bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin
Authors: Costelloe Elaine O , Stacey Katryn J , Antalis Toni M , Hume David A
Published: January 2018

We investigate the regulation of plasminogen activator inhibitor-2 (PAI-2) in murine macrophages. PAI-2 mRNA was inducible by bacterial lipopolysaccharide (LPS) in primary cells and macrophage-like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor α or interferon-β (IFN-β). PAI-2 mRNA levels generally varied inversely from those of its target, urokinase-type plasminogen activator (uPA), and the macrophage growth factor CSF-1, which induces uPA, inhibited PAI-2 expression in cells treated subsequently with LPS. Expression of PAI-2 was distinct from that of other LPS-inducible genes in terms of induction time course, LPS dose response, and sensitivity to co-stimulation with IFN-γ. Induction of PAI-2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heterogeneous expression in the parent line. The expression pattern of PAI-2 is discussed in terms of a possible role in LPS-induced pathology such as septicemia. J. Leukoc. Biol. 66: 172–182; 1999.
Suppression of cytokine-mediated β2-integrin activation on circulating neutrophils in critically ill patients
Authors: Rosenbloom Alan J , Pinsky Michael R , Napolitano Christopher , Nguyen Thu-Song , Levann Douglas , Pencosky Nicole , Dorrance Adrienne , Ray Barry K , Whiteside Theresa
Published: January 2018

The β2 integrin CD11b plays a central role in inflammation and the systemic inflammatory response syndrome (SIRS). The CD11b molecule activates in two ways: the density of membrane-bound CD11b up-regulates and the molecule undergoes a conformational change that confers adhesiveness to counter-receptors. We studied the kinetics of CD11b activation in patients with SIRS. We found a significantly diminished CD11b activation in response to tumor necrosis factor α (TNF-α). This affected all circulating polymorphonuclear neutrophils (PMN) and was an intrinsic property of the cells and not due to antagonism by soluble TNF-α receptors or loss of cellular receptors for TNF-α. Diminished responsiveness correlated with the severity of organ failure and lasted for months in some patients but had no impact on mortality. We speculate that reduced CD11b responsiveness in SIRS contributes to the high risk of recurrent infection, but that it may also be protective against excessive PMN activation within the vascular space. J. Leukoc. Biol. 65: 83–89; 1999.
Mechanisms of regulation of the MacMARCKS gene in macrophages by bacterial lipopolysaccharide
Authors: Chang Sandy , Stacey Katryn J , Chen Jianmin , Costelloe Elaine O , Aderem Alan , Hume David A
Published: January 2018

Bacterial lipopolysaccharide (LPS) stably induced the protein kinase C substrate, MacMARCKS, in murine resident peritoneal macrophages; initial induction of MacMARCKS mRNA was detected within 15 min and was protein synthesis-independent. This response was observed in the macrophage cell line RAW264, and occurred also in response to plasmid DNA, a partial mimetic of other responses to LPS. In murine bone marrow-derived macrophages, MacMARCKS was expressed constitutively due to induction by macrophage colony-stimulating factor. Nuclear run-on transcription revealed that, like tumor necrosis factor α (TNF-α), MacMARCKS was transcribed constitutively in RAW264 cells. The MacMARCKS promoter was sequenced to –1.7 kb and the transcription start site determined. Transient transfections of RAW264 cells revealed that the 113-bp GC-rich proximal promoter contained all the elements required for both high basal activity and 15- to 20-fold activation by LPS. J. Leukoc. Biol. 66: 528–534; 1999.
LPS-induced signals in activation of a caspase-3-like protease, a key enzyme regulating apoptotic cell damage into a macrophage-like cell line, J774.1, in the presence of cycloheximide
Authors: Karahashi Hisae , Amano Fumio
Published: January 2018

The earliest observed apoptotic change in a macrophage-like cell line, J774.1, treated with lipopolysaccharide (LPS) in the presence of cycloheximide (CHX) was a selective increase in caspase-3-like activity. The addition of polymyxin B, TPCK, herbimycin A, or genistein, all of which inhibited LPS-induced tumor necrosis factor α (TNF-α) production by macrophages, suppressed the activation of the caspase-3-like protease in these macrophages treated simultaneously with CHX. However, SB202190 and SB203580, inhibitors of MAP kinase, and PD98059, an inhibitor of MAP-kinase kinase (MEK), showed no effect on the activation of the caspase-3-like protease or on the cell damage of the macrophages treated with LPS and CHX, whereas they inhibited LPS-induced TNF-α production. These results suggest that some of the early signals in LPS-treated macrophages are common to the subsequent pathways for TNF-α production and caspase-3-like protease activation, but the later signals, like MAP-kinase kinase or MAP-kinase, are not involved in the pathways for caspase-3-like protease activation. J. Leukoc. Biol. 66: 689–696; 1999.
Nrampl: a link between intracellular iron transport and innate resistance to intracellular pathogens
Authors: Barton C Howard , Biggs Thelma E , Baker Stephen T , Bowen Holly , Atkinson Peter G P
Published: January 2018

