bluuebunny/crossref_metadata_2025 huggingface dataset:
Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3 (CCR3)
Authors: Grimaldi J Christopher , Yu Nai-Xuan , Grunig Gabrielle , Seymour Brian W P , Cottrez Françoise , Robinson Douglas S , Hosken Nancy , Ferlin Walter G , Wu Xiaoyan , Soto Hortensia , O'Garra Anne , Howard Maureen C , Coffman Robert L
Published: January 2018

We have generated rat monoclonal antibodies specific for the mouse eotaxin receptor, C-C chemokine receptor 3 (CCR3). Several anti-CCR3 mAbs proved to be useful for in vivo depletion of CCR3-expressing cells and immunofluorescent staining. In vivo CCR3 mAbs of the IgG2b isotype substantially depleted blood eosinophil levels in Nippostrongyus brasiliensis-infected mice. Repeated anti-CCR3 mAb treatment in these mice significantly reduced tissue eosinophilia in the lung tissue and bronchoalveolar lavage fluid. Flow cytometry revealed that mCCR3 was expressed on eosinophils but not on stem cells, dendritic cells, or cells from the thymus, lymph node, or spleen of normal mice. Unlike human Th2 cells, mouse Th2 cells did not express detectable levels of CCR3 nor did they give a measurable response to eotaxin. None of the mAbs were antagonists or agonists of CCR3 calcium mobilization. To our knowledge, the antibodies described here are the first mAbs reported to be specific for mouse eosinophils and to be readily applicable for the detection, isolation, and in vivo depletion of eosinophils. J. Leukoc. Biol. 65: 846–853; 1999.
Immunization with dendritic cells breaks immunodominance in CTL responses against minor histocompatibility and synthetic peptide antigens
Authors: Grufman Per , Sandberg Johan K , Wolpert Elisabeth Z , Kärre Klas
Published: January 2018

We have examined the mechanisms involved in immunodominance in two different experimental models: the cytotoxic T lymphocyte (CTL) response in B6 mice against minor histocompatibility antigens of BALB.B mice, and the response of B6 mice against a mixture of five synthetic peptides corresponding to well-defined immunogenic epitopes. The CTL responses in these models focus on a few dominant epitopes, whereas no or only weak responses can be detected against other subdominant epitopes. Neither of these immunodominance phenomena can be explained by insufficient presentation of subdominant epitopes in the presence of the dominant ones. Immunodominance could also be demonstrated in an in vitro system, in which B6 splenocytes primed with BALB.B could interfere with the CTL response against subdominant antigens. This interference was dependent on CD8+ T cells and on the simultaneous presentation of dominant and subdominant antigens on the same antigen-presenting cell, suggesting T cell competition around the antigen-presenting cell as a potential explanation. The immunodominance in both systems could be broken by immunization with dendritic cells (from BALB.B or from B6 loaded with peptides). This procedure allowed detection of CTL responses against both dominant and previously subdominant antigens. J. Leukoc. Biol. 66: 268–271; 1999.
Migration of Langerhans cells and dermal dendritic cells in skin organ cultures: augmentation by TNF-α and IL-1 β
Authors: Stoitzner Patrizia , Zanella Monica , Ortner Ulrike , Lukas Michael , Tagwerker Andrea , Janke Katrin , Lutz Manfred B , Schuler Gerold , Echtenacher Bernd , Ryffel Bernhard , Koch Franz , Romani Nikolaus
Published: January 2018

Migration from sites of antigen encounter to lymphoid organs is essential to the strong immunogenic function of dendritic cells (DC). In the skin, migration proceeds through dermal lymphatic vessels and is regulated in an incompletely understood way by inflammatory mediators. We studied the effects of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in mouse skin organ cultures by direct enumeration of migrating DC and by immunohistochemistry. (1) Neutralizing antibodies to TNF-α and IL-1β inhibited migration of DC, also in human skin explants (TNF-α). (2) TNF-α at low concentrations (50 U/mL) and IL-1β (50–3000 U/mL) augmented migration to about 150% of spontaneous migration. (3) High concentrations of TNF-α (5000 U/mL) inhibited migration by approximately 50%. (4) DC migration from skin explants of TNF-α/lymphotoxin-α double-deficient mice and TNF-receptor type 1 and 2 double knock-out mice was not impaired. (5) TNF-α effects were neutralized by anti-IL-1β, and vice versa. We conclude that in normal animals both TNF-α and IL-1 β are required for DC migration to occur. In the complete absence of one cytokine (TNF-α), however, backup mechanisms step in. J. Leukoc. Biol. 66: 462–470; 1999.
Monochloramine enhances Fas (APO-1/CD95)-induced apoptosis in Jurkat T cells
Authors: Ogino Tetsuya , Ma Yuxiang , Than Tin Aung , Omori Masako , Okada Shigeru
Published: January 2018

