bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights from mouse models of colitis
Authors: Boismenu Richard , Chen Yaping
Published: January 2018

Emerging studies using mouse models of experimental colitis are defining the nature of the immunological disturbances that initiate inflammation and destruction of the intestine. A better understanding of disease-promoting and -suppressing CD4+ T cells is providing insight into the mechanisms controlling immune responses within the intestinal compartment. Moreover, a role for distinct T cell populations, including intraepithelial γδT cells, in maintaining the physical integrity of the intestine was suggested by recent studies. Cytokine gene-knockout mice and anti-cytokine treatments remain important tools to define the pro- and anti-inflammatory functions of cytokines. These advances are fostering the design and evaluation of new therapeutic approaches that may eventually be applied to treat human inflammatory bowel disease. J. Leukoc. Biol. 67: 267–278; 2000.
Neurotransmitters of the sympathetic nerve terminal are powerful chemoattractants for monocytes
Authors: Straub Rainer H , Mayer Markus , Kreutz Marina , Leeb Sandra , Schölmerich Jürgen , Falk Werner
Published: January 2018

Macrophages in lymphoid organs are in close contact to nerve terminals of the sympathetic nervous system. Hence, these cells could be targets of neuronal modulation. We studied sympathetic neurotransmitters as chemoattractants enabling the aggregation of macrophages and nerve terminals. Norepinephrine (NE), neuropeptide Y (NPY), isoproterenol (β-adrenergic), p-aminoclonidine (α2-adrenergic), methoxamine (α1-adrenergic), and adenosine triphosphate (ATP) were used to study human monocyte and macrophage migration in 48-well Boyden chambers. NE stimulated chemotaxis of monocytes and macrophages at an optimal concentration of 10−10 M (P < 0.025). Isoproterenol, but not p-aminoclonidine or methoxamine, induced chemotaxis of monocytes (10−10 M, P < 0.05). In these studies, elevation of cAMP is a critical step in NE-induced chemotaxis of monocytes. NPY (10−11 M, P < 0.05) stimulated monocyte chemotaxis as well. ATP at 10−4 and 10−5 M stimulated undirected cell mobility (P < 0.05). All tested neurotransmitters of the sympathetic nerve terminal were potent chemoattractants. These findings may explain the close association of nerves and macrophages in tissue and lymphoid organs and may thus be of functional relevance in neuroimmunomodulation. J. Leukoc. Biol. 67: 553–558; 2000.
Analysis of interferon-γ-dependent and -independent pathways of macrophage activation
Authors: Paulnock Donna M , Demick Karen P , Coller Susan P
Published: January 2018

Macrophages are a cellular cornerstone of the innate immune response. The outcome of macrophage activity during development of an immune response to microbes results from macrophage activation by both organism-derived and host-derived factors. In order to more fully understand the spectrum of responses expressed by macrophages when encountering these distinct stimuli, we investigated the similarities and differences between interferon-γ receptor (IFN-γR)dependent macrophage activation and stimulation of macrophages through the Type A1 scavenger receptor (SR). We observed distinct patterns of macrophage activation depending on the nature of the ligand. IFN-γ and the SR ligand lipotechoic acid (LTA) induced largely non-overlapping sets of genes. The use of two additional SR ligands, maleylated bovine serum albumin and the polydeoxynucleo-tide poly dI:dC, revealed differences within SR activation-induced gene expression. We also observed that priming with IFN-γ resulted in an enhanced response to subsequent SR-mediated activation. These results suggest that full potentiation of macrophage activity during development of an antimicrobial immune response is achieved by activation of these cells through multiple receptors. J. Leukoc. Biol. 67: 677–682; 2000.
Coordinate activation of endogenous p38a, β, γ, and δ by inflammatory stimuli
Authors: Fearns C , Kline L , Gram H , Di Padova F , Zurini M , Han J , Ulevitch R J
Published: January 2018

