bluuebunny/crossref_metadata_2025_split huggingface dataset:
Millimeter spatial resolution in vivo sodium MRI of the human eye at 7 T using a dedicated radiofrequency transceiver array
Authors: Wenz Daniel , Kuehne Andre , Huelnhagen Till , Nagel Armin M. , Waiczies Helmar , Weinberger Oliver , Oezerdem Celal , Stachs Oliver , Langner Soenke , Seeliger Erdmann , Flemming Bert , Hodge Russell , Niendorf Thoralf 
Published: January 2018

PurposeThe aim of this study was to achieve millimeter spatial resolution sodium in vivo MRI of the human eye at 7 T using a dedicated six‐channel transceiver array. We present a detailed description of the radiofrequency coil design, along with electromagnetic field and specific absorption ratio simulations, data validation, and in vivo application.MethodsElectromagnetic field and specific absorption ratio simulations were performed. Transmit field uniformity was optimized by using a multi‐objective genetic algorithm. Transmit field mapping was conducted using a phase‐sensitive method. An in vivo feasibility study was carried out with 3‐dimensional density‐adapted projection reconstruction imaging technique.ResultsMeasured transmit field distribution agrees well with the one obtained from simulations. The specific absorption ratio simulations confirm that the radiofrequency coil is safe for clinical use. Our radiofrequency coil is light and conforms to an average human head. High spatial resolution (nominal 1.4 and 1.0 mm isotropic) sodium in vivo images of the human eye were acquired within scan times suitable for clinical applications (∼ 10 min).ConclusionsThree most important eye compartments in the context of sodium physiology were clearly delineated in all of the images: the vitreous humor, the aqueous humor, and the lens. Our results provide encouragement for further clinical studies. The implications for research into eye diseases including ocular melanoma, cataract, and glaucoma are discussed. Magn Reson Med 80:672–684, 2018. © 2018 International Society for Magnetic Resonance in Medicine.
Comparative Proteomics Studies of Insect Cuticle by Tandem Mass Spectrometry: Application of a Novel Proteomics Approach to the Pea Aphid Cuticular Proteins
Authors: Masson Victor , Arafah Karim , Voisin Sébastien , Bulet Philippe 
Published: January 2018

AbstractThe cuticle is a biological composite material consisting principally of N‐acetylglucosamine polymer embedded in cuticular proteins (CPs). CPs have been studied and characterized by mass spectrometry in several cuticular structures and in many arthropods. Such analyses were carried out by protein extraction using SDS followed by electrophoresis, allowing detection and identification of numerous CPs. To build a repertoire of cuticular structures from Bombyx mori, Apis mellifera and Anopheles gambiae the use of SDS and electrophoresis was avoided. Using the combination of hexafluoroisopropanol and of a surfactant compatible with MS, a high number of CPs was identified in An. gambiae wings, legs and antennae, and in the thoracic integument cuticle of Ap. mellifera pupae. The exoskeleton analysis of B. mori larvae allowed to identify 85 CPs from a single larva. Finally, the novel proteomics approach was tested on cuticles left behind after the molt from the fourth instar of Acyrthosiphon pisum. Analysis of these cast cuticles allowed to identify 100 Ac. pisum CPs as authentic cuticle constituents. These correspond to 68% of the total putative CPs previously annotated for this pea aphid. While this paper analyzes only the recovered cuticular proteins, peptides from many other proteins were also detected.
Experimental and numerical investigations of axially loaded RC walls restrained on three sides
Authors: Ho Nhat‐Minh , Doh Jeung‐Hwan 
Published: January 2018

