $704.72 ± $226.73 (P < .001). CEA identified IBICMs as a non-dominated strategy, with an incremental cost-effectiveness ratio of -$20,444.62 per life saved. HAI is significantly related with higher hospital mortality, longer length of stay, and higher hospitalization costs. IBICMs were confirmed to be cost-effective at Siriraj Hospital. Implementing this intervention could improve care quality and save costs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Quality assessment of published health economic analyses from South America.

PubMed

Machado, Márcio; Iskedjian, Michael; Einarson, Thomas R

2006-05-01

Health economic analyses have become important to healthcare systems worldwide. No studies have previously examined South America's contribution in this area. To survey the literature with the purpose of reviewing, quantifying, and assessing the quality of published South American health economic analyses. A search of MEDLINE (1990-December 2004), EMBASE (1990-December 2004), International Pharmaceutical Abstracts (1990-December 2004), Literatura Latino-Americana e do Caribe em Ciências da Saúde (1982-December 2004), and Sistema de Informacion Esencial en Terapéutica y Salud (1980-December 2004) was completed using the key words cost-effectiveness analysis (CEA), cost-utility analysis (CUA), cost-minimization analysis (CMA), and cost-benefit analysis (CBA); abbreviations CEA, CUA, CMA, and CBA; and all South American country names. Papers were categorized by type and country by 2 independent reviewers. Quality was assessed using a 12 item checklist, characterizing scores as 4 (good), 3 (acceptable), 2 (poor), 1 (unable to judge), and 0 (unacceptable). To be included in our investigation, studies needed to have simultaneously examined costs and outcomes. We retrieved 25 articles; one duplicate article was rejected, leaving 24 (CEA = 15, CBA = 6, CMA = 3; Brazil = 9, Argentina = 5, Colombia = 3, Chile = 2, Ecuador = 2, 1 each from Peru, Uruguay, Venezuela). Variability between raters was less than 0.5 point on overall scores (OS) and less than 1 point on all individual items. Mean OS was 2.6 (SD 1.0, range 1.4-3.8). CBAs scored highest (OS 2.8, SD 0.8), CEAs next (OS 2.7, SD 0.7), and CMAs lowest (OS 2.0, SD 0.5). When scored by type of question, definition of study aim scored highest (OS 3.0, SD 0.8), while ethical issues scored lowest (OS 1.5, SD 0.9). By country, Peru scored highest (mean OS 3.8) and Uruguay had the lowest scores (mean OS 2.2). A nonsignificant time trend was noted for OS (R2 = 0.12; p = 0.104). Quality scores of health economic analyses articles published in South America were rated poor to acceptable and lower than previous research from other countries. Thus, efforts are needed to improve the reporting quality of these analyses in South America. Future research should examine the region's level of expertise and educational opportunities for those in the field of health economics.

How Methodologic Differences Affect Results of Economic Analyses: A Systematic Review of Interferon Gamma Release Assays for the Diagnosis of LTBI

PubMed Central

Oxlade, Olivia; Pinto, Marcia; Trajman, Anete; Menzies, Dick

2013-01-01

Introduction Cost effectiveness analyses (CEA) can provide useful information on how to invest limited funds, however they are less useful if different analysis of the same intervention provide unclear or contradictory results. The objective of our study was to conduct a systematic review of methodologic aspects of CEA that evaluate Interferon Gamma Release Assays (IGRA) for the detection of Latent Tuberculosis Infection (LTBI), in order to understand how differences affect study results. Methods A systematic review of studies was conducted with particular focus on study quality and the variability in inputs used in models used to assess cost-effectiveness. A common decision analysis model of the IGRA versus Tuberculin Skin Test (TST) screening strategy was developed and used to quantify the impact on predicted results of observed differences of model inputs taken from the studies identified. Results Thirteen studies were ultimately included in the review. Several specific methodologic issues were identified across studies, including how study inputs were selected, inconsistencies in the costing approach, the utility of the QALY (Quality Adjusted Life Year) as the effectiveness outcome, and how authors choose to present and interpret study results. When the IGRA versus TST test strategies were compared using our common decision analysis model predicted effectiveness largely overlapped. Implications Many methodologic issues that contribute to inconsistent results and reduced study quality were identified in studies that assessed the cost-effectiveness of the IGRA test. More specific and relevant guidelines are needed in order to help authors standardize modelling approaches, inputs, assumptions and how results are presented and interpreted. PMID:23505412

Cost-effectiveness of Guided Self-help Treatment for Recurrent Binge Eating

PubMed Central

Lynch, Frances L.; Striegel-Moore, Ruth H.; Dickerson, John F.; Perrin, Nancy; DeBar, Lynn; Wilson, G. Terence; Kraemer, Helena C.

2010-01-01

Objective Adoption of effective treatments for recurrent binge-eating disorders depends on the balance of costs and benefits. Using data from a recent randomized controlled trial, we conducted an incremental cost-effectiveness analysis (CEA) of a cognitive behavioral therapy guided self-help intervention (CBT-GSH) to treat recurrent binge eating compared to treatment as usual (TAU). Method Participants were 123 adult members of an HMO (mean age = 37.2, 91.9% female, 96.7% non-Hispanic White) who met criteria for eating disorders involving binge eating as measured by the Eating Disorder Examination (EDE, Fairburn & Cooper, 1993). Participants were randomized either to treatment as usual (TAU) or TAU plus CBT-GSH. The clinical outcomes were binge-free days and quality-adjusted life years (QALYs); total societal cost was estimated using costs to patients and the health plan, and related costs. Results Compared to the group receiving TAU only, those who received TAU + CBT-GSH experienced 25.2 more binge-free days and had lower total societal costs of $427 over 12 months following the intervention (incremental CEA ratio -$20.23 per binge-free day or −$26,847 per QALY). Lower costs in the TAU + CBT-GSH group were due to reduced use of TAU services in that group, resulting in lower net costs for the TAU + CBT group despite the additional cost of CBT-GSH. Conclusions Findings support CBT-GSH dissemination for recurrent binge-eating treatment. PMID:20515208

Evaluation of predictive value of pleural CEA in patients with pleural effusions and histological findings: A prospective study and literature review.

PubMed

Tozzoli, Renato; Basso, Stefano M M; D'Aurizio, Federica; Metus, Paolo; Lumachi, Franco

2016-11-01

Pleural effusion recognizes heterogeneous etiology and pathogenesis and requires invasive diagnostic procedures. Usually, after pleural fluid analysis, 30-50% of patients with malignant pleural effusion exhibit negative pleural cytology, and the sensitivity of image-guided pleural needle-aspiration biopsy ranges between 60% and 70%. With the aim of differentiating between benign (BPE) and malignant (MPE) pleural effusions, several tumor markers have been assayed in the pleural fluid and the majority of studies focus on pleural carcinoembryonic antigen (p-CEA). The aims of this study were to evaluate (i) the diagnostic accuracy of p-CEA of patients with pleural effusions undergoing video-assisted thoracoscopic surgery (VATS) for diagnostic purpose, (ii) the relationship between p-CEA and serum CEA (s-CEA), and (iii) the usefulness of the p-CEA/s-CEA ratio in the diagnosis of malignant pleural effusions (MPE). We prospectively enrolled in the study 134 consecutive patients with pleural effusions, scheduled for having VATS and biopsy. The final diagnosis, based on histopathology of the VATS-guided specimens, was available for all patients. p-CEA and s-CEA was assayed with a chemiluminescence immunoassay method (CLIA), applied on the Maglumi 2000 Plus automated platform (SNIBE, Shenzen, China). The sensitivity and accuracy of p-CEA was significantly higher than that of pleural cytology at the same specificity comparing BPE with MPE and BPE with non-small lung cancer. The sensitivity of p-CEA and PC together reached 100% (BPE vs. NSCLC) and 91.5% (BPE vs. MPE excluding mesothelioma), respectively. The p-CEA measurement in patients with pleural effusion of uncertain etiology is a safe and cost-effective procedure, everywhere easily available, which may help clinicians in selecting patients for further evaluations. An elevated p-CEA level in a patient with pleural effusion and negative pleural cytology suggests the need of more invasive procedure (e.g. VATS-guided biopsies), whilst low p-CEA may support a follow-up. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Multilevel models for estimating incremental net benefits in multinational studies.

PubMed

Grieve, Richard; Nixon, Richard; Thompson, Simon G; Cairns, John

2007-08-01

Multilevel models (MLMs) have been recommended for estimating incremental net benefits (INBs) in multicentre cost-effectiveness analysis (CEA). However, these models have assumed that the INBs are exchangeable and that there is a common variance across all centres. This paper examines the plausibility of these assumptions by comparing various MLMs for estimating the mean INB in a multinational CEA. The results showed that the MLMs that assumed the INBs were exchangeable and had a common variance led to incorrect inferences. The MLMs that included covariates to allow for systematic differences across the centres, and estimated different variances in each centre, made more plausible assumptions, fitted the data better and led to more appropriate inferences. We conclude that the validity of assumptions underlying MLMs used in CEA need to be critically evaluated before reliable conclusions can be drawn. Copyright 2006 John Wiley & Sons, Ltd.

Guidelines for appropriate care: the importance of empirical normative analysis.

PubMed

Berg, M; Meulen, R T; van den Burg, M

2001-01-01

The Royal Dutch Medical Association recently completed a research project aimed at investigating how guidelines for 'appropriate medical care' should be construed. The project took as a starting point that explicit attention should be given to ethical and political considerations in addition to data about costs and effectiveness. In the project, two research groups set out to design guidelines and cost-effectiveness analyses (CEAs) for two circumscribed medical areas (angina pectoris and major depression). Our third group was responsible for the normative analysis. We undertook an explorative, qualitative pilot study of the normative considerations that played a role in constructing the guidelines and CEAs, and simultaneously interviewed specialists about the normative considerations that guided their diagnostic and treatment decisions. Explicating normative considerations, we argue, is important democratically: the issues at stake should not be left to decision analysts and guideline developers to decide. Moreover, it is a necessary condition for a successful implementation of such tools: those who draw upon these tools will only accept them when they can recognize themselves in the considerations implied. Empirical normative analysis, we argue, is a crucial tool in developing guidelines for appropriate medical care.

Comparative cost-effectiveness of policy instruments for reducing the global burden of alcohol, tobacco and illicit drug use.

PubMed

Chisholm, Dan; Doran, Chris; Shibuya, Kenji; Rehm, Jürgen

2006-11-01

Alcohol, tobacco and illicit drug use together pose a formidable challenge to international public health. Building on earlier estimates of the demonstrated burden of alcohol, tobacco and illicit drug use at the global level, this review aims to consider the comparative cost-effectiveness of evidence-based interventions for reducing the global burden of disease from these three risk factors. Although the number of published cost-effectiveness studies in the addictions field is now extensive (reviewed briefly here) there are a series of practical problems in using them for sector-wide decision making, including methodological heterogeneity, differences in analytical reference point and the specificity of findings to a particular context. In response to these limitations, a more generalised form of cost-effectiveness analysis (CEA) is proposed, which enables like-with-like comparisons of the relative efficiency of preventive or individual-based strategies to be made, not only within but also across diseases or their risk factors. The application of generalised CEA to a range of personal and non-personal interventions for reducing the burden of addictive substances is described. While such a development avoids many of the obstacles that have plagued earlier attempts and in so doing opens up new opportunities to address important policy questions, there remain a number of caveats to population-level analysis of this kind, particularly when conducted at the global level. These issues are the subject of the final section of this review.

Non-parametric methods for cost-effectiveness analysis: the central limit theorem and the bootstrap compared.

PubMed

Nixon, Richard M; Wonderling, David; Grieve, Richard D

2010-03-01

Cost-effectiveness analyses (CEA) alongside randomised controlled trials commonly estimate incremental net benefits (INB), with 95% confidence intervals, and compute cost-effectiveness acceptability curves and confidence ellipses. Two alternative non-parametric methods for estimating INB are to apply the central limit theorem (CLT) or to use the non-parametric bootstrap method, although it is unclear which method is preferable. This paper describes the statistical rationale underlying each of these methods and illustrates their application with a trial-based CEA. It compares the sampling uncertainty from using either technique in a Monte Carlo simulation. The experiments are repeated varying the sample size and the skewness of costs in the population. The results showed that, even when data were highly skewed, both methods accurately estimated the true standard errors (SEs) when sample sizes were moderate to large (n>50), and also gave good estimates for small data sets with low skewness. However, when sample sizes were relatively small and the data highly skewed, using the CLT rather than the bootstrap led to slightly more accurate SEs. We conclude that while in general using either method is appropriate, the CLT is easier to implement, and provides SEs that are at least as accurate as the bootstrap. (c) 2009 John Wiley & Sons, Ltd.

Challenges in Cost-Effectiveness Analysis Modelling of HPV Vaccines in Low- and Middle-Income Countries: A Systematic Review and Practice Recommendations.

PubMed

Ekwunife, Obinna I; O'Mahony, James F; Gerber Grote, Andreas; Mosch, Christoph; Paeck, Tatjana; Lhachimi, Stefan K

2017-01-01

Low- and middle-income countries (LMICs) face a number of challenges in implementing cervical cancer prevention programmes that do not apply in high-income countries. This review assessed how context-specific challenges of implementing cervical cancer prevention strategies in LMICs were accounted for in existing cost-effectiveness analysis (CEA) models of human papillomavirus (HPV) vaccination. The databases of MEDLINE, EMBASE, NHS Economic Evaluation Database, EconLit, Web of Science, and the Center for the Evaluation of Value and Risk in Health (CEA) Registry were searched for studies published from 2006 to 2015. A descriptive, narrative, and interpretative synthesis of data was undertaken. Of the 33 studies included in the review, the majority acknowledged cost per vaccinated girl (CVG) (26 studies) and vaccine coverage rate (21 studies) as particular challenges for LMICs, while nine studies identified screening coverage rate as a challenge. Most of the studies estimated CVG as a composite of different cost items. However, the basis for the items within this composite cost was unclear. The majority used an assumption rather than an observed rate to represent screening and vaccination coverage rates. CVG, vaccine coverage and screening coverage were shown by some studies through sensitivity analyses to reverse the conclusions regarding cost-effectiveness, thereby significantly affecting policy recommendations. While many studies recognized aspects of the particular challenges of HPV vaccination in LMICs, greater efforts need to be made in adapting models to account for these challenges. These include adapting costings of HPV vaccine delivery from other countries, learning from the outcomes of cervical cancer screening programmes in the same geographical region, and taking into account the country's previous experience with other vaccination programmes.

The U.S. Forest Service's analysis of cumulative effects to wildlife: A study of legal standards, current practice, and ongoing challenges on a National Forest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Courtney A., E-mail: courtney.schultz@colostate.edu

Cumulative effects analysis (CEA) allows natural resource managers to understand the status of resources in historical context, learn from past management actions, and adapt future activities accordingly. U.S. federal agencies are required to complete CEA as part of environmental impact assessment under the National Environmental Policy Act (NEPA). Past research on CEA as part of NEPA has identified significant deficiencies in CEA practice, suggested methodologies for handling difficult aspects of CEA, and analyzed the rise in litigation over CEA in U.S. courts. This article provides a review of the literature and legal standards related to CEA as it is donemore » under NEPA and then examines current practice on a U.S. National Forest, utilizing qualitative methods in order to provide a detailed understanding of current approaches to CEA. Research objectives were to understand current practice, investigate ongoing challenges, and identify impediments to improvement. Methods included a systematic review of a set of NEPA documents and semi-structured interviews with practitioners, scientists, and members of the public. Findings indicate that the primary challenges associated with CEA include: issues of both geographic and temporal scale of analysis, confusion over the purpose of the requirement, the lack of monitoring data, and problems coordinating and disseminating data. Improved monitoring strategies and programmatic analyses could support improved CEA practice.« less

Impact of a Value-based Formulary on Medication Utilization, Health Services Utilization, and Expenditures.

PubMed

Yeung, Kai; Basu, Anirban; Hansen, Ryan N; Watkins, John B; Sullivan, Sean D

2017-02-01

Value-based benefit design has been suggested as an effective approach to managing the high cost of pharmaceuticals in health insurance markets. Premera Blue Cross, a large regional health plan, implemented a value-based formulary (VBF) for pharmaceuticals in 2010 that explicitly used cost-effectiveness analysis (CEA) to inform medication copayments. The objective of the study was to determine the impact of the VBF. Interrupted time series of employer-sponsored plans from 2006 to 2013. Intervention group: 5235 beneficiaries exposed to the VBF. 11,171 beneficiaries in plans without any changes in pharmacy benefits. The VBF-assigned medications with lower value (estimated by CEA) to higher copayment tiers and assigned medications with higher value to lower copayment tiers. Primary outcome was medication expenditures from member, health plan, and member plus health plan perspectives. Secondary outcomes were medication utilization, emergency department visits, hospitalizations, office visits, and nonmedication expenditures. In the intervention group after VBF implementation, member medication expenditures increased by $2 per member per month (PMPM) [95% confidence interval (CI), $1-$3] or 9%, whereas health plan medication expenditures decreased by $10 PMPM (CI, $18-$2) or 16%, resulting in a net decrease of $8 PMPM (CI, $15-$2) or 10%, which translates to a net savings of $1.1 million. Utilization of medications moved into lower copayment tiers increased by 1.95 days' supply (CI, 1.29-2.62) or 17%. Total medication utilization, health services utilization, and nonmedication expenditures did not change. Cost-sharing informed by CEA reduced overall medication expenditures without negatively impacting medication utilization, health services utilization, or nonmedication expenditures.

A participatory approach for selecting cost-effective measures in the WFD context: the Mar Menor (SE Spain).

PubMed

Perni, Angel; Martínez-Paz, José M

2013-08-01

Achieving a good ecological status in water bodies by 2015 is one of the objectives established in the European Water Framework Directive. Cost-effective analysis (CEA) has been applied for selecting measures to achieve this goal, but this appraisal technique requires technical and economic information that is not always available. In addition, there are often local insights that can only be identified by engaging multiple stakeholders in a participatory process. This paper proposes to combine CEA with the active involvement of stakeholders for selecting cost-effective measures. This approach has been applied to the case study of one of the main coastal lagoons in the European Mediterranean Sea, the Mar Menor, which presents eutrophication problems. Firstly, face-to-face interviews were conducted to estimate relative effectiveness and relative impacts of a set of measures by means of the pairwise comparison technique. Secondly, relative effectiveness was used to estimate cost-effectiveness ratios. The most cost-effective measures were the restoration of watercourses that drain into the lagoon and the treatment of polluted groundwater. Although in general the stakeholders approved the former, most of them stated that the latter involved some uncertainties, which must be addressed before implementing it. Stakeholders pointed out that the PoM would have a positive impact not only on water quality, but also on fishing, agriculture and tourism in the area. This approach can be useful to evaluate other programmes, plans or projects related to other European environmental strategies. Copyright © 2013 Elsevier B.V. All rights reserved.

Mercury Information Clearinghouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chad A. Wocken; Michael J. Holmes; Dennis L. Laudal

2006-03-31

The Canadian Electricity Association (CEA) identified a need and contracted the Energy & Environmental Research Center (EERC) to create and maintain an information clearinghouse on global research and development activities related to mercury emissions from coal-fired electric utilities. With the support of CEA, the Center for Air Toxic Metals{reg_sign} (CATM{reg_sign}) Affiliates, and the U.S. Department of Energy (DOE), the EERC developed comprehensive quarterly information updates that provide a detailed assessment of developments in the various areas of mercury monitoring, control, policy, and research. A total of eight topical reports were completed and are summarized and updated in this final CEAmore » quarterly report. The original quarterly reports can be viewed at the CEA Web site (www.ceamercuryprogram.ca). In addition to a comprehensive update of previous mercury-related topics, a review of results from the CEA Mercury Program is provided. Members of Canada's coal-fired electricity generation sector (ATCO Power, EPCOR, Manitoba Hydro, New Brunswick Power, Nova Scotia Power Inc., Ontario Power Generation, SaskPower, and TransAlta) and CEA, have compiled an extensive database of information from stack-, coal-, and ash-sampling activities. Data from this effort are also available at the CEA Web site and have provided critical information for establishing and reviewing a mercury standard for Canada that is protective of environment and public health and is cost-effective. Specific goals outlined for the CEA mercury program included the following: (1) Improve emission inventories and develop management options through an intensive 2-year coal-, ash-, and stack-sampling program; (2) Promote effective stack testing through the development of guidance material and the support of on-site training on the Ontario Hydro method for employees, government representatives, and contractors on an as-needed basis; (3) Strengthen laboratory analytical capabilities through analysis and quality assurance programs; and (4) Create and maintain an information clearinghouse to ensure that all parties can keep informed on global mercury research and development activities.« less

Vaccinating Italian infants with a new multicomponent vaccine (Bexsero®) against meningococcal B disease: A cost-effectiveness analysis.

PubMed

Gasparini, Roberto; Landa, Paolo; Amicizia, Daniela; Icardi, Giancarlo; Ricciardi, Walter; de Waure, Chiara; Tanfani, Elena; Bonanni, Paolo; Lucioni, Carlo; Testi, Angela; Panatto, Donatella

2016-08-02

The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinating Italian infants less than 1 y of age with Bexsero®, as opposed to non-vaccination. The analysis was carried out by means of Excel Version 2011 and the TreeAge Pro® software Version 2012. Two basal scenarios that differed in terms of disease incidence (official and estimated data to correct for underreporting) were considered. In the basal scenarios, we considered a primary vaccination cycle with 4 doses (at 2, 4, 6 and 12 months of age) and 1 booster dose at the age of 11 y, the societal perspective and no cost for death. Sensitivity analyses were carried out in which crucial variables were changed over probable ranges. In Italy, on the basis of official data on disease incidence, vaccination with Bexsero® could prevent 82.97 cases and 5.61 deaths in each birth cohort, while these figures proved to be three times higher on considering the estimated incidence. The results of the CEA showed that the Incremental Cost Effectiveness Ratio (ICER) per QALY was €109,762 in the basal scenario if official data on disease incidence are considered and €26,599 if estimated data are considered. The tornado diagram indicated that the most influential factor on ICER was the incidence of disease. The probability of sequelae, the cost of the vaccine and vaccine effectiveness also had an impact. Our results suggest that vaccinating infants in Italy with Bexsero® has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable.

Vaccinating Italian infants with a new multicomponent vaccine (Bexsero®) against meningococcal B disease: A cost-effectiveness analysis

PubMed Central

Gasparini, Roberto; Landa, Paolo; Amicizia, Daniela; Icardi, Giancarlo; Ricciardi, Walter; de Waure, Chiara; Tanfani, Elena; Bonanni, Paolo; Lucioni, Carlo; Testi, Angela; Panatto, Donatella

2016-01-01

ABSTRACT The European Medicines Agency has approved a multicomponent serogroup B meningococcal vaccine (Bexsero®) for use in individuals of 2 months of age and older. A cost-effectiveness analysis (CEA) from the societal and Italian National Health Service perspectives was performed in order to evaluate the impact of vaccinating Italian infants less than 1 y of age with Bexsero®, as opposed to non-vaccination. The analysis was carried out by means of Excel Version 2011 and the TreeAge Pro® software Version 2012. Two basal scenarios that differed in terms of disease incidence (official and estimated data to correct for underreporting) were considered. In the basal scenarios, we considered a primary vaccination cycle with 4 doses (at 2, 4, 6 and 12 months of age) and 1 booster dose at the age of 11 y, the societal perspective and no cost for death. Sensitivity analyses were carried out in which crucial variables were changed over probable ranges. In Italy, on the basis of official data on disease incidence, vaccination with Bexsero® could prevent 82.97 cases and 5.61 deaths in each birth cohort, while these figures proved to be three times higher on considering the estimated incidence. The results of the CEA showed that the Incremental Cost Effectiveness Ratio (ICER) per QALY was €109,762 in the basal scenario if official data on disease incidence are considered and €26,599 if estimated data are considered. The tornado diagram indicated that the most influential factor on ICER was the incidence of disease. The probability of sequelae, the cost of the vaccine and vaccine effectiveness also had an impact. Our results suggest that vaccinating infants in Italy with Bexsero® has the ability to significantly reduce meningococcal disease and, if the probable underestimation of disease incidence is considered, routine vaccination is advisable. PMID:27163398

Evaluation of the ASCO Value Framework for Anticancer Drugs at an Academic Medical Center.

PubMed

Wilson, Leslie; Lin, Tracy; Wang, Ling; Patel, Tanuja; Tran, Denise; Kim, Sarah; Dacey, Katie; Yuen, Courtney; Kroon, Lisa; Brodowy, Bret; Rodondi, Kevin

2017-02-01

Anticancer drug prices have increased by an average of 12% each year from 1996 to 2014. A major concern is that the increasing cost and responsibility of evaluating treatment options are being shifted to patients. This research compared 2 value-based pricing models that were being considered for use at the University of California, San Francisco (UCSF) Medical Center to address the growing burden of high-cost cancer drugs while improving patient-centered care. The Medication Outcomes Center (MOC) in the Department of Clinical Pharmacy, University of California, San Francisco (UCSF), School of Pharmacy focuses on assessing the value of medication-related health care interventions and disseminating findings to the UCSF Medical Center. The High Cost Oncology Drug Initiative at the MOC aims to assess and adopt tools for the critical assessment and amelioration of high-cost cancer drugs. The American Society of Clinical Oncology (ASCO) Value Framework (2016 update) and a cost-effectiveness analysis (CEA) framework were identified as potential tools for adoption. To assess 1 prominent value framework, the study investigators (a) asked 8 clinicians to complete the ASCO Value Framework for 11 anticancer medications selected by the MOC; (b) reviewed CEAs assessing the drugs; (c) generated descriptive statistics; and (d) analyzed inter-rater reliability, convergence validity, and ranking consistency. On the scale of -20 to 180, the mean ASCO net health benefit (NHB) total score across 11 drugs ranged from 7.6 (SD = 7.8) to 53 (SD = 9.8). The Kappa coefficient (κ) for NHB scores across raters was 0.11, which is categorized as "slightly reliable." The combined κ score was 0.22, which is interpreted as low to fair inter-rater reliability. Convergent validity indicates that the correlation between NHB scores and CEA-based incremental cost-effectiveness ratios (ICERs) was low (-0.215). Ranking of ICERs, ASCO scores, and wholesale acquisition costs indicated different results between frameworks. The ASCO Value Framework requires further specificity before use in a clinical setting, since it currently results in low inter-rater reliability and validity. Furthermore, ASCO scores were unable to discriminate between drugs providing the most and least value. The evaluation provides specific areas of weakness that can be addressed in future updates of the ASCO framework to improve usability. Meanwhile, the UCSF Medical Center should rely on CEAs, which are highly accessible for the highlighted cancer drugs. The MOC role can include summarizing and disseminating available CEA studies for interpretation by clinicians and financial counselors around drug value. Funding for this research was contributed by the University of California, San Francisco, Medical Center Campus Strategic Initiative Program. The authors have no conflicts of interest to disclose. Study concept and design were contributed primarily by Wilson, along with Wang and Patel. Kim, Dacey, and Yuen collected the data, and data interpretation was performed by Wilson and Lin. The manuscript was written by Wilson, Lin, Wang, and Tran and revised by Lin, Redondi, Brodowy, and Kroon.

Cost-effectiveness of febrile neutropenia prevention with primary versus secondary G-CSF prophylaxis for adjuvant chemotherapy in breast cancer: a systematic review.

PubMed

Younis, T; Rayson, D; Jovanovic, S; Skedgel, C

2016-10-01

The adoption of primary (PP) versus secondary prophylaxis (SP) of febrile neutropenia (FN), with granulocyte colony-stimulating factors (G-CSF), for adjuvant chemotherapy (AC) regimens in breast cancer (BC) could be affected by its "value for money". This systematic review examined (i) cost-effectiveness of PP versus SP, (ii) FN threshold at which PP is cost-effective including the guidelines 20 % threshold and (iii) potential impact of G-CSF efficacy assumptions on outcomes. The systematic review identified all cost-effectiveness/cost-utility analyses (CEA/CUA) involving PP versus SP G-CSF for AC in BC that met predefined inclusion/exclusion criteria. Five relevant CEA/CUA were identified. These CEA/CUA examined different AC regimens (TAC = 2; FEC-D = 1; TC = 2) and G-CSF formulations (filgrastim "F" = 4; pegfilgrastim "P" = 4) with varying baseline FN-risk (range 22-32 %), mortality (range 1.4-6.0 %) and utility (range 0.33-0.47). The potential G-CSF benefit, including FN risk reduction with P versus F, varied among models. Overall, relative to SP, PP was not associated with good value for money, as per commonly utilized CE thresholds, at the baseline FN rates examined, including the consensus 20 % FN threshold, in most of these studies. The value for money associated with PP versus SP was primarily dependent on G-CSF benefit assumptions including reduced FN mortality and improved BC survival. PP G-CSF for FN prevention in BC patients undergoing AC may not be a cost-effective strategy at the guidelines 20 % FN threshold.

Positive and cost-effectiveness effect of spa therapy on the resumption of occupational and non-occupational activities in women in breast cancer remission: a French multicentre randomised controlled trial.

PubMed

Mourgues, Charline; Gerbaud, Laurent; Leger, Stéphanie; Auclair, Candy; Peyrol, Fleur; Blanquet, Marie; Kwiatkowski, Fabrice; Leger-Enreille, Anne; Bignon, Yves-Jean

2014-10-01

The main aim was to assess the effects of a spa treatment on the resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. A cost-effectiveness analysis (CEA) was also performed. A multicentre randomised controlled trial was carried out between 2008 and 2010 in the University Hospital of Auvergne and two private hospitals in Clermont-Ferrand, France. Eligible patients were women in complete breast cancer remission without contraindication for physical activities or cognitive disorders and a body mass index between 18.5 and 40 kg/m(2). The intervention group underwent spa treatment combined with consultation with dietician whereas the control underwent consultations with the dietician only. Of the 181 patients randomised, 92 and 89 were included in the intervention and the control groups, respectively. The CEA involved 90 patients, 42 from the intervention group and 48 from the control group. The main results showed a higher rate of resumption of occupational activities in the intervention group (p = 0.0025) and a positive effect of the intervention on the women's ability to perform occupational activities 12 months after the beginning of the study (p = 0.0014), and on their ability to perform family activities (p = 0.033). The stay in a thermal centre was cost-effective at 12 months. Spa treatment is a cost-effective strategy to improve resumption of occupational and non-occupational activities and the abilities of women in breast cancer remission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Applications of CELSS technology to controlled environment agriculture

NASA Technical Reports Server (NTRS)

Bates, Maynard E.; Bubenheim, David L.

1991-01-01

Controlled environment agriculture (CEA) is defined as the use of environmental manipulation for the commercial production of organisms, whether plants or animals. While many of the technologies necessary for aquaculture systems in North America is nevertheless doubling approximately every five years. Economic, cultural, and environmental pressures all favor CEA over field production for many non-commodity agricultural crops. Many countries around the world are already dependent on CEA for much of their fresh food. Controlled ecological life support systems (CELSS), under development at ARC, KSC, and JSC expand the concept of CEA to the extent that all human requirements for food, oxygen, and water will be provided regenerated by processing of waste streams to supply plant inputs. The CELSS will likely contain plants, humans, possibly other animals, microorganisms and physically and chemical processors. In effect, NASA will create engineered ecosystems. In the process of developing the technology for CELSS, NASA will develop information and technology which will be applied to improving the efficiency, reliability, and cost effectiveness for CEA, improving its resources recycling capabilities, and lessening its environmental impact to negligible levels.

Impact of a Value-Based Formulary on Medication Utilization, Health Services Utilization, and Expenditures

PubMed Central

Yeung, Kai; Basu, Anirban; Hansen, Ryan N.; Watkins, John B.; Sullivan, Sean D.

2016-01-01

Background Value-based benefit design has been suggested as an effective approach to managing the high cost of pharmaceuticals in health insurance markets. Premera Blue Cross, a large regional health plan, implemented a Value-Based Formulary (VBF) for pharmaceuticals in 2010 that explicitly used cost-effectiveness analysis (CEA) to inform medication copayments. Objective To determine the impact of the VBF. Design Interrupted time-series of employer-sponsored plans from 2006 to 2013. Subjects Intervention group: 5,235 beneficiaries exposed to the VBF. Control group: 11,171 beneficiaries in plans without any changes in pharmacy benefits. Intervention The VBF assigned medications with lower value (estimated by CEA) to higher copayment tiers and assigned medications with higher value to lower copayment tiers. Measures Primary outcome was medication expenditures from member, health plan, and member plus health plan perspectives. Secondary outcomes were medication utilization, emergency department visits, hospitalizations, office visits, and non-medication expenditures. Results In the intervention group after VBF implementation, member medication expenditures increased by $2 per member per month (PMPM) (95% CI, $1 to $3) or 9%, while health plan medication expenditures decreased by $10 PMPM (CI, $18 to $2) or 16%, resulting in a net decrease of $8 PMPM (CI, $15 to $2) or 10%, which translates to a net savings of $1.1 million. Utilization of medications moved into lower copayment tiers increased by 1.95 days’ supply (CI, 1.29 to 2.62) or 17%. Total medication utilization, health services utilization and non-medication expenditures did not change. Conclusions Cost-sharing informed by CEA reduced overall medication expenditures without negatively impacting medication utilization, health services utilization or non-medication expenditures. PMID:27579915

What can economics add to health technology assessment? Please not just another cost-effectiveness analysis!

PubMed

Bridges, John Fp

2006-02-01

Evidence based medicine is not only important for clinical practice, but national governments have embraced it through health technology assessment (HTA). HTA combines data from randomized controlled trials (RCT) and observational studies with an economic component (among other issues). HTA, however, is not taking full advantage of economics. This paper presents five areas in which economics may improve not only HTA, but the RCT methods that underpin it. HTA needs to live up to its original agenda of being a interdisciplinary field and draw methods not just from biostatistics, but from a range of discipline, including economics. By focusing only on cost effectiveness analysis (CEA), however, we go nowhere close to fulfilling this potential.

A pilot study to evaluate the feasibility of using willingness to pay as a measure of value in cancer supportive care: an assessment of amifostine cytoprotection.

PubMed

Dranitsaris, G

1997-11-01

The most commonly used method for pharmacoeconomic studies has been the cost-effectiveness analysis (CEA), where the outcome is expressed as an incremental cost per unit of effectiveness (e.g. quality-adjusted life years). Although CEA is a valuable tool for identifying therapies that are more effective and less expensive, deficiencies develop when a given treatment is both more expensive and more effective. An alternative that has not been investigated in the oncology setting is the willingness-to-pay (WTP) method. In this pilot study, a WTP strategy was utilized to estimate the value that the Canadian tax-paying public puts on amifostine, a new cytoprotective agent that reduces the risk of chemotherapy-induced toxicity. The method of WTP was used within the framework of a classical cost-benefit analysis to estimate the net cost or benefit of prophylactic amifostine in patients with ovarian cancer who were receiving chemotherapy. This included direct costs for amifostine administration and hospital savings secondary to the reduced incidence of antineoplastic toxicity. A random sample of 50 Canadian tax-payers were interviewed to ascertain their maximum WTP for the new drug. The WTP survey instrument was simple to administer and easily understood by participants. Respondents stated that they would be willing to pay an average of $Can3,476 (95% confidence interval = $Can2,275 to $Can4,676) as an income tax increase to be paid over their lifetime for the value offered by the product. The benefit was then subtracted from the overall cost of amifostine ($Can3,826). This produced a net cost of $Can350 per patient (95% confidence interval = -$Can850 to $Can1,551), suggesting a situation of cost neutrality. WTP as a measure of value for oncology products is feasible and should be considered for future economic evaluations. The strategy is currently being used at this institution to determine the net societal cost or benefit of other cancer supportive care therapies, such as epoetin-alfa.

Cost-effectiveness of additional blood screening tests in the Netherlands.

PubMed

Borkent-Raven, Barbara A; Janssen, Mart P; van der Poel, Cees L; Bonsel, Gouke J; van Hout, Ben A

2012-03-01

During the past decade, blood screening tests such as triplex nucleic acid amplification testing (NAT) and human T-cell lymphotropic virus type I or I (HTLV-I/II) antibody testing were added to existing serologic testing for hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV). In some low-prevalence regions these additional tests yielded disputable benefits that can be valuated by cost-effectiveness analyses (CEAs). CEAs are used to support decision making on implementation of medical technology. We present CEAs of selected additional screening tests that are not uniformly implemented in the EU. Cost-effectiveness was analyzed of: 1) HBV, HCV, and HIV triplex NAT in addition to serologic testing; 2) HTLV-I/II antibody test for all donors, for first-time donors only, and for pediatric recipients only; and 3) hepatitis A virus (HAV) for all donations. Disease progression of the studied viral infections was described in five Markov models. In the Netherlands, the incremental cost-effectiveness ratio (ICER) of triplex NAT is €5.20 million per quality-adjusted life-year (QALY) for testing minipools of six donation samples and €4.65 million/QALY for individual donation testing. The ICER for anti-HTLV-I/II is €45.2 million/QALY if testing all donations, €2.23 million/QALY if testing new donors only, and €27.0 million/QALY if testing blood products for pediatric patients only. The ICER of HAV NAT is €18.6 million/QALY. The resulting ICERs are very high, especially when compared to other health care interventions. Nevertheless, these screening tests are implemented in the Netherlands and elsewhere. Policy makers should reflect more explicit on the acceptability of costs and effects whenever additional blood screening tests are implemented. © 2011 American Association of Blood Banks.

The value and economic analysis of routine postoperative carotid duplex ultrasound surveillance after carotid endarterectomy.

PubMed

AbuRahma, Ali F; Srivastava, Mohit; AbuRahma, Zachary; Jackson, Will; Mousa, Albeir; Stone, Patrick A; Dean, L Scott; Green, Jason

2015-08-01

Several studies have reported on the role of postoperative duplex ultrasound surveillance after carotid endarterectomy (CEA) with varying results. Most of these studies had a small sample size or did not analyze cost-effectiveness. We analyzed 489 of 501 CEA patients with patch closure. All patients had immediate postoperative duplex ultrasound examination and were routinely followed up both clinically and with duplex ultrasound at regular intervals of 1 month, 6 months, 12 months, and every 12 months thereafter. A Kaplan-Meier analysis was used to estimate the rate of ≥50% and ≥80% post-CEA restenosis over time and the time frame of progression from normal to ≥50% or ≥80% restenosis. The cost of post-CEA duplex surveillance was also estimated. Overall, 489 patients with a mean age of 68.5 years were analyzed. Ten of these had residual postoperative ≥50% stenosis, and 37 did not undergo a second duplex ultrasound examination and therefore were not included in the final analysis. The mean follow-up was 20.4 months (range, 1-63 months), with a mean number of duplex ultrasound examinations of 3.6 (range, 1-7). Eleven of 397 patients (2.8%) with a normal finding on immediate postoperative duplex ultrasound vs 4 of 45 (8.9%) with mild stenosis on immediate postoperative duplex ultrasound progressed to ≥50% restenosis (P = .055). Overall, 15 patients (3.1%) had ≥50% restenosis, 9 with 50% to <80% and 4 with 80% to 99% (2 of these had carotid artery stenting reintervention), and 2 had late carotid occlusion. All of these were asymptomatic, except for one who had a transient ischemic attack. The mean time to ≥50% to <80% restenosis was 14.7 months vs 19.8 months for ≥80% restenosis after the CEA. Freedom from restenosis rates were 98%, 96%, 94%, 94%, and 94% for ≥50% restenosis and 99%, 98%, 97%, 97%, and 97% for ≥80% restenosis at 1 year, 2 years, 3 years, 4 years, and 5 years, respectively. Freedom from myocardial infarction, stroke, and deaths was not significantly different between patients with and without restenosis (100%, 93%, 83%, and 83% vs 94%, 91%, 86%, and 79% at 1 year, 2 years, 3 years, and 4 years, respectively; P = .951). The estimated charge of this surveillance was 3.6 × 489 (number of CEAs) × $800 (charge for carotid duplex ultrasound), which equals $1,408,320, to detect only four patients with ≥80% to 99% restenosis who may have been potential candidates for reintervention. This study shows that the value of routine postoperative duplex ultrasound surveillance after CEA with patch closure may be limited, particularly if the finding on immediate postoperative duplex ultrasound is normal or shows minimal disease. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Markov modeling and discrete event simulation in health care: a systematic comparison.

PubMed

Standfield, Lachlan; Comans, Tracy; Scuffham, Paul

2014-04-01

The aim of this study was to assess if the use of Markov modeling (MM) or discrete event simulation (DES) for cost-effectiveness analysis (CEA) may alter healthcare resource allocation decisions. A systematic literature search and review of empirical and non-empirical studies comparing MM and DES techniques used in the CEA of healthcare technologies was conducted. Twenty-two pertinent publications were identified. Two publications compared MM and DES models empirically, one presented a conceptual DES and MM, two described a DES consensus guideline, and seventeen drew comparisons between MM and DES through the authors' experience. The primary advantages described for DES over MM were the ability to model queuing for limited resources, capture individual patient histories, accommodate complexity and uncertainty, represent time flexibly, model competing risks, and accommodate multiple events simultaneously. The disadvantages of DES over MM were the potential for model overspecification, increased data requirements, specialized expensive software, and increased model development, validation, and computational time. Where individual patient history is an important driver of future events an individual patient simulation technique like DES may be preferred over MM. Where supply shortages, subsequent queuing, and diversion of patients through other pathways in the healthcare system are likely to be drivers of cost-effectiveness, DES modeling methods may provide decision makers with more accurate information on which to base resource allocation decisions. Where these are not major features of the cost-effectiveness question, MM remains an efficient, easily validated, parsimonious, and accurate method of determining the cost-effectiveness of new healthcare interventions.

Health Technology Assessment: Global Advocacy and Local Realities Comment on "Priority Setting for Universal Health Coverage: We Need Evidence-Informed Deliberative Processes, Not Just More Evidence on Cost-Effectiveness".

PubMed

Chalkidou, Kalipso; Li, Ryan; Culyer, Anthony J; Glassman, Amanda; Hofman, Karen J; Teerawattananon, Yot

2016-08-29

Cost-effectiveness analysis (CEA) can help countries attain and sustain universal health coverage (UHC), as long as it is context-specific and considered within deliberative processes at the country level. Institutionalising robust deliberative processes requires significant time and resources, however, and countries often begin by demanding evidence (including local CEA evidence as well as evidence about local values), whilst striving to strengthen the governance structures and technical capacities with which to generate, consider and act on such evidence. In low- and middle-income countries (LMICs), such capacities could be developed initially around a small technical unit in the health ministry or health insurer. The role of networks, development partners, and global norm setting organisations is crucial in supporting the necessary capacities. © 2017 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How have systematic priority setting approaches influenced policy making? A synthesis of the current literature.

PubMed

Kapiriri, Lydia; Razavi, Donya

2017-09-01

There is a growing body of literature on systematic approaches to healthcare priority setting from various countries and different levels of decision making. This paper synthesizes the current literature in order to assess the extent to which program budgeting and marginal analysis (PBMA), burden of disease & cost-effectiveness analysis (BOD/CEA), multi-criteria decision analysis (MCDA), and accountability for reasonableness (A4R), are reported to have been institutionalized and influenced policy making and practice. We searched for English language publications on health care priority setting approaches (2000-2017). Our sources of literature included PubMed and Ovid databases (including Embase, Global Health, Medline, PsycINFO, EconLit). Of the four approaches PBMA and A4R were commonly applied in high income countries while BOD/CEA was exclusively applied in low income countries. PBMA and BOD/CEA were most commonly reported to have influenced policy making. The explanations for limited adoption of an approach were related to its complexity, poor policy maker understanding and resource requirements. While systematic approaches have the potential to improve healthcare priority setting; most have not been adopted in routine policy making. The identified barriers call for sustained knowledge exchange between researchers and policy-makers and development of practical guidelines to ensure that these frameworks are more accessible, applicable and sustainable in informing policy making. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost-effectiveness analysis of a continuing care intervention for cocaine-dependent adults.

PubMed

McCollister, Kathryn; Yang, Xuan; McKay, James R

2016-01-01

The study conducts a cost-effectiveness analysis (CEA) of a continuing care Telephone Monitoring and Counseling (TMC) intervention for adults diagnosed with cocaine dependence. Participants were randomly assigned to a control condition of intensive outpatient treatment only (treatment-as-usual, or TAU; N=108), or to one of two treatment conditions featuring TMC (N=106) and TMC plus incentives (TMC-plus; N=107). Follow-up assessments were conducted over a 2-year period. Intervention and client costs were collected with the program and client versions of the Drug Abuse Treatment Cost Analysis Program (DATCAP). Effectiveness was measured as the number of days abstinent during follow-up. Secondary analyses consider alternative measures of effectiveness and the reduced societal costs of physical and mental health problems and criminal justice involvement. From the societal perspective, TMC dominates both TAU and TMC-plus as a cost-effective and cost-saving intervention. Results varied by substance-using status, however, with the subgroup of participants in TMC-plus that were using drugs at intake and early in treatment having the greatest number of days of abstinence and generating similar savings during follow-up than the TMC subgroup using drugs at intake. Telephone monitoring and counseling appears to be a cost-effective and potentially cost-saving strategy for reducing substance use among chronic substance users. Providing client incentives added to total intervention costs but did not improve overall effectiveness. Clinical Trials.gov Number: NCT00685659. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The use of cultured epithelial autograft in the treatment of major burn injuries: a critical review of the literature.

PubMed

Wood, F M; Kolybaba, M L; Allen, P

2006-06-01

The need to achieve rapid wound closure in patients with massive burns and limited skin donor sites led to the investigation of in vitro cellular expansion of keratinocytes. The use of cultured epithelial autografts (CEA) was first reported in the treatment of major burns in 1981. Since that time, support for the use of CEA has varied, ranging from 'a useful agent' to having 'no demonstrable effect on the outcome of extensively burned patients'. This critical review of the literature examines issues associated with the use of CEA and the introduction of the technology into clinical practice. The factors potentially limiting the use of cultured CEA are the time necessary to culture CEA sheets, the reliability of 'take', vulnerability of grafts on the newly healed surface, long-term durability and the cost implications of such treatment. The available literature was located and critically evaluated using the Australian National Health and Medical Research Council Guidelines. In the identified literature, the level of evidence to support the use of CEA in major burn injures is limited and often restricted to case studies and case series with no Level 1 evidence currently available. The main question arising 'Does CEA have a role in the treatment of major burns?' has proven difficult to answer due to the wide variation in both the quality of study design and the findings. At best, the literature review has highlighted areas of concern that have hindered the successful use of CEA. Our review critically evaluates the use of CEA and explores the advances in techniques towards attempting to improve reliable clinical implementation of CEA. The need for higher level research into the use of CEA is emphasised by this review.

The effect of cost construction based on either DRG or ICD-9 codes or risk group stratification on the resulting cost-effectiveness ratios.

PubMed

Chumney, Elinor C G; Biddle, Andrea K; Simpson, Kit N; Weinberger, Morris; Magruder, Kathryn M; Zelman, William N

2004-01-01

As cost-effectiveness analyses (CEAs) are increasingly used to inform policy decisions, there is a need for more information on how different cost determination methods affect cost estimates and the degree to which the resulting cost-effectiveness ratios (CERs) may be affected. The lack of specificity of diagnosis-related groups (DRGs) could mean that they are ill-suited for costing applications in CEAs. Yet, the implications of using International Classification of Diseases-9th edition (ICD-9) codes or a form of disease-specific risk group stratification instead of DRGs has yet to be clearly documented. To demonstrate the implications of different disease coding mechanisms on costs and the magnitude of error that could be introduced in head-to-head comparisons of resulting CERs. We based our analyses on a previously published Markov model for HIV/AIDS therapies. We used the Healthcare Cost and Utilisation Project Nationwide Inpatient Sample (HCUP-NIS) data release 6, which contains all-payer data on hospital inpatient stays from selected states. We added costs for the mean number of hospitalisations, derived from analyses based on either DRG or ICD-9 codes or risk group stratification cost weights, to the standard outpatient and prescription drug costs to yield an estimate of total charges for each AIDS-defining illness (ADI). Finally, we estimated the Markov model three times with the appropriate ADI cost weights to obtain CERs specific to the use of either DRG or ICD-9 codes or risk group. Contrary to expectations, we found that the choice of coding/grouping assumptions that are disease-specific by either DRG codes, ICD-9 codes or risk group resulted in very similar CER estimates for highly active antiretroviral therapy. The large variations in the specific ADI cost weights across the three different coding approaches was especially interesting. However, because no one approach produced consistently higher estimates than the others, the Markov model's weighted cost per event and resulting CERs were remarkably close in value to one another. Although DRG codes are based on broader categories and contain less information than ICD-9 codes, in practice the choice of whether to use DRGs or ICD-9 codes may have little effect on the CEA results in heterogeneous conditions such as HIV/AIDS.

Cost effectiveness of pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous stem cell transplantation in patients with lymphoma and myeloma: an economic evaluation of the PALM Trial.

PubMed

Perrier, Lionel; Lefranc, Anne; Pérol, David; Quittet, Philippe; Schmidt-Tanguy, Aline; Siani, Carole; de Peretti, Christian; Favier, Bertrand; Biron, Pierre; Moreau, Philippe; Bay, Jacques Olivier; Lissandre, Séverine; Jardin, Fabrice; Espinouse, Daniel; Sebban, Catherine

2013-04-01

Use of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) filgrastim accelerates neutrophil recovery following myelosuppressive chemotherapy. Since filgrastim requires multiple daily administrations, forms of rhG-CSF with a longer half life, including pegfilgrastim, have been developed. Pegfilgrastim is safe and effective in supporting neutrophil recovery and reducing febrile neutropenia after conventional chemotherapy. Pegfilgrastim has also been successfully used to support patients undergoing peripheral blood stem cell (PBSC) transplantation for haematological malignancies. To our knowledge, no cost-effectiveness analysis (CEA) of pegfilgrastim in this setting has been published yet. We undertook a CEA to compare a single injection of pegfilgrastim versus repeated administrations of filgrastim in patients who had undergone PBSC transplantation for lymphoma or myeloma. The CEA was set in France and covered a period of 100 ± 10 days from transplant. The CEA was designed as part of an open-label, multicentre, randomized phase II trial. Costs were assessed from the hospital's point of view and are expressed in 2009 euros. Costs computation focused on inpatient, outpatient, and home care. Costs in the two arms of the study were compared using the Mann-Whitney test. When differences were statistically significant, multiple regression analyses were performed in order to identify cost drivers. Incremental cost-effectiveness ratios (ICER) were calculated for the major endpoints of the trial; i.e., duration of febrile neutropenia (absolute neutrophil count [ANC] <0.5 × 10(9)/L and temperature ≥38 °C), duration of neutropenia (ANC <1.0 × 10(9)/L and ANC <0.5 × 10(9)/L), duration of thrombopenia (platelets <50 × 10(9)/L and <20 × 10(9)/L), and days with a temperature ≥38 °C). Uncertainty around the ICER was captured by a probabilistic analysis using a non-parametric bootstrap method. 151 patients were enrolled at ten French centres from October 2008 to September 2009. The mean total cost in the pegfilgrastim arm of the study (n = 74) was 25,024 (SD 9,945). That in the filgrastim arm (n = 76) was 28,700 (SD 20,597). Pegfilgrastim strictly dominated filgrastim for days of febrile neutropenia avoided, days of neutropenia (ANC <1.0 × 10(9)/L) avoided, days of thrombopenia (platelets <20 × 10(9)/L) avoided, and days with temperature ≥38 °C) avoided. Pegfilgrastim was less costly and less effective than filgrastim for the number of days with ANC <0.5 × 10(9)/L avoided and the number of days with platelets <50.0 × 10(9)/L avoided. Taking uncertainty into account, the probabilities that pegfilgrastim strictly dominated filgrastim were 67 % for febrile neutropenia, 86 % for neutropenia (ANC <1.0 × 10(9)/L), 59 % for thrombopenia (platelets <20 × 10(9)/L), 86 % for temperature ≥38 °C, 32 % for neutropenia (ANC <0.5 × 10(9)/L), and 43 % for thrombopenia (platelets <50 × 10(9)/L). Conversely, the probability that filgrastim strictly dominated pegfilgrastim for neutropenia (ANC <0.5 × 10(9)/L) is 5 %. This study found no evidence that the use of pegfilgrastim is associated with greater cost in lymphoma and myeloma patients after high-dose chemotherapy and PBSC transplantation.

PubMed Central

Turchetti, G.; Bellelli, S.; Palla, I.; Forli, F.

2011-01-01

SUMMARY The aim of the study consists in a systematic review concerning the economic evaluation of cochlear implant (CI) in children by searching the main international clinical and economic electronic databases. All primary studies published in English from January 2000 to May 2010 were included. The types of studies selected concerned partial economic evaluation, including direct and indirect costs of cochlear implantation; complete economic evaluation, including minimization of costs, cost-effectiveness analysis (CEA), cost-utility analysis (CUA) and cost-benefit analysis (CBA) performed through observational and experimental studies. A total of 68 articles were obtained from the database research. Of these, 54 did not meet the inclusion criteria and were eliminated. After reading the abstracts of the 14 articles selected, 11 were considered eligible. The articles were then read in full text. Furthermore, 5 articles identified by bibliography research were added manually. After reading 16 of the selected articles, 9 were included in the review. With regard to the studies included, countries examined, objectives, study design, methodology, prospect of analysis adopted, temporal horizon, the cost categories analyzed strongly differ from one study to another. Cost analysis, cost-effectiveness analysis and an analysis of educational costs associated with cochlear implants were performed. Regarding the cost analysis, only two articles reported both direct cost and indirect costs. The direct cost ranged between € 39,507 and € 68,235 (2011 values). The studies related to cost-effectiveness analysis were not easily comparable: one study reported a cost per QALY ranging between $ 5197 and $ 9209; another referred a cost of $ 2154 for QALY if benefits were not discounted, and $ 16,546 if discounted. Educational costs are significant, and increase with the level of hearing loss and type of school attended. This systematic review shows that the healthcare costs are high, but savings in terms of indirect and quality of life costs are also significant. Cochlear implantation in a paediatric age is cost-effective. The exiguity and heterogeneity of studies did not allow detailed comparative analysis of the studies included in the review. PMID:22287822

[Experience of a Break-Even Point Analysis for Make-or-Buy Decision.].

PubMed

Kim, Yunhee

2006-12-01

Cost containment through continuous quality improvement of medical service is required in an age of a keen competition of the medical market. Laboratory managers should examine the matters on make-or-buy decision periodically. On this occasion, a break-even point analysis can be useful as an analyzing tool. In this study, cost accounting and break-even point (BEP) analysis were performed in case that the immunoassay items showing a recent increase in order volume were to be in-house made. Fixed and variable costs were calculated in case that alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), ferritin, free thyroxine (fT4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), CA 125, CA 19-9, and hepatitis B envelope antibody (HBeAb) were to be tested with Abbott AxSYM instrument. Break-even volume was calculated as fixed cost per year divided by purchasing cost per test minus variable cost per test and BEP ratio as total purchasing costs at break-even volume divided by total purchasing costs at actual annual volume. The average fixed cost per year of AFP, CEA, PSA, ferritin, fT4, T3, TSH, CA 125, CA 19-9, and HBeAb was 8,279,187 won and average variable cost per test, 3,786 won. Average break-even volume was 1,599 and average BEP ratio was 852%. Average BEP ratio without including quality costs such as calibration and quality control was 74%. Because the quality assurance of clinical tests cannot be waived, outsourcing all of 10 items was more adequate than in-house make at the present volume in financial aspect. BEP analysis was useful as a financial tool for make-or-buy decision, the common matter which laboratory managers meet with.

Cost-Effectiveness analysis of Recovery Management Checkups (RMC) for adults with chronic substance use disorders: evidence from a four-year randomized trial

PubMed Central

McCollister, Kathryn E.; French, Michael T.; Freitas, Derek M.; Dennis, Michael L.; Scott, Christy K.; Funk, Rodney R.

2013-01-01

Aims This study performs the first cost-effectiveness analysis (CEA) of Recovery Management Checkups (RMC) for adults with chronic substance use disorders. Design Cost-effectiveness analysis of a randomized clinical trial of RMC. Participants were randomly assigned to a control condition of outcome monitoring (OM-only) or the experimental condition OM-plus-RMC, with quarterly follow-up for four years. Setting Participants were recruited from the largest central intake unit for substance abuse treatment in Chicago, Illinois, USA. Participants 446 participants who were 38 years old on average, 54 percent male, and predominantly African American (85%). Measurements Data on the quarterly cost per participant come from a previous study of OM and RMC intervention costs. Effectiveness is measured as the number of days of abstinence and number of substance-use-related problems. Findings Over the four-year trial, OM-plus-RMC cost on average $2,184 more than OM-only (p<0.01). Participants in OM-plus-RMC averaged 1,026 days abstinent and had 89 substance-use-related problems. OM-only averaged 932 days abstinent and reported 126 substance-use-related problems. Mean differences for both effectiveness measures were statistically significant (p<0.01). The incremental cost-effectiveness ratio for OM-plus-RMC was $23.38 per day abstinent and $59.51 per reduced substance-related problem. When additional costs to society were factored into the analysis, OM-plus-RMC was less costly and more effective than OM-only. Conclusions Recovery Management Checkups are a cost-effective and potentially cost-saving strategy for promoting abstinence and reducing substance-use-related problems among chronic substance users. PMID:23961833

Cost-effectiveness analysis of Recovery Management Checkups (RMC) for adults with chronic substance use disorders: evidence from a 4-year randomized trial.

PubMed

McCollister, Kathryn E; French, Michael T; Freitas, Derek M; Dennis, Michael L; Scott, Christy K; Funk, Rodney R

2013-12-01

This study performs the first cost-effectiveness analysis (CEA) of Recovery Management Checkups (RMC) for adults with chronic substance use disorders. Cost-effectiveness analysis of a randomized clinical trial of RMC. Participants were assigned randomly to a control condition of outcome monitoring (OM-only) or the experimental condition OM-plus-RMC, with quarterly follow-up for 4 years. Participants were recruited from the largest central intake unit for substance abuse treatment in Chicago, Illinois, USA. A total of 446 participants who were 38 years old on average, 54% male, and predominantly African American (85%). Data on the quarterly cost per participant come from a previous study of OM and RMC intervention costs. Effectiveness is measured as the number of days of abstinence and number of substance use-related problems. Over the 4-year trial, OM-plus-RMC cost on average $2184 more than OM-only (P < 0.01). Participants in OM-plus-RMC averaged 1026 days abstinent and had 89 substance use-related problems. OM-only averaged 932 days abstinent and reported 126 substance use-related problems. Mean differences for both effectiveness measures were statistically significant (P < 0.01). The incremental cost-effectiveness ratio for OM-plus-RMC was $23.38 per day abstinent and $59.51 per reduced substance-related problem. When additional costs to society were factored into the analysis, OM-plus-RMC was less costly and more effective than OM-only. Recovery Management Checkups are a cost-effective and potentially cost-saving strategy for promoting abstinence and reducing substance use-related problems among chronic substance users. © 2013 Society for the Study of Addiction.

A systematic review of health economic evaluation in adjuvant breast radiotherapy: Quality counted by numbers.

PubMed

Monten, Chris; Veldeman, Liv; Verhaeghe, Nick; Lievens, Yolande

2017-11-01

Evolving practice in adjuvant breast radiotherapy inevitably impacts healthcare budgets. This is reflected in a rise of health economic evaluations (HEE) in this domain. The available HEE literature was analysed qualitatively and quantitatively, using available instruments. HEEs published between 1/1/2000 and 31/10/2016 were retrieved through a systematic search in Medline, Cochrane and Embase. A quality-assessment using CHEERS (Consolidated Health Economic Evaluation Reporting Standards) was translated into a quantitative score and compared with Tufts Medical Centre CEA registry and Quality of Health Economic Studies (QHES) results. Twenty cost-effectiveness analyses (CEA) and thirteen cost comparisons (CC) were analysed. In qualitative evaluation, valuation or justification of data sources, population heterogeneity and discussion on generalizability, in addition to declaration on funding, were often absent or incomplete. After quantification, the average CHEERS-scores were 74% (CI 66.9-81.1%) and 75.6% (CI 70.7-80.5%) for CEAs and CCs respectively. CEA-scores did not differ significantly from Tufts and QHES-scores. Quantitative CHEERS evaluation is feasible and yields comparable results to validated instruments. HEE in adjuvant breast radiotherapy is of acceptable quality, however, further efforts are needed to improve comprehensive reporting of all data, indispensable for assessing relevance, reliability and generalizability of results. Copyright © 2017 Elsevier B.V. All rights reserved.

Combining Time-Driven Activity-Based Costing with Clinical Outcome in Cost-Effectiveness Analysis to Measure Value in Treatment of Depression

PubMed Central

Lindefors, Nils

2016-01-01

Background A major challenge of mental health care is to provide safe and effective treatment with limited resources. The main purpose of this study was to examine a value-based approach in clinical psychiatry when evaluating a process improvement initiative. This was accomplished by using the relatively new time driven activity based costing (TDABC) method within the more widely adopted cost-effectiveness analysis framework for economic evaluation of healthcare technologies. The objective was to evaluate the cost-effectiveness of allowing psychologists to perform post-treatment assessment previously performed by psychiatrists at an outpatient clinic treating depression using internet-based cognitive-behavioral therapy (ICBT). Methods Data was collected from 568 adult patients treated with ICBT for depression during 2013–2014. The TDABC methodology was used to estimate total healthcare costs, including development of process maps for the complete cycle of care and estimation of resource use and minute costs of staff, hospital space and materials based on their relative proportions used. Clinical outcomes were measured using the Patient Health Questionnaire depression scale (PHQ-9) before and after treatment and at 6-month follow-up. Cost-effectiveness analyses (CEA) was performed and the results presented as incremental net benefits (INB), cost-effectiveness acceptability curves (CEACs) and confidence ellipses to demonstrate uncertainty around the value of the organizational intervention. Outcomes Taking into account the complete healthcare process (from referral to follow-up assessment), treatment costs decreased from $709 (SD = $130) per patient in 2013 to $659 (SD = $134) in 2014 while treatment effectiveness was maintained; 27% had achieved full remission from depression after treatment (PHQ-9 < 5) during both 2013 and 2014 and an additional 35% and 33% had achieved partial remission in 2013 and 2014, respectively. At follow-up, 42% were in full remission after treatment during both 2013 and 2014; an additional 35% and 33% were in partial remission during 2013 and 2014, respectively. Confidence ellipses occupied the south-east (SE) and south-west (SW) quadrants of the incremental cost-effectiveness plane at both post-treatment and at follow-up, indicating that the ICBT treatment was less costly and equally effective after staff reallocation. Conclusion Treating patients to the target of full remission using psychologists instead of medical specialists for post-treatment assessment is cost-saving and consequently a more valuable use of limited resources. TDABC may be a useful tool for measuring resource costs, identifying quality improvement opportunities and evaluating the consequences of such initiatives. Combining TDABC with clinical outcome measures in CEA is potentially a useful approach in mental healthcare to estimate the value of process improvement initiatives. PMID:27798655

Combining Time-Driven Activity-Based Costing with Clinical Outcome in Cost-Effectiveness Analysis to Measure Value in Treatment of Depression.

PubMed

El Alaoui, Samir; Lindefors, Nils

2016-01-01

A major challenge of mental health care is to provide safe and effective treatment with limited resources. The main purpose of this study was to examine a value-based approach in clinical psychiatry when evaluating a process improvement initiative. This was accomplished by using the relatively new time driven activity based costing (TDABC) method within the more widely adopted cost-effectiveness analysis framework for economic evaluation of healthcare technologies. The objective was to evaluate the cost-effectiveness of allowing psychologists to perform post-treatment assessment previously performed by psychiatrists at an outpatient clinic treating depression using internet-based cognitive-behavioral therapy (ICBT). Data was collected from 568 adult patients treated with ICBT for depression during 2013-2014. The TDABC methodology was used to estimate total healthcare costs, including development of process maps for the complete cycle of care and estimation of resource use and minute costs of staff, hospital space and materials based on their relative proportions used. Clinical outcomes were measured using the Patient Health Questionnaire depression scale (PHQ-9) before and after treatment and at 6-month follow-up. Cost-effectiveness analyses (CEA) was performed and the results presented as incremental net benefits (INB), cost-effectiveness acceptability curves (CEACs) and confidence ellipses to demonstrate uncertainty around the value of the organizational intervention. Taking into account the complete healthcare process (from referral to follow-up assessment), treatment costs decreased from $709 (SD = $130) per patient in 2013 to $659 (SD = $134) in 2014 while treatment effectiveness was maintained; 27% had achieved full remission from depression after treatment (PHQ-9 < 5) during both 2013 and 2014 and an additional 35% and 33% had achieved partial remission in 2013 and 2014, respectively. At follow-up, 42% were in full remission after treatment during both 2013 and 2014; an additional 35% and 33% were in partial remission during 2013 and 2014, respectively. Confidence ellipses occupied the south-east (SE) and south-west (SW) quadrants of the incremental cost-effectiveness plane at both post-treatment and at follow-up, indicating that the ICBT treatment was less costly and equally effective after staff reallocation. Treating patients to the target of full remission using psychologists instead of medical specialists for post-treatment assessment is cost-saving and consequently a more valuable use of limited resources. TDABC may be a useful tool for measuring resource costs, identifying quality improvement opportunities and evaluating the consequences of such initiatives. Combining TDABC with clinical outcome measures in CEA is potentially a useful approach in mental healthcare to estimate the value of process improvement initiatives.

Incorporating social network effects into cost-effectiveness analysis: a methodological contribution with application to obesity prevention

PubMed Central

Konchak, Chad; Prasad, Kislaya

2012-01-01

Objectives To develop a methodology for integrating social networks into traditional cost-effectiveness analysis (CEA) studies. This will facilitate the economic evaluation of treatment policies in settings where health outcomes are subject to social influence. Design This is a simulation study based on a Markov model. The lifetime health histories of a cohort are simulated, and health outcomes compared, under alternative treatment policies. Transition probabilities depend on the health of others with whom there are shared social ties. Setting The methodology developed is shown to be applicable in any healthcare setting where social ties affect health outcomes. The example of obesity prevention is used for illustration under the assumption that weight changes are subject to social influence. Main outcome measures Incremental cost-effectiveness ratio (ICER). Results When social influence increases, treatment policies become more cost effective (have lower ICERs). The policy of only treating individuals who span multiple networks can be more cost effective than the policy of treating everyone. This occurs when the network is more fragmented. Conclusions (1) When network effects are accounted for, they result in very different values of incremental cost-effectiveness ratios (ICERs). (2) Treatment policies can be devised to take network structure into account. The integration makes it feasible to conduct a cost-benefit evaluation of such policies. PMID:23117559

Enhanced power generation and energy conversion of sewage sludge by CEA-microbial fuel cells.

PubMed

Abourached, Carole; Lesnik, Keaton Larson; Liu, Hong

2014-08-01

The production of methane from sewage sludge through the use of anaerobic digestion has been able to effectively offset energy costs for wastewater treatment. However, significant energy reserves are left unrecovered and effluent standards are not met necessitating secondary processes such as aeration. In the current study a novel cloth-electrode assembly microbial fuel cell (CEA-MFC) was used to generate electricity from sewage sludge. Fermentation pretreatment of the sludge effectively increased the COD of the supernatant and improved reactor performance. Using the CEA-MFC design, a maximum power density of 1200 mW m(-2) was reached after a fermentation pre-treatment time of 96 h. This power density represents a 275% increase over those previously observed in MFC systems. Results indicate continued improvements are possible and MFCs may be a viable modification to existing wastewater treatment infrastructure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cost-effectiveness of percutaneous coronary intervention with cobalt-chromium everolimus eluting stents versus bare metal stents: Results from a patient level meta-analysis of randomized trials.

PubMed

Ferko, Nicole; Ferrante, Giuseppe; Hasegawa, James T; Schikorr, Tanya; Soleas, Ireena M; Hernandez, John B; Sabaté, Manel; Kaiser, Christoph; Brugaletta, Salvatore; de la Torre Hernandez, Jose Maria; Galatius, Soeren; Cequier, Angel; Eberli, Franz; de Belder, Adam; Serruys, Patrick W; Valgimigli, Marco

2017-05-01

Second-generation drug eluting stents (DES) may reduce costs and improve clinical outcomes compared to first-generation DES with improved cost-effectiveness when compared to bare metal stents (BMS). We aimed to conduct an economic evaluation of a cobalt-chromium everolimus eluting stent (Co-Cr EES) compared with BMS in percutaneous coronary intervention (PCI). To conduct a cost-effectiveness analysis (CEA) of a cobalt-chromium everolimus eluting stent (Co-Cr EES) versus BMS in PCI. A Markov state transition model with a 2-year time horizon was applied from a US Medicare setting with patients undergoing PCI with Co-Cr EES or BMS. Baseline characteristics, treatment effects, and safety measures were taken from a patient level meta-analysis of 5 RCTs (n = 4,896). The base-case analysis evaluated stent-related outcomes; a secondary analysis considered the broader set of outcomes reported in the meta-analysis. The base-case and secondary analyses reported an additional 0.018 and 0.013 quality-adjusted life years (QALYs) and cost savings of $236 and $288, respectively with Co-Cr EES versus BMS. Results were robust to sensitivity analyses and were most sensitive to the price of clopidogrel. In the probabilistic sensitivity analysis, Co-Cr EES was associated with a greater than 99% chance of being cost saving or cost effective (at a cost per QALY threshold of $50,000) versus BMS. Using data from a recent patient level meta-analysis and contemporary cost data, this analysis found that PCI with Co-Cr EES is more effective and less costly than PCI with BMS. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Equity in Pharmaceutical Pricing and Reimbursement: Crossing the Income Divide in Asia Pacific.