Nramp1 (natural resistance-associated macrophage protein one) regulates intracellular pathogen proliferation and macrophage inflammatory responses. Murine Nramp1 exhibits a natural polymorphism with alleles termed resistant and susceptible. Alleles restrict or allow the proliferation of intracellular pathogens, respectively. Structural predictions suggest that Nramp1 encodes the prototypic member of a transporter family. Nramp1 exhibits sequence identity to Nramp2, which regulates intestinal and reticulocyte iron uptake. Based on this sequence identity we have initiated experiments for Nramp1 to investigate its role in macrophage iron homoeostasis and using a transfection approach in the RAW264.7 murine macrophagelike cell line, which lacks a functional Nramp1 gene. Nramp1 expression supports increased acute cytoplasmic influx of iron, detected using the fluorescent iron sensor dye calcein. Analysis of the endogenous iron sensors, iron regulatory protein 1 and 2, reveals a greater flux of iron in Nramp1-expressing cells and in its exclusion from the cytoplasm. Other work supports the prediction that Nramp1 is a phosphoprotein and the extent of phosphorylation changes in response to inflammatory cytokines. Together these data support the hypothesis that control of intracellular iron homoeostasis is a vital element used by phagocytes to control the proliferation of intracellular pathogens. J. Leukoc. Biol. 66: 757–762; 1999.
Down-regulation of the β-chemokine receptor CCR6 in dendritic cells mediated by TNF-α and IL-4
Authors: Carramolino Laura , Kremer Leonor , Goya íñigo , Varona Rosa , Buesa Jose María , Gutiérrez Julio , Zaballos Angel , Martínez-A. Carlos , Márquez Gabriel
Published: January 2018

Chemokines are involved in the control of dendritic cell (DC) trafficking, which is critical for the immune response. We have generated DC from human umbilical cord blood CD34+ progenitors cultured with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor α (TNF-α), and stem cell factor. Using an anti-CCR6 monoclonal antibody, we observed that these cells showed maximum expression of this β-chemokine receptor when they were immature, as determined by their relatively low expression of several DC maturation markers such as CD1a, CD11c, CD14, CD40, CD80, and CD83. Immature DC responded strongly to macrophage inflammatory protein-3α (MIP-3α), the CCR6 ligand, in migration and calcium mobilization assays. CCR6 expression decreased in parallel with the DC maturation induced by prolonged TNF-α treatments. Interleukin-4 was also able to decrease CCR6 protein levels. Our findings suggest that the MIP-3α/CCR6 interaction plays an important role in the trafficking of immature DC to chemokine production sites such as injured or inflamed peripheral tissues, where DC undergo maturation on contact with antigens. J. Leukoc. Biol. 66: 837–844; 1999.
Nature versus nurture in T cell cytokine production
Authors: Fitzpatrick David R , Kelso Anne
Published: January 2018

Both extrinsic and intrinsic factors influence the development of cytokine expression patterns in T lymphocytes. The models proposed to accommodate these factors are often separated into two types: deterministic (or instructional) and probabilistic (or stochastic). In this review we compare these two types of models and examine how they account for different stages of T cell cytokine responses to antigen stimulation. We conclude by showing how a reconciliation of the two types of models may be possible, perhaps through the regulatory potential of heritable epigenetic mechanisms. This type of reconciliation may open up new avenues for manipulating T cell cytokine expression and redirecting immune responses. J. Leukoc. Biol. 66: 869–875; 1999.
Changes in susceptibility to Fas-mediated apoptosis during differentiation of HL-60 cells
Authors: Ohashi Masaru , Iwase Masayasu , Nagumo Masao
Published: January 2018

The Fas-mediated pathway has been implicated as an important cellular pathway mediating apoptosis in diverse cell types. We conducted studies to examine the susceptibility to Fas-mediated apoptosis of HL-60 cells treated with differentiation-inducing factors such as dimethyl sulfoxide (DMSO), retinoic acid (RA), and 1α, 25 dihydroxyvitamin D3 (VD3). Although the expression of Fas antigen (Ag) and its mRNA showed a marked increase in HL-60 cells with cell differentiation, that of Bcl-2 protein and its mRNA revealed the reverse. The expression of caspase proteins such as caspases-3 and -8 was also enhanced during cell differentiation. DNA fragmentation, annexin V binding, and caspase activities increased in differentiated HL-60 cells with the addition of anti-Fas Ag antibody. These findings were more clearly demonstrated in DMSO- or RA-induced neutrophil-like cells than in VD3-induced monocyte-like cells. Therefore, susceptibility to Fas-mediated apoptosis showed an increase with differentiation of HL-60 cells, especially in the neutrophil lineage. These results suggest that the difference of susceptibility to Fas-mediated apoptosis among cell populations depends on the expression of Fas Ag, Bcl-2, and caspases. Cell maturation and susceptibility to Fas-mediated apoptosis may be linked in hematopoietic cells. J. Leukoc. Biol. 67: 374–380; 2000.
Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils
Authors: Alexander Shelia R , Kishimoto Takashi K , Walcheck Bruce
Published: January 2018

