bluuebunny/crossref_metadata_2025 huggingface dataset:
Calcitonin-gene related peptide (CGRP) inhibits interleukin-7-induced pre-B cell colony formation
Authors: Fernandez Stefan , Knopf Melissa A , McGillis Joseph P
Published: January 2018

Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with inflammatory and immunoregulatory activities. Its role in B lymphocyte development was investigated using a pre-B cell colony-forming assay. Physiological concentrations of CGRP inhibited pre-B cell responses to interleukin-7 (IL-7). Inhibition was specific in that it was blocked by the CGRP antagonist CGRP8-37. Adrenomedulin, substance P, and calcitonin had no effect on B cell precursor responses. Similar responses were observed with B220+/IgM− B cell precursors. Inhibition of IL-7 responses in B220+/IgM− cells suggests that CGRP has a direct effect on B cell precursors. Studies with cultured bone marrow-adherent cells found that CGRP also has an indirect effect on IL-7 responses. Cultured bone marrow-adherent cells were treated with CGRP for 24 h, and anti-CGRP was added to the supernatants to neutralize CGRP. Concentrations of CGRP as low as 0.01 nM induced a factor that inhibited colony formation. In contrast, CGRP did not induce an inhibitory factor in cultured bone marrow macrophages, suggesting that CGRP induces an inhibitory factor in some adherent cell other than macrophages. The results show that CGRP has both direct and indirect effects on developing B cells and support a role for CGRP as an inhibitor of early B cell development. J. Leukoc. Biol. 67: 669–676; 2000.
Abnormal down-regulation of PKC is responsible for giant granule formation in fibroblasts from CHS (beige) mice—a thiol proteinase inhibitor, E-64-d, prevents giant granule formation in beige fibroblasts
Authors: Tanabe Fuminori , Cui Shao-Hui , Ito Masahiko
Published: January 2018

We have previously reported that the abnormally rapid down-regulation of protein kinase C (PKC) activity is responsible for the cellular dysfunction in natural killer (NK) cells and polymorphonuclear leukocytes (PMNs) from Chediak-Higashi syndrome (beige) mice. In this report, we examined whether the down-regulation of PKC is associated with giant granule formation in fibroblasts from beige mice. In cultured beige fibroblasts, the membrane-bound PKC activity declined significantly after phorbol ester stimulation. We found that E-64-d, which is a thiol proteinase inhibitor and protects PKC from calpain-mediated proteolysis, reversed the declined PKC activity and prevented giant granule formation in beige fibroblasts. Moreover, E-64-d corrected the reduced lysosomal elastase and cathepsin G activity in beige fibroblasts. In contrast, specific PKC inhibitors, chelerythrin and calphostin C, promoted giant granule formation in normal fibroblasts. We also demonstrate that ceramide production is enhanced in beige fibroblasts and is involved in the rapid down-regulation of PKC. These results suggest that the accelerated breakdown of PKC observed in beige fibroblasts is caused by enhanced ceramide production and is also responsible for giant granule formation. J. Leukoc. Biol. 67: 749–755; 2000.
Inhibition of TNF-α processing and TACE-mediated ectodomain shedding by ethanol
Authors: Zhang Zili , Cork John , Ye Peng , Lei Dinghua , Schwarzenberger Paul O , Summer Warren R , Shellito Judd E , Nelson Steve , Kolls Jay K
Published: January 2018

Alcohol (EtOH) is a well-documented immunosuppressant. Acute EtOH-induced immunosuppression is partially due to suppression of tumor necrosis factor α (TNF-α) secretion. We investigated the mechanism of acute EtOH-induced TNF-α suppression in two monocytic cell lines, Mono Mac 6 and DRM. EtOH inhibited TNF-α secretion in a dose-dependent manner. However, TNF-α transcription was not affected by EtOH. Enzyme-linked immunosorbent assay and confocal microscopy showed that EtOH treatment increased cell-associated TNF-α. Ectodomain shedding of TNF-α from the cell surface is mediated by TNF-α converting enzyme (TACE). In contrast with TNF-α, EtOH did not inhibit interleukin-8 (IL-8) secretion, which does not require shedding. Furthermore, TNF p75 receptor shedding, a biomarker for TACE activity, was inhibited by EtOH in both cell lines. EtOH also inhibited TNF p75 receptor shedding in TACE-reconstituted fibroblasts, suggesting that EtOH inhibits the shedding process. These data show that acute EtOH exposure can posttranscriptionally suppress TNF-α production, resulting in specific defects in immune defense. J. Leukoc. Biol. 67: 856–862; 2000.
Serum-induced monocyte differentiation and monocyte chemotaxis are regulated by the p38 MAP kinase signal transduction pathway
Authors: Ayala Julia M , Goyal Shefali , Liverton Nigel J , Claremon Dave A , O'Keefe Stephen J , Hanlon William A
Published: January 2018