Monochloramine derivatives are physiological oxidants produced by activated neutrophils. We report the effects of chemically prepared monochloramine (NH2Cl) on Fas-induced apoptosis in Jurkat T cells. When the cells were pretreated with NH2Cl (20–70 μM), subsequent addition of apoptosis-inducing anti-Fas antibody resulted in a synergistic enhancement of apoptosis. Treatment of NH2Cl (50–70 μM) alone resulted in a slight but definite apoptosis. Caspase activities, as measured by DEVD and IETD cleavage activities, were also elevated synergistically by NH2Cl + anti-Fas antibody stimulation. Moreover, a broad caspase inhibitor, Z-VAD-fmk, almost completely inhibited the apoptosis induced by NH2Cl and/or anti-Fas antibody. Fas expression on the Jurkat cell surface was not affected by the NH2Cl treatment. After 3 h of NH2Cl treatment, when the apoptosis was beginning to increase, the cells showed cytochrome c release from mitochondria, proteolytic activation of caspase 9, and poly (ADP-ribose) polymerase cleavage, regardless of Fas stimulation. Z-VAD-fmk almost completely inhibited this poly (ADP-ribose) polymerase cleavage, but not cytochrome c release. By contrast, Fas stimulation alone resulted in neither cytochrome c release nor caspase 9 activation at 3 h, and the increase in the DEVD cleavage activity and apoptosis became evident at later time points. These results suggested that NH2Cl enhanced Fas-induced apoptosis through the cytochrome c release and caspase 9 activation at the early stage of apoptosis. Chloramines derived from acute inflammation may modify immune reactions, such as cell-mediated cytotoxicity and some autoimmune diseases, by the enhancement of Fas-induced apoptosis. J. Leukoc. Biol. 67: 46–52; 2000.
Cloning and expression of bovine p47-phoxand p67-phox: comparison with the human and murine homologs
Authors: Bunger Peggy L , Swain Steve D , Clements Mark K , Siemsen Daniel W , Davis Angela R , Gauss Katherine A , Quinn Mark T
Published: January 2018

Neutrophils play an essential role in bovine cellular host defense, and compromised leukocyte function has been linked to the development of respiratory and mucosal infections. During the host defense process, neutrophils migrate into infected tissues where they become activated, resulting in the assembly of neutrophil membrane and cytosolic proteins to form a superoxide anion-generating complex known as the NADPH oxidase. Two of the essential cytosolic components of the NADPH oxidase are p47-phox and p67-phox. Currently, only the human and murine homologs of these proteins have been sequenced. Because of the important role neutrophils play in bovine host defense, we carried out studies to clone, sequence, and express bovine p47-phox and p67-phox. Using polymerase chain reaction (PCR) cloning techniques and a bovine bone marrow cDNA library, we have cloned both of these bovine NADPH oxidase cytosolic components. Comparison of the bovine sequences with those of the human and murine homologs showed that they were highly conserved, but also revealed important information regarding key structural features of p47-phox and p67-phox, including location of putative phosphorylation sites. Functional expression of bovine p47-phox and p67-phox showed that these proteins could substitute for the human proteins in reconstituting NADPH oxidase activity in a cell-free assay system, again demonstrating the high degree of conservation between human and bovine homologs. This study greatly contributes to our understanding of the potential structural/functional regions of p47-phox and p67-phox as well as providing information that can be used to study the role of neutrophils in bovine inflammatory diseases. J. Leukoc. Biol. 67: 63–72; 2000.
Interleukin-16
Authors: Cruikshank William W , Kornfeld Hardy , Center David M
Published: January 2018

Interleukin 16 (IL-16) was initially described in 1982 as the first T cell chemoattractant. Through interaction with CD4, IL-16 has now been characterized as a chemoattractant for a variety of CD4+ immune cells. Recent in vivo studies have more fully characterized IL-16 as an immunom  odulatory cytokine that contributes to the regulatory process of CD4+ cell recruitment and activation at sites of inflammation in association with asthma and several autoimmune diseases. Since its cloning in 1994, IL-16 structure and function have been studied extensively. This review addresses the current data regarding IL-16 protein and gene structure; the expanding list of cells capable of generating IL-16; the direct interaction of IL-16 with its receptor, CD4; and the functional bioactivities of IL-16 as they relate to inflammation and HIV-1 infection. In addition, potential therapeutic modalities for IL-16 relating to inflammation and immune reconstitution in HIV-1 infection are also discussed. J. Leukoc. Biol. 67: 757–766; 2000.
Influence of morphology and dispersion stability of CNC modified with ethylene oxide derivatives on mechanical properties of PLA‐based nanocomposites
Authors: Góis Gelsoneide S. , Nepomuceno Neymara C. , França Carlos H.A. , Almeida Yeda M.B. , Hernandéz Eduardo P. , Oliveira Juliano E. , Oliveira Mauricio P. , Medeiros Eliton S. , Santos Amélia S.F.
Published: January 2018

