bluuebunny/crossref_metadata_2025 huggingface dataset:
L2‐L∞ filtering for a class of stochastic nonlinear systems with aperiodic sampling
Authors: Zhu Baolong , Suo Mingliang , Zhang Zhiping , Li Min , Li Shunli
Published: January 2018

This work investigates the problem of L2‐L∞ filtering for a class of stochastic nonlinear systems with nonuniform sampling. The sampled‐data filter developed in this paper is an impulsive differential system whose states change abruptly at every sampling instant. The resulting filtering error system is modeled as a stochastic nonlinear impulsive differential system. The goal is to propose a method for designing a target filter that ensures the stochastic asymptotic stability of the filtering error system and guarantees a prescribed L2‐L∞ performance. Based on a time‐varying Lyapunov functional, by virtue of a convex combination technique, a design method to achieve such a filter is formulated in the form of solving a set of linear matrix inequalities. The effectiveness of the proposed filtering strategy is shown via a numerical example of a stochastic Chua's circuit system.
Molecularly imprinted polymer nanocarriers for recognition and sustained release of diclofenac
Authors: Zheng Lei , Wang Hui , Cheng Xiaomin
Published: January 2018

In this study, a series of imprinted poly(methacrylic acid‐co‐ethylene glycol dimethacrylate) nanocarriers for diclofenac and corresponding nonimprinted polymer nanocarriers have been synthesized in 4 different types of solvents by precipitation polymerization. The products were characterized by Fourier transform infrared, scanning electron microscopy, dynamic light scattering, and Brunauer‐Emmett‐Teller measurement. Results showed that uniformly sized molecularly imprinted polymer (MIP) nanospheres with relatively good porosity could only be obtained in acetonitrile. The effects of solvents on the recognition and release properties of polymer particles were also carefully investigated. The binding experiments indicated that MIPs prepared in acetonitrile displayed much higher binding capacity than other MIPs with a maximum binding capacity of 65.18 mg g−1. The Scatchard analysis showed that synthetic MIPs have special recognition sites for diclofenac, while nonimprinted polymers have not. The Sips model could provide a best fit to the equilibrium data of nanocarriers over whole concentrations. The experimental data of an adsorption kinetic study were well fitted to the pseudo–second‐order kinetic model, indicating the chemisorption mechanism between diclofenac and MIPs in the process of adsorption. The drug release of diclofenac from MIPs could well be described by the Ritger‐Peppas model, suggesting a non‐Fickian diffusion mechanism. In addition, we successfully used MIPs to extract diclofenac at low levels from fetal bovine serum.
pH‐responsive starch microparticles for a tumor‐targeting implant
Authors: Kim Seong Kyeong , Park Hongsuk , Lee Jae Min , Na Kun , Lee Eun Seong
Published: January 2018

Much progress has been made toward stimuli‐responsive polysaccharide‐based selective tumor therapy not only because polysaccharides have nontoxic biodegradability and biocompatibility but also because their stimuli‐sensitive characteristics enable the proper transport of payloads into tumors. Here, we attempted to deliver an antitumor drug, doxorubicin (DOX), using starch‐based microparticles coupled with pH‐responsive 3‐(diethylamino)propylamine. The microparticles of starch conjugated with 3‐(diethylamino)propylamine (SDEAP) allowed for the change in hydrophobicity of SDEAPs in a pH‐dependent manner. The results revealed that SDEAPs effectively carried and released DOX and selectively killed tumor cells under acidic condition. Overall, this study suggests that DOX‐loaded SDEAPs can be further explored as a strategy for applications to acidic tumor‐targeting implants owing to the drug‐deliver efficiency and tumor selectivity.
The Sarda Sheep Host Fecal Proteome
Authors: Palomba Antonio , Tanca Alessandro , Addis Maria Filippa , Pagnozzi Daniela , Uzzau Sergio
Published: January 2018

The first characterization of the sheep fecal microbiota was recently reported, as obtained by using a multi meta‐omic approach. Here, the mass spectra generated by single‐run LC/high‐resolution MS in the context of that study were reanalyzed using a host‐specific database, in order to gain insights for the first time into the host fecal proteome of healthy Sarda sheep. On the whole, 5349 non‐redundant tryptic peptide sequences were identified, belonging to 1046 different proteins. The “core” fecal proteome (common to all animals) comprised 431 proteins, mainly related to biological processes as immune response and proteolysis. Proteins involved in the immune/inflammatory response and peptidases were specifically investigated. This dataset provides novel insights into the repertoire of proteins secreted in the sheep intestinal lumen, and constitutes the basis for future shotgun and targeted proteomics studies aimed at monitoring changes in the sheep fecal proteome in response to production variables, infectious/inflammatory states, and variations in the gut microbiota. Data are available via ProteomeXchange with identifier PXD006145.
Systematic Evaluation of Protein Sequence Filtering Algorithms for Proteoform Identification Using Top‐Down Mass Spectrometry
Authors: Kou Qiang , Wu Si , Liu Xiaowen
Published: January 2018