PubMed

Daems, Rutger; Maes, Edith; Glaetzer, Christoph

2013-05-01

The article takes a three-dimensional approach (triangulation) in defining international pricing policy for pharmaceuticals using cost-effectiveness analysis (CEA), willingness-to-pay (WTP) analysis, and ability-to-pay (ATP) analysis. It attempts to find a balance between the various economic methods of which some focus on effectiveness while others are geared toward incorporating equity in the equation. A critical review of the first two established economic methods and their ability to evaluate not only "efficacy" but also "fairness" in pricing decisions identifies a gap in the latter. Therefore, a third analytic method is presented that measures the ATP based on a country's score in the human development index of the United Nations Development Program for 120 countries. This approach allows practicing differential pricing among and within countries. To refine this equity-driven pricing concept, two additional parameters can be added to the model: the Oxford "Multidimensional Poverty Index" and the "Out-of-Pocket" or "Self Pay" health expenditure as reported by the World Bank. There is no hierarchy between the above three pricing methods. Because one method provides further insight into the other, however, it is recommended to start with CEA followed by WTP analysis. These types of analysis are closely linked in that the first provides the CE ratio for the compound investigated and the other sets the anticipated ceiling threshold of the payer's WTP (in a particular country). The ATP method provides a supplementary "equity" check and facilitates the process of equity-based differential pricing. A third method should be used in conjunction with the standard CEA and WTP analysis that measures the ATP with the human development index as yardstick to provide sustainable and equitable access to medicines. We recommend that ATP analysis becomes an additional practice in policy decision making and in defining international pricing strategies for pharmaceuticals. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Efficient induction of anti-tumor immunity by a TAT-CEA fusion protein vaccine with poly(I:C) in a murine colorectal tumor model.

PubMed

Park, Jung-Sun; Kim, Hye-Sung; Park, Hye-Mi; Kim, Chang-Hyun; Kim, Tai-Gyu

2011-11-03

Protein vaccines may be a useful strategy for cancer immunotherapy because recombinant tumor antigen proteins can be produced on a large scale at relatively low cost and have been shown to be safe for clinical application. However, protein vaccines have historically exhibited poor immunogenicity; thus, an improved strategy is needed for successful induction of immune responses. TAT peptide is a protein transduction domain composed of an 11-amino acid peptide (TAT(47-57): YGRKKRRQRRR). The positive charge of this peptide allows protein antigen fused with it to improve cell penetration. Poly(I:C) is a synthetic double-stranded RNA that is negatively charged and favors interaction with the cationic TAT peptide. Poly(I:C) has been reported on adjuvant role in tumor vaccine through promotion of immune responses. Therefore, we demonstrated that vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) can induce anti-tumor immunity in a murine colorectal tumor model. Splenocytes from mice vaccinated with a mixture of TAT-CEA fusion protein and poly(I:C) effectively induced CEA-specific IFN-γ-producing T cells and showed cytotoxic activity specific for MC-38-cea2 tumor cells expressing CEA. Vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) delayed tumor growth in MC-38-cea-2 tumor-bearing mice. Depletion of CD8(+) T cells and NK cells reversed the inhibition of tumor growth in an MC-38-cea2-bearing mice, indicating that CD8(+) T cells and NK cells are responsible for anti-tumor immunity by vaccine with a mixture of TAT-CEA fusion protein and poly(I:C). Taken together, these results suggest that poly(I:C) could be used as a potent adjuvant to induce the anti-tumor immunity of a TAT-CEA fusion protein vaccine in a murine colorectal tumor model. Copyright © 2011 Elsevier Ltd. All rights reserved.

Surrogate models for efficient stability analysis of brake systems

NASA Astrophysics Data System (ADS)

Nechak, Lyes; Gillot, Frédéric; Besset, Sébastien; Sinou, Jean-Jacques

2015-07-01

This study assesses capacities of the global sensitivity analysis combined together with the kriging formalism to be useful in the robust stability analysis of brake systems, which is too costly when performed with the classical complex eigenvalues analysis (CEA) based on finite element models (FEMs). By considering a simplified brake system, the global sensitivity analysis is first shown very helpful for understanding the effects of design parameters on the brake system's stability. This is allowed by the so-called Sobol indices which discriminate design parameters with respect to their influence on the stability. Consequently, only uncertainty of influent parameters is taken into account in the following step, namely, the surrogate modelling based on kriging. The latter is then demonstrated to be an interesting alternative to FEMs since it allowed, with a lower cost, an accurate estimation of the system's proportions of instability corresponding to the influent parameters.

Does the use of efficacy or effectiveness evidence in cost-effectiveness analysis matter?

PubMed

Dilokthornsakul, Piyameth; Chaiyakunapruk, Nathorn; Campbell, Jonathan D

2017-01-02

To test the association of clinical evidence type, efficacy-based or effectiveness-based ("E"), versus whether or not asthma interventions' cost-effectiveness findings are favorable. We conducted a systematic review of PubMed, EMBASE, Tufts CEA registry, Cochrane CENTRAL, and the UK National Health Services Economic Evaluation Database from 2009 to 2014. All cost-effectiveness studies evaluating asthma medication(s) were included. Clinical evidence type, "E," was classified as efficacy-based if the evidence was from an explanatory randomized controlled trial(s) or meta-analysis, while evidence from pragmatic trial(s) or observational study(s) was classified as effectiveness-based. We defined three times the World Health Organization cost-effectiveness willingness-to-pay (WTP) threshold or less as a favorable cost-effectiveness finding. Logistic regression tested the likelihood of favorable versus unfavorable cost-effectiveness findings against the type of "E." 25 cost-effectiveness studies were included. Ten (40.0%) studies were effectiveness-based, yet 15 (60.0%) studies were efficacy-based. Of 17 studies using endpoints that could be compared to WTP threshold, 7 out of 8 (87.5%) effectiveness-based studies yielded favorable cost-effectiveness results, whereas 4 out of 9 (44.4%) efficacy-based studies yielded favorable cost-effectiveness results. The adjusted odds ratio was 15.12 (95% confidence interval; 0.59 to 388.75) for effectiveness-based versus efficacy-based achieving favorable cost-effectiveness findings. More asthma cost-effectiveness studies used efficacy-based evidence. Studies using effectiveness-based evidence trended toward being more likely to disseminate favorable cost-effective findings than those using efficacy. Health policy decision makers should pay attention to the type of clinical evidence used in cost-effectiveness studies for accurate interpretation and application.

Efficacy, Safety, and Cost of Therapy of the Traditional Chinese Medicine, Catalpol, in Patients Following Surgical Resection for Locally Advanced Colon Cancer.

PubMed

Fei, Baogang; Dai, Wei; Zhao, Shouhe

2018-05-15

BACKGROUND The aim of this study was to evaluate the efficacy, safety, and cost of treatment of the traditional Chinese herbal medicine, catalpol, in patients following surgical resection for locally advanced colon cancer. MATERIAL AND METHODS The 345 patients who had undergone surgical resection for locally advanced colon adenocarcinoma, were divided into three groups: a placebo-treated group (n=115); patients treated with an intraperitoneal injection of 10 mg/kg catalpol twice a day for 12 weeks (treatment group) (n=115); patients treated with 5 mg/kg intravenous bevacizumab twice a week for 12 weeks (control group) (n=115). Serum levels of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) were measured. Patient overall survival (OS), cancer-free survival (CFS), adverse effects, and cost of therapy were evaluated. Statistical analysis included the Wilcoxon rank sum test and Tukey's test for clinicopathological response at 95% confidence interval (CI). RESULTS Patients in the catalpol-treated group had significantly reduced serum levels of CA 19-9 (p=0.0002, q=3.202), CEA (p=0.0002, q=3.007), MMP-2 (p£0.0001, q=6.883), and MMP-9 (p<0.0001, q=3.347). Only non-fatal adverse effects occurred in the catalpol treatment group (p<0.0001, q=5.375). OS and CFS were significantly increased in the catalpol treatment group compared with the placebo group (p<0.0001 q=7.586). The cost of catalpol treatment compared favorably with other treatments (p<0.0001, q=207.17). CONCLUSIONS In this preliminary study, treatment with the Chinese herbal medicine, catalpol, showed benefits in clinical outcome, at low cost, and with no serious complications.

The Missing Stakeholder Group: Why Patients Should be Involved in Health Economic Modelling.

PubMed

van Voorn, George A K; Vemer, Pepijn; Hamerlijnck, Dominique; Ramos, Isaac Corro; Teunissen, Geertruida J; Al, Maiwenn; Feenstra, Talitha L

2016-04-01

Evaluations of healthcare interventions, e.g. new drugs or other new treatment strategies, commonly include a cost-effectiveness analysis (CEA) that is based on the application of health economic (HE) models. As end users, patients are important stakeholders regarding the outcomes of CEAs, yet their knowledge of HE model development and application, or their involvement therein, is absent. This paper considers possible benefits and risks of patient involvement in HE model development and application for modellers and patients. An exploratory review of the literature has been performed on stakeholder-involved modelling in various disciplines. In addition, Dutch patient experts have been interviewed about their experience in, and opinion about, the application of HE models. Patients have little to no knowledge of HE models and are seldom involved in HE model development and application. Benefits of becoming involved would include a greater understanding and possible acceptance by patients of HE model application, improved model validation, and a more direct infusion of patient expertise. Risks would include patient bias and increased costs of modelling. Patient involvement in HE modelling seems to carry several benefits as well as risks. We claim that the benefits may outweigh the risks and that patients should become involved.

Cost-effectiveness analysis of routine pneumococcal vaccination in the UK: a comparison of the PHiD-CV vaccine and the PCV-13 vaccine using a Markov model.

PubMed

Delgleize, Emmanuelle; Leeuwenkamp, Oscar; Theodorou, Eleni; Van de Velde, Nicolas

2016-11-30

In 2010, the 13-valent pneumococcal conjugate vaccine (PCV-13) replaced the 7-valent vaccine (introduced in 2006) for vaccination against invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) in the UK. Using recent evidence on the impact of PCVs and epidemiological changes in the UK, we performed a cost-effectiveness analysis (CEA) to compare the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with PCV-13 in the ongoing national vaccination programme. CEA was based on a published Markov model. The base-case scenario accounted only for direct medical costs. Work days lost were considered in alternative scenarios. Calculations were based on serotype and disease-specific vaccine efficacies, serotype distributions and UK incidence rates and medical costs. Health benefits and costs related to IPD, pneumonia and AOM were accumulated over the lifetime of a UK birth cohort. Vaccination of infants at 2, 4 and 12 months with PHiD-CV or PCV-13, assuming complete coverage and adherence. The incremental cost-effectiveness ratio (ICER) was computed by dividing the difference in costs between the programmes by the difference in quality-adjusted life-years (QALY). Under our model assumptions, both vaccines had a similar impact on IPD and pneumonia, but PHiD-CV generated a greater reduction in AOM cases (161 918), AOM-related general practitioner consultations (31 070) and tympanostomy tube placements (2399). At price parity, PHiD-CV vaccination was dominant over PCV-13, saving 734 QALYs as well as £3.68 million to the National Health Service (NHS). At the lower list price of PHiD-CV, the cost-savings would increase to £45.77 million. This model projected that PHiD-CV would provide both incremental health benefits and cost-savings compared with PCV-13 at price parity. Using PHiD-CV could result in substantial budget savings to the NHS. These savings could be used to implement other life-saving interventions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[A future image of clinical inspection from health economics].

PubMed

Kakihara, Hiroaki

2006-06-01

Do you let medical costs increase in proportion to the growth rate of GDP? A way of thinking of the Council on Economic and Fiscal Policy. Should we exclude public medical insurance? It is not a problem, it is an absolute sum if you are effective. If there is no insurance, and individuals pay the total amount, there is no problem, but it is impossible. Economic development will cease if there is no insurance. As medical personnel, to offer good medical care with an appropriate cost. An appeal to the nation is necessary. Economic technical evaluation to identify a cheap method for each clinical inspection. Does medical insurance have a deficit? I. Japanese Health insurance system. (1) Health insurance union. When you look at the contribution money, it is originally 2,479,800,000,000 yen, with premium income and a profit of 45%. (2) Government management health insurance. When you look at the contribution money, it is originally 2,163,300,000,000 yen, with premium income and a profit of 36%. (1) + (2) Employed insurance meter. (3) Mutual aid. (4) National Health Insurance. II. A clinical economic method. III. Expense of medical care and its effect. A. Expense. B. A medical economic technical evaluation method. 1. Cost-effectiveness analysis CEA. 2. Cost utility analysis CUA. 3. Cost-benefit analysis CBA. 4. Expense minimization analysis.

Two-Level Weld-Material Homogenization for Efficient Computational Analysis of Welded Structure Blast-Survivability

NASA Astrophysics Data System (ADS)

Grujicic, M.; Arakere, G.; Hariharan, A.; Pandurangan, B.

2012-06-01

The introduction of newer joining technologies like the so-called friction-stir welding (FSW) into automotive engineering entails the knowledge of the joint-material microstructure and properties. Since, the development of vehicles (including military vehicles capable of surviving blast and ballistic impacts) nowadays involves extensive use of the computational engineering analyses (CEA), robust high-fidelity material models are needed for the FSW joints. A two-level material-homogenization procedure is proposed and utilized in this study to help manage computational cost and computer storage requirements for such CEAs. The method utilizes experimental (microstructure, microhardness, tensile testing, and x-ray diffraction) data to construct: (a) the material model for each weld zone and (b) the material model for the entire weld. The procedure is validated by comparing its predictions with the predictions of more detailed but more costly computational analyses.

Quantitative analysis of antigen for the induction of tolerance in carcinoembryonic antigen transgenic mice.

PubMed Central

Hasegawa, T; Isobe, K; Nakashima, I; Shimokata, K

1992-01-01

In order to analyse the amounts of antigen in the thymus for the induction of tolerance, several carcinoembryonic antigen (CEA) transgenic lines were established which expressed human CEA antigen with different amounts. The chimeric KSN nude mice transplanted with the thymus of the B601 line (in which CEA mRNA and CEA protein could be detected in various tissues) to kidney capsule showed tolerance to human CEA. On the other hand, the chimeric KSN nude mice transplanted with the thymus of the B602 or BC60 line (in which neither CEA mRNA nor CEA protein could be detected by Northern blot analysis and flow cytometry analysis) or normal C57BL/6 (B6) did not develop the tolerance to human CEA. However, the chimeric KSN nude mice transplanted simultaneously with thymus of the B6 and spleen of the B601 line became tolerant to human CEA antigen. In the case of systemic immunization with cells which had CEA antigen, the B601 line was tolerant to human CEA. Surprisingly, the B602 and BC60 lines were also tolerant to CEA molecule. These results indicate that not only the antigen present in the thymus but also the antigen which flows from the peripheral organs to the thymus may be necessary for the induction of CEA tolerance. Images Figure 1 PMID:1493931

A Systematic Review of the Level of Evidence in Economic Evaluations of Medical Devices: The Example of Vertebroplasty and Kyphoplasty.

PubMed

Martelli, Nicolas; Devaux, Capucine; van den Brink, Hélène; Pineau, Judith; Prognon, Patrice; Borget, Isabelle

2015-01-01

Economic evaluations are far less frequently reported for medical devices than for drugs. In addition, little is known about the quality of existing economic evaluations, particularly for innovative devices, such as those used in vertebroplasty and kyphoplasty. To assess the level of evidence provided by the available economic evaluations for vertebroplasty and kyphoplasty. A systematic review of articles in English or French listed in the MEDLINE, PASCAL, COCHRANE and National Health Service Economic Evaluation databases, with limits on publication date (up to the date of the review, March 2014). We included only economic evaluations of vertebroplasty or kyphoplasty. Editorial and methodological articles were excluded. Data were extracted from articles by two authors working independently and using two analysis grids to measure the quality of economic evaluations. Twenty-one studies met our inclusion criteria. All were published between 2008 and 2014. Eighteen (86%) were full economic evaluations. Cost-effectiveness analysis (CEA) was the most frequent type of economic evaluation, and was present in 11 (52%) studies. Only three CEAs complied fully with the British Medical Journal checklist. The quality of the data sources used in the 21 studies was high, but the CEAs conforming to methodological guidelines did not use high-quality data sources for all components of the analysis. This systematic review shows that the level of evidence in economic evaluations of vertebroplasty and kyphoplasty is low, despite the recent publication of a large number of studies. This finding highlights the challenges to be faced to improve the quality of economic evaluations of medical devices.

There is no benefit to universal carotid artery duplex screening before a major cardiac surgical procedure.

PubMed

Adams, Brian C; Clark, Ross M; Paap, Christina; Goff, James M

2014-01-01

Perioperative stroke is a devastating complication after cardiac surgery. In an attempt to minimize this complication, many cardiac surgeons routinely preoperatively order carotid artery duplex scans to assess for significant carotid stenosis. We hypothesize that the routine screening of preoperative cardiac surgery patients with carotid artery duplex scans detects few patients who would benefit from carotid intervention or that a significant carotid stenosis reliably predicts stroke risk after cardiac surgery. A retrospective review identified 1,499 patients who underwent cardiac surgical procedures between July 1999 and September 2010. Data collected included patient demographics, comorbidities, history of previous stroke, preoperative carotid artery duplex scan results, location of postoperative stroke, and details of carotid endarterectomy (CEA) procedures before, in conjunction with, or after cardiac surgery. Statistical methods included univariate analysis and Fisher's exact test. Twenty-six perioperative strokes were identified (1.7%). In the 21 postoperative stroke patients for whom there is complete carotid artery duplex scan data, 3 patients had a hemodynamically significant lesion (>70%) and 1 patient underwent unilateral carotid CEA for bilateral disease. Postoperative strokes occurred in the anterior cerebral circulation (69.2%), posterior cerebral circulation (15.4%), or both (15.4%). Patient comorbidities, preoperative carotid artery duplex scan screening velocities, or types of cardiac surgical procedure were not predictive for stroke. Thirteen patients (0.86%) underwent CEA before, in conjunction with, or after cardiac surgery. Two of these patients had symptomatic disease, 1 of whom underwent CEA before and the other after his cardiac surgery. Of the 11 asymptomatic patients, 2 underwent CEA before, 3 concurrently, and 6 after cardiac surgery. Left main disease (≥50% stenosis), previous stroke, and peripheral vascular disease were found to be statistically significant predictors of carotid revascularization. A cost analysis of universal screening resulted in an estimated net cost of $378,918 during the study period. The majority of postoperative strokes after cardiac surgery are not related to extracranial carotid artery disease and they are not predicted by preoperative carotid artery duplex scan screening. Consequently, universal carotid artery duplex scan screening cannot be recommended and a selective approach should be adopted. Published by Elsevier Inc.

Economic evaluation of Community Level Interventions for Pre-eclampsia (CLIP) in South Asian and African countries: a study protocol.

PubMed

Khowaja, Asif R; Mitton, Craig; Bryan, Stirling; Magee, Laura A; Bhutta, Zulfiqar A; von Dadelszen, Peter

2015-05-26

Globally, hypertensive disorders of pregnancy, particularly pre-eclampsia and eclampsia, are the leading cause of maternal and neonatal mortality, and impose substantial burdens on the families of pregnant women, their communities, and healthcare systems. The Community Level Interventions for Pre-eclampsia (CLIP) Trial evaluates a package of care applied at both community and primary health centres to reduce maternal and perinatal disabilities and deaths resulting from the failure to identify and manage pre-eclampsia at the community level. Economic evaluation of health interventions can play a pivotal role in priority setting and inform policy decisions for scale-up. At present, there is a paucity of published literature on the methodology of economic evaluation of large, multi-country, community-based interventions in the area of maternal and perinatal health. This study protocol describes the application of methodology for economic evaluation of the CLIP in South Asia and Africa. A mixed-design approach i.e. cost-effectiveness analysis (CEA) and qualitative thematic analysis will be used alongside the trial to prospectively evaluate the economic impact of CLIP from a societal perspective. Data on health resource utilization, costs, and pregnancy outcomes will be collected through structured questionnaires embedded into the pregnancy surveillance, cross-sectional survey and budgetary reviews. Qualitative data will be collected through focus groups (FGs) with pregnant women, household male-decision makers, care providers, and district level health decision makers. The incremental cost-effectiveness ratio will be calculated for healthcare system and societal perspectives, taking into account the country-specific model inputs (costs and outcome) from the CLIP Trial. Emerging themes from FGs will inform the design of the model, and help to interpret findings of the CEA. The World Health Organization (WHO) strongly recommends cost-effective interventions as a key aspect of achieving Millennium Development Goal (MDG)-5 (i.e. 75 % reduction in maternal mortality from 1990 levels by 2015). To date, most cost-effectiveness studies in this field have focused specifically on the diagnostic and clinical management of pre-eclampsia, yet rarely on community-based interventions in low-and-middle-income countries (LMICs). This study protocol will be of interest to public health scientists and health economists undertaking community-based trials in the area of maternal and perinatal health, particularly in LMICs. ClinicalTrials.gov: NCT01911494.

Evaluation of Health Economics in Radiation Oncology: A Systematic Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Timothy K.; Goodman, Chris D.; Boldt, R. Gabriel

Purpose: Despite the rising costs in radiation oncology, the impact of health economics research on radiation therapy practice analysis patterns is unclear. We performed a systematic review of cost-effectiveness analyses (CEAs) and cost-utility analyses (CUAs) to identify trends in reporting quality in the radiation oncology literature over time. Methods and Materials: A systematic review of radiation oncology economic evaluations up to 2014 was performed, using MEDLINE and EMBASE databases. The Consolidated Health Economic Evaluation Reporting Standards guideline informed data abstraction variables including study demographics, economic parameters, and methodological details. Tufts Medical Center CEA registry quality scores provided a basis formore » qualitative assessment of included studies. Studies were stratified by 3 time periods (1995-2004, 2005-2009, and 2010-2014). The Cochran-Armitage trend test and linear trend test were used to identify trends over time. Results: In total, 102 articles were selected for final review. Most studies were in the context of a model (61%) or clinical trial (28%). Many studies lacked a conflict of interest (COI) statement (67%), a sponsorship statement (48%), a reported study time horizon (35%), and the use of discounting (29%). There was a significant increase over time in the reporting of a COI statement (P<.001), health care payer perspective (P=.019), sensitivity analyses using multivariate (P=.043) or probabilistic methods (P=.011), incremental cost-effectiveness threshold (P<.001), secondary source utility weights (P=.010), and cost effectiveness acceptability curves (P=.049). There was a trend toward improvement in Tuft scores over time (P=.065). Conclusions: Recent reports demonstrate improved reporting rates in economic evaluations; however, there remains significant room for improvement as reporting rates are still suboptimal. As fiscal pressures rise, we will rely on economic assessments to guide our practice decisions and policies. We recommend improved adherence to published guidelines and further research to determine the clinical implications of our findings.« less

Evaluation of Health Economics in Radiation Oncology: A Systematic Review.

PubMed

Nguyen, Timothy K; Goodman, Chris D; Boldt, R Gabriel; Warner, Andrew; Palma, David A; Rodrigues, George B; Lock, Michael I; Mishra, Mark V; Zaric, Gregory S; Louie, Alexander V

2016-04-01

Despite the rising costs in radiation oncology, the impact of health economics research on radiation therapy practice analysis patterns is unclear. We performed a systematic review of cost-effectiveness analyses (CEAs) and cost-utility analyses (CUAs) to identify trends in reporting quality in the radiation oncology literature over time. A systematic review of radiation oncology economic evaluations up to 2014 was performed, using MEDLINE and EMBASE databases. The Consolidated Health Economic Evaluation Reporting Standards guideline informed data abstraction variables including study demographics, economic parameters, and methodological details. Tufts Medical Center CEA registry quality scores provided a basis for qualitative assessment of included studies. Studies were stratified by 3 time periods (1995-2004, 2005-2009, and 2010-2014). The Cochran-Armitage trend test and linear trend test were used to identify trends over time. In total, 102 articles were selected for final review. Most studies were in the context of a model (61%) or clinical trial (28%). Many studies lacked a conflict of interest (COI) statement (67%), a sponsorship statement (48%), a reported study time horizon (35%), and the use of discounting (29%). There was a significant increase over time in the reporting of a COI statement (P<.001), health care payer perspective (P=.019), sensitivity analyses using multivariate (P=.043) or probabilistic methods (P=.011), incremental cost-effectiveness threshold (P<.001), secondary source utility weights (P=.010), and cost effectiveness acceptability curves (P=.049). There was a trend toward improvement in Tuft scores over time (P=.065). Recent reports demonstrate improved reporting rates in economic evaluations; however, there remains significant room for improvement as reporting rates are still suboptimal. As fiscal pressures rise, we will rely on economic assessments to guide our practice decisions and policies. We recommend improved adherence to published guidelines and further research to determine the clinical implications of our findings. Copyright © 2016 Elsevier Inc. All rights reserved.

Surface expression and CEA binding of hnRNP M4 protein in HT29 colon cancer cells.

PubMed

Laguinge, Luciana; Bajenova, Olga; Bowden, Emma; Sayyah, Jacqueline; Thomas, Peter; Juhl, Hartmut

2005-01-01

Carcinoembryonic antigen (CEA) has been shown to participate in the progression and metastatic growth of colorectal cancer. However, its biological function remains elusive. Recently, we found that CEA protects colon cancer cells from undergoing apoptosis, suggesting a complex role that includes signal transduction activity. Additionally, it was reported that CEA binds to Kupffer cells and macrophages to a membrane-anchored homolog of heterogeneous nuclear protein M4 (hnRNP M4), which subsequently was named CEA-receptor (CEAR). Cytoplasmatic and membranous expression of CEAR in CEA-positive colon cancer tissues prompted us to analyze the CEA-CEAR interaction in HT29 colon cancer cells. Both, CEA and CEAR were found on the cell surface of HT29 cells, as demonstrated by confocal microscopy. Imaging analysis suggested co-localization and, thus, interaction of both molecules. To confirm this observation, immunoprecipitation experiments and Western blot analysis were performed and indicated binding of CEA and CEAR. Immunoprecipitation of CEA resulted in a pull down of CEAR. The pull down of CEAR correlated with the amount of CEA as demonstrated by ribozyme targeting of CEA. Finally, external treatment of HT29 cells with soluble CEA induced tyrosine phosphorylation of CEAR, suggesting a CEA-dependent role of CEAR in signal transduction. Future experiments will elucidate whether the CEA-CEAR interaction is involved in CEA's antiapoptotic role and mediates the prometastatic properties of CEA in colon cancer cells.

Can Economic Model Transparency Improve Provider Interpretation of Cost-effectiveness Analysis? Evaluating Tradeoffs Presented by the Second Panel on Cost-effectiveness in Health and Medicine.

PubMed

Padula, William V; McQueen, Robert Brett; Pronovost, Peter J

2017-11-01

The Second Panel on Cost-Effectiveness in Health and Medicine convened on December 7, 2016 at the National Academy of Medicine to disseminate their recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses (CEAs). Following its summary, panel proceedings included lengthy discussions including the field's struggle to disseminate findings efficiently through peer-reviewed literature to target audiences. With editors of several medical and outcomes research journals in attendance, there was consensus that findings of cost-effectiveness analyses do not effectively reach other researchers or health care providers. The audience members suggested several solutions including providing additional training to clinicians in cost-effectiveness research and requiring that cost-effectiveness models are made publicly available. However, there remains the questions of whether making economic modelers' work open-access through journals is fair under the defense that these models remain one's own intellectual property, or whether journals can properly manage the peer-review process specifically for cost-effectiveness analyses. In this article, we elaborate on these issues and provide some suggested solutions that may increase the dissemination and application of cost-effectiveness literature to reach its intended audiences and ultimately benefit the patient. Ultimately, it is our combined view as economic modelers and clinicians that cost-effectiveness results need to reach the clinician to improve the efficiency of medical practice, but that open-access models do not improve clinician access or interpretation of the economics of medicine.

The Carotid Revascularization Endarterectomy vs. Stenting Trial completes randomization: lessons learned and anticipated results.

PubMed

Lal, Brajesh K; Brott, Thomas G

2009-11-01

The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) completed randomization on July 18, 2008. Sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), the trial has enrolled 2,522 participants across North America and is the largest randomized clinical trial (RCT) comparing the efficacy of carotid artery stenting (CAS) to carotid endarterectomy (CEA). It is also the largest RCT to assess carotid revascularization in both symptomatic and asymptomatic patients with carotid artery stenosis. Conventional-risk patients with symptomatic carotid stenosis (> or =50% by angiography, > or =70% by ultrasound) or asymptomatic carotid stenosis (> or =60% by angiography, > or =70% by ultrasound) were randomized to both treatment arms in a 1:1 ratio. Eligibility criteria for CREST were similar to those of the previous NINDS-sponsored CEA RCTs. The investigational devices used in the CAS arm of the study are the RX Acculink stent and the RX Accunet embolic protection system, (Abbott Vascular, Santa Clara, Calif). The primary aim is to contrast the efficacy of CAS versus CEA in preventing stroke, myocardial infarction, and all-cause mortality during a 30-day peri-procedural period, and ipsilateral stroke over the follow-up period (extending up to four years). The secondary aims are to contrast the efficacy of CAS and CEA in men and women, the restenosis rates of the two procedures, health-related quality of life, and cost effectiveness of CAS and CEA. The conclusion of enrollment in CREST marks the end of a long recruitment period from 117 community and academic hospital centers across the United States and Canada. Each surgeon and interventionalist underwent a rigorous credentialing process that included performance-assessment of prior CEA and CAS procedures. Credentialing of interventionalists also included a review of additional CAS procedures enrolled into a CREST lead-in phase prior to entering patients into the randomized trial; 1564 patients were enrolled in the lead-in, the final pathway for the largest credentialing effort to date for any clinical trial. CREST will provide long-term follow-up after carotid revascularization based on systematic ultrasonographic and neurologic surveillance, and on quality of life and cost-effectiveness comparisons between CAS and CEA in the setting of a RCT. We present a brief description of the CREST protocol, impediments that were overcome during the trial, salient results from the lead-in phase of the trial, a summary of enrollment activities and characteristics of the final cohort, and a timeline for anticipated results from the randomized phase.

Should we provide oral health training for staff caring for people with intellectual disabilities in community based residential care? A cost-effectiveness analysis.

PubMed

Mac Giolla Phadraig, Caoimhin; Nunn, June; Guerin, Suzanne; Normand, Charles

2016-04-01

Oral health training is often introduced into community-based residential settings to improve the oral health of people with intellectual disabilities (ID). There is a lack of appropriate evaluation of such programs, leading to difficulty in deciding how best to allocate scarce resources to achieve maximum effect. This article reports an economic analysis of one such oral health program, undertaken as part of a cluster randomized controlled trial. Firstly, we report a cost-effectiveness analysis of training care-staff compared to no training, using incremental cost-effectiveness ratios (ICERs). Effectiveness was measured as change in knowledge, reported behaviors, attitude and self-efficacy, using validated scales (K&BAS). Secondly, we costed training as it was scaled up to include all staff within the service provider in question. Data were collected in Dublin, Ireland in 2009. It cost between €7000 and €10,000 more to achieve modest improvement in K&BAS scores among a subsample of 162 care-staff, in comparison to doing nothing. Considering scaled up first round training, it cost between €58,000 and €64,000 to train the whole population of staff, from a combined dental and disability service perspective. Less than €15,000-€20,000 of this was additional to the cost of doing nothing (incremental cost). From a dental perspective, a further, second training cycle including all staff would cost between €561 and €3484 (capital costs) and €5815 (operating costs) on a two yearly basis. This study indicates that the program was a cost-effective means of improving self-reported measures and possibly oral health, relative to doing nothing. This was mainly due to low cost, rather than the large effect. In this instance, the use of cost effectiveness analysis has produced evidence, which may be more useful to decision makers than that arising from traditional methods of evaluation. There is a need for CEAs of effective interventions to allow comparison between programs. Suggestions to reduce cost are presented. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Systematic Review of the Level of Evidence in Economic Evaluations of Medical Devices: The Example of Vertebroplasty and Kyphoplasty

PubMed Central

van den Brink, Hélène; Pineau, Judith; Prognon, Patrice; Borget, Isabelle

2015-01-01

Context Economic evaluations are far less frequently reported for medical devices than for drugs. In addition, little is known about the quality of existing economic evaluations, particularly for innovative devices, such as those used in vertebroplasty and kyphoplasty. Objective To assess the level of evidence provided by the available economic evaluations for vertebroplasty and kyphoplasty. Data Sources A systematic review of articles in English or French listed in the MEDLINE, PASCAL, COCHRANE and National Health Service Economic Evaluation databases, with limits on publication date (up to the date of the review, March 2014). Study Selection We included only economic evaluations of vertebroplasty or kyphoplasty. Editorial and methodological articles were excluded. Data Extraction Data were extracted from articles by two authors working independently and using two analysis grids to measure the quality of economic evaluations. Data Synthesis Twenty-one studies met our inclusion criteria. All were published between 2008 and 2014. Eighteen (86%) were full economic evaluations. Cost-effectiveness analysis (CEA) was the most frequent type of economic evaluation, and was present in 11 (52%) studies. Only three CEAs complied fully with the British Medical Journal checklist. The quality of the data sources used in the 21 studies was high, but the CEAs conforming to methodological guidelines did not use high-quality data sources for all components of the analysis. Conclusions This systematic review shows that the level of evidence in economic evaluations of vertebroplasty and kyphoplasty is low, despite the recent publication of a large number of studies. This finding highlights the challenges to be faced to improve the quality of economic evaluations of medical devices. PMID:26661078

Cost-Effectiveness Analysis of Heat and Moisture Exchangers in Mechanically Ventilated Critically Ill Patients.

PubMed

Menegueti, Mayra Goncalves; Auxiliadora-Martins, Maria; Nunes, Altacilio Aparecido

2016-08-01

Moisturizing, heating and filtering gases inspired via the mechanical ventilation (MV) circuits help to reduce the adverse effects of MV. However, there is still no consensus regarding whether these measures improve patient prognosis, shorten MV duration, decrease airway secretion and lower the incidence of ventilator associated pneumonia (VAP) and other complications. The aim of this study was to study the incremental cost-effectiveness ratio associated with the use of heat and moisture exchangers (HME) filter to prevent VAP compared with the heated humidifiers (HH) presently adopted by intensive care unit (ICU) services within the Brazilian Healthcare Unified System. This study was a cost-effectiveness analysis (CEA) comparing HME and HH in preventing VAP (outcome) in mechanically ventilated adult patients admitted to an ICU of a public university hospital. The analysis considered a period of 12 months; MV duration of 11 and 12 days for patients in HH and HME groups, respectively and a daily cost of R$ 16.46 and R$ 13.42 for HH and HME, respectively. HME was more attractive; costs ranged from R$ 21,000.00 to R$ 22,000.00 and effectiveness was close to 0.71, compared with a cost of R$ 30,000.00 and effectiveness between 0.69 and 0.70 for HH. HME and HH differed significantly for incremental effectiveness. Even after an effectiveness gain of 1.5% in favor of HH, and despite the wide variation in the VAP rate, the HME effectiveness remained stable. The mean HME cost-effectiveness was lower than the mean HH cost-effectiveness, being the HME value close to R$ 44,000.00. Our findings revealed that HH and HME differ very little regarding effectiveness, which makes interpretation of the results in the context of clinical practice difficult. Nonetheless, there is no doubt that HME is advantageous. This technology incurs lower direct cost.

Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: analysis with likelihood ratio and posttest probability in a follow-up study.

PubMed

Hara, Masayasu; Kanemitsu, Yukihide; Hirai, Takashi; Komori, Koji; Kato, Tomoyuki

2008-11-01

This study was designed to determine the efficacy of carcinoembryonic antigen (CEA) monitoring for screening patients with colorectal cancer by using posttest probability of recurrence. For this study, 348 (preoperative serum CEA level elevated: CEA+, n = 119; or normal: CEA-, n = 229) patients who had undergone potentially curative surgery for colorectal cancer were enrolled. After five-year follow-up with measurements of serum CEA levels and imaging workup, posttest probabilities of recurrence were calculated. Recurrence was observed in 39 percent of CEA+ patients and 30 percent in CEA- patients, and CEA levels were elevated in 33.3 percent of CEA+ patients and 17.5 percent of CEA- patients. With obtained sensitivity (68.4 percent, CEA+; 41 percent, CEA-), specificity (83 percent, CEA+; 91 percent, CEA-) and likelihood ratio (test positive: 4.0, CEA+; 4.4, CEA-; and test negative: 0.38, CEA+; 0.66, CEA-), posttest probability given the presence of CEA elevation in the CEA+ and CEA- was 72.2 and 65.5 percent, respectively, and that given the absence of CEA elevation was 20 and 22.2 percent, respectively. Whereas postoperative CEA elevation indicates recurrence with high probability, a normal postoperative CEA is not useful for excluding the probability of recurrence.

Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials.

PubMed

Howard, George; Roubin, Gary S; Jansen, Olav; Hendrikse, Jeroen; Halliday, Alison; Fraedrich, Gustav; Eckstein, Hans-Henning; Calvet, David; Bulbulia, Richard; Bonati, Leo H; Becquemin, Jean-Pierre; Algra, Ale; Brown, Martin M; Ringleb, Peter A; Brott, Thomas G; Mas, Jean-Louis

2016-03-26

Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups. In this meta-analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis. Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2·7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65-69 years compared with patients younger than 60 years was 2·16 (95% CI 1·13-4·13), with HRs of roughly 4·0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0·34). These changes underpinned a CAS-versus CEA periprocedural HR of 1·61 (95% CI 0·90-2·88) for patients aged 65-69 years and an HR of 2·09 (1·32-3·32) for patients aged 70-74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p≥0·09 for CAS and 0·83 for CEA), or between treatment groups (p=0·84). In these RCTs, CEA was clearly superior to CAS in patients aged 70-74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

PubMed Central

DAMONTI, A.; MORELLI, P.; MUSSI, M.; PATREGNANI, C.; GARAGIOLA, E.; FOGLIA, E.; PAGANI, R.; CARMINATI, R.; PORAZZI, E.

2015-01-01

Summary Introduction. The objective of this paper is the comparison between two different technologies used for the removal of a uterine myoma, a frequent benign tumor: the standard technology currently used, laparoscopy, and an innovative one, colpoceliotomy. It was considered relevant to evaluate the real and the potential effects of the two technologies implementation and, in addition, the consequences that the introduction or exclusion of the innovative technology would have for both the National Health System (NHS) and the entire community. Methods. The comparison between these two different technologies, the standard and the innovative one, was conducted using a Health Technology Assessment (HTA). In particular, in order to analyse their differences, a multi-dimensional approach was considered: effectiveness, costs and budget impact analysis data were collected, applying different instruments, such as the Activity Based Costing methodology (ABC), the Cost-Effectiveness Analysis (CEA) and the Budget Impact Analysis (BIA). Organisational, equity and social impact were also evaluated. Results. The results showed that the introduction of colpoceliotomy would provide significant economic savings to the Regional and National Health Service; in particular, a saving of € 453.27 for each surgical procedure. Discussion. The introduction of the innovative technology, colpoceliotomy, could be considered a valuable tool; one offering many advantages related to less invasiveness and a shorter surgical procedure than the standard technology currently used (laparoscopy). PMID:26900330

Stenting versus endarterectomy for restenosis following prior ipsilateral carotid endarterectomy: an individual patient data meta-analysis.

PubMed

Fokkema, Margriet; Vrijenhoek, Joyce E P; Den Ruijter, Hester M; Groenwold, Rolf H H; Schermerhorn, Marc L; Bots, Michiel L; Pasterkamp, Gerard; Moll, Frans L; De Borst, Gert Jan

2015-03-01

To study perioperative results and restenosis during follow-up of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) for restenosis after prior ipsilateral CEA in an individual patient data (IPD) meta-analysis. The optimal treatment strategy for patients with restenosis after CEA remains unknown. A comprehensive search of electronic databases (Medline, Embase) until July 1, 2013, was performed, supplemented by a review of references. Studies were considered for inclusion if they reported procedural outcome of CAS or CEA after prior ipsilateral CEA of a minimum of 5 patients. IPD were combined into 1 data set and an IPD meta-analysis was performed. The primary endpoint was perioperative stroke or death and the secondary endpoint was restenosis greater than 50% during follow-up, comparing CAS and CEA. In total, 13 studies were included, contributing to 1132 unique patients treated by CAS (10 studies, n = 653) or CEA (7 studies; n = 479). Among CAS and CEA patients, 30% versus 40% were symptomatic, respectively (P < 0.01). After adjusting for potential confounders, the primary endpoint did not differ between CAS and CEA groups (2.3% vs 2.7%, adjusted odds ratio 0.8, 95% confidence interval (CI): 0.4-1.8). Also, the risk of restenosis during a median follow-up of 13 months was similar for both groups (hazard ratio 1.4, 95% (CI): 0.9-2.2). Cranial nerve injury (CNI) was 5.5% in the CEA group, while CAS was in 5% associated with other procedural related complications. In patients with restenosis after CEA, CAS and CEA showed similar low rates of stroke, death, and restenosis at short-term follow-up. Still, the risk of CNI and other procedure-related complications should be taken into account.

Economics of image guidance and navigation in spine surgery.

PubMed

Al-Khouja, Lutfi; Shweikeh, Faris; Pashman, Robert; Johnson, J Patrick; Kim, Terrence T; Drazin, Doniel

2015-01-01

Image-guidance and navigation in spinal surgery is becoming more widely utilized. Several studies have shown the use of this technology to increase accuracy of pedicle screw placement, decrease the rates of revision surgery, and minimize radiation exposure. In this paper, the authors analyze the economics of image-guided surgery (IGS) and navigation in spine surgery. A literature review was performed using PubMed, the CEA Registry, and the National Health Service Economic Evaluation Database. Each article was screened for inclusion and exclusion criteria, including costs, reoperation, readmission rates, operating room time, and length of stay. Thirteen studies were included in the analysis. Six studies were identified to meet the inclusion criteria for reporting costs and seven met the criteria for analysis of efficacy. Average costs ranged from $17,650 to $39,643. Pedicle screw misplacement rates using IGS ranged from 1.20% to 15.07% while reoperation rates ranged from 0% to 7.42%. There is currently an insufficient amount of studies reporting on the economics of spinal navigation to accurately conclude on its cost-effectiveness in clinical practice. Although a few of these studies showed less costs associated with intraoperative imaging, none were able to establish a statistically significant difference. Preliminary findings drawn from this study indicate a possible cost-effectiveness advantage with IGS, but more comprehensive data on costs need to be reported in order to validate its utilization.

Cost-Effectiveness Analysis of Breast Cancer Control Interventions in Peru

PubMed Central

Zelle, Sten G.; Vidaurre, Tatiana; Abugattas, Julio E.; Manrique, Javier E.; Sarria, Gustavo; Jeronimo, José; Seinfeld, Janice N.; Lauer, Jeremy A.; Sepulveda, Cecilia R.; Venegas, Diego; Baltussen, Rob

2013-01-01

Objectives In Peru, a country with constrained health resources, breast cancer control is characterized by late stage treatment and poor survival. To support breast cancer control in Peru, this study aims to determine the cost-effectiveness of different breast cancer control interventions relevant for the Peruvian context. Methods We performed a cost-effectiveness analysis (CEA) according to WHO-CHOICE guidelines, from a healthcare perspective. Different screening, early detection, palliative, and treatment interventions were evaluated using mathematical modeling. Effectiveness estimates were based on observational studies, modeling, and on information from Instituto Nacional de Enfermedades Neoplásicas (INEN). Resource utilizations and unit costs were based on estimates from INEN and observational studies. Cost-effectiveness estimates are in 2012 United States dollars (US$) per disability adjusted life year (DALY) averted. Results The current breast cancer program in Peru ($8,426 per DALY averted) could be improved through implementing triennial or biennial screening strategies. These strategies seem the most cost-effective in Peru, particularly when mobile mammography is applied (from $4,125 per DALY averted), or when both CBE screening and mammography screening are combined (from $4,239 per DALY averted). Triennially, these interventions costs between $63 million and $72 million per year. Late stage treatment, trastuzumab therapy and annual screening strategies are the least cost-effective. Conclusions Our analysis suggests that breast cancer control in Peru should be oriented towards early detection through combining fixed and mobile mammography screening (age 45-69) triennially. However, a phased introduction of triennial CBE screening (age 40-69) with upfront FNA in non-urban settings, and both CBE (age 40-49) and fixed mammography screening (age 50-69) in urban settings, seems a more feasible option and is also cost-effective. The implementation of this intervention is only meaningful if awareness raising, diagnostic, referral, treatment and basic palliative services are simultaneously improved, and if financial and organizational barriers to these services are reduced. PMID:24349314

Cost-effectiveness analysis of breast cancer control interventions in Peru.

PubMed

Zelle, Sten G; Vidaurre, Tatiana; Abugattas, Julio E; Manrique, Javier E; Sarria, Gustavo; Jeronimo, José; Seinfeld, Janice N; Lauer, Jeremy A; Sepulveda, Cecilia R; Venegas, Diego; Baltussen, Rob

2013-01-01

In Peru, a country with constrained health resources, breast cancer control is characterized by late stage treatment and poor survival. To support breast cancer control in Peru, this study aims to determine the cost-effectiveness of different breast cancer control interventions relevant for the Peruvian context. We performed a cost-effectiveness analysis (CEA) according to WHO-CHOICE guidelines, from a healthcare perspective. Different screening, early detection, palliative, and treatment interventions were evaluated using mathematical modeling. Effectiveness estimates were based on observational studies, modeling, and on information from Instituto Nacional de Enfermedades Neoplásicas (INEN). Resource utilizations and unit costs were based on estimates from INEN and observational studies. Cost-effectiveness estimates are in 2012 United States dollars (US$) per disability adjusted life year (DALY) averted. The current breast cancer program in Peru ($8,426 per DALY averted) could be improved through implementing triennial or biennial screening strategies. These strategies seem the most cost-effective in Peru, particularly when mobile mammography is applied (from $4,125 per DALY averted), or when both CBE screening and mammography screening are combined (from $4,239 per DALY averted). Triennially, these interventions costs between $63 million and $72 million per year. Late stage treatment, trastuzumab therapy and annual screening strategies are the least cost-effective. Our analysis suggests that breast cancer control in Peru should be oriented towards early detection through combining fixed and mobile mammography screening (age 45-69) triennially. However, a phased introduction of triennial CBE screening (age 40-69) with upfront FNA in non-urban settings, and both CBE (age 40-49) and fixed mammography screening (age 50-69) in urban settings, seems a more feasible option and is also cost-effective. The implementation of this intervention is only meaningful if awareness raising, diagnostic, referral, treatment and basic palliative services are simultaneously improved, and if financial and organizational barriers to these services are reduced.

Risk aversion and uncertainty in cost-effectiveness analysis: the expected-utility, moment-generating function approach.

PubMed

Elbasha, Elamin H

2005-05-01

The availability of patient-level data from clinical trials has spurred a lot of interest in developing methods for quantifying and presenting uncertainty in cost-effectiveness analysis (CEA). Although the majority has focused on developing methods for using sample data to estimate a confidence interval for an incremental cost-effectiveness ratio (ICER), a small strand of the literature has emphasized the importance of incorporating risk preferences and the trade-off between the mean and the variance of returns to investment in health and medicine (mean-variance analysis). This paper shows how the exponential utility-moment-generating function approach is a natural extension to this branch of the literature for modelling choices from healthcare interventions with uncertain costs and effects. The paper assumes an exponential utility function, which implies constant absolute risk aversion, and is based on the fact that the expected value of this function results in a convenient expression that depends only on the moment-generating function of the random variables. The mean-variance approach is shown to be a special case of this more general framework. The paper characterizes the solution to the resource allocation problem using standard optimization techniques and derives the summary measure researchers need to estimate for each programme, when the assumption of risk neutrality does not hold, and compares it to the standard incremental cost-effectiveness ratio. The importance of choosing the correct distribution of costs and effects and the issues related to estimation of the parameters of the distribution are also discussed. An empirical example to illustrate the methods and concepts is provided. Copyright 2004 John Wiley & Sons, Ltd

National variation in preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery for asymptomatic carotid artery stenosis.

PubMed

Arous, Edward J; Simons, Jessica P; Flahive, Julie M; Beck, Adam W; Stone, David H; Hoel, Andrew W; Messina, Louis M; Schanzer, Andres

2015-10-01

Carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis is among the most common procedures performed in the United States. However, consensus is lacking regarding optimal preoperative imaging, carotid duplex ultrasound criteria, and ultimately, the threshold for surgery. We sought to characterize national variation in preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery for asymptomatic CEA. The Society for Vascular Surgery Vascular Quality Initiative (VQI) database was used to identify all CEA procedures performed for asymptomatic carotid artery stenosis between 2003 and 2014. VQI currently captures 100% of CEA procedures performed at >300 centers by >2000 physicians nationwide. Three analyses were performed to quantify the variation in (1) preoperative imaging, (2) carotid duplex ultrasound criteria, and (3) threshold for surgery. Of 35,695 CEA procedures in 33,488 patients, the study cohort was limited to 19,610 CEA procedures (55%) performed for asymptomatic disease. The preoperative imaging modality used before CEA varied widely, with 57% of patients receiving a single preoperative imaging study (duplex ultrasound imaging, 46%; computed tomography angiography, 7.5%; magnetic resonance angiography, 2.0%; cerebral angiography, 1.3%) and 43% of patients receiving multiple preoperative imaging studies. Of the 16,452 asymptomatic patients (89%) who underwent preoperative duplex ultrasound imaging, there was significant variability between centers in the degree of stenosis (50%-69%, 70%-79%, 80%-99%) designated for a given peak systolic velocity, end diastolic velocity, and internal carotid artery-to-common carotid artery ratio. Although 68% of CEA procedures in asymptomatic patients were performed for an 80% to 99% stenosis, 26% were performed for a 70% to 79% stenosis, and 4.1% were performed for a 50% to 69% stenosis. At the surgeon level, the range in the percentage of CEA procedures performed for a <80% asymptomatic carotid artery stenosis is from 0% to 100%. Similarly, at the center level, institutions range in the percentage of CEA procedures performed for a <80% asymptomatic carotid artery stenosis from 0% to 100%. Despite CEA being an extremely common procedure, there is widespread variation in the three primary determinants-preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery-of whether CEA is performed for asymptomatic carotid stenosis. Standardizing the approach to care for asymptomatic carotid artery stenosis will mitigate the significant downstream effects of this variation on health care costs. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Systematic review of drug administration costs and implications for biopharmaceutical manufacturing.

PubMed

Tetteh, Ebenezer; Morris, Stephen

2013-10-01

The acquisition costs of biologic drugs are often considered to be relatively high compared with those of nonbiologics. However, the total costs of delivering these drugs also depend on the cost of administration. Ignoring drug administration costs may distort resource allocation decisions because these affect cost effectiveness. The objectives of this systematic review were to develop a framework of drug administration costs that considers both the costs of physical administration and the associated proximal costs; and, as a case example, to use this framework to evaluate administration costs for biologics within the UK National Health Service (NHS). We reviewed literature that reported estimates of administration costs for biologics within the UK NHS to identify how these costs were quantified and to examine how differences in dosage forms and regimens influenced administration costs. The literature reviewed were identified by searching the Centre for Review and Dissemination Databases (DARE, NHS EED and HTA); EMBASE (The Excerpta Medica Database); MEDLINE (using the OVID interface); Econlit (EBSCO); Tufts Medical Center Cost Effectiveness Analysis (CEA) Registry; and Google Scholar. We identified 4,344 potentially relevant studies, of which 43 studies were selected for this systematic review. We extracted estimates of the administration costs of biologics from these studies. We found evidence of variation in the way that administration costs were measured, and that this affected the magnitude of costs reported, which could then influence cost effectiveness. Our findings suggested that manufacturers of biologic medicines should pay attention to formulation issues and their impact on administration costs, because these affect the total costs of healthcare delivery and cost effectiveness.

The Endocannabinoid System Tonically Regulates Inhibitory Transmission and Depresses the Effect of Ethanol in Central Amygdala

PubMed Central

Roberto, Marisa; Cruz, Maureen; Bajo, Michal; Siggins, George R; Parsons, Loren H; Schweitzer, Paul

2010-01-01

The central amygdala (CeA) has a major role in alcohol dependence and reinforcement, and behavioral and neurochemical evidence suggests a role for the endocannabinoid (eCB) system in ethanol binging and dependence. We used a slice preparation to investigate the physiological role of cannabinoids and their interaction with ethanol on inhibitory synaptic transmission in CeA. Superfusion of the cannabinoid receptor (CB1) agonist WIN55212-2 (WIN2) onto CeA neurons decreased evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) in a concentration-dependent manner, an effect prevented by the CB1 antagonists Rimonabant (SR141716, SR1) and AM251. SR1 or AM251 applied alone augmented IPSPs, revealing a tonic eCB activity that decreased inhibitory transmission in CeA. Paired-pulse analysis suggested a presynaptic CB1 mechanism. Intracellular BAPTA abolished the ability of AM251 to augment IPSPs, demonstrating the eCB-driven nature and postsynaptic origin of the tonic CB1-dependent control of GABA release. Superfusion of ethanol increased IPSPs and addition of WIN2 reversed the ethanol effect. Similarly, previous superfusion of WIN2 prevented subsequent ethanol effects on GABAergic transmission. The ethanol-induced augmentation of IPSPs was additive to CB1 blockade, ruling out a participation of CB1 in the action of acute ethanol. Our study points to an important role of CB1 in CeA in which the eCBs tonically regulate neuronal activity, and suggests a potent mechanism for modulating CeA tone during challenge with ethanol. PMID:20463657

Meta-analysis and meta-regression analysis of outcomes of carotid endarterectomy and stenting in the elderly.

PubMed

Antoniou, George A; Georgiadis, George S; Georgakarakos, Efstratios I; Antoniou, Stavros A; Bessias, Nikos; Smyth, John Vincent; Murray, David; Lazarides, Miltos K

2013-12-01

Uncertainty exists about the influence of advanced age on the outcomes of carotid revascularization. To undertake a comprehensive review of the literature and conduct an analysis of the outcomes of carotid interventions in the elderly. A systematic literature review was conducted to identify articles comparing early outcomes of carotid endarterectomy (CEA) or carotid stenting (CAS) in elderly and young patients. Combined overall effect sizes were calculated using fixed or random effects models. Meta-regression models were formed to explore potential heterogeneity as a result of changes in practice over time. RESULTS Our analysis comprised 44 studies reporting data on 512,685 CEA and 75,201 CAS procedures. Carotid stenting was associated with increased incidence of stroke in elderly patients compared with their young counterparts (odds ratio [OR], 1.56; 95% CI, 1.40-1.75), whereas CEA had equivalent cerebrovascular outcomes in old and young age groups (OR, 0.94; 95% CI, 0.88-0.99). Carotid stenting had similar peri-interventional mortality risks in old and young patients (OR, 0.86; 95% CI, 0.72-1.03), whereas CEA was associated with heightened mortality in elderly patients (OR, 1.62; 95% CI, 1.47-1.77). The incidence of myocardial infarction was increased in patients of advanced age in both CEA and CAS (OR, 1.64; 95% CI, 1.57-1.72 and OR, 1.30; 95% CI, 1.16-1.45, respectively). Meta-regression analyses revealed a significant effect of publication date on peri-interventional stroke (P = .003) and mortality (P < .001) in CAS. Age should be considered when planning a carotid intervention. Carotid stenting has an increased risk of adverse cerebrovascular events in elderly patients but mortality equivalent to younger patients. Carotid endarterectomy is associated with similar neurologic outcomes in elderly and young patients, at the expense of increased mortality.

Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma

PubMed Central

2010-01-01

Background The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Methods Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. Results The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. Conclusions CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients. PMID:21040522

Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma.

PubMed

Qiu, Miao-Zhen; Li, Zhuang-Hua; Zhou, Zhi-Wei; Li, Yu-Hong; Wang, Zhi-Qiang; Wang, Feng-Hua; Huang, Peng; Aziz, Fahad; Wang, Dao-Yuan; Xu, Rui-Hua

2010-10-31

The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients.

Missing data in trial‐based cost‐effectiveness analysis: An incomplete journey

PubMed Central

Gomes, Manuel; Carpenter, James R.

2018-01-01

SUMMARY Cost‐effectiveness analyses (CEA) conducted alongside randomised trials provide key evidence for informing healthcare decision making, but missing data pose substantive challenges. Recently, there have been a number of developments in methods and guidelines addressing missing data in trials. However, it is unclear whether these developments have permeated CEA practice. This paper critically reviews the extent of and methods used to address missing data in recently published trial‐based CEA. Issues of the Health Technology Assessment journal from 2013 to 2015 were searched. Fifty‐two eligible studies were identified. Missing data were very common; the median proportion of trial participants with complete cost‐effectiveness data was 63% (interquartile range: 47%–81%). The most common approach for the primary analysis was to restrict analysis to those with complete data (43%), followed by multiple imputation (30%). Half of the studies conducted some sort of sensitivity analyses, but only 2 (4%) considered possible departures from the missing‐at‐random assumption. Further improvements are needed to address missing data in cost‐effectiveness analyses conducted alongside randomised trials. These should focus on limiting the extent of missing data, choosing an appropriate method for the primary analysis that is valid under contextually plausible assumptions, and conducting sensitivity analyses to departures from the missing‐at‐random assumption. PMID:29573044

Approaches to Aggregation and Decision Making-A Health Economics Approach: An ISPOR Special Task Force Report [5].

PubMed

Phelps, Charles E; Lakdawalla, Darius N; Basu, Anirban; Drummond, Michael F; Towse, Adrian; Danzon, Patricia M

2018-02-01

The fifth section of our Special Task Force report identifies and discusses two aggregation issues: 1) aggregation of cost and benefit information across individuals to a population level for benefit plan decision making and 2) combining multiple elements of value into a single value metric for individuals. First, we argue that additional elements could be included in measures of value, but such elements have not generally been included in measures of quality-adjusted life-years. For example, we describe a recently developed extended cost-effectiveness analysis (ECEA) that provides a good example of how to use a broader concept of utility. ECEA adds two features-measures of financial risk protection and income distributional consequences. We then discuss a further option for expanding this approach-augmented CEA, which can introduce many value measures. Neither of these approaches, however, provide a comprehensive measure of value. To resolve this issue, we review a technique called multicriteria decision analysis that can provide a comprehensive measure of value. We then discuss budget-setting and prioritization using multicriteria decision analysis, issues not yet fully resolved. Next, we discuss deliberative processes, which represent another important approach for population- or plan-level decisions used by many health technology assessment bodies. These use quantitative information on CEA and other elements, but the group decisions are reached by a deliberative voting process. Finally, we briefly discuss the use of stated preference methods for developing "hedonic" value frameworks, and conclude with some recommendations in this area. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

What is the budget impact of a new treatment or new health technology arriving on the market?

PubMed

Dervaux, Benoit; Le Fur, Camille; Dubois, Sophie; Josseran, Anne

2017-02-01

In France, market access for innovative drugs (level I, II & III improvement of medical service rendered having significant impact on health insurance expenditure) involves medico-economic evaluation. In addition to cost-effectiveness analysis (CEA), budget impact analysis (BIA) can be performed, especially since the sustainability of the health insurance system has become a growing concern for all stakeholders. The members of the Giens 2016 round table discussed the contribution of BIA based on a review of the literature on distribution models, the participants' experiences including experience related to the modalities of hospital assessments, and examples from other countries. The round table established recommendations on four elements of interest: 1: the use of BIA from a contractual point of view - between manufacturers and the French Economic Committee for Health Products - during the price negotiations process, and from a prospective point of view within the framework of the annual review of budget expenditures; the definition of the target population and the rhythm of a health product's distribution are also major elements; 2: the interpretation of BIA results in light of CEA results: for what products and at what moment in the life cycle of these products; 3: the integration of the rhythm of a health product's distribution into the BIA; 4: preoccupations about how the level of health product implementation is integrated into the BIA in terms of opportunity cost and organisational quality for the promoter. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

Effect of heterogeneity of carcinoembryonic antigen on liver cell membrane binding and its kinetics of removal from circulation.

PubMed

Byrn, R A; Medrek, P; Thomas, P; Jeanloz, R W; Zamcheck, N

1985-07-01

Carcinoembryonic antigen (CEA) is a glycoprotein metabolized primarily by the liver. Subcellular fractions of rat liver were examined for CEA binding activity. Hepatocyte plasma membrane and microsome fractions bound CEA, and this binding shared the calcium requirement, neuraminidase sensitivity, and carbohydrate specificity of the hepatocyte asialoglycoprotein receptor. CEA had previously been shown to react with this galactose-specific receptor, in vivo, only following neuraminidase treatment. Galactose receptor binding of CEA was measured in three different purified CEA preparations. The fraction of CEA capable of binding to excess levels of galactose receptor on membranes varied (46.5%, 40.2%, and 4.7% for CEA-1, -2, and -3, respectively). These CEAs were shown to be 2.3%, 7.9%, and 0.7% as effective, respectively, as asialo-alpha 1-acid glycoprotein in inhibiting the binding of radiolabeled asialo-alpha 1-acid glycoprotein to liver cell membranes. Each of the three CEA preparations showed different clearance kinetics from the circulation of mice. Coinjection of asialo-alpha 1-acid glycoprotein with the CEAs revealed differing inhibition of the clearances. These results show that differences in the carbohydrate components of purified CEA preparations affect their rate of removal from circulation and thus possibly the relationship between CEA production and observed plasma levels in patients. The possible origin of these CEA differences is discussed with their clinical implications.

Cost-effectiveness of direct-acting antiviral regimen ombitasvir/paritaprevir/ritonavir in treatment-naïve and treatment-experienced patients infected with chronic hepatitis C virus genotype 1b in Japan.

PubMed

Virabhak, Suchin; Yasui, Kikuo; Yamazaki, Kiyotaka; Johnson, Scott; Mitchell, Dominic; Yuen, Cammy; Samp, Jennifer C; Igarashi, Ataru

2016-12-01

This study compared the cost-effectiveness of chronic hepatitis C virus (HCV) genotype 1b (GT1b) therapy ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) vs daclatasvir + asunaprevir (DCV/ASV) and no treatment in patients without cirrhosis. Cost-effectiveness analyses (CEAs) that compared OBV/PTV/r against DCV/ASV and sofosbuvir/ledipasvir (SOF/LDV) in Y93H mutation-negative, GT1b patients with and without cirrhosis were also included. A health state transition model was developed to capture the natural history of HCV. A CEA over a lifetime horizon was performed from the perspective of the public healthcare payer in Japan. Costs, health utilities, and rates of disease progression were derived from published studies. Sustained virologic response (SVR) rates of OBV/PTV/r and DCV/ASV were extracted from Japanese clinical trials. Analyses were performed for treatment-naïve and -experienced patients. Alternative scenarios and input parameter uncertainty on the results were tested. OBV/PTV/r exhibited superior clinical outcomes vs comparators. For OBV/PTV/r, DCV/ASV, and no treatment, the lifetime risk of decompensated cirrhosis in treatment-naïve patients without cirrhosis was 0.4%, 1.4%, and 9.2%, and hepatocellular carcinoma was 6.5%, 11.4%, and 49.9%, respectively. Quality-adjusted life years (QALYs) were higher in treatment-naïve and -experienced patients without cirrhosis treated with OBV/PTV/r (16.41 and 16.22) vs DCV/ASV (15.83 and 15.66) or no treatment (11.34 and 11.23). In treatment-naïve and -experienced patients without cirrhosis, the incremental cost-effectiveness ratios (ICERs) of OBV/PTV/r vs DCV/ASV were JPY 1,684,751/QALY and JPY 1,836,596/QALY, respectively; OBV/PTV/r was dominant compared with no treatment. In scenario analysis, including GT1b patients with and without cirrhosis who were Y93H mutation-negative, the ICER of OBV/PTV/r vs DCV/ASV was below the Japanese willingness-to-pay threshold of JPY 5 million/QALY, while the ICER of SOF/LDV vs OBV/PTV/r was above this threshold; thus, OBV/PTV/r was cost-effective. OBV/PTV/r appears to be a cost-effective treatment for chronic HCV GT1b infection against DCV/ASV. OBV/PTV/r dominates no treatment in patients without cirrhosis.

[A study of growth and malignancy grading of stomach and colorectal cancers by serial serum carcinoembryonic antigen levels analysis].

PubMed

Umehara, Y; Miyahara, T; Yoshida, M; Isobe, S; Oba, N; Harada, Y

1990-06-01

Changes in serum CEA levels were analyzed on a time-course basis in 33 patients with stomach cancer and 20 patients with colorectal cancer. A linear relationship between log CEA and time could be evaluated and individual CEA doubling time (CEA D.T.) was calculated. The results obtained are as follows. 1) The CEA D.T. was not constant from the onset of the disease to death in stomach cancer and colorectal cancer. 2) The CEA D.T. was distributed widely with 5 to 140 days in stomach cancer and 8 to 134 days in colorectal cancer. It tended to be shortened at the terminal stage in both tumors. 3) In terms of age, sex and histology, the CEA D.T. tended to be short in the young, female and poorly differentiated cancer. These background appeared to have an influence on the growth of tumor. 4) The CEA D.T. was well correlated with the period of survival of the patients with gastric cancer (r = 0.636, p less than 0.001). The analysis of serial CEA levels on a time-course basis is considered useful in studying the relationship between tumor-bearing hosts and malignancy of the tumor.

Discrete Event Simulation-Based Resource Modelling in Health Technology Assessment.

PubMed

Salleh, Syed; Thokala, Praveen; Brennan, Alan; Hughes, Ruby; Dixon, Simon

2017-10-01

The objective of this article was to conduct a systematic review of published research on the use of discrete event simulation (DES) for resource modelling (RM) in health technology assessment (HTA). RM is broadly defined as incorporating and measuring effects of constraints on physical resources (e.g. beds, doctors, nurses) in HTA models. Systematic literature searches were conducted in academic databases (JSTOR, SAGE, SPRINGER, SCOPUS, IEEE, Science Direct, PubMed, EMBASE) and grey literature (Google Scholar, NHS journal library), enhanced by manual searchers (i.e. reference list checking, citation searching and hand-searching techniques). The search strategy yielded 4117 potentially relevant citations. Following the screening and manual searches, ten articles were included. Reviewing these articles provided insights into the applications of RM: firstly, different types of economic analyses, model settings, RM and cost-effectiveness analysis (CEA) outcomes were identified. Secondly, variation in the characteristics of the constraints such as types and nature of constraints and sources of data for the constraints were identified. Thirdly, it was found that including the effects of constraints caused the CEA results to change in these articles. The review found that DES proved to be an effective technique for RM but there were only a small number of studies applied in HTA. However, these studies showed the important consequences of modelling physical constraints and point to the need for a framework to be developed to guide future applications of this approach.

Anti-social welfare functions: a reply to Hansen et al.

PubMed

Edlin, Richard

2004-09-01

We could reasonably expect society to give at least the same weight to the marginal utility of the poor as to the rich, and to the marginal utility of the ill as compared to the healthy. Whilst Hansen et al. [Journal of Health Economics (2004)], may be said to link CEA and CBA within a welfarist framework, the assumptions they require are inconsistent with these types of ethical preferences. Thus, the degree to which they employ a reasonable social welfare function is doubtful. This paper argues that any link between CEA and CBA will occur not within a welfarist framework but instead within a non-welfarist one in which it is unlikely that CBA results could be easily transformed into cost-effectiveness ratios.

Epidural Analgesia Versus Patient-Controlled Analgesia for Pain Relief in Uterine Artery Embolization for Uterine Fibroids: A Decision Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kooij, Sanne M. van der, E-mail: s.m.vanderkooij@amc.uva.nl; Moolenaar, Lobke M.; Ankum, Willem M.

Purpose: This study was designed to compare the costs and effects of epidural analgesia (EDA) to those of patient-controlled intravenous analgesia (PCA) for postintervention pain relief in women having uterine artery embolization (UAE) for systematic uterine fibroids. Methods: Cost-effectiveness analysis (CEA) based on data from the literature by constructing a decision tree to model the clinical pathways for estimating the effects and costs of treatment with EDA and PCA. Literature on EDA for pain-relief after UAE was missing, and therefore, data on EDA for abdominal surgery were used. Outcome measures were compared costs to reduce one point in visual analoguemore » score (VAS) or numeric rating scale (NRS) for pain 6 and 24 h after UAE and risk for complications. Results: Six hours after the intervention, the VAS was 3.56 when using PCA and 2.0 when using EDA. The costs for pain relief in women undergoing UAE with PCA and EDA were Euro-Sign 191 and Euro-Sign 355, respectively. The costs for EDA to reduce the VAS score 6 h after the intervention with one point compared with PCA were Euro-Sign 105 and Euro-Sign 179 after 24 h. The risk of having a complication was 2.45 times higher when using EDA. Conclusions: The results of this indirect comparison of EDA for abdominal surgery with PCA for UAE show that EDA would provide superior analgesia for post UAE pain at 6 and 24 h but with higher costs and an increased risk of complications.« less

Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.

PubMed

Demirel, Serdar; Attigah, Nicolas; Bruijnen, Hans; Ringleb, Peter; Eckstein, Hans-Henning; Fraedrich, Gustav; Böckler, Dittmar

2012-07-01

Carotid endarterectomy (CEA) is beneficial in patients with symptomatic carotid artery stenosis. However, randomized trials have not provided evidence concerning the optimal CEA technique, conventional or eversion. The outcome of 563 patients within the surgical randomization arm of the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE-1) trial was analyzed by surgical technique subgroups: eversion endarterectomy versus conventional endarterectomy with patch angioplasty. The primary end point was ipsilateral stroke or death within 30 days after surgery. Secondary outcome events included perioperative adverse events and the 2-year risk of restenosis, stroke, and death. Both groups were similar in terms of demographic and other baseline clinical variables. Shunt frequency was higher in the conventional CEA group (65% versus 17%; P<0.0001). The risk of ipsilateral stroke or death within 30 days after surgery was significantly greater with eversion CEA (9% versus 3%; P=0.005). There were no statistically significant differences in the rate of perioperative secondary outcome events with the exception of a significantly higher risk of intraoperative ipsilateral stroke rate in the eversion CEA group (4% versus 0.3%; P=0.0035). The 2-year risk of ipsilateral stroke occurring after 30 days was significantly higher in the conventional CEA group (2.9% versus 0%; P=0.017). In patients with symptomatic carotid artery stenosis, conventional CEA appears to be associated with better periprocedural neurological outcome than eversion CEA. Eversion CEA, however, may be more effective for long-term prevention of ipsilateral stroke. These findings should be interpreted with caution noting the limitations of the post hoc, nonrandomized nature of the analysis.

