bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Study of Long‐Term Interrelationships Among Adiposity‐Associated Biomarkers in Women
Authors: Baden Megu Y. , Hu Frank B. , Huang Tianyi
Published: December 2019

Objective

This study aimed to investigate the prospective interrelationships among biomarkers that may provide mechanistic insights into obesity‐related diseases.

Methods

A total of 850 women in the Nurses’ Health Study II with two fasting blood measurements (1996‐1999 and 2010‐2011) of adiponectin, leptin, soluble leptin receptor, insulin, retinol‐binding protein 4, high‐sensitivity C‐reactive protein (hsCRP), and interleukin‐6 were included. Biomarker interrelationships were examined in the following three ways: (1) cross‐sectional associations at baseline and follow‐up, (2) longitudinal associations of concurrent biomarker changes, and (3) prospective associations of each baseline biomarker with other biomarker changes.

Results

In cross‐sectional analyses, most biomarkers were correlated after multivariable adjustment including BMI, with the strongest correlations observed between leptin and insulin and between hsCRP and interleukin‐6. In longitudinal analyses, similar results were observed after multivariable adjustment including weight change. However, in prospective analyses, only three associations observed in cross‐sectional and longitudinal analyses were consistently significant (P < 0.05). Every doubling in baseline adiponectin was associated with −9.0% insulin change. The corresponding estimate was 9.3% for baseline leptin and hsCRP change and 3.1% for baseline hsCRP and leptin change.

Conclusions

Baseline adiponectin concentrations were inversely associated with subsequent insulin change, whereas baseline leptin concentrations were positively associated with hsCRP change and vice versa.
Experimental Evidence on the Impacts of Need‐Based Financial Aid: Longitudinal Assessment of the Wisconsin Scholars Grant
Authors: Anderson Drew M. , Broton Katharine M. , Goldrick‐Rab Sara , Kelchen Robert
Published: December 2019

We conduct the first long‐term experimental evaluation of a need‐based financial aid program, the privately funded Wisconsin Scholars Grant. Over multiple cohorts, the program failed to increase degree completion and graduate school enrollment up to 10 years after matriculation. The program did reduce time‐to‐degree for some students and modestly increased the number of STEM degrees earned. The lack of robust effects raises important questions about the conditions necessary for financial aid to benefit students.
Synthesis, characterization, and ionic conductivity of electrospun organic–inorganic hybrid gel electrolytes
Authors: Aytan Emre , Uğur Mustafa H. , Kayaman‐Apohan Nilhan
Published: December 2019

In this work, we described the synthesis of organic–inorganic hybrid gel electrolytes combining electrospinning, sol–gel, and ultraviolet (UV) curing techniques in order to investigate their ionic conductivity properties. First, 3‐glycidyloxypropyl trimethoxysilane modified polyamic acid and alkoxysilane functional poly(dimethyl siloxane) were electrospun together. Then, the following thermal imidization, the obtained fiber was cured in the UV curable gel formulation. To improve the interaction between fiber and gel matrix, 3‐(trimethoxysilyl)propyl methacrylate was partly hydrolyzed and then used as a bifunctional crosslinker. Finally, the membrane was soaked into 0.5 M LiFP6 salt solution to obtain organic–inorganic hybrid gel electrolytes. The chemical structure, ionic conductivity, and range of electrochemical stability window of the photocured nanocomposite electrolytes were investigated by using FTIR, thermogravimetric analysis, differential scanning calorimetry, electrochemical impedance spectroscopy, linear sweep voltammetry, and SEM analysis. The acquired results from experiments indicate that a convenient nanocomposite electrolyte for lithium‐ion batteries with high electrolyte (Li salt) uptake, adequate conductivity (1.02 × 10−3 S cm−1) at ambient temperature and electrochemically stable between 1 and 6 V had been prepared. POLYM. ENG. SCI., 60:619–629, 2020. © 2019 Society of Plastics Engineers
The regulation of ZCT1, a transcriptional repressor of monoterpenoid indole alkaloid biosynthetic genes in Catharanthus roseus
Authors: Mortensen Samuel , Weaver Jessica D. , Sathitloetsakun Suphinya , Cole Lauren F. , Rizvi Noreen F. , Cram Erin J. , Lee‐Parsons Carolyn W. T.
Published: December 2019

Cys2/His2‐type (C2H2) zinc finger proteins, such as ZCT1, are an important class of transcription factors involved in growth, development, and stress responses in plants. In the medicinal plant Catharanthus roseus, the zinc finger Catharanthus transcription factor (ZCT) family represses monoterpenoid indole alkaloid (MIA) biosynthetic gene expression. Here, we report the analysis of the ZCT1 promoter, which contains several hormone‐responsive elements. ZCT1 is responsive to not only jasmonate, as was previously known, but is also induced by the synthetic auxin, 1‐naphthalene acetic acid (1‐NAA). Through promoter deletion analysis, we show that an activation sequence‐1‐like (as‐1‐like)‐motif and other motifs contribute significantly to ZCT1 expression in seedlings. We also show that the activator ORCA3 does not transactivate the expression of ZCT1 in seedlings, but ZCT1 represses its own promoter, suggesting a feedback mechanism by which the expression of ZCT1 can be limited.
Structural characterization of aminoglycoside 4′‐O‐adenylyltransferase ANT(4′)‐IIb from Pseudomonas aeruginosa
Authors: Semper Cameron , Stogios Peter , Meziane‐Cherif Djalal , Evdokimova Elena , Courvalin Patrice , Savchenko Alexei
Published: December 2019