The aggregation state of cellulose nanocrystals modified with surfactants (CNC/S) in water and CNC/S powder dispersion stability in chloroform were studied and correlated with mechanical properties of nanocomposites with poly(lactic acid) (PLA). Four types of nonionic surfactants were used: PEG 300, PEG 1000, poly(ethylene glycol) monooleate, and Pluronic® L44 (PL44). The CNC/PL44 showed the smallest size of CNC aggregates dispersed in water before freeze‐drying, as determined by atomic force microscopy. The respective powder also showed the lowest decay rate of relative turbidity among CNC/S dispersions in chloroform. This, together with the improved surface coverage of CNC by PL44, verified by zeta potential (large change in the zeta potential of CNC/S dispersion in chloroform) and thermogravimetric analysis (improved thermal stability of CNC/S powder), yielded the highest tensile strength at break (TS) among PLA/CNC/S nanocomposites. Despite none of surfactants produced nanocomposites with TS higher than PLA or PLA/CNC, the aggregation state of CNC/S in water is well correlated with mechanical properties of PLA/CNC/S nanocomposites prepared by solvent casting. This correlation indicates that hornification cannot be avoided for the conditions used to prepare CNC/S powder and that there are two opposite effects in preparation of PLA/CNC/S nanocomposites. First, the effectiveness of steric barrier of nonionic surfactants against aggregation during freeze‐drying depends on complete surface coverage of CNC, together with hydration of stabilizing chain. Since hydration depends on hydrophilicity of stabilizing chain and compatibility with PLA depends on its nonpolar nature, this strategy alone seems not to be efficient to produce high‐performance nanocomposites. POLYM. COMPOS., 40:E399–E408, 2019. © 2018 Society of Plastics Engineers
Tunable Photoluminescence in WS2/WO3 Monolayer/Nanoparticles Hybrid Structure
Authors: Tao Lei , Zhao Shudong , Miao Peng , Yu Jianxin , Wang Xianjie , Wang Yi , Liu Zhiguo , Li Bingsheng , Wang Yang , Sui Yu
Published: January 2018

Photoluminescence (PL) of WS2 monolayer has attracted attention triggered by potential optoelectronic and photoelectric applications due to the largest direct band gap in WS2 monolayer among transition metal dichalcogenides. The PL of WS2 monolayer is dominated by charged excitons (trions) and bound excitons, which suppress the luminescence of free excitons. Herein, we report a one‐step growth of a nanosheet/nanoparticles hybrid structure to reduce the emission of bound excitons and trions in WS2 monolayer by surface passivation with WO3 nanoparticles. Peak positions of the PL spectra in WS2 monolayers depend on the density of WO3 nanoparticles on their surface. With increasing density of WO3 nanoparticles, the PL of WS2 monolayers experiences the transition from bound excitons and charged excitons (trions) to neutral excitons. These results suggest that the engineering of PL of WS2 monolayers may be realized by surface passivation using nanoparticles of wide band gap semiconductors.
A synthetic pathway for the production of 2-hydroxyisovaleric acid in Escherichia coli
Authors: Cheong Seokjung , Clomburg James M , Gonzalez Ramon
Published: January 2018

Synthetic biology, encompassing the design and construction of novel artificial biological pathways and organisms and the redesign of existing natural biological systems, is rapidly expanding the number of applications for which biological systems can play an integral role. In the context of chemical production, the combination of synthetic biology and metabolic engineering approaches continues to unlock the ability to biologically produce novel and complex molecules from a variety of feedstocks. Here, we utilize a synthetic approach to design and build a pathway to produce 2-hydroxyisovaleric acid in Escherichia coli and demonstrate how pathway design can be supplemented with metabolic engineering approaches to improve pathway performance from various carbon sources. Drawing inspiration from the native pathway for the synthesis of the 5-carbon amino acid l-valine, we exploit the decarboxylative condensation of two molecules of pyruvate, with subsequent reduction and dehydration reactions enabling the synthesis of 2-hydroxyisovaleric acid. Key to our approach was the utilization of an acetolactate synthase which minimized kinetic and regulatory constraints to ensure sufficient flux entering the pathway. Critical host modifications enabling maximum product synthesis from either glycerol or glucose were then examined, with the varying degree of reduction of these carbons sources playing a major role in the required host background. Through these engineering efforts, the designed pathway produced 6.2 g/L 2-hydroxyisovaleric acid from glycerol at 58% of maximum theoretical yield and 7.8 g/L 2-hydroxyisovaleric acid from glucose at 73% of maximum theoretical yield. These results demonstrate how the combination of synthetic biology and metabolic engineering approaches can facilitate bio-based chemical production.
Ending International Investment Agreements: Russia's Withdrawal from Participation in the Energy Charter Treaty
Authors: Voon Tania , Mitchell Andrew D.
Published: January 2018

When states withdraw from bilateral investment treaties or denounce multilateral treaties related to foreign investment, a range of intersecting questions arise in domestic and international law. Recent developments have demonstrated potential incongruities between domestic and international approaches to investment protection, including as regards the effectiveness of withdrawal and the implications for existing investments. This essay reflects on international and domestic disputes involving the withdrawal of the Russian Federation from participation in the Energy Charter Treaty (ECT) to highlight these interactions. These issues have become particularly pertinent today because more than 1,500 international investment agreements (IIAs) are nearing expiry of their initial term, providing an opportunity for termination. Moreover, some states have begun to terminate or denounce investment treaties, while many more are engaging in a process of renegotiation and reform. The Russian case study also highlights the potentially far-reaching effects of a state simply signing a treaty, even many years after the state has expressed its decision to withdraw from it, and notwithstanding tensions with the domestic legal framework.
Level-set simulations of a 2D topological rearrangement in a bubble assembly: effects of surfactant properties
Authors: Titta A. , Le Merrer M. , Detcheverry F. , Spelt P. D. M. , Biance A.-L.
Published: January 2018