Complex proteoforms contain various primary structural alterations resulting from variations in genes, RNA, and proteins. Top‐down mass spectrometry is commonly used for analyzing complex proteoforms because it provides whole sequence information of the proteoforms. Proteoform identification by top‐down mass spectral database search is a challenging computational problem because the types and/or locations of some alterations in target proteoforms are in general unknown. Although spectral alignment and mass graph alignment algorithms have been proposed for identifying proteoforms with unknown alterations, they are extremely slow to align millions of spectra against tens of thousands of protein sequences in high throughput proteome level analyses. Many software tools in this area combine efficient protein sequence filtering algorithms and spectral alignment algorithms to speed up database search. As a result, the performance of these tools heavily relies on the sensitivity and efficiency of their filtering algorithms. Here, we propose two efficient approximate spectrum‐based filtering algorithms for proteoform identification. We evaluated the performances of the proposed algorithms and four existing ones on simulated and real top‐down mass spectrometry data sets. Experiments showed that the proposed algorithms outperformed the existing ones for complex proteoform identification. In addition, combining the proposed filtering algorithms and mass graph alignment algorithms identified many proteoforms missed by ProSightPC in proteome‐level proteoform analyses.
Ultrasound effects on the activity of Aspergillus niger lipases in their application in dairy wastewater treatment
Authors: Golunski Simone M. , Mulinari Jessica , Camargo Aline Frumi , Venturin Bruno , Baldissarelli Daiane P. , Marques Camila Torbes , Vargas Gean D. L. P. , Colla Luciane Maria , Mossi Altemir , Treichel Helen
Published: January 2018

We evaluated the effect of ultrasound radiation on lipase activity. The experiments were conducted using a low‐cost crude enzyme extract. We then used this lipase to treat dairy effluent. The results of our study presented an increase of approximately 430% in the concentration of free fatty acids.
Integrating climate change adaptation strategies in urban planning and landscape design of Addis Ababa City, Ethiopia
Authors: Worku Hailu
Published: January 2018

Climate change (CC) is now recognized as posing a serious threat to the sustainable development of Addis Ababa city, Ethiopia. As a consequence, city authorities are showing increasing interest in combating CC by streamlining adaptation measures into city development planning through a comprehensive and integrated approach. Nevertheless, in the past, the integration of CC adaptation into urban planning (UP) and landscape design (LD) was not given adequate consideration by planners and designers due to lack of knowledge regarding CC and the efforts that can be taken to mitigate its effects. The objective of this work is:

• To summarize the current state of knowledge of, and conceptualization of, the core elements of CC impacts and responses in Addis Ababa in terms of their implications for UP and LD in the city;

• To develop a common understanding among urban planners and related professionals of how improvements in UP and LD can contribute to CC adaptation; and

• To mainstream CC in future UP and LD endeavors.

The results of this study show that integrating CC adaptation and other response options into UP and LD at the city, subcity/catchment, neighborhood, site/project, and building levels will enhance the sustainability of the city with respect to its resilience to flood risk hazards, water supply during drought periods, and urban heat island effects.
Retention of radiotransmitters tail‐mounted on 6 bird species
Authors: Stanton Richard A. , Burke Alicia D. , Carrlson Kaylan M. , Kesler Dylan C. , Faaborg John , Thompson Frank R.
Published: January 2018

Radiotransmitters can be tail‐mounted using cyanoacrylate glue and an accelerant rather than using a harness. Tail‐mounted transmitters are dropped or shed when the rectrices molt, which may reduce transmitter effects while providing retention times sufficient for most research objectives. However, retention times of tail‐mounted transmitters for birds are insufficiently described, and bias from not following all birds until transmitters are shed has been ignored. We studied transmitter retention of 106 birds of 6 species in the United States of America, 2010–2013, using direct observations and survival modeling based on radiotelemetry tracking. Cox proportional hazard survival models predicted median transmitter retention times from 4 to 53 days, depending on species. Our results suggest that researchers should anticipate premature (i.e., <30 days) tag loss rates from 15% to 38% for adult birds, and adjust permit and funding applications accordingly. However, predicted premature tag loss approached 100% for independent juvenile birds, which frequently appeared to disperse long distances, leading to few or no failure events to inform models. Overall, our results provide guidance for the design of future telemetry studies while demonstrating that tail‐mounting transmitters can yield adequate data for a variety of research objectives. © 2018 The Wildlife Society.
Função e qualidade de vida de pacientes com fratura do planalto tibial operados com placa bloqueada ou convencional: estudo comparativo
Authors: Schröder e Souza Bruno , Leite Thiago , Silva Tarsis , Candido Carlos , de Almeida Felipe , de Oliveira Valdeci
Published: January 2018

Comparar resultados clínicos, funcionais e de qualidade de vida de pacientes com fratura do planalto tibial operados com placa bloqueada ou convencional e comparar os custos hospitalares dos implantes.

Estudo comparativo de coortes transversal, retrospectivo, em uma série consecutiva de pacientes com fratura do planalto tibial tratados cirurgicamente entre agosto de 2015 e junho de 2016. Foram excluídos: menores de 18 anos; indivíduos incapazes de responder os questionários ou de comparecer para reavaliação; politraumatizados ou com lesões associadas no mesmo membro; pacientes não tratados com placa ou conservadoramente. Os autores compararam os custos dos implantes, a qualidade de vida (SF-12), o escore de Lysholm, a escala visual de dor e os parâmetros clínicos e radiográficos.