Aminoglycosides were one of the first classes of broad‐spectrum antibacterial drugs clinically used to effectively combat infections. The rise of resistance to these drugs, mediated by enzymatic modification, has since compromised their utility as a treatment option, prompting intensive research into the molecular function of resistance enzymes. Here, we report the crystal structure of aminoglycoside nucleotidyltransferase ANT(4′)‐IIb in apo and tobramycin‐bound forms at a resolution of 1.6 and 2.15 Å, respectively. ANT(4′)‐IIb was discovered in the opportunistic pathogen Pseudomonas aeruginosa and conferred resistance to amikacin and tobramycin. Analysis of the ANT(4′)‐IIb structures revealed a two‐domain organization featuring a mixed β‐sheet and an α‐helical bundle. ANT(4′)‐IIb monomers form a dimer required for its enzymatic activity, as coordination of the aminoglycoside substrate relies on residues contributed by both monomers. Despite harbouring appreciable primary sequence diversity compared to previously characterized homologues, the ANT(4′)‐IIb structure demonstrates a surprising level of structural conservation highlighting the high plasticity of this general protein fold. Site‐directed mutagenesis of active site residues and kinetic analysis provides support for a catalytic mechanism similar to those of other nucleotidyltransferases. Using the molecular insights provided into this ANT(4′)‐IIb‐represented enzymatic group, we provide a hypothesis for the potential evolutionary origin of these aminoglycoside resistance determinants.
Critical realism and complexity theory: Building a nonconstructivist systems research framework for effective governance analysis
Authors: Yang Yi
Published: December 2019

Complexity theory (CT) intends to reveal public management's unpredictable side but its empirical applications are scarce due to prevailing constructivist approaches that collapse larger systematic outcomes into micro agent actions and conflate them into movements of co‐constitution and co‐evolution, precluding effective analysis. How can we capture emergent properties and outcomes if we cannot delineate objects and subjects? How can we attribute causes and effects without fixed, stable entities? To address this significant weakness of theorization for a more effective CT framework, Margaret Archer's critical realist model solves this constructivist conflation dilemma—agents and systems, though interrelated, are distinct and stable entities—public management and governance process is thus the result of emergence from a learning‐to‐control process for rule‐makers, with structurally unpredictable inputs from the ruled whereby systematic features predate and condition (Time 1) individual actions, which can maintain or reproduce them (Time 3) during agent–system interactive processes (Time 2).
Outcomes with respect to extent of surgical resection for pediatric atypical teratoid rhabdoid tumors
Authors: Richards Alexandra , Ved Ronak , Murphy Christopher , Hennigan Dawn , Kilday John-Paul , Kamaly-Asl Ian , Mallucci Conor , Bhatti Imran , Patel Chirag , Leach Paul
Published: December 2019

Purpose

To evaluate overall survival for atypical teratoid rhabdoid tumors (ATRTs) in relation to extent of surgical resection.

Methods

The neurosurgical tumor databases from three UK Pediatric centers (University Hospital of Wales, Alder Hey and Royal Manchester Children’s Hospital) were analyzed. Patients with a diagnosis of ATRT were identified between 2000 and 2018. Data was collected regarding demographics, extent of resection, complications, and overall survival.

Results

Twenty-four patients diagnosed with ATRT underwent thirty-eight operations. The age range was 20 days to 147 months (median 17.5 months). The most common location for the tumor was the posterior fossa (nine patients; 38%). Six patients (25%) underwent a complete total resection (CTR), seven (29%) underwent a near total resection (NTR), eight (33.3%) underwent a subtotal resection (STR), and three patients (12.5%) had biopsy only. Two-thirds of patients who underwent a CTR are still alive, as of March 2019, compared to 29% in the NTR and 12.5% in the STR groups. Out of the thirty-eight operations, there were a total of twenty-two complications, of which the most common was pseudomeningocele (27%). The extent of surgical resection (p = 0.021), age at surgery (p = 0.00015), and the presence of metastases at diagnosis (0.015) significantly affected overall survival.