A liquid foam is a dispersion of gas bubbles in a liquid matrix containing surface-active agents. Its flow involves the relative motion of bubbles, which switch neighbours during a so-called topological rearrangement of type 1 (T1). The dynamics of T1 events, as well as foam rheology, have been extensively studied, and experimental results point to the key role played by surfactants in these processes. However, the complex and multiscale nature of the system has so far impeded a complete understanding of the mechanisms involved. In this work, we investigate numerically the effect of surfactants on the rheological response of a 2D sheared bubble cluster. To do so, a level-set method previously employed for simulation of two-phase flow has been extended to include the effects of surfactants. The dynamical processes of the surfactants – diffusion in the liquid and along the interface, adsorption/desorption at the interface – and their coupling with the flow – surfactant advection and Laplace and Marangoni stresses at the interface – are all taken into account explicitly. Through a systematic study of the Biot, capillary and Péclet numbers that characterise the surfactant properties in the simulation, we find that the presence of surfactants can affect the liquid/gas hydrodynamic boundary condition (from a rigid-like situation to a mobile one), which modifies the nature of the flow in the volume from a purely extensional situation to a shear. Furthermore, the work done by surface tension (the 2D analogue of the work by pressure forces), resulting from surfactant and interface dynamics, can be interpreted as an effective dissipation, which reaches a maximum for a Péclet number of order unity. Our results, obtained at high liquid fraction, should provide a reference point, with which experiments and models of T1 dynamics and foam rheology can be compared.
Electro-poroelastohydrodynamics of the endothelial glycocalyx layer
Authors: Sumets P. P. , Cater J. E. , Long D. S. , Clarke R. J.
Published: January 2018

We consider pressure-driven flow of an ion-carrying viscous Newtonian fluid through a non-uniformly shaped channel coated with a charged deformable porous layer, as a model for blood flow through microvessels that are lined with an endothelial glycocalyx layer (EGL). The EGL is negatively charged and electrically interacts with ions dissolved in the blood plasma. The focus here is on the interplay between electrochemical effects, and the pressure-driven flow through the microvessel. To analyse these effects we use triphasic mixture theory (TMT) which describes the coupled dynamics of the fluid phase, the elastic EGL, ion transport within the fluid and electric fields within the microvessel. The resulting equations are solved numerically using a coupled boundary–finite element method (BEM-FEM) scheme. However, in the physiological regime considered here, ion concentrations and electric potentials vary rapidly over a thin transitional region (Debye layer) that straddles the lumen–EGL interface, which is difficult to resolve numerically. Accordingly we analyse this region asymptotically, to determine effective jump conditions across the interface for BEM-FEM computations within the bulk EGL/lumen. Our results demonstrate that ion–EGL electrical interactions can influence the near-wall flow, causing it to become reversed. This alters the stresses exerted upon the vessel wall, which has implications for the hypothesised role of the EGL as a transmitter of mechanical signals from the blood flow to the endothelial vessel surface.
Threshold for the destabilisation of the ion-temperature-gradient mode in magnetically confined toroidal plasmas
Authors: Zocco A. , Xanthopoulos P. , Doerk H. , Connor J. W. , Helander P.
Published: January 2018

The threshold for the resonant destabilisation of ion-temperature-gradient (ITG) driven instabilities that render the modes ubiquitous in both tokamaks and stellarators is investigated. We discover remarkably similar results for both confinement concepts if care is taken in the analysis of the effect of the global shear ${\hat{s}}$. We revisit, analytically and by means of gyrokinetic simulations, accepted tokamak results and discover inadequacies of some aspects of their theoretical interpretation. In particular, for standard tokamak configurations, we find that global shear effects on the critical gradient cannot be attributed to the wave–particle resonance destabilising mechanism of Hahm & Tang (Phys. Plasmas, vol. 1, 1989, pp. 1185–1192), but are consistent with a stabilising contribution predicted by Biglari et al. (Phys. Plasmas, vol. 1, 1989, pp. 109–118). Extensive analytical and numerical investigations show that virtually no previous tokamak theoretical predictions capture the temperature dependence of the mode frequency at marginality, thus leading to incorrect instability thresholds. In the asymptotic limit ${\hat{s}}\unicode[STIX]{x1D704}\ll 1$, where $\unicode[STIX]{x1D704}$ is the rotational transform, and such a threshold should be solely determined by the resonant toroidal branch of the ITG mode, we discover a family of unstable solutions below the previously known threshold of instability. This is true for a tokamak case described by a local ${\hat{s}}-\unicode[STIX]{x1D6FC}$ local equilibrium, and for the stellarator Wendelstein 7-X, where these unstable solutions are present even for configurations with a small trapped-particle population. We conjecture they are of the Floquet type and derive their properties from the Fourier analysis of toroidal drift modes of Connor & Taylor (Phys. Fluids, vol. 30, 1987, pp. 3180–3185), and to Hill’s theory of the motion of the lunar perigee (Acta Math., vol. 8, 1886, pp. 1–36). The temperature dependence of the newly determined threshold is given for both confinement concepts. In the first case, the new temperature-gradient threshold is found to be rather insensitive to the temperature ratio $T_{i}/T_{e}$, at least for $T_{i}/T_{e}\lesssim 1$, and to be a growing function of the density gradient scale for $T_{i}/T_{e}\gtrsim 1$. For Wendelstein 7-X, the new critical temperature gradient is a growing function of the temperature ratio. The importance of these findings for the assessment of turbulence in stellarators and low-shear tokamak configurations is discussed.
Introduction: Institutions and economic development in South Asia
Authors: SULTAN ATIYAB , WASHBROOK DAVID
Published: January 2018