Foram observadas 45 fraturas no período, das quais 11 foram excluídas. Dos 34 pacientes, dois não compareceram à entrevista (seguimento de 94%). O tempo de seguimento foi 15,1 ± 4,8 meses. O grupo A (placa bloqueada) incluiu 22 pacientes (69%), com custo hospitalar médio dos implantes de R$ 4.125,39 (dp = R$1.634,79/paciente). O grupo B (placa convencional) incluiu dez pacientes (31%), a um custo médio de R$ 438,53 (dp = R$ 161,8/paciente; p < 0,00001). Para os demais parâmetros avaliados, não foram observadas diferenças significativas entre os grupos, exceto por um maior degrau articular no grupo A (2,7 mm ± 3,3 mm vs. 0,5 mm ± 1,6 mm; p = 0,02; TE = 0,90).

O custo dos implantes bloqueados para o tratamento das fraturas do planalto tibial é significativamente superior aos implantes convencionais, embora não tenham apresentado vantagem clínica, radiográfica, funcional ou de qualidade de vida, nos pacientes dessa amostra.
Psychological Attributes of Ultramarathoners
Authors: Buck Katherine , Spittler Jack , Reed Alex , Khodaee Morteza
Published: January 2018

Introduction

As the popularity of ultramarathon participation increases, there still exists a lack of understanding of the unique psychological characteristics of ultramarathon runners. The current study sought to investigate some of the psychological and behavioral factors that are involved in ultramarathon running.

Methods

We obtained information from participants of the Bear Chase Trail Race via an online survey. This race is a single-day, multidistance race consisting of a 10 k, half marathon, 50 k, 50 mi, and 100 k run in Lakewood, Colorado, at a base altitude of 1680 m with total altitude in climbs ranging from 663 to 2591 m. We correlated information from the Exercise Addiction Inventory and the Patient Health Questionnaire-2 and demographic information with race finish times.

Results

Out of 200 runners who started the race, 98 (48%) completed the survey. Over half of the runners were men (61.2%), and the average age was 39.0 years (SD±8.9; range 21–64 years). A number of respondents (20%) screened positive for exercise addiction concerns. Approximately 20% of our sample screened positive for depressive symptoms (Patient Health Questionnaire-2 score >3). The majority of participants reported receiving strong social support from current partners with regard to their ultramarathon running training time and goals.

Conclusions

Although only a screening, the number of positive screens on the Exercise Addiction Inventory suggests use of screening measures with an ultramarathon running population. Athletes with positive screening tests should be fully evaluated for depression and exercise addiction because this would enable appropriate athlete support and treatment referral.
The spontaneous puncture of thick liquid films
Authors: Néel B. , Villermaux E.
Published: January 2018

We call thick those films for which the disjoining pressure and thermal fluctuations are ineffective. Water films with thickness$h$in the$1{-}100~\unicode[STIX]{x03BC}\text{m}$range are thick, but are also known, paradoxically, to nucleate holes spontaneously. We have uncovered a mechanism solving the paradox, relying on the extreme sensitivity of the film to surface tension inhomogeneities. The surface tension of a free liquid film is lowered by an amount$\unicode[STIX]{x0394}\unicode[STIX]{x1D70E}$over a size$a$by chemical or thermal contamination. At the same time this spot diffuses (within a time$a^{2}/D$, with$D$the diffusion coefficient of the pollutant in the substrate), the Marangoni stress$\unicode[STIX]{x0394}\unicode[STIX]{x1D70E}/a$induces an inhomogeneous outward interstitial flow which digs the film within a time$\unicode[STIX]{x1D70F}_{0}\sim \sqrt{\unicode[STIX]{x1D70C}ha^{2}/\unicode[STIX]{x0394}\unicode[STIX]{x1D70E}}$, with$\unicode[STIX]{x1D70C}$the density of the liquid. When the Péclet number$Pe=a^{2}/D\unicode[STIX]{x1D70F}_{0}$is larger than unity, the liquid substrate motion reinforces the surface tension gradient, triggering a self-sustained instability insensitive to diffusional regularisation. Several experimental illustrations of the phenomenon are given, both qualitative and quantitative, including a precise study of the first instants of the unstable dynamics made by controlled perturbations of a Savart sheet at large$Pe$.
OP06 Past Speculations Of Future Health Technologies: What Did They Predict?
Authors: Doos Lucy , Packer Claire , Ward Derek , Simpson Sue , Stevens Andrew
Published: January 2018

INTRODUCTION:

Rapid technological innovation is leading to new health technologies and interventions becoming available to healthcare markets at increasing speed; these often cost more than current alternatives and significantly affect the cost of healthcare services and delivery (1). Identifying future technologies supports service preparedness, long-term planning, and strategic decision making. The aim of this study was to describe and classify health technologies predicted in fifteen forecasting studies according to their type, purpose and clinical use, and relate these to the original purpose and timing of the forecasting studies.

METHODS:

This was a descriptive study of predicted healthcare technologies identified in fifteen forecasting studies included in a previously published systematic review (2). Outcomes related to (i) each forecast study including country, year, intent and forecasting methods used, and (ii) the predicted technology type, purpose, targeted clinical area and forecast timeframe.