SummaryAxially loaded reinforced concrete (RC) walls in tilt‐up structures can be supported top and bottom only by floors or roof structures. However, RC walls are often combined to form I‐, C‐, T‐, and L‐shapes to make efficient use of the building area in multi‐storey buildings. With these configurations, walls may also be laterally supported on either or both sides by interconnecting walls. While many researchers have investigated the behaviours of RC walls, either in one‐way action or two‐way action supported on four sides with and without openings, limited research has been conducted on two‐way action walls supported on three sides (TW3S). As such, this paper experimentally and numerically investigates the behaviour of TW3S walls. Details of the 12 half‐scale walls tested, including experimental setup, failure loads, crack patterns, and load‐deflection characteristics, are reported. In addition, the Finite Element Method using ABAQUS software for investigating the behaviour of TW3S walls is described in detail. Finally, due to the conservative nature of code design equations and there being limited available methods for predicting the ultimate load of TW3S walls with openings, a rigid‐plastic approach has been proposed in this study to evaluate the failure load of TW3S walls.
OP03 Trends In The National Institute For Health And Care Excellence (NICE) Cancer Drugs Fund Reconsiderations
Authors: Liden Daniel , Pontynen Anson , Jaksa Ashley , Rubinstein Judith 
Published: January 2018

INTRODUCTION:As of July 2016, funding from England's Cancer Drugs Fund (CDF) is dispensed based on the results of National Institute for Health and Care Excellence (NICE) technology appraisal guidances instead of independent CDF appraisals (1). As part of this transition, NICE is reconsidering drugs previously funded through the CDF (2). This analysis examines CDF reconsiderations conducted between the inception of the new process in July and the end of 2016 to identify any possible trends.METHODS:We collected all NICE final technology appraisal guidances (3) completed before the end of 2016 and noted whether each drug was a CDF reconsideration, what the final decision was, and which factors impacted the decisions.RESULTS:We identified twenty-one NICE oncology reviews competed between July 2016 and the end of 2016. Of these reviews, eight were reconsiderations of drugs previously funded through the old CDF; the rest were new reviews. Only one drug evaluated in the reconsiderations received a negative decision. All the reconsiderations included confidential manufacturer discounts and all noted updated clinical data. End of life (EOL) criteria expanded the acceptable incremental cost-effectiveness ratio (ICER) range for some of the CDF reconsiderations.CONCLUSIONS:All the reconsiderations included updated clinical data and analyses, though it does not appear that updated clinical data were sufficient to bring ICERs to acceptable levels. This is to be expected as the old CDF process served as an alternate funding source for many drugs that did not or were unlikely to fare well under NICE's evaluations. The updated clinical data may have at least increased NICE's confidence in the accuracy of the ICERs. All of the reconsiderations included confidential manufacturer discounts to reach acceptable ICER ranges. The results of this first round of reconsiderations suggest that manufacturers prefer offering their drugs at lower prices to potentially losing National Health Service (NHS) reimbursement entirely.
OP07 Towards Better Outcomes: New Standard For Placing A Value On Health
Authors: Krabbe Paul 
Published: January 2018

INTRODUCTION:Cost-effectiveness analysis is probably the most often applied analysis in the field of Health Technology Assessment. Yet, there are major issues related to this analytical approach. Apart from the discussions about discounting, and which type of costs should be included in the analysis, there is discussion about the measurement of the health effects. The dominant economic and decision-making research paradigm that underpins present protocols to value health show flaws and limitations.METHODS:All existing generic health instruments (for example,. EuroQol five dimensions questionnaire, EQ-5D; Health Utilities Index, HUI; Short Form, SF-6D) used to collect values for health states use a small, fixed set of health domains. Descriptions of health states are created based on these domains and their levels. Subsequently, these descriptions are valued with special preference-based methods (measuring the quality or importance of something). When developing those instruments, patients’ opinions were not actively incorporated in the choice of domains, nor have patients’ preferences been considered in assessing weights to the domains and their levels.RESULTS:We developed a novel preference-based health measurement methodology that combines the strength of two existing measurement models for subjective phenomena: the discrete choice model and Rasch item response theory (1-3). This new approach is referred to as the multi-attribute preference response (MAPR) model. This is the first generic health preference-based model that is fully based on the perception and reporting from patients (experienced based) and is insensitive to adaptation mechanisms. Apart from being grounded on measurement theory, the valuation tasks are easy and attractive to perform in a self-completion setting. A first application based on this novel model has been worked out in a mobile app to measure the overall health condition of infants (reported by mothers).CONCLUSIONS:Our recently introduced and informative health measurement model overcomes many problems associated with the conventional methods.
OP58 Testing Of A Multiple Criteria Decision Analysis Value Framework With Decision Makers Across Europe
Authors: Angelis Aris , Linch Mark , Montibeller Gilberto , Molina-Lopez Teresa , Zawada Anna , Orze Kinga , Arickx Francis , Espín Jaime , Kanavos Panos 
Published: January 2018