The ‘weak’ and ‘flawed’ nature of South Asian institutions has become axiomatic in development discourse, with the persistence of this view outweighed only by its lack of concreteness. The fascination with institutions is noteworthy precisely because the most fundamental questions about them are still under debate: there is little agreement on the definition of institutions beyond generic statements, let alone an established consensus on which institutions engender development. Instead institutionalist explanations float far and wide, netting the blame for various policy failures, with a striking lack of critical inspection. This special issue is an attempt to bring together various perspectives on institutional change and economic development in South Asia in an attempt to problematize the very concept of institutions and their perceived role in fostering economic development. The geographical focus on South Asia furthers a central aim of this collection: to emphasize the contextual nature of institutions. This translates into a need for disaggregating secular institutional theory into its precise constraints and implications for particular spaces, moments, and contexts.
OP11 Structural Uncertainty In Economic Modelling For Smoking Cessation
Authors: Pennington Becky , Filby Alex , Taylor Matthew , Owen Lesley
Published: January 2018

INTRODUCTION:

Guidance for developing economic models recommend that model structure is carefully considered, and assumptions varied in sensitivity analysis (1). Models in smoking cessation have typically used cohort-level approaches, although recently discrete event simulations (DESs) have been developed (2). DESs allow additional flexibility such as modelling changing risk over time, and recurrent events. Our aim was to explore the impact of varying model structure and assumptions on the cost-effectiveness of smoking cessation programs.

METHODS:

We built a cohort state-transition model which related mortality to smoking status and considered the prevalence (based on smoking status) of five comorbidities associated with smoking, each of which has an associated cost and quality of life decrement. We additionally built a patient-level DES, using the Discretely Integrated Condition Event framework (3). The DES used the same data as the cohort model, except considering incidence for comorbidities rather than prevalence. We considered a population of smokers aged 16 years old and an intervention costing GBP827 on which 27 percent of people quit, compared with no treatment. We produced results using the two models for comparable scenarios, and ran additional scenarios considering different assumptions.

RESULTS:

In the cohort model, the incremental cost-effectiveness ratio (ICER) for intervention versus no treatment was GBP4,000/quality-adjusted life year (QALY). In the DES, modelling mortality linked to smoker status produced an ICER of GBP1,000/QALY and modelling mortality linked to comorbidities produced an ICER of GBP6,000/QALY. In the DES with mortality linked to comorbidities, varying the relative risk of comorbidities with time since quitting gave an ICER of GBP3,000/QALY. Including relapse increased the ICER to GBP21,000/QALY.

CONCLUSIONS:

The ICER for the smoking cessation program changes when model assumptions are varied, although the choice of DES versus cohort model appears to make a relatively small difference. Inclusion of relapse substantially changes the ICER, demonstrating the importance of long-term effects in economic models.
OP15 The Incremental Cost Of Delirium Following Aortic Valve Replacement
Authors: Clancy Seth , Potter Brian , Green Phil
Published: January 2018

INTRODUCTION:

Postoperative delirium has been associated with poorer long term survival in Transcatheter aortic valve replacement (TAVR) and Surgival aortic valve replacement (SAVR) patients. However, its effect on hospitalization costs and length of stay in these populations has not been formally assessed.

METHODS:

Using the Medicare Provider Analysis and Review File, we retrospectively analyzed elderly (80 years of age and older) Medicare patients receiving TAVR and SAVR in the United States during the 2015 fiscal year. ICD-9-CM codes were used to identify postoperative delirium diagnoses. The incremental hospital resource consumption, measured as hospital cost and length of stay, was estimated for patients with postoperative delirium during their TAVR or SAVR index hospitalization. Multivariate regression models were used for the adjusted cost estimates controlling for patient demographics, comorbidities, and complications.

RESULTS:

A total of 21,088 claims were available for analysis (12,114 TAVR and 8,974 SAVR). The mean age of the TAVR group was older compared to the SAVR group (87 versus 84; p < .001) and TAVR patients presented with a higher comorbidity burden (Charlson Index score 3.0 versus 2.1; p < .0001). TAVR patients experiencing postoperative delirium during the index hospitalization was 1.6 percent compared to 3.6 percent of surgical patients (p < .0001). For the overall cohort, the regression adjusted incremental cost of postoperative delirium was (USD15,592; p < .0001). Patients experiencing delirium also had significantly longer hospital length of stay (4.16 days; p < .0001). When stratified by treatment approach, the adjusted incremental cost was USD13,862 for TAVR (p < .0001) and USD16,656 for SAVR (p < .0001).

CONCLUSIONS:

While infrequent, postoperative delirium significantly increased hospital cost and length of stay following transcatheter or surgical aortic valve replacement (AVR). Despite a significantly higher comorbidity burden, TAVR was associated with lower postoperative delirium rates compared to SAVR. Moreover, post-TAVR delirium may be associated with less resource consumption than post-SAVR delirium. Future studies should seek to determine whether general anesthesia avoidance in appropriately selected transfemoral TAVR patients can further decrease rates of delirium.
OP25 Evidence Gathering Across Key Stakeholders Involved In Early Health Technology Assessment
Authors: Manetti Stefania , Burns Richéal , Turchetti Giuseppe
Published: January 2018

INTRODUCTION:

The adoption and reimbursement of a new or novel medical device frequently occurs after an economic evaluation of the innovation. One important factor for reimbursement rejections by the English National Institute for Health and and Care Excellence (NICE) Medical Technologies Evaluation Programme (MTEP) appears to be the little or no attention to early assessment (1). The aim of this study is to achieve a more in-depth and comprehensive understanding of the value of early Health Technology Assessment (HTA) for new medical devices.