RESULTS:

We identified 896 predicted health-related topics, of which 685 were health technologies. Of these, 19.1 percent were diagnostic or imaging tests and 14.3 percent devices or biomaterials; 38.1 percent were intended to treat or manage disease and 21.6 percent to diagnose or monitor disease. The most frequent targeted clinical areas were infectious diseases followed by cancer, circulatory and nervous system disorders. The mean timeframe for technology forecast was 11.6 years (Standard Deviation, SD = 6.6). The forecasting timeframe significantly differed by technology type (p = .002), the intent of the forecasting group (p < .0001), and the methods used (p < .0001).

CONCLUSIONS:

Our description and classification of predicted health-related technologies from prior forecasting studies provides an overview of the technological and clinical frontiers of innovation in health and healthcare provision.
OP21 Involving Clinical Experts In Prioritizing Topics For Health Technology Assessment: A Randomized Controlled Trial
Authors: Cook Andrew , Streit Elke , Davage Gill
Published: January 2018

INTRODUCTION:

The National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme commissions research to inform health services in the United Kingdom. The program prioritises research ideas from literature, guidelines, patients, and clinicians, to decide which research should be funded. We get clinical input on these ideas through (i) committees of clinicians and patients and (ii) seeking written advice from multiple clinicians — a refereeing process. Chairs of our committees suggested that the material we sent to clinicians was too extensive and the method of response too burdensome. We set out to determine whether reducing the information provided or burden of response would improve the engagement of clinicians with our processes, and hence improve the quality of advice provided, and the research available to health services.

METHODS:

We undertook a factorial randomized controlled trial (University of Southampton Faculty of Medicine Ethics Committee #8192, Trial registration: ACTRN12614000167662). Each participant was randomized to receive one of two types of material to comment on, and one of two means to respond. In the first allocation participants were randomised in a 1:1 ratio between receiving a ‘vignette’ (a briefing paper of up to ten pages discussing possible research = usual practice), or a ‘commissioning brief’ (a single page summarising the proposed research). In the second allocation, the method of response was randomized, between a structured form and free text email.

RESULTS:

We randomized 460 clinical experts, and 356 (77.4 percent) responded. The responses were graded for quality on a scale of 0 to 4 (higher scores better). Non-response was scored as 0. Analysis using ANOVA gave results of a structured response scoring .34 points (Standard Deviation, SD .36) over a freeform response (p = .02); and the commissioning brief as .04 points over a vignette (p = .81).

CONCLUSIONS:

This was the first randomized trial to take place inside the secretariat of the HTA program. The difference in quality score between the brief and the vignette allocations was neither statistically nor practically important. The difference between the structured and freeform response was statistically significant, and sufficiently large to be important in practice. While the choice of material to share with clinicians seems unimportant we have shown that it is worth sending a structured response form to experts.
OP40 First Case Of Disinvestment Using Real-World Evidence In Brazil
Authors: de Lemos Livia Pires , Guerra Augusto , Pereira Ramon , Gomes Rosangela , Godói Isabella , Diniz Isabela , Zimmermann Ivan , Santos Marisa , Bennie Marion , Godman Brian , Canuto Vania , Petramale Clarice , Acurcio Francisco
Published: January 2018

INTRODUCTION:

Beta-interferons are used as first-line therapy for relapsing-remitting multiple sclerosis in Brazil. In order to evaluate the possible inferiority of one of the beta-interferons available and support a guideline update, we conducted an eleven-year (January 2000 to December 2010) nationwide real-world performance assessment using the Unified Health System (SUS) databases.

METHODS:

We assessed whether patients using subcutaneous beta-interferon switched treatment, relapsed or died (composite event) earlier than patients using intramuscular beta-interferons. Patients without a dispensing registry longer than three months were censored. We used the Kaplan-Meier method to estimate the cumulative probability of persistence on initial treatment, and compared groups with the Log-rank test. The influence of the drug on the occurrence of event was assessed with Cox proportional hazards analysis.

RESULTS:

The number of patients included was 12,154, and the majority started treatment with subcutaneous beta-interferon-1a (45.7 percent), followed by subcutaneous beta-interferon-1b (27.7 percent) and by intramuscular beta-interferon (26.6 percent). Women represented 73.1 percent and the mean age was 38.93±11.34 years old. The group of patients who used intramuscular beta-interferon switched treatment, relapsed or died earlier (median 47 months; 95 percent Confidence Interval, CI 44–52) than patients using the subcutaneous beta-interferons, (69 months (95 percent CI 64–76) for beta- interferon 1a and 73 (95 percent CI 66–84) months for beta-interferon 1b) (p< .0001 for both comparisons). Accordingly, the use of intramuscular beta-interferon was associated with a higher probability of event (Hazard ratio, HR 1.38; 95 percent CI 1.29-1.48), while the use of the other beta-interferons had a protective effect (1a: HR .86; 95 percent CI .81-.92; 1b: HR .89; 95 percent CI .83-.95).