Evaluation of the CEAS model for barley yields in North Dakota and Minnesota

NASA Technical Reports Server (NTRS)

Barnett, T. L. (Principal Investigator)

1981-01-01

The CEAS yield model is based upon multiple regression analysis at the CRD and state levels. For the historical time series, yield is regressed on a set of variables derived from monthly mean temperature and monthly precipitation. Technological trend is represented by piecewise linear and/or quadriatic functions of year. Indicators of yield reliability obtained from a ten-year bootstrap test (1970-79) demonstrated that biases are small and performance as indicated by the root mean square errors are acceptable for intended application, however, model response for individual years particularly unusual years, is not very reliable and shows some large errors. The model is objective, adequate, timely, simple and not costly. It considers scientific knowledge on a broad scale but not in detail, and does not provide a good current measure of modeled yield reliability.

Age-dependent effects of carotid endarterectomy or stenting on cognitive performance.

PubMed

Wasser, Katrin; Hildebrandt, Helmut; Gröschel, Sonja; Stojanovic, Tomislav; Schmidt, Holger; Gröschel, Klaus; Pilgram-Pastor, Sara M; Knauth, Michael; Kastrup, Andreas

2012-11-01

Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (<68 years and ≥68 years); 27 healthy subjects served as a control group. In all patients clinical examinations, MRI scans and a neuropsychological test battery that assessed four major cognitive domains were performed immediately before, within 72 h, and 3 months after CEA or CAS. While patients <68 years of age showed no significant cognitive alteration after either CEA or CAS, a significant cognitive decline was observed in patients ≥68 years in both treatment groups (p = 0.001). Notably, this cognitive deterioration persisted in patients after CEA, whereas it was only transient in patients treated with CAS. These results demonstrate an age-dependent effect of CEA and CAS on cognitive functions. In contrast to the recently observed increased clinical complication rates in older subjects after CAS compared with CEA, CEA appears to be associated with a greater, persistent decline in cognitive performance than CAS in this subgroup of patients.

Increased resource utilization and overall morbidity are associated with general versus regional anesthesia for carotid endarterectomy in data collected by the Michigan Surgical Quality Collaborative.

PubMed

Hussain, Ahmad S; Mullard, Andrew; Oppat, William F; Nolan, Kevin D

2017-09-01

Advocates for performing carotid endarterectomy (CEA) under regional anesthesia (RA) cite reduction in hemodynamic instability and the ability for neurologic monitoring, but many still prefer general anesthesia (GA) as benefits of RA have not been clearly demonstrated, reliable RA may not be available in all centers, and a certain amount of movement by the patient during the procedure may not be uniformly tolerated. We evaluated the association of anesthesia type and perioperative morbidity and mortality as well as resource utilization in patients undergoing CEA using the Michigan Surgical Quality Collaborative (MSQC) database. Between 2012 and 2014, 4558 patients underwent CEA among the MSQC participating hospitals. Of these patients, 4008 underwent CEA under GA and 550 underwent CEA under RA. Data points were collected for each procedure, and a review of 30-day perioperative outcomes was conducted using the χ 2 test. Propensity score regression adjusted for case mix preoperative conditions as fixed effects, and a mixed model adjusted for site as a random effect. The two groups were similar in gender and incidence of hypertension, diabetes, congestive heart failure, and smoking history. The RA group tended to be of better functional status. After GA, there was a greater than twofold higher percentage of any morbidity (8.7% vs 4.2%). Further analysis demonstrated that patients undergoing GA had higher unadjusted rates for mortality (1.0% vs 0.0%), unplanned intubations (2.1% vs 0.6%), pneumonia (1.3% vs 0.0%), sepsis (0.8% vs 0.0%), and readmissions (9.2% vs 6.1%). Adjusting for case mix and random effect, there was statistically significantly higher overall morbidity (P = .0002), unplanned intubation (P = .0196), extended length of stay (P = .0007), emergency department visits (P = .0379), and readmissions (P = .0149) in the GA group. There was no statistically significant difference in incidence of myocardial infarction or cerebrovascular accident. Based on this analysis from the MSQC database, there is an associated increased morbidity and resource utilization with GA vs RA for CEA. This has implications for enterprise resource planning initiatives and the CEA value proposition in general, which is of special interest to both hospitals and payers. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Insurance Companies’ Perspectives on the Orphan Drug Pipeline

PubMed Central

Handfield, Robert; Feldstein, Josh

2013-01-01

Background Rare diseases are of increasing concern to private and public healthcare insurance plans. Largely neglected by manufacturers before the 1983 passing of the Orphan Drug Act (ODA), orphan drugs have become a commercialization target of steadily increasing importance to the healthcare industry. The ODA mandates the coverage of rare diseases, which are defined in research communities as diseases that are so infrequent that there is no reasonable expectation of a drugmaker recovering the cost of developing that drug. Objectives To determine the views of leading commercial US payers regarding providing access to and coverage for orphan drugs; to assess whether and to what degree cost-effectiveness analysis (CEA) is viewed by payers as relevant to rare disease coverage. Methods The study sample was identified through a call for action sent by America's Health Insurance Plans to its members, resulting in 4 interviews conducted and 3 completed surveys from a total of 7 companies. These 7 US health insurance companies represent approximately 75% of the US private insurance market by revenue and include approximately 157 million covered lives (using self-reported data from insurance companies). Representatives of 3 companies responded to the survey, and representatives of 4 companies were interviewed via the phone. The interviews were conducted with subject matter experts at each company and included 2 senior vice presidents of a pharmacy program, 1 chief medical director, and 1 head of pharmacoeconomics. The surveys were completed by 1 vice president of clinical pharmacy strategy, 1 chief pharmacy director, and 1 medical director. Results Based on the responses in this study, approximately 67% of US private insurance companies are concerned about orphan drugs, but only approximately 17% have developed meaningful strategies for addressing the cost of orphan drugs. Of the companies who do have such a strategy, 100% are unsure how to determine the best economic assessment tools to control orphan drug costs, and two thirds are relying on prior authorization as a means to control costs. More than 80% of the companies are not using cost-effectiveness methodologies with regard to rare diseases, generally because of a lack of the availability of medicines to facilitate such comparisons. CEA is used by less than 20% of our study sample of payers in dealing with orphan drug policies. Conclusions Evaluating cost-effectiveness is a valuable strategy for payers seeking to facilitate appropriate access and coverage decision-making related to orphan drugs, but it is not well understood or adapted by private insurance companies. Health economists, along with providers and payers, must work together to design rational methodologies to evaluate the value of orphan drugs, perhaps by adopting cost-effectiveness methodologies to consider a compound's total research and development and commercialization demands relative to its cost-effectiveness. PMID:24991385

Insurance companies' perspectives on the orphan drug pipeline.

PubMed

Handfield, Robert; Feldstein, Josh

2013-11-01

Rare diseases are of increasing concern to private and public healthcare insurance plans. Largely neglected by manufacturers before the 1983 passing of the Orphan Drug Act (ODA), orphan drugs have become a commercialization target of steadily increasing importance to the healthcare industry. The ODA mandates the coverage of rare diseases, which are defined in research communities as diseases that are so infrequent that there is no reasonable expectation of a drugmaker recovering the cost of developing that drug. To determine the views of leading commercial US payers regarding providing access to and coverage for orphan drugs; to assess whether and to what degree cost-effectiveness analysis (CEA) is viewed by payers as relevant to rare disease coverage. The study sample was identified through a call for action sent by America's Health Insurance Plans to its members, resulting in 4 interviews conducted and 3 completed surveys from a total of 7 companies. These 7 US health insurance companies represent approximately 75% of the US private insurance market by revenue and include approximately 157 million covered lives (using self-reported data from insurance companies). Representatives of 3 companies responded to the survey, and representatives of 4 companies were interviewed via the phone. The interviews were conducted with subject matter experts at each company and included 2 senior vice presidents of a pharmacy program, 1 chief medical director, and 1 head of pharmacoeconomics. The surveys were completed by 1 vice president of clinical pharmacy strategy, 1 chief pharmacy director, and 1 medical director. Based on the responses in this study, approximately 67% of US private insurance companies are concerned about orphan drugs, but only approximately 17% have developed meaningful strategies for addressing the cost of orphan drugs. Of the companies who do have such a strategy, 100% are unsure how to determine the best economic assessment tools to control orphan drug costs, and two thirds are relying on prior authorization as a means to control costs. More than 80% of the companies are not using cost-effectiveness methodologies with regard to rare diseases, generally because of a lack of the availability of medicines to facilitate such comparisons. CEA is used by less than 20% of our study sample of payers in dealing with orphan drug policies. Evaluating cost-effectiveness is a valuable strategy for payers seeking to facilitate appropriate access and coverage decision-making related to orphan drugs, but it is not well understood or adapted by private insurance companies. Health economists, along with providers and payers, must work together to design rational methodologies to evaluate the value of orphan drugs, perhaps by adopting cost-effectiveness methodologies to consider a compound's total research and development and commercialization demands relative to its cost-effectiveness.

Cost Utility Analysis of the Cervical Artificial Disc vs Fusion for the Treatment of 2-Level Symptomatic Degenerative Disc Disease: 5-Year Follow-up.

PubMed

Ament, Jared D; Yang, Zhuo; Nunley, Pierce; Stone, Marcus B; Lee, Darrin; Kim, Kee D

2016-07-01

The cervical total disc replacement (cTDR) was developed to treat cervical degenerative disc disease while preserving motion. Cost-effectiveness of this intervention was established by looking at 2-year follow-up, and this update reevaluates our analysis over 5 years. Data were derived from a randomized trial of 330 patients. Data from the 12-Item Short Form Health Survey were transformed into utilities by using the SF-6D algorithm. Costs were calculated by extracting diagnosis-related group codes and then applying 2014 Medicare reimbursement rates. A Markov model evaluated quality-adjusted life years (QALYs) for both treatment groups. Univariate and multivariate sensitivity analyses were conducted to test the stability of the model. The model adopted both societal and health system perspectives and applied a 3% annual discount rate. The cTDR costs $1687 more than anterior cervical discectomy and fusion (ACDF) over 5 years. In contrast, cTDR had $34 377 less productivity loss compared with ACDF. There was a significant difference in the return-to-work rate (81.6% compared with 65.4% for cTDR and ACDF, respectively; P = .029). From a societal perspective, the incremental cost-effective ratio (ICER) for cTDR was -$165 103 per QALY. From a health system perspective, the ICER for cTDR was $8518 per QALY. In the sensitivity analysis, the ICER for cTDR remained below the US willingness-to-pay threshold of $50 000 per QALY in all scenarios (-$225 816 per QALY to $22 071 per QALY). This study is the first to report the comparative cost-effectiveness of cTDR vs ACDF for 2-level degenerative disc disease at 5 years. The authors conclude that, because of the negative ICER, cTDR is the dominant modality. ACDF, anterior cervical discectomy and fusionAWP, average wholesale priceCE, cost-effectivenessCEA, cost-effectiveness analysisCPT, Current Procedural TerminologycTDR, cervical total disc replacementCUA, cost-utility analysisDDD, degenerative disc diseaseDRG, diagnosis-related groupFDA, US Food and Drug AdministrationICER, incremental cost-effectiveness ratioIDE, Investigational Device ExemptionNDI, neck disability indexQALY, quality-adjusted life yearsRCT, randomized controlled trialRTW, return-to-workSF-12, 12-Item Short Form Health SurveyVAS, visual analog scaleWTP, willingness-to-pay.

[Significance of CEA in gastric and colorectal cancer].

PubMed

Uehara, K; Miyamoto, Y; Izuo, M; Shiozaki, H; Aiba, S; Matsumoto, H

1985-04-01

The determination of serum CEA (Sandwich method) and CEA staining (PAP method) of excised specimens were performed in patients with gastric or colorectal cancer, and the biological characteristics of each cancer and the factors to increase serum CEA were studied with the following results: As colonic cancer has strong CEA productivity, serum CEA can be useful for the detection of cancer, and especially effective for the postoperative observation. Gastric cancer has weak CEA productivity, and serum CEA is not so useful in the detection of cancer and the judgement of resectability. The CEA positive rate of tissue with CEA staining was 80% in gastric cancer, 100% in colonic cancer, and were nearly equal to the CEA positive rate of serum in the group of terminal stage. In the mode of CEA staining of cancerous cells, IV type was observed most frequently in gastric cancer, and I type in colonic cancer. Among the resected cases showing more than 7ng/ml serum CEA, differentiated type, lymph node metastasis (+), the degree of tissue staining with CEA staining, the mode of cell staining O or I type in gastric cancer and I type in colonic cancer were observed in common.

At What Price? A Cost-Effectiveness Analysis Comparing Trial of Labour after Previous Caesarean versus Elective Repeat Caesarean Delivery

PubMed Central

Fawsitt, Christopher G.; Bourke, Jane; Greene, Richard A.; Everard, Claire M.; Murphy, Aileen; Lutomski, Jennifer E.

2013-01-01

Background Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland. Methods Using a decision analytic model, a cost-effectiveness analysis (CEA) was performed where the measure of health gain was quality-adjusted life years (QALYs) over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC) and ERCD. Delivery/procedure costs derived from primary data collection and combined both “bottom-up” and “top-down” costing estimations. Results Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD (€1,835.06 versus €4,039.87 per women, respectively), and QALYs were modestly higher (0.84 versus 0.70). Our findings were supported by probabilistic sensitivity analysis. Conclusions Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single comprehensive decision model. PMID:23484038

Novel flow cytometric analysis of the progress and route of internalization of a monoclonal anti-carcinoembryonic antigen (CEA) antibody.

PubMed

Ford, C H; Tsaltas, G C; Osborne, P A; Addetia, K

1996-03-01

A flow cytometric method of studying the internalization of a monoclonal antibody (Mab) directed against carcinoembryonic antigen (CEA) has been compared with Western blotting, using three human colonic cancer cell lines which express varying amounts of the target antigen. Cell samples incubated for increasing time intervals with fluoresceinated or unlabelled Mab were analyzed using flow cytometry or polyacrylamide gel electrophoresis and Western blotting. SDS/PAGE analysis of cytosolic and membrane components of solubilized cells from the cell lines provided evidence of non-degraded internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 min. Internalized anti-CEA was detected in the case of high CEA expressing cell lines (LS174T, SKCO1). Very similar results were obtained with an anti-fluorescein flow cytometric assay. Given that these two methods consistently provided comparable results, use of flow cytometry for the detection of internalized antibody is suggested as a rapid alternative to most currently used methods for assessing antibody internalization. The question of the endocytic route followed by CEA-anti-CEA complexes was addressed by using hypertonic medium to block clathrin mediated endocytosis.

AT1 receptor blockade in the central nucleus of the amygdala attenuates the effects of muscimol on sodium and water intake.

PubMed

Hu, B; Qiao, H; Sun, B; Jia, R; Fan, Y; Wang, N; Lu, B; Yan, J Q

2015-10-29

The blockade of the central nucleus of the amygdala (CeA) with the GABAA receptor agonist muscimol significantly reduces hypertonic NaCl and water intake by sodium-depleted rats. In the present study we investigated the effects of previous injection of losartan, an angiotensin II type-1 (AT1) receptor antagonist, into the CeA on 0.3M NaCl and water intake reduced by muscimol bilaterally injected into the same areas in rats submitted to water deprivation-partial rehydration (WD-PR) and in rats treated with the diuretic furosemide (FURO). Male Sprague-Dawley rats with stainless steel cannulas bilaterally implanted into the CeA were used. Bilateral injections of muscimol (0.2 nmol/0.5 μl, n=8 rats/group) into the CeA in WD-PR-treated rats reduced 0.3M NaCl intake and water intake, and pre-treatment of the CeA with losartan (50 μg/0.5 μl) reversed the inhibitory effect of muscimol. The negative effect of muscimol on sodium and water intake could also be blocked by pretreatment with losartan microinjected into the CeA in rats given FURO (n=8 rats/group). However, bilateral injections of losartan (50 μg/0.5 μl) alone into the CeA did not affect the NaCl or water intake. These results suggest that the deactivation of CeA facilitatory mechanisms by muscimol injection into the CeA is promoted by endogenous angiotensin II acting on AT1 receptors in the CeA, which prevents rats from ingesting large amounts of hypertonic NaCl and water. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

PubMed

Otoshi, Takehiro; Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

Cost-effectiveness analysis of TOC removal from slaughterhouse wastewater using combined anaerobic-aerobic and UV/H2O2 processes.

PubMed

Bustillo-Lecompte, Ciro Fernando; Mehrvar, Mehrab; Quiñones-Bolaños, Edgar

2014-02-15

The objective of this study is to evaluate the operating costs of treating slaughterhouse wastewater (SWW) using combined biological and advanced oxidation processes (AOPs). This study compares the performance and the treatment capability of an anaerobic baffled reactor (ABR), an aerated completely mixed activated sludge reactor (AS), and a UV/H2O2 process, as well as their combination for the removal of the total organic carbon (TOC). Overall efficiencies are found to be up to 75.22, 89.47, 94.53, 96.10, 96.36, and 99.98% for the UV/H2O2, ABR, AS, combined AS-ABR, combined ABR-AS, and combined ABR-AS-UV/H2O2 processes, respectively. Due to the consumption of electrical energy and reagents, operating costs are calculated at optimal conditions of each process. A cost-effectiveness analysis (CEA) is performed at optimal conditions for the SWW treatment by optimizing the total electricity cost, H2O2 consumption, and hydraulic retention time (HRT). The combined ABR-AS-UV/H2O2 processes have an optimal TOC removal of 92.46% at an HRT of 41 h, a cost of $1.25/kg of TOC removed, and $11.60/m(3) of treated SWW. This process reaches a maximum TOC removal of 99% in 76.5 h with an estimated cost of $2.19/kg TOC removal and $21.65/m(3) treated SWW, equivalent to $6.79/m(3) day. Copyright © 2014 Elsevier Ltd. All rights reserved.

Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: alcohol and CRF effects

PubMed Central

Herman, Melissa A.; Varodayan, Florence P.; Oleata, Christopher S.; Luu, George; Kirson, Dean; Heilig, Markus; Ciccocioppo, Roberto; Roberto, Marisa

2015-01-01

The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes. PMID:26519902

Expression of Colocasia esculenta tuber agglutinin in Indian mustard provides resistance against Lipaphis erysimi and the expressed protein is non-allergenic.

PubMed

Das, Ayan; Ghosh, Prithwi; Das, Sampa

2018-06-01

Transgenic Brassica juncea plants expressing Colocasia esculenta tuber agglutinin (CEA) shows the non-allergenic nature of the expressed protein leading to enhanced mortality and reduced fecundity of mustard aphid-Lipaphis erysimi. Lipaphis erysimi (common name: mustard aphid) is the most devastating sucking insect pest of Indian mustard (Brassica juncea L.). Colocasia esculenta tuber agglutinin (CEA), a GNA (Galanthus nivalis agglutinin)-related lectin has previously been reported by the present group to be effective against a wide array of hemipteran insects in artificial diet-based bioassays. In the present study, efficacy of CEA in controlling L. erysimi has been established through the development of transgenic B. juncea expressing this novel lectin. Southern hybridization of the transgenic plants confirmed stable integration of cea gene. Expression of CEA in T 0 , T 1 and T 2 transgenic plants was confirmed through western blot analysis. Level of expression of CEA in the T 2 transgenic B. juncea ranged from 0.2 to 0.47% of the total soluble protein. In the in planta insect bioassays, the CEA expressing B. juncea lines exhibited enhanced insect mortality of 70-81.67%, whereas fecundity of L. erysimi was reduced by 49.35-62.11% compared to the control plants. Biosafety assessment of the transgenic B. juncea protein containing CEA was carried out by weight of evidence approach following the recommendations by FAO/WHO (Evaluation of the allergenicity of genetically modified foods: report of a joint FAO/WHO expert consultation, 22-25 Jan, Rome, http://www.fao.org/docrep/007/y0820e/y0820e00.HTM , 2001), Codex (Codex principles and guidelines on foods derived from biotechnology, Food and Agriculture Organization of the United Nations, Rome; Codex, Codex principles and guidelines on foods derived from biotechnology, Food and Agriculture Organization of the United Nations, Rome, 2003) and ICMR (Indian Council of Medical Research, guidelines for safety assessment of food derived from genetically engineered plants, http://www.icmr.nic.in/guide/Guidelines%20for%20Genetically%20Engineered%20Plants.pdf , 2008). Bioinformatics analysis, pepsin digestibility, thermal stability assay, immuno-screening and allergenicity assessment in BALB/c mice model demonstrated that the expressed CEA protein from transgenic B. juncea does not incite any allergenic response. The present study establishes CEA as an efficient insecticidal and non-allergenic protein to be utilized for controlling mustard aphid and similar hemipteran insects through the development of genetically modified plants.

Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.

PubMed

Warlow, Shelley M; Robinson, Mike J F; Berridge, Kent C

2017-08-30

Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion. Copyright © 2017 the authors 0270-6474/17/378330-19$15.00/0.

Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine

PubMed Central

2017-01-01

Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion. PMID:28751460

Conceptual and methodological challenges to integrating SEA and cumulative effects assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunn, Jill, E-mail: jill.gunn@usask.c; Noble, Bram F.

The constraints to assessing and managing cumulative environmental effects in the context of project-based environmental assessment are well documented, and the potential benefits of a more strategic approach to cumulative effects assessment (CEA) are well argued; however, such benefits have yet to be clearly demonstrated in practice. While it is widely assumed that cumulative effects are best addressed in a strategic context, there has been little investigation as to whether CEA and strategic environmental assessment (SEA) are a 'good fit' - conceptually or methodologically. This paper identifies a number of conceptual and methodological challenges to the integration of CEA andmore » SEA. Based on results of interviews with international experts and practitioners, this paper demonstrates that: definitions and conceptualizations of CEA are typically weak in practice; approaches to effects aggregation vary widely; a systems perspective lacks in both SEA and CEA; the multifarious nature of SEA complicates CEA; tiering arrangements between SEA and project-based assessment are limited to non-existing; and the relationship of SEA to regional planning remains unclear.« less

International lessons in new methods for grading and integrating cost effectiveness evidence into clinical practice guidelines.

PubMed

Antioch, Kathryn M; Drummond, Michael F; Niessen, Louis W; Vondeling, Hindrik

2017-01-01

Economic evidence is influential in health technology assessment world-wide. Clinical Practice Guidelines (CPG) can enable economists to include economic information on health care provision. Application of economic evidence in CPGs, and its integration into clinical practice and national decision making is hampered by objections from professions, paucity of economic evidence or lack of policy commitment. The use of state-of-art economic methodologies will improve this. Economic evidence can be graded by 'checklists' to establish the best evidence for decision making given methodological rigor. New economic evaluation checklists, Multi-Criteria Decision Analyses (MCDA) and other decision criteria enable health economists to impact on decision making world-wide. We analyse the methodologies for integrating economic evidence into CPG agencies globally, including the Agency of Health Research and Quality (AHRQ) in the USA, National Health and Medical Research Council (NHMRC) and Australian political reforms. The Guidelines and Economists Network International (GENI) Board members from Australia, UK, Canada and Denmark presented the findings at the conference of the International Health Economists Association (IHEA) and we report conclusions and developments since. The Consolidated Guidelines for the Reporting of Economic Evaluations (CHEERS) 24 item check list can be used by AHRQ, NHMRC, other CPG and health organisations, in conjunction with the Drummond ten-point check list and a questionnaire that scores that checklist for grading studies, when assessing economic evidence. Cost-effectiveness Analysis (CEA) thresholds, opportunity cost and willingness-to-pay (WTP) are crucial issues for decision rules in CEA generally, including end-of-life therapies. Limitations of inter-rater reliability in checklists can be addressed by including more than one assessor to reach a consensus, especially when impacting on treatment decisions. We identify priority areas to generate economic evidence for CPGs by NHMRC, AHRQ, and other agencies. The evidence may cover demand for care issues such as involved time, logistics, innovation price, price sensitivity, substitutes and complements, WTP, absenteeism and presentism. Supply issues may include economies of scale, efficiency changes, and return on investment. Involved equity and efficiency measures may include cost-of-illness, disease burden, quality-of-life, budget impact, cost-effective ratios, net benefits and disparities in access and outcomes. Priority setting remains essential and trade-off decisions between policy criteria can be based on MCDA, both in evidence based clinical medicine and in health planning.

Systematic follow-up after curative surgery for colorectal cancer in Norway: a population-based audit of effectiveness, costs, and compliance.

PubMed

Körner, Hartwig; Söreide, Kjetil; Stokkeland, Pål J; Söreide, Jon Arne

2005-03-01

In this study, we analyzed the Norwegian guidelines for systematic follow-up after curative colorectal cancer surgery in a large single institution. Three hundred fourteen consecutive unselected patients undergoing curative surgery for colorectal cancer between 1996 and 1999 were studied with regard to asymptomatic curable recurrence, compliance with the program, and cost. Follow-up included carcinoembryonic antigen (CEA) interval measurements, colonoscopy, ultrasonography of the liver, and radiography of the chest. In 194 (62%) of the patients, follow-up was conducted according to the Norwegian guidelines. Twenty-one patients (11%) were operated on for curable recurrence, and 18 patients (9%) were disease free after curative surgery for recurrence at evaluation. Four metachronous tumors (2%) were found. CEA interval measurement had to be made most frequently (534 tests needed) to detect one asymptomatic curable recurrence. Follow-up program did not influence cancer-specific survival. Overall compliance with the surveillance program was 66%, being lowest for colonoscopy (55%) and highest for ultrasonography of the liver (85%). The total program cost was 228,117 euro (US 280,994 dollars), translating into 20,530 euro (US 25,289 dollars) for one surviving patient after surgery for recurrence. The total diagnosis yield with regard to disease-free survival after surgery for recurrence was 9%. Compliance was moderate. Whether the continuing implementation of such program and cost are justified should be debated.

Significant Association of Annual Hospital Volume With the Risk of Inhospital Stroke or Death Following Carotid Endarterectomy but Likely Not After Carotid Stenting: Secondary Data Analysis of the Statutory German Carotid Quality Assurance Database.

PubMed

Kuehnl, Andreas; Tsantilas, Pavlos; Knappich, Christoph; Schmid, Sofie; König, Thomas; Breitkreuz, Thorben; Zimmermann, Alexander; Mansmann, Ulrich; Eckstein, Hans-Henning

2016-11-01

Associations between hospital volume and the risk of stroke or death following carotid endarterectomy (CEA) and carotid artery stenting (CAS) on a national level in Germany were analyzed. Secondary data analysis using microdata from the nationwide statutory German quality assurance database on all surgical or endovascular carotid interventions on the extracranial carotid artery between 2009 and 2014. Hospitals were categorized into empirically determined quintiles according to the annual case volume. The resulting volume thresholds were 10, 25, 46, and 79 for CEA and 2, 6, 12, and 26 for CAS procedures. The primary outcome was any stroke or death before hospital discharge. For risk-adjusted analyses, a multilevel regression model was applied. The analysis included 161 448 CEA and 17 575 CAS procedures. In CEA patients, the crude risk of stroke or death decreased monotonically from 4.2% (95% confidence interval, 3.6%-4.9%) in low-volume hospitals (first quintile 1-10 CEA per year) to 2.1% (2.0%-2.2%) in hospitals providing ≥80 CEA per year (fifth quintile; P<0.001 for trend). The overall risk of any stroke or death in CAS patients was 3.7% (3.5%-4.0%), but no trend on annual volume was seen (P=0.304). Risk-adjusted analyses confirmed a significant inverse relationship between hospital volume (categorized or continuous) and the risk of stroke or death after CEA but not CAS procedures. An inverse volume-outcome relationship in CEA-treated patients was demonstrated. No significant association between hospital volume and the risk of stroke or death was found for CAS. © 2016 American Heart Association, Inc.

Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome.

PubMed

Konishi, Tsuyoshi; Shimada, Yoshifumi; Hsu, Meier; Tufts, Lauren; Jimenez-Rodriguez, Rosa; Cercek, Andrea; Yaeger, Rona; Saltz, Leonard; Smith, J Joshua; Nash, Garrett M; Guillem, José G; Paty, Philip B; Garcia-Aguilar, Julio; Gonen, Mithat; Weiser, Martin R

2018-03-01

Guidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown. To investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA. This retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified. Patients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA. Three-year recurrence-free survival (RFS) and hazard function curves over time were analyzed. A total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS. Elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

Meta‐analysis of the procedural risks of carotid endarterectomy and carotid artery stenting over time

PubMed Central

Lokuge, K.; de Waard, D. D.; Halliday, A.; Gray, A.; Bulbulia, R.

2017-01-01

Background Stroke/death rates within 30 days of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in RCTs inform current clinical guidelines. However, the risks may have changed in recent years with wider use of effective stroke prevention therapies, especially statins, improved patient selection and growing operator expertise. The aim of this study was to investigate whether the procedural stroke/death risks from CEA and CAS have changed over time. Methods MEDLINE and Embase were searched systematically from inception to May 2016 for observational cohort studies of CEA and CAS. Studies included reported on more than 1000 patients, with 30‐day outcomes after the procedure according to patients' symptom status (recent stroke or transient ischaemic attack). Restricted maximum likelihood random‐effects and meta‐regressions methods were used to synthesize procedural stroke/death rates of CEA and CAS according to year of study recruitment completion. Results Fifty‐one studies, including 223 313 patients undergoing CEA and 72 961 undergoing CAS, were reviewed. Procedural stroke/death risks of CEA decreased over time in symptomatic and asymptomatic patients. Risks were substantially lower in studies completing recruitment in 2005 or later, both in symptomatic (5·11 per cent before 2005 versus 2·68 per cent from 2005 onwards; P = 0·002) and asymptomatic (3·17 versus 1·50 per cent; P < 0·001) patients. Procedural stroke/death rates of CAS did not change significantly over time (4·77 per cent among symptomatic and 2·59 per cent among asymptomatic patients). There was substantial heterogeneity in event rates and recruitment periods were long. Conclusions Risks of procedural stroke/death following CEA appear to have decreased substantially. There was no evidence of a change in stroke/death rates following CAS. PMID:29205297

The cost-effectiveness of brief intervention versus brief treatment of Screening, Brief Intervention and Referral to Treatment (SBIRT) in the United States.

PubMed

Barbosa, Carolina; Cowell, Alexander; Dowd, William; Landwehr, Justin; Aldridge, Arnie; Bray, Jeremy

2017-02-01

To conduct a cost-effectiveness analysis (CEA) comparing the delivery of brief intervention (BI) with brief treatment (BT) within Screening, Brief Intervention and Referral to Treatment (SBIRT) programs. Quasi-experimental differences in observed baseline characteristics between BI and BT patients were adjusted using propensity score techniques. Incremental comparison of costs and health outcomes associated with BI and BT. Health-care settings in four US states participating in Substance Abuse and Mental Health Services Administration SBIRT grant programs. Ninety patients who received BT and 878 who received BI. Per-patient cost of SBIRT, patient demographics and six measures of substance use: proportion using alcohol, proportion using alcohol to intoxication, days of alcohol use, days of alcohol use to intoxication, proportion using drugs and days using drugs. BI and BT were associated with better outcomes. The cost of SBIRT was significantly higher for BT patients ($75.54 versus 16.32, 95% confidence interval, P < 0.01). BT would be cost-effective if the decision-maker had a willingness to pay of $8.90 for a 1 percentage point reduction in the probability of using any alcohol. For the other five outcomes, BT was less effective and more costly, and BI would be a better use of resources. It might be cost-effective to offer brief treatment if the goal is to abstain from alcohol. However, the higher effectiveness of brief treatment for this outcome is associated with considerable uncertainty and, because both brief intervention and brief treatment improve all outcomes, brief treatment does not appear to be a good use of resources. © 2017 Society for the Study of Addiction.

Prognostic Role of Carcinoembryonic Antigen Level after Preoperative Chemoradiotherapy in Patients with Rectal Cancer.

PubMed

Huh, Jung Wook; Yun, Seong Hyeon; Kim, Seok Hyung; Park, Yoon Ah; Cho, Yong Beom; Kim, Hee Cheol; Lee, Woo Yong; Park, Hee Chul; Choi, Doo Ho; Park, Joon Oh; Park, Young Suk; Chun, Ho-Kyung

2018-05-29

The prognostic role of post-chemoradiotherapy (CRT) carcinoembryonic antigen (CEA) level is not clear. We evaluated the prognostic significance of post-CRT CEA level in patients with rectal cancer after preoperative CRT. We reviewed 659 consecutive patients who underwent preoperative CRT and total mesorectal excision for non-metastatic rectal cancer. Patients were categorized into two groups according to post-CRT serum CEA level: low CEA (< 5 ng/mL) and high CEA (≥ 5 ng/mL). Median post-CRT CEA level was 1.7 ng/mL (range, 0.1-207.0). A high post-CRT level was significantly associated with ypStage, ypT category, tumor regression grade, and pre-CRT CEA level. The 5-year overall survival rate of the 659 patients was 87.8% with a median follow-up period of 57.0 months (range, 1.4-176.4). When the post-CRT CEA groups were divided into groups according to pre-CRT CEA level, the 5-year overall survival rates were significantly different (P < 0.001 and P = 0.001, respectively). Post-CRT CEA level was an independent prognostic factor for overall survival. Multivariate analysis revealed that operation method, differentiation, perineural invasion, postoperative chemotherapy, tumor regression grade, and post-CRT CEA level were independent prognostic factors for overall survival. The level of serum CEA after preoperative CRT was an independent prognostic factor for overall survival in patients with rectal cancer.

Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.

PubMed

Feng, Mei; Zhu, Jing; Liang, Liqun; Zeng, Ni; Wu, Yanqiu; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

2017-04-01

Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glascoe, Lee; Gowardhan, Akshay; Lennox, Kristin

In the interest of promoting the international exchange of technical expertise, the US Department of Energy’s Office of Emergency Operations (NA-40) and the French Commissariat à l'Energie Atomique et aux énergies alternatives (CEA) requested that the National Atmospheric Release Advisory Center (NARAC) of Lawrence Livermore National Laboratory (LLNL) in Livermore, California host a joint table top exercise with experts in emergency management and atmospheric transport modeling. In this table top exercise, LLNL and CEA compared each other’s flow and dispersion models. The goal of the comparison is to facilitate the exchange of knowledge, capabilities, and practices, and to demonstrate themore » utility of modeling dispersal at different levels of computational fidelity. Two modeling approaches were examined, a regional scale modeling approach, appropriate for simple terrain and/or very large releases, and an urban scale modeling approach, appropriate for small releases in a city environment. This report is a summary of LLNL and CEA modeling efforts from this exercise. Two different types of LLNL and CEA models were employed in the analysis: urban-scale models (Aeolus CFD at LLNL/NARAC and Parallel- Micro-SWIFT-SPRAY, PMSS, at CEA) for analysis of a 5,000 Ci radiological release and Lagrangian Particle Dispersion Models (LODI at LLNL/NARAC and PSPRAY at CEA) for analysis of a much larger (500,000 Ci) regional radiological release. Two densely-populated urban locations were chosen: Chicago with its high-rise skyline and gridded street network and Paris with its more consistent, lower building height and complex unaligned street network. Each location was considered under early summer daytime and nighttime conditions. Different levels of fidelity were chosen for each scale: (1) lower fidelity mass-consistent diagnostic, intermediate fidelity Navier-Stokes RANS models, and higher fidelity Navier-Stokes LES for urban-scale analysis, and (2) lower-fidelity single-profile meteorology versus higher-fidelity three-dimensional gridded weather forecast for regional-scale analysis. Tradeoffs between computation time and the fidelity of the results are discussed for both scales. LES, for example, requires nearly 100 times more processor time than the mass-consistent diagnostic model or the RANS model, and seems better able to capture flow entrainment behind tall buildings. As anticipated, results obtained by LLNL and CEA at regional scale around Chicago and Paris look very similar in terms of both atmospheric dispersion of the radiological release and total effective dose. Both LLNL and CEA used the same meteorological data, Lagrangian particle dispersion models, and the same dose coefficients. LLNL and CEA urban-scale modeling results show consistent phenomenological behavior and predict similar impacted areas even though the detailed 3D flow patterns differ, particularly for the Chicago cases where differences in vertical entrainment behind tall buildings are particularly notable. Although RANS and LES (LLNL) models incorporate more detailed physics than do mass-consistent diagnostic flow models (CEA), it is not possible to reach definite conclusions about the prediction fidelity of the various models as experimental measurements were not available for comparison. Stronger conclusions about the relative performances of the models involved and evaluation of the tradeoffs involved in model simplification could be made with a systematic benchmarking of urban-scale modeling. This could be the purpose of a future US / French collaborative exercise.« less

Endarterectomy achieves lower stroke and death rates compared with stenting in patients with asymptomatic carotid stenosis.

PubMed

Kakkos, Stavros K; Kakisis, Ioannis; Tsolakis, Ioannis A; Geroulakos, George

2017-08-01

It is currently unclear if carotid artery stenting (CAS) is as safe as carotid endarterectomy (CEA) for patients with significant asymptomatic stenosis. The aim of our study was to perform a systematic review and meta-analysis of trials comparing CAS with CEA. On March 17, 2017, a search for randomized controlled trials was performed in MEDLINE and Scopus databases with no time limits. We performed meta-analyses with Peto odds ratios (ORs) and 95% confidence intervals (CIs). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation method. The primary safety and efficacy outcome measures were stroke or death rate at 30 days and ipsilateral stroke at 1 year (including ipsilateral stroke and death rate at 30 days), respectively. Perioperative stroke, ipsilateral stroke, myocardial infarction (MI), and cranial nerve injury (CNI) were all secondary outcome measures. The systematic review of the literature identified nine randomized controlled trials reporting on 3709 patients allocated into CEA (n = 1479) or CAS (n = 2230). Stroke or death rate at 30 days was significantly higher for CAS (64/2176 [2.94%]) compared with CEA (27/1431 [1.89%]; OR, 1.57; 95% CI, 1.01-2.44; P = .044), with low level of heterogeneity beyond chance (I 2  = 0%). Also, stroke rate at 30 days was significantly higher for CAS (63/2176 [2.90%]) than for CEA (26/1431 [1.82%]; OR, 1.63; 95% CI, 1.04-2.54; P = .032; I 2  = 0%). MI at 30 days was nonsignificantly lower for CAS (12/1815 [0.66%]) compared with CEA (16/1070 [1.50%]; OR, 0.53; 95% CI, 0.24-1.14; P = .105; I 2  = 0%); however, CNI at 30 days was significantly lower for CAS (2/1794 [0.11%]) than for CEA (33/1061 [3.21%]; OR, 0.13; 95% CI, 0.07-0.26; P < .00001; I 2  = 0%). Regarding the long-term outcome of stroke or death rate at 30 days plus ipsilateral stroke during follow-up, this was significantly higher for CAS (79/2173 [3.64%]) than for CEA (35/1430 [2.45%]; OR, 1.51; 95% CI, 1.02-2.24; P = .04; I 2  = 0%). Quality of evidence for all stroke outcomes was graded moderate. Among patients with asymptomatic stenosis undergoing carotid intervention, there is moderate-quality evidence to suggest that CEA had significantly lower 30-day stroke and also stroke or death rates compared with CAS at the cost of higher CNI and nonsignificantly higher MI rates. The long-term efficacy of CEA in ipsilateral stroke prevention, taking into account perioperative stroke and death, was preserved during follow-up. There is an urgent need for high-quality research before a firm recommendation is made that CAS is inferior or not to CEA. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Mobile laboratories: An innovative and efficient solution for radiological characterization of sites under or after decommissioning.

PubMed

Goudeau, V; Daniel, B; Dubot, D

2017-04-21

During the operation and the decommissioning of a nuclear site the operator must assure the protection of the workers and the environment. It must furthermore identify and classify the various wastes, while optimizing the associated costs. At all stages of the decommissioning radiological measurements are performed to determine the initial situation, to monitor the demolition and clean-up, and to verify the final situation. Radiochemical analysis is crucial for the radiological evaluation process to optimize the clean-up operations and to the respect limits defined with the authorities. Even though these types of analysis are omnipresent in activities such as the exploitation, the monitoring, and the cleaning up of nuclear plants, some nuclear sites do not have their own radiochemical analysis laboratory. Mobile facilities can overcome this lack when nuclear facilities are dismantled, when contaminated sites are cleaned-up, or in a post-accident situation. The current operations for the characterization of radiological soils of CEA nuclear facilities, lead to a large increase of radiochemical analysis. To manage this high throughput of samples in a timely manner, the CEA has developed a new mobile laboratory for the clean-up of its soils, called SMaRT (Shelter for Monitoring and nucleAR chemisTry). This laboratory is dedicated to the preparation and the radiochemical analysis (alpha, beta, and gamma) of potentially contaminated samples. In this framework, CEA and Eichrom laboratories has signed a partnership agreement to extend the analytical capacities and bring on site optimized and validated methods for different problematic. Gamma-emitting radionuclides can usually be measured in situ as little or no sample preparation is required. Alpha and beta-emitting radionuclides are a different matter. Analytical chemistry laboratory facilities are required. Mobile and transportable laboratories equipped with the necessary tools can provide all that is needed. The main advantage of a mobile laboratory is its portability; the shelter can be placed in the vicinity of nuclear facilities under decommissioning, or of contaminated sites with infrastructures unsuitable for the reception and treatment of radioactive samples. Radiological analysis can then be performed without the disadvantages of radioactive material transport. This paper describes how this solution allows a fast response and control of costs, with a high analytical capacity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost-effectiveness and healthcare budget impact in Italy of inhaled corticosteroids and bronchodilators for severe and very severe COPD patients.

PubMed

Dal, Negro Roberto; Eandi, M; Pradelli, L; Iannazzo, S

2007-01-01

Current practice guidelines for the treatment of COPD recommend the use of combined inhaled corticosteroids and long-acting bronchodilators in severe and very severe patients (GOLD stages III and IV). The aim of this study was to evaluate, through a simulation model, the economic consequences of this recommendation in Italy. We developed a cost-effectiveness analysis (CEA) on five alternative therapeutic strategies (salmeterol/fluticasone, SF; formoterol! budesonide, FB; salmeterol alone, S; fluticasone alone, F; control, C). Published data on the Italian COPD population and efficacy data from international reference trials were fitted in a disease progression model based on a Markov chain representing severity stages and death. The yearly total direct costs of treating COPD patients in Italy was estimated at approximately Euro 7 billion, with a mean cost per patient per year of around Euro 2450. Mean survival of the cohort is 11.5 years. The C and F strategies were dominated (ie, are associated with worse outcomes and higher costs) by all alternatives. SF and FB were the most effective strategies, with a slight clinical superiority of SF, but they were also marginally more expensive than S. Incremental cost-effectiveness of SF vs S was Euro 679.5 per avoided exacerbation and Euro 3.3 per symptom-free day. Compared with current practice, the recommended use of combined inhaled corticosteroids and long-acting bronchodilators for severe and very severe COPD patients has the potential for improving clinical outcomes without increasing healthcare costs.

A monoclonal antibody against neem leaf glycoprotein recognizes carcinoembryonic antigen (CEA) and restricts CEA expressing tumor growth.

PubMed

Das, Arnab; Barik, Subhasis; Banerjee, Saptak; Bose, Anamika; Sarkar, Koustav; Biswas, Jaydip; Baral, Rathindranath; Pal, Smarajit

2014-10-01

Carcinoembryonic antigen (CEA) is one of the promising tumor antigens mainly associated with carcinoma of the colon, lung, breast, etc. and received wide attention for cancer immunotherapy. Neem leaf glycoprotein (NLGP), an effective immunomodulator, is able to generate humoral and cellular immune responses in murine tumor models. We have generated a monoclonal antibody (mAb) against NLGP by fusing NLGP-immunized mice splenocytes with nonsecretory myeloma cells. A highly anti-NLGP mAb secreting clone (1C8; IgG2a in nature) has been identified and propagated in culture. 1C8 recognizes human CEA as good as NLGP by enzyme linked immunosorbent assay, Western blotting, and immunoprecipitation. 1C8 detects CEA on colon cancer tissues by immunochistochemistry. By flow cytometry, 1C8 specifically reacts with CEA(+) human (Colo-205, HCT-116, and HT-29) and mouse (CT-26) colon cancer cells, but it showed minimum reactivity with CEA(-) human (MCF7, SiHa, and SCC084) and mouse (B16MelF10) cancer cells. This anti-NLGP 1C8 mAb revealed significant antitumor activity and better survivability in vivo in animals bearing mouse (CT-26 in BALB/c) and human (Colo-205 in athymic nude) CEA(+) cancer cells. 1C8 has no direct influence on proliferation and migration of CEA(+) cells, however, NK cell-dependent strong antibody-dependent cellular cytotoxicity reaction toward CEA(+) cells and normalization of angiogenesis are chiefly associated with tumor growth restriction. Obtained results provided a new immunotherapeutic approach for the effective management of CEA(+) tumors.

A lesson in business: cost-effectiveness analysis of a novel financial incentive intervention for increasing physical activity in the workplace

PubMed Central

2013-01-01

Background Recently both the UK and US governments have advocated the use of financial incentives to encourage healthier lifestyle choices but evidence for the cost-effectiveness of such interventions is lacking. Our aim was to perform a cost-effectiveness analysis (CEA) of a quasi-experimental trial, exploring the use of financial incentives to increase employee physical activity levels, from a healthcare and employer’s perspective. Methods Employees used a 'loyalty card’ to objectively monitor their physical activity at work over 12 weeks. The Incentive Group (n=199) collected points and received rewards for minutes of physical activity completed. The No Incentive Group (n=207) self-monitored their physical activity only. Quality of life (QOL) and absenteeism were assessed at baseline and 6 months follow-up. QOL scores were also converted into productivity estimates using a validated algorithm. The additional costs of the Incentive Group were divided by the additional quality adjusted life years (QALYs) or productivity gained to calculate incremental cost effectiveness ratios (ICERs). Cost-effectiveness acceptability curves (CEACs) and population expected value of perfect information (EVPI) was used to characterize and value the uncertainty in our estimates. Results The Incentive Group performed more physical activity over 12 weeks and by 6 months had achieved greater gains in QOL and productivity, although these mean differences were not statistically significant. The ICERs were £2,900/QALY and £2,700 per percentage increase in overall employee productivity. Whilst the confidence intervals surrounding these ICERs were wide, CEACs showed a high chance of the intervention being cost-effective at low willingness-to-pay (WTP) thresholds. Conclusions The Physical Activity Loyalty card (PAL) scheme is potentially cost-effective from both a healthcare and employer’s perspective but further research is warranted to reduce uncertainty in our results. It is based on a sustainable “business model” which should become more cost-effective as it is delivered to more participants and can be adapted to suit other health behaviors and settings. This comes at a time when both UK and US governments are encouraging business involvement in tackling public health challenges. PMID:24112295

A lesson in business: cost-effectiveness analysis of a novel financial incentive intervention for increasing physical activity in the workplace.

PubMed

Dallat, Mary Anne T; Hunter, Ruth F; Tully, Mark A; Cairns, Karen J; Kee, Frank

2013-10-10

Recently both the UK and US governments have advocated the use of financial incentives to encourage healthier lifestyle choices but evidence for the cost-effectiveness of such interventions is lacking. Our aim was to perform a cost-effectiveness analysis (CEA) of a quasi-experimental trial, exploring the use of financial incentives to increase employee physical activity levels, from a healthcare and employer's perspective. Employees used a 'loyalty card' to objectively monitor their physical activity at work over 12 weeks. The Incentive Group (n=199) collected points and received rewards for minutes of physical activity completed. The No Incentive Group (n=207) self-monitored their physical activity only. Quality of life (QOL) and absenteeism were assessed at baseline and 6 months follow-up. QOL scores were also converted into productivity estimates using a validated algorithm. The additional costs of the Incentive Group were divided by the additional quality adjusted life years (QALYs) or productivity gained to calculate incremental cost effectiveness ratios (ICERs). Cost-effectiveness acceptability curves (CEACs) and population expected value of perfect information (EVPI) was used to characterize and value the uncertainty in our estimates. The Incentive Group performed more physical activity over 12 weeks and by 6 months had achieved greater gains in QOL and productivity, although these mean differences were not statistically significant. The ICERs were £2,900/QALY and £2,700 per percentage increase in overall employee productivity. Whilst the confidence intervals surrounding these ICERs were wide, CEACs showed a high chance of the intervention being cost-effective at low willingness-to-pay (WTP) thresholds. The Physical Activity Loyalty card (PAL) scheme is potentially cost-effective from both a healthcare and employer's perspective but further research is warranted to reduce uncertainty in our results. It is based on a sustainable "business model" which should become more cost-effective as it is delivered to more participants and can be adapted to suit other health behaviors and settings. This comes at a time when both UK and US governments are encouraging business involvement in tackling public health challenges.

Deterministic Role of CEA and MSI Status in Predicting Outcome of CRC Patients: a Perspective Study Amongst Hospital Attending Eastern Indian Populations.

PubMed

Koyel, Banerjee; Priyabrata, Das; Rittwika, Bhattacharya; Swati, Dasgupta; Soma, Mukhopadhyay; Jayasri, Basak; Ashis, Mukhopadhyay

2017-12-01

Carcinoembryonic antigen (CEA) is an important deterministic factor in predicting colorectal carcinoma (CRC) progression. It is also evident that microsatellite instability (MSI) which results in a hypermutable phenotype of genomic DNA is common in CRC. Owing to the scarcity of reports from India, our aim of this study was to understand the clinicopathological correlations of CEA status with surgery and chemotherapy, correlate the same with socio-demographic status of the patients, determine the MSI status amongst them and understand the prognostic implications of CEA and MSI as CRC progression marker amongst patients. The serum CEA level was estimated by chemiluminescence assay (CLIA). Serum liver enzyme assay was carried out following the manufacturer's instructions using auto-analysers (E. Merck and Sera mol. Health Care, India). MSI analysis was carried out by PCR-SSCP. From our study, most frequently detected colorectal cancer was in 40-49 years age group (25.26%) with 61.05% male and 38.95% females. CEA showed a significant association with higher TNM staging, tumour size, smoking habit and MSI status ( p  < 0.05) but not with sex and site of cancer ( p  > 0.05). After surgery and chemotherapy, CEA and WBCs were decreased significantly ( p  < 0.05), while liver enzymes did not change significantly ( p  > 0.05). Overall, microsatellite instability was observed in approximately 40% of the populations. From our study, it was also evident that for both, MSI and abnormal CEA level predicted poor prognosis for the patient (by using Kaplan-Meier survival analysis; p  = 0.04). Thus, CEA and initial MSI status can be used as prognostic markers of CRC.

A comparison of benefit and economic value between two sound therapy tinnitus management options.

PubMed

Newman, Craig W; Sandridge, Sharon A

2012-02-01

Sound therapy coupled with appropriate counseling has gained widespread acceptance in the audiological management of tinnitus. For many years, ear level sound generators (SGs) have been used to provide masking relief and to promote tinnitus habituation. More recently, an alternative treatment device was introduced, the Neuromonics Tinnitus Treatment (NTT), which employs spectrally-modified music in an acoustic desensitization approach in order to help patients overcome the disturbing consequences of tinnitus. It is unknown, however, if one treatment plan is more efficacious and cost-effective in comparison to the other. In today's economic climate, it has become critical that clinicians justify the value of tinnitus treatment devices in relation to observed benefit. To determine perceived benefit from, and economic value associated with, two forms of sound therapy, namely, SGs and NTT. Retrospective between-subject clinical study. A sample of convenience comprised of 56 patients drawn from the Tinnitus Management Clinic at the Cleveland Clinic participated. Twenty-three patients selected SGs, and 33 patients selected NTT as their preferred sound therapy treatment option. Sound therapy benefit was quantified using the Tinnitus Handicap Inventory (THI). The questionnaire was administered before and 6 mo after initiation of tinnitus treatment. Prior to device fitting, all patients participated in a 1.5 hr group education session about tinnitus and its management. Economic value comparisons between sound therapy options were made using a cost-effectiveness analysis (CEA) and cost-utility analysis (CUA). THI scores indicated a significant improvement (p < 0.001) in tinnitus reduction for both treatment types between a pre- and 6 mo postfitting interval, yet there were no differences (p > 0.05) between the treatment alternatives at baseline or 6 mo postfitting. The magnitude of improvement for both SGs and NTT was dependent on initial perceived tinnitus handicap. Based on the CEA and CUA economic analyses alone, it appears that the SGs may be the more cost-effective alternative; however, the magnitude of economic value is a function of preexisting perceived tinnitus activity limitation/participation restriction. Both SGs and NTT provide significant reduction in perceived tinnitus handicap, with benefit being more pronounced for those patients having greater tinnitus problems at the beginning of therapy. Although the economic models favored the SGs over the NTT, there are several other critical factors that clinicians must take into account when recommending a specific sound therapy option. These include initial tinnitus severity complaints and a number of patient preference variables such as sound preference, listening acceptability, and lifestyle. American Academy of Audiology.

Surgical dissection of the internal carotid artery under flow control by proximal vessel clamping reduces embolic infarcts during carotid endarterectomy.

PubMed

Yoshida, Kazumichi; Kurosaki, Yoshitaka; Funaki, Takeshi; Kikuchi, Takayuki; Ishii, Akira; Takahashi, Jun C; Takagi, Yasushi; Yamagata, Sen; Miyamoto, Susumu

2014-01-01

To evaluate the efficacy of flow control of the internal carotid artery (ICA) by the clamping of the common carotid artery, external carotid artery, and superior thyroid artery during surgical ICA dissection to reduce ischemic complications after carotid endarterectomy (CEA). Sixty-seven patients (59 men; age, 70.5 ± 6.2 years) who underwent CEA by the same surgeon were retrospectively studied. Both conventional CEA (n = 29) and flow-control CEA (n = 38) were performed with the patient under general anesthesia and with the use of somatosensory-evoked potential and near-infrared spectroscopy monitoring as a guide for selective shunting. The number of new postoperative infarcts was assessed with preoperative and postoperative diffusion-weighted images (DWIs) obtained within 3 days of surgery. In addition to surgical technique, the effects of the following factors on new infarcts also were examined: age, side of ICA stenosis, high-grade stenosis, symptoms, and application of shunting. New postoperative DWI lesions were observed in 7 of 67 patients (10.4%), and none of them was symptomatic. With respect to operative technique, the incidence rate of DWI spots was significantly lower in the flow-control group (2.6%) than in the conventional group (20.7%), odds ratio: 0.069; 95% confidence interval: 0.006-0.779; P = 0.031). On multiple logistic regression analysis, age, side of ICA stenosis, high-grade stenosis, symptoms, and the use of internal shunting did not have significant effects on new postoperative DWI lesions, whereas technique did have an effect. The proximal flow-control technique for CEA helps avoid embolic complications during surgical ICA dissection. Copyright © 2014 Elsevier Inc. All rights reserved.

Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis.

PubMed

Yang, Yuan; Liu, Ya-Lan; Shi, Huan-Zhong

2017-01-01

The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established. This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE. The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies. Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94. In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura. © 2017 S. Karger AG, Basel.

Levels of CEA among vinyl chloride and polyvinyl chloride exposed workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, H.A.; Snyder, J.; Lewinson, T.

1978-09-01

In 1974, vinyl chloride exposed workers were found to have an increased risk of malignant disease (hemangiosarcoma of the liver). We have examined 1,147 workers exposed to vinyl chloride monomer in three VC/PVC polymerization plants, and 269 workers from a PVC extrusion plant manufacturing PVC textile leather, exposed to much lower concentrations of vinyl chloride. Included among the comprehensive clinical and laboratory studies conducted was the CEA titer. We obtained, respectively, 1,115 and 248 CEA titers. Multiple factors were demonstrated which affected the distribution of CEA titers. Cigarette use had the greatest effect, followed by history of specific past illnessesmore » and alcohol intake history. After removing these possible confounding effects, the distribution of CEA titers among the polymerization workers was significantly different from the extrusion plant group and from an unexposed comparison group. Of the six job categories analyzed, only production and maintenance workers had CEA titer distributions significantly different from the comparison group and the extrusion workers. The investigation demonstrates that occupational exposures in VC/PVC polymerization plants can cause elevations in the CEA titers of otherwise healthy individuals. Prospective follow-up is necessary before conclusions can be drawn concerning the usefulness of the CEA titer as a predictive indicator of possible increased risk.« less

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis.

PubMed

Sterne, Jonathan Ac; Bodalia, Pritesh N; Bryden, Peter A; Davies, Philippa A; López-López, Jose A; Okoli, George N; Thom, Howard Hz; Caldwell, Deborah M; Dias, Sofia; Eaton, Diane; Higgins, Julian Pt; Hollingworth, Will; Salisbury, Chris; Savović, Jelena; Sofat, Reecha; Stephens-Boal, Annya; Welton, Nicky J; Hingorani, Aroon D

2017-03-01

Warfarin is effective for stroke prevention in atrial fibrillation (AF), but anticoagulation is underused in clinical care. The risk of venous thromboembolic disease during hospitalisation can be reduced by low-molecular-weight heparin (LMWH): warfarin is the most frequently prescribed anticoagulant for treatment and secondary prevention of venous thromboembolism (VTE). Warfarin-related bleeding is a major reason for hospitalisation for adverse drug effects. Warfarin is cheap but therapeutic monitoring increases treatment costs. Novel oral anticoagulants (NOACs) have more rapid onset and offset of action than warfarin, and more predictable dosing requirements. To determine the best oral anticoagulant/s for prevention of stroke in AF and for primary prevention, treatment and secondary prevention of VTE. Four systematic reviews, network meta-analyses (NMAs) and cost-effectiveness analyses (CEAs) of randomised controlled trials. Hospital (VTE primary prevention and acute treatment) and primary care/anticoagulation clinics (AF and VTE secondary prevention). Patients eligible for anticoagulation with warfarin (stroke prevention in AF, acute treatment or secondary prevention of VTE) or LMWH (primary prevention of VTE). NOACs, warfarin and LMWH, together with other interventions (antiplatelet therapy, placebo) evaluated in the evidence network. Efficacy  Stroke, symptomatic VTE, symptomatic deep-vein thrombosis and symptomatic pulmonary embolism. Safety  Major bleeding, clinically relevant bleeding and intracranial haemorrhage. We also considered myocardial infarction and all-cause mortality and evaluated cost-effectiveness. MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library, reference lists of published NMAs and trial registries. We searched MEDLINE and PREMEDLINE In-Process & Other Non-Indexed Citations, EMBASE and The Cochrane Library. The stroke prevention in AF review search was run on the 12 March 2014 and updated on 15 September 2014, and covered the period 2010 to September 2014. The search for the three reviews in VTE was run on the 19 March 2014, updated on 15 September 2014, and covered the period 2008 to September 2014. Two reviewers screened search results, extracted and checked data, and assessed risk of bias. For each outcome we conducted standard meta-analysis and NMA. We evaluated cost-effectiveness using discrete-time Markov models. Apixaban (Eliquis ® , Bristol-Myers Squibb, USA; Pfizer, USA) [5 mg bd (twice daily)] was ranked as among the best interventions for stroke prevention in AF, and had the highest expected net benefit. Edoxaban (Lixiana ® , Daiichi Sankyo, Japan) [60 mg od (once daily)] was ranked second for major bleeding and all-cause mortality. Neither the clinical effectiveness analysis nor the CEA provided strong evidence that NOACs should replace postoperative LMWH in primary prevention of VTE. For acute treatment and secondary prevention of VTE, we found little evidence that NOACs offer an efficacy advantage over warfarin, but the risk of bleeding complications was lower for some NOACs than for warfarin. For a willingness-to-pay threshold of > £5000, apixaban (5 mg bd) had the highest expected net benefit for acute treatment of VTE. Aspirin or no pharmacotherapy were likely to be the most cost-effective interventions for secondary prevention of VTE: our results suggest that it is not cost-effective to prescribe NOACs or warfarin for this indication. NOACs have advantages over warfarin in patients with AF, but we found no strong evidence that they should replace warfarin or LMWH in primary prevention, treatment or secondary prevention of VTE. These relate mainly to shortfalls in the primary data: in particular, there were no head-to-head comparisons between different NOAC drugs. Calculating the expected value of sample information to clarify whether or not it would be justifiable to fund one or more head-to-head trials. This study is registered as PROSPERO CRD42013005324, CRD42013005331 and CRD42013005330. The National Institute for Health Research Health Technology Assessment programme.

Looking up, down, and sideways: Reconceiving cumulative effects assessment as a mindset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinclair, A. John, E-mail: jsincla@umanitoba.ca; Doelle, Meinhard, E-mail: mdoelle@dal.ca; Duinker, Peter N., E-mail: peter.duinker@dal.ca

Despite all the effort that has gone into defining, researching and establishing best practices for cumulative effects assessment (CEA), understanding remains weak and practice wanting. At one extreme of implementation, CEA can be described as merely an irritant to the completion of a project-specific environmental assessment (EA). At the other extreme, the conceptual view is that all effects in EA should be deemed cumulative unless demonstrated otherwise. Our purpose here is to consider how we might reconceive CEA as a mindset that is at the heart of absolutely every assessment of valued ecosystem component (VEC) to ensure that we understandmore » the relative contributions of various stressors and can decide when cumulative effects may foreclose future activities due to impacts on VECs. Conceptually, we ground the CEA mindset in the context of three lenses that must all be functioning and working together for the mindset to be operative: a technical lens; a law and policy lens; and a participatory lens. Our arguments are based on a review of the CEA, strategic effects assessment (SEA) and regional effects assessment literatures, an examination and consideration of Canadian EA and SEA case practice, and our combined professional experiences. Through using the Bay of Fundy in Canada as a case example, we establish the concept of the CEA mindset and an approach for moving forward with implementation. - Highlights: • Conceptualization of cumulative effects assessment as a mindset. • Elaboration of technical, law and policy and participation lenses critical to CEA • Coordination and integration of cumulative effects for valued ecosystem components • Application in Bay of Fundy ecosystem and terrestrial watershed.« less

Molecular Mechanism Underlying the Entomotoxic Effect of Colocasia esculenta Tuber Agglutinin against Dysdercus cingulatus

PubMed Central

Roy, Amit; Das, Sampa

2015-01-01

Colocasia esculenta tuber agglutinin (CEA), a mannose binding lectin, exhibits insecticidal efficacy against different hemipteran pests. Dysdercus cingulatus, red cotton bug (RCB), has also shown significant susceptibility to CEA intoxication. However, the molecular basis behind such entomotoxicity of CEA has not been addressed adequately. The present study elucidates the mechanism of insecticidal efficacy of CEA against RCB. Confocal and scanning electron microscopic analyses documented CEA binding to insect midgut tissue, resulting in an alteration of perimicrovillar membrane (PMM) morphology. Internalization of CEA into insect haemolymph and ovary was documented by western blotting analyses. Ligand blot followed by mass spectrometric identification revealed the cognate binding partners of CEA as actin, ATPase and cytochrome P450. Deglycosylation and mannose inhibition assays indicated the interaction to probably be mannose mediated. Bioinformatic identification of putative glycosylation or mannosylation sites in the binding partners further supports the sugar mediated interaction. Correlating entomotoxicity of CEA with immune histological and binding assays to the insect gut contributes to a better understanding of the insecticidal potential of CEA and endorses its future biotechnological application.

Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

PubMed Central

Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

2015-01-01

Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF. PMID:26503065

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

PubMed Central

Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

[Usefulness of preoperative assay CEA and CA 19-9 in colorectal cancer patients].

PubMed

Grotowski, M; Maruszyński, M; Piechota, W

2001-12-01

Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA19-9) are well known tumor markers expressed by colorectal cancer (CRC), particularly in advanced cases. In this study serological expression of CEA and CA19-9 concerning different clinicopathological factors and sensitivity of diagnosis of CRC by combination of both markers were evaluated. Eighty one patients with diagnosed CRC were in this study included. According to Dukes' classification there were 11 in stage A, 34 in stage B, 17 in stage C and 19 in stage D. Blood samples were collected before operation. CEA and CA19-9 were determined by MEIA (normal range 0-3 ng/ml for CEA and 0-37 U/ml for CA19-9). The statistical analysis revealed that the CEA well correlated with histological type, liver metastasis and term of symptoms. The CA19-9 well correlated with liver metastasis, peritoneal dissemination, nodal involvement and cancer localization. The levels of CEA and CA19-9 increased with stage of the tumor, but only in stage D the difference was statistically significant (for CEA p = 0.005, for CA19-9 p = 0.039). At time of diagnosis 50.6% of the patients had elevated serum levels of CEA and 29.6% of CA19-9. In combination of both antigens this elevation was in 54.3% of CRC patients. The common use of CEA and CA19-9 was more efficacious in identification of patients at high risk. The combination assay of CEA and CA19-9 did not cause a significant increase of sensitivity in diagnosis CRC.

The risk of carotid artery stenting compared with carotid endarterectomy is greatest in patients treated within 7 days of symptoms.

PubMed

Rantner, Barbara; Goebel, Georg; Bonati, Leo H; Ringleb, Peter A; Mas, Jean-Louis; Fraedrich, Gustav

2013-03-01

Among patients with symptomatic carotid artery stenosis, carotid artery stenting (CAS) is associated with a higher risk of periprocedural stroke or death than carotid endarterectomy (CEA). Uncertainty remains whether the balance of risk changes with time since the most recent ischemic event. We investigated the association of time between the qualifying ischemic event and treatment (0-7 days, 8-14 days, and >14 days) with the risk of stroke or death within 30 days after CAS or CEA in a pooled analysis of data from individual patients randomized in the Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial, and the International Carotid Stenting Study (ICSS). Data were analyzed with a fixed-effect binomial regression model adjusted for source trial. Information on time of qualifying event was available for 2839 patients. In the first 30 days after intervention, any stroke or death occurred significantly more often in the CAS group (110/1434 [7.7%]) compared with the CEA group (54/1405 [3.8%]; crude risk ratio, 2.0; 95% confidence interval, 1.5-2.7). Patients undergoing CEA within the first 7 days of the qualifying event had the lowest periprocedural stroke or death rate (3/106 [2.8%]). Patients treated with CAS in the same period had a 9.4% risk of periprocedural stroke or death (13/138; risk ratio CAS vs CEA: 3.4; 95% confidence interval, 1.01-11.8; adjusted for age, sex, and type of qualifying event). Patients treated between 8 and 14 days showed a periprocedural stroke or death rate of 3.4% (7/208) and 8.1% (19/234), respectively, for CEA and CAS. The latest treatment group had 4% complications in the CEA group (44/1091) and 7.3% in the CAS group (78/1062). The increase in risk of CAS compared with CEA appears to be greatest in patients treated within 7 days of symptoms. Early surgery might remain most effective in stroke prevention in patients with symptomatic carotid artery stenosis. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Global economic evaluations of rotavirus vaccines: A systematic review.

PubMed

Kotirum, Surachai; Vutipongsatorn, Naaon; Kongpakwattana, Khachen; Hutubessy, Raymond; Chaiyakunapruk, Nathorn

2017-06-08

World Health Organization (WHO) recommends Rotavirus vaccines to prevent and control rotavirus infections. Economic evaluations (EE) have been considered to support decision making of national policy. Summarizing global experience of the economic value of rotavirus vaccines is crucial in order to encourage global WHO recommendations for vaccine uptake. Therefore, a systematic review of economic evaluations of rotavirus vaccine was conducted. We searched Medline, Embase, NHS EED, EconLit, CEA Registry, SciELO, LILACS, CABI-Global Health Database, Popline, World Bank - e-Library, and WHOLIS. Full economic evaluations studies, published from inception to November 2015, evaluating Rotavirus vaccines preventing Rotavirus infections were included. The methods, assumptions, results and conclusions of the included studies were extracted and appraised using WHO guide for standardization of EE of immunization programs. 104 relevant studies were included. The majority of studies were conducted in high-income countries. Cost-utility analysis was mostly reported in many studies using incremental cost-effectiveness ratio per DALY averted or QALY gained. Incremental cost per QALY gained was used in many studies from high-income countries. Mass routine vaccination against rotavirus provided the ICERs ranging from cost-saving to highly cost-effective in comparison to no vaccination among low-income countries. Among middle-income countries, vaccination offered the ICERs ranging from cost-saving to cost-effective. Due to low- or no subsidized price of rotavirus vaccines from external funders, being not cost-effective was reported in some high-income settings. Mass vaccination against rotavirus was generally found to be cost-effective, particularly in low- and middle-income settings according to the external subsidization of vaccine price. On the other hand, it may not be a cost-effective intervention at market price in some high-income settings. This systematic review provides supporting information to health policy-makers and health professionals when considering rotavirus vaccination as a national program. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The health economics of attention deficit hyperactivity disorder in Germany. Part 2: Therapeutic options and their cost-effectiveness].

PubMed

Schlander, M; Trott, G-E; Schwarz, O

2010-03-01

Attention deficit hyperactivity disorder (ADHD) has been associated with a continuous increase of health care utilization and thus expenditures. This raises the issue of cost-effectiveness of health care provided for patients with ADHD. Comparative health economic evaluations generate relevant insights and typically report incremental cost-effectiveness ratios (ICERs) of alternatives versus an established standard. Typically, results of cost-effectiveness analyses (CEAs) are reported in terms of incremental cost-effectiveness ratios (ICERs). International evaluations, as well specific adaptations to Germany, indicate an acceptable to attractive cost-effectiveness--according to currently used international benchmarks--of an intense medication management strategy based on stimulants, primarily methylphenidate, with ICERs ranging from 20,000 EUR to 37,000 EUR per quality-adjusted life year (QALY) gained. Economic modeling studies also suggest cost-effectiveness of long-acting modified-release preparations of methylphenidate, owing to improved treatment compliance associated with simplified once daily administration schemes. Atomoxetine, in contrast, appears economically inferior compared to long-acting stimulants, given its higher acquisition costs and at best equal clinical effectiveness. There are currently no data supporting the cost-effectiveness of psychotherapeutic or behavioral interventions. Economic evaluations, which have been published to date, are generally limited by time horizons of up to 1 year and by their prevailing focus on ADHD core symptom improvement only. Therefore, further research into the cost-effectiveness of ADHD treatment strategies seems warranted.

Graphite paper-based bipolar electrode electrochemiluminescence sensing platform.