INTRODUCTION:We test in practice a Multiple Criteria Decision Analysis (MCDA) framework for the value assessment of a set of therapeutic options for the indication of hormone relapsed metastatic prostate cancer (mPC) through a series of simulation exercises with the participation of decision makers from different Health Technology Assessment (HTA)/insurance agencies across Europe, including TLV (Sweden), AETSA (Andalusia-Spain), INAMI-RIZIV (Belgium) and AOTMiT (Poland). The drugs evaluated were abiraterone, cabazitaxel and enzalutamide.METHODS:Using a multi-attribute value theory framework, past research outcomes and literature findings, an mPC-specific value tree was constructed incorporating relevant concerns as criteria. By adopting the MACBETH approach the different drugs were scored against the criteria through the development of value functions, relative weights were assigned to the criteria using a swing weighting technique, scores and weights were combined using an additive aggregation technique, and sensitivity analysis of results was conducted. All stages were informed through the participation of a small group of experts from each HTA/insurance agency at a series of decision conferences taking place in each country.RESULTS:Value parameters considered spanned the dimensions of therapeutic impact, safety profile, innovation level and socioeconomic impact. Overall weighted preference value scores were produced reflecting the performance of the treatments against the criteria while considering their relative importance. Order of treatments’ rankings was identical across all agencies, with enzalutamide scoring highest and cabazitaxel lowest. Therapeutic impact criteria always produced the greatest relative weight. Hypothetical priority setting decisions were made based on “value-for-money” grounds through the use of “cost per unit of value” metrics by incorporating purchasing costs.CONCLUSIONS:The MCDA framework tested possesses a number of characteristics that could facilitate decision making, including the systematic and explicit incorporation of value trade-offs as part of model assessment and the transparency throughout all its stages. Therefore, it has the prospects to act as a practical evaluation tool for value assessment and communication during the HTA process.
OP100 How Health Technology Assessment Is Adapting To Orphan Drugs In Canada – Not!
Authors: Wong-Rieger Durhane , Mills Ferg 
Published: January 2018

INTRODUCTION:Some countries have distinct pathways for drugs for rare diseases (DRDs) (1). In May 2014, the Canadian Agency for Technologies in Health (CADTH) rejected the option of a separate review pathway for DRDs, reiterating that “pharmacoeconomic analyses are critical for all types of drugs”. While the gap between positive recommendations for common and rare drugs may have narrowed, the rejection for DRDs is still proportionally much higher (2). The default has been to provincially negotiate drug access, for patient populations, subgroups or individuals. Still not wishing to create a separate pathway, in March 2016, CADTH produced a revised evaluation framework for “uncertain clinical and pharmacoeconomic evidence” and other considerations representing “significant unmet need” including rarity and difficulty to study because of small patient population”(3). This study analyzes recommendations for DRDs following the two CADTH revisions.METHODS:Methods used were: synthesis of previously conducted analyses of CADTH recommendations for rare and non-rare drugs, primary comparative analysis of CADTH recommendations for DRDs from 2004 to 2016, and qualitative analysis of two drugs submitted for both rare and non-rare conditions: everolimus (breast cancer, pancreatic neuroendocrine tumours, and tuberous sclerosis complex) and ibrutinib (chronic lymphocytic leukemia, small lymphocytic lymphoma, and Waldenström's Macroglobulinemia).RESULTS:Previous analyses found that DRDs received more negative recommendations than did non-rare drugs; both clinical and economic evidence were differentiating factors. The primary analysis provided an additional understanding of reasons for negative recommendations. There is low consistency across assessments and across the two CADTH review committees. The case studies illustrated the challenges for DRDs to overcome barriers of cost-effectiveness and certainty of clinical evidence, even with the revised framework.CONCLUSIONS:This research challenges the premise that Health Technology Assessment for all drugs can result in fair and equitable recommendations for DRDs. Moreover, assessments based on “significant unmet need” do not appear to provide consistent or equitable guidelines for addressing the issues specific to rare diseases.
OP106 The Impact Of Searching Fewer Databases In Health Technology Assessment Rapid Reviews
Authors: Wong Ruth , Cooper Katy , Martyn-St James Marrissa , Pandor Abdullah , Kaltenthaler Eva 
Published: January 2018