CONCLUSIONS:

The inferiority of intramuscular beta-interferon found in the real-world corroborates findings from head-to-head studies and systematic reviews conducted by Cochrane and the National Commission for Technology Incorporation in SUS (CONITEC/Brazil). This result led to disinvestment in intramuscular beta-interferon and was the first case of clinical guideline update using real-world evidence in Brazil.
OP77 Identifying Topics For Health Technology Assessment: The German “ThemenCheck Medizin”
Authors: Siering Ulrich , Thys Sarah , Mischke Claudia , Altenhofen Lutz
Published: January 2018

INTRODUCTION:

Clinicians, epidemiologists, economists and other non-medical professions are involved in the production of Health Technology Assessment (HTA) reports. In addition, patients or representatives from patient organizations, as well as the general public, are increasingly involved. In 2015 a new proposal process of topic selection for HTA reports was initiated by German legislation with the aim of more closely involving patients and the general public. The new process has been implemented by the Institute for Quality and Efficiency in Health Care (IQWiG) under the project title “ThemenCheck Medizin” (Topic Check Medicine).

METHODS:

Since July 2016, patients and the general public can propose topics for HTA reports to IQWiG, excluding topics on the assessment of drugs. The proposals are submitted via the IQWiG website www.themencheck-medizin.iqwig.de (available only in German). No specific expertize is required for the submission of a topic. On the basis of the proposals a selection committee (patient representatives appointed by patient organizations legitimized in Germany) choose up to fifteen topics deemed suitable for HTA reports. In 2017 the committe will be extended to include members of the general public. IQWiG makes the final decision on the selection of up to five topics per year for HTA reports.

RESULTS:

In the first proposal phase thirty proposals were submitted. The topics were allocated to the following categories: two for diagnostics; four for teeth; one for skin and hair; four for head and nerves; three for muscles, bones and joints; two for heart and circulation; four for cancer; two for children and adolescents; one for reproductive health and birth; and three for mental and emotional wellbeing. Four topics could not be considered because they either addressed the assessment of drugs or could not be transferred into an HTA question.

CONCLUSIONS:

Through “ThemenCheck Medizin” patients and the general public in Germany can actively be involved in the process of collecting proposals for HTA reports as well as in topic prioritization. The prerequisites for successful implementation were in particular the easy-to-use online form and IQWiG's support of persons submitting topics in their formulation of an HTA question. The integration of a selection committee of patient representatives was shown to be constructive and productive.
OP105 Systematically Reconstructing Trial Context-Role For CLUSTER Searches?
Authors: Booth Andrew , Sutton Anthea , Scope Alison , Leaviss Joanna
Published: January 2018

INTRODUCTION:

Randomized controlled trials (RCTs) of complex interventions are conducted in a context-specific environment. Principal trial reports, with a focus on main results, are unable to document adequately the context for an intervention, for example, word limits. Important context may be included in “sibling studies” (that is, studies conducted alongside the main trial, for example, process evaluations, and qualitative studies (1). This presentation explores (i) to what extent is it possible to use a systematic and parsimonious method to identify sibling studies and (ii) what is the potential value of yield from these studies?

METHODS:

The systematic CLUSTER approach (2) to follow up of index studies (Citations, Lead authors, Unpublished materials, Scholar, Theories, Early examples Related projects) has demonstrated the value of retrieved items in qualitative terms. However, the CLUSTER approach is painstaking and laborious and may be prohibitive within a time-tight Health Technology Assessment (HTA). A streamlined CLUSTER approach, using freely available Publish or Perish Software integrated with Google Scholar and Microsoft Excel, offers an economical way of building up “clusters” of study reports. A case study of a UK National Institute for Health Research (NIHR)-funded HTA on the management of medically unexplained symptoms in primary care, utilizing quantitative and qualitative research studies, is used to examine the practical application of the approach.

RESULTS:

Systematic comparison of yield from sifting with yield from the Publish or Perish software reveals (i) major trials for which corresponding qualitative studies were not previously identified, (ii) qualitative studies identified independently from, and potentially unlinked to, associated trials, (iii) associated trial reports (for example, protocols, feasibility studies, etc), economic evaluations and systematic reviews, and (iv) commentaries and correspondence; all with the potential to enhance understanding of trial context.

CONCLUSIONS:

The potential of the Publish or Perish-enabled CLUSTER approach to identify trials or qualitative studies, through “joining up” and mapping of clusters, potentially missed from separate quantitative/qualitative sift processes, means that it should be considered for any HTA that seeks to integrate quantitative and qualitative studies.
OP108 Health Intervention Assessment Report Adaptation: Tunisian Experience
Authors: Allouche Wafa , Brahem Asma Ben , Ouertatani Hella , Jameleddine Mouna , Grati Hela , Jlassi Khalil , Hammouda Mohamed Ben , Attieh Randa , Asua José , Gutiérrez-Ibarluzea Iñaki , Zghal Khaled
Published: January 2018

INTRODUCTION:

Health Technology Assessment (HTA) reports adaptation process is an important tool for emerging HTA agencies. INASanté (National Instance for Accreditation in Healthcare) has chosen to rely on this approach, to develop its first health intervention assessment report: comparative study of computed tomographic colonography versus standard colonoscopy for colorectal cancer screening.