The p38 family of mitogen-activated protein kinases is believed to mediate a variety of leukocyte responses to pro-inflammatory stimuli. There are four members of the p38 family, and although activation of the different members has been studied in transiently transfected cells much less is known about activation of the endogenous p38s, particularly in myeloid lineage cells. To investigate activation of endogenous p38s, we have made monoclonal antibodies specific for each p38 and have used these antibodies to study p38 activation by pro-inflammatory stimuli in several human monocytic cell lines. Without stimulation endogenous p38α kinase activity was readily detectable, whereas that of p38β, γ, and δ was barely measurable. In response to inflammatory stimuli, we observed a time- and dose-dependent activation of all four p38s. The kinetics of activation of each of the p38s were similar for each stimulus used, suggesting a common upstream activation pathway. Simultaneous activation of the p38s suggests that all four may be important in inflammation. J. Leukoc. Biol. 67: 705–711; 2000.
A molecular analysis of NKT cells: identification of a class-I restricted T cell-associated molecule (CRTAM)
Authors: Kennedy Jacqueline , Vicari Alain P , Saylor Vicki , Zurawski Sandra M , Copeland Neal G , Gilbert Debra J , Jenkins Nancy A , Zlotnik Albert
Published: January 2018

cDNA library subtraction techniques were used to identify transcripts expressed by activated mouse αβPTCR+ CD4−CD8− (double-negative; DN) T cells, a subset of natural killer T (NKT) cells. The most frequent cDNAs identified included the chemokines TCA3, macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and lymphotactin (LPTN), the cytokines interleukin-4 (IL-4) and interferon-γ (IFN-γ), and a granzyme. We also identified a new member of the immunoglobulin superfamily (Ig-SF). This molecule was designated class I-restricted T cell-associated molecule (CRTAM) as a result of its restricted expression pattern in T cells. Human CRTAM was also identified, and shares the same expression pattern as the mouse molecule. LPTN and CRTAM exhibit the same expression pattern in T cells, suggesting the existence of a gene expression program common to class I-MHC-restricted T cells. J. Leukoc. Biol. 67: 725–734; 2000.
Hypoxemia modifies circulating and exudate neutrophil number and functional responses in carrageenin-induced pleurisy in the rat
Authors: Tremblay Pierre-Benoît , Macari David MT , Martel Dominique , du Souich Patrick , Barja-Fidalgo Christina , Marleau Sylvie
Published: January 2018

To assess the effect of hypoxemia on the responses of polymorphonuclear neutrophils (PMN) during an inflammatory response, rats were maintained in a low FiO2 atmosphere (9% O2) or room air for 12 h before intrathoracic injection of carrageenin or intradermal injections of agonists. After 4 h, hypoxemic rats had 50% more circulating PMN in blood and 25% less PMN in pleural exudate, whereas the number of PMN in skin biopsies did not differ from controls. Following hypoxemia, basal adhesion of blood PMN to serum-coated plastic wells was unchanged, whereas fMLP-stimulated adhesion was 50% greater. In contrast, basal adhesion of exudate PMN was 72% greater. In hypoxemic rats, exudate PMN produced 64% more PMA-stimulated superoxide than blood PMN; furthermore, blood and exudate PMN produced 4.5- and 2-fold more LPS-stimulated nitric oxide than controls, respectively. These results show that a moderate level of hypoxemia may trigger mechanisms that will interfere with PMN emigration yet prime these cells for enhanced responses upon stimulation. J. Leukoc. Biol. 67: 785–792; 2000.
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

Purpose

The 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.

Methods

Electromagnetic 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.

Results

Measured 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).

Conclusions

Three 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

The 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

Axially 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.
The effect of phase change on stability of convective flow in a layer of volatile liquid driven by a horizontal temperature gradient
Authors: Grigoriev Roman O. , Qin Tongran
Published: January 2018

Buoyancy–thermocapillary convection in a layer of volatile liquid driven by a horizontal temperature gradient arises in a variety of situations. Recent studies have shown that the composition of the gas phase, which is typically a mixture of vapour and air, has a noticeable effect on the critical Marangoni number describing the onset of convection as well as on the observed convection pattern. Specifically, as the total pressure or, equivalently, the average concentration of air is decreased, the threshold of the instability leading to the emergence of convective rolls is found to increase rather significantly. We present a linear stability analysis of the problem which shows that this trend can be readily understood by considering the transport of heat and vapour through the gas phase. In particular, we show that transport in the gas phase has a noticeable effect even at atmospheric conditions, when phase change is greatly suppressed.
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.
PP007 Technology Adoption In Hospitals - Balancing Incentives - A Survey
Authors: Tal Orna , Tal Inbal
Published: January 2018

INTRODUCTION:

Health Technology Assessment (HTA) in the hospital framework involves evaluating safety and cost-effective benefits alongside additional perspectives. We must take into account: professional skills, patient mix, infrastructure costs, the competitive arena and promoting innovation as part of the hospital strategy. Within budgetary constraints, hospitals need to focus on clinical excellence, prioritizing selected technologies in key fields.