METHODS:

This study employs a mixed methods research strategy. Our informant interviews involved two types of key stakeholders: health economists in academia and professionals in medical devices firms with a professional role in research and development or market access departments. Our qualitative analysis focused on two samples from six universities (five in the United Kingdom, UK, and one in Italy) and six small to medium-sized enterprises (five in the UK, and one in Italy). Insights from field work interviews helped to design our complementary quantitative analysis.

RESULTS:

During thematic analysis, barriers to adoption of early HTA emerged across three domains. First, educational barriers (that is, what HTA/early HTA is and how to conduct it) influenced the foundation for the reimbursement strategy. Second, interviewees highlighted the presence of intrinsic barriers (for example, resources for translational and early preclinical research, reliability and reproducibility, evidence, and dissemination of sensitive information) within existing practices and knowledge. Third, several research gaps (that is, medical device classification, standardization of methods, guidelines for developers, and alignment of stakeholders perspectives) were identified. Finally, academics adopted early HTA to assess different aspects of a medical device early in development; however, developers were focused on the assessment of investment and safety/usability factors, especially for in-house evaluations.

CONCLUSIONS:

If decision makers expect developers to produce better quality evidence and society aims to optimize resources that is, not investing in non-cost-effective technologies, then the incorporation of a more robust analytical framework including a societal perspective is necessary to understand how early HTA can be embedded into all aspects of the development process.
OP27 Patient-Reported Outcome Measures In Carotid Artery Revascularization
Authors: Essat Munira , Aber Ahmed , Phillips Patrick , Poku Edith , Wood Helen Buckley , Howard Aoife , Palfreyman Simon , Kaltenthaler Eva , Jones Georgina , Michaels Jonathan
Published: January 2018

INTRODUCTION:

Patient-reported outcome measures (PROMs) provide a way to measure the impact of a disease and its associated treatments on the quality of life from the patients’ perspective. The aim of this review was to identify PROMs that have been developed and/or validated in patients with carotid artery disease (CAD) undergoing revascularization, and to assess their psychometric properties and examine suitability for research and clinical use.

METHODS:

Eight electronic databases including MEDLINE and CINAHL were searched from inception to May 2015 and updated in the MEDLINE database to February 2017. A two-stage search approach was used to identify studies reporting the development and/or validation of relevant PROMs in patients with CAD undergoing revascularization. Supplementary citation searching and hand-searching reference lists of included studies were also undertaken. The Consensus-based standards for the selection of health measurement instruments (COSMIN) and Oxford criteria were used to assess the methodological quality of the included studies, and the psychometric properties of the PROMs were evaluated using established assessment criteria.

RESULTS:

Six PROMs, reported in five studies, were identified: 36-Item Short Form Health Survey (SF-36), Euro-QoL-5-Dimension Scale (EQ-5D), Hospital Anxiety and Depression Scale (HADS), Dizziness Handicap Inventory (DHI), Quality of life for CAD scale by Ivanova 2015 and a disease-specific PROM designed by Stolker 2010. The rigour of the psychometric assessment of the PROMs were variable with most only attempting to assess a single psychometric criterion. No study reported evidence on criterion validity and test-retest reliability. The overall psychometric evaluation of all included PROMs was rated as poor.

CONCLUSIONS:

This review highlighted a lack of evidence in validated PROMs used for patients undergoing carotid artery revascularization. As a result, the development and validation of a new PROM for this patient population is warranted in order to provide data which can supplement traditional clinical outcomes (stroke >30 days post-procedural, myocardial infarction and death), and capture changes in health status and quality of life in patients to help inform treatment decisions.
OP45 Study On Effects Of Community-acquired Pneumonia Clinical Pathway On Antibiotics’ Utilization
Authors: Zhu Liping , Bai Jie , Xue Di
Published: January 2018

INTRODUCTION:

Drug overuse in healthcare settings is common in China. Clinical pathways are tools that provide the link between the best available evidence and clinical practice. This study aimed to determine if the clinical pathway of community-acquired pneumonia (CAP) had effects on the antibiotic use in patients with CAP.

METHODS:

The study was conducted in Shanghai, Hubei Province, and Gansu Province to represent high, middle, and low levels of socioeconomic status in 2015. In each region, three public tertiary general hospitals and three public secondary general hospitals were selected for chart review of antibiotics’ utilization in the patients with CAP during 2014. A multilevel logistic regression model was used in the study, with a dependent variable of appropriate utilization of antibiotics (right time, right type, and right combined use) and independent variables of hospital adoption of clinical pathway and patient characteristics (sex, age, severity of disease, and number of comorbidities).