PubMed

Zhang, Xin; Ding, Shou-Nian

2017-08-15

In this work, aiming at the construction of a disposable, wireless, low-cost and sensitive system for bioassay, we report a closed bipolar electrode electrochemiluminescence (BPE-ECL) sensing platform based on graphite paper as BPE for the first time. Graphite paper is qualified as BPE due to its unique properties such as excellent electrical conductivity, uniform composition and ease of use. This simple BPE-ECL device was applied to the quantitative analysis of oxidant (H 2 O 2 ) and biomarker (CEA) respectively, according to the principle of BPE sensing-charge balance. For the H 2 O 2 analysis, Pt NPs were electrodeposited onto the cathode through a bipolar electrodeposition approach to promote the sensing performance. As a result, this BPE-ECL device exhibited a wide linear range of 0.001-15mM with a low detection limit of 0.5µM (S/N=3) for H 2 O 2 determination. For the determination of CEA, chitosan-multi-walled carbon nanotubes (CS-MWCNTs) were employed to supply a hydrophilic interface for immobilizing primary antibody (Ab 1 ); and Au@Pt nanostructures were conjugated with secondary antibody (Ab 2 ) as catalysts for H 2 O 2 reduction. Under the optimal conditions, the BPE-ECL immunodevice showed a wide linear range of 0.01-60ngmL -1 with a detection limit of 5.0pgmL -1 for CEA. Furthermore, it also displayed satisfactory selectivity, excellent stability and good reproducibility. The developed method opened a new avenue to clinical bioassay. Copyright © 2017 Elsevier B.V. All rights reserved.

Divergent functions of the left and right central amygdala in visceral nociception

PubMed Central

Sadler, Katelyn E.; McQuaid, Neal A.; Cox, Abigail C.; Behun, Marissa N.; Trouten, Allison M.; Kolber, Benedict J.

2017-01-01

The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2–mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase–activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2–mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain–like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries. PMID:28225716

Divergent functions of the left and right central amygdala in visceral nociception.

PubMed

Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J

2017-04-01

The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bajenova, Olga, E-mail: o.bazhenova@spbu.ru; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034; Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178

2014-06-10

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA andmore » beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.« less

Regulation of gene expression in plasmid ColE1: delayed expression of the kil gene.

PubMed Central

Zhang, S P; Yan, L F; Zubay, G

1988-01-01

cea, imm, and kil are a cluster of three functionally related genes of the plasmid ColE1. The cea and kil genes are in the same inducible operon, with transcription being initiated from a promoter adjacent to the cea gene. The imm gene is located between the cea and kil genes, but it is transcribed in the opposite direction. Complementary interaction between the imm mRNA and the anti-imm sequences in the middle of the cea-kil transcript causes a pronounced delay in expression of the kil gene when the cea-kil operon is induced. A segment in the overlapping region between the cea and imm genes causes delayed expression of the kil gene in the absence of imm gene transcription. This delay effect increases the yields of colicin synthesized in induced cells. Images PMID:3142845

Factors associated with parent support for condom education and availability.

PubMed

AugsJoost, Brett; Jerman, Petra; Deardorff, Julianna; Harley, Kim; Constantine, Norman A

2014-04-01

Expanding condom-related knowledge and skills and reducing barriers to condom use have the potential to help reduce pregnancies and sexually transmitted infections among youth. These goals are sometimes addressed through condom education and availability (CEA) programs as part of sexuality education in school. Parents are a key constituency in efforts to implement such programs. A representative statewide sample of households with children (N = 1,093) in California was employed to examine parent support for CEA and the potential influences of demographics (gender, age, and Hispanic ethnicity), sociodemographics (education, religious affiliation, religious service attendance, and political ideology), and condom-related beliefs (belief in condom effectiveness and belief that teens who use condoms during sex are being responsible) on parent support for CEA. The parents in our sample reported a high level of support for CEA (M = 3.23 on a 4-point scale) and believing in a high level of condom effectiveness (M = 3.36 on a 4-point scale). In addition, 84% of the parents agreed that teens who use condoms during sex are being responsible. Hierarchical regression analyses showed that parents who were younger, Hispanic, with a lower educational attainment, without a religious affiliation, less religiously observant, and politically liberal were more supportive of CEA. After controlling for these demographic and sociodemographic factors, condom effectiveness and responsibility beliefs each added independently to the predictability of parent support for CEA. These findings suggest that parent education related to condom effectiveness could help increase support for school-based CEA programs.

Pre-clinical validation study of a miniaturized electrochemical immunoassay based on square wave voltammetry for early detection of carcinoembryonic antigen in human serum.

PubMed

Martínez-Mancera, Flavio Dolores; García-López, Patricia; Hernández-López, José Luis

2015-04-15

The ELISA format for measuring carcinoembryonic antigen (CEA) serves as a reference standard against which other assays are compared. Because the World Health Organization (WHO) increasingly recommends the use of serum CEA as a diagnostic tool for cancer, it is relevant to explore the reliability of the new decentralized CEA point-of-care-testing (POCT) technologies that are available to physicians and patients, in compliance with mandates of the clinical laboratories' regulatory agencies. Electrochemical immunoassay (ECIA) based on trace lead (Pb) analysis by anodic stripping techniques using sandwich-type immunocomplex conjugates: (MB)Ab/AgCEA/Ab(PbS), and a commercial ELISA test system with optical transmission. The ECIA provides better analytical performance than does the ELISA. The within assay precision coefficient of variance (%CVw) of the ECIA is lower than the value recommended by the Hong Kong Association of Medical Laboratories (HKAML), and the recoveries of CEA at 1.0, 5.0, 10.0, 25.0 and 50.0 ng/ml are in the range of 99-110% for control serum samples. The ECIA showed a minimal positive bias of 0.0267 ± 0.3270 ng/ml (P=0.9389). The proposed CEA screening technology can be practically employed for decentralized clinical analysis of CEA in human serum. Therefore, it can be viewed as a control method for personalized therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Patient risk perceptions for carotid endarterectomy: which patients are strongly averse to surgery?

PubMed

Bosworth, Hayden B; Stechuchak, Karen M; Grambow, Steven C; Oddone, Eugene Z

2004-07-01

Patient risk perception for surgery may be central to their willingness to undergo surgery. This study examined potential factors associated with patient aversion of surgery. This is a secondary data analysis of a prospective cohort study that examined patients referred for evaluation of carotid artery stenosis at five Veterans Affairs Medical Centers. The study collected demographic, clinical, and psychosocial information related to surgery. This analysis focused on patient response to a question assessing their aversion to surgery. Among the 1065 individuals, at the time of evaluation for carotid endarterectomy (CEA), 66% of patients had no symptoms, 16% had a transient ischemic attack, and 18% had stroke. Twelve percent of patients referred for CEA evaluation were averse to surgery. In adjusted analyses, increased age, black race, no previous surgery, lower level of chance locus of control, less trust of physicians, and less social support were significantly related to greater likelihood of surgery aversion among individuals referred for CEA evaluation. Patient degree of medical comorbidity and a validated measure of preoperative risk score were not associated with increased aversion to surgery. In previous work, aversion to CEA was associated with lack of receipt of CEA even after accounting for patient clinical appropriateness for surgery. We identified important patient characteristics associated with aversion to CEA. Interventions designed to assist patient decision making should focus on these more complex factors related to CEA aversion rather than the simple explanation of clinical usefulness.

Identity and relatedness as mediators between child emotional abuse and adult couple adjustment in women.

PubMed

Bigras, Noémie; Godbout, Natacha; Hébert, Martine; Runtz, Marsha; Daspe, Marie-Ève

2015-12-01

The empirical literature indicates that childhood emotional abuse (CEA) produces long lasting impairments in interpersonal relatedness and identity, often referred to as self-capacities. CEA has also been shown to negatively impact couple functioning. This study examined the role of identity and interpersonal conflicts in mediating the relationship between CEA and women's report of couple adjustment among 184 French Canadian women from the general population. Path analysis revealed that CEA was related to poorer couple adjustment through its impact on dysfunctional self-capacities and the experience of greater conflicts in relationships. Findings highlight the importance of assessing CEA to better explain couple adjustment in women with relationship difficulties and provide potential intervention targets based on the self-capacities framework. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aggregation and the Measurement of Health Care Costs

PubMed Central

Getzen, Thomas E

2006-01-01

Objective This study evaluated the extent to which the causes of variation in health care costs differ by the level at which observations are made. Methods More than 40 U.S. and international studies providing empirical estimates of the sources of variation in health care costs were reviewed and arrayed by size of observational units. A simplified graphical analysis demonstrating how estimated correlation coefficients change with the level and type of aggregation is presented. Results As the unit of observation becomes larger, association between health care costs and health status/morbidity becomes weaker and smaller in magnitude, while correlation with income (per capita GDP) becomes stronger and larger. Individual expenditure variation within a particular health care system is largely due to differences in health status, but across systems, morbidity has almost no effect on costs. For nations, differences in per capita income explain over 90 percent of the variation in both time series and cross section. Conclusions Units of observation used for analysis of health care costs must be matched to the units at which decision making occurs. The observed pattern of empirical results is consistent with a multilevel allocative model incorporating aggregate capacity constraints. To the extent that macro constraints determine total budgets at the national level, policy interventions at the micro level (substitution of generic pharmaceuticals, use of CEA for allocation of treatments, controls on construction and technology, etc.) can act to improve efficiency, equity and average health status, but will not usually reduce aggregate average per capita costs of medical care. PMID:16987309

Treatments for Metastatic Prostate Cancer (mPC): A Review of Costing Evidence.

PubMed

Norum, Jan; Nieder, Carsten

2017-12-01

Prostate cancer (PC) is the most common cancer in Western countries. More than one third of PC patients develop metastatic disease, and the 5-year expected survival in distant disease is about 35%. During the last few years, new treatments have been launched for metastatic castrate-resistant prostate cancer (mCRPC). We aimed to review the current literature on health economic analysis on the treatment of metastatic prostate cancer (mPC), compare the studies, summarize the findings and make the results available to administrators and decision makers. A systematic literature search was done for economic evaluations (cost-minimization, cost-effectiveness, cost-utility, cost-of-illness, cost-of-drug, and cost-benefit analyses). We employed the PubMed ® search engine and searched for publications published between 2012 and 2016. The terms used were "prostate cancer", "metastatic" and "cost". An initial screening of all headlines was performed, selected abstracts were analysed, and finally the full papers investigated. Study characteristics, treatment and comparator, country, type of evaluation, perspective, year of value, time horizon, efficacy data, discount rate, total costs and sensitivity analysis were analysed. The quality was assessed using the Quality of Health Economic Studies (QHES) instrument. A total of 227 publications were detected and screened, 58 selected for full-text assessment and 31 included in the final analyses. Despite the significant international literature on the treatment of mCRPC, there were only 15 studies focusing on cost-effectiveness analysis (CEA). Medical treatment constituted two thirds of the selected studies. Significant costs in the treatment of mCRPC were disclosed. In the pre-docetaxel setting, both abiraterone acetate (AA) and enzalutamide were concluded beyond accepted cost/quality-adjusted life year limits. In the docetaxel refractory setting, most studies concluded that enzalutamide was cost-effective and superior to AA. In most studies, cabazitaxel was not recommended, because of high cost. Looking at bone-targeting drugs, generic zoledronic acid (ZA) was recommended. External beam radiotherapy (EBRT) was analysed in three studies, and single fraction radiotherapy was concluded to be cost saving. Radium-223 was documented as beneficial, but costly. The quality of the studies was generally good, but sensitivity analyses, discounting and the measurement of health outcomes were present in less than two thirds of the selected studies. The treatment of mCRPC was associated with significant cost. In the post-docetaxel setting, single fraction radiotherapy and enzalutamide were considered cost-effective in most studies. Generic ZA was the recommended bone-targeting therapy.

Two Cases of Transiently Elevated Serum CEA Levels in Severe Hypothyroidism without Goiter.

PubMed

Sekizaki, Tomonori; Yamamoto, Chiho; Nomoto, Hiroshi

2018-04-27

Carcinoembryonic antigen (CEA), the level of which is known to increase in both patients with gastrointestinal cancers and those with non-neoplastic conditions, is one of the most widely-used tumor markers. Hypothyroidism is a common endocrinological disorder in which CEA levels can rise, and is sometimes overlooked as a diagnosis in the absence of typical symptoms or thyroid enlargement. We report the cases of two patients with non-goiterous severe hypothyroidism with markedly elevated CEA levels that effectively decreased with levothyroxine replacement therapy alone. Hypothyroidism should be considered as an important cause of unexplained high serum CEA levels in order to avoid unnecessary medical examination.

Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.

PubMed

Sano, K; Asahina, M; Uehara, T; Matsumoto, K; Araki, N; Okuyama, R

2017-12-01

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA. We performed comparative analysis of eccrine glands between sweat-preserved and non-sweating skin in four AIGA patients. Serum CEA concentrations in 22 cases with AIGA were measured with healthy volunteers. Furthermore, we semiquantitatively investigated dermcidin, FoxA1 and CEA expression in eccrine glands of 12 cases with AIGA and 5 cases with non-AIGA. Marked degranulation and shrinkage of dark cells consistently occurred in AIGA. Furthermore, high serum CEA concentrations were found in 14 of 22 AIGA patients (over 60%), but serum CEA levels were not correlated with CEA expression in eccrine glands. Dermcidin expression in dark cells apparently decreased in AIGA patients, severely in those with high serum CEA and moderately in those with low serum CEA, while well-preserved expression was found in non-AIGA subjects. Our study suggests morphological damage and molecular dysregulation of dark cells, leading to impairment of their functions in AIGA patients. Severely damaged dark cells correspond to high serum CEA. Accordingly, these pathological changes in eccrine dark cells may be involved in anhidrosis/hypohidrosis of AIGA. © 2017 European Academy of Dermatology and Venereology.

Linkages between childhood emotional abuse and marital satisfaction: The mediating role of empathic accuracy for hostile emotions

PubMed Central

Maneta, E.K.; Cohen, S.; Schulz, M.S.; Waldinger, R.J.

2014-01-01

Research linking childhood emotional abuse (CEA) and adult marital satisfaction has focused on individuals without sufficient attention to couple processes. Less attention has also been paid to the effects of CEA on the ability to read other’s emotions, and how this may be related to satisfaction in intimate relationships. In this study, 156 couples reported on histories of CEA, marital satisfaction and empathic accuracy of their partners’ positive and hostile emotions during discussion of conflicts in their relationships. Actor-Partner Interdependence Modeling was used to examine links between CEA and marital satisfaction, with empathic accuracy as a potential mediator. Both men’s and women’s CEA histories were linked not only with their own lower marital satisfaction but also with their partners’ lower satisfaction. Empathic accuracy for hostile emotions mediated the link between women’s CEA and their satisfaction and their partners’ satisfaction in the relationship. Findings suggest that a history of CEA is associated with difficulties with empathic accuracy, and that empathic inaccuracy in part mediates the association between CEA and adult marital dissatisfaction. PMID:25151303

Linkages between childhood emotional abuse and marital satisfaction: The mediating role of empathic accuracy for hostile emotions.

PubMed

Maneta, E K; Cohen, S; Schulz, M S; Waldinger, R J

2015-06-01

Research linking childhood emotional abuse (CEA) and adult marital satisfaction has focused on individuals without sufficient attention to couple processes. Less attention has also been paid to the effects of CEA on the ability to read other's emotions, and how this may be related to satisfaction in intimate relationships. In this study, 156 couples reported on histories of CEA, marital satisfaction and empathic accuracy of their partners' positive and hostile emotions during discussion of conflicts in their relationships. Actor-Partner Interdependence Modeling was used to examine links between CEA and marital satisfaction, with empathic accuracy as a potential mediator. Both men's and women's CEA histories were linked not only with their own lower marital satisfaction but also with their partners' lower satisfaction. Empathic accuracy for hostile emotions mediated the link between women's CEA and their satisfaction and their partners' satisfaction in the relationship. Findings suggest that a history of CEA is associated with difficulties with empathic accuracy, and that empathic inaccuracy in part mediates the association between CEA and adult marital dissatisfaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

cea-kil operon of the ColE1 plasmid.

PubMed Central

Sabik, J F; Suit, J L; Luria, S E

1983-01-01

We isolated a series of Tn5 transposon insertion mutants and chemically induced mutants with mutations in the region of the ColE1 plasmid that includes the cea (colicin) and imm (immunity) genes. Bacterial cells harboring each of the mutant plasmids were tested for their response to the colicin-inducing agent mitomycin C. All insertion mutations within the cea gene failed to bring about cell killing after mitomycin C treatment. A cea- amber mutation exerted a polar effect on killing by mitomycin C. Two insertions beyond the cea gene but within or near the imm gene also prevented the lethal response to mitomycin C. These findings suggest the presence in the ColE1 plasmid of an operon containing the cea and kil genes whose product is needed for mitomycin C-induced lethality. Bacteria carrying ColE1 plasmids with Tn5 inserted within the cea gene produced serologically cross-reacting fragments of the colicin E1 molecule, the lengths of which were proportional to the distance between the insertion and the promoter end of the cea gene. Images PMID:6298187

Collecting and analysing cost data for complex public health trials: reflections on practice.

PubMed

Batura, Neha; Pulkki-Brännström, Anni-Maria; Agrawal, Priya; Bagra, Archana; Haghparast-Bidgoli, Hassan; Bozzani, Fiammetta; Colbourn, Tim; Greco, Giulia; Hossain, Tanvir; Sinha, Rajesh; Thapa, Bidur; Skordis-Worrall, Jolene

2014-01-01

Current guidelines for the conduct of cost-effectiveness analysis (CEA) are mainly applicable to facility-based interventions in high-income settings. Differences in the unit of analysis and the high cost of data collection can make these guidelines challenging to follow within public health trials in low- and middle- income settings. This paper reflects on the challenges experienced within our own work and proposes solutions that may be useful to others attempting to collect, analyse, and compare cost data between public health research sites in low- and middle- income countries. We describe the generally accepted methods (norms) for collecting and analysing cost data in a single-site trial from the provider perspective. We then describe our own experience applying these methods within eight comparable cluster randomised, controlled, trials. We describe the strategies used to maximise adherence to the norm, highlight ways in which we deviated from the norm, and reflect on the learning and limitations that resulted. When the expenses incurred by a number of small research sites are used to estimate the cost-effectiveness of delivering an intervention on a national scale, then deciding which expenses constitute 'start-up' costs will be a nontrivial decision that may differ among sites. Similarly, the decision to include or exclude research or monitoring and evaluation costs can have a significant impact on the findings. We separated out research costs and argued that monitoring and evaluation costs should be reported as part of the total trial cost. The human resource constraints that we experienced are also likely to be common to other trials. As we did not have an economist in each site, we collaborated with key personnel at each site who were trained to use a standardised cost collection tool. This approach both accommodated our resource constraints and served as a knowledge sharing and capacity building process within the research teams. Given the practical reality of conducting randomised, controlled trials of public health interventions in low- and middle- income countries, it is not always possible to adhere to prescribed guidelines for the analysis of cost effectiveness. Compromises are frequently required as researchers seek a pragmatic balance between rigor and feasibility. There is no single solution to this tension but researchers are encouraged to be mindful of the limitations that accompany compromise, whilst being reassured that meaningful analyses can still be conducted with the resulting data.

Comparison of carotid endarterectomy and stenting in real world practice using a regional quality improvement registry

PubMed Central

Nolan, Brian W.; De Martino, Randall R.; Goodney, Philip P.; Schanzer, Andres; Stone, David H.; Butzel, David; Kwolek, Christopher J.; Cronenwett, Jack L.

2013-01-01

Objective Carotid artery stenting (CAS) vs endarterectomy (CEA) remains controversial and has been the topic of recent randomized controlled trials. The purpose of this study was to compare the practice and outcomes of CAS and CEA in a real world setting. Methods This is a retrospective analysis of 7649 CEA and 430 CAS performed at 17 centers from 2003 to 2010 within the Vascular Study Group of New England (VSGNE). The primary outcome measures were (1) any in-hospital stroke or death and (2) any stroke, death, or myocardial infarction (MI). Patients undergoing CEA in conjunction with cardiac surgery were excluded. Multivariate logistic regression was performed to identify predictors of stroke or death in patients undergoing CAS. Results CEA was performed in 17 centers by 111 surgeons, while CAS was performed in 6 centers by 30 surgeons and 8 interventionalists. Patient characteristics varied by procedure. Patients undergoing CAS had a higher prevalence of coronary artery disease, congestive heart failure, diabetes, and prior ipsilateral CEA. Embolic protection was used in 97% of CAS. Shunts were used in 48% and patches in 86% of CEA. The overall in-hospital stroke or death rate was higher among patients undergoing CAS (2.3% vs 1.1%; P = .03). Overall stroke, death, or MI (2.8% CAS vs 2.1% CEA; P = .32) were not different. Asymptomatic patients had similar rates of stroke or death (CAS 0.73% vs CEA 0.89%; P = .78) and stroke, death, or MI (CAS 1.1% vs CEA 1.8%; P = .40). Symptomatic patients undergoing CAS had higher rates of stroke or death (5.1% vs 1.6%; P = .001), and stroke, death, or MI (5.8% vs 2.7%; P = .02). By multivariate analysis, major stroke (odds ratio, 4.5; 95% confidence interval [CI], 1.9–10.8), minor stroke (2.7; CI, 1.5–4.8), prior ipsilateral CEA (3.2, CI, 1.7–6.1), age >80 (2.1; CI, 1.3–3.4), hypertension (2.6; CI, 1.0–6.3), and a history of chronic obstructive pulmonary disease (1.6; CI, 1.0–2.4) were predictors of stroke or death in patients undergoing carotid revascularization. Conclusions In our regional vascular surgical practices, the overall outcomes of CAS and CEA are similar for asymptomatic patients. However, symptomatic patients treated with CAS are at a higher risk for stroke or death. (J Vasc Surg 2012;56:990-6.) PMID:22579135

Detection of CEA in human serum using surface-enhanced Raman spectroscopy coupled with antibody-modified Au and γ-Fe₂O₃@Au nanoparticles.

PubMed

Lin, Yan; Xu, Guanhong; Wei, Fangdi; Zhang, Aixia; Yang, Jing; Hu, Qin

2016-03-20

In this present work, a rapid and simple method to detect carcinoembryonic antigen (CEA) was developed by using surface-enhanced Raman spectroscopy (SERS) coupled with antibody-modified Au and γ-Fe2O3@Au nanoparticles. First, Au@Raman reporter and γ-Fe2O3@Au were prepared, and then modified with CEA antibody. When CEA was present, the immuno-Au@Raman reporter and immuno-γ-Fe2O3@Au formed a complex through antibody-antigen-antibody interaction. The selective and sensitive detection of CEA could be achieved by SERS after magnetic separation. Under the optimal conditions, a linear relationship was observed between the Raman peak intensity and the concentration of CEA in the range of 1-50 ng mL(-1) with an excellent correlation coefficient of 0.9942. The limit of detection based on two times ratio of signal to noise was 0.1 ng/mL. The recoveries of CEA standard solution spiked with human serum samples were in the range of 88.5-105.9% with the relative standard deviations less than 17.4%. The method built was applied to the detection of CEA in human serum, and the relative deviations of the analysis results between the present method and electrochemiluminescence immunoassay were all less than 16.6%. The proposed method is practical and has a potential for clinic test of CEA. Copyright © 2016 Elsevier B.V. All rights reserved.

Favorable effects of carotid endarterectomy on baroreflex sensitivity and cardiovascular neural modulation: a 4-month follow-up.

PubMed

Dalla Vecchia, Laura; Barbic, Franca; Galli, Andrea; Pisacreta, Massimo; Gornati, Rosella; Porretta, Tiziano; Porta, Alberto; Furlan, Raffaello

2013-06-15

Carotid surgery variably modifies carotid afferent innervation, thus affecting arterial baroreceptor sensitivity. Low arterial baroreflex sensitivity is a well-known independent risk factor for cardiovascular diseases. The aim of this study was to assess the 4-mo effects of carotid endarterectomy (CEA) on arterial baroreceptor sensitivity and cardiovascular autonomic profile in patients with unilateral carotid stenosis. We enrolled 20 patients (72 ± 8 yr) with unilateral >70% carotid stenosis. ECG, beat-by-beat blood pressure, and respiration were continuously recorded before and 126 ± 9 days after CEA, at rest and during a 75° head-up tilt. Both pharmacological (modified Oxford technique, BRS) and spontaneous (index α, spectral analysis) arterial baroreflex sensitivity were assessed. Cardiovascular autonomic profile was evaluated by plasma catecholamines and spectral indexes of cardiac sympathovagal modulation [low-frequency R-R interval (LFRR), low frequency-to high frequency ratio (LF/HF), high-frequency R-R interval (HFRR)] and sympathetic vasomotor control [low-frequency systolic arterial pressure (LFSAP)] obtained from heart rate and SAP variability. After CEA, both the index α and BRS were higher (P < 0.02) at rest. SAP variance decreased both at rest and during tilt (P < 0.02). Before surgery, tilt did not modify the autonomic profile compared with baseline. After CEA, tilt increased LF/HF and LFSAP and reduced HFRR compared with rest (P < 0.02). Four months after CEA was performed, arterial baroreflex sensitivity was enhanced. Accordingly, the patients' autonomic profile had shifted toward reduced cardiac and vascular sympathetic activation and enhanced cardiac vagal activity. The capability to increase cardiovascular sympathetic activation in response to orthostasis was restored. Baroreceptor sensitivity improvement might play an additional role in the more favorable outcome observed in patients after carotid surgery.

Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

PubMed Central

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-01-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

Preoperative carcinoembryonic antigen and prognosis of colorectal cancer. An independent prognostic factor still reliable.

PubMed

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-04-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.

A scoping review of pediatric economic evaluation 1980-2014: do trends over time reflect changing priorities in evaluation methods and childhood disease?

PubMed

Sullivan, Shannon M; Tsiplova, Kate; Ungar, Wendy J

2016-10-01

Economic evaluations conducted in children have unique features compared to adults. Important developments in pediatric economic evaluation in recent years include new options for valuing health states for cost-utility analysis (CUA) and shifting child health priorities. The Pediatric Economic Database Evaluation (PEDE) project includes a comprehensive database of pediatric health economic evaluations published since 1980. The objective of this scoping review was to identify trends over time in the use of CUA and other analytic techniques, and the therapeutic areas chosen for study. Areas covered: Medical and grey literature were searched, key characteristics were extracted, frequencies were tabulated and cross-tabulations were performed. Differences between early (1980 and 1999) and late (2000 and 2014) periods were assessed using a chi-squared statistic. Of the 2,776 pediatric economic evaluations published between 1980 and 2014, substantially more were cost-effectiveness analyses (CEAs) and CUAs than cost benefit analyses and cost minimization analyses (63.9 and 24.9% versus 7.6 and 3.6%, respectively). This pattern was consistent regardless of the type of intervention, disease or age group studied. A trend toward higher proportions of CUAs and CEAs was evident in the later period (X 2 p < 0.0001). Other significant trends included a higher proportion of studies of preventive interventions (X 2 p < 0.0001), and more studies in children aged 1 to 12 years and fewer in perinates in the later period (X 2 p < 0.0001). Overall the most common disease class studied was infectious diseases (29.2%). Expert commentary: Pediatric economic evaluation continues to grow in volume and methodologic complexity. While CUAs have increased, whether their quality has improved remains unknown. Although most studies are in infectious disease, the volume of publications may not align with emerging child health priorities such as adolescent health, injury, developmental disabilities, mental health, and the use of personalized medicine. Increasing economic evaluations in these areas will enhance pediatric decision-making.

Application of the cultured epidermal autograft "JACE(®") for treatment of severe burns: Results of a 6-year multicenter surveillance in Japan.

PubMed

Matsumura, Hajime; Matsushima, Asako; Ueyama, Masashi; Kumagai, Norio

2016-06-01

In the 1970s, Green et al. developed a method that involved culturing keratinocyte sheets and used for treatment of burns. Since then, the take rate of cultured epidermal autograft (CEA) onto fascia, granulation tissue, or allografts has been extensively reported, while that on an artificial dermis in a large case series is not. Moreover, the contribution of CEA to patient survival has not been analyzed in a multicenter study. We conducted a 6-year multicenter surveillance on the application of the CEA "JACE(®") for treatment of burns >30% total body surface area (TBSA) across 118 Japanese hospitals. This surveillance included 216 patients and 718 graft sites for efficacy analysis. The CEA take rate at 4 weeks after grafting was evaluated, and safety was monitored until 52 weeks. In addition, the survival curve obtained in this study and the data obtained from the Tokyo Burn Unit Association (TBUA) were compared. The mean CEA take rates at week 4 were 66% (sites) and 68% (patients), and the rate on the artificial dermis was 65% for 226 sites. CEA application combined with wide split-thickness auto or patch autograft increased the CEA take rate. On comparison with the data obtained from the TBUA, which included data on individuals with burns of the same severity, CEA application was found to contribute to patient survival until 7 weeks after burn. We reported the take rate of CEA based on a 6-year multicenter surveillance. From our results, we found that the application of CEA is a useful treatment for the patients with extensive burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Changing vessel routes could significantly reduce the cost of future offshore wind projects.

PubMed

Samoteskul, Kateryna; Firestone, Jeremy; Corbett, James; Callahan, John

2014-08-01

With the recent emphasis on offshore wind energy Coastal and Marine Spatial Planning (CMSP) has become one of the main frameworks used to plan and manage the increasingly complex web of ocean and coastal uses. As wind development becomes more prevalent, existing users of the ocean space, such as commercial shippers, will be compelled to share their historically open-access waters with these projects. Here, we demonstrate the utility of using cost-effectiveness analysis (CEA) to support siting decisions within a CMSP framework. In this study, we assume that large-scale offshore wind development will take place in the US Mid-Atlantic within the next decades. We then evaluate whether building projects nearshore or far from shore would be more cost-effective. Building projects nearshore is assumed to require rerouting of the commercial vessel traffic traveling between the US Mid-Atlantic ports by an average of 18.5 km per trip. We focus on less than 1500 transits by large deep-draft vessels. We estimate that over 29 years of the study, commercial shippers would incur an additional $0.2 billion (in 2012$) in direct and indirect costs. Building wind projects closer to shore where vessels used to transit would generate approximately $13.4 billion (in 2012$) in savings. Considering the large cost savings, modifying areas where vessels transit needs to be included in the portfolio of policies used to support the growth of the offshore wind industry in the US. Copyright © 2014 Elsevier Ltd. All rights reserved.

CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

PubMed

Kozman, Mathew A; Fisher, Oliver M; Rebolledo, Bree-Anne J; Parikh, Roneil; Valle, Sarah J; Arrowaili, Arief; Alzahrani, Nayef; Liauw, Winston; Morris, David L

2018-03-01

Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported. Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC. Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03). CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior. © 2017 Wiley Periodicals, Inc.

Analgesic Effects of Duloxetine on Formalin-Induced Hyperalgesia and Its Underlying Mechanisms in the CeA

PubMed Central

Zhang, Lie; Yin, Jun-Bin; Hu, Wei; Zhao, Wen-Jun; Fan, Qing-Rong; Qiu, Zhi-Chun; He, Ming-Jie; Ding, Tan; Sun, Yan; Kaye, Alan D.; Wang, En-Ren

2018-01-01

In rodents, the amygdala has been proposed to serve as a key center for the nociceptive perception. Previous studies have shown that extracellular signal-regulated kinase (ERK) signaling cascade in the central nucleus of amygdala (CeA) played a functional role in inflammation-induced peripheral hypersensitivity. Duloxetine (DUL), a serotonin and noradrenaline reuptake inhibitor, produced analgesia on formalin-induced spontaneous pain behaviors. However, it is still unclear whether single DUL pretreatment influences formalin-induced hypersensitivity and what is the underlying mechanism. In the current study, we revealed that systemic pretreatment with DUL not only dose-dependently suppressed the spontaneous pain behaviors, but also relieved mechanical and thermal hypersensitivity induced by formalin hindpaw injection. Consistent with the analgesic effects of DUL on the pain behaviors, the expressions of Fos and pERK that were used to check the neuronal activities in the spinal cord and CeA were also dose-dependently reduced following DUL pretreatment. Meanwhile, no emotional aversive behaviors were observed at 24 h after formalin injection. The concentration of 5-HT in the CeA was correlated with the dose of DUL in a positive manner at 24 h after formalin injection. Direct injecting 5-HT into the CeA suppressed both the spontaneous pain behaviors and hyperalgesia induced by formalin injection. However, DUL did not have protective effects on the formalin-induced edema of hindpaw. In sum, the activation of CeA neurons may account for the transition from acute pain to long-term hyperalgesia after formalin injection. DUL may produce potent analgesic effects on the hyperalgesia and decrease the expressions of p-ERK through increasing the concentration of serotonin in the CeA. PMID:29692727

Analgesic Effects of Duloxetine on Formalin-Induced Hyperalgesia and Its Underlying Mechanisms in the CeA.

PubMed

Zhang, Lie; Yin, Jun-Bin; Hu, Wei; Zhao, Wen-Jun; Fan, Qing-Rong; Qiu, Zhi-Chun; He, Ming-Jie; Ding, Tan; Sun, Yan; Kaye, Alan D; Wang, En-Ren

2018-01-01

In rodents, the amygdala has been proposed to serve as a key center for the nociceptive perception. Previous studies have shown that extracellular signal-regulated kinase (ERK) signaling cascade in the central nucleus of amygdala (CeA) played a functional role in inflammation-induced peripheral hypersensitivity. Duloxetine (DUL), a serotonin and noradrenaline reuptake inhibitor, produced analgesia on formalin-induced spontaneous pain behaviors. However, it is still unclear whether single DUL pretreatment influences formalin-induced hypersensitivity and what is the underlying mechanism. In the current study, we revealed that systemic pretreatment with DUL not only dose-dependently suppressed the spontaneous pain behaviors, but also relieved mechanical and thermal hypersensitivity induced by formalin hindpaw injection. Consistent with the analgesic effects of DUL on the pain behaviors, the expressions of Fos and pERK that were used to check the neuronal activities in the spinal cord and CeA were also dose-dependently reduced following DUL pretreatment. Meanwhile, no emotional aversive behaviors were observed at 24 h after formalin injection. The concentration of 5-HT in the CeA was correlated with the dose of DUL in a positive manner at 24 h after formalin injection. Direct injecting 5-HT into the CeA suppressed both the spontaneous pain behaviors and hyperalgesia induced by formalin injection. However, DUL did not have protective effects on the formalin-induced edema of hindpaw. In sum, the activation of CeA neurons may account for the transition from acute pain to long-term hyperalgesia after formalin injection. DUL may produce potent analgesic effects on the hyperalgesia and decrease the expressions of p-ERK through increasing the concentration of serotonin in the CeA.

Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

PubMed Central

Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G.; Schweitzer, Paul; Parsons, Loren H.; Roberto, Marisa

2015-01-01

The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and type 1 cannabinoid receptor (CB1) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naïve rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not type 2 cannabinoid receptor (CB2) antagonism. After 2–3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naïve CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naïve and ethanol exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling. PMID:25940135

Protamine reduces bleeding complications associated with carotid endarterectomy without increasing the risk of stroke.

PubMed

Stone, David H; Nolan, Brian W; Schanzer, Andres; Goodney, Philip P; Cambria, Robert A; Likosky, Donald S; Walsh, Daniel B; Cronenwett, Jack L

2010-03-01

Controversy persists regarding the use of protamine during carotid endarterectomy (CEA) based on prior conflicting reports documenting both reduced bleeding as well as increased stroke risk. The purpose of this study was to determine the effect of protamine reversal of heparin anticoagulation on the outcome of CEA in a contemporary multistate registry. We reviewed a prospective regional registry of 4587 CEAs in 4311 patients performed by 66 surgeons from 11 centers in Northern New England from 2003-2008. Protamine use varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints were postoperative bleeding requiring reoperation as well as potential thrombotic complications, including stroke, death, and myocardial infarction (MI). Predictors of endpoints were determined by multivariate logistic regression after associated variables were identified by univariate analysis. Of the 4587 CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients (0.64%) in the protamine-treated group required reoperation for bleeding compared with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P = .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients, respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95% confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46, 95% CI, 0.26-0.81; P = .007) were independently associated with diminished reoperation for bleeding. A single center was associated with a significantly higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001). Independent of protamine use, consequences of reoperation for bleeding were significant, with a four-fold increase in MI, a seven-fold increase in stroke, and a 30-fold increase in death. Protamine reduced serious bleeding requiring reoperation during CEA without increasing the risk of MI, stroke, or death, in this large, contemporary registry. In light of significant complications referable to bleeding, liberal use of protamine during CEA appears warranted.

Efficacy and Safety of 3 Different Anesthesia Techniques Used in Total Hip Arthroplasty

PubMed Central

Liang, Chengwei; Wei, Jionglin; Cai, Xiaoxi; Lin, Weilong; Fan, Yongqian; Yang, Fengjian

2017-01-01

Background This study compared the efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty (THA). Material/Methods We allocated 198 patients preparing to undertake THA into 3 groups: general anesthesia group (GA group, n=66), caudal epidural anesthesia group (CEA group, n=66), and spinal-epidural anesthesia group (SEA group, n=66). We compared postoperative adverse effects occurring in patients of the 3 anesthesia groups. The Visual Analog Scale (VAS) score, Minimum Mental State Examination (MMSE) score, and β-amyloid (Aβ) expression were calculated to determine the effects of different anesthesia on the postoperative pain and cognitive dysfunction of patients. Results The CEA and SEA groups had lower rates of perioperative adverse effects than in the GA group. Patients in the GA group required significantly higher administration of analgesics after the surgery than those in CEA and SEA groups. Higher Aβ expression levels and VAS scores, as well as lower MMSE scores, were also seen in the GA group compared with the other 2 groups. Conclusions CEA and SEA were more effective than GA in THA, and CEA seemed to be a better anesthesia technique than SEA. PMID:28767640

[Economic evaluation on breast cancer screening in mainland China: a systematic review].

PubMed

Wang, L; Shi, J F; Huang, H Y; Zhu, J; Li, J; Fang, Y; Dai, M

2016-12-10

Objective: To gather available evidence related to the economic evaluation on breast cancer screening in mainland China and to provide reference for further research. Methods: A systematic review was conducted to identify articles in PubMed and three Chinese databases (CNKI, Wanfang and VIP) during 1995-2015. Data related to descriptive characteristics, rates on participation and detection for population-based studies, methods for model-based studies, types of economic evaluation and results, were extracted. A Consolidated Health Economic Evaluation Reporting Standards (CHEERS) was used to assess the reporting quality of included studies. Results: Of the 356 records searched in the databases, 13 studies (all published between 2012 and 2015) were included in the current paper involving 11 population-based studies and 3 model-based evaluations (1 study using both methods). Age of the participants who started to be engaged in the screening program ranged from 18 to 45 years old, but terminated at the age of 59 years or older. The screening modalities included single-used clinical breast examination, mammography and ultrasound or combined applications. Study persepectives were described in 7 studies, with 5 from the healthcare providers, and 2 from societal angles. Only 5 studies discounted cost or effectiveness. Out of 11 papers, 9 showed the results on cost-effectiveness analysis (CEA) that reporting the cost per breast cancer detection, with median as 145.0 thousand Chinese Yuan (CNY), ranging from 49.7 thousand to 2 293.0 thousand CNY. From 4 papers with results of cost-utility analysis (CUA), the cost per quality adjusted life year (QALY) gained or cost per disability adjusted life year (DALY) averted, were evaluated. The incremental cost-effectiveness ratio (ICER) was from 2.9 thousand to 270.7 thousand CNY (GDP per capita of China was CNY 49.3 thousand in 2015). In 13 studies, the quality of reporting varied, with an average score of 14.5 (range: 9.5-21.0). In the domains of study perspective, discounting, ICER and uncertainty, all the scores of equalities were relatively levels. Conclusions: Currently, evidence on economic evaluation of breast cancer screening in mainland China remained limited and weakly comparable, particularly model-based studies. Comprehensive analysis from societal perspective and QALY or DALY related cost-utility analysis should be implemented.

Nanoporous Glass Integrated in Volumetric Bar-Chart Chip for Point-of-Care Diagnostics of Non-Small Cell Lung Cancer.

PubMed

Li, Ying; Xuan, Jie; Song, Yujun; Qi, Wenjin; He, Bangshun; Wang, Ping; Qin, Lidong

2016-01-26

Point-of-care (POC) testing has the potential to enable rapid, low-cost, and large-scale screening. POC detection of a multiplexed biomarker panel can facilitate the early diagnosis of non-small cell lung cancer (NSCLC) and, thus, may allow for more timely surgical intervention for life-saving treatment. Herein, we report the nanoporous glass (NPG) integrated volumetric bar-chart chip (V-Chip) for POC detection of the three NSCLC biomarkers CEA, CYFRA 21-1, and SCCA, by the naked eye. The 3D nanostructures in the NPG membrane efficiently increase the number of binding sites for antibodies and decrease the diffusion distance between antibody and antigen, enabling the low detection limit and rapid analysis time of the NPG-V-Chip. We utilized the NPG-V-Chip to test the NSCLC biomarker panel and found that the limit of detection can reach 50 pg/mL (10-fold improvement over the original V-Chip), and the total assay time can be decreased from 4 to 0.5 h. We then detected CEA in 21 serum samples from patients with common cancers, and the on-chip results showed good correlation with the clinical results. We further assayed 10 lung cancer samples using the device and confirmed the results obtained using conventional ELISA methods. In summary, the NPG-V-Chip platform has the ability of multiplex, low detection limit, low cost, lack of need for accessory equipment, and rapid analysis time, which may render the V-Chip a useful platform for quantitative POC detection in resource-limited settings and personalized diagnostics.

Risk factor analysis of new brain lesions associated with carotid endarterectmy.

PubMed

Lee, Jae Hoon; Suh, Bo Yang

2014-01-01

Carotid endarterectomy (CEA) is the standard treatment for carotid artery stenosis. New brain ischemia is a major concern associated with CEA and diffusion weighted imaging (DWI) is a good imaging modality for detecting early ischemic brain lesions. We aimed to investigate the surgical complications and identify the potential risk factors for the incidence of new brain lesions (NBL) on DWI after CEA. From January 2006 to November 2011, 94 patients who had been studied by magnetic resonance imaging including DWI within 1 week after CEA were included in this study. Data were retrospectively investigated by review of vascular registry protocol. Seven clinical variables and three procedural variables were analyzed as risk factors for NBL after CEA. The incidence of periprocedural NBL on DWI was 27.7%. There were no fatal complications, such as ipsilateral disabling stroke, myocardial infarction or mortality. A significantly higher incidence of NBL was found in ulcer positive patients as opposed to ulcer negative patients (P = 0.029). The incidence of NBL after operation was significantly higher in patients treated with conventional technique than with eversion technique (P = 0.042). Our data shows CEA has acceptable periprocedural complication rates and the existence of ulcerative plaque and conventional technique of endarterectomy are high risk factors for NBL development after CEA.

Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal

PubMed Central

Wang, Li; Shen, Minjie; Jiang, Changyou

2016-01-01

Background: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood. Method: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal–induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+ interneurons in the CeA. Result: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity of CeA PV+ interneurons attenuated the morphine withdrawal–induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA. Conclusion: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA. PMID:27385383

Enhancing the sensitivity of mid-IR quantum cascade laser-based cavity-enhanced absorption spectroscopy using RF current perturbation.

PubMed

Manfred, Katherine M; Kirkbride, James M R; Ciaffoni, Luca; Peverall, Robert; Ritchie, Grant A D

2014-12-15

The sensitivity of mid-IR quantum cascade laser (QCL) off-axis cavity-enhanced absorption spectroscopy (CEAS), often limited by cavity mode structure and diffraction losses, was enhanced by applying a broadband RF noise to the laser current. A pump-probe measurement demonstrated that the addition of bandwidth-limited white noise effectively increased the laser linewidth, thereby reducing mode structure associated with CEAS. The broadband noise source offers a more sensitive, more robust alternative to applying single-frequency noise to the laser. Analysis of CEAS measurements of a CO(2) absorption feature at 1890  cm(-1) averaged over 100 ms yielded a minimum detectable absorption of 5.5×10(-3)  Hz(-1/2) in the presence of broadband RF perturbation, nearly a tenfold improvement over the unperturbed regime. The short acquisition time makes this technique suitable for breath applications requiring breath-by-breath gas concentration information.

Estimating the cost of cervical cancer screening in five developing countries

PubMed Central

Goldhaber-Fiebert, Jeremy D; Goldie, Sue J

2006-01-01

Background Cost-effectiveness analyses (CEAs) can provide useful information to policymakers concerned with the broad allocation of resources as well as to local decision makers choosing between different options for reducing the burden from a single disease. For the latter, it is important to use country-specific data when possible and to represent cost differences between countries that might make one strategy more or less attractive than another strategy locally. As part of a CEA of cervical cancer screening in five developing countries, we supplemented limited primary cost data by developing other estimation techniques for direct medical and non-medical costs associated with alternative screening approaches using one of three initial screening tests: simple visual screening, HPV DNA testing, and cervical cytology. Here, we report estimation methods and results for three cost areas in which data were lacking. Methods To supplement direct medical costs, including staff, supplies, and equipment depreciation using country-specific data, we used alternative techniques to quantify cervical cytology and HPV DNA laboratory sample processing costs. We used a detailed quantity and price approach whose face validity was compared to an adaptation of a US laboratory estimation methodology. This methodology was also used to project annual sample processing capacities for each laboratory type. The cost of sample transport from the clinic to the laboratory was estimated using spatial models. A plausible range of the cost of patient time spent seeking and receiving screening was estimated using only formal sector employment and wages as well as using both formal and informal sector participation and country-specific minimum wages. Data sources included primary data from country-specific studies, international databases, international prices, and expert opinion. Costs were standardized to year 2000 international dollars using inflation adjustment and purchasing power parity. Results Cervical cytology laboratory processing costs were I$1.57–3.37 using the quantity and price method compared to I$1.58–3.02 from the face validation method. HPV DNA processing costs were I$6.07–6.59. Rural laboratory transport costs for cytology were I$0.12–0.64 and I$0.14–0.74 for HPV DNA laboratories. Under assumptions of lower resource efficiency, these estimates increased to I$0.42–0.83 and I$0.54–1.06. Estimates of the value of an hour of patient time using only formal sector participation were I$0.07–4.16, increasing to I$0.30–4.80 when informal and unpaid labor was also included. The value of patient time for traveling, waiting, and attending a screening visit was I$0.68–17.74. With the total cost of screening for cytology and HPV DNA testing ranging from I$4.85–40.54 and I$11.30–48.77 respectively, the cost of the laboratory transport, processing, and patient time accounted for 26–66% and 33–65% of the total costs. From a payer perspective, laboratory transport and processing accounted for 18–48% and 25–60% of total direct medical costs of I$4.11–19.96 and I$10.57–28.18 respectively. Conclusion Cost estimates of laboratory processing, sample transport, and patient time account for a significant proportion of total cervical cancer screening costs in five developing countries and provide important inputs for CEAs of alternative screening modalities. PMID:16887041

Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report.

PubMed

Ramsey, Scott D; Willke, Richard J; Glick, Henry; Reed, Shelby D; Augustovski, Federico; Jonsson, Bengt; Briggs, Andrew; Sullivan, Sean D

2015-03-01

Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Genomic Islands in Pathogenic Filamentous Fungus Aspergillus fumigatus

USDA-ARS?s Scientific Manuscript database

We present the genome sequences of a new clinical isolate, CEA10, of an important human pathogen, Aspergillus fumigatus, and two closely related, but rarely pathogenic species, Neosartorya fischeri NRRL181 and Aspergillus clavatus NRRL1. Comparative genomic analysis of CEA10 with the recently sequen...

Nociceptin/orphanin FQ decreases glutamate transmission and blocks ethanol-induced effects in the central amygdala of naive and ethanol-dependent rats.

PubMed

Kallupi, Marsida; Varodayan, Florence P; Oleata, Christopher S; Correia, Diego; Luu, George; Roberto, Marisa

2014-04-01

The central nucleus of the amygdala (CeA) mediates several addiction-related processes and nociceptin/orphanin FQ (nociceptin) regulates ethanol intake and anxiety-like behaviors. Glutamatergic synapses, in the CeA and throughout the brain, are very sensitive to ethanol and contribute to alcohol reinforcement, tolerance, and dependence. Previously, we reported that in the rat CeA, acute and chronic ethanol exposures significantly decrease glutamate transmission by both pre- and postsynaptic actions. In this study, using electrophysiological techniques in an in vitro CeA slice preparation, we investigated the effects of nociceptin on glutamatergic transmission and its interaction with acute ethanol in naive and ethanol-dependent rats. We found that nociceptin (100-1000 nM) diminished basal-evoked compound glutamatergic receptor-mediated excitatory postsynaptic potentials (EPSPs) and spontaneous and miniature EPSCs (s/mEPSCs) by mainly decreasing glutamate release in the CeA of naive rats. Notably, nociceptin blocked the inhibition induced by acute ethanol (44 mM) and ethanol blocked the nociceptin-induced inhibition of evoked EPSPs in CeA neurons of naive rats. In neurons from chronic ethanol-treated (ethanol-dependent) rats, the nociceptin-induced inhibition of evoked EPSP amplitude was not significantly different from that in naive rats. Application of [Nphe1]Nociceptin(1-13)NH2, a nociceptin receptor (NOP) antagonist, revealed tonic inhibitory activity of NOP on evoked CeA glutamatergic transmission only in ethanol-dependent rats. The antagonist also blocked nociceptin-induced decreases in glutamatergic responses, but did not affect ethanol-induced decreases in evoked EPSP amplitude. Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses.

The impact of childhood emotional abuse and experiential avoidance on maladaptive problem solving and intimate partner violence.

PubMed

Bell, Kathryn M; Higgins, Lorrin

2015-04-16

The purpose of the current study was to examine the joint influences of experiential avoidance and social problem solving on the link between childhood emotional abuse (CEA) and intimate partner violence (IPV). Experiential avoidance following CEA may interfere with a person's ability to effectively problem solve in social situations, increasing risk for conflict and interpersonal violence. As part of a larger study, 232 women recruited from the community completed measures assessing childhood emotional, physical, and sexual abuse, experiential avoidance, maladaptive social problem solving, and IPV perpetration and victimization. Final trimmed models indicated that CEA was indirectly associated with IPV victimization and perpetration via experiential avoidance and Negative Problem Orientation (NPO) and Impulsivity/Carelessness Style (ICS) social problem solving strategies. Though CEA was related to an Avoidance Style (AS) social problem solving strategy, this strategy was not significantly associated with IPV victimization or perpetration. Experiential avoidance had both a direct and indirect effect, via NPO and ICS social problem solving, on IPV victimization and perpetration. Findings suggest that CEA may lead some women to avoid unwanted internal experiences, which may adversely impact their ability to effectively problem solve in social situations and increase IPV risk.

The Impact of Childhood Emotional Abuse and Experiential Avoidance on Maladaptive Problem Solving and Intimate Partner Violence

PubMed Central

Bell, Kathryn M.; Higgins, Lorrin

2015-01-01

The purpose of the current study was to examine the joint influences of experiential avoidance and social problem solving on the link between childhood emotional abuse (CEA) and intimate partner violence (IPV). Experiential avoidance following CEA may interfere with a person’s ability to effectively problem solve in social situations, increasing risk for conflict and interpersonal violence. As part of a larger study, 232 women recruited from the community completed measures assessing childhood emotional, physical, and sexual abuse, experiential avoidance, maladaptive social problem solving, and IPV perpetration and victimization. Final trimmed models indicated that CEA was indirectly associated with IPV victimization and perpetration via experiential avoidance and Negative Problem Orientation (NPO) and Impulsivity/Carelessness Style (ICS) social problem solving strategies. Though CEA was related to an Avoidance Style (AS) social problem solving strategy, this strategy was not significantly associated with IPV victimization or perpetration. Experiential avoidance had both a direct and indirect effect, via NPO and ICS social problem solving, on IPV victimization and perpetration. Findings suggest that CEA may lead some women to avoid unwanted internal experiences, which may adversely impact their ability to effectively problem solve in social situations and increase IPV risk. PMID:25893570

Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors.

PubMed

Zhu, Kuiyu; Zhang, Ye; Li, Zengyao; Zhou, Fan; Feng, Kang; Dou, Huiqiang; Wang, Tong

2015-08-05

Primary hepatic carcinoma (PHC) is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs) with polydimethylsiloxane (PDMS) microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.

Surface-enhanced Raman scattering study of carcinoembryonic antigen in serum from patients with colorectal cancers

NASA Astrophysics Data System (ADS)

Chen, Gang; Chen, Yanping; Zheng, Xiongwei; He, Cheng; Lu, Jianping; Feng, Shangyuan; Chen, Rong; Zeng, Haisan

2013-12-01

In this work, we developed a SERS platform for quantitative detection of carcinoembryonic antigen (CEA) in serum of patients with colorectal cancers. Anti-CEA-functionalized 4-mercaptobenzoic acid-labeled Au/Ag core-shell bimetallic nanoparticles were prepared first and then used to analyze CEA antigen solutions of different concentrations. A calibration curve was established in the range from 5 × 10-3 to 5 × 105 ng/mL. Finally, this new SERS probe was applied for quantitative detection of CEA in serum obtained from 26 colorectal cancer patients according to the calibration curve. The results were in good agreement with that obtained by electrochemical luminescence method, suggesting that SERS immunoassay has high sensitivity and specificity for CEA detection in serum. A detection limit of 5 pg/ml was achieved. This study demonstrated the feasibility and great potential for developing this new technology into a clinical tool for analysis of tumor markers in the blood.

Safety of carotid endarterectomy while on clopidogrel (Plavix). Clinical article.

PubMed

Wait, Scott D; Abla, Adib A; Killory, Brendan D; Starke, Robert M; Spetzler, Robert F; Nakaji, Peter

2010-10-01

Many patients undergoing carotid endarterectomy (CEA) regularly take clopidogrel, a permanent platelet inhibitor. The authors sought to determine whether taking clopidogrel in the period before CEA leads to more bleeding or other complications. The authors performed a retrospective, institutional review board–approved review of 182 consecutive patients who underwent CEA. Clinical, radiographic, and surgical data were gleaned from hospital and clinic records. Analysis was based on the presence or absence of clopidogrel in patients undergoing CEA and was performed twice by considering clopidogrel use within 8 days and within 5 days of surgery to define the groups. Taking clopidogrel within 8 days before surgery resulted in no statistical increase in any measure of morbidity or death. Taking clopidogrel within 5 days was associated with a small but significant increase in operative blood loss and conservatively managed postoperative neck swelling. No measure of permanent morbidity or death was increased in either clopidogrel group. Findings in this study support the safety of preoperative clopidogrel in patients undergoing CEA.

The zebrafish maternal-effect gene cellular atoll encodes the centriolar component sas-6 and defects in its paternal function promote whole genome duplication.

PubMed

Yabe, Taijiro; Ge, Xiaoyan; Pelegri, Francisco

2007-12-01

A female-sterile zebrafish maternal-effect mutation in cellular atoll (cea) results in defects in the initiation of cell division starting at the second cell division cycle. This phenomenon is caused by defects in centrosome duplication, which in turn affect the formation of a bipolar spindle. We show that cea encodes the centriolar coiled-coil protein Sas-6, and that zebrafish Cea/Sas-6 protein localizes to centrosomes. cea also has a genetic paternal contribution, which when mutated results in an arrested first cell division followed by normal cleavage. Our data supports the idea that, in zebrafish, paternally inherited centrosomes are required for the first cell division while maternally derived factors are required for centrosomal duplication and cell divisions in subsequent cell cycles. DNA synthesis ensues in the absence of centrosome duplication, and the one-cycle delay in the first cell division caused by cea mutant sperm leads to whole genome duplication. We discuss the potential implications of these findings with regards to the origin of polyploidization in animal species. In addition, the uncoupling of developmental time and cell division count caused by the cea mutation suggests the presence of a time window, normally corresponding to the first two cell cycles, which is permissive for germ plasm recruitment.

Economic modelling of diagnostic and treatment pathways in National Institute for Health and Care Excellence clinical guidelines: the Modelling Algorithm Pathways in Guidelines (MAPGuide) project.

PubMed

Lord, J; Willis, S; Eatock, J; Tappenden, P; Trapero-Bertran, M; Miners, A; Crossan, C; Westby, M; Anagnostou, A; Taylor, S; Mavranezouli, I; Wonderling, D; Alderson, P; Ruiz, F

2013-12-01

National Institute for Health and Care Excellence (NICE) clinical guidelines (CGs) make recommendations across large, complex care pathways for broad groups of patients. They rely on cost-effectiveness evidence from the literature and from new analyses for selected high-priority topics. An alternative approach would be to build a model of the full care pathway and to use this as a platform to evaluate the cost-effectiveness of multiple topics across the guideline recommendations. In this project we aimed to test the feasibility of building full guideline models for NICE guidelines and to assess if, and how, such models can be used as a basis for cost-effectiveness analysis (CEA). A 'best evidence' approach was used to inform the model parameters. Data were drawn from the guideline documentation, advice from clinical experts and rapid literature reviews on selected topics. Where possible we relied on good-quality, recent UK systematic reviews and meta-analyses. Two published NICE guidelines were used as case studies: prostate cancer and atrial fibrillation (AF). Discrete event simulation (DES) was used to model the recommended care pathways and to estimate consequent costs and outcomes. For each guideline, researchers not involved in model development collated a shortlist of topics suggested for updating. The modelling teams then attempted to evaluate options related to these topics. Cost-effectiveness results were compared with opinions about the importance of the topics elicited in a survey of stakeholders. The modelling teams developed simulations of the guideline pathways and disease processes. Development took longer and required more analytical time than anticipated. Estimates of cost-effectiveness were produced for six of the nine prostate cancer topics considered, and for five of eight AF topics. The other topics were not evaluated owing to lack of data or time constraints. The modelled results suggested 'economic priorities' for an update that differed from priorities expressed in the stakeholder survey. We did not conduct systematic reviews to inform the model parameters, and so the results might not reflect all current evidence. Data limitations and time constraints restricted the number of analyses that we could conduct. We were also unable to obtain feedback from guideline stakeholders about the usefulness of the models within project time scales. Discrete event simulation can be used to model full guideline pathways for CEA, although this requires a substantial investment of clinical and analytic time and expertise. For some topics lack of data may limit the potential for modelling. There are also uncertainties over the accessibility and adaptability of full guideline models. However, full guideline modelling offers the potential to strengthen and extend the analytical basis of NICE's CGs. Further work is needed to extend the analysis of our case study models to estimate population-level budget and health impacts. The practical usefulness of our models to guideline developers and users should also be investigated, as should the feasibility and usefulness of whole guideline modelling alongside development of a new CG. This project was funded by the Medical Research Council and the National Institute for Health Research through the Methodology Research Programme [grant number G0901504] and will be published in full in Health Technology Assessment; Vol. 17, No. 58. See the NIHR Journals Library website for further project information.

Comparative Study of Carcinoembryonic Antigen Tumor Marker in Stomach and Colon Cancer Patients in Khyber Pakhtunkhwa.

PubMed

Ahmad, Bashir; Gul, Bushra; Ali, Sajid; Bashir, Shumaila; Mahmood, Nourin; Ahmad, Jamshed; Nawaz, Seema

2015-01-01

Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis would be helpful to prevent/stop cancer from progressing to severe stage. In Khyber Pakhtunkhwa, Pakistan, most of the time, tumors are diagnosed with endoscopy and biopsy; therefore rare studies exist regarding the diagnosis of gastrointestinal (GIT) carcinomas based on tumor markers, especially CEA. This study made a comparative analysis of CEA in admitted hospitalized stomach and colon cancer patients diagnosed as GIT with biopsy. In this study, a total of 66 cases were included. The level of CEA was determined in the blood of these patients using ELISA technique. Out of 66 patients, the level of CEA was high in 59.1% of the total, 60.7% in colon cancer patients and 57.9 % in stomach cancer patients. Moreover, the incidence of colorectal and stomach cancer was greater in males as compared to females. Patients were more of the age group of 40- 60 and the level of CEA was comparatively higher in patients (51.5%) with histology which was moderately differentiated, than patients with well differentiated and poorly differentiated tumor histology. CEA level was high in more than 50% of the total patients. Moreover, CEA exhibited higher sensitivity for colon than stomach cancer.

Collecting and analysing cost data for complex public health trials: reflections on practice

PubMed Central

Batura, Neha; Pulkki-Brännström, Anni-Maria; Agrawal, Priya; Bagra, Archana; Haghparast-Bidgoli, Hassan; Bozzani, Fiammetta; Colbourn, Tim; Greco, Giulia; Hossain, Tanvir; Sinha, Rajesh; Thapa, Bidur; Skordis-Worrall, Jolene

2014-01-01

Background Current guidelines for the conduct of cost-effectiveness analysis (CEA) are mainly applicable to facility-based interventions in high-income settings. Differences in the unit of analysis and the high cost of data collection can make these guidelines challenging to follow within public health trials in low- and middle- income settings. Objective This paper reflects on the challenges experienced within our own work and proposes solutions that may be useful to others attempting to collect, analyse, and compare cost data between public health research sites in low- and middle-income countries. Design We describe the generally accepted methods (norms) for collecting and analysing cost data in a single-site trial from the provider perspective. We then describe our own experience applying these methods within eight comparable cluster randomised, controlled, trials. We describe the strategies used to maximise adherence to the norm, highlight ways in which we deviated from the norm, and reflect on the learning and limitations that resulted. Results When the expenses incurred by a number of small research sites are used to estimate the cost-effectiveness of delivering an intervention on a national scale, then deciding which expenses constitute ‘start-up’ costs will be a nontrivial decision that may differ among sites. Similarly, the decision to include or exclude research or monitoring and evaluation costs can have a significant impact on the findings. We separated out research costs and argued that monitoring and evaluation costs should be reported as part of the total trial cost. The human resource constraints that we experienced are also likely to be common to other trials. As we did not have an economist in each site, we collaborated with key personnel at each site who were trained to use a standardised cost collection tool. This approach both accommodated our resource constraints and served as a knowledge sharing and capacity building process within the research teams. Conclusions Given the practical reality of conducting randomised, controlled trials of public health interventions in low- and middle- income countries, it is not always possible to adhere to prescribed guidelines for the analysis of cost effectiveness. Compromises are frequently required as researchers seek a pragmatic balance between rigor and feasibility. There is no single solution to this tension but researchers are encouraged to be mindful of the limitations that accompany compromise, whilst being reassured that meaningful analyses can still be conducted with the resulting data. PMID:24565214

Diagnostic value of soluble B7-H4 and carcinoembryonic antigen in distinguishing malignant from benign pleural effusion.

PubMed

Jing, Xiaogang; Wei, Fei; Li, Jing; Dai, Lingling; Wang, Xi; Jia, Liuqun; Wang, Huan; An, Lin; Yang, Yuanjian; Zhang, Guojun; Cheng, Zhe

2018-03-01

To explore the diagnostic value of joint detection of soluble B7-H4 (sB7-H4) and carcinoembryonic antigen (CEA) in identifying malignant pleural effusion (MPE) from benign pleural effusion (BPE). A total of 97 patients with pleural effusion specimens were enrolled from The First Affiliated Hospital of Zhengzhou University between June 2014 and December 2015. All cases were categorized into malignant pleural effusion group (n = 55) and benign pleural effusion group (n = 42) according to etiologies. Enzyme-linked immunosorbent assay was applied to examine the levels of sB7-H4 in pleural effusion and meanwhile CEA concentrations were detected by electro-chemiluminescence immunoassays. Receiver operating characteristic (ROC) curve was established to assess the diagnostic value of sB7-H4 and CEA in pleural effusion. The correlation between sB7-H4 and CEA levels was analyzed by Pearson's product-moment. The concentrations of sB7-H4 and CEA in MPE exhibited obviously higher than those of BPE ([60.08 ± 35.04] vs. [27.26 ± 9.55] ng/ml, P = .000; [41.49 ± 37.16] vs. [2.41 ± 0.94] ng/ml, P = .000). The AUC area under ROC curve of sB7-H4 and CEA was 0.884 and 0.954, respectively. Two cutoff values by ROC curve analysis of sB7-H4 36.5 ng/ml and CEA 4.18 ng/ml were obtained, with a corresponding sensitivity (81.82%, 87.28%), specificity (90.48%, 95.24%), accuracy (85.57%, 90.72%), positive predictive value (PPV) (91.84%, 96.0%), negative predictive value (NPV) (79.17%, 85.11%), positive likelihood ratio (PLR) (8.614, 18.327), and negative likelihood ratio (NLR) (0.201, 0.134). When sB7-H4 and CEA were combined to detect pleural effusion, it obtained a higher sensitivity 90.91% and specificity 97.62%. Furthermore, correlation analysis result showed that the level of sB7-H4 was correlated with CEA level (r = .770, P = .000). sB7-H4 was a potentially valuable tumor marker in the differentiation between BPE and MPE. The combined detection of sB7-H4 and CEA could improve the diagnostic sensitivity and specificity for MPE. © 2017 John Wiley & Sons Ltd.

Short-Term Results of Carotid Endarterectomy and Stenting After the Introduction of Carotid Magnetic Resonance Imaging: A Single-Institution Retrospective Study.

PubMed

Fukumitsu, Ryu; Yoshida, Kazumichi; Kurosaki, Yoshitaka; Torihashi, Koichi; Sadamasa, Nobutake; Koyanagi, Masaomi; Narumi, Osamu; Sato, Tsukasa; Chin, Masaki; Handa, Akira; Yamagata, Sen; Miyamoto, Susumu

2017-05-01

Although carotid artery stenting (CAS) has been gaining popularity as an alternative to carotid endarterectomy (CEA), perioperative stroke rate following contemporary CAS remains significantly higher than stroke rate after CEA. The purpose of this study was to assess perioperative (within 30 days) therapeutic results in patients with carotid stenosis (CS) after introduction of preoperative carotid magnetic resonance imaging plaque evaluation in a single center performing both CEA and CAS. Based on prospectively collected data for patients with CS who were scheduled for carotid revascularization, retrospective analysis was conducted of 295 consecutive patients with CS. An intervention was selected after consideration of periprocedural risks for both CEA and CAS. Concerning risk factors for CAS, results of magnetic resonance imaging plaque evaluation were emphasized with a view toward reducing embolic complications. CAS was performed in 114 patients, and CEA was performed in 181 patients. Comparing baseline characteristics of the 295 patients, age, T1 signal intensity of plaque, symptomatic CS, urgent intervention, and diabetes mellitus differed significantly between CAS and CEA groups. Among patients who underwent CAS, new hyperintense lesions on diffusion-weighted imaging were confirmed in 47 patients. New hyperintense lesions on diffusion-weighted imaging were recognized in 21.4% of patients who underwent CEA (n = 39), significantly less frequent than in patients who underwent CAS. The overall short-term outcome of CEA and CAS is acceptable. Preoperative carotid magnetic resonance imaging evaluation of plaque might contribute to low rates of ischemic complications in CAS. Copyright © 2017 Elsevier Inc. All rights reserved.

Value of combining serum carcinoembryonic antigen and PET/CT in predicting EGFR mutation in non-small cell lung cancer.

PubMed

Gu, Jincui; Xu, Siqi; Huang, Lixia; Li, Shaoli; Wu, Jian; Xu, Junwen; Feng, Jinlun; Liu, Baomo; Zhou, Yanbin

2018-02-01

We sought to investigate the associations between pretreatment serum Carcinoembryonic antigen (CEA) level, 18 F-Fluoro-2-deoxyglucose ( 18 F-FDG) uptake value of primary tumor and epidermal growth factor receptor ( EGFR ) mutation status in non-small cell lung cancer (NSCLC). We retrospectively reviewed medical records of 210 NSCLC patients who underwent EGFR mutation test and 18 F-FDG positron emission tomography/computed tomography (PET/CT) scan before anti-tumor therapy. The associations between EGFR mutations and patients' characteristics, serum CEA, PET/CT imaging characteristics maximal standard uptake value (SUVmax) of the primary tumor were analyzed. Receiver-operating characteristic (ROC) curve was used to assess the predictive value of these factors. EGFR mutations were found in 70 patients (33.3%). EGFR mutations were more common in high CEA group (CEA ≥7.0 ng/mL) than in low CEA group (CEA <7.0 ng/mL) (40.4% vs . 27.6%; P=0.05). Females (P<0.001), non-smokers (P<0.001), patients with adenocarcinoma (P<0.001) and SUVmax <9.0 (P=0.001) were more likely to be EGFR mutation-positive. Multivariate analysis revealed that gender, tumor histology, pretreatment serum CEA level, and SUVmax were the most significant predictors for EGFR mutations. The ROC curve revealed that combining these four factors yielded a higher calculated AUC (0.80). Gender, histology, pretreatment serum CEA level and SUVmax are significant predictors for EGFR mutations in NSCLC. Combining these factors in predicting EGFR mutations has a moderate diagnostic accuracy, and is helpful in guiding anti-tumor treatment.

Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons

PubMed Central

Roberto, Marisa; Madamba, Samuel G.; Moore, Scott D.; Tallent, Melanie K.; Siggins, George R.

2003-01-01

We examined the interaction of ethanol with the γ-aminobutyric acid (GABA)ergic system in neurons of slices of the rat central amygdala nucleus (CeA), a brain region thought to be critical for the reinforcing effects of ethanol. Brief superfusion of 11–66 mM ethanol significantly increased GABA type A (GABAA) receptor-mediated inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in most CeA neurons, with a low apparent EC50 of 20 mM. Acute superfusion of 44 mM ethanol increased the amplitude of evoked GABAA IPSPs and IPSCs in 70% of CeA neurons. The ethanol enhancement of IPSPs and IPSCs occurred to a similar extent in the presence of the GABA type B (GABAB) receptor antagonist CGP 55845A, suggesting that this receptor is not involved in the ethanol effect on CeA neurons. Ethanol superfusion also decreased paired-pulse facilitation of evoked GABAA IPSPs and IPSCs and always increased the frequency and sometimes the amplitude of spontaneous miniature GABAA IPSCs as well as responses to local GABA application, indicating both presynaptic and postsynaptic sites of action for ethanol. Thus, the CeA is the first brain region to reveal, without conditional treatments such as GABAB antagonists, consistent, low-dose ethanol enhancement of GABAergic transmission at both pre- and postsynaptic sites. These findings add further support to the contention that the ethanol–GABA interaction in CeA plays an important role in the reinforcing effects of ethanol. PMID:12566570

Pituitary Adenylate Cyclase-Activating Peptide in the Central Amygdala Causes Anorexia and Body Weight Loss via the Melanocortin and the TrkB Systems.