METHODS:

Following consultations with healthcare professionals, the PICO question related to the colorectal cancer screening issue in Tunisia was determined. A literature search strategy covering 10 years (2006-2016) was carried out. Several databases including HTA on the net were explored. Then two independent reviewers conducted literature screening and realized a PRISMA flow diagram. Full text selected reports were submitted to three critical appraisal tools: PRISMA checklist, INAHTA checklist and Critical Appraisal Tools (FLC 2.0). The EUnetHTA adaptation toolkit was used to determine reports adaptability by assessing relevance, reliability and transferability. A structured study of the Tunisian context based on a qualitative data analysis was elaborated. The data synthesis and reporting were finalized with the contribution of a working group. Then an external peer review was conducted before the report dissemination.

RESULTS:

Eighty reports were screened to finally retain four eligible. After a critical appraisal performed by two independent reviewers, two reports from the Canadian Agency for Drug and Technolgies in Healthcare and AETSA were selected to be assessed using the EUnetHTA adaptation toolkit. Regarding transferability criteria, the second report was retained. The context study has consisted in a qualitative analysis of seventeen individual interviews with healthcare professionals involved in colorectal cancer screening issues and an up to date Tunisian literature review. The final adapted report was a combination between relevant extracted data from AETSA report and synthesis of the Tunisian context analysis.

CONCLUSIONS:

This HTA report represents a tool for policy makers to establish the appropriate colorectal cancer screening program for the Tunisian context. HTA reports adaptation process is the best way to give evidence on emerging technologies without wasting time and resources.
OP110 Survey Of Health Technology Assessment Evaluation Strategies For Patient And Public Involvement
Authors: Weeks Laura , Polisena Julie , Scott Anna , Holtorf Anke-Peggy , Staniszewska Sophie , Facey Karen
Published: January 2018

INTRODUCTION:

Although there is increased awareness of patient and public involvement (PPI) among Health Technology Assessment (HTA) organizations, evaluations of PPI initiatives are relatively scarce. Our objective as members of HTAi's Patient and Citizen Involvement Group (PCIG) was to advance understanding of the range of evaluation strategies adopted by HTA organizations and their potential usefulness.

METHODS:

In March 2016, a survey was sent to HTA organizations through the International Network of Agencies for Health Technology Assessment (INAHTA) and contacts of members of HTAi's PCIG. Respondents were asked about their organizational structure; how patients and members of the public are involved; whether and how PPI initiatives have been evaluated, and, if so, which facilitators and challenges to evaluation were found and how results were used and disseminated.

RESULTS:

Fifteen programs from twelve countries responded that involved patient (14/15) and members of the public (10/15) in HTA activities. Seven programs evaluated their PPI activities, including participant satisfaction (5/7), process evaluations (5/7) and impact evaluations (4/7). Evaluation results were used to improve PPI activities, identify education and training needs, and direct strategic priorities. Facilitators and challenges revolved around the need for stakeholder buy-in, sufficient resources, senior leadership, and including patients in evaluations. Participants also provided suggestions based on their experiences for others embarking on this work, for example including patients and members of the public in the process.

CONCLUSIONS:

We identified a small but diverse set of HTA organizations internationally that are evaluating their PPI activities. Our results add to the limited literature by documenting a range of evaluation strategies that reflect the range of rationales and approaches to PPI in HTA. It will be important for HTA organizations to draw on formal evaluation theories and methods when planning future evaluations, and to also share their approaches and experiences with evaluation.
OP116 Cost-Effectiveness Of Sacubitril/Valsartan In Heart Failure
Authors: Lin Liang , Aziz Mohamed Ismail Abdul , Wu David Bin-Chia , Ng Kwong
Published: January 2018

INTRODUCTION:

Heart failure (HF) is a major public health problem worldwide and in Asia. Sacubitril/valsartan reduces cardiovascular death and hospitalizations for HF. However, decision makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of current standard of care.

METHODS:

Using a Markov model, we projected lifetime clinical and economic outcomes of sacubitril/valsartan versus enalapril for 66-year-old patients with HF in Singapore. Key health states included New York Heart Association (NYHA) classes; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Probabilities of events were based on the PARADIGM-HF trial. The uncertain treatment effect of sacubtril/valsartan in Asian patients was modelled using a hazard ratio (HR) of 1 as upper limit in sensitivity analyses. Utilities were obtained from published literature. Local national epidemiological and cost data were applied. Analyses were conducted from the Singapore healthcare payer's perspective. Both one-way and Probabilistic Sensitivity Analyses (PSA) based on 10,000 Monte Carlo simulations were performed.

RESULTS:

Compared to enalapril, sacubitril/valsartan was associated with an incremental cost-effectiveness ratio (ICER) of SGD74k (USD52k) per quality-adjusted life year (QALY) gained. The cost-effectiveness of sacubitril/valsartan was highly dependent on its effectiveness in reducing the risk of cardiovascular death. However, this was uncertain, particularly in the Asian subgroup, where results were not statistically significant. In sensitivity analyses using results from Asian patients, the ICERs ranged from SGD41k (USD30k) to SGD1.3 million (USD 0.94 million) per QALY gained. PSA showed the probability of sacubitril/valsartan being cost-effective was below 1 percent, 12 percent and 71 percent at thresholds of SGD20k (USD14k), SGD50k (USD36k) and SGD100k (USD 72k) per QALY gained, respectively.