METHODS:

A survey was conducted among thirty-five mid-level managers; department directors and head nurses from eight medical centers. The data was collected from a structured questionnaire scoping five fields: clinical efficiency, risk, benefit, contribution of relevant “players” for decision making and impact of adoption.

RESULTS:

Personal characteristics of the responders correlated with certain trends: managers with longer seniority ranked life-saving higher than younger managers, as did men in comparison to women. Participants from the peripheral regions ranked improvement in quality of life higher than respondents from the center of the country. The importance of functional improvement of the patient was graded higher by nurses, compared to the physicians.

In operative aspects, improving staff communication was considered significantly higher among experienced managers, women, staff members in the central region hospitals and among nurses in comparison to physicians. Women ranked improvement of medical standards and guidelines higher, irrespective of their professional sector. At initial stages of the technology lifespan, scientific evidence on effectiveness was found to have a stronger influence on adoption decisions than national guidelines.

Budgetary repercussions of adopting a new technology were ranked significantly higher in the central region. Experienced managers attributed greater impact to economic issues than younger managers.

Social dimensions, such as providing care for a large population, reaching the target population, improvement of service and patient preferences were graded significantly higher by women.

CONCLUSIONS:

The survey highlights the insights of managers for decision making on adopting technologies in hospitals. These decisions need to integrate clinical advantages, competitive markets and national strategies with personal and professional parameters assists in bridging the gaps between local hospital activities and governance.
PP019 Clostridium Difficile Infection Diagnosis: Hospital-based Health Technology Assessment
Authors: Senna Kátia , Santos Marisa , Tura Bernardo
Published: January 2018

INTRODUCTION:

Clostridium difficile infection is the leading cause of nosocomial diarrhea in developed countries and may progress to pseudomembranous colitis, sepsis and death. The risk factors are antibiotics use, advanced age and prolonged hospitalization. The diagnosis of Clostridium difficile infection is based on clinical history in combination with laboratory tests, which detect the Clostridium difficile presence or toxins. Clostridium difficile remains in spore form contaminating the environment and requiring measures to prevent hospital transmission. Tests with more accurate results to identify true carriers of Clostridium difficile allow the clinician to determine a safer treatment. This study evaluated accuracy and cost-effectiveness of the real-time polymerase chain reaction compared with the enzyme-linked immunosorbent assay from the perspective of a Brazilian public cardiology hospital.

METHODS:

A study diagram was constructed by type of test, linking the data of prevalence in hospital, accuracy and direct costs of tests. The costs were based on a hypothetical population comparing two strategies to identify the incremental expenditure between technologies. The analysis included comparisons for each test versus no test, and with each other. The prices were converted to the American currency taking into account the date of purchase of each product and respective price.

RESULTS:

For real-time polymerase chain reaction test versus no test, 214 patients would have tested to justify one empirical treatment suspension, at a cost of USD90,926.46. For enzyme-linked immunosorbent assay test, to prevent one unnecessary treatment, 375 patients would have to be tested at a cost of USD6,603.75. In the comparative analysis, only a single false-positive patient would have the treatment suspended after performing 375 real-time polymerase chain reaction tests at USD424.89 each one (USD159,333.75 in total). An incremental cost of USD152,730.00 may be necessary to benefit a single patient by discontinuing empirical treatment.