PubMed

Iemolo, Attilio; Ferragud, Antonio; Cottone, Pietro; Sabino, Valentina

2015-07-01

Growing evidence suggests that the pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor system represents one of the main regulators of the behavioral, endocrine, and autonomic responses to stress. Although induction of anorexia is a well-documented effect of PACAP, the central sites underlying this phenomenon are poorly understood. The present studies addressed this question by examining the neuroanatomical, behavioral, and pharmacological mechanisms mediating the anorexia produced by PACAP in the central nucleus of the amygdala (CeA), a limbic structure implicated in the emotional components of ingestive behavior. Male rats were microinfused with PACAP (0-1 μg per rat) into the CeA and home-cage food intake, body weight change, microstructural analysis of food intake, and locomotor activity were assessed. Intra-CeA (but not intra-basolateral amygdala) PACAP dose-dependently induced anorexia and body weight loss without affecting locomotor activity. PACAP-treated rats ate smaller meals of normal duration, revealing that PACAP slowed feeding within meals by decreasing the regularity and maintenance of feeding from pellet-to-pellet; postprandial satiety was unaffected. Intra-CeA PACAP-induced anorexia was blocked by coinfusion of either the melanocortin receptor 3/4 antagonist SHU 9119 or the tyrosine kinase B (TrKB) inhibitor k-252a, but not the CRF receptor antagonist D-Phe-CRF(12-41). These results indicate that the CeA is one of the brain areas through which the PACAP system promotes anorexia and that PACAP preferentially lessens the maintenance of feeding in rats, effects opposite to those of palatable food. We also demonstrate that PACAP in the CeA exerts its anorectic effects via local melanocortin and the TrKB systems, and independently from CRF.

Dexamethasone minimizes the risk of cranial nerve injury during CEA.

PubMed

Regina, Guido; Angiletta, Domenico; Impedovo, Giovanni; De Robertis, Giovanni; Fiorella, Marialuisa; Carratu', Maria Rosaria

2009-01-01

The incidence of cranial and cervical nerve injury during carotid endarterectomy (CEA) ranges from less than 7.6% to more than 50%. Lesions are mainly due to surgical maneuvers such as traction, compression, tissue electrocoagulation, clamping, and extensive dissections. The use of dexamethasone (DEX) and its beneficial effects in spinal cord injuries have already been described. We investigated whether DEX could also be beneficial to minimize the incidence of cranial and cervical nerve injury during CEA. To evaluate whether dexamethasone is able to reduce the incidence of cranial nerve injuries. From March 1999 through April 2006, 1126 patients undergoing CEA because of high-grade carotid stenosis were enrolled and randomized by predetermined randomization tables into two groups. The first group, "A", included 586 patients that all received an intravenous administration of dexamethasone following a therapeutic scheme. The second group, "B", included 540 control subjects that received the standard pre- and postoperative therapy. All patients were submitted to a deep cervical plexus block, eversion carotid endarterectomy, and selective shunting. Three days after the operation, an independent neurologist and otorhinolaryngologist evaluated the presence of cranial nerve deficits. All patients (group A and group B) showing nerve injuries continued the treatment (8 mg of dexamethasone once in the morning) for 7 days and were re-evaluated after 2 weeks, 30 days, and every 3 months for 1 year. Recovery time took from 2 weeks to 12 months, with a mean time of 3.6 months. The chi(2) test was used to compare the two groups and to check for statistical significance. The incidence of cranial nerve dysfunction was higher in group B and the statistical analysis showed a significant effect of dexamethasone in preventing the neurological damage (P = .0081). The incidence of temporary lesions was lower in group A and the chi(2) test yielded a P value of .006. No statistically significant differences were found when comparing the effect of dexamethasone in men and women. In addition, dexamethasone had no statistically significant effect on the incidence of permanent cranial nerve injuries. Finally, no adverse effect related to the administration of dexamethasone was observed. Perioperative administration of dexamethasone is effective in minimizing the incidence of temporary cranial nerve injuries during CEA.

French Atomic Energy Commission Decommissioning Programme and Feedback Experience - 12230

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guiberteau, Ph.; Nokhamzon, J.G.

Since the French Atomic and Alternatives Energy Commission (CEA) was founded in 1945 to carry out research programmes on use of nuclear, and its application France has set up and run various types of installations: research or prototypes reactors, process study or examination laboratories, pilot installations, accelerators, nuclear power plants and processing facilities. Some of these are currently being dismantled or must be dismantled soon so that the DEN, the Nuclear Energy Division, can construct new equipment and thus have available a range of R and D facilities in line with the issues of the nuclear industry of the future.more » Since the 1960's and 1970's in all its centres, the CEA has acquired experience and know-how through dismantling various nuclear facilities. The dismantling techniques are nowadays operational, even if sometimes certain specific developments are necessary to reduce the cost of operations. Thanks to availability of techniques and guarantees of dismantling programme financing now from two dedicated funds, close to euro 15,000 M for the next thirty years, for current or projected dismantling operations, the CEA's Nuclear Energy Division has been able to develop, when necessary, its immediate dismantling strategy. Currently, nearly thirty facilities are being dismantled by the CEA's Nuclear Energy Division operational units with industrial partners. Thus the next decade will see completion of the dismantling and radioactive clean-up of the Grenoble site and of the facilities on the Fontenay-aux-Roses site. By 2016, the dismantling of the UP1 plant at Marcoule, the largest dismantling work in France, will be well advanced, with all the process equipment dismantled. After an overview of the French regulatory framework, the paper will describe the DD and R (Decontamination Decommissioning and Remediation) strategy, programme and feedback experience inside the CEA's Nuclear Energy Division. A special feature of dismantling operations at the CEA comes from the diversity of facilities to be dismantled, which are predominantly research facilities and therefore have no series advantage. There is tremendous operating feedback, however. For more than twenty years in all its centres, the CEA has acquired experience and know-how through dismantling research reactors or critical models and laboratories or plants. The dismantling techniques are nowadays operational, even if sometimes certain specific developments are necessary to reduce the cost of operations. Thanks to availability of techniques and guarantees of dismantling programme financing from two dedicated funds, close to euro 15,000 Millions for the next thirty years, for current or projected dismantling operations, the Nuclear Energy Division has been able to develop, when necessary, its immediate dismantling strategy. Currently, nearly thirty facilities are being dismantled by the CEA's Nuclear Energy Division operational units with industrial partners. Thus the next decade will see completion of the dismantling and radioactive clean-up of the Grenoble site and of the facilities on the Fontenay-aux-Roses site. By 2020, the dismantling of the UP1 plant at Marcoule, one of the largest dismantling works in the world, will be well advanced, with all the process equipment dismantled. (authors)« less

Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

PubMed

Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

2014-04-01

The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

The CEA-/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells.

PubMed

Yan, Chang; Hu, Yibing; Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

2016-12-06

Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA-/lo) levels of CEA. Our findings show that the abundance of CEA-/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA-/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA-/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA-/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA-/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA-/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies.

Mass transport phenomena in microgravity: Preliminary results of the first MEPHISTO flight experiment

NASA Technical Reports Server (NTRS)

Favier, Jean Jacques; Garandet, J. P.; Rouzaud, A.; Camel, D.

1994-01-01

The MEPHISTO space program is the result of a cooperative effort that involves the French nuclear and space agencies (Commissariat a l'energie atomique, CEA - Centre National d'Etudes Spatiales, CNES) and the American National Aeronautics and Space Administration (NASA). The scientific studies and apparatus development were funded in the frame of the GRAMME agreement between CEA and CNES, the flight costs being taken in charge by NASA. Six flight opportunities are scheduled, with alternating French and American principal investigators. It is the purpose of this paper to briefly present MEPHISTO along with the preliminary results obtained during its first flight on USMP-1 in October 1992.

Long-term comparative effectiveness of carotid stenting versus carotid endarterectomy in a large tertiary care vascular surgery practice.

PubMed

Garvin, Robert P; Ryer, Evan J; Berger, Andrea L; Elmore, James R

2018-03-31

Carotid interventional trials have strict inclusion and exclusion criteria that make translation of their results to the real-world population challenging. Furthermore, the specialty of the operating surgeon and the role of clinical decision-making are not well studied. This study compares the effectiveness of carotid endarterectomy (CEA) vs carotid artery stenting (CAS) in a real-world setting when the procedure is performed by fellowship-trained vascular surgeons. A retrospective study was conducted of all consecutive patients undergoing CEA and CAS performed by vascular surgeons in a large rural tertiary health care system from 2004 to 2014. Postoperative outcomes of stroke, acute myocardial infarction (AMI), and death were analyzed at 30 days and during the long term (median follow-up of 5.5 years for CEA and 4.8 years for CAS). Standard statistical analysis was performed. Differences in long-term outcomes were expressed as cumulative incidence functions for nondeath outcomes (stroke and AMI), which account for the high death rate in this population of vascular patients, and as Kaplan-Meier curves for death itself. From January 1, 2004, through December 31, 2014, there were 2331 carotid interventions performed (CEA, 1853; CAS, 478), all by fellowship-trained vascular surgeons. The average age of the patients was 71 years, and 63% were male, with more men in the CAS group (61.5% vs 67.8%; P = .011). Preoperatively, 30% of patients were symptomatic, and 77% of patients had high-grade stenosis in the 70% to 99% range. CEA patients were more likely to have preoperative hypertension (89.7% vs 86.2%; P = .029) and were less likely to have a history of cardiovascular disease (53.4% vs 59.4%; P = .018). There were no significant differences in 30-day outcomes between CEA and CAS (stroke, 1.1% vs 1.3% [P = .743]; AMI, 2.2% vs 1.7% [P = .474]; death, 0.7% vs 0.6% [P = .859]) or long-term outcomes (stroke, 6.8% vs 7.7% [P = .321]; AMI, 22.7% vs 21.0% [P = .886]; death, 28.4% vs 28.2% [P = .122]). The short- and long-term outcomes after CEA vs CAS are similar when the procedure is performed in a real-world setting by fellowship-trained vascular surgeons. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Risk Factors For Stroke, Myocardial Infarction, or Death Following Carotid Endarterectomy: Results From the International Carotid Stenting Study.

PubMed

Doig, D; Turner, E L; Dobson, J; Featherstone, R L; de Borst, G J; Stansby, G; Beard, J D; Engelter, S T; Richards, T; Brown, M M

2015-12-01

Carotid endarterectomy (CEA) is standard treatment for symptomatic carotid artery stenosis but carries a risk of stroke, myocardial infarction (MI), or death. This study investigated risk factors for these procedural complications occurring within 30 days of endarterectomy in the International Carotid Stenting Study (ICSS). Patients with recently symptomatic carotid stenosis >50% were randomly allocated to endarterectomy or stenting. Analysis is reported of patients in ICSS assigned to endarterectomy and limited to those in whom CEA was initiated. The occurrence of stroke, MI, or death within 30 days of the procedure was reported by investigators and adjudicated. Demographic and technical risk factors for these complications were analysed sequentially in a binomial regression analysis and subsequently in a multivariable model. Eight-hundred and twenty-one patients were included in the analysis. The risk of stroke, MI, or death within 30 days of CEA was 4.0%. The risk was higher in female patients (risk ratio [RR] 1.98, 95% CI 1.02-3.87, p = .05) and with increasing baseline diastolic blood pressure (dBP) (RR 1.30 per +10 mmHg, 95% CI 1.02-1.66, p = .04). Mean baseline dBP, obtained at the time of randomization in the trial, was 78 mmHg (SD 13 mmHg). In a multivariable model, only dBP remained a significant predictor. The risk was not related to the type of surgical reconstruction, anaesthetic technique, or perioperative medication regimen. Patients undergoing CEA stayed a median of 4 days before discharge, and 21.2% of events occurred on or after the day of discharge. Increasing diastolic blood pressure was the only independent risk factor for stroke, MI, or death following CEA. Cautious attention to blood pressure control following symptoms attributable to carotid stenosis could reduce the risks associated with subsequent CEA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuropeptide Y Opposes Alcohol Effects on GABA Release in Amygdala and Blocks the Transition to Alcohol Dependence

PubMed Central

Gilpin, Nicholas W.; Misra, Kaushik; Herman, Melissa A.; Cruz, Maureen T.; Koob, George F.; Roberto, Marisa

2011-01-01

Background During the transition to alcohol and drug addiction, neuromodulator systems in the extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence on inhibitory GABA neurons in central amygdala (CeA). Methods This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking by making rats dependent on alcohol via alcohol vapor inhalation. This study also utilized intracellular and whole-cell recording techniques to determine the effects of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naïve and alcohol-dependent rats. Results Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated with alcohol dependence, as well as gradual increases in alcohol responding by intermittently tested non-dependent controls. NPY decreased baseline GABAergic transmission and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing GABA release via actions at presynaptic Y2 receptors. Conclusions These results highlight NPY modulation of GABAergic signaling in central amygdala as a promising pharmacotheraputic target for the treatment of alcoholism. GABA neurons in the CeA likely constitute a major point of convergence for neuromodulator systems recruited during the transition to alcohol dependence. PMID:21459365

Guidelines for the use of carotid endarterectomy: current recommendations from the Canadian Neurosurgical Society.

PubMed

Findlay, J M; Tucker, W S; Ferguson, G G; Holness, R O; Wallace, M C; Wong, J H

1997-09-15

To develop guidelines on the suitability of patients for carotid endarterectomy (CEA). For atherosclerotic carotid stenosis that has resulted in retinal or cerebral ischemia: antiplatelet drugs or CEA. For asymptomatic carotid stenosis: CEA or no surgery. Risk of stroke and death. Trials comparing CEA with nonsurgical management of carotid stenosis. Greatest weight was given to findings that were highly significant both statistically and clinically. Benefit: reduction in the risk of stroke. Major harms: iatrogenic stroke, cardiac complications and death secondary to surgical manipulations of the artery or the systemic stress of surgery. Costs were not considered. CEA is clearly recommended for patients with surgically accessible internal carotid artery (ICA) stenoses equal to or greater than 70% of the more distal, normal ICA lumen diameter, providing: (1) the stenosis is symptomatic, causing transient ischemic attacks or nondisabling stroke (including retinal infarction); (2) there is no worse distal, ipsilateral, carotid distribution arterial disease; (3) the patient is in stable medical condition; and (4) the rates of major surgical complications (stroke and death) among patients of the treating surgeon are less than 6%. Surgery is not recommended for asymptomatic stenoses of less than 60%. Symptomatic stenoses of less than 70% and asymptomatic stenoses of greater than 60% are uncertain indications. For these indications, consideration should be given to (1) patient presentation, age and medical condition; (2) plaque characteristics such as degree of narrowing, the presence of ulceration and any documented worsening of the plaque over time; (3) other cerebral arterial stenoses or occlusions, or cerebral infarcts identified through neuroimaging; and (4) surgical complication rates at the institution. CEA should not be considered for asymptomatic stenoses unless the combined stroke and death rate among patients of the surgeon is less than 3%. These guidelines generally agree with position statements prepared by other organizations in recent years, and with a January 1995 consensus statement by a group of experts assembled by the American Heart Association.

Age modifies the relative risk of stenting versus endarterectomy for symptomatic carotid stenosis--a pooled analysis of EVA-3S, SPACE and ICSS.

PubMed

Bonati, L H; Fraedrich, G

2011-02-01

Recent randomised controlled trials comparing carotid artery stenting (CAS) with endarterectomy (CEA) for the treatment of symptomatic carotid stenosis were not powered to investigate differences in risks in specific patient subgroups. We therefore performed a pooled analysis of individual patient data from the Symptomatic Severe Carotid Stenosis trial (EVA-3S), the Stent-Protected Angioplasty versus Carotid Endarterectomy trial (SPACE), and the International Carotid Stenting Study (ICSS). Individual data from all 3433 patients randomised and analysed in these trials were pooled and analysed with fixed-effect binomial regression models adjusted for source trial. The primary outcome event was any stroke or death. In the first 120 days after randomisation (ITT analysis), the primary outcome event occurred in 153/1725 patients in the CAS group (8.9%) compared with 99/1708 patients in the CEA group (5.8%, risk ratio [RR] 1.53, 95% confidence interval [CI] 1.20-1.95, p = 0.0006; absolute risk difference 3.2, 95% CI 1.4-4.9). Age was the only subgroup variable which significantly modified the treatment effect: in patients <70 years old (the median age), the 120-day stroke or death risk was 5.8% in CAS and 5.7% in CEA (RR 1.00, 0.68-1.47); in patients 70 years or older, there was an estimated two-fold increase in risk with CAS over CEA (12.0% vs. 5.9%, RR 2.04, 1.48-2.82, interaction p = 0.0053). Endarterectomy was safer in the short-term than stenting, because of an increased risk of stroke associated with stenting in patients over the age of 70 years. Stenting should be avoided in older patients, but may be as safe as endarterectomy in younger patients. Determination of the efficacy and ultimate balance between the two procedures requires further data on long-term stroke recurrence. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Kinetics of anti-carcinoembryonic antigen antibody internalization: effects of affinity, bivalency, and stability

PubMed Central

Schmidt, Michael M.; Thurber, Greg M.

2010-01-01

Theoretical analyses suggest that the cellular internalization and catabolism of bound antibodies contribute significantly to poor penetration into tumors. Here we quantitatively assess the internalization of antibodies and antibody fragments against the commonly targeted antigen carcinoembryonic antigen (CEA). Although CEA is often referred to as a non-internalizing or shed antigen, anti-CEA antibodies and antibody fragments are shown to be slowly endocytosed by LS174T cells with a half-time of 10–16 h, a time scale consistent with the metabolic turnover rate of CEA in the absence of antibody. Anti-CEA single chain variable fragments (scFvs) with significant differences in affinity, stability against protease digestion, and valency exhibit similar uptake rates of bound antibody. In contrast, one anti-CEA IgG exhibits unique binding and trafficking properties with twice as many molecules bound per cell at saturation and significantly faster cellular internalization after binding. The internalization rates measured herein can be used in simple computational models to predict the microdistribution of these antibodies in tumor spheroids. PMID:18408925

Literature review of cranial nerve injuries during carotid endarterectomy.

PubMed

Sajid, M S; Vijaynagar, B; Singh, P; Hamilton, G

2007-01-01

In the recent prospective randomised trials on carotid endarterectomy (CEA), the incidence of cranial nerve injuries (CNI) are reported to be higher than in previously published studies. The objective of this study is to review the incidence of post CEA cranial nerve injury and to discover whether it has changed in the last 25 years after many innovations in vascular surgery. Generic terms including carotid endarterectomy, cranial nerve injuries, post CEA complications and cranial nerve deficit after neck surgery were used to search a variety of electronic databases. Based on selection criteria, decisions regarding inclusion and exclusion of primary studies were made. The incidence of CNI before and after 1995 was compared. We found 31 eligible studies from the literature. Patients who underwent CEA through any approach were included in the study. All patients had cranial nerves examined both before and after surgery. The total number of patients who had CEA before 1995 was 3521 with 10.6% CNI (352 patients) and after 1995, 7324 patients underwent CEA with 8.3% CNI (614 patients). Cranial nerves XII, X and VII were most commonly involved (rarely IX and XI). Statistical analysis showed that the incidence of CNI has decreased (X(2) = 5.89 + 0.74 = 6.63 => p-value = 0.0100). CNI is still a significant postoperative complication of carotid endarterectomy. Despite increasing use of CEA, the incidence of CNI has decreased probably because of increased awareness of the possibility of cranial nerve damage.

Carotid Artery Stenting Trials: Conduct, Results, Critique, and Current Recommendations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macdonald, Sumaira, E-mail: sumaira.macdonald@nuth.nhs.uk

2012-02-15

The carotid stenting trialists have demonstrated persistence and determination in comparing an evolving technique, carotid artery stenting (CAS), against a mature and exacting standard for carotid revascularisation, carotid endarterectomy (CEA). This review focuses on their endeavours. A total of 12 1-on-1 randomised trials comparing CAS and CEA have been reported; 6 of these can be considered major, and 5 of these reflect (in part) current CAS standards of practice and form the basis of this review. At least 18 meta-analyses seeking to compare CAS and CEA exist. These are limited by the quality and heterogeneity of the data informing themmore » (e.g., five trials were stopped prematurely such that they collectively failed to reach recruitment target by >4000 patients). The Carotid Stenting Trialists' Collaboration Publication represents a prespecified meta-analysis of European trials that were sufficiently similar to allow valid conclusions to be drawn; these trials and conclusions will be explored. When the rate of myocardial infarction (MI) is rigorously assessed, CAS and CEA are equivalent for the composite end point of stroke/death and MI, with more minor strokes for CAS and more MIs for CEA. These outcomes have a discrepant impact on quality of life and subsequent mortality. The all-stroke death outcomes for patients <70 years old are equivalent, with more minor strokes occurring in the elderly during CAS than CEA. There are significantly more severe haematomas and cranial nerve injuries after CEA. The influence of experience on outcome cannot be underestimated.« less

Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

PubMed

Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

2017-01-01

The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

Visual Aids for Improving Patient Decision Making in Severe Symptomatic Carotid Stenosis.

PubMed

Fridman, Sebastian; Saposnik, Gustavo; Sposato, Luciano A

2017-12-01

Because of the large amount of information to process and the limited time of a clinical consult, choosing between carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS) can be confusing for patients with severe symptomatic internal carotid stenosis (ICA). We aim to develop a visual aid tool to help clinicians and patients in the decision-making process of selecting between CEA and CAS. Based on pooled analysis from randomized controlled trials including patients with symptomatic and severe ICA (SSICA), we generated visual plots comparing CEA with CAS for 3 prespecified postprocedural time points: (1) any stroke or death at 4 months, and (2) any stroke or death in the first 30 days and ipsilateral stroke thereafter at 5 years and (3) at 10 years. A total of 4574 participants (2393 assigned to CAS, and 2361 to CEA) were included in the analyses. For every 100 patients with SSICA, 6 would develop any stroke or death in the CEA group compared with 9 undergoing CAS at 4 months (hazard ratio [HR] 1.53; 95%CI 1.20-1.95). At 5 years, 7 patients in the CEA group would develop any periprocedural stroke or death and ipsilateral stroke thereafter versus 12 undergoing CAS (HR 1.72; 95%CI 1.24-2.39), compared with 10 patients in the CEA and 13 in the CAS groups at 10 years (HR 1.17; 95%CI 0.82-1.66). Visual aids presented in this study could potentially help patients with severe symptomatic internal carotid stenosis to better weigh the risks and benefits of CEA versus CAS as a function of time, allowing for the prioritization of personal preferences, and should be prospectively assessed. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

PubMed Central

Kadayifci, Abdurrahman; Al-Haddad, Mohammad; Atar, Mustafa; Dewitt, John M.; Forcione, David G.; Sherman, Stuart; Casey, Brenna W.; Fernandez-del Castillo, Carlos; Schmidt, C. Max; Pitman, Martha B.; Brugge, William R.

2016-01-01

Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use. PMID:27092317

A risk factor-based predictive model of outcomes in carotid endarterectomy: the National Surgical Quality Improvement Program 2005-2010.

PubMed

Bekelis, Kimon; Bakhoum, Samuel F; Desai, Atman; Mackenzie, Todd A; Goodney, Philip; Labropoulos, Nicos

2013-04-01

Accurate knowledge of individualized risks and benefits is crucial to the surgical management of patients undergoing carotid endarterectomy (CEA). Although large randomized trials have determined specific cutoffs for the degree of stenosis, precise delineation of patient-level risks remains a topic of debate, especially in real world practice. We attempted to create a risk factor-based predictive model of outcomes in CEA. We performed a retrospective cohort study involving patients who underwent CEAs from 2005 to 2010 and were registered in the American College of Surgeons National Quality Improvement Project database. Of the 35 698 patients, 20 015 were asymptomatic (56.1%) and 15 683 were symptomatic (43.9%). These patients demonstrated a 1.64% risk of stroke, 0.69% risk of myocardial infarction, and 0.75% risk of death within 30 days after CEA. Multivariate analysis demonstrated that increasing age, male sex, history of chronic obstructive pulmonary disease, myocardial infarction, angina, congestive heart failure, peripheral vascular disease, previous stroke or transient ischemic attack, and dialysis were independent risk factors associated with an increased risk of the combined outcome of postoperative stroke, myocardial infarction, or death. A validated model for outcome prediction based on individual patient characteristics was developed. There was a steep effect of age on the risk of myocardial infarction and death. This national study confirms that that risks of CEA vary dramatically based on patient-level characteristics. Because of limited discrimination, it cannot be used for individual patient risk assessment. However, it can be used as a baseline for improvement and development of more accurate predictive models based on other databases or prospective studies.

Strengthening cost-effectiveness analysis in Thailand through the establishment of the health intervention and technology assessment program.

PubMed

Tantivess, Sripen; Teerawattananon, Yot; Mills, Anne

2009-01-01

Capacity is limited in the developing world to conduct cost-effectiveness analysis (CEA) of health interventions. In Thailand, there have been concerted efforts to promote evidence-based policy making, including the introduction of economic appraisals within health technology assessment (HTA). This paper reviews the experience of this lower middle-income country, with an emphasis on the creation of the Health Intervention and Technology Assessment Program (HITAP), including its mission, management structures and activities. Over the past 3 decades, several HTA programmes were implemented in Thailand but not sustained or developed further into a national institute. As a response to increasing demands for HTA evidence including CEA information, the HITAP was created in 2007 as an affiliate unit of a semi-autonomous research arm of the Ministry of Public Health. An advantage of this HTA programme over previous initiatives was that it was hosted by a research institute with long-term experience in conducting health systems and policy research and capacity building of its research staff, and excellent research and policy networks. To deal with existing impediments to conducting health economics research, the main strategies of the HITAP were carefully devised to include not only capacity strengthening of its researchers and administrative staff, but also the development of essential elements for the country's health economic evaluation methodology. These included, for example, methodological guidelines, standard protocols and benchmarks for resource allocation, many of which have been adopted by national policy-making bodies including the three major public health insurance plans. Networks and collaborations with domestic and foreign institutes have been sought as a means of resource mobilization and exchange. Although the HITAP is well financed by a number of government agencies and international organizations, the programme is vulnerable to shortages of qualified research staff, as most staff work on a part-time or temporary basis. To enhance the utilization of its research findings by policy makers, practitioners and consumers, the HITAP has adopted the principles of technical excellence, policy relevance, transparency, effective communication and participation of key stakeholders. These principles have been translated into good practice at every step of HTA management. In 2007 and 2008, the HITAP carried out assessments of a wide range of health products, medical procedures and public health initiatives. Although CEA and other economic evaluation approaches were employed in these studies, the tools and underlying efficiency goal were considered inadequate to provide complete information for prioritization. As suggested by official stakeholders, some of the projects investigated broader issues of management, feasibility, performance and socio-political implications of interventions. As yet, it is unclear what role HITAP research and associated recommendations have played in policy decisions. It is hoped that the lessons drawn on the creation of the HITAP and its experience during the first 2 years, as well as information on its main strategies and management structures, may be helpful for other resource-constrained countries when considering how best to strengthen their capacity to conduct economic appraisals of health technologies and interventions.

Carotid Artery Stent Placement and Carotid Endarterectomy: A Challenge for Urgent Treatment after Stroke-Early and 12-Month Outcomes in a Comprehensive Stroke Center.

PubMed

Rocco, Alessandro; Sallustio, Fabrizio; Toschi, Nicola; Rizzato, Barbara; Legramante, Jacopo; Ippoliti, Arnaldo; Marchetti, Andrea Ascoli; Pampana, Enrico; Gandini, Roberto; Diomedi, Marina

2018-06-20

To compare feasibility, 12-month outcome, and periprocedural and postprocedural risks between carotid artery stent (CAS) placement and carotid endarterectomy (CEA) performed within 1 week after transient ischemic attack (TIA) or mild to severe stroke onset in a single comprehensive stroke center. Retrospective analysis of prospective data collected from 1,148 patients with ischemic stroke admitted to a single stroke unit between January 2013 and July 2015 was conducted. Among 130 consecutive patients with symptomatic carotid stenosis, 110 (10 with TIA, 100 with stroke) with a National Institutes of Health Stroke Scale (NIHSS) score < 20 and a prestroke modified Rankin Scale (mRS) score < 2 were eligible for CAS placement or CEA and treated according to the preference of the patient or a surrogate. Periprocedural (< 48 h) and postprocedural complications, functional outcome, stroke, and death rate up to 12 months were analyzed. Sixty-two patients were treated with CAS placement and 48 were treated with CEA. Several patients presented with moderate or major stroke (45.8% CEA, 64.5% CAS). NIHSS scores indicated slightly greater severity at onset in patients treated with a CAS vs CEA (6.6 ± 5.7 vs 4.2 ± 3.4; P = .08). Complication rates were similar between groups. mRS scores showed a significant improvement over time and a significant interaction with age in both groups. Similar incidences of death or stroke were shown on survival analysis. A subanalysis in patients with NIHSS scores ≥ 4 showed no differences in complication rate and outcome. CAS placement and CEA seem to offer early safe and feasible secondary stroke prevention treatments in experienced centers, even after major atherosclerotic stroke. Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.

Capillary electrophoresis-chemiluminescence detection for carcino-embryonic antigen based on aptamer/graphene oxide structure.

PubMed

Zhou, Zi-Ming; Feng, Zhe; Zhou, Jun; Fang, Bi-Yun; Qi, Xiao-Xiao; Ma, Zhi-Ya; Liu, Bo; Zhao, Yuan-Di; Hu, Xue-Bin

2015-02-15

A new strategy is proposed for determination of carcino-embryonic antigen (CEA) based on aptamer/graphene oxide (Apt/GO) by capillary electrophoresis-chemiluminescence (CE-CL) detection system. CEA aptamer conjugated with horseradish peroxidase (HRP) firstly mixes with GO, and the CL will be quenched because the stack of HRP-Apt on GO leads to chemiluminescence resonance energy transfer (CRET). When CEA exists, the specific combination of HRP-Apt and CEA can form HRP-Apt-CEA complex, which dissociates from GO. Then, the CL catalyzed by HRP-Apt-CEA complex can be detected without any CRET, and the content of CEA can be estimated by the CL intensity. It has been proved that the interference issue resulted from free HRP-Apt is solved well by mixing GO firstly with HRP-Apt, which blocks the free HRP-Apt's CL signal due to CL quenching effect of GO; and the interference resulted from GO to CL is also solved by CE, then the sensitivity and accuracy can be greatly improved. Results also showed that the CL intensity had a linear relationship with the concentration of CEA in the range from 0.0654 to 6.54 ng/mL, and the limit of detection was approximately 4.8 pg/mL (S/N = 3). This proposed method with high specificity offers a new way for separation and determination of biomolecule, and has good potential in application of biochemistry and bioanalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Top-down nanofabrication of silicon nanoribbon field effect transistor (Si-NR FET) for carcinoembryonic antigen detection.

PubMed

Bao, Zengtao; Sun, Jialin; Zhao, Xiaoqian; Li, Zengyao; Cui, Songkui; Meng, Qingyang; Zhang, Ye; Wang, Tong; Jiang, Yanfeng

2017-01-01

Sensitive and quantitative detection of tumor markers is highly required in the clinic for cancer diagnosis and consequent treatment. A field-effect transistor-based (FET-based) nanobiosensor emerges with characteristics of being label-free, real-time, having high sensitivity, and providing direct electrical readout for detection of biomarkers. In this paper, a top-down approach is proposed and implemented to fulfill a novel silicon nano-ribbon FET, which acts as biomarker sensor for future clinical application. Compared with the bottom-up approach, a top-down fabrication approach can confine width and length of the silicon FET precisely to control its electrical properties. The silicon nanoribbon (Si-NR) transistor is fabricated on a Silicon-on-Insulator (SOI) substrate by a top-down approach with complementary metal oxide semiconductor (CMOS)-compatible technology. After the preparation, the surface of Si-NR is functionalized with 3-aminopropyltriethoxysilane (APTES). Glutaraldehyde is utilized to bind the amino terminals of APTES and antibody on the surface. Finally, a microfluidic channel is integrated on the top of the device, acting as a flowing channel for the carcinoembryonic antigen (CEA) solution. The Si-NR FET is 120 nm in width and 25 nm in height, with ambipolar electrical characteristics. A logarithmic relationship between the changing ratio of the current and the CEA concentration is measured in the range of 0.1-100 ng/mL. The sensitivity of detection is measured as 10 pg/mL. The top-down fabricated biochip shows feasibility in direct detecting of CEA with the benefits of real-time, low cost, and high sensitivity as a promising biosensor for tumor early diagnosis.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. PMID:26245970

Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the Second REVEAL Trial.

PubMed

Baumann, Leslie; Goldberg, David J; Stein Gold, Linda; Tanghetti, Emil A; Lain, Edward; Kaufman, Joely; Weng, Emily; Berk, David R; Ahluwalia, Gurpreet

2018-03-01

Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(3):290-298.

A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer.

PubMed

Murgas, Paola; Bustamante, Nicolás; Araya, Nicole; Cruz-Gómez, Sebastián; Durán, Eduardo; Gaete, Diana; Oyarce, César; López, Ernesto; Herrada, Andrés Alonso; Ferreira, Nicolás; Pieringer, Hans; Lladser, Alvaro

2018-02-01

Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8 + T cells, as depletion of circulating CD8 + T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.

Kappa Opioid Receptor-Mediated Dysregulation of GABAergic Transmission in the Central Amygdala in Cocaine Addiction

PubMed Central

Kallupi, Marsida; Wee, Sunmee; Edwards, Scott; Whitfield, Tim W.; Oleata, Christopher S.; Luu, George; Schmeichel, Brooke E.; Koob, George F.; Roberto, Marisa

2013-01-01

Background Studies have demonstrated an enhanced dynorphin/kappa-opioid receptor (KOR) system following repeated cocaine exposure, but few reports have focused on neuroadaptations within the central amygdala (CeA). Methods We identified KOR-related physiological changes in the CeA following escalation of cocaine self-administration in rats. We used in vitro slice electrophysiological (intracellular and whole-cell recordings) methods to assess whether differential cocaine access in either 1h (short access, ShA) or 6h (long access, LgA) sessions induced plasticity at CeA GABAergic synapses, or altered the sensitivity of these synapses to KOR agonism (U50488) or antagonism (nor-BNI). We then determined the functional effects of CeA KOR blockade in cocaine-related behaviors. Results Baseline evoked GABAergic transmission was enhanced in the CeA from ShA and LgA rats compared to cocaine-naïve rats. Acute cocaine (1 uM) application significantly decreased GABA release in all groups (naïve, ShA, and LgA rats). Application of U50488 (1 uM) significantly decreased GABAergic transmission in the CeA from naïve rats, but increased it in LgA rats. Conversely, nor-BNI (200 nM) significantly increased GABAergic transmission in the CeA from naïve rats, but decreased it in LgA rats. Nor-BNI did not alter the acute cocaine-induced inhibition of GABAergic responses. Finally, CeA microinfusion of nor-BNI blocked cocaine-induced locomotor sensitization and attenuated the heightened anxiety-like behavior observed during withdrawal from chronic cocaine exposure in the defensive burying paradigm. Conclusion Together these data demonstrate that CeA dynorphin/KOR systems are dysregulated following excessive cocaine exposure and suggest KOR antagonism as a viable therapeutic strategy for cocaine addiction. PMID:23751206

Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway.

PubMed

Liu, Jiemin; Jin, Haifeng; Foreman, Robert D; Lei, Yong; Xu, Xiaohong; Li, Shiying; Yin, Jieyun; Chen, Jiande D Z

2015-07-01

The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P < 0.05). CEA reduced both postprandial blood glucose and HbA1c (P < 0.05). CEA delayed gastric emptying (P < 0.03) and increased small intestinal transit (P < 0.02). CEA increased fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R (2) = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01). CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

Preparation and characterization of a novel skin substitute.

PubMed

Castagnoli, Carlotta; Fumagalli, Mara; Alotto, Daniela; Cambieri, Irene; Casarin, Stefania; Ostorero, Alessia; Casimiri, Raffaella; Germano, Patrizia; Pezzuto, Carla; Stella, Maurizio

2010-01-01

Autologous epidermal cell cultures (CEA) represent a possibility to treat extensive burn lesions, since they allow a significative surface expansion which cannot be achieved with other surgical techniques based on autologous grafting. Moreover currently available CEA preparations are difficult to handle and their take rate is unpredictable. This study aimed at producing and evaluating a new cutaneous biosubstitute made up of alloplastic acellular glycerolized dermis (AAGD) and CEA to overcome these difficulties. A procedure that maintained an intact basement membrane was developed, so as to promote adhesion and growth of CEA on AAGD. Keratinocytes were seeded onto AAGD and cultured up to 21 days. Viability tests and immunohistochemical analysis with specific markers were carried out at 7, 14, and 21 days, to evaluate keratinocyte adhesion, growth, and maturation. Our results support the hypothesis that this newly formed skin substitute could allow its permanent engraftment in clinical application.

Air Quality Cumulative Effects Assessment for U.S. Air Force Bases.

DTIC Science & Technology

1998-01-29

forecasted activities. Consideration of multimedia effects and transmedia impacts is important, however, in CEA. Any quantification method developed...substantive areas, such as water quality, ecology, planing, archeology , and landscape architecture? 9. Are there public concerns due to the impact risks of...methods developed for CEA should consider multimedia effects and transmedia impacts. Portions of this research can be used, or modified, to address other

Validation of Carotid Artery Revascularization Coding in Ontario Health Administrative Databases.

PubMed

Hussain, Mohamad A; Mamdani, Muhammad; Saposnik, Gustavo; Tu, Jack V; Turkel-Parrella, David; Spears, Julian; Al-Omran, Mohammed

2016-04-02

The positive predictive value (PPV) of carotid endarterectomy (CEA) and carotid artery stenting (CAS) procedure and post-operative complication coding were assessed in Ontario health administrative databases. Between 1 April 2002 and 31 March 2014, a random sample of 428 patients were identified using Canadian Classification of Health Intervention (CCI) procedure codes and Ontario Health Insurance Plan (OHIP) billing codes from administrative data. A blinded chart review was conducted at two high-volume vascular centers to assess the level of agreement between the administrative records and the corresponding patients' hospital charts. PPV was calculated with 95% confidence intervals (CIs) to estimate the validity of CEA and CAS coding, utilizing hospital charts as the gold standard. Sensitivity of CEA and CAS coding were also assessed by linking two independent databases of 540 CEA-treated patients (Ontario Stroke Registry) and 140 CAS-treated patients (single-center CAS database) to administrative records. PPV for CEA ranged from 99% to 100% and sensitivity ranged from 81.5% to 89.6% using CCI and OHIP codes. A CCI code with a PPV of 87% (95% CI, 78.8-92.9) and sensitivity of 92.9% (95% CI, 87.4-96.1) in identifying CAS was also identified. PPV for post-admission complication diagnosis coding was 71.4% (95% CI, 53.7-85.4) for stroke/transient ischemic attack, and 82.4% (95% CI, 56.6-96.2) for myocardial infarction. Our analysis demonstrated that the codes used in administrative databases accurately identify CEA and CAS-treated patients. Researchers can confidently use administrative data to conduct population-based studies of CEA and CAS.

The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer.

PubMed

Wang, Peng; Piao, Yingzhe; Zhang, Xiaohui; Li, Wenliang; Hao, Xishan

2013-01-01

We aimed to investigate the concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid (CSF) and to explore their clinical value in the meningeal carcinomatosis (MC) of lung cancer. So that, sensitive and specificity of CSF examination can be improved in the initial diagnosis of MC. A total of 35 lung cancer patients and 35 patients with benign brain tumor in the same period enrolled in this study. The concentrations of tumor markers CEA, CYFRA 21-1 and NSE in CSF and peripheral blood were examined. The concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum and CSF were obviously higher than that of benign disease group. In MC patients, the concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum were significant lower than that in CSF. The maximum of Youden's index was identified as the cutoff value of indicator of MC in three tumor markers in CSF which were CEA > 4.7 μg/L, NSE > 14.6 μg/L and CYFRA21-1 > 5.5 μg/L respectively. Based on the cutoff values, the CEA had the highest sensitivity while the CYFRA21-1 had the highest specificitiy. Three tumor markers in the CSF had higher positive rate than those in blood serum. We combined the levels of CEA, NSE and CYFRA21-1 in CSF to diagnosis of MC. Positive of CEA or CYFRA21-1 had the greatest sensitivity of 100% while the specificity of 91.4%; the positive of both CEA and CYFRA21-1 had the highest specificity of 100% while the sensitivity of 74.3%. Both positive predictive value and negative predictive value were 100% when combination positive were confirmed when the all three markers were positive. The combination of CEA and CYFRA21-1 can be recommended in early screening of meningeal carcinoma. Especially, for the patient who was difficult to be diagnosed by CSF histology and MRI, it will be a useful auxiliary marker in diagnosis of MC. The combination of CEA, NSE and CYFRA21-1 can be an effective clinically confirmation and exclusively diagnose indictor of MC.

[Diagnostic values of type III Procollagen N-terminal peptide and combination assay of type III procollagen N-terminal peptide with CEA and CA 19-9 in gastric cancer].

PubMed

Akazawa, S; Harada, A; Futatsuki, K

1984-07-01

It is known that interstitial collagens are initially synthesized as precursors (procollagen), which possess extra peptide segments at both ends of the molecules. The authors attempted to detect the aminoterminal peptide of type III procollagen (type III-N-peptide) and also to measure the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) together in sera of patients with gastric cancer. The results showed that: (1) mean serum levels and positive ratios of the type III-N-peptide increased as the clinical stage of the patients with gastric cancer advanced; (2) serum levels of the type III-N-peptide were not correlated either with those of CEA or CA 19-9; (3) positive ratios of type III-N-peptide, CEA and CA 19-9 were 51.7%, 44.8% and 48.3%, respectively: (4) positive ratio in combination of the type III-N-peptide with CEA was 69.3% and that in combination of the type III-N-peptide with CEA and CA 19-9 was 72.4%. These results suggest that type III-N-peptide is available for diagnosis of gastric cancer and, that the combination assay of type III-N-peptide with CEA and CA 19-9 is more effective than a single assay for diagnosis.

77 FR 41940 - Clearing Exemption for Certain Swaps Entered Into by Cooperatives

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-17

... Act Section 4(c)(1) of the CEA provides that, in order to promote responsible economic or financial... members of the cooperative promotes greater economic efficiency and lower costs for the members. The... responsible economic and financial innovation and fair competition. The Commission requests public comment on...

Ex vivo PD-L1/PD-1 pathway blockade reverses dysfunction of circulating CEA specific T cells in pancreatic cancer patients

PubMed Central

Chen, Y; Xue, SA; Behboudi, S; Mohammad, GH; Pereira, SP; Morris, EC

2017-01-01

Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer (PC). In this study, we have characterised the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2 restricted peptide, pCEA691–699, isolated from the peripheral T cell repertoire of PC patients and sought to determine if ex vivo PD-L1 & TIM3 blockade could enhance CTL function. CD8+ T cell lines were generated from peripheral blood mononuclear cells (PBMCs) of 18 HLA-A2+ patients with PC and from 15 healthy controls. In vitro peptide specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and CSFE cytotoxicity assays using pancreatic cancer cell lines as targets. Cytokine secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18PC patients, with two CTL lines able to recognise and kill both CEA691 peptide-loaded T2 cells and CEA+ HLA-A2+ pancreatic cancer cell lines. In the presence of ex vivo PD-L1 blockade, functional CEA691-specific CD8+ T cell responses, including IFN-γ secretion and proliferation, were enhanced and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes. These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T cell repertoire of PC patients and that their function can be enhanced by PD-L1 blockade. PMID:28710313

Importance of the Postoperative Carcinoembryonic Antigen Level during Follow-Up after Curative Resection in Patients with Liver Metastatic Colorectal Carcinoma.

PubMed

Hashimoto, Takuzo; Itabashi, Michio; Ogawa, Shinpei; Hirosawa, Tomoichiro; Bamba, Yoshiko; Kaji, Sanae; Ubukata, Mamiko; Shimizu, Satoru; Sugihara, Kenichi; Kameoka, Shingo

2014-06-01

To validate the conventional Japanese grading of liver metastasis for no residual tumor resection in Stage IV colorectal cancer (CRC) with liver metastasis and to identify risk factors for postoperative recurrence. The subjects of this study were 1792 Stage IV CRC patients with liver metastasis. In 1792 cases, including unresectable cases, there was a significantly different prognosis by grade (P < 0.0001). In 421 R0 cases, there was no significant difference between Grade A and Grade B (P = 0.8527). In 381 cases without extra-hepatic metastasis, the prognosis was not significantly different among three grades. On multivariate analysis, carcinoembryonic antigen within 3 months from R0 operation (3M-CEA) was an independent risk factor regardless of extrahepatic metastasis. There was a significantly different prognosis (P < 0.0001) among Grade A', defined as a normal 3M-CEA level, Grade B', defined as Grade A or B and an abnormal 3M-CEA level, and Grade C', defined as Grade C and an abnormal 3M-CEA level. The postoperative CEA level is an important risk factor during follow-up after curative resection in patients with liver metastatic colorectal carcinoma. The combination of the 3M-CEA level and conventional grading of liver metastasis is useful for follow-up of R0 resection cases.

Internal carotid artery rupture caused by carotid shunt insertion

PubMed Central

Illuminati, Giulio; Caliò, Francesco G.; Pizzardi, Giulia; Vietri, Francesco

2015-01-01

Introduction Shunting is a well-accepted method of maintaining cerebral perfusion during carotid endarterectomy (CEA). Nonetheless, shunt insertion may lead to complications including arterial dissection, embolization, and thrombosis. We present a complication of shunt insertion consisting of arterial wall rupture, not reported previously. Presentation of case A 78-year-old woman underwent CEA combined with coronary artery bypass grafting (CABG). At the time of shunt insertion an arterial rupture at the distal tip of the shunt was detected and was repaired via a small saphenous vein patch. Eversion CEA and subsequent CABG completed the procedure whose postoperative course was uneventful. Discussion Shunting during combined CEA-CABG may be advisable to assure cerebral protection from possible hypoperfusion due to potential hemodynamic instability of patients with severe coronary artery disease. Awareness and prompt management of possible shunt-related complications, including the newly reported one, may contribute to limiting their harmful effect. Conclusion Arterial wall rupture is a possible, previously not reported, shunt-related complication to be aware of when performing CEA. PMID:26255001

Breath Analysis Using Laser Spectroscopic Techniques: Breath Biomarkers, Spectral Fingerprints, and Detection Limits

PubMed Central

Wang, Chuji; Sahay, Peeyush

2009-01-01

Breath analysis, a promising new field of medicine and medical instrumentation, potentially offers noninvasive, real-time, and point-of-care (POC) disease diagnostics and metabolic status monitoring. Numerous breath biomarkers have been detected and quantified so far by using the GC-MS technique. Recent advances in laser spectroscopic techniques and laser sources have driven breath analysis to new heights, moving from laboratory research to commercial reality. Laser spectroscopic detection techniques not only have high-sensitivity and high-selectivity, as equivalently offered by the MS-based techniques, but also have the advantageous features of near real-time response, low instrument costs, and POC function. Of the approximately 35 established breath biomarkers, such as acetone, ammonia, carbon dioxide, ethane, methane, and nitric oxide, 14 species in exhaled human breath have been analyzed by high-sensitivity laser spectroscopic techniques, namely, tunable diode laser absorption spectroscopy (TDLAS), cavity ringdown spectroscopy (CRDS), integrated cavity output spectroscopy (ICOS), cavity enhanced absorption spectroscopy (CEAS), cavity leak-out spectroscopy (CALOS), photoacoustic spectroscopy (PAS), quartz-enhanced photoacoustic spectroscopy (QEPAS), and optical frequency comb cavity-enhanced absorption spectroscopy (OFC-CEAS). Spectral fingerprints of the measured biomarkers span from the UV to the mid-IR spectral regions and the detection limits achieved by the laser techniques range from parts per million to parts per billion levels. Sensors using the laser spectroscopic techniques for a few breath biomarkers, e.g., carbon dioxide, nitric oxide, etc. are commercially available. This review presents an update on the latest developments in laser-based breath analysis. PMID:22408503

[Stent and surgery for symptomatic carotid stenosis. SPACE study results].

PubMed

Ringleb, P A; Hacke, W

2007-10-01

The SPACE trial compared risk and effectiveness of stent-supported angioplasty (CAS) vs carotid endarterectomy (CEA) using a noninferiority design in patients with symptomatic stenoses. Intention-to-treat analysis of the entire study population of 1,214 patients showed that primary endpoint events (ipsilateral stroke or death between randomisation and day 30) occurred in 6.92% of the CAS group and 6.45% of the CEA group. The 95% confidence interval (CI) of the absolute risk difference ranged from -1.94% to +2.87%, therefore the noninferiority was not proven. The same was true for the analysis of protocols. No significant differences between the two treatment methods were found in primary or any of the secondary endpoints. There were also no differences in short-term prevention. The endpoint 'ipsilateral ischemic stroke or vascular death between randomisation and 6 months' occurred in 7.4% of the CAS and 6.5% of the CEA patients (odds ratio 1.16, 95% confidence interval 0.74-1.82). Instent restenoses were significantly more common in the CAS group (4.6% vs 2.2%, odds ratio 2.14, 95% CI 1.10-4.18). Surgery remains the gold standard in treatment of patients with symptomatic carotid artery stenosis. Stent-supported angioplasty can be an alternative only in the hands of an experienced interventionalist with proven low periprocedural complication rate.

Neuropeptide Y in the central nucleus of amygdala regulates the anxiolytic effect of agmatine in rats.

PubMed

Taksande, Brijesh G; Kotagale, Nandkishor R; Gawande, Dinesh Y; Bharne, Ashish P; Chopde, Chandrabhan T; Kokare, Dadasaheb M

2014-06-01

In the present study, modulation of anxiolytic action of agmatine by neuropeptide Y (NPY) in the central nucleus of amygdala (CeA) is evaluated employing Vogel's conflict test (VCT) in rats. The intra-CeA administration of agmatine (0.6 and 1.2µmol/rat), NPY (10 and 20pmol/rat) or NPY Y1/Y5 receptors agonist [Leu(31), Pro(34)]-NPY (30 and 60pmol/rat) significantly increased the number of punished drinking licks following 15min of treatment. Combination treatment of subeffective dose of NPY (5pmol/rat) or [Leu(31), Pro(34)]-NPY (15pmol/rat) and agmatine (0.3µmol/rat) produced synergistic anxiolytic-like effect. However, intra-CeA administration of selective NPY Y1 receptor antagonist, BIBP3226 (0.25 and 0.5mmol/rat) produced anxiogenic effect. In separate set of experiment, pretreatment with BIBP3226 (0.12mmol/rat) reversed the anxiolytic effect of agmatine (0.6µmol/rat). Furthermore, we evaluated the effect of intraperitoneal injection of agmatine (40mg/kg) on NPY-immunoreactivity in the nucleus accumbens shell (AcbSh), lateral part of bed nucleus of stria terminalis (BNSTl) and CeA. While agmatine treatment significantly decreased the fibers density in BNSTl, increase was noticed in AcbSh. In addition, agmatine reduced NPY-immunoreactive cells in the AcbSh and CeA. Immunohistochemical data suggest the enhanced transmission of NPY from the AcbSh and CeA. Taken together, this study suggests that agmatine produced anxiolytic effect which might be regulated via modulation of NPYergic system particularly in the CeA. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

SPACE-2: A Missed Opportunity to Compare Carotid Endarterectomy, Carotid Stenting, and Best Medical Treatment in Patients with Asymptomatic Carotid Stenoses.

PubMed

Eckstein, H-H; Reiff, T; Ringleb, P; Jansen, O; Mansmann, U; Hacke, W

2016-06-01

Because of recent advances in best medical treatment (BMT), it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit, in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses. The aim was to compare the stroke-preventive effects of BMT alone, with that of BMT in combination with carotid endarterectomy (CEA) or carotid artery stenting (CAS) in patients with high grade asymptomatic extracranial carotid artery stenosis. SPACE-2 was planned as a three-armed, randomized controlled trial (BMT alone vs. CEA plus BMT vs. CAS plus BMT, ISRCTN 78592017). However, because of slow patient recruitment, the three-arm study design was amended (July 2013) to become two parallel randomized studies (BMT alone vs. CEA plus BMT, and BMT alone vs. CAS plus BMT). The change in study design did not lead to any significant increase in patient recruitment, and trial recruitment ceased after recruiting 513 patients over a 5 year period (CEA vs. BMT (n = 203); CAS vs. BMT (n = 197), and BMT alone (n = 113)). The 30 day rate of death/stroke was 1.97% for patients undergoing CEA, and 2.54% for patients undergoing CAS. No strokes or deaths occurred in the first 30 days after randomization in patients randomized to BMT. There were several potential reasons for the low recruitment rates into SPACE-2, including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial, an inability to convince patients (who had come "mentally prepared" that an intervention was necessary) to accept BMT, and other economic constraints. Because of slow recruitment rates, SPACE-2 had to be stopped after randomizing only 513 patients. The German Research Foundation will provide continued funding to enable follow up of all recruited patients, and it is also planned to include these data in any future meta-analysis prepared by the Carotid Stenosis Trialists Collaboration. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Elucidating the relation between childhood emotional abuse and depressive symptoms in adulthood: The mediating role of maladaptive interpersonal processes

PubMed Central

Massing-Schaffer, Maya; Liu, Richard T.; Kraines, Morganne A.; Choi, Jimmy Y.; Alloy, Lauren B.

2015-01-01

Objective The purpose of this study is to assess the potential unique and relative mediating effects of three interpersonal risk factors (i.e., excessive reassurance-seeking [ERS], negative feedback seeking [NFS], and rejection sensitivity [RS]) in the relationship between childhood emotional abuse (CEA) and depressive symptoms. Method One hundred eighty-five undergraduates were followed over a four-month interval. Participants completed assessments of childhood abuse history, ERS, NFS, and RS, and depressive symptoms at baseline, as well as depressive symptoms at four-month followup. Results Findings from single-mediator analyses indicated that RS and NFS, but not ERS, mediated the relationship between CEA and prospective depressive symptoms, after accounting for childhood sexual and physical abuse, as well as baseline depressive symptoms. In our multi-mediator model, only RS remained a significant mediator of the relationship between CEA and prospective depressive symptoms. Conclusions The current study provides preliminary evidence that negative behavioral styles may function as a mechanism linking prior experiences of CEA to subsequent depressive symptoms. Clinical implications of these findings suggest that targeting maladaptive behavioral tendencies, particularly RS, may be an effective adjunct in behavioral modification treatments of CEA victims at risk for depression. PMID:26246650

Study of Laminar Flame 2-D Scalar Values at Various Fuel to Air Ratios Using an Imaging Fourier-Transform Spectrometer and 2-D CFD Analysis

DTIC Science & Technology

2013-03-01

NASA- Glenn’s Chemical Equilibrium with Applications (CEA) program. UNICORN CFD predictions were in excellent agreement with CEA calculations at...49 Appendix A – UNICORN CFD Inputs and Instruction .....................................................50 Appendix B – NASA-Glenn...17 Figure 7: Schematic of UNICORN CFD card setup. ........................................................ 18 Figure 8: Averaged flame

Spanish Pre-University Students' Use of English: CEA Results from the University Entrance Examination

ERIC Educational Resources Information Center

Diez-Bedmar, Maria Belen

2011-01-01

In this paper an updated overview of the main errors that Spanish students make when writing the English exam in the University Entrance Examination is provided. To do so, a Computer-aided Error Analysis (CEA) (Dagneaux, Denness & Granger, 1998) was conducted on a representative sample of the students who took the exam in June 2008 in Jaen,…

Systematic preoperative coronary angiography and stenting improves postoperative results of carotid endarterectomy in patients with asymptomatic coronary artery disease: a randomised controlled trial.

PubMed

Illuminati, G; Ricco, J-B; Greco, C; Mangieri, E; Calio', F; Ceccanei, G; Pacilè, M A; Schiariti, M; Tanzilli, G; Barillà, F; Paravati, V; Mazzesi, G; Miraldi, F; Tritapepe, L

2010-02-01

To evaluate the usefulness of systematic coronary angiography followed, if needed, by coronary artery angioplasty (percutaneous coronary intervention (PCI)) on the incidence of cardiac ischaemic events after carotid endarterectomy (CEA) in patients without evidence of coronary artery disease (CAD). From January 2005 to December 2008, 426 patients, candidates for CEA, with no history of CAD and with normal cardiac ultrasound and electrocardiography (ECG), were randomised into two groups. In group A (n=216) all the patients had coronary angiography performed before CEA. In group B, all the patients had CEA without previous coronary angiography. In group A, 66 patients presenting significant coronary artery lesions at angiography received PCI before CEA. They subsequently underwent surgery under aspirin (100 mg day(-1)) and clopidogrel (75 mg day(-1)). CEA was performed within a median delay of 4 days after PCI (range: 1-8 days). Risk factors, indications for CEA and surgical techniques were comparable in both groups (p>0.05). The primary combined endpoint of the study was the incidence of postoperative myocardial ischaemic events combined with the incidence of complications of coronary angiography. Secondary endpoints were death and stroke rates after CEA and incidence of cervical haematoma. Postoperative mortality was 0% in group A and 0.9% in group B (p=0.24). One postoperative stroke (0.5%) occurred in group A, and two (0.9%) in group B (p=0.62). No postoperative myocardial event was observed in group A, whereas nine ischaemic events were observed in group B, including one fatal myocardial infarction (p=0.01). Binary logistic regression analysis demonstrated that preoperative coronary angiography was the only independent variable that predicted the occurrence of postoperative coronary ischaemia after CEA. The odds ratio for coronary angiography (group A) indicated that when holding all other variables constant, a patient having preoperative coronary angiography before carotid surgery was 4 times less likely to have a cardiac ischaemic event after carotid surgery. No complications related to coronary angiography were observed and no cervical haematomas occurred in patients undergoing surgery under aspirin and clopidogrel in this study. Systematic preoperative coronary angiography, possibly followed by PCI, significantly reduces the incidence of postoperative myocardial events after CEA in patients without clinical evidence of CAD. Copyright (c) 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes.

PubMed

Imamura, Michiko; Morimoto, Takashi; Nomura, Takashi; Michishita, Shintaro; Nishimukai, Arisa; Higuchi, Tomoko; Fujimoto, Yukie; Miyagawa, Yoshimasa; Kira, Ayako; Murase, Keiko; Araki, Kazuhiro; Takatsuka, Yuichi; Oh, Koshi; Masai, Yoshikazu; Akazawa, Kouhei; Miyoshi, Yasuo

2018-02-12

Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections.

PubMed

Alhadeff, Amber L; Holland, Ruby A; Nelson, Alexandra; Grill, Harvey J; De Jonghe, Bart C

2015-08-05

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. Copyright © 2015 the authors 0270-6474/15/3511094-11$15.00/0.

Clinical value of jointly detection serum lactate dehydrogenase/pleural fluid adenosine deaminase and pleural fluid carcinoembryonic antigen in the identification of malignant pleural effusion.

PubMed

Zhang, Fan; Hu, Lijuan; Wang, Junjun; Chen, Jian; Chen, Jie; Wang, Yumin

2017-09-01

Limited data are available for the diagnostic value, and for the diagnostic sensitivity and specificity of joint detection of serum lactate dehydrogenase (sLDH)/pleural fluid adenosine deaminase (pADA) and pleural fluid carcinoembryonic antigen (pCEA) in malignant pleural effusion (MPE). We collected 987 pleural effusion specimens (of which 318 were malignant pleural effusion, 374 were tubercular pleural effusion, and 295 were parapneumonic effusion specimens) from the First Affiliated Hospital of Wenzhou Medical University from July 2012 to March 2016. The pADA, sLDH, pleural fluid LDH (pLDH), serum C-reactive protein (sCRP), pleural fluid protein, pCEA, white blood cell (WBC), and red blood cell (RBC) were analyzed, and the clinical data of each group were collected for statistical analysis. The level of sLDH/pADA, pCEA, and RBC from the MPE group was markedly higher than the tuberculosis pleural effusion (TB) group (Mann-Whitney U=28422.000, 9278.000, 30518, P=.000, .000, .000) and the parapneumonic pleural fluid group (Mann-Whitney U=5972.500, 7113.000, 36750.500, P=.000, .000, .000). The receiver operating characteristic curve ROC showed that the area under the ROC curve (AUC) (=0.924, 0.841) of pCEA and sLDH/pADA (cutoff=4.9, 10.6) were significantly higher than other markers for the diagnosis of MPE. Thus, joint detection of pCEA and sLDH/pADA suggested that the sensitivity, specificity, and AUC was 0.94, 81.70, and 94.32 at the cutoff 0.16 and diagnostic performance was higher than pCEA or sLDH/pADA. Joint detection of sLDH/pADA and pCEA can be used as a good indicator for the identification of benign and MPE with higher sensitivity and specificity than pCEA or sLDH/pADA. © 2016 Wiley Periodicals, Inc.

PREFACE: Nanosafe 2012: International Conferences on Safe Production and Use of Nanomaterials

NASA Astrophysics Data System (ADS)

Tardif, François

2013-04-01

Welcome from the organizers The rapidly developing field of nanotechnology opens up many exciting opportunities and benefits for new materials with significantly improved properties as well as some revolutionary applications in the fields of energy, environment, medicine, etc. These new materials potentially pave the way to considerable innovations in many industries of the 21st century although associated risks must be perfectly under control for workers, consumers and the environment. So, one can easily understand why Nanosafety is now considered as a specific new scientific area, gaining in importance and maturity every day. Following the successful outcome of the two past international conferences on the safe production and use of nanomaterials: Nanosafe 2008 and 2010, the organizing committee has the pleasure of welcoming again to Grenoble some of the most famous specialists of the field in the world. In addition to the standard issues addressed in previous nanosafe conferences such as Toxicology, Eco-toxicology, Expology, Detection, Life Cycle Analysis, Regulation and Standardization, new topics of great interest will be dealt with this year, concerning Governance and practical Risk Management for OSH experts and Societal issues. In order to enhance the exchanges and conviviality three debates werw organized around Nano Governance, Toxicology and Ethics. We hope that you will appreciate this new Nanosafe edition like the previous ones. This is your Nanosafe conference, please enjoy. The Nanosafe conference organisers François Tardif and Frédéric Shuster Management Vanessa Gaultier Francois TardifFrederic ShusterVanessa Gaultier François TardifFrédéric Shuster Vanessa Gaultier Local Organizing Committee Vanessa GAULTIER (CEA) François TARDIF (CEA) Dominique BAGUET (CEA) Frédédric SHUSTER (CEA) Yves SICARD (CEA) Catherine DURAND (CEA) Didier MOLKO (MINATEC) International Scientific Committee Chair: Frédéric SCHUSTER (CEA, FR) François TARDIF (CEA, FR) Co-chair: Georgios KATALAGARIANAKIS (EC, BE) Mélanie AUFFAN (CEREGE, FR) Jorge BOCZKOWSKI (INSERM, FR) Jean-Yves BOTTERO (CEREGE, FR) Jacques BOUILLARD (INERIS, FR) Derk BROUWER (TNO, NL) Marie CARRIERE (CEA, FR) Claude EMOND (U. MONTREAL, CA) Cassandra ENGEMAN (UCSB, USA) Eric GAFFET (CNRS, FR) François GENSDARMES (IRSN, FR) Alexei GRINBAUM (CEA, FR) Antje GROBE (U.STUTTGART, DE) Peter HOET (KUL, BE) Eric QUEMENEUR (CEA, FR) Olivier LE BIHAN (INERIS, FR) Robert MUIR (NANEUM, UK) Tinh NGUYEN (NIST, USA) Bernd NOWACK (EMPA, CH) Günter OBERDÖRSTER (U. ROCHESTER, USA) David PUI (U. MINNESOTA, USA) Michael RIEDIKER (IST, CH) Yves SAMSON (CEA, FR) Ken TAKEDA (U. TOKYO, JP) Olivier WITSCHGER (INRS, FR) The PDF contains a list of sponsor logos, the conference programme and planning documents.

Protocol for the economic evaluation of a complex intervention to improve the mental health of maltreated infants and children in foster care in the UK (The BeST? services trial)

PubMed Central

Boyd, Kathleen Anne; Minnis, Helen; Donaldson, Julia; Brown, Kevin; Boyer, Nicole R S; McIntosh, Emma

2018-01-01

Introduction Children who have experienced abuse and neglect are at increased risk of mental and physical health problems throughout life. This places an enormous burden on individuals, families and society in terms of health services, education, social care and judiciary sectors. Evidence suggests that early intervention can mitigate the negative consequences of child maltreatment, exerting long-term positive effects on the health of maltreated children entering foster care. However, evidence on cost-effectiveness of such complex interventions is limited. This protocol describes the first economic evaluation of its kind in the UK. Methods and analysis An economic evaluation alongside the Best Services Trial (BeST?) has been prospectively designed to identify, measure and value key resource and outcome impacts arising from the New Orleans intervention model (NIM) (an infant mental health service) compared with case management (CM) (enhanced social work services as usual). A within-trial economic evaluation and long-term model from a National Health Service/Personal Social Service and a broader societal perspective will be undertaken alongside the National Institute for Health Research (NIHR)–Public Health Research Unit (PHRU)-funded randomised multicentre BeST?. BeST? aims to evaluate NIM compared with CM for maltreated children entering foster care in a UK context. Collection of Paediatric Quality of Life Inventory (PedsQL) and the recent mapping of PedsQL to EuroQol-5-Dimensions (EQ-5D) will facilitate the estimation of quality-adjusted life years specific to the infant population for a cost–utility analysis. Other effectiveness outcomes will be incorporated into a cost-effectiveness analysis (CEA) and cost-consequences analysis (CCA). A long-term economic model and multiple economic evaluation frameworks will provide decision-makers with a comprehensive, multiperspective guide regarding cost-effectiveness of NIM. The long-term population health economic model will be developed to synthesise trial data with routine linked data and key government sector parameters informed by literature. Methods guidance for population health economic evaluation will be adopted (lifetime horizon, 1.5% discount rate for costs and benefits, CCA framework, multisector perspective). Ethics and dissemination Ethics approval was obtained by the West of Scotland Ethics Committee. Results of the main trial and economic evaluation will be submitted for publication in a peer-reviewed journal as well as published in the peer-reviewed NIHR journals library (Public Health Research Programme). Trial registration number NCT02653716; Pre-results. PMID:29540420

Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer.

PubMed

Jiang, Z F; Wang, M; Xu, J L

2018-02-01

Thymidine kinase 1 (TK1) is a tumor biomarker in human malignancies. The purpose of this study was to evaluate the diagnostic efficiency of this marker for lung cancer using the combined analysis of carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), neuron specific enolase (NSE) and TK1. From 2013 to 2014, 147 patients with lung cancer and 228 patients with lung benign diseases who were admitted to our hospital were reviewed. Peripheral blood samples were collected for the detection of TK1, CEA, CYFRA21-1 and NSE. The diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic regression equations. The serum levels of TK1, CEA, CYFRA21-1 and NSE were significantly higher than those in patients with lung benign diseases (all P<0.05). The TK1 concentration was dependent on TNM stage (P=0.005). The ROC curve analyses showed that the diagnostic value of TK1 combined with CEA, CYFRA21-1 and NSE in lung cancer was significantly higher than that of each biomarker alone (all P<0.0001). In addition, TK1 combined with CEA, CYFRA21-1, or NSE could also improve the diagnosis of the squamous cell carcinoma, adenocarcinoma and small cell lung cancer subtypes, respectively. The combined detection of TK1 and the other three markers significantly improved the diagnosis of lung cancer. Furthermore, the detection of TK1 combined with that of CYFRA21-1, CEA or NSE increased the diagnostic value of TK1 for lung squamous cell carcinoma, adenocarcinoma and SCLC, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of unilatral- and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine-induced place conditioning in male Wistar rat.

PubMed

Mohammadian, Zahra; Sahraei, Hedayat; Meftahi, Gholam Hossein; Ali-Beik, Hengameh

2017-03-01

The rostral ventral tegmental area (VTAR) and central nucleus of amygdala (CeA) are considered the main regions for induction of psychological dependence on abused drugs, such as morphine. The main aim of this study was to investigate the transient inhibition of each right and left side as well as both sides of the VTAR and the CeA by lidocaine (2%) on morphine reward properties using the conditioned place preference (CPP) method. Male Wistar rats (250±20 g) 7 days after recovery from surgery and cannulation were conditioned to morphine (7.5 mg/kg) in CPP apparatus. Five minutes before morphine injection in conditioning phase, lidocaine was administered either uni- or bilaterally into the VTAR (0.25 μL/site) or CeA (0.5 μL/site). The results revealed that lidocaine administration into the left side, but not the right side of the VTAR and the CeA reduced morphine CPP significantly. The reduction was potentiated when lidocaine was injected into both sides of the VTAR and the CeA. The number of compartment crossings was reduced when lidocaine was injected into both sides of the VTAR and the CeA as well as the left side. Rearing was reduced when lidocaine was injected into the right, but not the left side of the VTAR. Sniffing and rearing increased when animals received lidocaine in the right side and reduced in the group that received lidocaine in the left side of the CeA. It was concluded that the right and the left side of VTAR and the CeA play different roles in morphine-induced activity and reward. © 2016 John Wiley & Sons Australia, Ltd.

Deep brain stimulation in the central nucleus of the amygdala decreases 'wanting' and 'liking' of food rewards.

PubMed

Ross, Shani E; Lehmann Levin, Emily; Itoga, Christy A; Schoen, Chelsea B; Selmane, Romeissa; Aldridge, J Wayne

2016-10-01

We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever-pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self-stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory-excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an 'information lesion' that not only decreased motivational 'wanting' of food rewards, but also blocked 'liking' of rewards. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Highly sensitive and selective lateral flow immunoassay based on magnetic nanoparticles for quantitative detection of carcinoembryonic antigen.