The signaling factors that direct the rapid shedding of L-selectin from neutrophils upon chemoattractant stimulation are poorly understood. Protein kinase C (PKC) has been implicated, yet previous studies have relied on the use of phorbol esters and nonselective kinase inhibitors. We treated neutrophils with various selective kinase inhibitors to evaluate their effects on N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced L-selectin shedding. We found that three selective inhibitors of PKC, structurally related to staurosporine, largely blocked both fMLP- and phorbol 12-myristate 13-acetate (PMA)-induced L-selectin shedding; however, these inhibitors did not affect fMLP-induced up-regulation of Mac-1 (CD11b/CD18) expression, which has been shown not to involve PKC. Other selective serine, threonine, and tyrosine kinase inhibitors were found not to block fMLP-induced L-selectin shedding. These findings provide more definitive evidence for the role of PKC in chemoattractant-induced L-selectin proteolysis. It is interesting that certain highly selective PKC inhibitors, not structurally related to staurosporine, were found to directly induce L-selectin shedding from neutrophils. J. Leukoc. Biol. 67: 415–422; 2000.
Regulation of adaptive immune responses by innate cells expressing NK markers and antigen-transporting macrophages
Authors: Stein-Streilein J , Sonoda K-H , Faunce D , Zhang-Hoover J
Published: January 2018

A continuing theme of work done in our laboratory involves regulation of adaptive immune response by innate cells, in general, and immune-regulation by natural killer (NK) and NKT cells, in particular. Studies include work with the lung and the eye. In addition to immune surveillance of tumor cells, the NK cell is often associated with secreting cytokines that contribute to the creation of microenvironments conducive to Th1 responses and with defense mechanisms that lessen the initial infecting viral load. Reported studies show that the NKT cells support both T helper cell responses (type 1 and 2), as well as their being absolutely central to the development of antigen-specific T-regulatory cells involved in peripheral tolerance. Because of the multifunctional capabilities of the NKT cell, we propose that yet another cell, such as the antigen-presenting cell (APC), may influence the effector pathway of the NKT cell. We postulate that the APC that transports the antigen from the entry environment provides both trafficking and activation signals for innate cells in the secondary lymphoid organs. Evidence is presented that macrophage-derived signals selectively recruit NKT cells and bias their cytokine synthesis. Data imply that, just as occurs in immune inflammation, a collection of innate and adaptive immune cells interact within the secondary lymphoid tissue to generate antigen-specific tolerance in the periphery. J. Leukoc. Biol. 67: 488–494; 2000.
NF-κB-dependent fractalkine induction in rat aortic endothelial cells stimulated by IL-1β, TNF-α, and LPS
Authors: Garcia Gabriela E , Xia Yiyang , Chen Shizhong , Wang Yibin , Ye Richard D , Harrison Jeffrey K , Bacon Kevin B , Zerwes Hans-Guenter , Feng Lili
Published: January 2018

Fractalkine is an endothelial cell-derived CX3C chemokine that is chemotactic mainly to mononuclear cells. Fractalkine was induced in rat aortic endothelial cells (RAEC) by interleu-kin-1β (IL-1β), tumor necrosis factor α (TNF-α), and lipopolysaccharide (LPS) transcriptionally and translationally. This induction correlated with increased NF-κB DNA binding activity as determined by gel mobility shift assay. Supershift assays revealed that the NF-κB subunits p50 and p65 were responsible for κB binding. Accordingly, we examined the role of NF-κB in fractalkine induction in RAEC through the use of an adenovirus-mediated mutant IκB as a specific inhibitor. Delivery of a dominant-negative form of IκBα in RAEC dramatically reduced the induction of fractalkine by these stimuli, suggesting a role for NF-κB activation in fractalkine induction. The inhibition of fractalkine expression by two potent NF-κB inhibitors, sulfasalazine and sanguinarine, further supported the central role of NF-κB in fractalkine transcription regulation and suggested a novel therapeutic target aimed at modulating leukocyte endothelial cell interaction. J. Leukoc. Biol. 67: 577–584; 2000.
Diazepam-binding inhibitor-derived peptides induce intracellular calcium changes and modulate human neutrophil function
Authors: Cosentino Marco , Marino Franca , Cattaneo Simona , Di Grazia Laura , Francioli Cristina , Fietta Anna Maria , Lecchini Sergio , Frigo Gianmario
Published: January 2018

We studied the effects of two diazepambinding inhibitor (DBI)-derived peptides, triakonta-tetraneuropeptide (DBI 17–50, TTN) and eiksoneuropeptide (DBI 51–70, ENP), on cytosolic free Ca2+ concentrations ([Ca2+]i), chemotaxis, superoxide anion (O) generation, and phagocytosis in human neutrophils. Both TTN and ENP induced a rapid and transient rise of [Ca2+]i. The effect of TTN depended on the presence of extracellular Ca2+, whereas the effect of ENP also persisted after extracellular Ca2+ chelation. TTN induced neutrophil chemotaxis, stimulated O generation, and enhanced phagocytosis. ENP did not affect cell migration and oxidative metabolism but enhanced phagocytosis. Both peptides modulated N-formylmethionyl-leucyl-phenylalanine- and phorbol myristate acetate-induced O generation. Because neutrophils express benzodiazepine receptors of the peripheral type (pBRs) and DBI-derived peptides may interact with such receptors, we investigated the possible role of pBRs in TTN- or ENP-induced effects. The synthetic pBR ligand RO 5-4864 increased [Ca2+]i through extracellular Ca2+ influx and this effect was prevented by the pBR antagonist PK-11195. RO 5-4864, however, was ineffective on neutrophil migration and O generation and only slightly affected phagocytosis. Moreover, PK-11195 delayed the [Ca2+]i rise induced by TTN but did not significantly affect its extent, and had no effect on the [Ca2+]i rise induced by ENP. We conclude that DBI-derived peptides induce [Ca2+]i changes and modulate neutrophil function mainly through pBR-independent pathways. In view of the wide cell and tissue distribution of DBI in the brain and in peripheral organs, modulation of neutrophil function by DBI-derived peptides may be relevant for both the neuroimmune network and the development and regulation of the inflammatory processes. J. Leukoc. Biol. 67:637–643; 2000.
Prognostic significance of nonsustained ventricular tachycardia in patients receiving cardiac resynchronization therapy for primary prevention: Analysis of the Japan cardiac device treatment registry database
Authors: Yokoshiki Hisashi , Shimizu Akihiko , Mitsuhashi Takeshi , Furushima Hiroshi , Sekiguchi Yukio , Manaka Tetsuyuki , Nishii Nobuhiro , Ueyama Takeshi , Morita Norishige , Okamura Hideo , Nitta Takashi , Hirao Kenzo , Okumura Ken ,   Members of the Implantable Cardioverter‐Defibrillator (ICD) Committee of the Japanese Heart Rhythm Society
Published: January 2018