Regulation by the p38 mitogen-activated protein (MAP) kinase signaling pathway of monocytic inflammatory functions was evaluated using L-790,070, a potent and selective inhibitor of p38 MAP kinase. Three major functions of monocytes were investigated: differentiation, chemotaxis, and phagocytosis. L-790,070 inhibited serum-induced monocyte differentiation with an IC50 of 0.5 nM. Monocyte chemotaxis induced by RANTES, macrophage inflammatory protein-1α (MIP-1α), monocyte chemotactic protein-1 (MCP-1), and fMLP were all sensitive to L-790,070. When titrated, L-790,070 inhibited MCP-1-induced chemotaxis in a concentration-dependent manner with an IC50 of 0.3 nM. However, the ability of serum-derived macrophages to phagocytose apoptotic neutrophils was unaffected by L-790,070. The concentration with which L-790,070 inhibited both differentiation and chemotaxis was similar to that necessary to inhibit p38 MAP kinase activation of MAPKAP kinase (0.3 nM) in response to stimulation by lipopolysaccharide. Therefore, the data in this report suggest that the mechanism by which L-790,070 blocked monocyte differentiation and prevented chemotaxis was by inhibiting p38 MAP kinase activity. J. Leukoc. Biol. 67: 869–875; 2000.
High‐Throughput Production With Improved Functionality and Graphitization of Carbon Fine Fibers Developed from Sodium Chloride‐Polyacrylonitrile Precursors
Authors: Akia Mandana , Cremar Lee , Seas Manuel , Villarreal Jahaziel , Valdez Alejandra , Alcoutlabi Mataz , Lozano Karen
Published: January 2018

Fine polyacrylonitrile (PAN) fibers were produced through a scalable centrifugal spinning process. Sodium chloride (NaCl) was added to the PAN‐dimethylformamide solution to decrease the surface tension and consequently promote a decrease in fiber diameter while increasing the fiber output. The fiber preparation process involved the centrifugal spinning of the PAN‐based solution; developed fibers were stabilized in air at 240°C followed by carbonization at 800°C under a Nitrogen atmosphere. The addition of sodium chloride to the PAN solution led to a 37% decrease in the carbon fiber diameter. The carbon fibers were analyzed by scanning electron microcopy, transmission electron microscopy (TEM), X‐ray diffraction, X‐ray photoelectron spectroscopy (XPS) and electrochemical experiments. The TEM results revealed improved graphitization with the addition of sodium chloride. The XPS analysis showed increased functionality (e.g. O2) on the surface of carbon fibers obtained from PAN/NaCl precursor fibers. A significant improvement was achieved in the electrochemical performance of carbon fibers made from PAN/NaCl precursor fibers compared to those made from pure PAN precursor fibers. POLYM. ENG. SCI., 58:2047–2054, 2018. © 2018 Society of Plastics Engineers
iTRAQ‐Based Proteomic Analysis Exploring the Influence of Hypoxia on the Proteome of Dental Pulp Stem Cells under 3D Culture
Authors: Dou Lei , Yan Qifang , Liang Panpan , Zhou Pengfei , Zhang Yan , Ji Ping
Published: January 2018

Hypoxic preconditioning is commonly applied to enhance mesenchymal stem cells (MSCs) therapeutic effect before transplantation. Elucidating the effect of hypoxic preconditioning would be beneficial for improved application. However, the influence of hypoxia on dental tissue derived MSCs cultured in 3D was unknown. Thus, the present study is to investigate gene expression and proteome of dental pulp stem cells (DPSCs) after hypoxic preconditioning. DPSCs were isolated, cultured in a 3D system under the normoxic and hypoxic conditions. The gene expression was examined with reverse transcription polymerase chain reaction, and the proteome was analyzed using iTRAQ‐based mass spectrometry. The expressions of HIF‐1α, VEGFA, KDR at mRNA level was upregulated while BMP‐2 was downregulated. Two thousand one hundred and fifteen proteins were identified and 57 proteins exhibited significant differences after hypoxic preconditioning (30 up‐regulated, 27 down‐regulated). Bioinformatic analysis revealed the majority of up‐regulated proteins are involved in cellular process, angiogenesis, protein binding and transport, regulation of response to stimulus, metabolic processes, and immune response. Increased IL‐6 and decreased TGF‐1β protein expression under hypoxic condition were verified by ELISA. Hypoxic preconditioning partly affected the gene and protein expression in DPSCs under 3D culture and may enhance the efficacy of MSCs transplantation.
Reductive Alkaline Release of N‐Glycans Generates a Variety of Unexpected, Useful Products
Authors: Figl Rudolf , Altmann Friedrich
Published: January 2018

Release of O‐glycans by reductive β‐elimination has become routine in many glyco‐analytical laboratories and concomitant release of N‐glycans has repeatedly been observed. Revisiting this somewhat forgotten mode of N‐glycan release revealed that all kinds of N‐glycans including oligomannosidic and complex‐type N‐glycans from plants with 3‐linked fucose and from mammals with or without 6‐linked fucose and with sialic acid could be recovered. However, the mass spectra of the obtained products revealed very surprising facts. Even after 16 h incubation in 1 M sodium borohydride, a large part of the glycans occurred in reducing form. Moreover, about one third emerged in the form of the stable amino‐functionalized 1‐amino‐1‐deoxy‐glycitol. When avoiding acidic conditions, considerable amounts of glycosylamine were observed. In addition, a compound with a reduced asparagine and de‐N‐acetylation products, in particular of sialylated glycans, was seen. The relative yields of the products reducing glycosylamine, reducing N‐glycan, 1‐amino‐1‐deoxy‐glycitol or glycitol could be controlled by the release conditions, foremost by temperature and borohydride concentration. Thus, chemical release of N‐glycans constitutes a cost‐saving alternative to enzymatic hydrolysis for the preparation of precursors for the production of reference compounds for various formats of N‐glycan analysis. Moreover, it allows to obtain a stable amino‐functionalized glycan derivative, which can be employed to construct glycan arrays or affinity matrices.
Nebulized hypertonic saline in infants hospitalized with moderately severe bronchiolitis due to RSV infection: A multicenter randomized controlled trial
Authors: Morikawa Yoshihiko , Miura Masaru , Furuhata Megumi Y. , Morino Saeko , Omori Tae , Otsuka Masahiro , Chiga Michiko , Obonai Toshimasa , Hataya Hiroshi , Kaneko Tetsuji , Ishikura Kenji , Honda Masataka , Hasegawa Yukihiro ,   on behalf of the Tokyo Pediatric Clinical Research Network
Published: January 2018