RESULTS:

Twelve surveyed hospitals (66.67 percent) adopted CAP clinical pathways and 354 cases (66.29 percent) were from these twelve hospitals (CP group). Among the total utilization of antibiotics (796 times) in eighteen types of antibiotics used in patients with CAP, the five recommended types of antibiotics accounted for 82.16 percent.

The percentages of cases that got initial antibiotics in time were 90.60 percent in the CP group and 76.11 percent in the non-CP group. The compliance rate for appropriate types of antibiotic utilization was 88.36 percent in CP group, much higher than that in non-CP group (70.22 percent). For 244 cases that used combined antibiotics, the compliance rate for the recommended combinations of antibiotics was 20.12 percent in the CP group, but 1.25 percent in the non-CP group. After controlling patients’ characteristics, the patients in the CP group got more appropriate antibiotics than those in the non-CP group.

CONCLUSIONS:

Adoption of the CAP clinical pathway in hospitals can improve antibiotics' utilization.
OP50 European Assessments Of Medical Devices: Avenues For Improvement
Authors: Hawlik Katharina , Rummel Patrick , Wild Claudia
Published: January 2018

INTRODUCTION:

European collaboration in Health Technology Assessments (HTAs) has gained increasing recognition in recent years, not only on pharmaceutical products but also on high-risk medical devices. For medical devices, quality assessments of efficacy and safety are particularly important due to the weak market authorization in Europe. Strengthening efforts towards better collaboration thus plays a pivotal role to reduce overlap and save resources. This study explored the level of redundancy in HTA assessments of medical devices in Europe in order to identify areas for better collaboration.

METHODS:

We performed an analysis of European HTA reports of medical devices regarding their timing in relation to market authorization, the respective level of evidence used and the overlaps in topics. The ADVANCE HTA database from 2014 was used to select a cohort group of ten high-risk medical devices. A systematic search was conducted to identify all relevant, European HTA reports investigating the ten devices within a time span of 12 years (2003-2015). We analysed the number of annual assessments per technology and evaluated activity patterns, late and early assessors, and minimum evidence requirements.

RESULTS:

The results revealed the amount of redundancies in European HTA production: the number of reports per technology ranged from a minimum of five to a maximum of twenty-two over a time-span of 12 years. Within a single year, one technology was assessed up to six times by different HTA institutes in Europe. Out of fourteen countries included in the evaluation, two countries assessed each technology, and seven countries assessed more than seven out of the ten technologies.

CONCLUSIONS:

The findings indicate that more efficient collaboration is needed to save scarce resources and time of HTA institutes. Efficient collaboration as such needs to shift the focus beyond the time span of one year, and start building on each others work from previous assessments.
OP61 Cost-Utility Analyses Of Biologics For Refractory Ulcerative Colitis
Authors: Davies Sophia Campbell , Inserra Chiara , Muserra Gaetana , Piacenza Mariagrazia , Ardizzone Sandro , Saporito Tommaso
Published: January 2018

INTRODUCTION:

Although many biologics (Bs) have been approved for the treatment of moderate-to-severe Ulcerative Colitis (UC) in patients who have responded inadequately to conventional therapy, the selection of Bs is controversial due to the lack of head-to-head trials. Indirect economic comparisons of these costly drugs are available from National Healthcare perspectives that are not the Italian ones. Therefore, the objective is to evaluate cost-utility of Bs for the treatment of refractory moderate-to-severe UC both in Italy and in the Lombardy Region.

METHODS:

A Markov model (considering three transition states: remission, clinical response, relapse) was constructed using the software R 3.3.1 markovchain-package to evaluate incremental cost-utility ratios (ICUR) of adalimumab (ADA), infliximab (IFX), infliximab biosimilar (IFX-B), golimumab (GOL) and vedolizumab (VED) treatments of patients over a 10-year time horizon from the perspective of the Italian (N) and Lombardy Region (R) healthcare system. Clinical parameters were derived from clinical trials. Costs (actualized by – 1.5 percent) were obtained from the National database and Regional public tender. Utility was expressed as QALY (Quality-Adjusted Life Years).

RESULTS:

Costs per treatment were different from a N and R perspective (ADA -55 percent; IFX -16.7 percent; IFX-B -29.6 percent; GOL -9.6 percent; VED -10 percent). Direct healthcare costs (treatment cost, visits, laboratory tests, hospital admissions) were calculated over 10 years of treatment per patient: ADA (N: EUR114,227, R: EUR68,314, -40.2 percent), IFX (N: EUR130,595, R: EUR103,081, -21 percent), IFX-B (N: EUR110,438, R: EUR78,852, -28.6 percent), GOL (N: EUR118,602, R: EUR96,922, -18.3 percent), VED (N: EUR113,852, R: EUR102,932, -9.6 percent) with associated QALY respectively of 6.68, 6.66, 6.66, 6.70, 7.02. From a N perspective, IFX-B was dominating compared to all other treatments. The ICUR of VED/IFX-B was EUR9,483 for 10 years (willingness to pay EUR948/QALY). From a R perspective, ADA was dominating compared to all other treatments. The ICUR of VED/ADA was EUR101,818 for 10 years (Willingness to Pay, WTP EUR10,182/QALY).