PubMed

Liu, Fangming; Zhang, Honglian; Wu, Zhenhua; Dong, Haidao; Zhou, Lin; Yang, Dawei; Ge, Yuqing; Jia, Chunping; Liu, Huiying; Jin, Qinghui; Zhao, Jianlong; Zhang, Qiqing; Mao, Hongju

2016-12-01

Carcinoembryonic antigen (CEA) is an important biomarker in cancer diagnosis. Here, we present an efficient, selective lateral-flow immunoassay (LFIA) based on magnetic nanoparticles (MNPs) for in situ sensitive and accurate point-of-care detection of CEA. Signal amplification mechanism involved linking of detection MNPs with signal MNPs through biotin-modified single-stranded DNA (ssDNA) and streptavidin. To verify the effectiveness of this modified LFIA system, the sensitivity and specificity were evaluated. Sensitivity evaluation showed a broad detection range of 0.25-1000ng/ml for CEA protein by the modified LFIA, and the limit of detection (LOD) of the modified LFIA was 0.25ng/ml, thus producing significant increase in detection threshold compared with the traditional LFIA. The modified LFIA could selectively recognize CEA in presence of several interfering proteins. In addition, this newly developed assay was applied for quantitative detection of CEA in human serum specimens collected from 10 randomly selected patients. The modified LFIA system detected minimum 0.27ng/ml of CEA concentration in serum samples. The results were consistent with the clinical data obtained using commercial electrochemiluminescence immunoassay (ECLIA) (p<0.01). In conclusion, the MNPs based LFIA system not only demonstrated enhanced signal to noise ratio, it also detected CEA with higher sensitivity and selectivity, and thus has great potential to be commercially applied as a sensitive tumor marker filtration system. Copyright © 2016 Elsevier B.V. All rights reserved.

Risk modelling study for carotid endarterectomy.

PubMed

Kuhan, G; Gardiner, E D; Abidia, A F; Chetter, I C; Renwick, P M; Johnson, B F; Wilkinson, A R; McCollum, P T

2001-12-01

The aims of this study were to identify factors that influence the risk of stroke or death following carotid endarterectomy (CEA) and to develop a model to aid in comparative audit of vascular surgeons and units. A series of 839 CEAs performed by four vascular surgeons between 1992 and 1999 was analysed. Multiple logistic regression analysis was used to model the effect of 15 possible risk factors on the 30-day risk of stroke or death. Outcome was compared for four surgeons and two units after adjustment for the significant risk factors. The overall 30-day stroke or death rate was 3.9 per cent (29 of 741). Heart disease, diabetes and stroke were significant risk factors. The 30-day predicted stroke or death rates increased with increasing risk scores. The observed 30-day stroke or death rate was 3.9 per cent for both vascular units and varied from 3.0 to 4.2 per cent for the four vascular surgeons. Differences in the outcomes between the surgeons and vascular units did not reach statistical significance after risk adjustment. Diabetes, heart disease and stroke are significant risk factors for stroke or death following CEA. The risk score model identified patients at higher risk and aided in comparative audit.

Comparison of CEAS and Williams-type models for spring wheat yields in North Dakota and Minnesota

NASA Technical Reports Server (NTRS)

Barnett, T. L. (Principal Investigator)

1982-01-01

The CEAS and Williams-type yield models are both based on multiple regression analysis of historical time series data at CRD level. The CEAS model develops a separate relation for each CRD; the Williams-type model pools CRD data to regional level (groups of similar CRDs). Basic variables considered in the analyses are USDA yield, monthly mean temperature, monthly precipitation, and variables derived from these. The Williams-type model also used soil texture and topographic information. Technological trend is represented in both by piecewise linear functions of year. Indicators of yield reliability obtained from a ten-year bootstrap test of each model (1970-1979) demonstrate that the models are very similar in performance in all respects. Both models are about equally objective, adequate, timely, simple, and inexpensive. Both consider scientific knowledge on a broad scale but not in detail. Neither provides a good current measure of modeled yield reliability. The CEAS model is considered very slightly preferable for AgRISTARS applications.

Assessment of children's emotional adjustment: construction and validation of a new instrument.

PubMed

Thorlacius, Ö; Gudmundsson, E

2015-09-01

The present study describes the Children's Emotional Adjustment Scale (CEAS), a 47-item parent-reported scale designed to capture children's emotional functioning on four continuous dimensions. A large community sample of mothers of children (n = 606) aged 6-13 years was used to examine the psychometric properties of the CEAS. Exploratory and confirmatory factor analysis supported the hypothesized four-factor structure of the instrument: (1) temper control; (2) anxiety control; (3) mood repair; and (4) social assertiveness. Cronbach's alphas for the factors were consistently above 0.90, and convergent validity of the factors was satisfactory with maternal ratings of child psychopathology. Children rated by their mothers as having emotional problems in the clinical range on the Strengths and Difficulties Questionnaire had significantly lower scores on the CEAS scales. The CEAS is a psychometrically sound instrument, covering healthy emotional adjustment as well as maladjustment. The scale might prove to be valuable in the assessment and screening of behaviours underlying child psychopathology. © 2014 John Wiley & Sons Ltd.

A framework for assessing cumulative effects in watersheds: an introduction to Canadian case studies.

PubMed

Dubé, Monique G; Duinker, Peter; Greig, Lorne; Carver, Martin; Servos, Mark; McMaster, Mark; Noble, Bram; Schreier, Hans; Jackson, Lee; Munkittrick, Kelly R

2013-07-01

From 2008 to 2013, a series of studies supported by the Canadian Water Network were conducted in Canadian watersheds in an effort to improve methods to assess cumulative effects. These studies fit under a common framework for watershed cumulative effects assessment (CEA). This article presents an introduction to the Special Series on Watershed CEA in IEAM including the framework and its impetus, a brief introduction to each of the articles in the series, challenges, and a path forward. The framework includes a regional water monitoring program that produces 3 core outputs: an accumulated state assessment, stressor-response relationships, and development of predictive cumulative effects scenario models. The framework considers core values, indicators, thresholds, and use of consistent terminology. It emphasizes that CEA requires 2 components, accumulated state quantification and predictive scenario forecasting. It recognizes both of these components must be supported by a regional, multiscale monitoring program. Copyright © 2013 SETAC.

Changes in Gene Expression within the Extended Amygdala following Binge-Like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats

PubMed Central

McBride, William J.; Kimpel, Mark W.; McClintick, Jeanette N.; Ding, Zheng-Ming; Edenberg, Howard J.; Liang, Tiebing; Rodd, Zachary A.; Bell, Richard L.

2014-01-01

The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by male adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30 % ethanol for 3 one-h sessions/day for 5 consecutive days/week for 3 weeks. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5 – 3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR = 0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in biological processes involved with cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce changes in neuronal function. PMID:24355552

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance.

PubMed

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-03-01

Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA.Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis.Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131-3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247-3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257-3.555; P = .005), 2.450 (95% CI: 1.420-4.226; P = .001), and 2.265 (95% CI: 1.304-3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS.CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression.

Activation of the Jasmonic Acid Pathway by Depletion of the Hydroperoxide Lyase OsHPL3 Reveals Crosstalk between the HPL and AOS Branches of the Oxylipin Pathway in Rice

PubMed Central

Tang, Jiuyou; Wang, Weihong; Zhang, Fengxia; Wang, Guodong; Chu, Jinfang; Yan, Cunyu; Wang, Taoqing; Chu, Chengcai; Li, Chuanyou

2012-01-01

The allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches of the oxylipin pathway, which underlie the production of jasmonates and aldehydes, respectively, function in plant responses to a range of stresses. Regulatory crosstalk has been proposed to exist between these two signaling branches; however, there is no direct evidence of this. Here, we identified and characterized a jasmonic acid (JA) overproduction mutant, cea62, by screening a rice T-DNA insertion mutant library for lineages that constitutively express the AOS gene. Map-based cloning was used to identify the underlying gene as hydroperoxide lyase OsHPL3. HPL3 expression and the enzyme activity of its product, (E)-2-hexenal, were depleted in the cea62 mutant, which resulted in the dramatic overproduction of JA, the activation of JA signaling, and the emergence of the lesion mimic phenotype. A time-course analysis of lesion formation and of the induction of defense responsive genes in the cea62 mutant revealed that the activation of JA biosynthesis and signaling in cea62 was regulated in a developmental manner, as was OsHPL3 activity in the wild-type plant. Microarray analysis showed that the JA-governed defense response was greatly activated in cea62 and this plant exhibited enhanced resistance to the T1 strain of the bacterial blight pathogen Xanthomonasoryzaepvoryzae (Xoo). The wounding response was attenuated in cea62 plants during the early stages of development, but partially recovered when JA levels were elevated during the later stages. In contrast, the wounding response was not altered during the different developmental stages of wild-type plants. These findings suggest that these two branches of the oxylipin pathway exhibit crosstalk with regards to biosynthesis and signaling and cooperate with each other to function in diverse stress responses. PMID:23209649

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance

PubMed Central

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-01-01

Abstract Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA. Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis. Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131–3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247–3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257–3.555; P = .005), 2.450 (95% CI: 1.420–4.226; P = .001), and 2.265 (95% CI: 1.304–3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS. CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression. PMID:29517661

Epidural analgesia in patients with traumatic rib fractures: a systematic review of randomised controlled trials.

PubMed

Duch, P; Møller, M H

2015-07-01

Traumatic rib fractures are a common condition associated with considerable morbidity and mortality. Observational studies have suggested improved outcome in patients receiving continuous epidural analgesia (CEA). The aim of the present systematic review of randomised controlled trials (RCTs) was to assess the benefit and harm of CEA compared with other analgesic interventions in patients with traumatic rib fractures. We performed a systematic review with meta-analysis and trial sequential analysis (TSA). Eligible trials were RCTs comparing CEA with other analgesic interventions in patients with traumatic rib fractures. Cumulative relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were estimated, and risk of systematic and random errors was assessed. The predefined primary outcome measures were mortality, pneumonia and duration of mechanical ventilation. A total of six trials (n = 223) were included; all were judged as having a high risk of bias. In the conventional meta-analyses, there was no statistically significant difference in mortality (RR 2.18, 95% CI 0.21-22.42; P = 0.51; I(2)  = 0%), duration of mechanical ventilation (MD -7.53, 95% CI -16.32 to 1.26; P = 0.09; I(2)  = 91%) or pneumonia (RR 0.49, 95% CI 0.19-1.25; P = 0.13; I(2)  = 0%) between CEA and other analgesic interventions. Subgroup analyses and sensitivity analyses, including TSA confirmed the results. The quality and quantity of evidence for the use of CEA in patients with traumatic rib fractures is low, and there is no firm evidence for benefit or harm of CEA compared with other analgesic interventions. Well-powered RCTs with low risk of bias reporting clinically relevant patient-centred outcome measures are needed. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Reliability of plain radiographic parameters for developmental dysplasia of the hip in children.

PubMed

Upasani, Vidyadhar V; Bomar, James D; Parikh, Gaurav; Hosalkar, Harish

2012-07-01

Few studies have evaluated the reliability and reproducibility of the femoral neck-shaft angle (NSA), center-edge angle (CEA), and acetabular index (AI) in young children with developmental dysplasia of the hip (DDH). We wanted to determine whether these parameters could be used reliably by practitioners. Fifty radiographs from 21 children with DDH were reviewed. Analysis was performed by three observers, at two time periods. The intra- and inter-observer reliability for each measure was assessed. At time period one, we noted a "high" level of agreement between observers when measuring the NSA, a "low" level when measuring the CEA, and a "moderate" level when measuring the AI. At time period two, we noted a "very high" level of agreement between observers when measuring the NSA and a "high" level when measuring the CEA and AI. When comparing the measurements of observer 1 at the two different time periods, we noted nearly "very high" agreement when measuring the NSA, a "moderate" agreement when measuring the CEA, and a "high" agreement for the AI. In comparing the measurements of observer 2, we noted "very high" agreement for the NSA and "high" agreement for the CEA and AI. In comparing the measurements for observer 3, we noted nearly "very high" agreement for the NSA, nearly "high" agreement for the CEA, and "high" agreement for the AI. It is difficult to reliably measure three-dimensional pelvic morphology on a frontal plane radiograph, especially when important pelvic landmarks have yet to ossify.

The predictive value of preoperative carcinoembryonic antigen level in the prognosis of colon cancer.

PubMed

Kirat, Hasan T; Ozturk, Ersin; Lavery, Ian C; Kiran, Ravi P

2012-10-01

We evaluated factors associated with an increased preoperative carcinoembryonic antigen (CEA) level for colon cancer patients undergoing elective curative surgery and assessed whether this was associated with prognosis when accounting for other potential confounders. Prospectively accrued data of patients with stage I, II, and III colon cancer undergoing surgery (1980-2008) were retrieved retrospectively. Patients with a preoperative CEA level greater than 5 ng/mL (group B) were compared with those with a CEA level of 5 ng/mL or less (group A). There were 651 patients (379 men) with a median age of 67 years (range, 21-94 y) and a median follow-up period of 5.9 years. Groups A (n = 451) and B (n = 200) had similar ages and tumor locations. Group B had larger tumors; more patients with T3 and N1/N2; and more patients with stage II/III tumors, and hence greater use of chemotherapy (P = .04). On multivariate analysis, patient age, tumor stage, and differentiation were associated with oncologic outcomes. A CEA level greater than 5 ng/mL was not associated independently with recurrence, recurrence-free survival (P = .47), or overall survival (P = .3). An increased preoperative CEA level is a marker for a more advanced tumor stage. For adequately staged patients, a high preoperative CEA level is not associated independently with oncologic outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

Only limited evidence available for the effectiveness and cost effectiveness of dental auxiliaries.

PubMed

Richards, Derek

2013-01-01

Medline, Embase, CINAHL, LILACS, Cochrane Database of Systematic Reviews, OpenGrey (System for Information on Grey Literature in Europe [SIGLE]-based), Scirus, Science.gov, Cost-Effective Analysis (CEA) Registry, European Network of Health Economics Evaluation Databases (EURON-HEED), ClinicalTrials.gov and Health Services Research Projects in Progress (HSRProj) databases. They also contacted 20 separate organisations. All study designs were considered with no limits on dates, age of study, language or country. Government reports, peer-reviewed publications, dissertations and theses were included. Editorials, opinion pieces, educational pieces, narrative reviews, abstracts without full-text availability and raw data such as those from national oral health surveys were excluded. Study quality and risk of bias was assessed. Data extraction was conducted independently, and meta-analysis was planned for the data, but only a qualitative synthesis could be conducted. Eighteen observational studies were included, 13 were considered to be at high risk of bias, five at moderate risk and one at low risk. They were conducted in Australia, Canada, Hong Kong, New Zealand and the United States. All the studies were related to dental caries with only studies involving dental nurses and therapists meeting the inclusion criteria. No studies regarding cost effectiveness, irreversible diagnostic procedures or diseases other than caries were in included. The authors concluded that the quality of the evidence was poor. They found that in select groups in which participants received irreversible dental treatment from teams that included midlevel providers, caries increment, caries severity or both decreased across time; however, there was no difference in caries increment, caries severity or both compared with those in populations in which dentists provided all irreversible treatment. In select groups in which participants had received irreversible dental treatment from teams that included midlevel providers, there was a decrease in untreated caries across time and a decrease in untreated caries compared with that in populations in which dentists provided all treatment.

Cost-effectiveness of tobacco control policies and programmes targeting adolescents: a systematic review.

PubMed

Leão, Teresa; Kunst, Anton E; Perelman, Julian

2018-02-01

Consistent evidence shows the importance of preventing smoking at young ages, when health behaviours are formed, with long-term consequences on health and survival. Although tobacco control policies and programmes targeting adolescents are widely promoted, the cost-effectiveness of such interventions has not been systematically documented. We performed a systematic review on the cost-effectiveness of policies and programmes preventing tobacco consumption targeting adolescents. We systematically reviewed literature on the (i) cost and effectiveness of (ii) prevention policies targeting (iii) smoking by (iv) adolescents. PubMed, Web of Science, Cochrane, CEA-TUFTS, Health Economic Evaluations, Wiley Online Library, Centre for Reviews and Dissemination Database, the National Institute for Health and Care Excellence and Google Scholar databases were used, and Google search engine was used for other grey literature review. We obtained 793 full-text papers and 19 grey literature documents, from which 16 studies fulfilled the inclusion criteria. Of these, only one was published in the last 5 years, and 15 were performed in high-income countries. Eight analyzed the cost-effectiveness of school-based programmes, five focused on media campaigns and three on legal bans. Policies and programmes were found to be cost-effective in all studies, and both effective and cost-saving in about half of the studies. Evidence is scarce and relatively obsolete, and rarely focused on the evaluation of legal bans. Moreover, no comparisons have been made between different interventions or across different contexts and implementation levels. However, all studies conclude that smoking prevention policies and programmes amongst adolescents are greatly worth their costs. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association.

Internal carotid artery rupture caused by carotid shunt insertion.

PubMed

Illuminati, Giulio; Caliò, Francesco G; Pizzardi, Giulia; Vietri, Francesco

2015-01-01

Shunting is a well-accepted method of maintaining cerebral perfusion during carotid endarterectomy (CEA). Nonetheless, shunt insertion may lead to complications including arterial dissection, embolization, and thrombosis. We present a complication of shunt insertion consisting of arterial wall rupture, not reported previously. A 78-year-old woman underwent CEA combined with coronary artery bypass grafting (CABG). At the time of shunt insertion an arterial rupture at the distal tip of the shunt was detected and was repaired via a small saphenous vein patch. Eversion CEA and subsequent CABG completed the procedure whose postoperative course was uneventful. Shunting during combined CEA-CABG may be advisable to assure cerebral protection from possible hypoperfusion due to potential hemodynamic instability of patients with severe coronary artery disease. Awareness and prompt management of possible shunt-related complications, including the newly reported one, may contribute to limiting their harmful effect. Arterial wall rupture is a possible, previously not reported, shunt-related complication to be aware of when performing CEA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The clinical effectiveness and cost-effectiveness of testing for cytochrome P450 polymorphisms in patients with schizophrenia treated with antipsychotics: a systematic review and economic evaluation.

PubMed

Fleeman, N; McLeod, C; Bagust, A; Beale, S; Boland, A; Dundar, Y; Jorgensen, A; Payne, K; Pirmohamed, M; Pushpakom, S; Walley, T; de Warren-Penny, P; Dickson, R

2010-01-01

To determine whether testing for cytochrome P450 (CYP) polymorphisms in adults entering antipsychotic treatment for schizophrenia leads to improvement in outcomes, is useful in medical, personal or public health decision-making, and is a cost-effective use of health-care resources. The following electronic databases were searched for relevant published literature: Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA) Registry and the Centre for Health Economics website. In addition, publicly available information on various genotyping tests was sought from the internet and advisory panel members. A systematic review of analytical validity, clinical validity and clinical utility of CYP testing was undertaken. Data were extracted into structured tables and narratively discussed, and meta-analysis was undertaken when possible. A review of economic evaluations of CYP testing in psychiatry and a review of economic models related to schizophrenia were also carried out. For analytical validity, 46 studies of a range of different genotyping tests for 11 different CYP polymorphisms (most commonly CYP2D6) were included. Sensitivity and specificity were high (99-100%). For clinical validity, 51 studies were found. In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found. The only other significant finding linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the inclusion criteria for clinical utility. One economic evaluation assessing the costs and benefits of CYP testing for prescribing antidepressants and 28 economic models of schizophrenia were identified; none was suitable for developing a model to examine the cost-effectiveness of CYP testing. Tests for determining genotypes appear to be accurate although not all aspects of analytical validity were reported. Given the absence of convincing evidence from clinical validity studies, the lack of clinical utility and economic studies, and the unsuitability of published schizophrenia models, no model was developed; instead key features and data requirements for economic modelling are presented. Recommendations for future research cover both aspects of research quality and data that will be required to inform the development of future economic models.

Relationship of serum CEA levels to tumour size and CEA content in nude mice bearing colonic-tumour xenografts.

PubMed Central

Lewis, J. C.; Keep, P. A.

1981-01-01

The relationship of serum carcinoembryonic antigen (CEA) levels to tumour size and antigen content was studied in nude mice bearing well differentiated, mucinous human colonic-tumour xenografts. Blood samples were taken from normal nude mice and others bearing xenografts, whose size had been calculated from in vivo measurements; saline and KCl extracts were made of a proportion of these tumours. Sera and tissue extracts were assayed for CEA activity by double-antibody radioimmunoassay. Extracts were also made from the livers and spleens of tumour-bearing and normal nude mice. All normal sera and 78% of sera from tumour-bearing animals had CEA values less than 11.4 ng/ml. No clear correlation was found between serum CEA levels greater than 11.4 ng/ml and tumour size or weight, or between serum CEA and tumour CEA concentrations or total CEA burden. The concentration of CEA in those tumours tested varied from 1 to 22 microgram/g. Our results confirm and extend the conclusions reached by others (Stragand et al., 1980) studying the significance of serum CEA levels with xenograft model systems. The complexity of factors contributing to circulating CEA is discussed in the light of our findings. Images Fig. 1 PMID:7284235

Demonstration of monoclonal anti-carcinoembryonic antigen (CEA) antibody internalization by electron microscopy, western blotting and radioimmunoassay.

PubMed

Tsaltas, G; Ford, C H; Gallant, M

1992-01-01

One of the important factors affecting the action of monoclonal antibodies (Mabs) or immunoconjugates on tumour sites depends on whether the Mab is internalized by the cancer cells in question. The underexplored subject of internalization is discussed in this paper, and a number of in vitro techniques for investigating internalization are evaluated, using a model which consists of a well characterized anti-carcinoembryonic antigen (anti-CEA) Mab and a number of CEA expressing human cancer cell lines. Employing two alternative radiolabeling assays, evidence for internalization of the anti-CEA Mab by a CEA-positive colorectal cancer cell line (LS174T) was obtained throughout the time intervals examined (5 min to 150 min). Electronmicroscopy employing horseradish-peroxidase labeled anti-CEA Mab and control antibody permitted direct visualization of anti-CEA Mab-related staining in intracellular compartments of a high CEA-expressor human colorectal cell line (SKCO1). Finally Western blots of samples derived from cytosolic and membrane components of solubilized cells from lung and colonic cancer cell lines provided evidence for internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 minutes. Internalized anti-CEA was detected in all CEA expressing cell lines (LS174T, SKCO1, BENN) but not in the case of a very low CEA expressor line (COLO 320).

Effects of selective excitotoxic lesions of the nucleus accumbens core, anterior cingulate cortex, and central nucleus of the amygdala on autoshaping performance in rats.

PubMed

Cardinal, Rudolf N; Parkinson, John A; Lachenal, Guillaume; Halkerston, Katherine M; Rudarakanchana, Nung; Hall, Jeremy; Morrison, Caroline H; Howes, Simon R; Robbins, Trevor W; Everitt, Barry J

2002-08-01

The nucleus accumbens core (AcbC), anterior cingulate cortex (ACC), and central nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.

Complications after carotid endarterectomy are related to surgical errors in less than one-fifth of cases. Swedvasc--The Swedish Vascular Registry and The Quality Committee for Carotid Artery Surgery.

PubMed

Troëng, T; Bergqvist, D; Norrving, B; Ahari, A

1999-07-01

to study possible relations between indications, contraindications and surgical technique and stroke and/or death within 30 days of carotid endarterectomy (CEA). analysis of hospital records for patients identified in a national vascular registry. during 1995-1996, 1518 patients were reported to the Swedish Vascular Registry - Swedvasc. Among these the sixty-five with a stroke and/or death within 30 days were selected for study. Complete surgical records were reviewed by three approved reviewers using predetermined criteria for indications and possible errors. an error of surgical technique or postoperative management was found in eleven patients (17%). In six cases (9%) the indication was inappropriate or there was an obvious contraindication. The indication was questionable in fourteen (21.5%). Half of the patients (52.5%) had surgery for an appropriate indication, and no contraindication or error in surgical technique or management was identified. more than half the complications of CEA represent the "method cost", i.e. the indication, risk and surgical technique were correct. However, the stroke and/or death rate might be reduced if all operations conformed to agreed criteria. Copyright 1999 W.B. Saunders Company Ltd.

Comparative Review of the Treatment Methodologies of Carotid Stenosis

PubMed Central

Bae, Coney; Szuchmacher, Mauricio; Chang, John B.

2015-01-01

The treatment of carotid stenosis entails three methodologies, namely, medical management, carotid angioplasty and stenting (CAS), as well as carotid endarterectomy (CEA). The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) have shown that symptomatic carotid stenosis greater than 70% is best treated with CEA. In asymptomatic patients with carotid stenosis greater than 60%, CEA was more beneficial than treatment with aspirin alone according to the Asymptomatic Carotid Atherosclerosis (ACAS) and Asymptomatic Carotid Stenosis Trial (ACST) trials. When CAS is compared with CEA, the CREST resulted in similar rates of ipsilateral stroke and death rates regardless of symptoms. However, CAS not only increased adverse effects in women, it also amplified stroke rates and death in elderly patients compared with CEA. CAS can maximize its utility in treating focal restenosis after CEA and patients with overwhelming cardiac risk or prior neck irradiation. When performing CEA, using a patch was equated to a more durable result than primary closure, whereas eversion technique is a new methodology deserving a spotlight. Comparing the three major treatment strategies of carotid stenosis has intrinsic drawbacks, as most trials are outdated and they vary in their premises, definitions, and study designs. With the newly codified best medical management including antiplatelet therapies with aspirin and clopidogrel, statin, antihypertensive agents, strict diabetes control, smoking cessation, and life style change, the current trials may demonstrate that asymptomatic carotid stenosis is best treated with best medical therapy. The ongoing trials will illuminate and reshape the treatment paradigm for symptomatic and asymptomatic carotid stenosis. PMID:26417191

A clinical rule (sex, contralateral occlusion, age, and restenosis) to select patients for stenting versus carotid endarterectomy: systematic review of observational studies with validation in randomized trials.

PubMed

Touzé, Emmanuel; Trinquart, Ludovic; Felgueiras, Rui; Rerkasem, Kittipan; Bonati, Leo H; Meliksetyan, Gayané; Ringleb, Peter A; Mas, Jean-Louis; Brown, Martin M; Rothwell, Peter M

2013-12-01

Compared with carotid endarterectomy (CEA), carotid angioplasty and stenting (CAS) is associated with a higher risk of procedural stroke or death especially in patients with symptomatic stenosis. However, after the perioperative period, risk is similar with both treatments, suggesting that CAS could be an acceptable option in selected patients. We performed systematic reviews of observational studies of procedural risks of CEA or CAS and extracted data on 9 predefined risk factors (age, contralateral carotid occlusion, coronary artery disease, diabetes mellitus, sex, hypertension, peripheral artery disease, and type and side of stenosis). We calculated pooled relative risks of procedural stroke or death. Factors with differential effects on risk of CAS versus CEA were identified by interaction tests and used to derive a rule. The rule was tested using individual patient data from randomized trials of CAS versus CEA from the Carotid Stenting Trialists' Collaboration (CSTC). We identified 170 studies. The effects of sex, contralateral occlusion, age, and restenosis (SCAR) on the procedural risk of stroke or death differed. Patients with contralateral occlusion or restenosis and women<75 years were at relatively low risk for CAS (SCAR negative), with all others being high risk (SCAR positive). Among the 3049 patients in the CSTC validation, 694 (23%) patients were SCAR negative. The pooled RR of procedural stroke and death with CAS versus CEA was 0.93 (0.49-1.77; P=0.83) in SCAR-negative and 2.41 (1.68-3.45; P<0.0001) in SCAR-positive patients (P [interaction]=0.05). The SCAR rule is potentially useful to identify patients in whom CAS has a similar risk of perioperative stroke or death to CEA.

Number and cost of claims linked to minor cervical trauma in Europe: results from the comparative study by CEA, AREDOC and CEREDOC.

PubMed

Chappuis, Guy; Soltermann, Bruno

2008-10-01

Comparative epidemiological study of minor cervical spine trauma (frequently referred to as whiplash injury) based on data from the Comité Européen des Assurances (CEA) gathered in ten European countries. To determine the incidence and expenditure (e.g., for assessment, treatment or claims) for minor cervical spine injury in the participating countries. Controversy still surrounds the basis on which symptoms following minor cervical spine trauma may develop. In particular, there is considerable disagreement with regard to a possible contribution of psychosocial factors in determining outcome. The role of compensation is also a source of constant debate. The method followed here is the comparison of the data from different areas of interest (e.g., incidence of minor cervical spine trauma, percentage of minor cervical spine trauma in relationship to the incidence of bodily trauma, costs for assessment or claims) from ten European countries. Considerable differences exist regarding the incidence of minor cervical spine trauma and related costs in participating countries. France and Finland have the lowest and Great Britain the highest incidence of minor cervical spine trauma. The number of claims following minor cervical spine trauma in Switzerland is around the European average; however, Switzerland has the highest expenditure per claim at an average cost of 35,000.00 euros compared to the European average of 9,000.00 euros. Furthermore, the mandatory accident insurance statistics in Switzerland show very large differences between German-speaking and French- or Italian-speaking parts of the country. In the latter the costs for minor cervical spine trauma expanded more than doubled in the period from 1990 to 2002, whereas in the German-speaking part they rose by a factor of five. All the countries participating in the study have a high standard of medical care. The differences in claims frequency and costs must therefore reflect a social phenomenon based on the different cultural attitudes and medical approach to the problem including diagnosis. In Switzerland, therefore, new ways must be found to try to resolve the problem. The claims treatment model known as "Case Management" represents a new approach in which accelerated social and professional reintegration of the injured party is attempted. The CEA study emphasizes the fundamental role of medicine in that it postulates a clear division between the role of the attending physician and the medical expert. It also draws attention to the need to train medical professionals in the insurance business to the extent that they can interact adequately with insurance professionals. The results of this study indicate that the usefulness of the criterion of so-called typical clinical symptoms, which is at present applied by the courts to determine natural causality and has long been under debate, is inappropriate and should be replaced by objective assessment (e.g. accident and biomechanical analysis). In addition, the legal concept of adequate causality should be interpreted in the same way in both third party liability and social security law, which is currently not the case.

Short-term results of a randomized trial examining timing of carotid endarterectomy in patients with severe asymptomatic unilateral carotid stenosis undergoing coronary artery bypass grafting.

PubMed

Illuminati, Giulio; Ricco, Jean-Baptiste; Caliò, Francesco; Pacilè, Maria Antonietta; Miraldi, Fabio; Frati, Giacomo; Macrina, Francesco; Toscano, Michele

2011-10-01

This study evaluated the timing of carotid endarterectomy (CEA) in the prevention of stroke in patients with asymptomatic carotid stenosis >70% receiving a coronary artery bypass graft (CABG). From January 2004 to December 2009, 185 patients with unilateral asymptomatic carotid artery stenosis >70%, candidates for CABG, were randomized into two groups. In group A, 94 patients received a CABG with previous or simultaneous CEA. In group B, 91 patients underwent CABG, followed by CEA. All patients underwent preoperative helical computed tomography scans, excluding significant atheroma of the ascending aorta or aortic arch. Baseline characteristics of the patients, type of coronary artery lesion, and preoperative myocardial function were comparable in the two groups. In group A, all patients underwent CEA under general anesthesia with the systematic use of a carotid shunt, and 79 patients had a combined procedure and 15 underwent CEA a few days before CABG. In group B, all patients underwent CEA, 1 to 3 months after CABG, also under general anesthesia and with systematic carotid shunting. Two patients (one in each group) died of cardiac failure in the postoperative period. Operative mortality was 1.0% in group A and 1.1% in group B (P = .98). No strokes occurred in group A vs seven ipsilateral ischemic strokes in group B, including three immediate postoperative strokes and four late strokes, at 39, 50, 58, and 66 days, after CABG. These late strokes occurred in patients for whom CEA was further delayed due to an incomplete sternal wound healing or because of completion of a cardiac rehabilitation program. The 90-day stroke and death rate was 1.0% (one of 94) in group A and 8.8% (eight of 91) in group B (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.01-0.91; P = .02). Logistic regression analysis showed that only delayed CEA (OR, 14.2; 95% CI, 1.32-152.0; P = .03) and duration of cardiopulmonary bypass (OR, 1.06; 95% CI, 1.02-1.11; P = .004) reliably predicted stroke or death at 90 days. This study suggests that previous or simultaneous CEA in patients with unilateral severe asymptomatic carotid stenosis undergoing CABG could prevent stroke better than delayed CEA, without increasing the overall surgical risk. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

μ-Opioid Receptors Selectively Regulate Basal Inhibitory Transmission in the Central Amygdala: Lack of Ethanol Interactions

PubMed Central

Kang-Park, Maeng-Hee; Kieffer, Brigitte L.; Roberts, Amanda J.; Roberto, Marisa; Madamba, Samuel G.; Siggins, George Robert; Moore, Scott D.

2009-01-01

Endogenous opioid systems are implicated in the actions of ethanol. For example, μ-opioid receptor (MOR) knockout (KO) mice self-administer less alcohol than the genetically intact counterpart wild-type (WT) mice (Roberts et al., 2000). MOR KO mice also exhibit less anxiety-like behavior than WT mice (Filliol et al., 2000). To investigate the neurobiological mechanisms underlying these behaviors, we examined the effect of ethanol in brain slices from MOR KO and WT mice using sharp-electrode and whole-cell patch recording techniques. We focused our study in the central nucleus of the amygdala (CeA) because it is implicated in alcohol drinking behavior and stress behavior. We found that the amplitudes of evoked inhibitory postsynaptic currents (IPSCs) or inhibitory postsynaptic potentials (IPSPs) were significantly greater in MOR KO mice than WT mice. In addition, the baseline frequencies of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents were significantly greater in CeA neurons from MOR KO than WT mice. However, ethanol enhancements of evoked IPSP and IPSC amplitudes and the frequency of miniature IPSCs were comparable between WT and MOR KO mice. Baseline spontaneous and miniature excitatory postsynaptic currents (EPSCs) and ethanol effects on EPSCs were not significantly different between MOR KO and WT mice. Based on knowledge of CeA circuitry and projections, we hypothesize that the role of MOR- and GABA receptor-mediated mechanisms in CeA underlying reinforcing effects of ethanol operate independently, possibly through pathway-specific responses within CeA. PMID:18854491

Alchemy to reason: Effective use of Cumulative Effects Assessment in resource management

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hegmann, George, E-mail: george.hegmann@stantec.com; Yarranton, G.A., E-mail: yarran@shaw.ca

2011-09-15

Cumulative Effects Assessment (CEA) is a tool that can be useful in making decisions about natural resource management and allocation. The decisions to be made include those (i) necessary to construct planning and regulatory frameworks to control development activity so that societal goals will be achieved and (ii) whether or not to approve individual development projects, with or without conditions. The evolution of CEA into a more successful tool cannot occur independently of the evolution of decision making processes. Currently progress is painfully slow on both fronts. This paper explores some opportunities to accelerate improvements in decision making in naturalmore » resource management and in the utility of CEA as a tool to assist in making such decisions. The focus of the paper is on how to define the public interest by determining what is acceptable.« less

Rosacea assessment by erythema index and principal component analysis segmentation maps

NASA Astrophysics Data System (ADS)

Kuzmina, Ilona; Rubins, Uldis; Saknite, Inga; Spigulis, Janis

2017-12-01

RGB images of rosacea were analyzed using segmentation maps of principal component analysis (PCA) and erythema index (EI). Areas of segmented clusters were compared to Clinician's Erythema Assessment (CEA) values given by two dermatologists. The results show that visible blood vessels are segmented more precisely on maps of the erythema index and the third principal component (PC3). In many cases, a distribution of clusters on EI and PC3 maps are very similar. Mean values of clusters' areas on these maps show a decrease of the area of blood vessels and erythema and an increase of lighter skin area after the therapy for the patients with diagnosis CEA = 2 on the first visit and CEA=1 on the second visit. This study shows that EI and PC3 maps are more useful than the maps of the first (PC1) and second (PC2) principal components for indicating vascular structures and erythema on the skin of rosacea patients and therapy monitoring.

Dual antiplatelet therapy reduces stroke but increases bleeding at the time of carotid endarterectomy.

PubMed

Jones, Douglas W; Goodney, Philip P; Conrad, Mark F; Nolan, Brian W; Rzucidlo, Eva M; Powell, Richard J; Cronenwett, Jack L; Stone, David H

2016-05-01

Controversy persists regarding the perioperative management of clopidogrel among patients undergoing carotid endarterectomy (CEA). This study examined the effect of preoperative dual antiplatelet therapy (aspirin and clopidogrel) on in-hospital CEA outcomes. Patients undergoing CEA in the Vascular Quality Initiative were analyzed (2003-2014). Patients on clopidogrel and aspirin (dual therapy) were compared with patients taking aspirin alone preoperatively. Study outcomes included reoperation for bleeding and thrombotic complications defined as transient ischemic attack (TIA), stroke, or myocardial infarction. Secondary outcomes were in-hospital death and composite stroke/death. Univariate and multivariable analyses assessed differences in demographics and operative factors. Propensity score-matched cohorts were derived to control for subgroup heterogeneity. Of 28,683 CEAs, 21,624 patients (75%) were on aspirin and 7059 (25%) were on dual therapy. Patients on dual therapy were more likely to have multiple comorbidities, including coronary artery disease (P < .001), congestive heart failure (P < .001), and diabetes (P < .001). Patients on dual therapy were also more likely to have a drain placed (P < .001) and receive protamine during CEA (P < .001). Multivariable analysis showed that dual therapy was independently associated with increased reoperation for bleeding (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20-2.42; P = .003) but was protective against TIA or stroke (OR, 0.61; 95% CI, 0.43-0.87; P = .007), stroke (OR, 0.63; 95% CI, 0.41-0.97; P = .03), and stroke/death (OR, 0.66; 95% CI, 0.44-0.98; P = .04). Propensity score matching yielded two groups of 4548 patients and showed that patients on dual therapy were more likely to require reoperation for bleeding (1.3% vs 0.7%; P = .004) but less likely to suffer TIA or stroke (0.9% vs 1.6%; P = .002), stroke (0.6% vs 1.0%; P = .04), or stroke/death (0.7% vs 1.2%; P = .03). Within the propensity score-matched groups, patients on dual therapy had increased rates of reoperation for bleeding regardless of carotid symptom status. However, asymptomatic patients on dual therapy demonstrated reduced rates of TIA or stroke (0.6% vs 1.5%; P < .001), stroke (0.4% vs 0.9%; P = .01), and composite stroke/death (0.5% vs 1.0%; P = .02). Among propensity score-matched patients with symptomatic carotid disease, these differences were not statistically significant. Preoperative dual antiplatelet therapy was associated with a 40% risk reduction for neurologic events but also incurred a significant increased risk of reoperation for bleeding after CEA. Given its observed overall neurologic protective effect, continued dual antiplatelet therapy throughout the perioperative period is justified. Initiating dual therapy in all patients undergoing CEA may lead to decreased neurologic complication rates. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

SONOlysis in prevention of Brain InfaRctions During Internal carotid Endarterectomy (SONOBIRDIE) trial - study protocol for a randomized controlled trial.

PubMed

Hrbáč, Tomáš; Netuka, David; Beneš, Vladimír; Nosáľ, Vladimír; Kešnerová, Petra; Tomek, Aleš; Fadrná, Táňa; Beneš, Vladimír; Fiedler, Jiří; Přibáň, Vladimír; Brozman, Miroslav; Langová, Kateřina; Herzig, Roman; Školoudík, David

2017-01-17

Carotid endarterectomy (CEA) is a beneficial procedure for selected patients with an internal carotid artery (ICA) stenosis. Surgical risk of CEA varies from between 2 and 15%. The aim of the study is to demonstrate the safety and effectiveness of sonolysis (continual transcranial Doppler monitoring, TCD) using a 2-MHz diagnostic probe with maximal diagnostic energy on the reduction of the incidence of stroke, transient ischemic attack (TIA) and brain infarction detected using magnetic resonance imaging (MRI) by the activation of the endogenous fibrinolytic system during CEA. Design: a multicenter, randomized, double-blind, sham-controlled trial. international, multicenter trial for patients with at least 70% symptomatic or asymptomatic ICA stenosis undergoing CEA. patients with symptomatic or asymptomatic ICA stenosis of at least 70% are candidates for CEA; a sufficient temporal bone window for TCD; aged 40-85 years, functionally independent; provision of signed informed consent. Randomization: consecutive patients will be assigned to the sonolysis or control (sham procedure) group by computer-generated 1:1 randomization. Prestudy calculations showed that a minimum of 704 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10% would be lost to follow-up or refuse to participate in the study (estimated 39 endpoints). the primary endpoint is the incidence of stroke or TIA during 30 days after CEA and the incidence of new ischemic lesions on brain MRI performed 24 h after CEA in the sonolysis and control groups. Secondary endpoints are occurrence of death, any stroke, or myocardial infarction within 30 days, changes in cognitive functions 1 year post procedure related to pretreatment scores, and number of new lesions and occurrence of new lesions ≥0.5 mL on post-procedural brain MRI. descriptive statistics and linear/logistic multiple regression models will be performed. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. Reduction of the periprocedural complications of CEA using sonolysis as a widely available and cheap method may significantly increase the safety of CEA and extend the indication criteria for CEA. ClinicalTrials.gov, NCT02398734 . Registered on 20 March 2015.

In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26.

PubMed

Watanabe, N; Oriuchi, N; Sugiyama, S; Kuroki, M; Matsuoka, Y; Tanada, S; Murata, H; Inoue, T; Sasaki, Y

1999-01-01

The purpose of this study was to assess the potential for radio-immunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 +/- 0.95% vs. 11.9 +/- 0.55% at 100 ng/mL of soluble CEA, 83.5 +/- 2.84% vs. 54.0 +/- 2.54% at 10(7) of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 +/- 3.50% ID/g vs. 14.4 +/- 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 +/- 2.10% ID/g vs. 8.01 +/- 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 +/- 1.70% ID/g vs. 8.10 +/- 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

All-in-one bioprobe devised with hierarchical-ordered magnetic NiCo2O4 superstructure for ultrasensitive dual-readout immunosensor for logic diagnosis of tumor marker.

PubMed

Dai, Hong; Gong, Lingshan; Zhang, Shupei; Xu, Guifang; Li, Yilin; Hong, Zhensheng; Lin, Yanyu

2016-03-15

A new enzyme-free all-in-one bioprobe, consisted of hematin decorated magnetic NiCo2O4 superstructure (ATS-MNS-Hb), was designed for ultrasensitive photoelectrochemical and electrochemical dual-readout immunosensing of carcinoembryonic antigen (CEA) on carbon nanohorns (CNH) support. Herein, the MNS, possessed hierarchical-ordered structure, good porosity and magnetism, acted as nanocarrier to absorb abundant Hb molecular after functionalization, providing a convenient collection means by magnetic control as well as enhanced dual-readout sensing performances. CNH superstructures were employed as support to immobilize abounding captured antibodies, and then as-designed dual mode bioprobe, covalent binding with secondary antibody of CEA, was introduced for ultrasensitive detection of CEA by sandwich immunosensing. Photoelectrochemical response originated from plentiful hematin molecular, a excellent photosensitizer with good visible light harvesting efficiency, absorbed by functionalized porous MNS. The resultant concentration dependant linear calibration range was from 10 fg/mL to 1 ng/mL with ultralow detection limit of 10 fg/mL. For electrochemical process, catalase-like property of MNS was validated, moreover, MNS-Hb hybrid exhibited much higher mimic enzyme catalytic activity and evidently amplified electrocatalytic signal, performing a wide dynamic linear range from 1 ng/mL to 40 ng/mL with low detection limit of 1 ng/mL. Additionally, due to the improved accuracy of dual signals detection, the exact diagnoses of serum samples were gotten by operating resulting dual signals with AND logic system. This work demonstrated the promising application of MNS in developing ultrasensitive, cost-effective and environment friendly dual-readout immunosensor and accurate diagnoses strategy for tumor markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Measurement of Lung Cancer Tumor Markers in a Glass Wool Company Workers Exposed to Respirable Synthetic Vitreous Fiber and Dust.

PubMed

Abtahi, Shabnam; Malekzadeh, Mahyar; Nikravan, Ghafour; Ghaderi, Abbas

2018-01-01

Occupational exposures to respirable synthetic vitreous fiber (SVF) and dust are associated with many lung diseases including lung cancer. Low-dose computed tomography is used for screening patients who are highly suspicious of having lung carcinoma. However, it seems not to be cost-effective. Serum biomarkers could be a useful tool for the surveillance of occupational exposure, by providing the possibility of diagnosing lung cancer in its early stages. To determine if serum carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1 levels in workers exposed more than normal population to respirable SVF and dust may be used as indicators of progression towards lung cancer. An analytic cross-sectional study, including 145 personnel of a glass wool company, along with 25 age-matched healthy individuals, was conducted to investigate the relationship between occupational exposure to respirable SVFs and dust and serum levels of two lung/pleura serum tumor markers, CEA and CYFRA 21-1, measured by ELISA. Individuals exposed to higher than the recommended levels of respirable SVF had higher serum concentrations of CEA and CYFRA 21-1, compared to controls (p=0.008 and 0.040, respectively), as well as in comparison to those exposed to lower than recommended OSHA levels (p=0.046 and 0.033, respectively). Workers with >9 years work experience, had significantly (p=0.045) higher levels of serum CYFRA 21-1 than those with ≤9 years of experience. It seems that working for >9 years in sites with detectable levels of respirable SVF and dust would increase the levels of known lung cancer serum tumor markers. Transferring these workers to sites with respirable SVF concentrations lower than the limit of detection in the air is recommended.

EXAMINING EVIDENCE IN U.S. PAYER COVERAGE POLICIES FOR MULTI-GENE PANELS AND SEQUENCING TESTS

PubMed Central

Chambers, James D.; Saret, Cayla J.; Anderson, Jordan E.; Deverka, Patricia A.; Douglas, Michael P.; Phillips, Kathryn A.

2017-01-01

Objectives The aim of this study was to examine the evidence payers cited in their coverage policies for multi-gene panels and sequencing tests (panels), and to compare these findings with the evidence payers cited in their coverage policies for other types of medical interventions. Methods We used the University of California at San Francisco TRANSPERS Payer Coverage Registry to identify coverage policies for panels issued by five of the largest US private payers. We reviewed each policy and categorized the evidence cited within as: clinical studies, systematic reviews, technology assessments, cost-effectiveness analyses (CEAs), budget impact studies, and clinical guidelines. We compared the evidence cited in these coverage policies for panels with the evidence cited in policies for other intervention types (pharmaceuticals, medical devices, diagnostic tests and imaging, and surgical interventions) as reported in a previous study. Results Fifty-five coverage policies for panels were included. On average, payers cited clinical guidelines in 84 percent of their coverage policies (range, 73–100 percent), clinical studies in 69 percent (50–87 percent), technology assessments 47 percent (33–86 percent), systematic reviews or meta-analyses 31 percent (7–71 percent), and CEAs 5 percent (0–7 percent). No payers cited budget impact studies in their policies. Payers less often cited clinical studies, systematic reviews, technology assessments, and CEAs in their coverage policies for panels than in their policies for other intervention types. Payers cited clinical guidelines in a comparable proportion of policies for panels and other technology types. Conclusions Payers in our sample less often cited clinical studies and other evidence types in their coverage policies for panels than they did in their coverage policies for other types of medical interventions. PMID:29065945

EXAMINING EVIDENCE IN U.S. PAYER COVERAGE POLICIES FOR MULTI-GENE PANELS AND SEQUENCING TESTS.

PubMed

Chambers, James D; Saret, Cayla J; Anderson, Jordan E; Deverka, Patricia A; Douglas, Michael P; Phillips, Kathryn A

2017-01-01

The aim of this study was to examine the evidence payers cited in their coverage policies for multi-gene panels and sequencing tests (panels), and to compare these findings with the evidence payers cited in their coverage policies for other types of medical interventions. We used the University of California at San Francisco TRANSPERS Payer Coverage Registry to identify coverage policies for panels issued by five of the largest US private payers. We reviewed each policy and categorized the evidence cited within as: clinical studies, systematic reviews, technology assessments, cost-effectiveness analyses (CEAs), budget impact studies, and clinical guidelines. We compared the evidence cited in these coverage policies for panels with the evidence cited in policies for other intervention types (pharmaceuticals, medical devices, diagnostic tests and imaging, and surgical interventions) as reported in a previous study. Fifty-five coverage policies for panels were included. On average, payers cited clinical guidelines in 84 percent of their coverage policies (range, 73-100 percent), clinical studies in 69 percent (50-87 percent), technology assessments 47 percent (33-86 percent), systematic reviews or meta-analyses 31 percent (7-71 percent), and CEAs 5 percent (0-7 percent). No payers cited budget impact studies in their policies. Payers less often cited clinical studies, systematic reviews, technology assessments, and CEAs in their coverage policies for panels than in their policies for other intervention types. Payers cited clinical guidelines in a comparable proportion of policies for panels and other technology types. Payers in our sample less often cited clinical studies and other evidence types in their coverage policies for panels than they did in their coverage policies for other types of medical interventions.

Effects of amygdala lesions on overexpectation phenomena in food cup approach and autoshaping procedures.

PubMed

Holland, Peter C

2016-08-01

Prediction error (PE) plays a critical role in most modern theories of associative learning, by determining the effectiveness of conditioned stimuli (CS) or unconditioned stimuli (US). Here, we examined the effects of lesions of central (CeA) or basolateral (BLA) amygdala on performance in overexpectation tasks. In 2 experiments, after 2 CSs were separately paired with the US, they were combined and followed by the same US. In a subsequent test, we observed losses in strength of both CSs, as expected if the negative PE generated on reinforced compound trials encouraged inhibitory learning. CeA lesions, known to interfere with PE-induced enhancements in CS effectiveness, reduced those losses, suggesting that normally the negative PE also enhances cue associability in this task. BLA lesions had no effect. When a novel cue accompanied the reinforced compound, it acquired net conditioned inhibition, despite its consistent pairings with the US, consonant with US effectiveness models. That acquisition was unaffected by either CeA or BLA lesions, suggesting different rules for assignment of credit of changes in cue strength and cue associability. Finally, we examined a puzzling autoshaping phenomenon previously attributed to overexpectation effects. When a previously food-paired auditory cue was combined with the insertion of a lever and paired with the same food US, the auditory cue not only failed to block conditioning to the lever, but also lost strength, as in an overexpectation experiment. This effect was abolished by BLA lesions but unaffected by CeA lesions, suggesting it was unrelated to other overexpectation effects. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effects of amygdala lesions on overexpectation phenomena in food cup approach and autoshaping procedures

PubMed Central

Holland, Peter C.

2016-01-01

Prediction error (PE) plays a critical role in most modern theories of associative learning, by determining the effectiveness of conditioned or unconditioned stimuli (CS or USs). Here, we examined the effects of lesions of central (CeA) or basolateral (BLA) amygdala on performance in overexpectation tasks. In two experiments, after two CSs were separately paired with the US, they were combined and followed by the same US. In a subsequent test, we observed losses in strength of both CSs, as expected if the negative PE generated on reinforced compound trials encouraged inhibitory learning. CeA lesions, known to interfere with PE-induced enhancements in CS effectiveness, reduced those losses, suggesting that normally the negative PE also enhances cue associability in this task. BLA lesions had no effect. When a novel cue accompanied the reinforced compound, it acquired net conditioned inhibition, despite its consistent pairings with the US, consonant with US effectiveness models. That acquisition was unaffected by either CeA or BLA lesions, suggesting different rules for assignment of credit of changes in cue strength and cue associability. Finally, we examined a puzzling autoshaping phenomenon previously attributed to overexpectation effects. When a previously-food-paired auditory cue was combined with the insertion of a lever and paired with the same food US, the auditory cue not only failed to block conditioning to the lever, but also lost strength, as in an overexpectation experiment. This effect was abolished by BLA lesions but unaffected by CeA lesions, suggesting it was unrelated to other overexpectation effects. PMID:27176564

Alternative forms of lethality in mitomycin C-induced bacteria carrying ColE1 plasmids

PubMed Central

Suit, Joan L.; Fan, M.-L. Judy; Sabik, Joseph F.; Labarre, Robert; Luria, S. E.

1983-01-01

We have studied the physiological effects of mitomycin C induction on cells carrying ColE1 plasmids with differing configurations of three genes: the structural gene coding for colicin (cea), a gene responsible for mitomycin C lethality (kil) that we located as part of an operon with cea, and the immunity (imm) gene, which lies near cea but is not in the same operon. kil is close to or overlaps imm. When cea+ plasmids are present mitomycin C induction results in 100-fold or greater increases in the level of colicin. Within an hour after induction more than 90% of cells carrying cea+kil+ plasmids are killed and macromolecular synthesis stops, capacity for transport of proline, thiomethyl β-D-galactoside, and α-methyl glucoside is lost, and the membrane becomes abnormally permeable as indicated by an increased accessibility of intracellular β-galactosidase to the substrate o-nitrophenyl β-D-galactoside. All of these events occur when a cea-kil+imm+ plasmid is present and none does when the plasmid is cea+kil-imm+, so the damage can be attributed solely to the Kil function and not to the presence of colicin. However, cells carrying a cea+kil-imm- plasmid are killed upon induction, apparently by action of endogenous colicin on the nonimmune cytoplasmic membrane. The pattern of accompanying physiological damage is distinguished from the kil+-associated damage by an enhancement of α-methyl glucoside uptake and accumulation and efflux of α-methyl glucoside 6-phosphate and by an absence of the alteration in membrane permeability for o-nitrophenyl β-D-galactoside. These features are typical of colicin E1 action on the membrane. The induced damage is not prevented by trypsin and occurs in cells of a strain specifically tolerant to exogenous colicin E1, indicating that the attack is from inside the cell. PMID:6403939

Serum CEA levels in patients with gastric carcinoma correlate with the tumorigenicity of their xenografts in nude mice.

PubMed

Kiyama, T; Onda, M; Tokunaga, A; Okuda, T; Mizutani, T; Yoshiyuki, T; Shimizu, Y; Nishi, K; Matsukura, N; Tanaka, N

1991-01-01

We examined the correlation among preoperative serum carcinoembryonic antigen (CEA) levels, staining properties of the tumors by CEA immunohistochemistry and the tumorigenicity of their xenografts in nude mice, in 28 patients with gastric cancer. Eleven (40 per cent) of them were positive for serum CEA (greater than or equal to 2.5 ng/ml) and seven (25 per cent) of the xenografts were tumorigenic in nude mice. All the tumorigenic cases were positive for serum CEA (p less than 0.001) and the mean value of the serum CEA level in the patients with tumorigenic neoplasms was 20.8 ng/ml, being significantly higher than that (1.4 ng/ml) in the patients with non-tumorigenic neoplasms (p less than 0.001). Twenty-five of the 28 carcinomas (89 per cent) were positive for CEA staining in their cancer cells by the ABC method and CEA localization correlated with tumorigenicity (p less than 0.05). These results suggest that the serum CEA level in patients is correlated with the tumorigenicity of their gastric carcinoma xenografts in nude mice and may account for the poor prognosis of patients with high serum CEA.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Clinically Relevant Reduction in Persistent Facial Erythema of Rosacea on the First Day of Treatment With Oxymetazoline Cream 1.0.

PubMed

Tanghetti, Emil A; Dover, Jeffrey S; Goldberg, David J; Dhawan, Sunil S; Luo, Lei; Berk, David R; Ahluwalia, Gurpreet; Alvandi, Nancy

2018-06-01

Persistent facial erythema is a clinically challenging feature of rosacea. To evaluate persistent erythema reduction on the first day of treatment from pooled data from two pivotal trials of topical oxymetazoline cream 1.0% (oxymetazoline) in persistent facial erythema of rosacea. In two identically designed, phase 3, multicenter trials, adults with moderate to severe persistent facial erythema of rosacea (Clinician Erythema Assessment [CEA] grade ≥3 and Subject Self-Assessment [SSA] grade ≥3) were randomized 1:1 to once-daily topical oxymetazoline or vehicle; the primary efficacy endpoint was ≥2-grade composite CEA and SSA improvement from baseline on day 29. This post hoc analysis evaluated the proportion of patients achieving ≥1-grade composite and individual CEA and SSA improvement at 1, 3, 6, 9, and 12 hours postdose on day 1 (N=885). Significantly more patients achieved ≥1-grade composite and individual CEA and SSA improvement with the first application of oxymetazoline than with vehicle (P less than 0.001) at all postdose time points, beginning with hour 1. Day 1 safety assessments were similar between treatments. Short-term, post hoc analysis. A ≥1-grade improvement in persistent erythema achieved after the first dose of once-daily topical oxymetazoline demonstrated clinically meaningful improvement from the beginning of therapy. J Drugs Dermatol. 2018;17(6):621-626.

Accuracy of administrative data versus clinical data to evaluate carotid endarterectomy and carotid stenting

PubMed Central

Bensley, Rodney P; Yoshida, Shunsuke; Lo, Ruby C; Fokkema, Margriet; Hamdan, Allen D; Wyers, Mark C; Chaikof, Elliot L; Schermerhorn, Marc L

2013-01-01

Objectives Administrative data have been used to compare carotid endarterectomy (CEA) and carotid artery stenting (CAS). However, there are limitations in defining symptom status, CMS high-risk status, as well as complications. Therefore, we did a direct comparison between administrative data and physician chart review as well as between data collected for the National Surgical Quality Improvement Program (NSQIP) and physician chart review for CEA and CAS. Methods We performed an outcomes analysis on all CEA and CAS procedures from 2005–2011. We obtained ICD-9 diagnosis codes from hospital discharge records regarding symptom status, high-risk status, and perioperative stroke. We also obtained data on all CEA patients submitted to NSQIP over the same time period. A physician then performed a chart review of the same patients to determine symptom status, high-risk status, and perioperative strokes and the results were compared. Results We identified 1342 patients who underwent CEA or CAS between 2005–2011 and 392 patients who underwent CEA that were submitted to NSQIP. Administrative data identified fewer symptomatic patients (17.0% vs. 34.0%), fewer physiologic high-risk patients (9.3% vs. 23.0%), fewer anatomic high-risk patients (0% vs. 15.2%), and a similar proportion of perioperative strokes (1.9% vs. 2.0%). However, administrative data identified 8 false positive and 9 false negative perioperative strokes. NSQIP data identified more symptomatic patients compared to chart review (44.1% vs. 30.3%), fewer physiologic high-risk patients (13.0% vs. 18.6%), fewer anatomic high-risk patients (0% vs. 6.6%), and a similar proportion of perioperative strokes (1.5% vs. 1.8%, only 1 false negative stroke and no false positives). Conclusions Administrative data are unreliable for determining symptom status, high-risk status, and perioperative stroke and should not be used to analyze CEA and CAS. NSQIP data do not adequately identify high-risk patients, but do accurately identify perioperative strokes and to a lesser degree, symptom status. PMID:23490294

Standard duplex criteria overestimate the degree of stenosis after eversion carotid endarterectomy.

PubMed

Benzing, Travis; Wilhoit, Cameron; Wright, Sharee; McCann, P Aaron; Lessner, Susan; Brothers, Thomas E

2015-06-01

The eversion technique for carotid endarterectomy (eCEA) offers an alternative to longitudinal arteriotomy and patch closure (pCEA) for open carotid revascularization. In some reports, eCEA has been associated with a higher rate of >50% restenosis of the internal carotid when it is defined as peak systolic velocity (PSV) >125 cm/s by duplex imaging. Because the conformation of the carotid bifurcation may differ after eCEA compared with native carotid arteries, it was hypothesized that standard duplex criteria might not accurately reflect the presence of restenosis after eCEA. In a case-control study, the outcomes of all patients undergoing carotid endarterectomy by one surgeon during the last 10 years were analyzed retrospectively, with a primary end point of PSV >125 cm/s. Duplex flow velocities were compared with luminal diameter measurements for any carotid computed tomography arteriography or magnetic resonance angiography study obtained within 2 months of duplex imaging, with the degree of stenosis calculated by the methodology used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) as well as cross-sectional area (CSA) reduction. Simulations were generated and analyzed by computational model simulations of the eCEA and pCEA arteries. Eversion and longitudinal arteriotomy with patch techniques were used in 118 and 177 carotid arteries, respectively. Duplex follow-up was available in 90 eCEA arteries at a median of 16 (range, 2-136) months and in 150 pCEA arteries at a median of 41 (range, 3-115) months postoperatively. PSV >125 cm/s was present at some time during follow-up in 31% of eCEA and pCEA carotid arteries, each, and in the most recent duplex examination in 7% after eCEA and 21% after pCEA (P = .003), with no eCEA and two pCEA arteries occluding completely during follow-up (P = .29). In 19 carotid arteries with PSV >125 cm/s after angle correction (median, 160 cm/s; interquartile range, 146-432 cm/s) after eCEA that were subsequently examined by axial imaging, the mean percentage stenosis was 8% ± 11% by NASCET, 11% ± 5% by ECST, and 20% ± 9% by CSA criteria. For eight pCEA arteries with PSV >125 cm/s (median velocity, 148 cm/s; interquartile range, 139-242 cm/s), the corresponding NASCET, ECST, and CSA stenoses were 8% ± 35%, 26% ± 32%, and 25% ± 33%, respectively. NASCET internal carotid diameter reduction of at least 50% was noted by axial imaging after two of the eight pCEAs, and the PSV exceeded 200 cm/s in each case. The presence of hemodynamically significant carotid artery restenosis may be overestimated by standard duplex criteria after eCEA and perhaps after pCEA. Insufficient information currently exists to determine what PSV does correspond to hemodynamically significant restenosis. Published by Elsevier Inc.

Enhanced peroxidase-like properties of Au@Pt DNs/NG/Cu2+ and application of sandwich-type electrochemical immunosensor for highly sensitive detection of CEA.

PubMed

Lv, Hui; Li, Yueyun; Zhang, Xiaobo; Gao, Zengqiang; Zhang, Chunyan; Zhang, Shuan; Dong, Yunhui

2018-07-30

Effective treatment of cancer depends upon the early detection of the tumor marker. Here, we report on the development of a new immunosensor for early detection of carcinoembryonic antigen (CEA). Cubic Au@Pt dendritic nanomaterials functionalized nitrogen-doped graphene loaded with copper ion (Au@Pt DNs/NG/Cu 2+ ) with enhanced peroxidase-like properties was synthesized as labels to effectively capture and immobilize secondary anti-CEA. The Au@Pt DNs with more active surface area could efficiently enhance electrocatalysis for reduction of hydrogen peroxide (H 2 O 2 ). Meanwhile, with good conductivity and large specific surface area, NG can immobilize a large amount of Au@Pt DNs. Furthermore, after adsorbed Cu 2+ can further promote the redox of H 2 O 2 and amplify the signal of the immunosensor. For the immobilization of primary antibodies, Au nanoparticles functionalized polydopamine (Au@PDA) were used as transducing materials to modify glassy carbon electrodes and enhance the electron transfer efficiently. Under optimal conditions, the immunosensor exhibited a satisfactory response to CEA with a limit detection of 0.167 pg/mL and linear detection range from 0.5 pg/mL to 50 ng/mL. Based on the high sensitivity and specificity of the immunosensor, we propose this multiple amplified biosensor for early detection of CEA. Copyright © 2018 Elsevier B.V. All rights reserved.

Esophagitis with eosinophil infiltration associated with congenital esophageal atresia and stenosis.

PubMed

Yamada, Yoshiyuki; Nishi, Akira; Kato, Masahiko; Toki, Fumiaki; Yamamoto, Hideki; Suzuki, Norio; Hirato, Junko; Hayashi, Yasuhide

2013-01-01

The esophagus is physiologically devoid of eosinophils, so their presence would suggest some underlying pathology. The prevalence of eosinophilic esophagitis (EoE) has steadily increased in Western countries. Previous studies have described EoE in association with congenital esophageal atresia (CEA), which is the most common congenital anomaly of the esophagus. However, the association remains unclear. We performed a retrospective histological analysis examining for eosinophil infiltration in the esophagus of patients with CEA following surgical repair or congenital esophageal stenosis (CES) who underwent esophageal biopsy or surgical resection in our hospital between 2005 and 2012. There were 6 patients with CEA following surgical repair or CES who had eosinophil-dominant infiltration in the esophagus. All had associated allergic disorders, including food allergies in 4. Moreover, all except for one fulfilled the histological criteria of EoE. Impairment of eosinophil infiltration and symptomatic improvement were observed in those treated with a proton pump inhibitor (PPI), either alone or in combination with steroids after esophageal dilatation. These findings suggest that CEA repair or CES in conjunction with allergic conditions and coexisting gastroesophageal reflux disease (GERD) may induce greater esophageal eosinophilic inflammation. In addition, esophageal dilatation followed by PPI treatment, alone or with steroids, may be a therapeutic strategy that can provide symptomatic relief by reducing eosinophilic inflammation in esophageal strictures or GERD associated with CEA or CES. Copyright © 2013 S. Karger AG, Basel.

Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress.

PubMed

Lee, Myung Gwon; Shin, Joong Ho; Bae, Chae Yun; Choi, Sungyoung; Park, Je-Kyun

2013-07-02

We report a contraction-expansion array (CEA) microchannel device that performs label-free high-throughput separation of cancer cells from whole blood at low Reynolds number (Re). The CEA microfluidic device utilizes hydrodynamic field effect for cancer cell separation, two kinds of inertial effects: (1) inertial lift force and (2) Dean flow, which results in label-free size-based separation with high throughput. To avoid cell damages potentially caused by high shear stress in conventional inertial separation techniques, the CEA microfluidic device isolates the cells with low operational Re, maintaining high-throughput separation, using nondiluted whole blood samples (hematocrit ~45%). We characterized inertial particle migration and investigated the migration of blood cells and various cancer cells (MCF-7, SK-BR-3, and HCC70) in the CEA microchannel. The separation of cancer cells from whole blood was demonstrated with a cancer cell recovery rate of 99.1%, a blood cell rejection ratio of 88.9%, and a throughput of 1.1 × 10(8) cells/min. In addition, the blood cell rejection ratio was further improved to 97.3% by a two-step filtration process with two devices connected in series.

Terahertz Real-Time Imaging Uncooled Arrays Based on Antenna-Coupled Bolometers or FET Developed at CEA-Leti

NASA Astrophysics Data System (ADS)

Simoens, François; Meilhan, Jérôme; Nicolas, Jean-Alain

2015-10-01

Sensitive and large-format terahertz focal plane arrays (FPAs) integrated in compact and hand-held cameras that deliver real-time terahertz (THz) imaging are required for many application fields, such as non-destructive testing (NDT), security, quality control of food, and agricultural products industry. Two technologies of uncooled THz arrays that are being studied at CEA-Leti, i.e., bolometer and complementary metal oxide semiconductor (CMOS) field effect transistors (FET), are able to meet these requirements. This paper reminds the followed technological approaches and focuses on the latest modeling and performance analysis. The capabilities of application of these arrays to NDT and security are then demonstrated with experimental tests. In particular, high technological maturity of the THz bolometer camera is illustrated with fast scanning of large field of view of opaque scenes achieved in a complete body scanner prototype.

Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis).

PubMed

Bagaria, Bhawna; Sood, Sadhna; Sharma, Rameshwaram; Lalwani, Soniya

2013-09-01

To determine the clinical serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic (ROC) curves were plotted. Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined: in esophageal cancer, sensitivity=28%, negative predictive value (NPV)=61.72%, and AUC=0.742 
(SE=0.05), with a significance level of P<0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 (SE=0.05), with a significance level of P<0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 
(SE=0.04), with a significance level of P<0.0001. The sensitivity of CA19-9 was also evaluated: in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 (SE =0.05), with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 (SE =0.05), with a significance level of P<0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.580 (SE =0.05), with a significance level of P=0.1670. The following were the sensitivities of CEA/CA19-9 combined: in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 (95% CI: 0.0159-0.322); gastric cancer, sensitivity=58%, NPV=70.42%, SE=0.072 (95% CI: -0.0866-0.198); and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 (95% CI: 0.137-0.415). CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

Evaluation of the CEAS trend and monthly weather data models for soybean yields in Iowa, Illinois, and Indiana

NASA Technical Reports Server (NTRS)

French, V. (Principal Investigator)

1982-01-01

The CEAS models evaluated use historic trend and meteorological and agroclimatic variables to forecast soybean yields in Iowa, Illinois, and Indiana. Indicators of yield reliability and current measures of modeled yield reliability were obtained from bootstrap tests on the end of season models. Indicators of yield reliability show that the state models are consistently better than the crop reporting district (CRD) models. One CRD model is especially poor. At the state level, the bias of each model is less than one half quintal/hectare. The standard deviation is between one and two quintals/hectare. The models are adequate in terms of coverage and are to a certain extent consistent with scientific knowledge. Timely yield estimates can be made during the growing season using truncated models. The models are easy to understand and use and are not costly to operate. Other than the specification of values used to determine evapotranspiration, the models are objective. Because the method of variable selection used in the model development is adequately documented, no evaluation can be made of the objectivity and cost of redevelopment of the model.

Rimonabant Precipitates Anxiety in Rats Withdrawn from Palatable Food: Role of the Central Amygdala

PubMed Central

Blasio, Angelo; Iemolo, Attilio; Sabino, Valentina; Petrosino, Stefania; Steardo, Luca; Rice, Kenner C; Orlando, Pierangelo; Iannotti, Fabio Arturo; Di Marzo, Vincenzo; Zorrilla, Eric P; Cottone, Pietro

2013-01-01

The anti-obesity medication rimonabant, an antagonist of cannabinoid type-1 (CB1) receptor, was withdrawn from the market because of adverse psychiatric side effects, including a negative affective state. We investigated whether rimonabant precipitates a negative emotional state in rats withdrawn from palatable food cycling. The effects of systemic administration of rimonabant on anxiety-like behavior, food intake, body weight, and adrenocortical activation were assessed in female rats during withdrawal from chronic palatable diet cycling. The levels of the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), and the CB1 receptor mRNA and the protein in the central nucleus of the amygdala (CeA) were also investigated. Finally, the effects of microinfusion of rimonabant in the CeA on anxiety-like behavior, and food intake were assessed. Systemic administration of rimonabant precipitated anxiety-like behavior and anorexia of the regular chow diet in rats withdrawn from palatable diet cycling, independently from the degree of adrenocortical activation. These behavioral observations were accompanied by increased 2-AG, CB1 receptor mRNA, and protein levels selectively in the CeA. Finally, rimonabant, microinfused directly into the CeA, precipitated anxiety-like behavior and anorexia. Our data show that (i) the 2-AG-CB1 receptor system within the CeA is recruited during abstinence from palatable diet cycling as a compensatory mechanism to dampen anxiety, and (ii) rimonabant precipitates a negative emotional state by blocking the beneficial heightened 2-AG-CB1 receptor signaling in this brain area. These findings help elucidate the link between compulsive eating and anxiety, and it will be valuable to develop better pharmacological treatments for eating disorders and obesity. PMID:23793355

Glucose oxidase-initiated cascade catalysis for sensitive impedimetric aptasensor based on metal-organic frameworks functionalized with Pt nanoparticles and hemin/G-quadruplex as mimicking peroxidases.