INTRODUCTION:Multiple databases are often searched in Health Technology Assessment systematic reviews. However in rapid reviews, time and resources are limited and modifications to the search methodology may be necessary. In this retrospective study, the impact of searching fewer databases for three completed rapid reviews (i) Severe Mental Illness (SMI), (ii) Cannabis Cessation (CC), iii) Premature Ejaculation (PE) for the United Kingdom National Institute for Health Research was investigated.METHODS:The database coverage and indexing of the study references from the reviews were initially identified. The impact of fewer databases searched was then tested by (i) the number of studies that might be missed, (ii) the number of records for sifting and (iii) the overall rapid review conclusions.RESULTS:A total of 178 included study references were found in the reviews (SMI n = 14 for 13 studies, CC n = 34 for 33 studies, PE n = 130 for 102 studies). Searching Medline only for SMI, Medline+Embase for CC, Medline+Embase+Cochrane Library for PE, would result in 1902 (74 percent), 466 (43 percent) and 240 (11 percent) fewer records needed to sift, respectively. There would also be a total of ten ‘would be missed’ references (SMI n = 1, CC n = 5 and PE n = 4). However, nine out of the ten references were found to have no or minimal impact on the overall findings of the reviews. The ten references were secondary reports of an included study, papers that lacked sufficient data for meta-analysis such as a conference abstract or an ongoing trial.CONCLUSIONS:From the three reviews examined, limiting the search to fewer databases had no or minimal impact on the review conclusions despite the variable number of studies that would be missed and records needed to sift. More exploration during the scoping search prior to commencing the review will aid the decision on whether to limit the search to fewer databases.
OP107 Sources Used To Find Studies For Systematic Reviews Of Economic Evaluations
Authors: Wood Hannah , Arber Mick , Isojarvi Jaana , Glanville Julie 
Published: January 2018

INTRODUCTION:Evidence about which information resources should be searched to identify economic evaluations (EEs) of healthcare interventions when conducting a systematic review (SR) predates closure of the National Health Service Economic Evaluation Database (NHS EED) and Health Economic Evaluations Database (HEED). We assessed which databases are now the best sources of EEs and identify the most efficient combination of databases, taking into account the order in which databases could be searched.METHODS:We gathered a reference set of EEs from published reviews of EEs undertaken to inform Health Technology Assessments (HTA). We calculated yield and relative recall (RR) (number of reference set records identified / total number of records in reference set) for each database, and combination of databases. We assessed the order in which databases should be searched, to identify the most efficient combination of databases to identify the reference set. We report the characteristics of records not included in any database studied and implications for identifying this type of evidence.RESULTS:To date, a reference set of fifty-five EEs from seven HTAs has been processed. Embase and Scopus each yielded 53/55 records (RR .96). MEDLINE yielded 52/55 (RR .95). Embase or Scopus included all of the journal publications in the reference set; no additional unique records were provided by MEDLINE, CEA Registry, EconLit, or Science and Social Science Citation Indexes. The two records that were not identified were unpublished evidence, one of which was included in the National Institute for Health Research (NIHR) HTA database. Processing will continue until we reach the threshold of a reference set of 350 records.CONCLUSIONS:Preliminary results suggest that searching two or three databases may be most efficient, provided that resources are searched using appropriate strategies. Searchers should concentrate on developing search strategies that work well in those databases to ensure adequate sensitivity, and use freed time to identify grey literature.
OP133 Health Technology Assessment In Brazil: A 5-year Review Of Brazilian Health System (CONITEC) Activities
Authors: Rabelo Roberta , Canuto Vania , Petramale Clarice , Mega Tacila 
Published: January 2018