CONCLUSIONS:

National and Regional cost-utility analyses produced different results. As Regional price discounts can occur, local analysis is needed to estimate the economic impact of therapies to ensure optimal choice.
OP76 Economic Contributions Of Older Adults In Europe
Authors: Bloom David , Khoury Alexander , Sevilla Jaypee
Published: January 2018

INTRODUCTION:

Europe's population is aging rapidly. Europeans aged 60 years and over formed only 16 percent of Europe's total population in 1980, but they now constitute 24 percent and will grow to 34 percent by 2050 (1). These challenges may be expected in the form of tighter labor markets, lower savings rates, and slower economic growth, as well as fiscal stress from lower earnings and tax revenue and increased pension and healthcare spending.

We may, however, overestimate the magnitude of these challenges and make poorer policy choices if we underestimate the productive contributions that older adults make to society. The literature measuring these productive contributions is regrettably underdeveloped, as is the literature on what policies can enhance such contributions.

This study focuses on the market and non-market productive contributions of older adults in Europe and addresses three questions:

(i)

What is the nature and magnitude of the contributions made by older adults in Europe?

(ii)

How do those contributions vary by country, time, and age, and how are they likely to evolve as the relative size of older cohorts swells?

(iii)

How might changes in policy, institutions, behavior, and health likely influence the economic effects of population aging in Europe?

METHODS:

These research questions are explored using multivariate statistical tools to analyze rich data from multiple countries and waves of the Survey of Health, Ageing, and Retirement in Europe (SHARE) and the English Longitudinal Study of Ageing (ELSA).

RESULTS:

Older adults in Europe make significant productive contributions in the form of labor force participation, caregiving for family and friends, and volunteering. These contributions vary widely by country and are correlated with age, health status, official retirement age, and population age structure.

CONCLUSIONS:

The economic effects of population aging in Europe can be significantly moderated by effective retirement and healthcare policy.
OP89 Using Economic Evidence To Set Priorities In Ghana: The Case Of Malaria
Authors: Addo Rebecca , Hall Jane , Goodall Stephen , Haas Marion
Published: January 2018

INTRODUCTION:

Malaria remains the number one cause of morbidity and mortality in Ghana. Since 1961, several malaria control strategies have been adopted, some of which were discontinued due to funding. In spite of the numerous malaria control strategies in place, its prevalence continues to rise. Priority setting using economic evidence has been proven to ensure efficient use of resources in a cost-effective manner (1). This study, therefore, sought to examine economic evaluation studies conducted on malaria in Ghana and their influence on malaria control policies.

METHODS:

A systematic search was conducted in databases including Medline and Embase to identify relevant Malaria economic evaluation studies conducted in Ghana up to December 2016. Malaria control policies formulated in Ghana over the years were also reviewed. The economic studies were examined alongside the policies to establish their influence on them.

RESULTS:

A total of eight studies were identified, all of which were conducted in response to a global directive on malaria control and funded by international agencies. All studies were cost-effective; five evaluating preventive measures and the remaining evaluating treatment. The studies used different methodological approaches, rendering the comparison between alternatives impossible.

Most malaria control initiatives are funded by international agencies, hence its abandonment when funding ceases. Although the majority of economic studies addressed some of these policies, none of them directly influenced their adoption. These policies were rather influenced by global malaria control initiatives. Also, malaria chemoprophylaxis; demonstrated as cost-effective by three studies, is not on the Ghana malaria control policy (2,3).

CONCLUSIONS:

To ensure sustainability of malaria control strategies and subsequently reduce its prevalence, Ghana must invest financially into economic analysis for formulating and implementation of these policies. Also, the use of economic evidence by policy makers can be promoted, should researchers adopt a methodological guideline for its conduct that ensures comparability of results.
OP92 Addressing Challenges Of Implementing A Health Technology Assessment Framework In South Africa
Authors: Mueller Jani
Published: January 2018

INTRODUCTION:

South Africa is in the process of providing comprehensive health insurance to all its citizens, thus paving the pathway for Health Technology Assessment (HTA) to play a significant role in provision of safe and effective healthcare. The National Department of Health (DoH) has a published framework and Health Technology Act and strategies since the 1990s to improve health outcomes, and service and delivery of care. The purpose of this study is to explore challenges faced in the implementation of the framework and policies.

METHODS:

The study will be based on review and analysis of health technology policies and legislations introduced in South Africa since the 1990s. These documents are available from the DoH archive. The review from this grey literature was supplemented by information collected from a self-completion questionnaire, which was distributed to key stakeholders. Respondents were identified by direct contact with ministries of health and professional bodies, and included health professionals from the public and private healthcare sector, for example, practitioners, experts from hospitals, and industry representatives. The questionnaire addressed issues pertaining to decision making regarding health service delivery and the status of HTA in the country.

RESULTS:

The framework lays out the strategy to facilitate appropriate utilization of health technologies and includes among others, an HTA section. Fragmented use of HTA or parts thereof has been observed in the public and private health care sector. Furthermore, the respondents pointed out that decisions on health technology can be political, institutional or professionally driven whereas they all agreed that a formal and institutional implementation of HTA would improve healthcare service.

CONCLUSIONS:

The goal to achieve universal health care provides an excellent window of opportunity for formal use of HTA in policy- and decision-making. However, (i) the inadequate number of trained professionals and education and training opportunities (ii) lack of awareness and understanding of the principles of HTA and its impact on the improvement of health care are among the many challenges faced by the system. It has also been observed that national and regional champions can act as change agents and would have a snowball effect.