CONCLUSIONS:

Given the uncertain ICER, sacubtril/valsartan may not provide good value for money compared to enalapril in reducing cardiovascular morbidity and mortality in patients with HF at the current daily cost. Our study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering HF therapy.
OP138 Access To Orphan Drugs In The United Kingdom And Other European Countries
Authors: Zamora Bernarda , Garau Martina , Maignen François , O'Neill Phill , Mestre-Ferrandiz Jorge
Published: January 2018

INTRODUCTION:

Under the Orphan Regulation, the European Medicines Agency (EMA) intended to incentivize the research and development of new treatments for rare and life-threatening conditions. Marketing authorisation of orphan medicinal products (OMPs) by the EMA is only the first step, as medicines are made available to patients when reimbursement or Health Technology Assessment (HTA) decisions are implemented by national health systems. We analyzed the availability and access to OMPs in the United Kingdom (UK), France, Germany, Italy and Spain. We compared the availability, which is the possibility to prescribe a given OMP, to the access, which refers to the full or partial reimbursement by the public health service.

METHODS:

We collected data on launches, HTA decisions, any centralized commissioning and/or reimbursement decision for all the OMPs authorised since 2000 in the UK countries (England, Scotland and Wales), France, Germany, Italy and Spain.

RESULTS:

Since the Orphan Regulation inception, the EMA granted marketing authorization to 143 OMPs. These OMPs are most widely accessible in Germany and France. Reimbursement in Germany is immediate after authorization. France and Italy present a delay of 19 months from authorization to reimbursement, which is shorter than in other countries. In England, less than 50 percent of centrally authorised OMPs are routinely funded by the National Health Service (NHS), including one-third of these recommended by the National Institute for Health and Care Excellence (NICE), and those reimbursed via commissioning policies and the Cancer Drugs Fund.

CONCLUSIONS:

The assessment of degree of access to OMPs across Europe is limited by differences in the national HTA and reimbursement systems and the heterogeneous information made publicly available on their decisions. Nonetheless, our study suggests that the primary purpose to grant equal availability to OMPs to the patients in the Eropean Union via the implementation of the orphan regulation was partially achieved with important variations of access observed across the countries included in our study.
PP023 Applying Oncology Patient Registries As A Health Technology Assessment Tool
Authors: Kostyuk Alexander , Kostyuk Alexandr , Akanov Amangali
Published: January 2018

INTRODUCTION:

The limited healthcare resources have to be invested efficiently; Health Technology Assessment (HTA) is applied ever more often in many health care systems for “rational decision-making”. The oncology patient registries (OPR) track the eligibility of patients and the complete flow of treatments, guaranteeing appropriateness in use of pharmaceutical products, according to approved indications.

METHODS:

Normative legal acts and other regulatory documents in the field of oncology medical and pharmaceutical activity, include content and maintenance oncology registries. The system, process and information analysis, direct observation, comparative analysis, logical modelling, sociological methods (surveys and expert opinions) are applied.

RESULTS:

A temporary coverage/funding of oncology drugs often requires additional collection of data on safety, effectiveness, cost-effectiveness, and the appropriate use of the drug. Many of the oncology drugs show little or marginal effectiveness at time of approval and reimbursement agencies demand further data before deciding whether to cover the new drug. Pragmatic clinical trials, patient access schemes and standard data requirements on patient relevant outcomes in OPR are some of the approaches to generate further evidence and to fill the gap between knowledge on efficacy at time of approval and demanded knowledge on effectiveness for coverage decisions. For each monitored drug, patients eligible for treatment are registered in the specific therapeutic indication dynamic monitoring database to collect epidemiologic and clinical data, including data on the safety profile, and ex-post information missing at first evaluation stage.

CONCLUSIONS:

OPR provide a detailed view of the morbidity, mortality and resource utilization associated with an oncologies diseases entity. This data is of prime importance in coming to decisions on coverage of a drug or treatment. The collation of information is also quick and efficient owing to better methods of data management. OPR of Kazakhstan are equipped with sophisticated data processing software and technologies.
PP030 Socioeconomics Of Cardiac Rehabilitation: A Meta-Analysis
Authors: Ge Yin , Takura Tomoyuki , Nozomi Ebata
Published: January 2018

INTRODUCTION:

The Guidelines for Rehabilitation in Patients with Cardiovascular Disease recommends convalescent cardiac rehabilitation (CR) as the standard treatment for patients with ST elevation myocardial infarction (STEMI) (class I, evidence level B) (1). However, health economic evaluation of cardiac rehabilitation (CR) is limited.

METHODS:

This systematic review, meta-analysis study elucidated the cost-effectiveness of CR in the short term. The target population in this study included convalescent and comprehensive CR patients with coronary artery disease (CAD), most with myocardial infarction (MI). We used mortality, life years (LY, expected life years), medical costs, and cost-effectiveness as the evaluation parameters in this analysis. We set medical costs in the analysis associated with testing, diagnosis, and treatment during the observation period related to CR. For cost-effectiveness analysis, we analyzed medical cost per LY. We examined the differences in effects for two comparisons (CR versus Usual Care, UC) using the Risk Ratio (RR) and Standardized Mean Difference (SMD). We assumed the standard deviation (SD) of cost effectiveness in this study by applying the error propagation.