Introduction

The efficacy of nebulized hypertonic saline (HS) therapy for shortening hospital length of stay (LOS) or improving bronchiolitic symptoms remains controversial. Most studies enrolled small numbers of subjects and did not consider the role of respiratory syncytial virus (RSV), the most common cause of acute bronchiolitis. Our aim was to evaluate the efficacy and safety of nebulized HS therapy for acute bronchiolitis due to RSV in moderately ill hospitalized infants.

Materials and Methods

This was an open‐label, multicenter, randomized controlled trial comparing a nebulized HS treatment group with a normal saline (NS) group. The subjects, 128 infants with bronchiolitis due to RSV, were admitted to five hospitals in Tokyo, Japan. Three‐percent HS or NS was administered via bronchodilator four times daily post‐admission. The primary outcome was LOS, defined as the time until the patients fulfilled the discharge criteria, namely, absence of fever, no need for supplemental oxygen, and adequate feeding. Survival analysis was conducted in accordance with the intention‐to‐treat principle.

Results

The baseline characteristics were similar between the two groups. There was no significant overall difference in LOS between the groups (4.81 ± 2.14 days in HS vs 4.61 ± 2.18 days in NS; P = 0.60). Survival analysis by log‐rank test also showed no significance (P = 0.62). Multivariate adjustment did not significantly alter the results. The treatment was well‐tolerated, with no adverse effects attributable to the use of HS.

Conclusions

Nebulized HS therapy did not significantly reduce LOS among infants with bronchiolitis due to RSV.
A new reliability analysis method for repairable systems with closed‐loop feedback links
Authors: Yi Xiao‐Jian , Shi Jian , Dhillon B.S. , Hou Peng , Dong Hai‐Ping
Published: January 2018

A new reliability analysis method for repairable systems with closed‐loop feedback link (CLFL) is proposed based on GO methodology. A method for creating new function GO operators is used to describe the CLFL. Next, methods for deducing the formulae of the new GO function are proposed. In addition, a 2‐level GO model is proposed for the GO operation of repairable systems with CLFL. And then, quantitative and qualitative analysis methods for repairable systems with CLFL based on the GO method are proposed, and a process for analyzing repairable systems with CLFL based on the new GO method is formulated. Finally, we used this new GO method to analyze the reliability of an electro‐hydraulic servo speed control system and a power‐shift steering transmission control system for a heavy vehicle. To verify the feasibility, advantages, and reasonability of the new GO method, we compared our results with those obtained by fault tree analysis, Monte Carlo Simulation, and an existing GO method using serial and parallel structures to represent the CLFL. All in all, the proposed method overcomes the limitations of the existing methods as well as increasing its applicability. And it provides a new approach for reliability analysis of repairable systems with CLFL.
Student Experiences in the Second Year: Advancing Strategies for Success Beyond the First Year of College
Authors: Sterling Althea J.
Published: January 2018

Institutions typically invest heavily in the first‐year experience to promote persistence, yet colleges are also experiencing a pattern of attrition in the second year. The second year is viewed as a period in which students encounter increasing academic, developmental, and social demands, yet the institution tends to provide less support relative to the first year. Using the interpretative phenomenological approach, this article explores sophomores’ perception and understanding of their experience and the intentional approaches institutions can adopt in promoting their success. Semistructured interviews were conducted to analyze students’ experiences in the second year. The findings suggest that sophomores are in the process of establishing their identity, re‐evaluating their purpose and collegiate experience; consequently the need for a different kind of support is apparent. Second‐year students are experiencing an internal transition and are still in need of year‐specific support to successfully meet the demands of progressing through college.
Nanocrystal–Polymer Particles: Extended Delivery Carriers for Osteoarthritis Treatment
Authors: Maudens Pierre , Seemayer Christian Alexander , Thauvin Cédric , Gabay Cem , Jordan Olivier , Allémann Eric
Published: January 2018