Background

Whether nonsustained ventricular tachycardia (NSVT) is a marker of increased risk of sustained ventricular tachyarrhythmias (VTAs) remains to be established in patients receiving cardiac resynchronization therapy with a defibrillator (CRT‐D) for primary prevention.

Methods

Among the follow‐up data of the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2011 and August 2015, information regarding a history of NSVT before the CRT‐D implantation for primary prevention had been registered in 269 patients. Outcomes were compared between two groups with and without NSVT: NSVT group (n = 179) and No NSVT group (n = 90).

Results

There was no significant difference with regard to age, gender, and NYHA class between the two groups. Left ventricular ejection fraction (LVEF) was 25.6% in the NSVT group and 28.0% in the No NSVT group (P = .046). The rate of appropriate therapy at 24 months was 26.0% and 18.4% in the NSVT and No NSVT groups (P = .22), respectively. Survival free from heart failure death was reduced in the NSVT group, as compared with the No NSVT group, with the rate of 90.2% vs 97.2% at 24 months (P = .030). A multivariate analysis identified a history of NSVT, anemia, and no use of angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin‐receptor blocker (ARB) as predictors of heart failure death.

Conclusions

NSVT appears to be a surrogate marker of severe heart failure rather than a substrate for subsequent sustained VTAs in patients with CRT‐D for primary prevention.
Validation of the Stanford Leisure‐Time Activity Categorical Item (L‐Cat) using armband activity monitor data
Authors: Ross K. M. , Leahey T. M. , Kiernan M.
Published: January 2018

Objective

Accurate assessment of physical activity (PA) in public health and healthcare settings remains a challenge given limitations of existing brief assessment tools. The Stanford Leisure‐Time Activity Categorical Item (L‐Cat), a single item with six categories, has previously demonstrated excellent reliability and adequate validity relative to pedometer steps. However, pedometers cannot assess key dimensions of PA intensity or duration.

Methods

We evaluated the L‐Cat's criterion validity and sensitivity to change relative to objectively measured Sensewear armband activity monitors among 76 adults with overweight/obesity (mean age 50.8 ± 11.9 years, BMI = 33.1 ± 3.4 kg m−2) at baseline and end of a 6‐month behavioural weight management pilot trial.

Results

At baseline, L‐Cat category was associated with armband‐measured daily steps (Spearman's ρ = 0.41, p < 0.001), total weekly minutes of moderate/vigorous‐intensity PA (MVPA) (ρ = 0.40, p < 0.001) and weekly minutes of MVPA accumulated in bouts ≥10 min (ρ = 0.47, p < 0.0001). Participants increasing ≥1 L‐Cat category from baseline to 6 months had greater increases in steps (1,110.1 ± 1,852.1 vs. −18.0 ± 2,005.6 steps/d, p = 0.032), total minutes of MVPA (145.7 ± 180.6 vs. −2.1 ± 215.8 min/week, p = 0.007) and greater weight losses (−7.4 ± 7.7% vs. −3.1 ± 4.8%, p = 0.013) than those who stayed the same/decreased L‐Cat categories.

Conclusion

The L‐Cat demonstrated adequate criterion validity and excellent sensitivity to change relative to objectively measured PA among behavioural weight management pilot trial participants. The L‐Cat may be particularly useful for identifying individuals at lower activity levels and when using all six categories.
Protective effect of boiogito extract with glucosamine HCl against adjuvant‐induced arthritis in rats
Authors: Takenaga Mitsuko , Niimi Jun , Hamaguchi Akemi , Asano Teita , Tsuchiya Reiko , Ohta Yuki , Yudoh Kazuo , Inoue Hajime
Published: January 2018

Aim

The effect of boiogito extract combined with glucosamine HCl was assessed in adjuvant‐induced arthritis (AIA) rats.

Methods

Rats received a daily oral mixture of boiogito extract (125 mg/kg) and glucosamine HCl (80 mg/kg) before and after once‐off adjuvant injection. Treatment was continued up to the day when blood and/or tissue were collected (day 12 or day 21). Paw swelling, arthritis score, and inflammatory mediators were assessed.