INTRODUCTION:Since the creation of the National Committee for Health Technology Incorporation in the Brazilian Health System (CONITEC), a new phase started in the public Brazilian Health System (SUS): a continuous updating of the system based on Health Technology Assessment (HTA). CONITEC was created by federal law in 2012 and is responsible for advising the Ministry of Health regarding the incorporation or disinvestment of health technologies. The whole process involves a strong interaction with society, including the composition of the committee, which has the participation of the National Health Council. The objective of this study was to describe the results of CONITEC in five years of operation.METHODS:This is a retrospective descriptive study, based on information from the database (period 2012–2016) and CONITEC's website.RESULTS:Since 2012, CONITEC assessed 541 technologies, including drugs (360), health products (71) and procedures (110); 303 assessment requests came from SUS agencies and institutions and the other 238 requests from pharmaceutical companies, medical societies, patient associations and the judiciary bodies. In this period, there were 190 public consultations, during which more than 24,000 feedback from society were received. The average time for evaluation was 146 days. The committee recommended the incorporation of 186 technologies into SUS, the disinvestment of 43 and was unfavorable to the incorporation of 88, generating a budgetary impact of approximately BRL2.5 billion (USD764 million).CONCLUSIONS:From 2012–2016, CONITEC tripled the average annual incorporation of new technologies compared to the period 2006–2011. In this process, it was necessary to assess efficacy, safety and cost-effectiveness of technologies, generating positive results for the expansion of access, health gains for patients and sustainability for the system. It should be considered that the use of evidence for decision making strengthens transparency in public management and the development of active processes of information, communication and social participation.
OP136 Clinical Benefit Of Oncological Therapies At The Time Of Approval
Authors: Grössmann Nicole , Wild Claudia 
Published: January 2018

INTRODUCTION:In the last decade an increasing number of high-priced, new cancer treatments received marketing authorization in Europe. What is actually known about the clinical benefit of those therapies at the time of approval needs to be elucidated in order to inform decisions about the use and reimbursement of these novel treatment options. Thus, the aim of the current analysis was to systematically investigate oncological therapies approved between January 2009 and April 2016. We extracted, as well as quantified the level of knowledge of the clinical benefit at the time of marketing authorization.METHODS:To assess the benefit of new interventions as well as expanded indications, we extracted the median gain of the two study endpoints: progression-free survival (PFS) and overall survival (OS). Information is based on approval documents provided by the European Medicines Agency (EMA) and assessments from the Austrian Horizon Scanning programme (HSO). We included all cancer therapies approved in Europe between 1 January 2009 and 15 April 2016.RESULTS:Cancer drugs for 134 new indications approved since 2009 were identified. In the case of thirty-seven indications (27 percent), no data was available for PFS or for OS. A positive difference in median overall survival was reached by seventy-six licensed indications (55.5 percent); twenty-two (16 percent) of them showed a difference of more than three months. Regarding the study endpoint progression-free survival, an improvement was shown in ninety indications (65.2 percent).CONCLUSIONS:Scarce knowledge regarding the clinical benefit of anti-cancer therapies is available at the time of approval. In addition, the survival benefit of the approved indications is less than three months in the majority of approved therapies.