CONCLUSIONS:

The Real-time polymerase chain reaction test has restrictions as a test of choice for the diagnosis of Clostridium difficile infection, in services with low disease prevalence. It undergoes a significant change in its positive predictive value and does not offer a great impact in the clinical diagnosis.
PP020 Decision-Making Beyond Evidence Alone – Topic Prioritization For Health Technology Assessment
Authors: Ju Hong , Ng Kwong , Teo Elaine , Khoo Daphne
Published: January 2018

INTRODUCTION:

The number of health technologies needing evaluation far outweighs available resources, and most Health Technology Assessment (HTA) agencies use criteria-based frameworks for topic prioritization (1,2). Despite variability, most frameworks include clinical, economic and budget impact. Some limitations of current frameworks lack mentioning of any explicit political/ethical deliberation and an evaluation on the potential impact of the HTAs (1).

METHODS:

During a topic prioritization for HTA, Left Ventricular Assist Device (LVAD) as destination therapy for adults with end-stage heart failure was submitted. The prioritization criteria used were largely in line with those described above. We also included criteria on ethical/equity consideration and the potential impact of an HTA on decision making. A literature search was conducted to gather clinical and economic evidence on LVAD for the target population, supplemented by local data on potential need for and budget impact of providing a LVAD service.

RESULTS:

LVAD was scored high on clinical, economic and budget impact with a moderately high need, which would generally subject it to an HTA in order to inform a policy decision. However LVAD was also considered as a technology with a high impact on ethical and political grounds, given that it is a technology offering survival and quality-of-life benefits for a small group of patients for whom effective treatment is otherwise lacking. Through deliberation, the prioritization panel concluded that the impact of an HTA would be low, as a policy decision on whether a LVAD program should be funded would go beyond evidence. Therefore an HTA was not recommended for LVAD.

CONCLUSIONS:

To inform decision making, an evaluation on the potential impact of the HTA itself taking into account of the ethical/political consideration of funding a technology is of equal importance as the evidence alone. Subsequently, limited HTA resources can be reserved for technologies where an HTA can truly make a difference.
PP038 EQ-5D-3L Electronic Version Development For The Brazilian Population
Authors: Miguel Sandro , Bagattini Ângela , Camey Suzi , Polanczyk Carisi , Cruz Luciane
Published: January 2018

INTRODUCTION:

Quality of Life (QoL) is considered to be an important outcome which is widely used in Health Technology Assessment (HTA). In economic evaluations QoL is represented by quality-adjusted life years (QALYs) - adding utility scores to the years of life lived in a determined health status (1). The EuroQol - 5 dimensions (EQ-5D) is a QoL questionnaire that generates utility scores and provides a simple and generic measure of health (2). Electronic QoL instruments have been reported equivalent to paper-based methods, however no studies have assessed agreement between EQ-5D application methods in Brazil (3). Thus, our study aimed to evaluate the measurement equivalence between the original (paper) and adapted (tablet) versions of the EQ-5D-3L Brazilian questionnaire.

METHODS:

A cross-sectional study was conducted on 509 adult individuals selected at random in economically different regions of two major Brazilian cities. EQ-5D-3L and Visual Analogue Scale, paper and tablet versions, were applied. Subjects were randomized to two groups; one group assigned for test-retest assessment using only electronic media (tablet-tablet), and a crossover group - half of which answered the tablet version before the paper questionnaire (tablet-paper), and the other half which answered the tablet version after the paper questionnaire (paper-tablet). There was a washout period of a minimum of 24 hours and maximum of 7 days between applications. The Intraclass Correlation Coefficient (ICC) and kappa coefficient were used to determine the agreement between methods. The level of significance was set at .05 for all analyses.

RESULTS:

Females predominated in all groups, and the mean age ranged from 41 to 44 years. In the crossover group the obtained ICC values were: .76 (CI .58–.89) for EQ-5D scores and .77 (CI .68–.84) for Visual Analogue Scale (VAS) scores in the tablet-paper subjects; .83 (CI .75–.89) for EQ-5D scores and .75 (CI .67–.85) for VAS scores in the paper-tablet subjects. In the test-retest group, the ICC values were .85 (CI .73–.91) for EQ-5D scores, .79 (CI .66–.87) for VAS scores. Kappa values were higher than .69 in test-retest group. Internal consistency was similar between methods.