Results

Combined treatment was more effective for AIA than either agent alone. Both serum nitric oxide (NO) and tissue NO were significantly suppressed in the adjuvant‐uninjected hind paw on day 12. Boiogito extract significantly reduced the tissue level of matrix metalloproteinase (MMP)‐13. In addition, interleukin (IL)‐1β‐induced MMP‐13 by SW1353 chondrocytes was dose‐dependently suppressed by boiogito extract, while glucosamine HCl had little effect. IL‐1β‐induced phosphorylation of extracellular signal‐related kinase (ERK) was inhibited by the combination of boiogito extract and glucosamine HCl, but was most strongly suppressed by glucosamine HCl alone.

Conclusion

Combined treatment with boiogito extract and glucosamine HCl had a protective effect against AIA in rats. This effect was related to strong suppression of MMP‐13 production (mainly by boiogito extract) and inhibition of inflammatory mediator production via ERK signaling (mainly by glucosamine HCl).
Rethinking urban water management in Addis Ababa in the face of climate change: An urgent need to transform from traditional to sustainable system
Authors: Worku Hailu
Published: January 2018

Urban water management in Addis Ababa, Ethiopia, is of significant concern to the city government owing to the growing demand for water, poor urban water management practices, insufficient and ineffective infrastructures, and climate change. The objective of this study is to review current water resources and management practices, consider the sustainability of the urban water cycle in relation to climate change, and devise a feasible strategy for a sustainable urban water management system. The results of this study show that the situation as it is now is not sustainable at current levels of demand and supply, either in terms of the systems’ management practices, or in terms of the challenges posed by climate change. An Integrated Urban Water Management strategy that covers the entire urban water cycle, including diversification of water sources, protection and conservation of water, sustainable exploitation, distribution, and consumption and wastewater management, water recycling, nutrient reuse, and safe wastewater disposal, should be implemented as soon as practicable.
Increased frequency of AMP‐activated protein kinase‐positive spinal motor neurons after sciatic nerve injury in a mouse model
Authors: Qi Bao , Cao Gui‐Jun , Li Qing‐Wei , Chen Guo‐Wu , Liang Xiao , Wang Yu‐Zhong , Meng Chun‐Yang
Published: January 2018

The role of AMP‐activated protein kinase (AMPK) in the regulation of energy metabolism and the control of skeletal muscle regeneration post injury has been described previously. It remains unknown whether this metabolic sensor plays a role in the mechanism of axonal regeneration post injury. In this study, we used a sciatic nerve crushed mouse model to detect the expression of AMPK in sciatic nerve and spinal motor neurons at 1 week, 2 weeks and 3 weeks after injury by immunofluorescence staining. Electrophysiological and histopathological studies were used to confirm the nerve injury and regeneration. Our results showed that frequency of AMPK‐positive spinal motor neurons was significantly higher on day 7 after sciatic nerve crush (SNC) and peaked on day 14. No expression of AMPK was detected in axons of the sciatic nerve before and after the injury. Taken together, our study suggested a possible role of AMPK in the mechanism of motor nerve regeneration after injury.
Rethinking Institutions: Innovation and institutional change in India's informal economy
Authors: HARRISS-WHITE BARBARA
Published: January 2018

India has the largest informal, unregistered economy in the world, infrastructurally backward, yet vital for both growth and livelihoods. In the first section of this article, five economic institutions that shape this economy are introduced: small firms, informality, non-metropolitan towns, innovation and innovation systems, and the state's regulative impact on the economy it does not directly regulate. In the second section, we trace the development of the commodity economy of a South Indian town taken for case study over 40 years, before exploring three kinds of innovation in the third section: invention, adaptive, and adoptive innovation. In the fourth section, the formal and informal institutions that nurture informal innovation are analysed: family business, business associations, banks and finance, informal insurance and gold, hybrid state–private institutions, and informal innovation inside the state. The conclusion confirms the innovative dynamism of the informal economy and the complex pathways of institutional change that both shape, and are shaped by, innovation.
OP01 Cross Border Cooperation On High-Cost-Capital Investments In Health
Authors: Rosian-Schikuta Ingrid , Bobek Julia , Laschkolnig Anja , Ostermann Herwig , Mildschuh Stephan , Pertl Daniela , Stürzlinger Heidi , Zsifkovits Johannes , Zuba Martin
Published: January 2018

INTRODUCTION:

The medical equipment sector is characterized by a large share of overall health budgets spent for the provision of capital investment goods such as medical scanners and radiotherapy units. A high variability in provision and utilization rates of medical equipment can be observed too. The objective for this study was to contribute to effective cross-border cooperation between European Union (EU)-Member States by pooling resources for high-cost medical equipment investments (1).

METHODS:

Potential cost-intensive and highly specialised medical equipment, where cross-border investment resource pooling may be recommended, were identified by a combined evidence search and expert consultation. An efficiency assessment of medical equipment potential savings for EU-countries was done by a benchmark-approach and a best-practice-approach. Furthermore six examples for cross-border cooperation were investigated and two surveys have been conducted.

RESULTS:

The following medical equipment can be considered as cost-intensive and highly specialized across EU-Member States: Magnetic Resonance Imaging (MRI) scanners, Computed Tomography (CT) scanners, Stereotactic systems and Surgical robots.