Conclusions

Although these patients are a highly vulnerable group, maximal resection is recommended where possible, for the best chance of long-term survival. However, near total resections are likely beneficial when compared with subtotal resections and biopsy alone. Maximal surgical resection should be combined with adjuvant therapies for the best long-term outcomes.
Is the subtropical jet shifting poleward?
Authors: Maher Penelope , Kelleher Michael E. , Sansom Philip G. , Methven John
Published: December 2019

The tropics are expanding poleward at about $$0.5{^\circ }$$0.5∘ per decade in observations. This poleward expansion of the circulation is consistently reported using Hadley cell edge metrics and lower-atmospheric tropical edge metrics. However, some upper-atmospheric tropical metrics report smaller trends that are often not significant. One such upper-atmospheric metric is the subtropical jet latitude, which has smaller trends compared to the Hadley cell edge. In this study we investigate the robustness of the weak trends in the subtropical jet position by introducing a new method for locating the subtropical jet, and examining the trends and variability of the subtropical jet latitude. We introduce the tropopause gradient method based on the peak gradient in potential temperature along the dynamic tropopause. Using this method we find the trends in the subtropical jet latitude are indeed much smaller than $$0.5{^\circ }$$0.5∘ per decade, consistent with previous studies. We also find that natural variability within the subtropical jet latitude would not prevent trends from being detected if they were similar to the Hadley cell edge, as trends greater than 0.24$${^\circ }$$∘ per decade could reliably be detected using monthly data or 0.09$${^\circ }$$∘ per decade using daily data. Despite the poleward expansion of the tropics, there is no robust evidence to suggest the subtropical jet is shifting poleward in either hemisphere. Neither the current diagnostic methods nor natural variability can account for the small subtropical jet trends. The most likely explanation, which requires further investigation, is that the subtropical jet position is not tied dynamically to the Hadley cell edge.
Once bitten, twice shy? Lessons learned from an experiment to liberalize price regulations for dental care
Authors:   ADVOCATE Consortium, Trescher Anna-Lena , Listl Stefan , van der Galien Onno , Gabel Frank , Kalmus Olivier
Published: December 2019

In 2012, The Netherlands established the so-called “free market experiment”, which allowed providers of dental care to set the prices for their dental services themselves. The introduction of market mechanisms is intended to improve the quality of care and to contribute to cost containment, but increasing health expenditures for citizens have been observed in this context. Using large-volume health insurance claims data and exploiting the 2012 experiment in Dutch dental care, we identified the effects of a liberalization of service prices. Using pooled regression with individual fixed effects, we analyzed changes in utilization patterns of prevention-oriented dental services in response to the experiment as well as the elasticities in demand in response to variations in out-of-pocket (OOP) prices. We found substantial increases in prices and patients’ OOP contributions for dental services following the liberalization with differences in increases between types of services. In response to the experiment, the proportion of treatment sessions containing preventive-oriented services decreased significantly by 3.4% among adults and by 5.3% for children and adolescents. Estimates of short-run price elasticities of demand for different services point towards differences in price sensitivity. One potential explanation for the observed variations in prices and utilization could be different extents of asymmetric information for first-stage and follow-on services. Price liberalization seems to have affected the composition of treatment sessions towards a decreasing use of preventive services, suggesting a shift in the reason for seeing a dental care provider from a regular-preventive perspective to a symptom-based restorative approach.
The early detection of and rapid response (EDRR) to invasive species: a conceptual framework and federal capacities assessment
Authors: Reaser Jamie K. , Burgiel Stanley W. , Kirkey Jason , Brantley Kelsey A. , Veatch Sarah D. , Burgos-Rodríguez Jhoset
Published: December 2019

Globalization necessitates that we address the negative externalities of international trade and transport, including biological invasion. The US government defines invasive species to mean, “with regard to a particular ecosystem, a non-native organism whose introduction causes, or is likely to cause, economic or environmental harm, or harm to human, animal, or plant health.” Here we address the role of early detection of and rapid response to invasive species (EDRR) in minimizing the impact of invasive species on US interests. We provide a review of EDRR’s usage as a federal policy and planning term, introduce a new conceptual framework for EDRR, and assess US federal capacities for enacting well-coordinated EDRR. Developing a national EDRR program is a worthwhile goal; our assessment nonetheless indicates that the federal government and its partners need to overcome substantial conceptual, institutional, and operational challenges that include establishing clear and consistent terminology use, strategically identifying and communicating agency functions, improving interagency budgeting, facilitating the application of emerging technologies and other resources to support EDRR, and making information relevant to EDRR preparedness and implementation more readily accessible. This paper is the first in a special issue of Biological Invasions that includes 12 complementary papers intended to inform the development and implementation of a national EDRR program.
Lessons in Casual Sex: Narratives of Young Swedish Women
Authors: Tholander Michael , Tour Ninni
Published: December 2019

This study focuses on the narratives of four young Swedish women who were interviewed about their experiences of heterosexual casual sex. The analyses are based on a phenomenological approach and provide insight into a highly complex sexual practice, which the participants often portray as having lacked transparent communication, balance of power, and satisfying sex—three key dimensions of an everyday “sexual democracy.” However, the participants also claim to have dealt with these problematic issues, hence pointing to the socializing role that early sexual experiences have for young women. Thus, if the participants’ own perspectives of events are accepted, sexual empowerment might best be understood as individually colored, experience-based, developmental processes rather than as something that is brought about primarily through collective, formal sex education.
Controllable drilling parameter optimization for roller cone and polycrystalline diamond bits
Authors: Darwesh Ali K. , Rasmussen Thorkild M. , Al-Ansari Nadhir
Published: December 2019