CONCLUSIONS:

Paper and tablet versions of the EQ-5D were equivalent. Test-retest and crossover agreement was high and the acceptability of the methods was similar.
PP061 Direct Cost Of Physiotherapeutic Devices Judicialization In Brazil
Authors: Moraes Dominique , Tarbes Luciana , de Veras Bruna , Santos Marisa
Published: January 2018

INTRODUCTION:

The “Judicialization of health” is a judicial option, provided by the Brazilian constitution, which aims to guarantee the access of the population to healthcare products or services to which they were denied or that were otherwise unavailable on the Unified Health System (SUS) (1). This highlights deficiencies in public policies (2). Considering the progressive impact of the judicialization on the budget and the lack of real-world evidence on the subject, the objective was to describe the judicialization profile of physiotherapeutic devices in the city of Rio de Janeiro and to estimate the spending on them within the system.

METHODS:

The profile was traced based on the analysis of the processes (n = 243) submitted to the Technical Advice Unit of the Rio de Janeiro Justice Court between May 2013 and September 2015, which litigated the provision of physiotherapeutic devices. Direct cost information was obtained from both public and private sources. The analysis was carried out using the SUS perspective.

RESULTS:

About 63 percent of the patients were over 60 years old. The majority of the requests were due to chronic respiratory diseases, the most common being obstructive sleep apnea-syndrome (31 percent), chronic obstructive pulmonary disease (14 percent) and pulmonary fibrosis (11 percent). The most judicialized devices were continuous positive airway pressure (21 percent), oxygen concentrator (17 percent) and portable oxygen cylinder (13 percent). None of these devices are currently covered by SUS. The expenses related to the purchase of the devices pleaded was approximately USD812,500 over 29 months.

CONCLUSIONS:

The total spend on these devices were considered very high when compared to Rio de Janeiro's health budgetary capacity. This scenario could be worse if this type of demand were not planned, and needed to be accomplished quickly with urgent purchases. The results obtained shows that judicialization phenomenon has a meaningful impact on the economic viability of the Brazilian healthcare system.
PP092 Real World Data: Biologic Treatment For Naive Patients In Lazio Region
Authors: Mecozzi Alessandra , Marcellusi Andrea , Sciattella Paolo , Mennini Francesco
Published: January 2018

INTRODUCTION:

The introduction of new biologic treatments has radically changed the management of Immune-mediated inflammatory diseases (IMID). Due to the high costs of the treatments a strong control and monitoring of claims databases could help decision makers to understand the consequences of their decisions.

The objective of the study was to identify the cohort of biologics treatment-naïve patients in the years 2011–2013 in the Lazio region (6 millions of inhabitants), in order to investigate the parameters influencing the biologic treatment expense at the regional level.

METHODS:

Patients were enrolled based on administrative databases of the Lazio region. Treatment-naïve patients were defined as subjects who did not have a prescription in the two years before the index prescription. Switcher patients were defined as those who had an Anatomical Therapeutic Chemical classification (ATC) prescription different than the one at enrolment, within one year of the index date. Treatment adherence was estimated as the number of doses actually prescribed as compared to the number indicated in the Summary of Product Characteristics (SPC).

RESULTS:

From a total number of 10,120 patients treated with biologic drugs between 2011–2013 in the Lazio region, 2,929 were estimated as treatment-naïve patients (42 percent male). The most frequently used drugs were etanercept (31 percent), adalimumab (30 percent) and infliximab (17 percent). Considering the disease treatment distribution, 28.6 percent of patients were treated for rheumatoid arthritis, 25.5 percent for psoriatic arthritis, 16.4 percent for psoriasis and the remaining patients for other diseases. Some patients switched biologic therapy (367), of which 22.6 percent were within the first 120 days. Total mean adherence was estimated in 87.7 percent: 21.5 percent of patients showed a low adherence (SPC< 60 percent) while 18.1 percent were estimated as dose increase patients (SPC>110 percent), 11.4 percent for rheumatic diseases, 32.3 percent for dermatological diseases and 26.9 percent for inflammatory bowel disease.

CONCLUSIONS:

The study provides a map of the current treatment settinga with biologics in the Lazio region considering the disease, adherence and prescribed treatments. A considerable number of treatment-naïve patients were identified (2,929), 12.5 percent of whom switched ATC within 1 year. Total mean adherence was estimated in 87.7 percent, low adherence occurred in 21.5 percent of patients, while dose-increase was in 18.1 percent.