The efficiency assessment using the benchmark approach was performed for MRI, CT scanners, Positron Emission Tomography (PET) scanners, Angiography units, Gamma cameras and Lithotriptors. The results of the best-practice approach showed potential cost savings due to under-or overutilization per device group and EU-Member State. However, as this analysis offers a view on health systems on a very macro level it was not possible to give detailed insights at the country-level.

The six selected cross-border examples demonstrated a wide variety of options regarding the structure, extent and organization of cross-border cooperation: Five of six cross-border examples were cooperation close to the border, in four of six examples EU funds played an important role.

CONCLUSIONS:

The study highlighted that cross-border cooperation in the field of cost-intensive/highly specialized medical equipment could bring economic advantages for many EU-Member States. Despite this, still only little is done by EU-Member States in terms of cooperation. Reasons are diverse and can be ascribed to lacking information, differences of national health systems, organizational and administrative hurdles, and lacking political support.
OP75 Implementing Risk Stratification In Primary Care: A Qualitative Study
Authors: Porter Alison , Snooks Helen , Kingston Mark , Davies Jan , Hutchings Hayley , Whitman Shirley , Watkins Alan , Evans Bridie , Bailey-Jones Kerry , Burge-Jones Deborah , Dale Jeremy , Fitzsimmons Deborah , Harrison Jane , Howson Helen , Heaven Martin , John Gareth , Lewis Leo , Philips Ceri , Sewell Bernadette , Warm Daniel , Williams Victoria , Russell Ian
Published: January 2018

INTRODUCTION:

A predictive risk stratification tool (PRISM) to estimate a patient's risk of an emergency hospital admission in the following year was trialled in general practice in an area of the United Kingdom. PRISM's introduction coincided with a new incentive payment (‘QOF’) in the regional contract for family doctors to identify and manage the care of people at high risk of emergency hospital admission.

METHODS:

Alongside the trial, we carried out a complementary qualitative study of processes of change associated with PRISM's implementation. We aimed to describe how PRISM was understood, communicated, adopted, and used by practitioners, managers, local commissioners and policy makers. We gathered data through focus groups, interviews and questionnaires at three time points (baseline, mid-trial and end-trial). We analyzed data thematically, informed by Normalisation Process Theory (1).

RESULTS:

All groups showed high awareness of PRISM, but raised concerns about whether it could identify patients not yet known, and about whether there were sufficient community-based services to respond to care needs identified. All practices reported using PRISM to fulfil their QOF targets, but after the QOF reporting period ended, only two practices continued to use it. Family doctors said PRISM changed their awareness of patients and focused them on targeting the highest-risk patients, though they were uncertain about the potential for positive impact on this group.

CONCLUSIONS:

Though external factors supported its uptake in the short term, with a focus on the highest risk patients, PRISM did not become a sustained part of normal practice for primary care practitioners.
OP78 Patient Involvement In European Health Technology Assessment Focus Group With Cardiac Patients
Authors: Ettinger Sabine , Mayer Julia , Stanak Michal , Wild Claudia
Published: January 2018

INTRODUCTION:

Involving patients in defining the scope of health technology assessments is recognized as a valuable strategy that ensures that patient-relevant outcomes are considered.

The aim of this project was to pilot the focus group approach with cardiac patients in a European rapid assessment on the wearable cardioverter defibrillator, to improve involvement processes, to identify neglected outcomes, and to explore the potential of this methodology for eliciting the patients views on their disease and the wearable cardioverter defibrillator therapy.

METHODS:

An e-mail was sent to members of the nine regional associations of the Austrian Organization for Heart and Lung Transplant Patients to identify eligible participants. Guiding questions for the discussion were developed based upon a hand search of patient involvement initiatives and a review of appropriate literature. The 4-hour meeting was moderated by a patient support expert and recorded upon approval of participants. The anonymized transcript was analyzed using framework analysis.

RESULTS:

Ten eligible patients responded, of which five men, aged between 55 and 73 years (mean 65 years) from Austria and Germany, were able to participate. All respondents experienced heart transplantation, and four had received an implantable cardioverter defibrillator before.

Participants reported that experiencing a sense of security was crucial to them and that they expected to do sports and live a life with few limitations, despite receiving a therapy. A wearable cardioverter defibrillator was hence not considered a long-term solution due to expected restrictions in living a ‘normal’ life.

Challenges included the identification of participants representative of this patient group and the complexity of patient histories.

CONCLUSIONS:

The focus group approach proved useful in the wearable cardioverter defibrillator assessment. Gathered results informed the inclusion of outcomes relevant to the target group and revealed patients views on health-related quality of life. Lessons learned guide us in further improving patient involvement processes within the European Network for HTA (EUnetHTA) project.
PP029 Hospitalizations And Costs In Bipolar Disorder Patients Initiating Long-acting Injectable Antipsychotics
Authors: Greene Mallik , Yan Tingjian , Chang Eunice , Hartry Ann , Broder Michael
Published: January 2018

INTRODUCTION:

Existing studies have not investigated the effectiveness of one long-acting injectable antipsychotic (LAI) versus another in preventing hospitalizations among patients with bipolar disorder (BD). This study was conducted to compare all-cause inpatient healthcare utilization and associated costs among BD patients who initiated LAIs.