PubMed

Zhou, Xingxing; Guo, Shijing; Gao, Jiaxi; Zhao, Jianmin; Xue, Shuyan; Xu, Wenju

2017-12-15

Based on cascade catalysis amplification driven by glucose oxidase (GOx), a sensitive electrochemical impedimetric aptasensor for protein (carcinoembryonic antigen, CEA as tested model) was proposed by using Cu-based metal-organic frameworks functionalized with Pt nanoparticles, aptamer, hemin and GOx (Pt@CuMOFs-hGq-GOx). CEA aptamer loaded onto Pt@CuMOFs was bound with hemin to form hemin@G-quadruplex (hGq) with mimicking peroxidase activity. Through sandwich-type reaction of target CEA and CEA aptamers (Apt1 and Apt2), the obtained Pt@CuMOFs-hGq-GOx as signal transduction probes (STPs) was captured to the modified electrode interface. When 3,3-diaminobenzidine (DAB) and glucose were introduced, the cascade reaction was initiated by GOx to catalyze the oxidation of glucose, in situ generating H 2 O 2 . Simultaneously, the decomposition of the generated H 2 O 2 was greatly promoted by Pt@CuMOFs and hGq as synergistic peroxide catalysts, accompanying with the significant oxidation process of DAB and the formation of nonconductive insoluble precipitates (IPs). As a result, the electron transfer in the resultant sensing interface was effectively hindered and the electrochemical impedimetric signal (EIS) was efficiently amplified. Thus, the high sensitivity of the proposed CEA aptasensor was successfully improved with 0.023pgmL -1 , which may be promising and potential in assaying certain clinical disease related to CEA. Copyright © 2017 Elsevier B.V. All rights reserved.

Label-free fluorimetric detection of CEA using carbon dots derived from tomato juice.

PubMed

Miao, Hong; Wang, Lan; Zhuo, Yan; Zhou, Zinan; Yang, Xiaoming

2016-12-15

A facile-green strategy to synthesize carbon dots (CDs) with a quantum yield (QY) of nearly 13.9% has been built up, while tomato juice served as the carbon source. Interestingly, not only the precursor of CDs and the whole synthesis procedure were environmental-friendly, but this type of CDs also exhibited multiple advantages including high fluorescent QY, excellent photostability, non-toxicity and satisfactory stability. Significantly, a label-free sensitive assay for detecting carcinoembryonic antigen (CEA) in a continuous and recyclable way has been proposed on the basis of adsorption and desorption of aptamers by the surface of CDs through a competitive mechanism. To be specific, the richness of carboxyl groups of the CDs enabled strong adsorption of ssDNA to the surface of CDs through π-π stacking interactions, resulting in the effective fluorescence quenching by forming CDs-aptamer complexes. The stronger binding affinity between CEA and CEA-aptamer than the π-π stacking interactions has been taken advantage to achieve immediate recovery of the fluorescence of CDs once CEA was introduced. Thereby, quantitative evaluation of CEA concentration in a broad range from 1ngmL(-1) to 0.5ngmL(-1) with the detection limit of 0.3ngmL(-1) was realized in this way. This strategy can be applied in a recyclable way, broadening the sensing application of CDs with biocompatibility. Besides, the CDs were used for cell imaging, potentiating them towards diverse purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

Neem leaf glycoprotein enhances carcinoembryonic antigen presentation of dendritic cells to T and B cells for induction of anti-tumor immunity by allowing generation of immune effector/memory response.

PubMed

Sarkar, Koustav; Goswami, Shyamal; Roy, Soumyabrata; Mallick, Atanu; Chakraborty, Krishnendu; Bose, Anamika; Baral, Rathindranath

2010-08-01

Vaccination with neem leaf glycoprotein matured carcinoembryonic antigen (CEA) pulsed dendritic cells (DCs) enhances antigen-specific humoral and cellular immunity against CEA and restricts the growth of CEA(+) murine tumors. NLGP helps better CEA uptake, processing and presentation to T/B cells. This vaccination (DCNLGPCEA) elicits mitogen induced and CEA specific T cell proliferation, IFN gamma secretion and induces specific cytotoxic reactions to CEA(+) colon tumor cells. In addition to T cell response, DCNLGPCEA vaccine generates anti-CEA antibody response, which is principally IgG2a in nature. This antibody participates in cytotoxicity of CEA(+) cells in antibody-dependent manner. This strong anti-CEA cellular and humoral immunity protects mice from tumor development and these mice remained tumor free following second tumor inoculation, indicating generation of effector memory response. Evaluation of underlying mechanism suggests vaccination generates strong CEA specific CTL and antibody response that can completely prevent the tumor growth following adoptive transfer. In support, significant upregulation of CD44 on the surface of lymphocytes from DCNLGPCEA immunized mice was noticed with a substantial reduction in L-selectin (CD62L). (c) 2010 Elsevier B.V. All rights reserved.

The cost-effectiveness of enzyme replacement therapy (ERT) for the infantile form of Pompe disease: comparing a high-income country's approach (England) to that of a middle-income one (Colombia).

PubMed

Castro-Jaramillo, Héctor E

2012-01-01

Determining the cost-effectiveness of enzyme replacement therapy (ERT) for the classical infantile form of Pompe disease (complete acid a-glucosidase deficiency-related) in two different settings: England and Colombia. Pompe disease is very rare (1:40,000 births incidence). A literature review was made and historic databases searched for National Health Service (NHS) reimbursed costs in England and by health insurers in Colombia; expert opinion was elicited. Two Markov models were constructed for comparing both countries; alive with symptoms and dead were the transition states used. Patients aged < 6 months receiving ERT were assumed to have 75 % survival rate and better health-related quality of life (HR-QoL) compared to those without treatment (0.700 HR- QoL using the EQ-5D scale). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was £234,307.7 for England and £109,991 for Colombia. Uncertainty about Anal HR-QoL with ERT, disease progression and cost from palliative care had the biggest impact on the ICER in both models. If ERT costs were reduced to 10,000 times per dose and HR-QoL was 0.750-0.820 ICER, then £165,000 could be attainable for England and £65,000 for Colombia. Transaction costs per case in Colombia were high. ERT was more effective than no ERT in treating infantile Pompe disease, but high levels of uncertainty still remain about survival and progression rates and QoL in the long-run. ICERs were high compared to CE thresholds. Manufacturers' ERT costs and monopoly had a major impact on Anal CEA results.

A dye-sensitized solar cell acting as the electrical reading box of an immunosensor: Application to CEA determination.

PubMed

Truta, Liliana A A N A; Moreira, Felismina T C; Sales, M Goreti F

2018-06-01

Monitoring cancer biomarkers in biological fluids has become a key tool for disease diagnosis, which should be of easy access anywhere in the world. The possibility of reducing basic requirements in the field of electrochemical biosensing may open doors in this direction. This work proposes for this purpose an innovative electrochemical immunosensing system using a photovoltaic cell as an electrical reading box. Immunosensing ensures accuracy, the electrochemical-ground of the device ensures sensitivity and detectability, and the photovoltaic cell drives the system towards electrical autonomy. As proof-of-concept, Carcinoembryonic antigen (CEA) was used herein, a cancer biomarker of clinical relevance. In brief, a conductive glass with a fluorine doped tin oxide film was used as conductive support and modified with anti-CEA by means of a bottom-up approach. All stages involved in the biochemical modification of the FTO surface were followed by electrochemical techniques, namely electrochemical impedance spectroscopy and cyclic voltammetry. This electrode acted as counter electrode of a dye-sensitized solar cells, and the electrical output of this cell was monitored for the different concentrations of CEA. Under optimized conditions, the device displayed a linear behaviour against CEA concentration, from 5 pg/mL to 15 ng/mL. The immunosensor was applied to the analysis of CEA in urine from healthy individual and spiked with the antigen. Overall, the presented approach demonstrates that photovoltaic cells may be employed as an electrical reading box of electrochemical biosensors, yielding a new direction towards autonomous electrochemical biosensing. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Concordance of Carcinoembryonic Antigen Ratio and Response Evaluation Criteria in Solid Tumors as Prognostic Surrogate Indicators of Metastatic Colorectal Cancer Patients Treated with Chemotherapy.

PubMed

Huang, Sheng-Chieh; Lin, Jen-Kou; Lin, Tzu-Chen; Chen, Wei-Shone; Yang, Shung-Haur; Wang, Huann-Sheng; Lan, Yuan-Tzu; Lin, Chun-Chi; Jiang, Jeng-Kai; Chang, Shih-Ching

2015-07-01

Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. The CEA ratio was significantly correlated with different chemotherapy regimens (p < 0.001), pre-treatment CEA level (p < 0.001), lymphovascular invasion (p = 0.006), and tumor differentiation (p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival (p < 0.001). These two methods for evaluating treatment response were highly correlated (p < 0.001). CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings.

Mitral Valve Clip for Treatment of Mitral Regurgitation: An Evidence-Based Analysis

PubMed Central

Ansari, Mohammed T.; Ahmadzai, Nadera; Coyle, Kathryn; Coyle, Doug; Moher, David

2015-01-01

Background Many of the 500,000 North American patients with chronic mitral regurgitation may be poor candidates for mitral valve surgery. Objective The objective of this study was to investigate the comparative effectiveness, harms, and cost-effectiveness of percutaneous mitral valve repair using mitral valve clips in candidates at prohibitive risk for surgery. Data Sources We searched articles in MEDLINE, Embase, and the Cochrane Library published from 1994 to February 2014 for evidence of effectiveness and harms; for economic literature we also searched NHS EED and Tufts CEA registry. Grey literature was also searched. Review Methods Primary studies were sought from existing systematic reviews that had employed reliable search and screening methods. Newer studies were sought by searching the period subsequent to the last search date of the review. Two reviewers screened records and assessed study validity. We used the Cochrane risk of bias tool for randomized, generic assessment for non-randomized studies, and the Phillips checklist for economic studies. Results Ten studies including 1 randomized trial were included. The majority of the direct comparative evidence compared the mitral valve clip repair with surgery in patients not particularly at prohibitive surgical risk. Irrespective of degenerative or functional chronic mitral regurgitation etiology, evidence of effectiveness and harms is inconclusive and of very low quality. Very-low-quality evidence indicates that percutaneous mitral valve clip repair may provide a survival advantage, at least during the first 1 to 2 years, particularly in medically managed chronic functional mitral regurgitation. Because of limitations in the design of studies, the cost-effectiveness of mitral valve clips in patients at prohibitive risk for surgery also could not be established. Limitations Because of serious concerns of risk of bias, indirectness, and imprecision, evidence is of very low quality. Conclusions No meaningful conclusions can be drawn about the comparative effectiveness, harms, and cost-effectiveness of mitral valve clips in the population with chronic mitral regurgitation who are at prohibitive risk for surgery. PMID:26379810

Carcinoembryonic antigen (CEA) levels in hookah smokers, cigarette smokers and non-smokers.

PubMed

Sajid, Khan Mohammad; Parveen, Riffat; Durr-e-Sabih; Chaouachi, Kamal; Naeem, Ayisha; Mahmood, Rubaida; Shamim, Rahat

2007-12-01

To find CEA levels in smokers of different categories (hookah smokers, cigarette smokers smoking different brands of cigarettes and different number of cigarettes per day) and to correlate CEA levels with type and rate of smoking. A total of 122 cigarette smokers (115 men and 7 women) and 14 hookah smokers (all men) with age ranging from 16-80 years were studied. CEA levels were also measured in 36 non-smokers who served as controls. Enhanced chemilumiscent immunometeric technique was applied to measure CEA levels in our subjects. The mean CEA levels of cigarette smokers were compared with the mean CEA levels observed in hookah smokers (7.16 +/- 10.4 ng/ml) and non-smokers (2.15 +/- 0.68 ng/ml). The mean value of CEA level observed in cigarette smokers, 9.19 +/- 14.9 ng/ml (n=122) was significantly higher than the levels in non-smokers and hookah smokers (p < 0.0067). It was also observed that CEA levels increased with the number of cigarettes smoked per day. The highest levels were observed in smokers who smoke more than 31 cigarettes per day. The smokers that use relatively cheaper brands of cigarettes had higher levels of CEA compared to those who use high quality brands. It was concluded that the brands of cigarettes (which were ranked on the basis of price) and the rate of smoking both play an important role in raising the CEA levels. Further the common belief that hookah also called narghile or shisha is a relatively safe mode of smoking is not completely correct; a significant proportion of hookah smokers have high levels of CEA although mean levels of hookah smokers were low compared to cigarette smokers.

Protocol for the economic evaluation of a complex intervention to improve the mental health of maltreated infants and children in foster care in the UK (The BeST? services trial).

PubMed

Deidda, Manuela; Boyd, Kathleen Anne; Minnis, Helen; Donaldson, Julia; Brown, Kevin; Boyer, Nicole R S; McIntosh, Emma

2018-03-14

Children who have experienced abuse and neglect are at increased risk of mental and physical health problems throughout life. This places an enormous burden on individuals, families and society in terms of health services, education, social care and judiciary sectors. Evidence suggests that early intervention can mitigate the negative consequences of child maltreatment, exerting long-term positive effects on the health of maltreated children entering foster care. However, evidence on cost-effectiveness of such complex interventions is limited. This protocol describes the first economic evaluation of its kind in the UK. An economic evaluation alongside the Best Services Trial (BeST?) has been prospectively designed to identify, measure and value key resource and outcome impacts arising from the New Orleans intervention model (NIM) (an infant mental health service) compared with case management (CM) (enhanced social work services as usual). A within-trial economic evaluation and long-term model from a National Health Service/Personal Social Service and a broader societal perspective will be undertaken alongside the National Institute for Health Research (NIHR)-Public Health Research Unit (PHRU)-funded randomised multicentre BeST?. BeST? aims to evaluate NIM compared with CM for maltreated children entering foster care in a UK context. Collection of Paediatric Quality of Life Inventory (PedsQL) and the recent mapping of PedsQL to EuroQol-5-Dimensions (EQ-5D) will facilitate the estimation of quality-adjusted life years specific to the infant population for a cost-utility analysis. Other effectiveness outcomes will be incorporated into a cost-effectiveness analysis (CEA) and cost-consequences analysis (CCA). A long-term economic model and multiple economic evaluation frameworks will provide decision-makers with a comprehensive, multiperspective guide regarding cost-effectiveness of NIM. The long-term population health economic model will be developed to synthesise trial data with routine linked data and key government sector parameters informed by literature. Methods guidance for population health economic evaluation will be adopted (lifetime horizon, 1.5% discount rate for costs and benefits, CCA framework, multisector perspective). Ethics approval was obtained by the West of Scotland Ethics Committee. Results of the main trial and economic evaluation will be submitted for publication in a peer-reviewed journal as well as published in the peer-reviewed NIHR journals library (Public Health Research Programme). NCT02653716; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Multispecies breath analysis faster than a single respiratory cycle by optical-feedback cavity-enhanced absorption spectroscopy

NASA Astrophysics Data System (ADS)

Ventrillard-Courtillot, Irene; Gonthiez, Thierry; Clerici, Christine; Romanini, Daniel

2009-11-01

We demonstrate a first application, of optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) to breath analysis in a medical environment. Noninvasive monitoring of trace species in exhaled air was performed simultaneous to spirometric measurements on patients at Bichat Hospital (Paris). The high selectivity of the OF-CEAS spectrometer and a time response of 0.3 s (limited by sample flow rate) allowed following the evolution of carbon monoxide and methane concentrations during individual respiratory cycles, and resolving variations among different ventilatory patterns. The minimum detectable absorption on this time scale is about 3×10-10 cm-1. At the working wavelength of the instrument (2.326 μm), this translates to concentration detection limits of ~1 ppbv (45 picomolar, or ~1.25 μg/m3) for CO and 25 ppbv for CH4, well below concentration values found in exhaled air. This same instrument is also able to provide measurement of NH3 concentrations with a detection limit of ~10 ppbv however, at present, memory effects do not allow its measurement on fast time scales.

Resource utilisation and costs in predementia and dementia: a systematic review protocol

PubMed Central

Landeiro, Filipa; Wace, Helena; Ghinai, Isaac; Nye, Elsbeth; Mughal, Seher; Walsh, Katie; Roberts, Nia; Lecomte, Pascal; Wittenberg, Raphael; Wolstenholme, Jane; Handels, Ron; Roncancio-Diaz, Emilse; Potashman, Michele H; Tockhorn-Heidenreich, Antje; Gray, Alastair M

2018-01-01

Introduction Dementia is the fastest growing major cause of disability globally with a mounting social and financial impact for patients and their families but also to health and social care systems. This review aims to systematically synthesise evidence on the utilisation of resources and costs incurred by patients and their caregivers and by health and social care services across the full spectrum of dementia, from its preceding preclinical stage to end of life. The main drivers of resources used and costs will also be identified. Methods and analysis A systematic literature review was conducted in MEDLINE, EMBASE, CDSR, CENTRAL, DARE, EconLit, CEA Registry, TRIP, NHS EED, SCI, RePEc and OpenGrey between January 2000 and beginning of May 2017. Two reviewers will independently assess each study for inclusion and disagreements will be resolved by a third reviewer. Data will be extracted using a predefined data extraction form following best practice. Study quality will be assessed with the Effective Public Health Practice Project quality assessment tool. The reporting of costing methodology will be assessed using the British Medical Journal checklist. A narrative synthesis of all studies will be presented for resources used and costs incurred, by level of disease severity when available. If feasible, the data will be synthesised using appropriate statistical techniques. Ethics and dissemination Included articles will be reviewed for an ethics statement. The findings of the review will be disseminated in a related peer-reviewed journal and presented at conferences. They will also contribute to the work developed in the Real World Outcomes across the Alzheimer’s disease spectrum for better care: multi-modal data access platform (ROADMAP). Trial registration number CRD42017071413. PMID:29362261

Polyaniline modified flexible conducting paper for cancer detection

NASA Astrophysics Data System (ADS)

Kumar, Saurabh; Sen, Anindita; Kumar, Suveen; Augustine, Shine; Yadav, Birendra K.; Mishra, Sandeep; Malhotra, Bansi D.

2016-05-01

We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrode has sensitivity of 13.9 μA ng-1 ml cm2, shelf life of 22 days, and can be used to estimate CEA in the range of 2-20 ng ml-1. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.

Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells.

PubMed

Aarons, Cary B; Bajenova, Olga; Andrews, Charles; Heydrick, Stanley; Bushell, Kristen N; Reed, Karen L; Thomas, Peter; Becker, James M; Stucchi, Arthur F

2007-01-01

The liver is the most common site for metastasis by colorectal cancer, and numerous studies have shown a relationship between serum carcinoembryonic antigen (CEA) levels and metastasis to this site. CEA activates hepatic macrophages or Kupffer cells via binding to the CEA receptor (CEA-R), which results in the production of cytokines and the up-regulation of endothelial adhesion molecules, both of which are implicated in hepatic metastasis. Since tissue macrophages implicated in the metastatic process can often be difficult to isolate, the aim of this study was to develop an in vitro model system to study the complex mechanisms of CEA-induced macrophage activation and metastasis. Undifferentiated, human monocytic THP-1 (U-THP) cells were differentiated (D-THP) to macrophages by exposure to 200 ng/ml phorbol myristate acetate (PMA) for 18 h. Immunohistochemistry showed two CEA-R isoforms present in both U- and D-THP cells. The receptors were localized primarily to the nucleus in U-THP cells, while a significant cell-surface presence was observed following PMA-differentiation. Incubation of D-THP-1 cells with CEA resulted in a significant increase in tumor necrosis factor-alpha (TNF-alpha) release over 24 h compared to untreated D-THP-1 or U-THP controls confirming the functionality of these cell surface receptors. U-THP cells were unresponsive to CEA. Attachment of HT-29 cells to human umbilical vein endothelial cells significantly increased at 1 h after incubation with both recombinant TNF-alpha and conditioned media from CEA stimulated D-THP cells by six and eightfold, respectively. This study establishes an in vitro system utilizing a human macrophage cell line expressing functional CEA-Rs to study activation and signaling mechanisms of CEA that facilitate tumor cell attachment to activated endothelial cells. Utilization of this in vitro system may lead to a more complete understanding of the expression and function of CEA-R and facilitate the design of anti-CEA-R therapeutic modalities that may significantly diminish the metastatic potential of CEA overexpressing colorectal tumors.

Neuropeptide Y (NPY) in the central nucleus of the amygdala (CeA) does not affect ethanol-reinforced responding in binge-drinking, nondependent rats.

PubMed

Henderson, Angela N; Czachowski, Cristine L

2012-03-01

The central nucleus of the amygdala (CeA) has been implicated as having a significant role in mediating alcohol-drinking behavior. Neuropeptide Y (NPY) has been investigated as a potential pharmacotherapeutic due to its ability to attenuate ethanol intake, particularly when administered into the CeA. Previous research suggests, though the evidence is somewhat conflicting, that the efficacy of NPY is contingent upon genetic background and/or prior history of ethanol dependence in rats. However, studies looking at the effects of NPY in nonselected animals lacking a history of ethanol dependence have two factors that could impact the interpretation of the results: ethanol history/selection AND relatively low baseline ethanol intakes as compared to ethanol-dependent and/or genetically selected controls. The purpose of the present study was to generate higher baseline ethanol intakes upon which to examine the effects of NPY on ethanol and sucrose drinking in nonselected rats using a binge drinking model. Long Evans rats were trained to complete a single response requirement resulting in access to either 2% sucrose (Sucrose Group) or 2% sucrose/10% ethanol (Ethanol Group) for a 20-min drinking session. On treatment days, rats were bilaterally microinjected into the CeA with aCSF or one of three doses of NPY (0.25μg, 0.50μg, or 1.00μg/.5μL). Subjects in the Ethanol Group were consuming an average of 1.2g/kg of ethanol (yielding BELs of ~90mg%) during the 20min access period following aCSF treatments. The results revealed that NPY had no effect on either sucrose or ethanol consumption or on appetitive responding (latency to respond). Overall, the findings indicate that even a history of binge-like ethanol consumption is not sufficient to recruit CeA NPY activity, and are consistent with previous studies showing that the role of NPY in regulating ethanol reinforcement in the CeA may be contingent upon a prior history of ethanol dependence. Copyright © 2011 Elsevier Inc. All rights reserved.

77 FR 2613 - Registration of Swap Dealers and Major Swap Participants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

...The Commodity Futures Trading Commission (Commission or CFTC) is adopting regulations under the Commodity Exchange Act (Act or CEA) that establish the process for the registration of swap dealers (SDs) and major swap participants (MSPs, and collectively with SDs, Swaps Entities) and that require Swaps Entities to become and remain members of a registered futures association (RFA). The Commission is also adopting regulations that define an ``associated person'' of an SD or MSP as a natural person and that implement the prohibition on a Swaps Entity permitting an associated person who is statutorily disqualified from registration from effecting or being involved in effecting swaps on behalf of the Swaps Entity. The Commission is adopting these regulations in accordance with section 4s of the CEA, which was recently added to the CEA by the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act).

Carotid Artery Stenting, Endarterectomy, or Medical Treatment Alone: The Debate Is Not Over

PubMed Central

Kassaian, Seyed Ebrahim; Goodarzynejad, Hamidreza

2011-01-01

The management of carotid artery stenosis reduces the risk of stroke and its related deaths. Management options include risk factor modification and medical therapy, carotid endarterectomy (CEA), and carotid artery stenting (CAS). Although several randomized controlled trials (RCTs), mostly conducted in late-1980s and mid-1990s, have proved CEA to be effective in the prevention of ipsilateral ischemic events in selected patients with carotid artery stenosis, aggressive risk factor modification and medical therapy with recently introduced antiplatelet agents, statins, and more effective antihypertensive medications may have reduced compelling indications for immediate surgery in asymptomatic populations. Also recently, due to improvements in percutaneous techniques and carotid stents, CAS has received wide attention as a potential alternative to CEA. Herein, we review the recent data on the management options of carotid artery stenosis and seek to identify the most appropriate treatment strategy in selected patients with carotid artery stenosis. PMID:23074598

AuNPs/CNOs/SWCNTs/chitosan-nanocomposite modified electrochemical sensor for the label-free detection of carcinoembryonic antigen.

PubMed

Rizwan, Mohammad; Elma, Syazwani; Lim, Syazana Abdullah; Ahmed, Minhaz Uddin

2018-06-01

In this work, a nanocomposite of gold nanoparticles (AuNPs), carbon nano-onions (CNOs), single-walled carbon nanotubes (SWCNTs) and chitosan (CS) (AuNPs/CNOs/SWCNTs/CS) was prepared for the development of highly sensitive electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA), clinical tumor marker. Firstly, layer-by-layer fabrication of the CEA-immunosensors was studied using cyclic voltammetry (CV) and square wave voltammetry (SWV). By combining the advantages of large surface area and electronic properties of AuNPs, CNOs, SWCNTs, and film forming properties of CS, AuNPs/CNOs/SWCNTs/CS-nanocomposite-modified glassy carbon electrode showed a 200% increase in effective surface area and electronic conductivity. The calibration plot gave a negative linear relationship between log[concentration] of CEA and electrical current with a correlation coefficient of 0.9875. The CEA-immunosensor demonstrated a wide linear detection range of 100 fg mL -1 to 400 ng mL -1 with a low detection limit of 100 fg mL -1 . In addition to high sensitivity, reproducibility and large stability, CEA-immunosensor provided an excellent selectivity and resistant-to-interference in the presence of other antigens in serum and hence a potential to be used with real samples. Copyright © 2018 Elsevier B.V. All rights reserved.

The relationship between return on investment and quality of study methodology in workplace health promotion programs.

PubMed

Baxter, Siyan; Sanderson, Kristy; Venn, Alison J; Blizzard, C Leigh; Palmer, Andrew J

2014-01-01

To determine the relationship between return on investment (ROI) and quality of study methodology in workplace health promotion programs. Data were obtained through a systematic literature search of National Health Service Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE), Health Technology Database (HTA), Cost Effectiveness Analysis (CEA) Registry, EconLit, PubMed, Embase, Wiley, and Scopus. Included were articles written in English or German reporting cost(s) and benefit(s) and single or multicomponent health promotion programs on working adults. Return-to-work and workplace injury prevention studies were excluded. Methodological quality was graded using British Medical Journal Economic Evaluation Working Party checklist. Economic outcomes were presented as ROI. ROI was calculated as ROI = (benefits - costs of program)/costs of program. Results were weighted by study size and combined using meta-analysis techniques. Sensitivity analysis was performed using two additional methodological quality checklists. The influences of quality score and important study characteristics on ROI were explored. Fifty-one studies (61 intervention arms) published between 1984 and 2012 included 261,901 participants and 122,242 controls from nine industry types across 12 countries. Methodological quality scores were highly correlated between checklists (r = .84-.93). Methodological quality improved over time. Overall weighted ROI [mean ± standard deviation (confidence interval)] was 1.38 ± 1.97 (1.38-1.39), which indicated a 138% return on investment. When accounting for methodological quality, an inverse relationship to ROI was found. High-quality studies (n = 18) had a smaller mean ROI, 0.26 ± 1.74 (.23-.30), compared to moderate (n = 16) 0.90 ± 1.25 (.90-.91) and low-quality (n = 27) 2.32 ± 2.14 (2.30-2.33) studies. Randomized control trials (RCTs) (n = 12) exhibited negative ROI, -0.22 ± 2.41(-.27 to -.16). Financial returns become increasingly positive across quasi-experimental, nonexperimental, and modeled studies: 1.12 ± 2.16 (1.11-1.14), 1.61 ± 0.91 (1.56-1.65), and 2.05 ± 0.88 (2.04-2.06), respectively. Overall, mean weighted ROI in workplace health promotion demonstrated a positive ROI. Higher methodological quality studies provided evidence of smaller financial returns. Methodological quality and study design are important determinants.

Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

PubMed

Varodayan, F P; Khom, S; Patel, R R; Steinman, M Q; Hedges, D M; Oleata, C S; Homanics, G E; Roberto, M; Bajo, M

2018-01-04

Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress. © The Author(s) 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

CESAR5.3: Isotopic depletion for Research and Testing Reactor decommissioning

NASA Astrophysics Data System (ADS)

Ritter, Guillaume; Eschbach, Romain; Girieud, Richard; Soulard, Maxime

2018-05-01

CESAR stands in French for "simplified depletion applied to reprocessing". The current version is now number 5.3 as it started 30 years ago from a long lasting cooperation with ORANO, co-owner of the code with CEA. This computer code can characterize several types of nuclear fuel assemblies, from the most regular PWR power plants to the most unexpected gas cooled and graphite moderated old timer research facility. Each type of fuel can also include numerous ranges of compositions like UOX, MOX, LEU or HEU. Such versatility comes from a broad catalog of cross section libraries, each corresponding to a specific reactor and fuel matrix design. CESAR goes beyond fuel characterization and can also provide an evaluation of structural materials activation. The cross-sections libraries are generated using the most refined assembly or core level transport code calculation schemes (CEA APOLLO2 or ERANOS), based on the European JEFF3.1.1 nuclear data base. Each new CESAR self shielded cross section library benefits all most recent CEA recommendations as for deterministic physics options. Resulting cross sections are organized as a function of burn up and initial fuel enrichment which allows to condensate this costly process into a series of Legendre polynomials. The final outcome is a fast, accurate and compact CESAR cross section library. Each library is fully validated, against a stochastic transport code (CEA TRIPOLI 4) if needed and against a reference depletion code (CEA DARWIN). Using CESAR does not require any of the neutron physics expertise implemented into cross section libraries generation. It is based on top quality nuclear data (JEFF3.1.1 for ˜400 isotopes) and includes up to date Bateman equation solving algorithms. However, defining a CESAR computation case can be very straightforward. Most results are only 3 steps away from any beginner's ambition: Initial composition, in core depletion and pool decay scenario. On top of a simple utilization architecture, CESAR includes a portable Graphical User Interface which can be broadly deployed in R&D or industrial facilities. Aging facilities currently face decommissioning and dismantling issues. This way to the end of the nuclear fuel cycle requires a careful assessment of source terms in the fuel, core structures and all parts of a facility that must be disposed of with "industrial nuclear" constraints. In that perspective, several CESAR cross section libraries were constructed for early CEA Research and Testing Reactors (RTR's). The aim of this paper is to describe how CESAR operates and how it can be used to help these facilities care for waste disposal, nuclear materials transport or basic safety cases. The test case will be based on the PHEBUS Facility located at CEA - Cadarache.

Spray-on-skin cells in burns: a common practice with no agreed protocol.

PubMed

Allouni, Ammar; Papini, Remo; Lewis, Darren

2013-11-01

Cultured epithelial autograft (CEA) has been used for skin coverage after burn wound excision since 1981. It is used in burn units and centres throughout the U.K.; however, there appears to be no agreed standards of practice. We aimed to investigate the experience and current practice with its usage in the management of acute burn injury. An online survey was sent to twenty-five burns consultants in the U.K., who are members of the British Burn Association. We received 14 responses. Rarely have the responders agreed to the same practice in most of the questions. Different choices were given by responders with regards the indications for cell culture, techniques used, primary and secondary dressings used, first wound review timing, and measures used to evaluate outcomes. In the current economic environment, the NHS needs to rationalize services on the basis of cost effectiveness. CEA is an expensive procedure that requires an adequately sterile laboratory, special equipments and highly experienced dedicated staff. When dealing with expensive management options, it is important to have an agreed protocol that can form the standard that can be referred to when auditing practices and results to improve burn management and patients' care. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Parameters of blood count and tumor markers in patients with borderline ovarian tumors: a retrospective analysis and relation to staging.

PubMed

Nomelini, Rosekeila Simões; da Silva, Taísa Morete; Tavares Murta, Beatriz Martins; Murta, Eddie Fernando Candido

2012-01-01

The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n = 13) and stage IB-IIIC (n = 8). The unpaired t-test and Fisher's exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P < 0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

Layer-by-layer multienzyme assembly for highly sensitive electrochemical immunoassay based on tyramine signal amplification strategy.

PubMed

Zhou, Jun; Tang, Juan; Chen, Guonan; Tang, Dianping

2014-04-15

A new sandwich-type electrochemical immunosensor based on nanosilver-doped bovine serum albumin microspheres (Ag@BSA) with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for quantitative monitoring of biomarkers (carcinoembryonic antigen, CEA, used in this case) by coupling enzymatic biocatalytic precipitation with tyramine signal amplification strategy on capture antibody-modified glassy carbon electrode. Two immunosensing protocols (with and without tyramine signal amplification) were also investigated for the detection of CEA and improved analytical features were acquired with tyramine signal amplification strategy. With the labeling method, the performance and factors influencing the electrochemical immunoassay were studied and evaluated in detail. Under the optimal conditions, the electrochemical immunosensor exhibited a wide dynamic range of 0.005-80 ng mL(-1) toward CEA standards with a low detection limit of 5.0 pg mL(-1). Intra- and inter-assay coefficients of variation were below 11%. No significant differences at the 0.05 significance level were encountered in the analysis of 6 clinical serum specimens and 6 spiked new-born cattle serum samples between the electrochemical immunoassay and the commercialized electrochemiluminescent immunoassay method for the detection of CEA. © 2013 Published by Elsevier B.V.

Graphene oxide-labeled sandwich-type impedimetric immunoassay with sensitive enhancement based on enzymatic 4-chloro-1-naphthol oxidation.

PubMed

Hou, Li; Cui, Yuling; Xu, Mingdi; Gao, Zhuangqiang; Huang, Jianxin; Tang, Dianping

2013-09-15

A new sandwich-type impedimetric immunosensor based on functionalized graphene oxide nanosheets with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for the detection of carcinoembryonic antigen (CEA) by coupling with enzymatic biocatalytic precipitation of 4-chloro-1-naphthol (4-CN) on the captured antibody-modified glassy carbon electrode. Two molecular tags (with and without the graphene oxide nanosheets) were investigated for the detection of CEA and improved analytical features were acquired with the graphene-based labeling. With the labeling method, the performance and factors influencing the properties of the impedimetric immunosensors were also studied and evaluated. Under the optimal conditions, the dynamic concentration range of the impedimetric immunosensors spanned from 1.0pgmL(-1) to 80ngmL(-1) CEA with a detection limit (LOD) of 0.64pgmL(-1). Intra- and inter-assay coefficients of variation were less than 7.5% and 11%, respectively. Additionally, the methodology was evaluated for CEA analysis of 10 clinical serum samples and 5 diluted serum samples, receiving in a good accordance with the results obtained by the impedimetric immunoassay and the commercialized electrochemiluminescent method. Copyright © 2013 Elsevier B.V. All rights reserved.

[Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

PubMed

Chen, Yan; Zheng, Yu-hong; Lin, Ying-ying; Hu, Min-hua; Chen, Yan-song

2011-11-01

To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

NASA Astrophysics Data System (ADS)

Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin

2015-04-01

The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L- 1 and 0.054 μg L- 1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L- 1) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2-50 μg L- 1. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications.

Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy.

PubMed

Ottaiano, Alessandro; Napolitano, Maria; Capozzi, Monica; Tafuto, Salvatore; Avallone, Antonio; Scala, Stefania

2017-11-16

Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography- computed tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA. The patient received maintenance therapy with bevacizumab which was stopped in December 2013 for patient choice. In October 2014, a new increase in CEA was documented and PET-CT scan showed lung metastases. Analysis of RAS status revealed the absence of mutations, then the patient started a second-line chemotherapy with fluorouracile, folinic acid, irinotecan (folfiri) and panitumumab achieving, in January 2015, a complete response and normalization of CEA. Thereafter, folfiri was discontinued for toxicity; furthermore, upon the third occurrence of a grade 3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the original dose and it was administered every three weeks. Until presentation of this case, the patient maintains a complete response, has no symptoms of disease and CEA is normal. Interestingly, this patient presented a high proportion of circulating natural killer (NK) cells (35.1%) with high cytotoxic activity against tumor cells. Study on the role of NK in patients with advanced colorectal cancer are ongoing.

[A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

PubMed

Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

2005-12-01

A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

Polyaniline modified flexible conducting paper for cancer detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Saurabh; Sen, Anindita; Kumar, Suveen

We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrodemore » has sensitivity of 13.9 μA ng{sup −1} ml cm{sup 2}, shelf life of 22 days, and can be used to estimate CEA in the range of 2–20 ng ml{sup −1}. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.« less

Primary closure after carotid endarterectomy is not inferior to other closure techniques.

PubMed

Avgerinos, Efthymios D; Chaer, Rabih A; Naddaf, Abdallah; El-Shazly, Omar M; Marone, Luke; Makaroun, Michel S

2016-09-01

Primary closure after carotid endarterectomy (CEA) has been much maligned as an inferior technique with worse outcomes than in patch closure. Our purpose was to compare perioperative and long-term results of different CEA closure techniques in a large institutional experience. A consecutive cohort of CEAs between January 1, 2000, and December 31, 2010, was retrospectively analyzed. Closure technique was used to divide patients into three groups: primary longitudinal arteriotomy closure (PRC), patch closure (PAC), and eversion closure (EVC). End points were perioperative events, long-term strokes, and restenosis ≥70%. Multivariate regression models were used to assess the effect of baseline predictors. There were 1737 CEA cases (bilateral, 143; mean age, 71.4 ± 9.3 years; 56.2% men; 35.3% symptomatic) performed during the study period with a mean clinical follow-up of 49.8 ± 36.4 months (range, 0-155 months). More men had primary closure, but other demographic and baseline symptoms were similar between groups. Half the patients had PAC, with the rest evenly distributed between PRC and EVC. The rate of nerve injury was 2.7%, the rate of reintervention for hematoma was 1.5%, and the length of hospital stay was 2.4 ± 3.0 days, with no significant differences among groups. The combined stroke and death rate was 2.5% overall and 3.9% and 1.7% in the symptomatic and asymptomatic cohort, respectively. Stroke and death rates were similar between groups: PRC, 11 (2.7%); PAC, 19 (2.2%); EVC, 13 (2.9%). Multivariate analysis showed baseline symptomatic disease (odds ratio, 2.4; P = .007) and heart failure (odds ratio, 3.1; P = .003) as predictors of perioperative stroke and death, but not the type of closure. Cox regression analysis demonstrated, among other risk factors, no statin use (hazard ratio, 2.1; P = .008) as a predictor of ipsilateral stroke and severe (glomerular filtration rate <30 mL/min/1.73 m(2)) renal insufficiency (hazard ratio, 2.6; P = .032) as the only predictor of restenosis ≥70%. Type of closure did not have any predictive value. In our study, baseline risk factors and statin use, but not the type of closure, affect perioperative and long-term outcomes after CEA. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

CEA monitoring of palliative treatment for colorectal carcinoma.

PubMed Central

Herrera, M A; Chu, T M; Holyoke, E D; Mittelman, A

1977-01-01

Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable. PMID:64132

MATERNAL TRAUMA AFFECTS PRENATAL MENTAL HEALTH AND INFANT STRESS REGULATION AMONG PALESTINIAN DYADS.

PubMed

Isosävi, Sanna; Diab, Safwat Y; Kangaslampi, Samuli; Qouta, Samir; Kankaanpää, Saija; Puura, Kaija; Punamäki, Raija-Leena

2017-09-01

We examined how diverse and cumulated traumatic experiences predicted maternal prenatal mental health and infant stress regulation in war conditions and whether maternal mental health mediated the association between trauma and infant stress regulation. Participants were 511 Palestinian mothers from the Gaza Strip who reported exposure to current war trauma (WT), past childhood emotional (CEA) and physical abuse, socioeconomic status (SES), prenatal mental health problems (posttraumatic stress disorder and depression symptoms), and perceived stress during their secondtrimester of pregnancy as well as infant stress regulation at 4 months. While all trauma types were associated with high levels of prenatal symptoms, CEA had the most wide-ranging effects and was uniquely associated with depression symptoms. Concerning infant stress regulation, mothers' CEA predicted negative affectivity, but only among mothers with low WT. Against hypothesis, the effects of maternal trauma on infant stress regulation were not mediated by mental health symptoms. Mothers' higher SES was associated with better infant stress regulation whereas infant prematurity and male sex predisposed for difficulties. Our findings suggest that maternal childhood abuse, especially CEA, should be a central treatment target among war-exposed families. Cumulated psychosocial stressors might increase the risk for transgenerational problems. © 2017 Michigan Association for Infant Mental Health.

The carcinoembryonic antigen IgV-like N domain plays a critical role in the implantation of metastatic tumor cells.

PubMed

Abdul-Wahid, Aws; Huang, Eric H-B; Cydzik, Marzena; Bolewska-Pedyczak, Eleonora; Gariépy, Jean

2014-03-01

The human carcinoembryonic antigen (CEA) is a cell adhesion molecule involved in both homotypic and heterotypic interactions. The aberrant overexpression of CEA on adenocarcinoma cells correlates with their increased metastatic potential. Yet, the mechanism(s) by which its adhesive properties can lead to the implantation of circulating tumor cells and expansion of metastatic foci remains to be established. In this study, we demonstrate that the IgV-like N terminal domain of CEA directly participates in the implantation of cancer cells through its homotypic and heterotypic binding properties. Specifically, we determined that the recombinant N terminal domain of CEA directly binds to fibronectin (Fn) with a dissociation constant in the nanomolar range (K(D) 16 ± 3 nM) and interacts with itself (K(D) 100 ± 17 nM) and more tightly to the IgC-like A(3) domain (K(D) 18 ± 3 nM). Disruption of these molecular associations through the addition of antibodies specific to the CEA N or A(3)B(3) domains, or by adding soluble recombinant forms of the CEA N, A(3) or A(3)B(3) domains or a peptide corresponding to residues 108-115 of CEA resulted in the inhibition of CEA-mediated intercellular aggregation and adherence events in vitro. Finally, pretreating CEA-expressing murine colonic carcinoma cells (MC38.CEA) with rCEA N, A3 or A(3)B(3) modules blocked their implantation and the establishment of tumor foci in vivo. Together, these results suggest a new mechanistic insight into how the CEA IgV-like N domain participates in cellular events that can have a macroscopic impact in terms of cancer progression and metastasis. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Contralateral occlusion is not a clinically important reason for choosing carotid artery stenting for patients with significant carotid artery stenosis.

PubMed

Brewster, Luke P; Beaulieu, Robert; Kasirajan, Karthik; Corriere, Matthew A; Ricotta, Joseph J; Patel, Siddharth; Dodson, Thomas F

2012-11-01

Contralateral carotid artery occlusion by itself carries an increased risk of stroke. Carotid endarterectomy (CEA) in the presence of contralateral carotid artery occlusion has high reported rates of perioperative morbidity and mortality. Our objective was to determine if there is a clinical benefit to patients who receive carotid artery stenting (CAS) compared to CEA in the presence of contralateral carotid artery occlusion. We conducted a retrospective medical chart review over a 4.5-year institutional experience of persons with contralateral carotid artery occlusion and ipsilateral carotid artery stenosis who underwent CAS or CEA. The main outcome measures were 30-day cardiac, stroke, and mortality rate, and midterm mortality. Of a total of 713 patients treated for carotid artery stenosis during this time period, 57 had contralateral occlusion (~8%). Thirty-nine of these patients were treated with CAS, and 18 with CEA. The most common indications for CAS were prior neck surgery (18), contralateral internal carotid occlusion (nine), and prior neck radiation (seven). The average age was 70 ± 8.5 for CEA and 66.7 ± 9.3 for CAS (P = .20). Both groups were predominantly men (CEA 12 of 18; CAS 28 of 39; P = .76), with similar prevalence of symptomatic lesions (CEA 8 of 18, CAS 20 of 39; P = .77). Two patients died within 30 days in the CAS group (5%). No deaths occurred within 30 days in the CEA group (P = .50); the mortality rate for CAS and CEA combined was 3.5%. No perioperative strokes or myocardial infarction occurred in either group. Two transient ischemic attacks occurred after CAS. At mean follow-up of 29.4 ± 16 months (CEA) and 28 ± 14.4 months (CAS; range, 1.5-48.5 months), seven deaths occurred in the CAS group and one in the CEA group (17.9% vs 5.5%; P = .40). There were two reinterventions in the CAS group for in-stent restenosis and there were no reoperations in the CEA group. Although CEA and CAS can both be performed with good perioperative results and acceptable midterm mortality, the observed outcomes do not support use of contralateral carotid artery occlusion as a selection criterion for CAS over CEA in the absence of other indications. Copyright © 2012 Society for Vascular Surgery. All rights reserved.

Accuracy of administrative data versus clinical data to evaluate carotid endarterectomy and carotid stenting.

PubMed

Bensley, Rodney P; Yoshida, Shunsuke; Lo, Ruby C; Fokkema, Margriet; Hamdan, Allen D; Wyers, Mark C; Chaikof, Elliot L; Schermerhorn, Marc L

2013-08-01

Administrative data have been used to compare carotid endarterectomy (CEA) and carotid artery stenting (CAS). However, there are limitations in defining symptom status, Centers for Medicare and Medicaid Services high-risk status, as well as complications. Therefore, we did a direct comparison between administrative data and physician chart review as well as between data collected for the National Surgical Quality Improvement Program (NSQIP) and physician chart review for CEA and CAS. We performed an outcomes analysis on all CEA and CAS procedures from 2005 to 2011. We obtained International Classification of Diseases, Ninth Revision diagnosis codes from hospital discharge records regarding symptom status, high-risk status, and perioperative stroke. We also obtained data on all CEA patients submitted to NSQIP over the same time period. One of the study authors (R.B.) then performed a chart review of the same patients to determine symptom status, high-risk status, and perioperative strokes and the results were compared. We identified 1342 patients who underwent CEA or CAS between 2005 and 2011 and 392 patients who underwent CEA that were submitted to NSQIP. Administrative data identified fewer symptomatic patients (17.0% vs 34.0%), physiologic high-risk patients (9.3% vs 23.0%), and anatomic high-risk patients (0% vs 15.2%). Although administrative data identified a similar proportion of perioperative strokes (1.9% vs 2.0%), this was due to the fact that these data identified eight false positive and nine false negative perioperative strokes. NSQIP data identified more symptomatic patients compared with chart review (44.1% vs 30.3%), fewer physiologic high-risk patients (13.0% vs 18.6%), fewer anatomic high-risk patients (0% vs 6.6%), and a similar proportion of perioperative strokes (1.5% vs 1.8%, only one false negative stroke and no false positives). Administrative data are unreliable for determining symptom status, high-risk status, and perioperative stroke and should not be used to analyze CEA and CAS. NSQIP data do not adequately identify high-risk patients, but do accurately identify perioperative strokes and to a lesser degree, symptom status. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Thermodynamics of Gas Turbine Cycles with Analytic Derivatives in OpenMDAO

NASA Technical Reports Server (NTRS)

Gray, Justin; Chin, Jeffrey; Hearn, Tristan; Hendricks, Eric; Lavelle, Thomas; Martins, Joaquim R. R. A.

2016-01-01

A new equilibrium thermodynamics analysis tool was built based on the CEA method using the OpenMDAO framework. The new tool provides forward and adjoint analytic derivatives for use with gradient based optimization algorithms. The new tool was validated against the original CEA code to ensure an accurate analysis and the analytic derivatives were validated against finite-difference approximations. Performance comparisons between analytic and finite difference methods showed a significant speed advantage for the analytic methods. To further test the new analysis tool, a sample optimization was performed to find the optimal air-fuel equivalence ratio, , maximizing combustion temperature for a range of different pressures. Collectively, the results demonstrate the viability of the new tool to serve as the thermodynamic backbone for future work on a full propulsion modeling tool.

Orexin-1 receptor antagonist in central nucleus of the amygdala attenuates the acquisition of flavor-taste preference in rats.

PubMed

Risco, Severiano; Mediavilla, Cristina

2014-11-01

Previous studies demonstrated that the intracerebroventricular administration of SB-334867-A, a selective antagonist of orexin OX1R receptors, blocks the acquisition of saccharin-induced conditioned flavor preference (CFP) but not LiCl-induced taste aversion learning (TAL). Orexinergic fibers from the lateral hypothalamus end in the central nucleus of the amygdala (CeA), which expresses orexin OX1R receptors. Taste and sensory inputs also are present in CeA, which may contribute to the development of taste learning. This study analyzed the effect of two doses (1.5 and 6μg/0.5μl) of SB-334867-A administered into the CeA on flavor-taste preference induced by saccharin and on TAL induced by a single administration of LiCl (0.15M, 20ml/kg, i.p.). Outcomes indicate that inactivation of orexinergic receptors in the CeA attenuates flavor-taste preference in a two-bottle test (saccharin vs. water). Intra-amygdalar SB-334867-A does not affect gustatory processing or the preference for the sweet taste of saccharin given that SB-334867-A- and DMSO-treated groups (control animals) increased the intake of the saccharin-associated flavor across training acquisition sessions. Furthermore, SB-334867-A in the CeA does not block TAL acquisition ruling out the possibility that functional inactivation of OX1R receptors interferes with taste processing. Orexin receptors in the CeA appear to intervene in the association of a flavor with orosensory stimuli, e.g., a sweet and pleasant taste, but could be unnecessary when the association is established with visceral stimuli, e.g., lithium chloride. These data suggest that orexinergic projections to the CeA may contribute to the reinforcing signals facilitating the acquisition of taste learning and the change in hedonic evaluation of the taste, which would have important implications for the OX1R-targeted pharmacological treatment of eating disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats

PubMed Central

Dumais, Kelly M.; Alonso, Andrea G.; Bredewold, Remco; Veenema, Alexa H.

2016-01-01

We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5 ng/0.5 µl/side) or OT (100 pg/0.5 µl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest towards juvenile conspecifics in males. PMID:27235738

Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

NASA Astrophysics Data System (ADS)

Borges, Ana; Sousa, Inês; Castro, Luis

2017-06-01

This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary.

Increased mortality associated with elevated carcinoembryonic antigen in insurance applicants.

PubMed

Stout, Robert L; Fulks, Michael; Dolan, Vera F; Magee, Mark E; Suarez, Luis

2007-01-01

Determine the relationship between the carcinoembryonic antigen (CEA) value and all-cause mortality in life insurance applicants aged 50 years and over. By use of the Social Security Master Death Index, mortality was examined in 115,590 insurance applicants aged 50 and up for whom blood samples for CEA were submitted to the Clinical Reference Laboratory. Results were stratified by CEA value (<5 ng/mL, 5 to 9.9 ng/mL, 10+ ng/mL), smoking status, and age groups (50-59 years, 60-69 years, and 70 years and up). Relative mortality is increased at CEA values between 5 and 9.9 ng/mL and further increased at 10+ ng/mL for all age groups, with the most dramatic increase at the youngest ages. Excess mortality appears to last at least 3 to 4 years after the elevated result. Five-year all-cause mortality in applicants with CEA values of 10+ ng/mL is 25.2% with a mortality ratio relative to those with a CEA <5 ng/mL of 1156%. This study shows that CEA can detect the risk of early excess mortality in life insurance applicants; CEA levels of 5 ng/mL and over may be of concern. CEA testing beginning at age 50 years for life insurance applicants could capture 4.6% of early mortality if the threshold for further evaluation was set at 10 ng/mL. Only 0.4% of all applicants aged 50 and over have CEA values at or above this threshold.

The Central Nucleus of the Amygdala and Corticotropin-Releasing Factor: Insights into Contextual Fear Memory

PubMed Central

Pitts, Matthew W.; Todorovic, Cedomir; Blank, Thomas; Takahashi, Lorey K.

2009-01-01

The central nucleus of the amygdala (CeA) has been traditionally viewed in fear conditioning to serve as an output neural center that transfers conditioned information formed in the basolateral amygdala to brain structures that generate emotional responses. Recent studies suggest that the CeA may also be involved in fear memory consolidation. In addition, corticotropin-releasing factor systems were shown to facilitate memory consolidation in the amygdala, which contains a high density of CRF immunoreactive cell bodies and fibers in the lateral part of the CeA (CeAl). However, the involvement of CeA CRF in contextual fear conditioning remains poorly understood. Therefore, we first conducted a series of studies using fiber-sparing lesion and reversible inactivation methods to assess the general role of the CeA in contextual fear. We then used identical training and testing procedures to compare and evaluate the specific function of CeA CRF using CRF antisense oligonucleotides (CRF ASO). Rats microinjected with ibotenic acid, muscimol, or a CRF ASO into the CeA prior to contextual fear conditioning showed typical levels of freezing during acquisition training but exhibited significant reductions in contextual freezing in a retention test 48 h later. Furthermore, CeA inactivation induced by either muscimol or CRF ASO administration immediately prior to retention testing did not impair freezing, suggesting that the previously observed retention deficits were due to inhibition of consolidation rather than fear expression. Collectively, our results suggest CeA involvement in the consolidation of contextual fear memory and specifically implicate CeA CRF as an important mediator. PMID:19494159

The minimal cost of life in space.

PubMed

Drysdale, A E; Rutkze, C J; Albright, L D; LaDue, R L

2004-01-01

The cost of keeping people alive in space is assessed from a theoretical viewpoint and using two actual designs for plant growth systems. While life support is theoretically not very demanding, our ability to implement life support is well below theoretical limits. A theoretical limit has been calculated from requirements and the state of the art for plant growth has been calculated using data from the BIO-Plex PDR and from the Cornell CEA prototype system. The very low efficiency of our current approaches results in a high mission impact, though we can still see how to get a significant reduction in cost of food when compared to supplying it from Earth. Seeing the distribution of costs should allow us to improve our current designs. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

The minimal cost of life in space

NASA Technical Reports Server (NTRS)

Drysdale, A. E.; Rutkze, C. J.; Albright, L. D.; LaDue, R. L.

2004-01-01

The cost of keeping people alive in space is assessed from a theoretical viewpoint and using two actual designs for plant growth systems. While life support is theoretically not very demanding, our ability to implement life support is well below theoretical limits. A theoretical limit has been calculated from requirements and the state of the art for plant growth has been calculated using data from the BIO-Plex PDR and from the Cornell CEA prototype system. The very low efficiency of our current approaches results in a high mission impact, though we can still see how to get a significant reduction in cost of food when compared to supplying it from Earth. Seeing the distribution of costs should allow us to improve our current designs. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer.

PubMed

Wang, Weigang; Xu, Xiaoqin; Tian, Baoguo; Wang, Yan; Du, Lili; Sun, Ting; Shi, Yanchun; Zhao, Xianwen; Jing, Jiexian

2017-07-01

This study aims to understand the diagnostic value of serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and tissue polypeptide-specific antigen (TPS) in metastatic breast cancer (MBC). A total of 164 metastatic breast cancer patients in Shanxi Cancer Hospital were recruited between February 2016 and July 2016. 200 breast cancer patients without metastasis in the same period were randomly selected as the control group. The general characteristics, immunohistochemical, and pathological results were investigated between the two groups, and tumor markers were determined. There were statistical differences in the concentration and the positive rates of CEA, CA19-9, CA125, CA15-3, and TPS between the MBC and control group (P<0.05). The highest sensitivity was in CEA and the highest specificity was in CA125 for the diagnosis of MBC when using a single tumor marker at 56.7% and 97.0%, respectively. In addition, two tumor markers were used for the diagnosis of MBC and the CEA and TPS combination had the highest diagnostic sensitivity with 78.7%, while the CA15-3 and CA125 combination had the highest specificity of 91.5%. Analysis of tumor markers of 164 MBC found that there were statistical differences in the positive rates of CEA and CA15-3 between bone metastases and other metastases (χ 2 =6.00, P=0.014; χ 2 =7.32, P=0.007, respectively). The sensitivity and specificity values of the CEA and CA15-3 combination in the diagnosis of bone metastases were 77.1% and 45.8%, respectively. The positive rate of TPS in the lung metastases group was lower than in other metastases (χ 2 =8.06, P=0.005).There were significant differences in the positive rates of CA15-3 and TPS between liver metastases and other metastases (χ 2 =15.42, P<0.001; χ 2 =9.72, P=0.002, respectively). The sensitivity and specificity of the CA15-3 and TPS combination in the diagnosis of liver metastases were 92.3% and 45.6%, respectively, and the positive rate of CEA in triple-negative metastatic breast cancer is lower than in other subtypes (χ 2 =4.80, P=0.028). Therefore, serum CEA, CA19-9, CA125, CA15-3, and TPS can be used in the diagnosis of MBC, and different combinations of tumor markers have varying diagnostic value. Copyright © 2017 Elsevier B.V. All rights reserved.

[Antigens (CEA and CA 19-9) in diagnosis and prognosis colorectal cancer].

PubMed

Grotowski, Maciej

2002-01-01

carcinoembryonic antigen (CEA) was first described more than three decades ago, when its presence was demonstrated in fetal gut tissue and in tumors from gastrointestinal tract. Subsequently, CEA was detected in the circulation of patients and recognized as a serum marker for colorectal cancer. This tumor marker has not been advocated as a screening test for colorectal cancer, however a preoperative CEA serum level is useful for diagnosis and prognosis of recurrence and survival in colorectal cancer patients. The levels of CEA increased with increasing tumor stage. Expression of carbohydrate antigen (CA 19-9) has been described in various malignancies and also in colorectal cancer. This antigen also has not been advocated as a screening test for colorectal cancer. The levels of CA 19-9 increased in advanced stages of colorectal cancer. Despite its lower sensitivity than CEA in early stages of colorectal cancer, the combination of both antigens can provided more information than CEA alone for prognosis of recurrence and survival in those patients.

Combination of long noncoding RNA MALAT1 and carcinoembryonic antigen for the diagnosis of malignant pleural effusion caused by lung cancer.

PubMed

Wang, Wan-Wei; Zhou, Xi-Lei; Song, Ying-Jian; Yu, Chang-Hua; Zhu, Wei-Guo; Tong, Yu-Suo

2018-01-01

Long noncoding RNAs (lncRNAs) are present in body fluids, but their potential as tumor biomarkers has never been investigated in malignant pleural effusion (MPE) caused by lung cancer. The aim of this study was to assess the clinical significance of lncRNAs in pleural effusion, which could potentially serve as diagnostic and predictive markers for lung cancer-associated MPE (LC-MPE). RNAs from pleural effusion were extracted in 217 cases of LC-MPE and 132 cases of benign pleural effusion (BPE). Thirty-one lung cancer-associated lncRNAs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The level of carcinoembryonic antigen (CEA) was also determined. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were established to evaluate the sensitivity and specificity of the identified lncRNAs and other biomarkers. The correlations between baseline pleural effusion lncRNAs expression and response to chemotherapy were also analyzed. Three lncRNAs ( MALAT1 , H19 , and CUDR ) were found to have potential as diagnostic markers in LC-MPE. The AUCs for MALAT1 , H19 , CUDR , and CEA were 0.891, 0.783, 0.824, and 0.826, respectively. Using a logistic model, the combination of MALAT1 and CEA (AUC, 0.924) provided higher sensitivity and accuracy in predicting LC-MPE than CEA (AUC, 0.826) alone. Moreover, baseline MALAT1 expression in pleural fluid was inversely correlated with chemotherapy response in patients with LC-MPE. Pleural effusion lncRNAs were effective in differentiating LC-MPE from BPE. The combination of MALAT1 and CEA was more effective for LC-MPE diagnosis.

Anti-quorum sensing activity of flavonoid-rich fraction from Centella asiatica L. against Pseudomonas aeruginosa PAO1.

PubMed

Vasavi, H S; Arun, A B; Rekha, P D

2016-02-01

Inhibition of quorum sensing (QS), a cell-density dependent regulation of gene expression in bacteria by autoinducers is an attractive strategy for the development of antipathogenic agents. In this study, the anti-QS activity of the ethanolic extract of the traditional herb Centella asiatica was investigated by the biosensor bioassay using Chromobacterium violaceum CV026. The effect of ethyl acetate fraction (CEA) from the bioassay-guided fractionation of ethanol extract on QS-regulated violacein production in C. violaceum ATCC12472 and pyocyanin production, proteolytic and elastolytic activities, swarming motility, and biofilm formation in Pseudomonas aeruginosa PAO1 were evaluated. Possible mechanism of QS-inhibitory action on autoinducer activity was determined by measuring the acyl homoserine lactone using C. violaceum ATCC31532. Anti-QS compounds in the CEA fraction were identified using thin layer chromatography biosensor overlay assay. Ethanol extract of C. asiatica showed QS inhibition in C. violaceum CV026. Bioassay-guided fractionation of ethanol extract revealed that CEA was four times more active than the ethanol extract. CEA, at 400 μg/mL, completely inhibited violacein production in C. violaceum ATCC12472 without significantly affecting growth. CEA also showed inhibition of QS-regulated phenotypes, namely, pyocyanin production, elastolytic and proteolytic activities, swarming motility, and biofilm formation in P. aeruginosa PAO1 in a concentration-dependent manner. Thin layer chromatography of CEA with biosensor overlay showed anti-QS spot with an Rf value that corresponded with that of standard kaempferol. The anti-QS nature of C. asiatica herb can be further exploited for the formulation of drugs targeting bacterial infections where pathogenicity is mediated through QS. Copyright © 2014. Published by Elsevier B.V.

Proper exercise decreases plasma carcinoembryonic antigen levels with the improvement of body condition in elderly women.

PubMed

Ko, Il-Gyu; Park, Eung-Mi; Choi, Hye-Jung; Yoo, Jaehyun; Lee, Jong-Kyun; Jee, Yong-Seok

2014-05-01

Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.

MT-7716, a novel selective nonpeptidergic NOP receptor agonist, effectively blocks ethanol-induced increase in GABAergic transmission in the rat central amygdala

PubMed Central

Kallupi, Marsida; Oleata, Christopher S.; Luu, George; Teshima, Koji; Ciccocioppo, Roberto; Roberto, Marisa

2014-01-01

The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. A large body of evidence shows that Nociceptin/Orphanin FQ (N/OFQ) regulates ethanol intake and anxiety-like behavior. In the rat, ethanol significantly augments CeA GABA release, whereas N/OFQ diminishes it. Using electrophysiological techniques in an in vitro slice preparation, in this study we investigated the effects of a nonpeptidergic NOP receptor agonist, MT-7716 [(R)-2-3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl-N-methylacetamide hydrochloride hydrate], and its interaction with ethanol on GABAergic transmission in CeA slices of naïve rats. We found that MT-7716 dose-dependently (100–1000 nM) diminished evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) and increased paired-pulse facilitation (PPF) ratio of these evoked IPSPs, suggesting a presynaptic site of action of the MT-7716 by decreasing GABA release at CeA synapses. The presynaptic action of MT-7716 was also supported by the significant decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) induced by the nociceptin receptor (NOP) agonist. Interestingly, MT-7716 prevented the ethanol-induced augmentation of evoked IPSPs. A putative selective NOP antagonist, [Nphe1]Nociceptin(1–13)NH2, totally prevented the MT-7716-induced inhibition of IPSP amplitudes indicating that MT-7716 exerts its effect through NOPs. These data provide support for an interaction between the nociceptin and GABAergic systems in the CeA and for the anti-alcohol properties of the NOP activation. The development of a synthetic nonpeptidergic NOP receptor agonist such as MT-7716 may represent a useful therapeutic target for alcoholism. PMID:24600360

Enhanced GABAergic transmission in the central nucleus of the amygdala of genetically selected Marchigian Sardinian rats: alcohol and CRF effects

PubMed Central

Herman, Melissa; Kallupi, Marsida; Luu, George; Oleata, Christopher; Heilig, Markus; Koob, George F.; Ciccocioppo, Roberto; Roberto, Marisa

2012-01-01

The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. Alcohol dependence is associated with increased corticotropin releasing factor (CRF) influence on CeA GABA release and CRF type 1 receptor (CRF1) antagonists prevent the excessive alcohol consumption associated with dependence. Genetically-selected Marchigian Sardinian (msP) rats have an overactive extrahypothalamic CRF1 system, are highly sensitive to stress, and display an innate preference for alcohol. The present study examined differences in CeA GABAergic transmission and the effects of ethanol, CRF and a CRF1 antagonist in msP, Sprague-Dawley, and Wistar rats using an electrophysiological approach. We found no significant differences in membrane properties or mean amplitude of evoked GABAA-inhibitory postsynaptic potentials (IPSPs). However, paired-pulse facilitation (PPF) ratios of evoked IPSPs were significantly lower and spontaneous miniature inhibitory postsynaptic current (mIPSC) frequencies were higher in msP rats, suggesting increased CeA GABA release in msP as compared to Sprague-Dawley and Wistar rats. The sensitivity of spontaneous GABAergic transmission to ethanol (44 mM), CRF (200 nM) and CRF1 antagonist (R121919, 1 μM) was comparable in msP, Sprague Dawley, and Wistar rats. However, a history of ethanol drinking significantly increased the baseline mIPSC frequency and decreased the effects of a CRF1 antagonist in msP rats, suggesting increased GABA release and decreased CRF1 sensitivity. These results provide electrophysiological evidence that msP rats display distinct CeA GABAergic activity as compared to Sprague Dawley and Wistar rats. The elevated GABAergic transmission observed in naïve mSP rats is consistent with the neuroadaptations reported in Sprague Dawley rats after the development of ethanol dependence. PMID:23220399

[Effects of carotid endarterectomy on cognitive function in patients with carotid stenosis].

PubMed

Wang, Qi; Zhang, Ming; Huang, Dian; Zhou, Yu; Qiao, Tong

2014-08-01

To investigate the theraputic effects of carotid endarterectomy (CEA) on cognitive function in patients with carotid stenosis (CAS) and congnitive impairment. CEA was performed on 38 patients with CAS from December 2011 to July 2013. There were 26 male and 12 female patients, with an average age of (70 ± 7) years. Patients was underwent neuropsychological examinations (NPEs) including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at 1 week before and 6 weeks after treatment. Cerebral perfusion was assessed with MR perfusion-weighted imaging and diffusion-weighted inmaging at 1 week before and 6 weeks after treatment. All of the 38 patients completed NPEs and MRI at baseline and 6 weeks after CEA. After therapy, the parameters and the extents of abnormal perfusion was improved, including the decrease of time to peak (29 ± 9 vs. 23 ± 4), relative mean transit time (22 ± 8 vs. 14 ± 6), arrive time (21 ± 8 vs. 15 ± 4) and relative cerebral blood volume (11.6 ± 3.5 vs. 7.5 ± 3.2) (t = 1.31 to 5.24, all P < 0.05). Significant improvement in MoCA (20.4 ± 1.5 vs. 22.0 ± 1.6, t = -4.25, P = 0.000) but MMSE (26.16 ± 1.35 vs. 26.47 ± 1.52, t = -0.96, P = 0.341) was observed. CEA significantly improved the assessment of visuospacial/constructive abilities (2.4 ± 0.9 vs. 2.8 ± 0.7), naming (2.0 ± 0.7 vs. 2.3 ± 0.6), abstraction (1.2 ± 0.7 vs. 1.6 ± 0.6) and attention (2.3 ± 0.6 vs. 2.6 ± 0.5) (t = 0.015 to 0.029, P = 0.015). CEA can improve the cognitive function of patients with carotid stenosis as well as the cerebral perfusion of patients and has therapeutic effects on vascular mild cognitive impairment.

Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.

PubMed

Stingele, Robert; Berger, Jürgen; Alfke, Karsten; Eckstein, Hans-Henning; Fraedrich, Gustav; Allenberg, Jens; Hartmann, Marius; Ringleb, Peter A; Fiehler, Jens; Bruckmann, H; Hennerici, M; Jansen, O; Klein, G; Kunze, A; Marx, P; Niederkorn, K; Schmiedt, W; Solymosi, L; Zeumer, H; Hacke, W

2008-03-01

Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

Stroke/Death Rates Following Carotid Artery Stenting and Carotid Endarterectomy in Contemporary Administrative Dataset Registries: A Systematic Review.

PubMed

Paraskevas, K I; Kalmykov, E L; Naylor, A R

2016-01-01

Randomised trials have reported higher stroke/death rates after carotid artery stenting (CAS) versus carotid endarterectomy (CEA). Despite this, the 2011 American Heart Association (AHA) guidelines expanded CAS indications, partly because of the Carotid Revascularization Endarterectomy versus Stenting Trial, but also because of improving outcomes in industry sponsored CAS Registries. The aim of this systematic review was: (i) to compare stroke/death rates after CAS/CEA in contemporary dataset registries, (ii) to examine whether published stroke/death rates after CAS fall within AHA thresholds, and, (iii) to see if there had been a decline (over time) in procedural risk after CAS/CEA. PubMed/Medline, Embase, and Cochrane databases were systematically searched according to the recommendations of the PRISMA statement from January 1, 2008 until February 23, 2015 for administrative dataset registries reporting outcomes after both CEA and CAS. Twenty-one registries reported outcomes involving more than 1,500,000 procedures. Stroke/death after CAS was significantly higher than after CEA in 11/21 registries (52%) involving "average risk for CEA" asymptomatic patients and in 11/18 registries (61%) involving "average risk for CEA" symptomatic patients. In another five registries, CAS was associated with higher stroke/death rates than CEA for both symptomatic and asymptomatic patients, but formal statistical comparison was not reported. CAS was associated with stroke/death rates that exceeded risk thresholds recommended by the AHA in 9/21 registries (43%) involving "average risk for CEA" asymptomatic patients and in 13/18 registries (72%) involving "average risk for CEA" symptomatic patients. In 5/18 registries (28%), the procedural risk after CAS in "average risk" symptomatic patients exceeded 10%. Data from contemporary administrative dataset registries suggest that stroke/death rates following CAS remain significantly higher than after CEA and often exceed accepted AHA thresholds. There was no evidence of a sustained decline in procedural risk after CAS. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Processing of carcinoembryonic antigen by Kupffer cells: recognition of a penta-peptide sequence.