RESULTS:

We reviewed fifty-nine studies and identified three that matched our selection criteria. The studies had the following characteristics: two randomized clinical trials and one systematic review/meta-analysis; a control that does not include exercise in patients with CAD; an observation period longer than 1 year; adapting medical costs, LY, cost/LY, and mortality as the evaluation index. In total, 129,272 patients were included. Meta-analysis results revealed that the CR arm significantly improved LY (SMD: -.78, 95 percent Confidence Interval (CI): -1.37, -.19) compared with UC. Similar to LY, the CR arm significantly improved the mortality (SMD: .57, 95 percent CI: .22, 1.47) compared with UC arm. Since medical costs showed a high tendency (SMD:.02, 95 percent CI: -.08, .13), cost/LY demonstrated no improvement (SMD: .00; 95 percent CI: -.17, .18). Substantial statistical heterogeneity was observed between the studies with respect to LY and cost/LY.

CONCLUSIONS:

While sufficient evidence to conclude health economic efficiency is not available at present, these results suggest that CR is not potentially cost-effective in the short term.
PP086 Horizon Scanning In Multiple Sclerosis Decisions In Brazil
Authors: de Souza Andrea Brígida , Vidal Avila , Gomes Pollyanna , Canuto Vania , Petramale Clarice
Published: January 2018

INTRODUCTION:

In Brazil, the pharmaceutical sector has requested an individual incorporation in the Brazilian public health system (SUS) for each new drug for multiple sclerosis that receives sanitary authorization for marketing. Horizon Scanning within Brazilian Ministry of Health has played a key role in the recommendations made by the National Committee for Health Technology Incorporation (CONITEC). Horizon Scanning seeks to predict which technologies have potential to impact health care in SUS, before their formal request. This study aims to present the impact of horizon scanning in two assessments made by CONITEC on drugs to treat Multiple Sclerosis.

METHODS:

Grey literature was searched to find new and emerging drugs for multiple sclerosis treatment. Regulatory agencies were also searched: European Medicines Agency (EMA), Food and Drug Administration (FDA) and Brazilian Regulation and Health Surveillance Agency (Anvisa). A pre-defined standardized form was used. Information extracted about each drug was identified as: drugs name, mechanism of action, indication, administration route, finished phases of clinical trial and registration in other countries.

RESULTS:

In 2014, horizon scanning identified seven drugs while CONITEC was assessing Fingolimod for multiple sclerosis. In this case, the drug's administration route was a differential, as only three new drugs identified were also orally administrated. Thus, Fingolimod received a positive recommendation for incorporation. In 2016, horizon scanning identified fourteen drugs while Teriflunomide was under assessment. At this moment, the orally administrated Fingolimod was already available and it was identified other eight new drugs with the same route. Therefore, the initial recommendation was against its incorporation.

CONCLUSIONS:

Horizon scanning has proved to be of major importance for assisting recommendation-making process of the committee. In the two cases presented, horizon scanning information could predict which technologies were being developed and could be registered in Brazil. These new technologies had influenced the recommendations made by CONITEC's members. As a result, a horizon scanning section in all CONITEC's reports became mandatory.
PP094 Autologous Stem Cell Transplantation For Multiple Sclerosis
Authors: Giske Liv , Frønsdal Katrine , Lauvrak Vigdis , Stoinska-Schneider Anna , Fure Brynjar
Published: January 2018

INTRODUCTION:

Multiple Sclerosis (MS) is an inflammatory neurological disease. The standard treatment is disease modifying drugs which may alleviate symptoms and slow the progress of disability, but not lead to remission. Autologous Hematopoetic Stem Cell Transplantation (AHSCT) is a new technology for treatment of MS in Norway. Disease remission in some patients treated with AHSCT has been postulated, in particular in patients in the early course of disease with high disease activity classified as having Relapsing-remitting multiple sclerosis (RRMS), but severe complications have also been reported.

METHODS:

We conducted a systematic literature search. No restrictions were set in terms of study design, although case series should include at least ten patients with a majority having RRMS. We performed a cost analysis from a healthcare perspective with a time frame of one year.

RESULTS:

One randomized controlled trial (RCT) (n = 21, RRMS = 7), one registry study (n = 345), and seven case series (n = 442, RRMS = 277) without control groups were included. Estimated transplant-related mortality was 2 percent or lower. Serious adverse events, such as infections, were common during follow-up. Stabilization or improvement in neurological status was reported in 63 percent to 89 percent of the patients after three years, and the number of Gd+ and T2 lesion volume assessed by Magnetic Resonance Imaging was reduced. The quality of evidence assessed using the “Grading of Recommendation Assessment, Development, and Evaluation” tool was low for transplant-related mortality and very low for the other outcomes. HSCT costs were approximately between 480,000 and 605,000 Norwegian kroner per patient in the intervention year. A heterogeneous disease progression, significant risks associated with the method, lack of effective treatment options, and uncertainty about the benefit versus risk, implies that any decision to offer HSCT in the treatment of MS is ethically challenging.

CONCLUSIONS:

The main limitation in this HTA is the absence of controlled studies, which introduces a high risk of bias. Studies without control groups, including mainly patients with RRMS, reported that disease activity could be delayed or stopped for a period of up to three years in several patients, whereas adverse events were common. Ethical considerations are associated with significant uncertainty of benefit versus harm. The low level of evidence implies the need for controlled trials.