METHODS:

This retrospective cohort analysis used the Truven Health Analytics MarketScan® Commercial and Medicaid claims database. Bipolar patients >18 years with at least one claim for one of the following LAIs were identified between 1 January 2013 and 30 June 2014 (identification period): aripiprazole, haloperidol, paliperidone, and risperidone. The first day of initiating an LAI was considered the index date. Logistic regression and generalized linear regression models were conducted to estimate risk of inpatient hospitalization and associated costs during the 1-year follow up.

RESULTS:

A total of 1,540 BD patients initiated an LAI: 14.5 percent aripiprazole, 16.3 percent risperidone, 21.0 percent haloperidol, and 48.1 percent paliperidone. With the aripiprazole cohort as the reference group, the odds of having any inpatient hospitalizations were significantly higher in haloperidol [Odds Ratio, OR (95 percent Confidence Interval, CI): 1.49 (1.01 - 2.19)] and risperidone [1.78 (1.19 - 2.66)] cohorts. The paliperidone cohort also had a higher risk of having a hospitalization than aripiprazole, but the difference was not statistically significant (p>.05). Among LAI initiators having any inpatient hospitalizations, the adjusted mean all-cause inpatient costs were lowest in the aripiprazole cohort (USD26,002), followed by risperidone (USD27,937), haloperidol (USD30,411), and paliperidone (USD33,240). However, the cost difference was not statistically significant.

CONCLUSIONS:

Our study findings highlight the value of aripiprazole in reducing all-cause inpatient hospitalizations and associated costs among patients with BD during the 1-year follow-up. It is worthwhile to note that bipolar diagnoses were identified from healthcare claims coded for reimbursement purposes, thus misclassification was possible. Future studies are warranted to understand the impact of LAI use in a longer period of time.
PP054 The All Wales Patient Reported Outcome Measures (PROMs), Patient Reported Experience Measures (PREMs) and Effectiveness Program
Authors: Withers Kathleen , Palmer Robert , Carolan-Rees Grace
Published: January 2018

INTRODUCTION:

Prudent health care aims to do the minimum needed to achieve the greatest patient benefit. This aim relies on the availability of evidence on the safety and efficacy of interventions to support decision making. The principles of prudent healthcare support co-production, whereby service users contribute to service provision. Collection of patient reported data is becoming more widespread, however use of this data to inform decision making is limited.

METHODS:

A national patient reported outcome measures (PROMs) program has been formed supported by the Welsh Government, Welsh Health Boards and the NHS Wales Informatics Service. An electronic platform has been developed to facilitate collection of PROMs and patient reported experience measures (PREMs) from patients treated in secondary care. We collected baseline PROMs where possible and invited patients to submit PROMs and PREMs post-treatment. Data collected included EuroQuol five dimensions questionnaire (EQ5D), co-morbidities, body mass index (BMI), smoking history and alcohol intake. Disease specific tools were used where available and responses linked to clinical data. Individual level data will be available during clinic consultations, and collated data analyzed on national and health board levels to assess clinical effectiveness. The platform is currently being piloted in several sites across Wales.

RESULTS:

Initial baseline pilot data from hip replacement patients found that over 55 percent of responders were classed as overweight or obese, with over 80 percent carrying out less than the national guidelines for exercise.

The baseline scores for hip patients were; EQ-5D Index (Mean .29, median .29, range (-.59 -1)), EuroQol-visual analogue scales (EQ-VAS) (Mean 57.8, median 60, range (0:100)), and Oxford Hip Score (Mean 14.9, median 14, range (0:48)).

When compared to baseline scores collected by NHS England in 2015/16 (1), the average EQ5D Index and Oxford Hip Score collected in Wales was lower than that in England (p< .05).

CONCLUSIONS:

The program will provide a large dataset from patients across all of Wales with data on numerous chronic and acute conditions. The data collected will facilitate service improvements and will inform decision making as part of the prudent healthcare agenda.
PP085 A Scoping Review Of Emergency Assessment And Referral Of Suspected Transient Ischemic Attack
Authors: Hampton Chelsey , Evans Bridie , Ali Khalid , Bulger Jenna , Ford Gary , Moore Chris , Porter Alison , Pryce Alan , Quinn Tom , Seagrove Anne , Snooks Helen , Whitman Shirley , Rees Nigel , Jones Matthew
Published: January 2018

INTRODUCTION:

Patients who experience Transient Ischaemic Attack (TIA) should be assessed and treated in a specialist clinic to reduce risk of further TIA or stroke. But referrals are often delayed. We aimed to identify published studies describing pathways for emergency assessment and referral of patients with suspected TIA at first medical contact: primary care; ambulance services; and emergency department.

METHODS:

We conducted a scoping literature review. We searched four databases (PubMed, CINAHL, Web of Science, Scopus). We screened studies for eligibility. We extracted and analysed data to describe setting, assessment and referral processes reported in primary research on referral of suspected TIA patients directly to specialist outpatient services.