Oil well drilling data from 23 oil wells in northern Iraq are analyzed and optimized controllable drilling parameters are found. The most widely used Bourgoyne and Young (BY) penetration rate model have been chosen for roller cone bits, and parameters were extracted to adjust for other bit types. In this regard, the collected data from real drilling operation have initially been averaged in short clusters based on changes in both lithology and bottom hole assemblies. The averaging was performed to overcome the issues related to noisy data negative effect and the lithological homogeneity assumption. Second, the Dmitriy Belozerov modifications for polycrystalline diamond bits compacts have been utilized to correct the model to the bit weight. The drilling formulas were used to calculate other required parameters for the BYM. Third, threshold weight for each cluster was determined through the relationship between bit weight and depth instead of the usual Drill of Test. Fourth, coefficients of the BYM were calculated for each cluster using multilinear regression. Fifth, a new model was developed to find the optimum drill string rotation based on changes in torque and bit diameter with depth. The above-developed approach has been implemented successfully on 23 oil wells field data to find optimum penetration rate, weight on bit and string rotation.
Boosting High-Rate Zinc-Storage Performance by the Rational Design of Mn2O3 Nanoporous Architecture Cathode
Authors: Feng Danyang , Gao Tu-Nan , Zhang Ling , Guo Bingkun , Song Shuyan , Qiao Zhen-An , Dai Sheng
Published: December 2019

Manganese oxides are regarded as one of the most promising cathode materials in rechargeable aqueous Zn-ion batteries (ZIBs) because of the low price and high security. However, the practical application of Mn2O3 in ZIBs is still plagued by the low specific capacity and poor rate capability. Herein, highly crystalline Mn2O3 materials with interconnected mesostructures and controllable pore sizes are obtained via a ligand-assisted self-assembly process and used as high-performance electrode materials for reversible aqueous ZIBs. The coordination degree between Mn2+ and citric acid ligand plays a crucial role in the formation of the mesostructure, and the pore sizes can be easily tuned from 3.2 to 7.3 nm. Ascribed to the unique feature of nanoporous architectures, excellent zinc-storage performance can be achieved in ZIBs during charge/discharge processes. The Mn2O3 electrode exhibits high reversible capacity (233 mAh g−1 at 0.3 A g−1), superior rate capability (162 mAh g−1 retains at 3.08 A g−1) and remarkable cycling durability over 3000 cycles at a high current rate of 3.08 A g−1. Moreover, the corresponding electrode reaction mechanism is studied in depth according to a series of analytical methods. These results suggest that rational design of the nanoporous architecture for electrode materials can effectively improve the battery performance.
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An Introduction: International Law as Instrument
Authors: Ingber Rebecca , Jain Neha , Moloo Rahim
Published: December 2019

Discussions of international law often focus on questions of constraint and prohibition. This year's Annual Meeting considered the role of international law as an instrument. Actors on the international stage use a variety of tools to address their concerns, from climate change to economic development; from humanitarian crises to cross-border disputes; from commercial regulation to global trade. Governments and international organizations employ diplomacy and coercion, corporations use negotiation and persuasion, and non-governmental organizations engage in fact-finding and advocacy. And all of these actors affect and are affected by international law and use the international legal system to effectuate change and solve problems.
Cold War I, Post-Cold War, and Cold War II: The Overarching Contexts for Peacekeeping, Human Rights, and NATO
Authors: Doyle Michael
Published: December 2019

Peacekeeping, human rights, and the North Atlantic Treaty Organization (NATO) have flourished in complementary contrast with each other. Their relationship has reflected the constraints and opportunities provided by three geopolitical eras since World War II. The first (the first Cold War) began in about 1948 and lasted until 1988; the second (the Post-Cold War Liberal Primacy) ran from 1989 to around 2012; finally, since 2012 the world has been threatened with the emergence of a second Cold War.
Beyond National Jurisdiction: Cyberspace
Authors: Keitner Chimène I.
Published: December 2019

The signature topic of “beyond national jurisdiction” stems from the recognition that there are still significant governance gaps in the international legal system. Given that human activity is now extending into different geographic areas as well as into the “virtual environment” of cyberspace, the need arises to coordinate and potentially to regulate such activity.
Background: Introductory Remarks by Jeannette M.E. Tramhel
Authors: Tramhel Jeannette M.E.
Published: December 2019

This is a panel on agricultural trade; but it is not just a trade law panel. As has been clearly recognized in the 2030 Agenda for Sustainable Development, the Sustainable Development Goals (SDGs) are “integrated and indivisible.” Lawyers, too, are called upon to look at these complex issues through an integrated lens. Accordingly, although this panel will examine SDG #2 through the lens of trade, we will attempt to do so using an integrated and holistic perspective. After providing the contextual background, the panel will consider first, the role of export subsidies and the importance of their elimination and secondly, the broader implications of trade for food security and the actualization of SDG #2.
Remarks by Christina Cerna
Authors: Cerna Christina
Published: December 2019