An efficient treatment for osteoarthritis (OA) can benefit from the local release of a high therapeutic dose over an extended period of time. Such a treatment will minimize systemic side effects and avoid the inconvenience of frequent injections. To this aim, nanocrystal–polymer particles (NPPs) are developed by combining the advantages of nanotechnology and microparticles. Nanocrystals are produced by wet milling kartogenin (KGN), which is known to promote chondrogenesis and to foster chondroprotection. A fluorescent biodegradable polymer is synthesized for intravital particle tracking. Polymer microparticles with 320 nm embedded KGN nanocrystals (KGN‐NPPs) show a high drug loading of 31.5% (w/w) and an extended drug release of 62% over 3 months. In vitro, these particles do not alter mitochondrial activity in cultured human OA synoviocytes. In vivo, KGN‐NPPs demonstrate higher bioactivity than a KGN solution in a murine mechanistic OA model based on histological assessment (Osteoarthritis Research Society International score), epiphyseal thickness (microcomputed tomography), OA biomarkers (e.g., vascular endothelial growth factor, Adamts5), and prolonged intra‐articular persistence (fluorescence analysis). This work provides proof‐of‐concept of a novel and innovative extended drug delivery system with the potential to treat human OA.
Experimental study of benzene, toluene, ethylbenzene, and xylene (BTEX) contributions in the air pollution of Tehran, Iran
Authors: Asadi M , Mirmohammadi M
Published: January 2018

Urbanization and development are associated with air pollution, including emissions of volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene, and xylene (BTEX). For this study, we measured and investigated the outdoor concentrations of BTEX in Tehran, Iran. National Institute for Occupational Safety and Health (NIOSH, 1996) methods were applied to measure the concentrations of BTEX in winter and spring of 2015 at 46 air monitoring stations. BETX concentrations were also measured at 19 monitoring stations in June and July of 2003. In 2003, BTEX compound pollutants were observed at greater concentration in the eastern, central, and southern zones of Tehran than in other zones. The average concentrations of the BTEX compounds were 238 parts per billion (ppb), 130 ppb, 69 ppb, and 118 ppb, respectively, for benzene, toluene, ethylbenzene, and xylene. The benzene to toluene (B/T) ratios ranged from 0.8 to 3.2, which indicated that the gasoline used in the city was of poor quality at that time. In 2015, the BTEX concentrations in District 19 (south of Tehran) were higher than in the eastern and central regions, which included restricted “traffic zones” and the extensive development of public transportation systems. In the restricted traffic zones, only public vehicles, such as buses, taxis, ambulances, etc., and other authorized vehicles are allowed to operate. By ameliorating the quality of gasoline, encouraging the use of late model private cars, and development of subway and public transportation during the years between 2003 and 2015, the BTEX concentrations have fallen to levels that comply with Iran's air quality standards. The 2015 measurements revealed that the average concentrations of the BTEX compounds were 5.3, 9.2, 1.5, and 2.6 ppb, respectively. The B/T ratio fluctuated from 0.39 to 0.76, demonstrating the remarkable role that vehicle traffic plays in BTEX pollution.
Minimizing disruptions caused by damming and ensuring the health of downstream ecosystems
Authors: Mata‐Lima Herlander , Alvino‐Borba A. , Vasquez Ivan Y. Salazar , da Silva Jakelline Jard , Incau Bruno Hernandez , Almeida José A.
Published: January 2018

In view of the Brazilian Ten‐Year Energy Expansion Plan 2021, this article presents a discussion on environmental flow (e‐flow). The authors analyze the literature to show the evolution of publications concerning e‐flow releases from the perspective of ecosystems services preservation considering results from different case studies from throughout the world. Finally, two main recommendations are drawn regarding e‐flow are: (1) performing a holistic approach to e‐flow planning, including hydrological, hydraulic, water quality, habitat, and riparian zone considerations; and (2) installing in new structures adequate bottom outlets to allow a range of adjustable e‐flow from reservoir dams to reproduce natural flow variations.
An historical overview and update of wolf–moose interactions in northeastern Minnesota
Authors: Mech L. David , Fieberg John , Barber‐Meyer Shannon
Published: January 2018

Wolf (Canis lupus) and moose (Alces americanus) populations in northeastern Minnesota, USA, have fluctuated for decades and, based on helicopter counts, moose numbers declined to a new low from 2006 to about 2012. Other steep declines were found in 1991 and 1998 during periods when moose counts were done with fixed‐wing aircraft; these declines also appeared to be real. Winter wolf numbers, monitored in part of the moose range, had been increasing since about 2002 to the highest population in decades in 2009. However, from 2009 to 2016, wolves decreased precipitously, and the moose‐population decline leveled off from 2012 to 2017. Calf:population ratios from 1985 to 1997 and from 2005 to 2016 were inversely related to wolf numbers in the wolf‐study area the previous winter both as wolves increased and decreased in abundance. Similarly, log annual growth rates of moose numbers were negatively correlated with counts of wolves in the prior year. Other factors such as nutrition and parasites, and possibly climate change, likely have been involved in the recent moose decline. However, wolves, as in other areas, appear to have contributed to the decline in the northeastern Minnesota moose population at least in part through predation on calves, supporting earlier reports. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.
Dynamics of a liquid plug in a capillary tube under cyclic forcing: memory effects and airway reopening
Authors: Signe Mamba S. , Magniez J. C. , Zoueshtiagh F. , Baudoin M.
Published: January 2018