RESULTS:

We identified eight studies in nine papers from five countries: 1/9 randomized trial; 6/9 before-and-after designs; 2/9 descriptive account. Five pathways were used by family doctors and three by Emergency Department (ED) physicians. None were used by paramedics. Clinicians identified TIA patients using a checklist incorporating the ABCD2 tool to describe risk of further stroke, online decision support tool or clinical judgement. They referred to a specialist clinic, either directly or via a telephone helpline. Anti-platelet medication was often given, usually aspirin unless contraindicated. Some patients underwent neurological and blood tests before referral and discharge. Five studies reported reduced incident of stroke at 90 days, from 6–10 percent predicted rate to 1.2-2.1 percent actual rate. Between 44 percent and 83 percent of suspected TIA cases in these studies were directly referred to stroke clinics through the pathways.

CONCLUSIONS:

Research literature has focused on assessment and referral by family doctors and ED physicians to reduce hospitalization of TIA patients. No pathways for paramedic use were reported. Since many suspected TIA patients present to ambulance services, effective pre-hospital assessment and referral pathways are needed. We will use review results to develop a paramedic referral pathway to test in a feasibility trial.
PP091 A Follow Up Study On Transcatheter Aortic Valve Implantation (TAVI)
Authors: Kelles Silvana Marcia , dos Santos Augusto Cesar Soares , Azevedo Daniela , Carvalho Lélia Maria de Almeida , Rodrigues Luíza de Oliveira , Fernandes Mariana Ribeiro , Horta Maria da Glória Cruvinel , Avelar Sandra de Oliveira Sapori
Published: January 2018

INTRODUCTION:

Severe aortic stenosis with symptoms or left ventricular dysfunction has commonly a poor prognosis. Aortic valve replacement is usually performed for these patients aiming at improving their functional class and survival rate. Transcatheter aortic valve implantation (TAVI) is often presented as an option in patients with high surgical risk for conventional surgical valve replacement.(1) Nonetheless, in this group of patients, the literature has yielded conflicting evidence suggesting that benefits of TAVI for patients of high or intermediate surgical risk is not consistent.(2,3)

METHODOLOGY:

This retrospective study aimed to evaluate the mortality rate from a cohort of patients after the correction of aortic valve dysfunction with TAVI. It consisted of a convenience sample of patients at high risk for open surgery for the correction of aortic valve dysfunction treated with TAVI from 2013 to 2016. All included patients were being provided healthcare assistance by a private nonprofit health maintenance organization (HMO) operating in Belo Horizonte, Brazil. Since TAVI is not currently covered by the Brazilian supplementary healthcare system, reimbursements were enforced by lawsuits. Data was extracted from an administrative database, using the software Oracle Business Intelligence®. Continuous variables were expressed as mean and standard deviation. The Kaplan-Meier method was used to adjust the 1-year survival curve using the software STATA 13.1 (Stata Corp, College Station, TX, USA). This historical cohort resulted in no interventions, neither during the course of the instituted treatment nor after the observed outcome. Privacy of subjects and the confidentiality of their personal information were handled in accordance to the ethical principles of the Declaration of Helsinki.

RESULTS:

Overall, seventeen patients with a mean age of 80.5 years (68-91) underwent TAVI; 59 percent were women. Peri-operative mortality rate was 23.5 percent (n = 4) and accumulated overall one-year mortality was 35.3 percent (n = 6). Mean length of hospital stay was 26.9 ± 16.6 days. Prolonged hospital stay (≥ 7 days) occurred in 14/17 cases (82.3 percent), with a maximum of 51 days.

CONCLUSIONS:

In similarity to our findings, other authors described a high early and late mortality rate in patients undergoing TAVI. The strategy to use TAVI as an alternative in patients at high risk for open surgery is still under debate and should be carefully discussed taking into consideration the local team expertise as well as local healthcare available recourses.
PP096 European Union-Health Technology Assessments For Medical Devices - How To Overcome Reimbursement Divergence
Authors: Hemmerling Jana , Eberle Karolin , Hogger Sara , Gupta Maike , Ullraum Anna , Seemüller Silke
Published: January 2018

INTRODUCTION:

National Health Technology Assessments (HTAs) for medical devices are crucial to regulate the quality and costs of healthcare systems. However, there is diversity in several aspects among European countries. Consequently, controversial results might arise, generating contrary reimbursement decisions. The European Network for Health Technology Assessment (EUnetHTA) is an interface platform for the harmonization of HTA information across Europe. The European Commission expects national uptake of a European HTA. Thus, European HTAs might overcome the diversity of national HTA requirements.

METHODS:

We aimed to compare German and European HTAs for medical devices regarding processes, methods, timelines, and involvement of medical device companies. Therefore we analyzed guidelines, requirements, and output of EUnetHTA and compared those aspects with the German G-BA (Federal Joint Committee, Gemeinsamer Bundesausschuss) standard and IQWiG (Institute for Quality and Efficiency in Health Care, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen) methods.

RESULTS:

We found differences between the European and German HTAs for medical devices regarding timelines, involvement of medical device companies, body of evidence, use of surrogate endpoints, and methodology. European HTAs for medical devices reflect the clinical reality by integrating the existing evidence (including real world data) and by using comprehensive statistical methods for medical devices. In contrast, German HTAs for medical device-based technologies are long lasting and are often restricted to a small body of evidence.

CONCLUSIONS:

As a conclusion, similar to pharmaceuticals, the European HTA framework might also become a worldwide platform for HTAs of medical device-based technologies with the potential to harmonize reimbursement decisions and patients health care across countries on the basis of clinical reality.