I am pleased and honored to be chairing this panel this morning. Regrettably, Fatsah Ouguergouz of the African Court of Human and Peoples' Rights had a death in the family and had to travel to Algeria and could not be with us today.
Introductory Remarks by Cora True-Frost
Authors: True-Frost Cora
Published: December 2019

Good afternoon, and welcome! Before we opened this panel, in an informal survey, a few of our audience members shared that they have had experience working with disability issues. The central inquiry of this panel is how disability currently is integrated into international law, and what changes are underway.
North American Humanitarian Response Initiative: DRR and Response Preparedness
Authors: Bookmiller Kirsten Nakjavani
Published: December 2019

It is a privilege to be with you today here at ASIL, in my current capacity as a Project Lead with the North American Humanitarian Response Initiative (NAHRI). At the heart of my comments today are essentially two main themes. First, all of our Initiative efforts over the past twenty-four months remain deeply intertwined with the ethic of Sendai and continue to be so. Second, while I hesitate to use the word “law” when I am working within the project—it can make those who are not in law a bit nervous—you will see with regard to NAHRI that the fundamental challenges that we have been attempting to work through are in fact legal challenges, and in the end I believe the solutions are also legally based. It is within this spirit that I will give my presentation.
Adjudicating States’ International Climate Change Obligations Before International Courts and Tribunals
Authors: Henin Paula F.
Published: December 2019

States have undertaken increasingly ambitious climate change mitigation and adaptation commitments under the United Nations Framework Convention on Climate Change (UNFCCC)1 and instruments adopted thereunder, notably the 1997 Kyoto Protocol2 and the 2015 Paris Agreement.3
The Dynamics of International Dispute Resolution Business in the Belt and Road
Authors: Gu Weixia
Published: December 2019

China's Belt and Road Initiative (BRI) ambitiously aspires toward expanding regional markets and facilitating economic integration across Asia and Europe. It has been regarded as a game-changer on the landscape of dispute resolution market, triggering a proliferation of “adjudication business.” This report examines the dynamics of international dispute resolution in context of the BRI, discussed from the three following perspectives: (1) BRI investors and disputants; (2) three major means of dispute resolution on offer; and (3) institutions involved.
Making Sense of U.S. Trade Policy: What Recent Negotiations Can Tell Us
Authors: Manak Inu
Published: December 2019

U.S. trade policy is not what it used to be. Since the U.S. withdrawal from the Trans-Pacific Partnership in January 2017, Indo-Pacific trade relations have been in constant flux. It is not clear where U.S. trade policy will end up, particularly with regard to its relationship with China. However, the conclusion of two renegotiations of previous U.S. trade agreements can tell us generally about the new U.S. approach and what this means for our trading partners. I will discuss developments from the renegotiation of the Korea-U.S. free trade agreement (KORUS) and the U.S.-Mexico-Canada Agreement (USMCA) as a replacement for the North American Free Trade Agreement (NAFTA).
Introductory Remarks by Kabir Duggal
Authors: Duggal Kabir
Published: December 2019

Thank you all for coming, on behalf of the Private International Law Group of the American Society of International Law—we go by PILIG. If you are not a member, please sign up. Signing up is free, if you are a member of ASIL.
Monistic Argumentation
Authors: Bosley Richard
Published: December 2019

On those occasions on which one gives an interpretation of a work both scanty in remains and obscure in meaning I would take it to be appropriate to insist that one's task is not to argue that one's interpretation is certainly correct but rather to argue that it is probably correct. It is accordingly not my task to argue that it is not possible that other interpretations of Parmenides’ Way of Truth are correct. Nor do I increase the likelihood of my own by decreasing that of theirs.

I seek to give an interpretation which is rich enough to disclose the springs of monism. I am primarily concerned to show how we may understand those arguments which leave us with the conclusion that there is only one thing to know.
OP16 Assessing The Viability Of Medical Equipment Procurement In Hospital
Authors: Avdeyev Andrey , Benberin Valeriy , Shanazarov Nasrulla , Kudaibergenova Maigul , Kaptagayeva Aigul , Hailey David , Zhumagali Yenglik , Magzumova Raushan , Makalkina Larissa
Published: December 2019

Introduction

ABC-VEN analysis is an easy method of clinical and economic analysis on the costs of drug coverage and an important tool for monitoring and ensuring the rational use of medicines. However, this methodology is difficult to apply in assessing the viability of medical equipment procurement (MEP) in hospital. Using a combined model of ABC analysis and Multiple criteria decision analysis (MCDA) may be more appropriate to apply to MEP.

Methods

We created five standardized criteria, which present the main results of assessment of the viability of MEP for implementing new health technologies (HTs). These criteria address the following: 1) Novelty/innovation; 2) Comparative clinical effectiveness and safety; 3) Relevance (demand); 4) Economic effectiveness; and 5) Payback period. Based on these criteria we determine the threshold values of priority for MEP: 1) High priority; 2) Medium priority; 3) Low priority.

Results

Using the ABC model and five standardized criteria, we analyzed all proposals from the Hospital units for implementing new HTs connected with MEP for 2018. In total, proposals contained 11 items of ME, among them three items were in group A (27%), two items were in group B (18%), and six items were in group C (55%). All items were high priority for procurement with the exception of one item from group B with medium priority. Items with low priority were not revealed which can be considered as a direct indicator of the operational effectiveness of Hospital-based HTA Unit. Excluding ME with a medium priority from the procurement plan would reduce Hospital costs by 13.5 percent.

Conclusions

Combined ABC and MCDA analysis in the process of assessment the viability of MEP can give the opportunity to make comparative assessment of different types of ME based on standardized criteria; determine the priority for procurement of new ME; and avoid the influence of subjective factors of the managerial decision-making process in hospital.
OP21 Enhancing Capability: Patient Impact In Ultra-Orphan Conditions
Authors: Tonkinson Amanda , Livingstone Heidi , Upadhyaya Sheela , Leng Gillian
Published: December 2019

Introduction

Written evidence is submitted to the National Institute for Heath and Care Excellence (NICE) by patient organisations for all ultra-orphan evaluations. To enhance the capability of patient involvement at NICE and to further develop understanding of how patient generated evidence and input in ultra-orphan conditions can support the Health Technology Assessment (HTA) agencies beyond 2020, the Public Involvement Programme systematically reviews the impact the evidence has on committee decision making.

Methods

This study captured data from September 2017 to August 2018 for seven ultra-orphan evaluations. A paper questionnaire was given to each committee member to complete for each evaluation and entered in to an online system for analysis. Findings were used to inform the committee views which were highlighted in feedback letters to the patient groups. The questions included: how much impact and what sort of impact the patients had; both qualitative and quantitative data; and, a specific question on clarification of quality of life data

Results

We obtained 83 responses showing the submissions: had a moderately high or high impact; gave the committee particular insight into quality of life data not provided elsewhere; provided new evidence; interpret the data from other sources; and, demonstrated consistency with other sources

Conclusions

Patient evidence is particularly useful for ultra-orphan conditions where other forms of evidence are limited. Patients can provide a unique insight into the burden of disease, the patient population, any updates of treatments and the impact on patient and carers. They provide real life data to the committee including information that standard Quality Adjusted Life Years measures do not. Evidence varied by condition with impact themes highlighting the effects on patient and carers including fear, stress and anxiety. The examples are recorded, updated annually and will be shared with national patient groups and offered internationally through the HTAi Interest Group on Patient and Citizen Involvement.
OP27 Engaging Patients: The EuroCAB Programme
Authors: Houyez François , Camp Rob
Published: December 2019

Introduction

When developing a health technology that requires clinical studies, developers institute working relations with clinical investigators. In certain diseases areas, patients' representatives create their own advisory boards, which proved their utility in the early 90s, in particular for the development of products to treat HIV infection. Inspired by this model, where patients with a same disease join and meet with relevant developers and discuss all aspects of the research, the European Organisation for Rare Diseases (EURORDIS) proposes a new programme of such Community Advisory Boards for Rare Diseases (CAB).

Methods

For this programme, EURORDIS invites developers to sign a Charter of principles when engaging with patients, and provides guidelines on CABs, together with a mentoring programme for patients’ networks that are less experienced with the development and the evaluation of health technologies. CABs are driven by patients who set their agenda, who sign a Memorandum of Understanding with each developer, and who organise the sessions. Sessions typically last for two to four days during which different meetings with different developers can take place, or trainings. All meetings can take place under confidentiality arrangements, and minutes are written to keep track and to follow-up with all points discussed. Participants and agendas are made public

Results

As of 2018, four CABs exist and operate (for tuberous sclerosis complex, for scleroderma, for cystic fibrosis, for Duchenne muscular dystrophy) and 18 others are in discussion with many due to start in 2019. Topics discussed cover the target population, the study feasibility, the endpoints including patient reported outcomes, the comparator choice and/or the acceptance of a placebo controlled trial, the quality of life, the practical aspects of the trials, and the identification of previously unknown or unmet patient needs/preferences. For products which are more advanced in their life-cycle, discussions can also cover compassionate use, pricing policy, relative efficacy etc.

Conclusions

This represents a well-structured programme for the engagement of patients, where collective thinking and exchange between different patients ensure high quality dialogue with developers and can inform HTA also.
OP44 Robot-Assisted Surgery: Joint HTA To Inform Australian Policy And Funding
Authors: Fennessy Paul , Clements Vanessa , Hibbitt Olivia
Published: December 2019

Introduction

Robot-Assisted Surgery (RAS) has been available in Australia since 2003. There are 50 da Vinci RAS systems in Australia (18 in NSW and 12 in Victoria) with most in the private hospital sector. In Australia the capital cost of a da Vinci RAS system is up to AUD 4 million (USD 2.8 million), which excludes annual maintenance fees of AUD 250,000 (USD 175,000) and consumable costs of AUD 3,500 (USD 2,450) for each procedure.

Methods

The NSW Ministry of Health and Victorian Department of Health and Human Services commissioned a health technology assessment (HTA) to explore the benefits, risks and economic implications of surgical robotics, which involved a review of the peer reviewed literature, a cost benefit analysis of public sector patients who received RAS and broad stakeholder consultation to document current perspectives on RAS applications.

Results

RAS is as safe and effective as other surgical modalities when performed by sufficiently skilled surgeons, although evidence generally comes from small studies with limited follow-up time and few studies report long term mortality, morbidity or patient-reported outcomes. Comparative benefits of RAS are uncertain as most studies conclude little or no difference in procedure related or functional outcomes. While RAS reduces length of stay, which offers patient and health system benefits, this is insufficient to fully offset high capital and consumable costs currently charged to Australian providers. Government and clinical stakeholders identified that establishing an RAS service requires consideration of important factors, including: i) Governance is critical; ii) Higher case volumes may improve financial viability; and iii) a need for state-wide/national standards for surgeon training and credentialing.

Conclusions

RAS is as safe and effective as other modalities when performed by skilled surgeons. However, uncertainty remains around long-term outcomes and clinical and cost effectiveness. An accredited training program, monitoring and evaluation will be critical to ensure outcomes data inform ongoing evidence assessment and government policy and investment.
OP49 MAIC-ing Use Of Trials? Study Of Matching-Adjusted Indirect Comparisons
Authors: Leahy Joy , Walsh Cathal
Published: December 2019

Introduction

When conducting a Network Meta-Analysis (NMA) for a Health Technology Assessment (HTA), the submitting company typically will have access to Individual Patient Data (IPD) from their own trials, but only aggregate data (AgD) for the comparator. In this case, they can re-weight the IPD so that the covariate characteristics in the IPD trials match that of the AgD trials, using the increasingly popular method of Matching-Adjusted Indirect Comparison (MAIC).

Methods

We carried out a simulation study to investigate this method in a Bayesian setting. We simulated three IPD trials comparing treatments A and B (AB-IPD trials), and one aggregate data trial comparing treatments B and C (BC-AgD trial). We investigated two options of weighting covariates: 1. all three studies are weighted separately to match the BC-AgD trial (MAIC Separate Trials). 2. patients are weighted across all three IPD studies to match the BC-AgD trial, but the NMA still considers each trial separately (MAIC Pooled Trials). We compared the results of the MAIC to a standard NMA and a mixed IPD/AgD NMA. We applied these methods to a network of treatments for multiple myeloma.

Results

MAIC can provide more accurate estimates of the relative treatment effects than a standard NMA in the BC-AgD trial population. However, MAIC may decrease the accuracy of the relative treatment effects in the overall population. Treatment rankings were unchanged when applying MAIC to the multiple myeloma network.

Conclusions

MAIC is beneficial as a sensitivity analysis to demonstrate that results hold across patient populations. If there is a difference in relative treatment effects attributable to population imbalances, then it is useful to be able to quantify this difference. However, we recommend using either a standard NMA or a mixed IPD/AgD NMA for the base case analysis, given the potential bias that can arise in an MAIC.
OP75 Facts And Values In Health Technology Assessment: The Case Of Non-Invasive Prenatal Testing
Authors: Bloemen Bart , Jansen Maarten , Rijke Wouter , Oortwijn Wija , Vanderwilt Gert
Published: December 2019

Introduction

Health Technology Assessment (HTA) is where facts and values meet: the evidence that is considered relevant to the assessment of a technology depends on the value framework used. In the context of the European project VALIDATE (Values in doing assessments of healthcare technologies), we assessed to what extent this interplay between facts and values is acknowledged in HTA reports on non-invasive prenatal testing (NIPT). Our aim is to gain a better understanding of this fact-value relationship, and to contribute to the development of capacity for ethical analyses in HTA.

Methods

Five reviewers independently analyzed HTA reports on NIPT, obtained from the National Institute for Health Research (NIHR) HTA database, by answering a structured questionnaire on: (i) arguments, values, and conclusions; (ii) relations between values and collected evidence; (iii) operationalizations of the values involved. Ethical argumentation was analyzed using the method of specifying norms. This method holds that for general, abstract ethical principles to reach concrete cases, principles need to be specified in such a way as to achieve maximal coherence between different value commitments and practice. The results of the analysis were discussed in joint meetings to arrive at a consensus on interpretation.

Results

Our results show that the pivotal role of values in defining what counts as relevant evidence and why, is rarely acknowledged. The same holds for the importance of specifying values as a means to achieve greater coherence between the use of healthcare technologies and a range of values.

Conclusions

There is ample room for improvement in clarifying the role of values in HTA: they can serve to explain and justify what evidence is considered relevant to the assessment of a healthcare technology. Recognizing that abstract values need specification in order to reach concrete cases opens up new opportunities for exploring in what way values are affected by healthcare technologies.
OP86 Exploring Public Utilization Data For Primary Care Education Programs
Authors: Mak Jason , Granger Renee
Published: December 2019

Introduction

NPS MedicineWise delivers nationwide educational programs to improve quality use of medicines and medical tests in Australia. Targeted horizon scanning approaches are required to detect and address emerging challenges in the healthcare landscape such as overutilization and unexpectedly high expenditure on medicines and medical tests. Publicly available utilization and expenditure data from the Australian Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Schedule (MBS) may provide insights into identifying potential areas for intervention.

Methods

Five financial years (2013-18) of publicly available PBS/MBS data was extracted from Australian Government websites and clustered according to medicine class, disease groups or anatomical therapeutic chemical classification (ATC). Usage and expenditure trends were explored with signals of potential inappropriate use identified as unusual spikes or changes.

Results

PBS data showed two fixed dose combination inhalers for respiratory conditions, three direct oral anticoagulants, four analgesics (including opioids) and two blood glucose lowering agents had high volume and expenditure growths in the 2016-17 financial year. Cholesterol-reducing medicines and anti-hypertensives also commonly had high utilisation growth. The highest growth classified by ATC level two codes were for urologicals. These signals were collated into themes of stroke prevention, cardiovascular, respiratory, pain management and type two diabetes. MBS data on pathology tests showed viral and bacterial testing had the highest growth, followed by vitamin B12 testing and vitamin D testing. Magnetic resonance imaging had the highest growth in expenditure and volume of services of the various imaging modalities and X-ray of the lower leg had the highest volume of services.

Conclusions

Several medicines and medical tests were detected as possible targets for interventions based on high volume or expenditure growth. Themes identified from the data can then be further investigated and contextualized to inform topic areas for primary care education to support quality use of medicines and medical tests.
OP91 Developing A Celtic Connections Regional Health Technology Assessment Alliance
Authors: Myles Susan
Published: December 2019

Introduction

The Irish, Scottish and Welsh national Health Technology Assessment (HTA) bodies (Health Information and Quality Authority, Health Technology Assessment Group, Scottish Health Technologies Group, Health Technology Wales) have recently (2018) established a ‘Celtic connections’ regional HTA alliance on non-medicine technologies. The primary purpose is to add value by realizing potential economies of scale and scope in non-medicine HTA efforts.

Methods

A Memorandum of Understanding (MoU) was agreed to: formalize collaboration and partnership working; improve shared understanding of work programs and processes; collaborate on and co-produce evidence reviews of mutual interest; increase both the volume and range of technology topics for which advice is developed in each nation; promote knowledge exchange; and enhance professional and personal development for each agency's staff.

Results

Early benefits include: collaboration on one technology topic resulting in the production of bespoke guidance in three countries; an update of a partner's rapid review; identification of a further potential topic collaboration (sacral nerve stimulation); a six month senior staff secondment; and reciprocal observer membership on each country's national committees. Other general benefits have included: reduced duplication of effort; improved quality assurance through ‘critical friend’ peer review; enhanced access to methodological advice and a broader range of stakeholders; and development of a forum for discussion and peer support.

Conclusions

The alliance offers real potential to optimize use of the scarce resources for non-medicine technologies across the three countries and increase evidence review and guidance volume through adapting or co-producing outputs. Longer term benefits are anticipated to include: improved knowledge exchange; advancing skills of staff; building and broadening capacity through shared learning and access to a wider professional peer group; improved staff recruitment and retention; production of joint publications and other modes of dissemination; and increased profile for each country's work.
OP109 The Need For Building Pharmacists’ Health Technology Assessment Capacity; The Nigerian Scenario
Authors: Chukwu Otuto Amarauche , Chukwu Chizaram
Published: December 2019

Introduction

The role of Health technology assessment (HTA) as a systematic approach in the evaluation of health interventions and technologies is becoming increasingly important as the quest for attaining universal health coverage globally continues to increase. Some developed countries in Europe and the Americas now apply HTA extensively in healthcare policy decisions, however, developing regions and countries like sub-Saharan Africa and Nigeria respectively, seem not to be making significant progress in this area. Given that evidence suggests that Nigeria and indeed several countries in sub-Saharan Africa are performing poorly on most healthcare indices as the region continues to be ravaged by predictable and avoidable epidemics and disease outbreaks, the need to build HTA capacity has never been more paramount.

Methods

A review of HTA capability in Nigeria was done. Pharmacists in Nigeria's Capital were randomly sampled. Semi-structured questionnaires were administered. Descriptive statistics were used in data analysis. P values less than 0.05 were considered to be significant.

Results

In Nigeria, there is no institution tasked with undertaking HTA and there seems to be limited knowledge, capacity and awareness on the issue. Pharmacists, being the most accessible healthcare professionals according to evidence, are a key group that could play an active role in HTA and its implementation in developing countries like Nigeria. However, out of 322 pharmacists randomly sampled, 93 percent were not aware of HTA and its application in healthcare decision-making.

Conclusions

There is no paucity of healthcare programs and plans in Nigeria but they seem to fail due to lack of evidence-based assessment, decision-making and implementation. Hence, there is an increasing need to raise awareness on the importance of HTA in healthcare decision-making; strengthen HTA capacity by developing and sustaining institutional capacity and adequate human resource for HTA; and creating regional annexes of HTA organizations in Africa.