In this paper, we investigate both experimentally and theoretically the dynamics of a liquid plug driven by a cyclic periodic forcing inside a cylindrical rigid capillary tube. First, it is shown that, depending on the type of forcing (flow rate or pressure cycle), the dynamics of the liquid plug can either be stable and periodic, or conversely accelerative and eventually leading to plug rupture. In the latter case, we identify the sources of the instability as: (i) the cyclic diminution of the plug viscous resistance to motion due to the decrease in the plug length and (ii) a cyclic reduction of the plug interfacial resistance due to a lubrication effect. Since the flow is quasi-static and the forcing periodic, this cyclic evolution of the resistances relies on the existence of flow memories stored in the length of the plug and the thickness of the trailing film. Second, we show that, contrary to unidirectional pressure forcing, cyclic forcing enables breaking of large plugs in a confined space although it requires longer times. All the experimentally observed tendencies are quantitatively recovered from an analytical model. This study not only reveals the underlying physics but also opens up the prospect for the simulation of ‘breathing’ of liquid plugs in complex geometries and the determination of optimal cycles for obstructed airways reopening.
OP16 A Patient-centered Value Framework For Healthcare In Hemophilia
Authors: O'Mahony Brian , Dolan Gerard , Nugent Diane , Goodman Clifford
Published: January 2018

INTRODUCTION:

Hemophilia is a rare, inherited bleeding disorder affecting an estimated 400,000 people worldwide (1). Characterized by spontaneous bleeding and long-term, irreversible joint damage, persons with hemophilia are often limited in normal day-to-day activities, including work/school, and require comprehensive care at specialized treatment centers. With replacement therapies extending survival by decades and vastly improving quality of life (QoL), routine prophylaxis is considered the standard-of-care in developed countries. However, due to the cost of replacement factor, access to treatment remains a challenge, and increased scrutiny over funding has been augmented by growing demands on healthcare budgets (2). Thus, the hemophilia community shares a unified goal of objectively defining patient-centered value in hemophilia care.

METHODS:

Using a three-tiered outcomes hierarchy model initially described by Porter (3), an international, multidisciplinary panel of health economics outcomes researchers and hemophilia experts developed a value framework for decision makers to assess value of various healthcare interventions in hemophilia.

RESULTS:

The three tiers for assessing value are: (i) Health status achieved/retained; (ii) Process of recovery; and (iii) Sustainability of health. Tier one measures survival, quality of life (QoL), and hemophilia-specific outcomes of bleeding frequency, musculoskeletal complications, and severe bleeds, as well as function/activity (that is, lifestyle impairment). Tier two measures time to initial treatment or recovery and time missed at education/work, as well as disutility of care (that is, inhibitor development, pathogen transmission/infections, orthopedic intervention, and venous access). Tier three measures avoidance of bleeds, maintenance of productive lives, and long-term health, while capturing long-term consequences of insufficient therapy or age-related complications. Applicability of the framework can be demonstrated in areas of healthcare delivery, treatment regimen, and innovation for new therapies.

CONCLUSIONS:

This value framework represents an initial collaboration with stakeholders to define and organize an array of patient-centric outcomes of importance in hemophilia into a practical tool that can influence treatment and funding decisions in hemophilia care.
OP120 Recommendations From The Newly Developed French National Authority For Health (HAS) Guide On Budget Impact
Authors: Ghabri Salah , Pouillé Anne Isabelle , Autin Erwan , Rumeau-Pichon Catherine , Scemama Olivier , Josselin Jean Michel
Published: January 2018

INTRODUCTION:

Budget impact analysis (BIA) provides short and medium-term estimated effect of new health interventions on budgets and resources. Since January 2016, BIA is required as part of economic dossiers submitted to the French National Authority for Health (HAS) by manufacturers for innovative drugs with an expected 2-year sales revenue above EUR50 million. To this end and in order to promote good practices for conducting BIA, HAS developed a guide for BIA.

Our objectives are:

–

to present the guide development method and the resulting recommendations;

–

to compare the HAS BIA guide with existing BIA guides.

METHODS:

The HAS guide development process rests on findings derived from a systematic literature review on BIA methodology, an HAS retrospective investigation of BIA, public consultation, international expert advice, and approval from the HAS Board and Committee of Health Economic and Public Evaluation (CEESP). Relevant publications were identified through Pubmed and EMBASE and the grey literature (search dates: January 2000 to June 2016).

RESULTS:

The search strategy captured 144 publications of which 31 were retained (14 methodological papers, 12 national guides and 5 learned society recommendations). On the basis of this result, an extraction template was designed to synthesize the methodological aspects of BIA. Based on its research findings, HAS developed its first BIA guide which includes recommendations on the following main topics: BIA definition, perspective, populations, time horizon, compared scenarios, BIA models, costing, discounting, choice of clinical data, reporting of BIA and uncertainty exploration.

Compared to existing BIA guides from other Health Technology Assessment (HTA) agencies, the HAS guide specifically described issues relating to off-label use of drugs, disease-related costs and scenario analysis.

CONCLUSIONS:

It is expected that the HAS BIA guide will improve the quality, transparency and standardization of BIA in France. It should also enhance the usefulness of BIA as an essential part of a comprehensive economic assessment of health care interventions.
PP064 Registration Of Healthcare Mobile Apps In Brazil
Authors: Bezerra Benefran , Alves Eduardo
Published: January 2018

INTRODUCTION:

The use of applications (app) on mobile phones to health care is a trend. Its applications range from the use as energy calculators, monitoring clinical parameters, as well association with medical devices, personal health records or used to request appointments (1). Thus, it is intended to evaluate the regulatory instruments available in Brazil as to their sufficiency to analyze this new technology.

METHODS:

Assessment of regulatory instruments for mobile app registration by the Brazillian Health Regulatory Agency (Anvisa) (2). The main variables in the form of Class I and II are: Submission type, Postal Code, Electronic Site, Product code, Classification Rule, Class, Indication of Use / Purpose, Principle of Operation, Platform, Target Audience, Type of Environment, Compatibility, Safety Characteristics, Technical Standards used, Product Origin.

RESULTS:

Since 2010, the registration of software in Anvisa has been observed. The evaluation of Class I and II software is performed through the registration analysis to be completed by the requesting company. Class III (high risk) software is registered as a medical device embedded software (2).

Anvisa's analysis of the software still depends directly on the application for registration of the companies. In this way most of the analyzed software are for use by health professionals and health services.

CONCLUSIONS:

There are Brazilian regulations for health products with software registration forecast, however its use as a health service still lacks studies mainly with the trends of new information and communication technologies (3).

The regulation of mobile applications becomes difficult because applications are freely downloaded in virtual stores, their domains are usually in foreign territory and their use is given directly by the user.
PP103 Characteristics Of Systems Applied To Language Rehabilitation
Authors: Núñez José , Rivas Ronald , Galvan Pedro , Grossling Benicio
Published: January 2018

INTRODUCTION:

In Paraguay the main cause of Traumatic Brain Injury are the accidents in ground transportation. According to data from the Basic Health Indicators 2013 of the Ministry of Public Health and Social Welfare, the regions with the highest rate of accidents in ground transportation are located in the rural zone of the country. Linguistic or communication disorder, attention and memory are the first functions that must be rehabilitated. Is essential to improve the patient's language skills to intervene the other cognitive functions. The objective of this study is to determine if free augmentative communication systems have the characteristics necessary for the cognitive rehabilitation of the language to provide a low cost solution for Traumatic Brain Injury patients in rural areas of the country.

METHODS:

A list of seven characteristics that contributed to verbal comprehension and expression, reading and writing, logical-verbal reasoning and numeration and calculation were compiled and compared to the Gazespeaker, which is a free augmentative communication system.

RESULTS:

The Gazespeaker meets the seven characteristics required for language rehabilitation.

CONCLUSIONS:

For patients with Traumatic Brain Injury are required low cost tools and ease-to-use like the Gazespeaker. It is a good augmentative communication system which satisfies all the characteristics required for a good language rehabilitation. In addition, this free software allows the use of an eye tracking device that can be applied to patients with Traumatic Brain Injury and severe motor deficit.
VP21 Telemedicine As A Tool For Public Health Planning
Authors: Galvan Pedro , Velazquez Miguel , Rivas Ronald , Benitez Gualberto , Barrios Antonio , Hilario Enrique
Published: January 2018

INTRODUCTION:

The telediagnostic systems can achieve relevant epidemiological information from local community needs to global countrywide opportunities. In this context the telemedicine applications should be directed to gain the prevalence of pathologies towards developing better equity in the provision of services (1), and greater concern for the effectiveness and usefulness of health technologies in remote locations without access to specialists (2). This study, has evaluated the results of a telemedicine system in remote public regional and district hospitals in Paraguay (3), in order to show the epidemiological trends in communities of a low income country.

METHODS:

This prospective study used the results of telemedicine for diagnosis in remote regional and district hospitals to evaluate a as tool to determine the prevalence of pathologies countrywide over three years (2014-16). For these purposes, type and frequency of pathology diagnosed was determined. Sampling was non-probabilistic of convenience.

RESULTS:

A total of 182,406 telediagnoses were performed in 54 hospitals. The electrocardiography (ECG) diagnosis performed in the 52 hospitals were normal (62.1 percent), unspecified arrhythmias (12.5 percent), sinus bradycardia (10.4 percent), left ventricular hypertrophy (4.1 percent), sinus tachycardia (4.4 percent), right bundle branch block (3.5 percent), ischemia (1.4 percent), atrial fibrillation (1.0 percent) and left bundle branch block (0.6 percent). Teletomography was performed in twelve hospitals, where 54.4 percent corresponded to skull as a consequence of accidents (motorcycles) and cerebrovascular diseases, 13.8 percent chest, 6.2 percent dorsal spine, 5.4 percent abdominal and the rest the other anatomical regions. Regarding electroencephalography (EEG), antecedents of seizure (54.3 percent), evolutionary control (14.0 percent), headache (11.5 percent), cognitive impairment (2.0 percent), attention deficit in children (learning) (2.0 percent), brain death (1.0 percent), abnormal movements (0.8 percent), and sleep disturbances (0.3 percent) were diagnosed. The nineteen ultrasound studies corresponded to prenatal controls.

CONCLUSIONS:

Despite the results of the telediagnosis implemented in the public health system to determine the prevalence of pathologies countrywide, a widespread use-assessment should be analyzed before deciding a large diffusion as a tool for public health planning.
VP47 Health Technology Assessment Of Intensive Care Ventilators For Pediatric Patients
Authors: Faggiano Francesco , Andellini Martina , Nocchi Federico , Capussotto Carlo , Sabusco Francesca , Derrico Pietro , Ritrovato Matteo
Published: January 2018

INTRODUCTION:

The purpose of the study was to evaluate different type and manufacturers of intensive care ventilators in order to support the healthcare decision-making process about the choice to adopt the best available technology for ventilation of pediatric patient in intensive care units at Bambino Gesù Children's Hospital.

METHODS:

The technology assessment process was developed by using a new methodology, the Decision-oriented Health Technology Assessment (HTA) (DoHTA), a new implementation of the European Network for Health Technology Assessment (EUnetHTA) CoreModel, integrating the Analytic Hierarchy Process (1). A literature review was carried out to gather evidence on safety and overall effectiveness of different kind of intensive care ventilators, with several ventilation modalities and strategies. The synthesis of scientific evidence, and results of the specific context analysis resulted in the definition of components of the decisional hierarchy structure, consisting in detailed characteristics of the technology's performances covering the aspects on feasibility, safety, efficacy, costs, and organizational and technical characteristics of the technology. A subgroup of these indicators has been included in a checklist form for the evaluation of different type and manufacturers of intensive care ventilators, each of which was tested in three independent runs performed in three different departments. In addition, an economic evaluation was also carried out.

RESULTS:

Preliminary DoHTA results showed that the domains with the highest impacts within the evaluation are safety and clinical effectiveness (34.8 percent and 25.7 percent, respectively) followed by organizational aspects, technical characteristics of technology and costs and economic evaluation. The final objective is to define the alternatives’ ranking through a comparison between alternative technologies’ performances.

CONCLUSIONS:

The technology assessment project allowed to identify strengths and limits of the most recent intensive care ventilator’ models in the specific contexts of use by involving all health professionals interested, and eventually identify the best option for the hospital.
VP57 Test-Retest Reliability Analysis Of The Patient Reported Outcomes Burdens And Experiences (PROBE) Study Questionnaire Test-Retest Reliability Analysis Of The PROBE Study Questionnaire
Authors: Skinner Mark , Chai-Adisaksopha Chatree , Curtis Randall , Frick Neil , Matino Davide , Nichol Michael , Noone Declan , O'Mahony Brian , Page David , Stonebraker Jeff , Iorio Alfonso
Published: January 2018

INTRODUCTION:

The Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire was developed with direct patient involvement in questionnaire design, conduct and analysis using patient-centered outcomes to assess health status in patients with hemophilia (PWH). Phase 1 confirmed robustness of the methodology and feasibility. Phase 2a investigated individual test-retest reliability. Phase 2b will explore population level reproducibility.

METHODS:

PWH and non-PWH individuals who attended a hemophilia-related workshop were asked to complete the PROBE questionnaire 3 times (paper-based survey on 2 consecutive days and then a web-based version). Test-retest reliability was analyzed using the percentage agreement and Kappa statistic. Kappa coefficient interpretation .81-1.00 almost perfect, .61- .80 substantial; .41- .60 moderate; .21 -.40 fair; .00 -.20, slight; and < .00 poor agreement.

RESULTS:

Sixty-three participants from twenty-one countries were enrolled with a median age of 50 (range 14–76) years. Of these, thirty (47.6 percent) were PWH or carriers, thirty-three (52.5 percent) were participants with no known bleeding disorders. On general health domain, Kappa coefficients ranged from .69 to .92, indicating substantial to almost perfect agreement, for all items. Reliability of the web-based questionnaire showed moderate to substantial agreement for all except one item. For the hemophilia-related domain, Kappa coefficients ranged from .5-1.0. Of these, five of eleven items were in perfect agreement (Kappa = 1.0). Reliability of web-based questionnaire items were in substantial to almost perfect agreement. For overall health related quality of life, the EuroQol five dimensions questionnaire (EQ-5D) had Kappa coefficients of .62 to .92. Intraclass correlation coefficient of visual analog scale (VAS) was .90 (95 percent Confidence Interval, CI; .83-.94). Test-retest reliability was comparable between hemophilia patients and participants with no known bleed.

CONCLUSIONS:

Phase 2a demonstrated individual test-retest reliability and suggests PROBE is a reliable tool to assess Patient Reported Outcomes in PWH. The Web-based questionnaire has an acceptable agreement with the standard paper-based version in all domains. PROBE Phase 2b, to demonstrate reproducibility at the population level, is on-going. To date, 1,039 participants have been recruited from 10 countries.
VP81 Health Technology Assessment And Rare Disease Decision Making: Focus On Orphan Drugs
Authors: Raycheva Ralitsa , Stefanov Rumen
Published: January 2018

INTRODUCTION:

Health Technology Assessment (HTA) is applied to determine the value of innovative technologies. It usually relies on robust assessment of the clinical cost-effectiveness of the technology, while clinical and economic evidence required for this purpose are often not available for orphan drugs (OD) (1,2). The objective of the study is to undertake a systematic comparison between HTA agencies worldwide in order to identify similarities and differences in the methods and processes in HTA of OD.

METHODS:

A cross-sectional web-based survey was conducted between September 2013 and May 2015. The data were obtained from a semi-structured questionnaire. We received responces from 161 HTA organizations based in 39 countries.

RESULTS:

HTA of OD is performed by agencies in South America (38.5 percent), followed by agencies in Australia (37.5 percent) and Europe (36.1 percent). The agencies in high income countries produce more assessments of OD (36.8 percent), which in 31.2 percent they determine as innovative technologies compared with 11.8 percent of the units based in low income countries and active in OD assessment (11.1 percent). We prove association (p< .05) between (i) the type of HTA and income per capita; the level at which the organization operates; its main activity; and the level of recommendation dissemination; (ii) the main target group and consumers of the final HTA product; the stage of evolution of the technology, on which it is likely to be assessed; and approaches to identify innovative technologies. The most active in the preparation of HTA reports are biomedical companies or other organizations in the private sector (50.0 percent) and organizations in the pharmaceutical and/or medical industry (66.7 percent). HTA bodies that assess OD develop (36.0 percent) and distribute recommendations (35.9 percent) nationally; their main activity is to produce guidelines for good clinical practice (46.9 percent). Agencies that perform OD assessment are active in evaluation of innovative (37.2 percent) and emerging (35.9 percent) technologies, which are able to be identified by developing early warning systems (32.0 percent).

CONCLUSIONS:

Making coverage decisions based on HTA recommendations control the technologies introduction into the healthcare system, that is why it's very important that this tool is properly adjusted to the specific needs of OD assessment (3).
VP194 Health Technology Assessment Applied To Nurse Retention And Development: A Sickle Cell Example
Authors: Lavenberg Julia , Mitchell Matthew , Williams Kendal , Umscheid Craig
Published: January 2018

INTRODUCTION:

Health Technology Assessment (HTA) methods are usually applied to the evaluation of drugs, devices, and procedures. We have used HTA to promote evidence-based decision-making on topics relating to staffing and career development for healthcare professionals. Interventions to reduce the stress associated with caring for patients who need repeated hospitalization such as patients with sickle cell disease are thought to improve job satisfaction and nurse retention, but is there scientific evidence to support them?

METHODS:

We systematically searched Medline, CINAHL, PsycINFO, Cochrane, and Joanna Briggs Institute databases for published studies evaluating interventions targeting healthcare personnel. Searches combined tems for sickle cell disease with terms for job stress, turnover, and other career-related outcomes. We evaluated the quality of individual studies using standardized checklists and constructed evidence tables.

RESULTS:

We found one randomized trial (RCT) of an education program for nurses and physicians, a pre-post analysis of a communication skills and cultural awareness program, and a case study of a nurse support group. The RCT found that an education program significantly improved participants attitude towards patients but did not measure any outcomes relating to caregiver stress or job satisfaction. The pre-post study found that a communication skills program significantly improved nurses confidence in their ability to communicate with patients. The case study reported that nurses found the support group useful and felt their attitudes were improved, but there was no control group to compare their responses to. The education program was graded as moderate-strength evidence and the other programs had low-strength evidence. There was no meta-analysis or other data synthesis of the results because of the differing interventions and outcome measures.

CONCLUSIONS:

There have been few quantitative scientific evaluations of the effectiveness of interventions to reduce the stress nurses feel when caring for sickle cell disease patient. The studies that have been published have favorable conclusions towards these interventions, but the strength of evidence is not high.
Management of cancer-associated venous thromboembolism – a case-based practical approach
Authors: Voigtlaender Minna , Langer Florian
Published: January 2018

Abstract. In patients with solid tumours or haematological malignancies, venous thromboembolism (VTE) is a leading cause of death and significantly contributes to morbidity and healthcare resource utilization. Current practice guidelines recommend long-term anticoagulation with low-molecular-weight heparin (LMWH) as the treatment of choice for cancer-associated VTE, based on clinical trial data showing an overall improved safety and efficacy profile of LMWH compared to vitamin K antagonists. However, several open questions remain, e. g. with regard to the intensity and duration of LMWH therapy; moreover, recent real-world evidence indicates that adherence to parenteral anticoagulation with LMWH over the course of treatment is poor in clinical practice. In this regard, the direct oral factor Xa or thrombin inhibitors (DOACs) have emerged as potential alternatives in the management of patients with cancer-associated VTE, albeit findings from randomized controlled studies with a direct head-to-head comparison of DOACs with LMWH, the current standard of care, are still lacking. Based on the case of a lymphoma patient experiencing symptomatic pulmonary embolism during immunochemotherapy, this article aims at both highlighting the current state-of-the-art approach to cancer-associated VTE and pointing out some of the unresolved, controversial issues clinicians have to face when taking care of haematology and oncology patients with already established or with high risk of developing VTE. These issues include the management of patients with incidental pulmonary embolism or thrombocytopenia, the use of DOACs, and the initiation of pharmacological thromboprophylaxis in non-surgical cancer patients.
UV Radiation Associates With State Income Through Complex Cognitive Ability in the USA
Authors: León Federico R. , Burga-León Andrés
Published: January 2018

Abstract. Economic development and national intelligence decline with proximity to the equator. Absolute latitude associates with both, income and IQ, but the nature of their relationship is ambiguous. This study applied structural equation modeling using secondary data pertaining to the 48 contiguous states of the United States of America to test the hypothesis that UV (ultraviolet) radiation associates with income through complex cognitive ability vis-a-vis the hypothesis that UV radiation associates with complex cognitive ability through income. The resulting evidence was consistent with the ability → income pathway and unsupportive of the income → ability model. The findings uphold the cognitive capitalism perspective and may throw light on the evolvement of regional differences in the USA.