PubMed

Gangopadhyay, A; Thomas, P

1996-10-01

Carcinoembryonic antigen (CEA) binds to an 80-kDa cell surface receptor on Kupffer cells via the peptide sequence PELPK (residues 108-112) located at the hinge region between the N and Al immunoglobulin-like domains. This study is aimed at analyzing the specificity of the peptide binding, determining biodistribution of 80-kDa receptor, and processing of CEA by this receptor. We synthesized a number of bovine serum albumin (BSA) derivatives carrying PELPK and related sequences. A series of peptides (YPELPK, YPDLPK, YPDLPR, and YPELGK) were conjugated to bovine serum albumin using N-hydroxysuccinimidyl-4-azidobenzoate. When 125I peptide conjugates, CEA, and BSA were injected intravenously into rats CEA and the PELPK-albumin conjugate were cleared rapidly. The other peptide conjugates and BSA cleared at a much slower rate. Activity of 125I-labeled CEA and PELPK-albumin conjugate per gram of tissue was highest for the liver and spleen. Clearance of 125I-CEA was inhibited by the presence of higher concentrations of the PELPK-albumin conjugate. With isolated rat Kupffer cells, only CEA and the PELPK-albumin conjugate were bound and internalized in vitro and CEA binding was inhibited by higher concentrations of the PELPK-albumin conjugate. Similarly, binding of the PELPK-albumin conjugate was inhibited by the presence of unlabeled CEA. Use of a heterobifunctional cross linking agent demonstrated reaction of the PELPK-albumin with an 80-kDa protein on the Kupffer cell surface by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). This semisynthetic ligand (PELPK-albumin) allows us to examine the function of the 80-kDa receptor without interference due to other properties of CEA including its ability to bind lectins and to cause homotypic aggregation of cells. The consequences of CEA binding to the 80-kDa receptor may have implications in the development of hepatic metastasis from colorectal cancer.

Economic Evaluations in the Diagnosis and Management of Traumatic Brain Injury: A Systematic Review and Analysis of Quality.

PubMed

Alali, Aziz S; Burton, Kirsteen; Fowler, Robert A; Naimark, David M J; Scales, Damon C; Mainprize, Todd G; Nathens, Avery B

2015-07-01

Economic evaluations provide a unique opportunity to identify the optimal strategies for the diagnosis and management of traumatic brain injury (TBI), for which uncertainty is common and the economic burden is substantial. The objective of this study was to systematically review and examine the quality of contemporary economic evaluations in the diagnosis and management of TBI. Two reviewers independently searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment Database, EconLit, and the Tufts CEA Registry for comparative economic evaluations published from 2000 onward (last updated on August 30, 2013). Data on methods, results, and quality were abstracted in duplicate. The results were summarized quantitatively and qualitatively. Of 3539 citations, 24 economic evaluations met our inclusion criteria. Nine were cost-utility, five were cost-effectiveness, three were cost-minimization, and seven were cost-consequences analyses. Only six studies were of high quality. Current evidence from high-quality studies suggests the economic attractiveness of the following strategies: a low medical threshold for computed tomography (CT) scanning of asymptomatic infants with possible inflicted TBI, selective CT scanning of adults with mild TBI as per the Canadian CT Head Rule, management of severe TBI according to the Brain Trauma Foundation guidelines, management of TBI in dedicated neurocritical care units, and early transfer of patients with TBI with nonsurgical lesions to neuroscience centers. Threshold-guided CT scanning, adherence to Brain Trauma Foundation guidelines, and care for patients with TBI, including those with nonsurgical lesions, in specialized settings appear to be economically attractive strategies. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

PubMed

Dong, Dong; Zhang, Lufang; Jia, Li; Ji, Wei; Wang, Zhiyong; Ren, Li; Niu, Ruifang; Zhou, Yunli

2018-06-01

Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.

Ghrelin Increases GABAergic Transmission and Interacts with Ethanol Actions in the Rat Central Nucleus of the Amygdala

PubMed Central

Cruz, Maureen T; Herman, Melissa A; Cote, Dawn M; Ryabinin, Andrey E; Roberto, Marisa

2013-01-01

The neural circuitry that processes natural rewards converges with that engaged by addictive drugs. Because of this common neurocircuitry, drugs of abuse have been able to engage the hedonic mechanisms normally associated with the processing of natural rewards. Ghrelin is an orexigenic peptide that stimulates food intake by activating GHS-R1A receptors in the hypothalamus. However, ghrelin also activates GHS-R1A receptors on extrahypothalamic targets that mediate alcohol reward. The central nucleus of the amygdala (CeA) has a critical role in regulating ethanol consumption and the response to ethanol withdrawal. We previously demonstrated that rat CeA GABAergic transmission is enhanced by acute and chronic ethanol treatment. Here, we used quantitative RT-PCR (qRT-PCR) to detect Ghsr mRNA in the CeA and performed electrophysiological recordings to measure ghrelin effects on GABA transmission in this brain region. Furthermore, we examined whether acute or chronic ethanol treatment would alter these electrophysiological effects. Our qRT-PCR studies show the presence of Ghsr mRNA in the CeA. In naive animals, superfusion of ghrelin increased the amplitude of evoked inhibitory postsynaptic potentials (IPSPs) and the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Coapplication of ethanol further increased the ghrelin-induced enhancement of IPSP amplitude, but to a lesser extent than ethanol alone. When applied alone, ethanol significantly increased IPSP amplitude, but this effect was attenuated by the application of ghrelin. In neurons from chronic ethanol-treated (CET) animals, the magnitude of ghrelin-induced increases in IPSP amplitude was not significantly different from that in naive animals, but the ethanol-induced increase in amplitude was abolished. Superfusion of the GHS-R1A antagonists 𝒟-Lys3-GHRP-6 and JMV 3002 decreased evoked IPSP and mIPSC frequency, revealing tonic ghrelin activity in the CeA. 𝒟-Lys3-GHRP-6 and JMV 3002 also blocked ghrelin-induced increases in GABAergic responses. Furthermore, 𝒟-Lys3-GHRP-6 did not affect ethanol-induced increases in IPSP amplitude. These studies implicate a potential role for the ghrelin system in regulating GABAergic transmission and a complex interaction with ethanol at CeA GABAergic synapses. PMID:22968812

Irinotecan as a new agent for urachal cancer.

PubMed

Kume, Haruki; Tomita, Kyoichi; Takahashi, Sayuri; Fukutani, Keiko

2006-01-01

The urachal carcinoma, in a 64-year-old male with multiple lung metastases, had shown the resistance to several anti-neoplastic agents including cisplatinum, methotrexate, 5-FU, doxorubicin, epirubicin, and mitomycin C. Because the tumor was adenocarcinoma producing mucin and serum carcinoembryonic antigen (CEA) increased, which resembled colorectal carcinoma, we administrated Irinotecan, which was very effective as the CEA decreased from 98.3 to 38.7 ng/ml and the pulmonary metastatic lesions were reduced by 60%. To our knowledge, this is the first case with urachal carcinoma in which Irinotecan was effective. Copyright (c) 2006 S. Karger AG, Basel.

A Prospective Examination of the Relations between Emotional Abuse and Anxiety: Moderation by Distress Tolerance

PubMed Central

Banducci, Anne N.; Lejuez, C.W.; Dougherty, Lea R.; MacPherson, Laura

2016-01-01

Objective Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across five years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Method Community youth (N = 244) were annually assessed across five years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Results Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Conclusions Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time. PMID:27501698

A Prospective Examination of the Relations Between Emotional Abuse and Anxiety: Moderation by Distress Tolerance.

PubMed

Banducci, Anne N; Lejuez, C W; Dougherty, Lea R; MacPherson, Laura

2017-01-01

Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across 5 years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Community youth (N = 244) were annually assessed across 5 years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time.

Gender Differences in Treatment of Severe Carotid Stenosis After TIA

PubMed Central

Poisson, Sharon N.; Johnston, S. Claiborne; Sidney, Stephen; Klingman, Jeffrey G.; Nguyen-Huynh, Mai N.

2010-01-01

Background and Purpose Gender differences in carotid endarterectomy (CEA) rates after transient ischemic attack (TIA) are not well studied, though some reports suggest that eligible men are more likely to have CEA than women after stroke. Methods We retrospectively identified all patients diagnosed with TIA and ≥70% carotid stenosis on ultrasound in 2003-2004 from 19 emergency departments. Medical records were abstracted for clinical data, 90-day follow-up events including stroke, cardiovascular events or death, CEA within 6 months, and post-operative 30-day outcomes. We assessed gender as a predictor of CEA and its complications, adjusting for demographic and clinical variables, as well as time to CEA between groups. Results Of 299 patients identified, 47% were women. Women were older with higher presenting SBP and less likely to smoke or to have CAD or diabetes. Fewer women (36.4%) had CEA than men (53.8%) (p=0.004). Reasons for withholding surgical treatment were similar in women and men, and there were no differences in follow-up stroke, CV event, postoperative complications or death. Time to CEA was also significantly delayed in women. Conclusions Women with severe carotid stenosis and recent TIA are less likely to undergo CEA than men, and surgeries are more delayed. PMID:20651270

A physician-led initiative to improve clinical documentation results in improved health care documentation, case mix index, and increased contribution margin.

PubMed

Aiello, Francesco A; Judelson, Dejah R; Durgin, Jonathan M; Doucet, Danielle R; Simons, Jessica P; Durocher, Dawn M; Flahive, Julie M; Schanzer, Andres

2018-05-04

Clinical documentation is the key determinant of inpatient acuity of illness and payer reimbursement. Every inpatient hospitalization is placed into a diagnosis related group with a relative value based on documented procedures, conditions, comorbidities and complications. The Case Mix Index (CMI) is an average of these diagnosis related groups and directly impacts physician profiling, medical center profiling, reimbursement, and quality reporting. We hypothesize that a focused, physician-led initiative to improve clinical documentation of vascular surgery inpatients results in increased CMI and contribution margin. A physician-led coding initiative to educate physicians on the documentation of comorbidities and conditions was initiated with concurrent chart review sessions with coding specialists for 3 months, and then as needed, after the creation of a vascular surgery documentation guide. Clinical documentation and billing for all carotid endarterectomy (CEA) and open infrainguinal procedures (OIPs) performed between January 2013 and July 2016 were stratified into precoding and postcoding initiative groups. Age, duration of stay, direct costs, actual reimbursements, contribution margin (CM), CMI, rate of complication or comorbidity, major complication or comorbidity, severity of illness, and risk of mortality assigned to each discharge were abstracted. Data were compared over time by standardizing Centers for Medicare and Medicaid Services (CMS) values for each diagnosis related group and using a CMS base rate reimbursement. Among 458 CEA admissions, postcoding initiative CEA patients (n = 253) had a significantly higher CMI (1.36 vs 1.25; P = .03), CM ($7859 vs $6650; P = .048), and CMS base rate reimbursement ($8955 vs $8258; P = .03) than precoding initiative CEA patients (n = 205). The proportion of admissions with a documented major complication or comorbidity and complication or comorbidity was significantly higher after the coding initiative (43% vs 27%; P < .01). Among 504 OIPs, postcoding initiative patients (n = 227) had a significantly higher CMI (2.23 vs 2.05; P < .01), actual reimbursement ($23,203 vs $19,909; P < .01), CM ($12,165 vs $8840; P < .01), and CMS base rate reimbursement ($14,649 vs $13,496; P < .01) than precoding initiative patients (n = 277). The proportion of admissions with a documented major complication or comorbidity and complication or comorbidity was significantly higher after the coding initiative (61% vs 43%; P < .01). For both CEA and OIPs, there were no differences in age, duration of stay, total direct costs, or primary insurance status between the precoding and postcoding patient groups. Accurate and detailed clinical documentation is required for key stakeholders to characterize the acuity of inpatient admissions and ensure appropriate reimbursement; it is also a key component of risk-adjustment methods for assessing quality of care. A physician-led documentation initiative significantly increased CMI and CM. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Patient characteristics and outcomes of carotid endarterectomy and carotid artery stenting: analysis of the German mandatory national quality assurance registry - 2003 to 2014.

PubMed

Kallmayer, M A; Tsantilas, P; Knappich, C; Haller, B; Storck, M; Stadlbauer, T; Kühnl, A; Zimmermann, A; Eckstein, H H

2015-12-01

In Germany, every surgical or endovascular procedure on the extracranial carotid artery is documented in a mandatory quality assurance registry. The purpose of this study is to describe the patient characteristics, the indications for treatment, and the short-term outcomes as well as to analyse the corresponding trends from 2003 to 2014. Data on demographics, peri-procedural measures, and outcomes were extracted from the annual quality reports published by the Federal Agency for Quality Assurance and the Institute for Applied Quality Improvement and Research in Health Care. Data were available from 2003 to 2014 for carotid endarterectomy (CEA) and from 2012 to 2014 for carotid artery stenting (CAS). The primary outcome event of this study is any stroke or death until discharge from hospital. Temporal trends of categorical variables were statistically analysed using the Cochran-Armitage test for trend. Between 2003 and 2014, 309,405 CEAs and 18,047 CAS procedures were documented in the database; 68.1% of all patients were male. The mean age of patients treated with CEA increased from 68.9 years in 2003 to 70.9 years in 2014. The proportion of patients with ASA stages III to V increased from 65% to 71% in CEA, whereas it decreased from 44% to 41% in CAS patients. 53.1% of all CEAs were performed for asymptomatic patients (group A), 34.4% for symptomatic patients treated electively (group B), and 11.2% a in a collective group including other indications for CEA or CAS (such as recurrent stenosis, carotid aneurysms, emergency treatment due to stroke-in-evolution). The corresponding data for CAS are 49.3%, 26.1% and 26.3% respectively. In group B, the interval between the neurological index event and CEA decreased from 28 to 8 days (P<0.001). In patients treated with CAS, this interval was 9 days in 2012 (no further data available). On average, 67.1% and 48.2% of surgically treated patients as well as 77.8% and 69.8% of CAS patients were neurologically assessed before and after the procedure, respectively. From 2003 to 2014, CEA procedures were performed more frequently in locoregional anesthesia (10.1% to 29.1%, P<0.001). The same trend was observed for the application of the eversion technique (37.0% to 41.6%, P<0.001), the neurophysiological monitoring (49.8% to 61.8%, P<0.001), and the intra-procedural assessment of the treated artery (44.5% to 69.7%, P<0.001). In contrast, shunting was used less frequently (48.1% to 43.0%, P<0.001). Averagely 95.7% of all endovascular procedures were performed using stent-angioplasty. In 54.2% a protection device was used. Nitinol and bare metal stents were used in 74.1% and 21.4% of cases, respectively. The in-hospital rate of any stroke or death decreased from 2.0% to 1.1% in asymptomatic patients treated with CEA without a contralateral stenosis ≥75% or occlusion, P<0.001). In patients treated with CAS this rate did not increase (1.7% to 1.8%, p=0.909). The corresponding rates in CEA and CAS patients with severe contralateral stenosis or occlusion varied between 1.9%-3.1% and 2.2%-2.6%, respectively. In symptomatic patients (group B) with a stenosis of 50 percent or more, the rate of any stroke or death decreased significantly after CEA from 4.2% to 2.4% (P<0.001) and remained stable after CAS (3.9% to 3.5%, P=0.577). This report on 327,452 carotid procedures analysed one of the largest quality registries on CEA and CAS worldwide. Data indicate that treated patients became older and sicker, whereas in contrast, the in-hospital rates of stroke or death are decreasing over time.

Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior.

PubMed

Mendes, Natalia Ferreira; Castro, Gisele; Guadagnini, Dioze; Tobar, Natalia; Cognuck, Susana Quiros; Elias, Lucila Leico Kagohara; Boer, Patricia Aline; Prada, Patricia Oliveira

2017-05-01

Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent. Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term results of a randomized controlled trial analyzing the role of systematic pre-operative coronary angiography before elective carotid endarterectomy in patients with asymptomatic coronary artery disease.

PubMed

Illuminati, G; Schneider, F; Greco, C; Mangieri, E; Schiariti, M; Tanzilli, G; Barillà, F; Paravati, V; Pizzardi, G; Calio', F; Miraldi, F; Macrina, F; Totaro, M; Greco, E; Mazzesi, G; Tritapepe, L; Toscano, M; Vietri, F; Meyer, N; Ricco, J-B

2015-04-01

To evaluate the potential benefit of systematic preoperative coronary-artery angiography followed by selective coronary-artery revascularization on the incidence of myocardial infarction (MI) in patients undergoing carotid endarterectomy (CEA) without a previous history of coronary artery disease (CAD). We randomised 426 patients who were candidates for CEA, with no history of CAD, a normal electrocardiogram (ECG), and a normal cardiac ultrasound. In group A (n = 216) all patients underwent coronary angiography before CEA. In group B (n = 210) CEA was performed without coronary angiography. Patients were not blinded for relevant assessments during follow-up. Primary end-point was the occurrence of MI at 3.5 years. The secondary end-point was the overall survival rate. Median length of follow-up was 6.2 years. In group A, coronary angiography revealed significant coronary artery stenosis in 68 patients (31.5%). Among them, 66 underwent percutaneous Intervention (PCI) prior to CEA and 2 received combined CEA and coronary-artery bypass grafting (CABG). Postoperatively, no MI was observed in group A, whereas 6 MI occurred in group B, one of which was fatal (p = .01). During the study period, 3 MI occurred in group A (1.4%) and 33 were observed in group B (15.7%), 6 of which were fatal. The Cox model demonstrated a reduced risk of MI for patients in group A receiving coronary angiography (HR,.078; 95% CI, 0.024-0.256; p < .001). In addition, patients with diabetes and patients <70 years presented with an increased risk of MI. Survival analysis at 6 years by Kaplan-Meier estimates was 95.6 ± 3.2% in Group A and 89.7 ± 3.7% in group B (Log Rank = 6.54, p = .01). In asymptomatic coronary-artery patients, systematic coronary angiography prior to CEA followed by selective PCI or CABG significantly reduces the incidence of late MI and increases long-term survival. (ClinicalTrials.gov number, NCT02260453). Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

THE ROLE OF AMYGDALAR MU OPIOID RECEPTORS IN ANXIETY-RELATED RESPONSES IN TWO RAT MODELS

PubMed Central

Wilson, Marlene A.; Junor, Lorain

2009-01-01

Amygdala opioids such as enkephalin appear to play some role in the control of anxiety and the anxiolytic effects of benzodiazepines, although the opioid receptor subtypes mediating such effects are unclear. This study compared the influences of mu opioid receptor (MOR) activation in the central nucleus of the amygdala (CEA) on unconditioned fear or anxiety-like responses in two models, the elevated plus maze and the defensive burying test. The role of MOR in the anxiolytic actions of the benzodiazepine agonist diazepam was also examined using both models. Either the MOR agonist [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO) or the MOR antagonists Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) or β-funaltrexamine (FNA) were bilaterally infused into the CEA of rats prior to testing. The results show that microinjection of DAMGO in the CEA decreased open arm time in the plus maze, while CTAP increased open arm behaviors. In contrast, DAMGO injections in the CEA reduced burying behaviors and increased rearing following exposure to a predator odor, suggesting a shift in the behavioral response in this context. Amygdala injections of the MOR agonist DAMGO or the MOR antagonist CTAP failed to change the anxiolytic effects of diazepam in either test. Our results demonstrate that MOR activation in the central amygdala exerts distinctive effects in two different models of unconditioned fear or anxiety-like responses, and suggest that opioids may exert context-specific regulation of amygdala output circuits and behavioral responses during exposure to potential threats (open arms of the maze) versus discrete threats (predator odor). PMID:18216773

Development and characterisation of MCT detectors for space astrophysics at CEA

NASA Astrophysics Data System (ADS)

Boulade, O.; Baier, N.; Castelein, P.; Cervera, C.; Chorier, P.; Destefanis, G.; Fièque, B.; Gravrand, O.; Guellec, F.; Moreau, V.; Mulet, P.; Pinsard, F.; Zanatta, J.-P.

2017-11-01

The Laboratoire Electronique et Traitement de l'Information (LETI) of the Commissariat à l'Energie Atomique (CEA, Grenoble, France) has been involved in the development of infrared detectors based on HgCdTe (MCT) material for over 30 years, mainly for defence and security programs [1]. Once the building blocks are developed at LETI (MCT material process, diode technology, hybridization, …), the industrialization is performed at SOFRADIR (also in Grenoble, France) which also has its own R&D program [2]. In past years, LETI also developed infrared detectors for space astrophysics in the mid infrared range - the long wave detector of the ISOCAM camera onboard ISO - as well as in the far infrared range - the bolometer arrays of the Herschel/PACS photometer unit -, both instruments which were under the responsibility of the Astrophysics department of CEA (IRFU/SAp, Saclay, France). Nowadays, the infrared detectors used in space and ground based astronomical instruments all come from vendors in the US. For programmatic reasons - increase the number of available vendors, decrease the cost, mitigate possible export regulations, …- as well as political ones - spend european money in Europe -, the European Space Agency (ESA) defined two roadmaps (one in the NIR-SWIR range, one in the MWIR-LWIR range) that will eventually allow for the procurement of infrared detectors for space astrophysics within Europe. The French Space Agency (CNES) also started the same sort of roadmaps, as part of its contribution to the different space missions which involve delivery of instruments by French laboratories. It is important to note that some of the developments foreseen in these roadmaps also apply to Earth Observations. One of the main goal of the ESA and CNES roadmaps is to reduce the level of dark current in MCT devices at all wavelengths. The objective is to use the detectors at the highest temperature where the noise induced by the dark current stays compatible with the photon noise, as the detector operating temperature has a very strong impact at system level. A consequence of reaching low levels of dark current is the need for very low noise readout circuits. CEA and SOFRADIR are involved in a number of activities that have already started in this framework. CEA/LETI does the development of the photo-voltaic (PV) layers - MCT material growth, diode technologies-, as well as some electro-optical characterisation at wafer, diode and hybrid component levels, and CEA/IRFU/SAp does all the electro-optical characterisation involving very low flux measurements (mostly dark current measurements). Depending of the program, SOFRADIR can also participate in the development of the hybrid components, for instance the very low noise readout circuits (ROIC) can be developed either at SOFRADIR or at CEA/LETI. Depending of the component specifications, the MCT epitaxy can be either liquid phase (LPE, which is the standard at SOFRADIR for production purposes) or molecular beam (MBE), the diode technology can be n/p (standard at LETI and SOFRADIR) or p/n (under development for several years now) [3], and the input stage of the ROIC can be Source Follower per Detector (SFD for very low flux low noise programs) or Capacitive Trans Impedance Amplifier (CTIA for intermediate flux programs) [4]. This paper will present the different developments and results obtained so far in the two NIR-SWIR and MWIR-LWIR spectral ranges, as well as the perspectives for the near future. CEA/LETI is also involved in the development of MCT Avalanche Photo Diodes (APD) that will be discussed in other papers [5,6].

A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment.

PubMed

Liu, Ko-Jiunn; Chao, Tsu-Yi; Chang, Jang-Yang; Cheng, Ann-Lii; Ch'ang, Hui-Ju; Kao, Woei-Yau; Wu, Yu-Chen; Yu, Wei-Lan; Chung, Tsai-Rong; Whang-Peng, Jacqueline

2016-08-24

To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment. Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA. No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients. The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses. ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005.

Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats.

PubMed

Dumais, Kelly M; Alonso, Andrea G; Bredewold, Remco; Veenema, Alexa H

2016-08-25

We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5ng/0.5μl/side) or OT (100pg/0.5μl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest toward juvenile conspecifics in males. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

A peptide sequence on carcinoembryonic antigen binds to a 80kD protein on Kupffer cells.

PubMed

Thomas, P; Petrick, A T; Toth, C A; Fox, E S; Elting, J J; Steele, G

1992-10-30

Clearance of carcinoembryonic antigen (CEA) from the circulation is by binding to Kupffer cells in the liver. We have shown that CEA binding to Kupffer cells occurs via a peptide sequence YPELPK representing amino acids 107-112 of the CEA sequence. This peptide sequence is located in the region between the N-terminal and the first immunoglobulin like loop domain. Using native CEA and peptides containing this sequence complexed with a heterobifunctional crosslinking agent and ligand blotting with biotinylated CEA and NCA we have shown binding to an 80kD protein on the Kupffer cell surface. This binding protein may be important in the development of hepatic metastases.

Comparison of the quantitative determination of soil organic carbon in coastal wetlands containing reduced forms of Fe and S

NASA Astrophysics Data System (ADS)

Passos, Tassia R. G.; Artur, Adriana G.; Nóbrega, Gabriel N.; Otero, Xosé L.; Ferreira, Tiago O.

2016-06-01

The performance of the Walkley-Black wet oxidation chemical method for soil organic carbon (SOC) determination in coastal wetland soils (mangroves, coastal lagoons, and hypersaline tidal flats) was evaluated in the state of Ceará along the semiarid coast of Brazil, assessing pyrite oxidation and its effects on soil C stock (SCS) quantification. SOC determined by the chemical oxidation method (CWB) was compared to that assessed by means of a standard elemental analyzer (CEA) for surficial samples (<30 cm depth) from the three wetland settings. The pyrite fraction was quantified in various steps of the chemical oxidation method, evaluating the effects of pyrite oxidation. Regardless of the method used, and consistent with site-specific physicochemical conditions, higher pyrite and SOC contents were recorded in the mangroves, whereas lower values were found in the other settings. CWB values were higher than CEA values. Significant differences in SCS calculations based on CWB and CEA were recorded for the coastal lagoons and hypersaline tidal flats. Nevertheless, the CWB and CEA values were strongly correlated, indicating that the wet oxidation chemical method can be used in such settings. In contrast, the absence of correlation for the mangroves provides evidence of the inadequacy of this method for these soils. Air drying and oxidation decrease the pyrite content, with larger effects rooted in oxidation. Thus, the wet oxidation chemical method is not recommended for mangrove soils, but seems appropriate for SOC/SCS quantification in hypersaline tidal flat and coastal lagoon soils characterized by lower pyrite contents.

Analysis of Phenix end-of-life natural convection test with the MARS-LMR code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeong, H. Y.; Ha, K. S.; Lee, K. L.

The end-of-life test of Phenix reactor performed by the CEA provided an opportunity to have reliable and valuable test data for the validation and verification of a SFR system analysis code. KAERI joined this international program for the analysis of Phenix end-of-life natural circulation test coordinated by the IAEA from 2008. The main objectives of this study were to evaluate the capability of existing SFR system analysis code MARS-LMR and to identify any limitation of the code. The analysis was performed in three stages: pre-test analysis, blind posttest analysis, and final post-test analysis. In the pre-test analysis, the design conditionsmore » provided by the CEA were used to obtain a prediction of the test. The blind post-test analysis was based on the test conditions measured during the tests but the test results were not provided from the CEA. The final post-test analysis was performed to predict the test results as accurate as possible by improving the previous modeling of the test. Based on the pre-test analysis and blind test analysis, the modeling for heat structures in the hot pool and cold pool, steel structures in the core, heat loss from roof and vessel, and the flow path at core outlet were reinforced in the final analysis. The results of the final post-test analysis could be characterized into three different phases. In the early phase, the MARS-LMR simulated the heat-up process correctly due to the enhanced heat structure modeling. In the mid phase before the opening of SG casing, the code reproduced the decrease of core outlet temperature successfully. Finally, in the later phase the increase of heat removal by the opening of the SG opening was well predicted with the MARS-LMR code. (authors)« less

Optogenetic Excitation of Central Amygdala Amplifies and Narrows Incentive Motivation to Pursue One Reward Above Another

PubMed Central

Warlow, Shelley M.; Berridge, Kent C.

2014-01-01

Choosing one reward above another is important for achieving adaptive life goals. Yet hijacked into excessive intensity in disorders such as addiction, single-minded pursuit becomes maladaptive. Here, we report that optogenetic channelrhodopsin stimulation of neurons in central nucleus of amygdala (CeA), paired with earning a particular sucrose reward in rats, amplified and narrowed incentive motivation to that single reward target. Therefore, CeA rats chose and intensely pursued only the laser-paired sucrose reward while ignoring an equally good sucrose alternative. In contrast, reward-paired stimulation of basolateral amygdala did not hijack choice. In a separate measure of incentive motivation, CeA stimulation also increased the progressive ratio breakpoint or level of effort exerted to obtain sucrose reward. However, CeA stimulation by itself failed to support behavioral self-stimulation in the absence of any paired external food reward, suggesting that CeA photo-excitation specifically transformed the value of its external reward (rather than adding an internal reinforcement state). Nor did CeA stimulation by itself induce any aversive state that motivated escape. Finally, CeA stimulation also failed to enhance ‘liking’ reactions elicited by sucrose taste and did not simply increase the general motivation to eat. This pattern suggests that CeA photo-excitation specifically enhances and narrows incentive motivation to pursue an associated external reward at the expense of another comparable reward. PMID:25505310

[Significance of the TPS cytokeratin marker in the postoperative follow up of colorectal carcinoma patients].

PubMed

Rupert, K; Holubec, L; Nosek, J; Houdek, K; Topolcan, O; Treska, V

2009-08-01

Examination of tumour markers conducive to follow up of the patients with colorectal carcinoma. The tumour markers were examined in the population of patients with primarily established and histologically verified colorectal adenocarcinoma. The resection therapy resulted in the decrease in post-operative CEA levels. There were no changes in pre- and post-operative CA 19-9 levels; unlike with post-operative TPS levels having been significantly increased, probably due to reparation processes resulting from the surgery. It can be concluded that pre- and post-operative CEA levels are the most suitable markers to check the effect of surgery. With a 95%-specificity for the establishment of recidives, the highest sensitivity was reached with TPS (83%); the sensitivities of the classical tumour markers CEA and CA 19-9 were significantly lower (41% and 25%, respectively). The results should be interpreted with caution due to a small number of relapses regarding a short follow up and rather local-regional character of the recidives. However, TPS seems to be a promising marker for the follow up of the patients with colorectal carcinoma. Thus, an ideal combination seems to be that of CEA and TPS.

Prescription of Guideline-Based Medical Therapies at Discharge After Carotid Artery Stenting and Endarterectomy: An NCDR Analysis.

PubMed

Aronow, Herbert D; Kennedy, Kevin F; Wayangankar, Siddharth A; Katzen, Barry T; Schneider, Peter A; Abou-Chebl, Alex; Rosenfield, Kenneth A

2016-09-01

Carotid artery revascularization was previously found to incrementally reduce stroke risk among patients with carotid stenosis treated with medical therapy. However, the frequency with which optimal medical therapies are used at discharge after carotid endarterectomy (CEA) and carotid artery stenting (CAS) is not known, and the influence of patient, operator, and hospital characteristics on the likelihood of prescription is poorly understood. In a retrospective cohort study of 23 112 patients undergoing CAS or CEA between January 2007 and June 2012 at US hospitals participating in the CARE registry (Carotid Artery Revascularization and Endarterectomy), we examined antiplatelet therapy and statin utilization at discharge. Hierarchical multivariable logistic regression was used in adjusted analyses. Antiplatelet agents and statins were prescribed at discharge in 99% and 78%, respectively, after CAS and 93% and 75%, respectively, after CEA. After adjustment, antiplatelet therapy was more often prescribed after CAS than CEA (odds ratio 2.4 [95% confidence interval 1.68-3.45]), but statin prescription was equally likely (odds ratio 1.11 [95% confidence interval 0.84-1.49]). Operator specialty (medical>radiology/surgery) and hospital community setting (suburban>urban>rural) independently predicted antiplatelet and statin agent use at discharge, whereas hospital geographic location (Northeast>Midwest/South>West) predicted use of statins but not antiplatelet therapy at discharge. US antiplatelet agent and statin discharge prescription rates were suboptimal after both CAS and CEA and varied by revascularization modality, operating physician specialty, and hospital characteristics. Improved and more uniform utilization after these procedures will be critical to the success of comprehensive stroke risk reduction efforts. © 2016 American Heart Association, Inc.

Alu–based cell-free DNA: a novel biomarker for screening of gastric cancer

PubMed Central

Zhao, Jianmei; Shen, Xianjuan; Jing, Rongrong; Yu, Juan; Li, Li; Shi, Yingjuan; Zhang, Lurong; Wang, Zhiwei; Cong, Hui

2017-01-01

Gastric cancer (GC) is the fourth most common cancer and the second major cause of cancer-related deaths worldwide. In our previous study, a novel and sensitive method for quantifying cell-free DNA (CFD) in human blood was established and tested for its ability to predict patients with tumor. We want to investigate CFD expression in the sera of GC patients in an attempt to explore the clinical significance of CFD in improving the early screening of GC and monitoring GC progression by the branched DNA (bDNA)-based Alu assay. The concentration of CFD was quantitated by bDNA-based Alu assay. CEA, CA19-9, C72-4 and CA50 concentrations were determined by ABBOTT ARCHITECT I2000 SR. We found the CFD concentrations have significant differences between GC patients, benign gastric disease (BGD) patients and healthy controls (P < 0.05). CFD were weakly correlated with CEA (r = −0.197, P < 0.05) or CA50 (r = 0.206, P < 0.05), and no correlation with CA19-9 (r = −0.061, P > 0.05) or CA72-4 (r = 0.011, P > 0.05). In addition, CFD concentrations were significantly higher in stage I GC patients than BGD patients and healthy controls (P < 0.05), but there was no significant difference in CEA, CA19-9 and CA50 among the three traditional tumor markers (P > 0.05). Our analysis showed that CFD was more sensitive than CEA, CA19-9, CA72-4 or CA50 in early screening of GC. Compared with CEA, CA19-9, CA72-4 and CA50, CFD may prove to be a better biomarker for the screening of GC, thus providing a sensitive biomarker for screening and monitoring progression of GC. PMID:28903321

Pretargeting of carcinoembryonic antigen-expressing cancers with a trivalent bispecific fusion protein produced in myeloma cells.

PubMed

Rossi, Edmund A; Chang, Chien-Hsing; Losman, Michele J; Sharkey, Robert M; Karacay, Habibe; McBride, William; Cardillo, Thomas M; Hansen, Hans J; Qu, Zhengxing; Horak, Ivan D; Goldenberg, David M

2005-10-01

To characterize a novel trivalent bispecific fusion protein and evaluate its potential utility for pretargeted delivery of radionuclides to tumors. hBS14, a recombinant fusion protein that binds bispecifically to carcinoembryonic antigen (CEA) and the hapten, histamine-succinyl-glycine (HSG), was produced by transgenic myeloma cells and purified to near homogeneity in a single step using a novel HSG-based affinity chromatography system. Biochemical characterization included size-exclusion high-performance liquid chromatography (SE-HPLC), SDS-PAGE, and isoelectric focusing. Functional characterization was provided by BIAcore and SE-HPLC. The efficacy of hBS14 for tumor pretargeting was evaluated in CEA-expressing GW-39 human colon tumor-bearing nude mice using a bivalent HSG hapten (IMP-241) labeled with (111)In. Biochemical analysis showed that single-step affinity chromatography provided highly purified material. SE-HPLC shows a single protein peak consistent with the predicted molecular size of hBS14. SDS-PAGE analysis shows only two polypeptide bands, which are consistent with the calculated molecular weights of the hBS14 polypeptides. BIAcore showed the bispecific binding properties and suggested that hBS14 possesses two functional CEA-binding sites. This was supported by SE-HPLC immunoreactivity experiments. All of the data suggest that the structure of hBS14 is an 80 kDa heterodimer with one HSG and two CEA binding sites. Pretargeting experiments in the mouse model showed high uptake of radiopeptide in the tumor, with favorable tumor-to-nontumor ratios as early as 3 hours postinjection. The results indicate that hBS14 is an attractive candidate for use in a variety of pretargeting applications, particularly tumor therapy with radionuclides and drugs.

Efficacy and safety of stenting for elderly patients with severe and symptomatic carotid artery stenosis: a critical meta-analysis of randomized controlled trials.

PubMed

Ouyang, Yi-An; Jiang, Yugang; Yu, Mengqiang; Zhang, Yunze; Huang, Hao

2015-01-01

To investigate both short-term and long-term therapeutic efficacy and safety of carotid artery stenting (CAS) and carotid artery endarterectomy (CEA) for elderly patients with severe and symptomatic carotid artery stenosis. PubMed, EMBASE, Cochrane Library, Clinical Trials Register Centers, and Google Scholar were comprehensively searched. After identifying relevant randomized controlled trials, methodological quality was assessed by using Cochrane tools of bias assessment. Meta-analysis was performed by RevMan software, and subgroup analyses according to different follow-up periods were also conducted. Sixteen articles of nine randomized controlled trials containing 6,984 patients were included. Compared with CEA, CAS was associated with high risks of stroke during periprocedural 30 days (risk ratio [RR]=1.47, 95% confidence interval [CI]: 1.15-1.88), 48 months (RR=1.37, 95% CI: 1.11-1.70), and >48 months (RR=1.76, 95% CI: 1.34-2.31). There was no significant difference in the aspects of death, disabling stroke, or death at any time between the groups. For other periprocedural complications, CAS decreased the risk of myocardial infarction (RR=0.44, 95% CI: 0.26-0.75), cranial nerve palsy (RR=0.09, 95% CI: 0.04-0.22) and hematoma (RR=0.31, 95% CI: 0.14-0.68) compared with CEA, while it increased the risk of bradycardia or hypotension (RR=8.45, 95% CI 2.91-24.58). Compared with CEA, CAS reduced hematoma, periprocedural myocardial infarction, and cranial nerve palsy, while it was associated with higher risks of both short-term and long-term nondisabling stroke. And they seemed to be equivalent in other outcome measures. As regards to its minimal invasion, it should be applied only in specific patients.

The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning

PubMed Central

Keifer, Orion P.; Hurt, Robert C.; Ressler, Kerry J.

2015-01-01

The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. PMID:26328883

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

PubMed

Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

2015-01-01

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

[Usefulness of evaluation of carcinoembryonic antigen (CEA) and soluble fragments of cytokeratin 18-th (TPS) in postoperative monitoring of patients with colorectal cancer].

PubMed

Sandelewski, Artur; Kokocińska, Danuta; Partyka, Robert; Kocot, Jacek; Starzewski, Jacek; Chanek, Izabela; Jałowiecki, Przemysław

2005-06-01

The aim of this study is to diagnose the evaluation of concentration of CEA and TPS in postoperative monitoring of patients with colorectal cancer. We measured 178 consecutive patients with histopathologically confirmed colorectal cancer: 101 men and 78 women ages 22-86 (average age 54.7). Markers' CEA nad TPS concentration were evaluated before operation and every month after operation during the first 3 months and then every 3 months during 2 years. Relapse was detected in 47 patients. In postoperative period in non-relapse group the mean (the average) concentration of CEA was 1.92+/-2.03 ng/ml and TPS 65.54+/-33.96 U/l and respectively in relapse group for CEA was 1.92+/-2.03 ng/ml and for TPS 65.54+/-33.96 U/l. The obtained results in investigated group show significantly statistical. The relapse was confirmed by using CEA concentration in 42 patients (89.4%). In case of TPS concentration relapse was confirmed in 38 patients (80.85%). The relapse was detected in 45 patients (95.74) if increase in CEA or TPS concentration was treated as a way of detecting relapse. TPS markers point out that the increase of TPS concentartion may be ahead of relapse symptoms at about 2-6 months. TPS is a useful marker in postoperative monitoring of patients with colorectal cancer. The evaluation of TPS concentration allow to diagnose the recurrence of colorectal cancer earlier than by using burden markers--CEA. Common evaluation of TPS and CEA increase sensitivity in detection of relapse in patients with colorectal cancer.

Cerebral hyperperfusion following carotid endarterectomy: diagnostic utility of intraoperative transcranial Doppler ultrasonography compared with single-photon emission computed tomography study.

PubMed

Ogasawara, Kuniaki; Inoue, Takashi; Kobayashi, Masakazu; Endo, Hidehoko; Yoshida, Kenji; Fukuda, Takeshi; Terasaki, Kazunori; Ogawa, Akira

2005-02-01

Cerebral hyperperfusion syndrome is a rare but serious complication of carotid endarterectomy (CEA). The aim of the present study was to determine whether intraoperative blood flow velocity (BFV) monitoring in the middle cerebral artery (MCA) by using transcranial Doppler ultrasonography (TCD) could be used as a reliable technique to detect cerebral hyperperfusion following CEA by comparing findings with those of brain single photon emission CT (SPECT). Intraoperative BFV monitoring was attempted in 67 patients undergoing CEA for treatment of ipsilateral internal carotid artery (ICA) stenosis (> or =70%). Cerebral blood flow (CBF) was also assessed using SPECT, which was performed before and immediately after CEA. Intraoperative BFV monitoring was achieved in 60 patients. Of the 60 patients, post-CEA hyperperfusion (CBF increase > or =100%, compared with preoperative values) was observed in six patients. The sensitivity, specificity, and positive predictive value of the BFV increases immediately after declamping of the ICA for detecting post-CEA hyperperfusion was 100%, 94% and 67%, respectively, with a cut-off point 2.0-fold that of preclamping BFV. The sensitivity and specificity of the BFV increases at the end of the procedure for detecting post-CEA hyperperfusion were 100% for both parameters, with cut-off points of 2.0- to 2.2-fold BFV of preclamping value. Hyperperfusion syndrome developed in two patients with post-CEA hyperperfusion, but intracerebral hemorrhage did not occur. In one of these two patients, BFV monitoring was not possible because of failure to obtain an adequate bone window. Intraoperative MCA BFV monitoring by using TCD is a less reliable method to detect cerebral hyperperfusion following CEA than postoperative MCA BFV monitoring, provided adequate monitoring can be achieved.

Mouse models expressing human carcinoembryonic antigen (CEA) as a transgene: Evaluation of CEA-based cancer vaccines

PubMed Central

Hance, Kenneth W.; Zeytin, Hasan E.; Greiner, John W.

2010-01-01

In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens might be exploited as targets for active specific immunotherapy, specifically human cancer vaccines. Not too long ago such an approach would have been met with considerable skepticism because the immune system was believed to be a rigid discriminator between self and non-self which, in turn, protected the host from a variety of pathogens. That viewpoint has been challenged in recent years by a series of studies indicating that antigenic determinants of self have not induced absolute host immune tolerance. Moreover, under specific conditions that evoke danger signals, peptides from self-antigen can be processed by the antigen-presenting cellular machinery, loaded onto the major histocompatibility antigen groove to serve as targets for immune intervention. Those findings provide the rationale to investigate a wide range of tumor-associated antigens, including differentiation antigens, oncogenes, and tumor suppressor genes as possible immune-based targets. One of those tumor-associated antigens is the carcinoembryonic antigen (CEA). Described almost 40 years ago, CEA is a Mr 180–200,000 oncofetal antigen that is one of the more widely studied human tumor-associated antigens. This review will provide: (i) a brief overview of the CEA gene family, (ii) a summary of early preclinical findings on overcoming immune tolerance to CEA, and (iii) the rationale to develop mouse models which spontaneously develop gastrointestinal tumors and express the CEA transgene. Those models have been used extensively in the study of overcoming host immune tolerance to CEA, a self, tumor-associated antigen, and the experimental findings have served as the rationale for the design of early clinical trials to evaluate CEA-based cancer vaccines. PMID:15888344

Clinical and cost-effectiveness, safety and acceptability of community intravenous antibiotic service models: CIVAS systematic review.

PubMed

Mitchell, E D; Czoski Murray, C; Meads, D; Minton, J; Wright, J; Twiddy, M

2017-04-20

Evaluate evidence of the efficacy, safety, acceptability and cost-effectiveness of outpatient parenteral antimicrobial therapy (OPAT) models. A systematic review. MEDLINE, EMBASE, CINAHL, Cochrane Library, National Health Service (NHS) Economic Evaluation Database (EED), Research Papers in Economics (RePEc), Tufts Cost-Effectiveness Analysis (CEA) Registry, Health Business Elite, Health Information Management Consortium (HMIC), Web of Science Proceedings, International Pharmaceutical Abstracts, British Society for Antimicrobial Chemotherapy website. Searches were undertaken from 1993 to 2015. All studies, except case reports, considering adult patients or practitioners involved in the delivery of OPAT were included. Studies combining outcomes for adults and children or non-intravenous (IV) and IV antibiotic groups were excluded, as were those focused on process of delivery or clinical effectiveness of 1 antibiotic over another. Titles/abstracts were screened by 1 reviewer (20% verified). 2 authors independently screened studies for inclusion. 128 studies involving >60 000 OPAT episodes were included. 22 studies (17%) did not indicate the OPAT model used; only 29 involved a comparator (23%). There was little difference in duration of OPAT treatment compared with inpatient therapy, and overall OPAT appeared to produce superior cure/improvement rates. However, when models were considered individually, outpatient delivery appeared to be less effective, and self-administration and specialist nurse delivery more effective. Drug side effects, deaths and hospital readmissions were similar to those for inpatient treatment, but there were more line-related complications. Patient satisfaction was high, with advantages seen in being able to resume daily activities and having greater freedom and control. However, most professionals perceived challenges in providing OPAT. There were no systematic differences related to the impact of OPAT on treatment duration or adverse events. However, evidence of its clinical benefit compared with traditional inpatient treatment is lacking, primarily due to the dearth of good quality comparative studies. There was high patient satisfaction with OPAT use but the few studies considering practitioner acceptability highlighted organisational and logistic barriers to its delivery. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Clinical and cost-effectiveness, safety and acceptability of community intravenous antibiotic service models: CIVAS systematic review

PubMed Central

Czoski Murray, C; Meads, D; Minton, J; Twiddy, M

2017-01-01

Objective Evaluate evidence of the efficacy, safety, acceptability and cost-effectiveness of outpatient parenteral antimicrobial therapy (OPAT) models. Design A systematic review. Data sources MEDLINE, EMBASE, CINAHL, Cochrane Library, National Health Service (NHS) Economic Evaluation Database (EED), Research Papers in Economics (RePEc), Tufts Cost-Effectiveness Analysis (CEA) Registry, Health Business Elite, Health Information Management Consortium (HMIC), Web of Science Proceedings, International Pharmaceutical Abstracts, British Society for Antimicrobial Chemotherapy website. Searches were undertaken from 1993 to 2015. Study selection All studies, except case reports, considering adult patients or practitioners involved in the delivery of OPAT were included. Studies combining outcomes for adults and children or non-intravenous (IV) and IV antibiotic groups were excluded, as were those focused on process of delivery or clinical effectiveness of 1 antibiotic over another. Titles/abstracts were screened by 1 reviewer (20% verified). 2 authors independently screened studies for inclusion. Results 128 studies involving >60 000 OPAT episodes were included. 22 studies (17%) did not indicate the OPAT model used; only 29 involved a comparator (23%). There was little difference in duration of OPAT treatment compared with inpatient therapy, and overall OPAT appeared to produce superior cure/improvement rates. However, when models were considered individually, outpatient delivery appeared to be less effective, and self-administration and specialist nurse delivery more effective. Drug side effects, deaths and hospital readmissions were similar to those for inpatient treatment, but there were more line-related complications. Patient satisfaction was high, with advantages seen in being able to resume daily activities and having greater freedom and control. However, most professionals perceived challenges in providing OPAT. Conclusions There were no systematic differences related to the impact of OPAT on treatment duration or adverse events. However, evidence of its clinical benefit compared with traditional inpatient treatment is lacking, primarily due to the dearth of good quality comparative studies. There was high patient satisfaction with OPAT use but the few studies considering practitioner acceptability highlighted organisational and logistic barriers to its delivery. PMID:28428184

Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study.

PubMed

Nathrath, W B; Arnholdt, H; Wilson, P D

1982-01-01

14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

Amplification of the antigen-antibody interaction from quartz crystal microbalance immunosensors via back-filling immobilization of nanogold on biorecognition surface.

PubMed

Tang, Dian-Quan; Zhang, Da-Jun; Tang, Dian-Yong; Ai, Hua

2006-10-20

A new quartz crystal microbalance immunoassay method based on a novel transparent immunoaffinity reactor was developed for clinical immunoassay. To construct such an affinity reactor, resonators with a frequency of 10 MHz were fabricated by affinity binding of functionalized gold nanoparticles (nanogold) to quartz crystal with immobilized specific ligand for the label-free analysis of the affinity reaction between a ligand and its receptor. [Recombinant human tumor markers, carcinoembryonic antigen (CEA) was chosen as a model ligand.] The binding of target molecules onto the immobilized antibodies decreased the sensor's resonant frequency, and the frequency shift was proportional to the CEA concentration in the range of 3.0-50 ng/ml with a detection limit of 1.5 ng/ml at a signal/noise ration of 3. A glycine-HCl solution (pH 2.3) was used to release antigen-antibody complexes from the biorecognition surface. Good reusability was exhibited. Moreover, spiking various levels of CEA into normal human sera was diagnosed using the proposed immunoassay. Analytical results show the precision of the developed immunoassay is acceptable, implying a promising alternative approach for detecting CEA in clinical immunoassay. Compared with the conventional enzyme-linked immunosorbent assay, the proposed immunoassay system was simple and rapid without multiple labeling and separation steps. Importantly, the proposed immunoassay system could be further developed for the immobilization of other antigens or biocompounds.

'Not good enough:' Exploring self-criticism's role as a mediator between childhood emotional abuse & adult binge eating.

PubMed

Feinson, Marjorie C; Hornik-Lurie, Tzipi

2016-12-01

Empirical studies have identified emotional abuse in childhood (CEA) as a risk factor with long-term implications for psychological problems. Indeed, recent studies indicate it is more prevalent than behavioral forms of abuse, (i.e. childhood sexual and physical abuse) and the childhood trauma most clearly associated with subsequent eating pathology in adulthood. However, relatively little is understood about the mechanisms linking these distal experiences. This study explores three psychological mechanisms - self-criticism (SC), depression and anxiety symptoms - as plausible mediators that may account for the relationship between CEA and binge eating (BE) among adult women. Detailed telephone interviews conducted with a community-based sample of 498 adult women (mean age 44) assess BE, CEA and SC along with the most frequently researched psychological variables, anxiety and depression. Regression analyses reveal that BE is partially explained by CEA along with the three mediators. Bootstrapping analysis, which compares multiple mediators within a single model using thousands of repeated random sampling observations from the data set, reveals a striking finding: SC is the only psychological variable that makes a significant contribution to explaining BE severity. The unique role of punitive self-evaluations vis-à-vis binge eating warrants additional research and, in the interim, that clinicians consider broadening treatment interventions accordingly. Copyright © 2016. Published by Elsevier Ltd.

Significance of CEA and VEGF as Diagnostic Markers of Colorectal Cancer in Lebanese Patients.

PubMed

Dbouk, Hashem A; Tawil, Ayman; Nasr, Fahd; Kandakarjian, Loucine; Abou-Merhi, Raghida

2007-11-08

Carcinoembryonic antigen and vascular endothelial growth factors are among the most important prognostic markers of colorectal cancer. Testing for these markers independently has been of limited value in screening for this tumor. The aim of this study is to determine the importance of simultaneous blood CEA and VEGF level determinations in diagnosis of colorectal cancer. Thirty-six patients diagnosed with colorectal cancer along with eight healthy controls were tested by ELISA for CEA and VEGF levels in serum and plasma, respectively. The positive predictive value of these markers was 95.4% for CEA and 89.5% for VEGF, and for combined CEA and VEGF was also high at 88%. Combined CEA and VEGF blood level assay constitutes a useful panel in detecting patients with colorectal cancer. Positive results allow selection of a subgroup of patients with a high tumor risk; therefore, such tests comprise valuable tumor diagnostic tests to add to current detection methods.

An institutional study of time delays for symptomatic carotid endarterectomy.

PubMed

Charbonneau, Philippe; Bonaventure, Paule Lessard; Drudi, Laura M; Beaudoin, Nathalie; Blair, Jean-François; Elkouri, Stéphane

2016-12-01

The aim of this study was to assess time delays between first cerebrovascular symptoms and carotid endarterectomy (CEA) at a single center and to systematically evaluate causes of these delays. Consecutive adult patients who underwent CEAs between January 2010 and September 2011 at a single university-affiliated center (Centre Hospitalier de l'Université Montréal-Hôtel-Dieu Hospital, Montreal) were identified from a clinical database and operative records. Covariates of interest were extracted from electronic medical records. Timing and nature of the first cerebrovascular symptoms were also documented. The first medical contact and pathway of referral were also assessed. When possible, the ABCD 2 score (age, blood pressure, clinical features, duration of symptoms, and diabetes) was calculated to calculate further risk of stroke. The nonparametric Wilcoxon test was used to assess differences in time intervals between two variables. The Kruskal-Wallis test was used to assess differences in time intervals in comparing more than two variables. A multivariate linear regression analysis was performed using covariates that were determined to be statistically significant in our sensitivity analyses. The cohort consisted of 111 patients with documented symptomatic carotid stenosis undergoing surgical intervention. Thirty-nine percent of all patients were operated on within 2 weeks from the first cerebrovascular symptoms. The median time between the occurrence of the first neurologic symptom and the CEA procedure was 25 (interquartile range [IQR], 11-85) days. The patient-dependent delay, defined as the median delay between the first neurologic symptom and the first medical contact, was 1 (IQR, 0-14) day. The medical-dependent delay was defined as the time interval between the first medical contact and CEA. This included the delay between the first medical contact and the request for surgery consultation (median, 3 [IQR, 1-10] days). The multivariate regression model demonstrated that the emergency physician as referral source (P = .0002) was statistically significant for reducing CEA delay. Patients who were investigated as an outpatient (P = .02), first medical contact with a general practitioner (P = .0002), and hospital center I as referral center (P = .045) were also found to be statistically significant to extend CEA delay when the model was adjusted over all covariates. In this center, there was no correlation between ABCD 2 risk score and waiting time for surgery. The majority of our cohort falls short of the recommended 2-week interval to perform CEA. Factors contributing to reduced CEA delay were presentation to an emergency department, in-patient investigations, and a stroke center where a vascular surgeon is available. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer

PubMed Central

Treasure, Tom; Monson, Kathryn; Fiorentino, Francesca; Russell, Christopher

2014-01-01

Objective In patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit? Design A randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative. Setting 58 hospitals in the UK. Participants From 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms. Interventions ‘Second-look’ surgery with intention to remove any recurrence discovered. Primary outcome measure Survival. Results By February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival. Conclusions The trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years. Trial registration number ISRCTN76694943. PMID:24823671

First experience using cultured epidermal autografts in Taiwan for burn victims of the Formosa Fun Coast Water Park explosion, as part of Japanese medical assistance.

PubMed

Matsumura, Hajime; Harunari, Nobuyuki; Ikeda, Hiroto

2016-05-01

On June 27, 2015, a flammable starch-based powder exploded at Formosa Fun Coast in Taipei, Taiwan, injuring 499 people, and more than 200 people were in critical condition with severe burns. Although a cultured epidermal autograft (CEA) was not approved or used in clinical practice, the Taiwan Food and Drug Administration requested a Japanese CEA manufacturer to donate CEA for the burn victims as part of international medical assistance. The authors cooperated in this project and participated in the patient selection, wound bed management for CEA, and technical assistance for CEA use. Here, we provide an overview of the project. Nine patients were enrolled, and two patients were excluded from the skin biopsy; seven skin biopsies were collected approximately 1 month after the disaster. The average TBSA% burned was 81.0%, and the mean age was 20.1 years. CEA was grafted in five patients; wound closure had been obtained in one patient, and one patient was severely ill at the time of grafting. The CEA was combined with a wide split auto mesh graft or patch graft. The mean re-epithelization rate at 4 weeks after the grafting was 84.2% by patient, and all of the patients survived. Although this project had many obstacles to overcome, CEA grafting was successful and contributed to wound closure and survival. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Optogenetic excitation of central amygdala amplifies and narrows incentive motivation to pursue one reward above another.

PubMed

Robinson, Mike J F; Warlow, Shelley M; Berridge, Kent C

2014-12-10

Choosing one reward above another is important for achieving adaptive life goals. Yet hijacked into excessive intensity in disorders such as addiction, single-minded pursuit becomes maladaptive. Here, we report that optogenetic channelrhodopsin stimulation of neurons in central nucleus of amygdala (CeA), paired with earning a particular sucrose reward in rats, amplified and narrowed incentive motivation to that single reward target. Therefore, CeA rats chose and intensely pursued only the laser-paired sucrose reward while ignoring an equally good sucrose alternative. In contrast, reward-paired stimulation of basolateral amygdala did not hijack choice. In a separate measure of incentive motivation, CeA stimulation also increased the progressive ratio breakpoint or level of effort exerted to obtain sucrose reward. However, CeA stimulation by itself failed to support behavioral self-stimulation in the absence of any paired external food reward, suggesting that CeA photo-excitation specifically transformed the value of its external reward (rather than adding an internal reinforcement state). Nor did CeA stimulation by itself induce any aversive state that motivated escape. Finally, CeA stimulation also failed to enhance 'liking' reactions elicited by sucrose taste and did not simply increase the general motivation to eat. This pattern suggests that CeA photo-excitation specifically enhances and narrows incentive motivation to pursue an associated external reward at the expense of another comparable reward. Copyright © 2014 the authors 0270-6474/14/3416567-14$15.00/0.

Opposite Effects of Basolateral Amygdala Inactivation on Context-Induced Relapse to Cocaine Seeking after Extinction versus Punishment.

PubMed

Pelloux, Yann; Minier-Toribio, Angelica; Hoots, Jennifer K; Bossert, Jennifer M; Shaham, Yavin

2018-01-03

Studies using the renewal procedure showed that basolateral amygdala (BLA) inactivation inhibits context-induced relapse to cocaine-seeking after extinction. Here, we determined whether BLA inactivation would also inhibit context-induced relapse after drug-reinforced responding is suppressed by punishment, an animal model of human relapse after self-imposed abstinence due to adverse consequences of drug use. We also determined the effect of central amygdala (CeA) inactivation on context-induced relapse.We trained rats to self-administer cocaine for 12 d (6 h/d) in Context A and then exposed them to either extinction or punishment training for 8 d in Context B. During punishment, 50% of cocaine-reinforced lever-presses produced an aversive footshock of increasing intensity (0.1-0.5 or 0.7 mA). We then tested the rats for relapse to cocaine seeking in the absence of cocaine or shock in Contexts A and B after BLA or CeA injections of vehicle or GABA agonists (muscimol-baclofen). We then retrained the rats for cocaine self-administration in Context A, repunished or re-extinguished lever pressing in Context B, and retested for relapse after BLA or CeA inactivation.BLA or CeA inactivation decreased context-induced relapse in Context A after extinction in Context B. BLA, but not CeA, inactivation increased context-induced relapse in Context A after punishment in Context B. BLA or CeA inactivation provoked relapse in Context B after punishment but not extinction. Results demonstrate that amygdala's role in relapse depends on the method used to achieve abstinence and highlights the importance of studying relapse under abstinence conditions that more closely mimic the human condition. SIGNIFICANCE STATEMENT Relapse to drug use during abstinence is often provoked by re-exposure to the drug self-administration environment or context. Studies using the established extinction-reinstatement rodent model of drug relapse have shown that inactivation of the basolateral amygdala inhibits context-induced drug relapse after extinction of the drug-reinforced responding. Here, we determined whether basolateral amygdala inactivation would also inhibit relapse after drug-reinforced responding is suppressed by punishment, a model of human relapse after self-imposed abstinence. Unexpectedly, we found that basolateral amygdala inactivation had opposite effects on relapse provoked by re-exposure to the drug self-administration environment after extinction versus punishment. Our results demonstrate that depending on the historical conditions that lead to abstinence, amygdala activity can either promote or inhibit relapse. Copyright © 2018 the authors 0270-6474/18/380051-09$15.00/0.

76 FR 41375 - Retail Foreign Exchange Transactions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... retail customers. The rule also describes various requirements with which national banks, Federal... section 2(c)(2)(B)(i)(I) of the CEA with a retail customer \\5\\ except pursuant to a rule or regulation of... the CEA. \\3\\ The CEA defines ``financial institution'' as including ``a depository institution (as...

[Sensitivity, specificity and prognostic value of CEA in colorectal cancer: results of a Tunisian series and literature review].

PubMed

Bel Hadj Hmida, Y; Tahri, N; Sellami, A; Yangui, N; Jlidi, R; Beyrouti, M I; Krichen, M S; Masmoudi, H

2001-01-01

In order to determine the sensitivity of CEA in the diagnosis of colo-rectal carcinoma, we studied a series of 48 patients with colo-rectal carcinoma (1992-1996). The sensitivity was at 52% with a reference value of 5 ng/ml and 68.7% for a reference value of 2.5 ng/ml. With a reference value of 5 ng/ml, the sensitivity of CEA was at 37% only for patients with colo-rectal carcinoma at Dukes B stage, 66.6% for patients at stage C and 75% for patients at stage D. The dosage of CEA was carried out with a sandwich immunoenzymatic technique in tube. There is no statistic significant correlation between the pre-operative rate of CEA and the localisation of the tumor and its histologic type; in contrast, it was significantly correlated with the ganglionnary metastasis. A significant relationship between the pre-operative rate of CEA and the Dukes stage was found for a reference value of 10 ng/ml but not for a reference value of 5 ng/ml. We calculated the specificity of the CEA for the cancers of colon and rectum which was at 76.98% with a reference value of 5 ng/ml and 86% with a reference value of 10 ng/ml.

Prospective randomised trial of early cytotoxic therapy for recurrent colorectal carcinoma detected by serum CEA.

PubMed Central

Hine, K R; Dykes, P W

1984-01-01

Of 663 patients treated with radical surgery for colorectal cancer, 52 showed a progressive rise in serum carcinoembryonic antigen (CEA) with no other evidence of recurrent disease and were randomised in a prospective study of chemotherapy. Twenty six patients in the treatment group received 5FU and methyl CCNU from the time of randomisation and the remaining 26 controls were given further therapy only if there were clinical indications. All patients were followed for five years or until their death and all but one (control) developed clinical evidence of recurrence. Overall there was no significant difference between the two groups with respect to disease free interval and survival. Whereas the rise in CEA in controls was generally progressive, marked inflections on the CEA curves were seen in the majority of patients receiving early treatment. Eight of 26 treated patients showed a fall in CEA of greater than 20% two months after starting therapy. These patients had a median disease free interval of 90 weeks and a median survival of 107 weeks, these figures being longer than those of treated patients who did not show a fall in CEA and control patients. The serum CEA therefore appeared to give important prognostic information in patients receiving cytotoxic treatment. Early therapy was generally well tolerated. PMID:6376291

The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning.

PubMed

Keifer, Orion P; Hurt, Robert C; Ressler, Kerry J; Marvar, Paul J

2015-09-01

The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. ©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.

Suppression of Murine Colitis and its Associated Cancer by Carcinoembryonic Antigen-Specific Regulatory T Cells

PubMed Central

Blat, Dan; Zigmond, Ehud; Alteber, Zoya; Waks, Tova; Eshhar, Zelig

2014-01-01

The adoptive transfer of regulatory T cells (Tregs) offers a promising strategy to combat pathologies that are characterized by aberrant immune activation, including graft rejection and autoinflammatory diseases. Expression of a chimeric antigen receptor (CAR) gene in Tregs redirects them to the site of autoimmune activity, thereby increasing their suppressive efficiency while avoiding systemic immunosuppression. Since carcinoembryonic antigen (CEA) has been shown to be overexpressed in both human colitis and colorectal cancer, we treated CEA-transgenic mice that were induced to develop colitis with CEA-specific CAR Tregs. Two disease models were employed: T-cell-transfer colitis as well as the azoxymethane–dextran sodium sulfate model for colitis-associated colorectal cancer. Systemically administered CEA-specific (but not control) CAR Tregs accumulated in the colons of diseased mice. In both model systems, CEA-specific CAR Tregs suppressed the severity of colitis compared to control Tregs. Moreover, in the azoxymethane–dextran sodium sulfate model, CEA-specific CAR Tregs significantly decreased the subsequent colorectal tumor burden. Our data demonstrate that CEA-specific CAR Tregs exhibit a promising potential in ameliorating ulcerative colitis and in hindering colorectal cancer development. Collectively, this study provides a proof of concept for the therapeutic potential of CAR Tregs in colitis patients as well as in other autoimmune inflammatory disorders. PMID:24686242

Diagnostic test pepsinogen I and combination with tumor marker CEA in gastric cancer

NASA Astrophysics Data System (ADS)

Sembiring, J.; Sarumpaet, K.; Ganie, R. A.

2018-03-01

Gastric cancer (GC) is the fifth leading cause of cancer and the third leading cause of cancer-related mortality globally. Human pepsinogens (HP) are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and GC. HP are biochemically and immunochemically classified into two groups: pepsinogen I (PG I) and PG II. Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in normal mucosal cells but increased amounts are associated with adenocarcinoma, especially colorectal cancer. CEA in combination with other tumour markers can be used in pre-operative staging and thereby assist in the planning of the type of surgery required and future management options. The purpose of this study was to diagnose test PG I and combination with tumor marker CEA in 32 patients suspected with GC. There was a significant difference in levels of CEA between GC group with non-GC with a value p <0.001. PGI sensitivity was 70.58% and specificity 93.3%. The sensitivity of PGI and CEA combination of 94.1% and specificity 80%. The area of AUC obtained was 92.7% at 95% confidence interval (82.7-100%). This AUC value indicated that the value of diagnostic accuracy of the PGI and CEA combinations of 92.7%.

The Central Amygdala Nucleus is Critical for Incubation of Methamphetamine Craving

PubMed Central

Li, Xuan; Zeric, Tamara; Kambhampati, Sarita; Bossert, Jennifer M; Shaham, Yavin

2015-01-01

Cue-induced methamphetamine seeking progressively increases after withdrawal but mechanisms underlying this ‘incubation of methamphetamine craving' are unknown. Here we studied the role of central amygdala (CeA), ventral medial prefrontal cortex (vmPFC), and orbitofrontal cortex (OFC), brain regions implicated in incubation of cocaine and heroin craving, in incubation of methamphetamine craving. We also assessed the role of basolateral amygdala (BLA) and dorsal medial prefrontal cortex (dmPFC). We trained rats to self-administer methamphetamine (10 days; 9 h/day, 0.1 mg/kg/infusion) and tested them for cue-induced methamphetamine seeking under extinction conditions during early (2 days) or late (4–5 weeks) withdrawal. We first confirmed that ‘incubation of methamphetamine craving' occurs under our experimental conditions. Next, we assessed the effect of reversible inactivation of CeA or BLA by GABAA+GABAB receptor agonists (muscimol+baclofen, 0.03+0.3 nmol) on cue-induced methamphetamine seeking during early and late withdrawal. We also assessed the effect of muscimol+baclofen reversible inactivation of vmPFC, dmPFC, and OFC on ‘incubated' cue-induced methamphetamine seeking during late withdrawal. Lever presses in the cue-induced methamphetamine extinction tests were higher during late withdrawal than during early withdrawal (incubation of methamphetamine craving). Muscimol+baclofen injections into CeA but not BLA decreased cue-induced methamphetamine seeking during late but not early withdrawal. Muscimol+baclofen injections into dmPFC, vmPFC, or OFC during late withdrawal had no effect on incubated cue-induced methamphetamine seeking. Together with previous studies, results indicate that the CeA has a critical role in incubation of both drug and non-drug reward craving and demonstrate an unexpected dissociation in mechanisms of incubation of methamphetamine vs cocaine craving. PMID:25475163

Impact of repeated asenapine treatment on FosB/ΔFosB expression in neurons of the rat central nucleus of the amygdala: colocalization with corticoliberine (CRH) and effect of an unpredictable mild stress preconditioning.

PubMed

Majercikova, Z; Kiss, A

2015-04-01

FosB/ΔFosB expression in the central amygdalar nucleus (CeA) in response to repeated asenapine (ASE) treatment (an atypical antipsychotic used for the treatment of schizophrenia) was studied in normal rats and rats preconditioned with chronic unpredictable variable mild stress (CMS). The goal of this study was to reveal whether repeated ASE treatment for 14 days may: 1) induce FosB/ΔFosB expression in the amygdala, 2) activate CRH-synthesizing neurons in the CeA, and 3) interfere with 21 days lasting concomitant CMS preconditioning. Four groups of animals were studied: controls and ASE-, CMS-, and CMS+ASE-treated ones. CMS consisted of the restrain, social isolation, crowding, swimming, and cold and lasted 21 days. The ASE and CMS+ASE groups were from the 7th day of the experiment treated with ASE (0.3 mg/kg, subcutaneously - s.c.) twice a day, i.e. together for 14 days. Controls and CMS groups were treated with saline (300 µl/rat, s.c.) twice a day for 14 days. All the animals were sacrificed on the 22nd day, i.e. 16-18 hours after the last treatments. Single FosB/ΔFosB, FosB/ΔFosB colocalizations with CRH, and CRH immunolabeled perikarya were investigated in the CeA using a combined light and fluorescent immunohistochemistry. The distribution aspect of the black FosB/ΔFosB profiles was homogeneous over the whole CeA and no significant differences in the number of FosB/ΔFosB profiles between the individual groups of the rats really occurred. The level of colocalization pattern of FosB/ΔFosB in CRH perikarya was also very similar between the individual groups and in each case it reached approximately 10% of double-labeling. No differences were also seen in the number of CRH immunolabeled perikarya. The density of CRH nerve projections within the CeA was very alike in the individual groups of animals investigated. The study provides a new anatomical/functional finding about the lack of the stimulatory effect of the repeated ASE treatment on the expression of FosB/ΔFosB, FosB/ΔFosB/CRH colocalizations, and CRH immunolabeled perikarya number in the CeA. In addition, CMS preconditioning itself neither stimulated nor inhibited FosB/ΔFosB expression, nor altered the impact of ASE on the activity of CRH neurons in the CeA.

Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population.

PubMed

Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

2016-12-12

BACKGROUND The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. MATERIAL AND METHODS Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. RESULTS We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31-7.89 ng/ml (males) and 1.01-7.10 ng/ml (females); CEA, 0.51-4.86 ng/ml (males) and 0.35-3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). CONCLUSIONS Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups.