bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of the toxic effects of titanium dioxide nanoparticles in blood, liver, muscles, and brain of a Neotropical detritivorous fish
Authors: Carmo Talita L. L. , Siqueira Priscila R. , Azevedo Vinícius C. , Tavares Driele , Pesenti Emanuele C. , Cestari Marta M. , Martinez Cláudia B. R. , Fernandes Marisa N.
Published: January 2019

The toxicity of titanium dioxide nanoparticles (TiO2‐NP) in the blood, liver, muscle, and brain of a Neotropical detritivorous fish, Prochilodus lineatus, was tested. Juvenile fish were exposed to 0, 1, 5, 10, and 50 mg L−1 of TiO2‐NP for 48 hours (acute exposure) or 14 days (subchronic exposure) to evaluate changes in hematology, red blood cell (RBC) genotoxicity/mutagenicity, liver function (reactive oxygen species (ROS) production, antioxidant responses, detoxification, and histopathology), acetylcholinesterase (AChE) activity in muscles and brain, and Ti bioaccumulation. TiO2‐NP did not cause genetic damage to RBC, but acutely decreased white blood cells (WBC) and increased monocytes. Subchronically, RBC decreased, mean cell volume and hemoglobin increased, and WBC and lymphocytes decreased. Therefore, NP has the potential to affect immune system and increase energy expenditure, reducing the fish's ability to avoid predator and to resist pathogens. In the liver, acute exposure decreased ROS and increased glutathione (GSH) content, while subchronic exposure decreased superoxide dismutase activity and increased glutathione‐S‐transferase (GST) activity and GSH content. GSH and GST seem to play an essential role in metabolizing NP and ROS, likely increasing hepatocytes' metabolic rate, which may be the cause of observed cell hypertrophy, disarrangement of hepatic cords and degenerative morphological alterations. Although most studies indicate that the kidney is responsible for metabolizing and/or eliminating TiO2‐NP, this study shows that the liver also has a main role in these processes. Nevertheless, Ti still accumulated in the liver, muscle, and brain and decreased muscular AChE activity after acute exposure, showing neurotoxic potential. More studies are needed to better understand the biochemical pathways TiO2‐NP are metabolized and how its bioaccumulation may affect fish homeostasis and survival in the environment.
On the determination of the Biot modulus of poroelastic cylinder
Authors: Dudarev Vladimir V. , Mnukhin Roman M. , Vatulyan Alexander O. , Nedin Rostislav D. , Gusakov Dmitriy V.
Published: January 2019

The paper is concerned with a problem of radial vibrations of an inhomogeneous poroelastic cylinder by means of the acoustic sounding method. We have carried out the analysis of the amplitude‐frequency characteristic of the cylinder depending on the variation law of the Biot modulus and have considered the inverse problem on the determination of this law by the available data of the amplitude‐frequency characteristic measured in a given frequency range. The solution of the inverse problem has been obtained on the basis of the iterative process constructed, when the correction to the current form of the reconstructed function was defined by the derived Fredholm integral equation of the first kind. A number of examples of the reconstruction of the variation laws of the Biot modulus are presented. The reconstruction accuracy is estimated, and the recommendations on a successful implementation of the proposed approach are provided.
Analytic bootstrap for boundary CFT
Authors: Bissi Agnese , Hansen Tobias , Söderberg Alexander
Published: January 2019

Abstract

We propose a method to analytically solve the bootstrap equation for two point functions in boundary CFT. We consider the analytic structure of the correlator in Lorentzian signature and in particular the discontinuity of bulk and boundary conformal blocks to extract CFT data. As an application, the correlator 〈ϕϕ〉 in ϕ
4 theory at the Wilson-Fisher fixed point is computed to order ϵ
2 in the ϵ expansion.
Definitive Chemoradiotherapy Versus Trimodality Therapy for Resectable Oesophageal Carcinoma: Meta‐analyses and Systematic Review of Literature
Authors: Voeten Daan M. , den Bakker Chantal M. , Heineman David J. , Ket Johannes C. F. , Daams Freek , van der Peet Donald L.
Published: January 2019

Background

Standard therapy for loco‐regionally advanced, resectable oesophageal carcinoma is trimodality therapy (TMT) consisting of neoadjuvant chemoradiotherapy and oesophagectomy. Evidence of survival advantage of TMT over organ‐preserving definitive chemoradiotherapy (dCRT) is inconclusive. The aim of this study is to compare survival between TMT and dCRT.

Methods

A systematic review and meta‐analyses were conducted. Randomised controlled trials and observational studies on resectable, curatively treated, oesophageal carcinoma patients above 18 years were included. Three online databases were searched for studies comparing TMT with dCRT. Primary outcomes were 1‐, 2‐, 3‐ and 5‐year overall survival rates. Risk of bias was assessed using the Cochrane risk of bias tools for RCTs and cohort studies. Quality of evidence was evaluated according to Grading of Recommendation Assessment, Development and Evaluation.

Results

Thirty‐two studies described in 35 articles were included in this systematic review, and 33 were included in the meta‐analyses. Two‐, three‐ and five‐year overall survival was significantly lower in dCRT compared to TMT, with relative risks (RRs) of 0.69 (95% CI 0.57–0.83), 0.76 (95% CI 0.63–0.92) and 0.57 (95% CI 0.47–0.71), respectively. When only analysing studies with equal patient groups at baseline, no significant differences for 2‐, 3‐ and 5‐year overall survival were found with RRs of 0.83 (95% CI 0.62–1.10), 0.81 (95% CI 0.57–1.14) and 0.63 (95% CI 0.36–1.12).

Conclusion

These meta‐analyses do not show clear survival advantage for TMT over dCRT. Only a non‐significant trend towards better survival was seen, assuming comparable patient groups at baseline. Non‐operative management of oesophageal carcinoma patients might be part of a personalised and tailored treatment approach in future. However, to date hard evidence proving its non‐inferiority compared to operative management is lacking.
Effects of Discontinue Rules on Psychometric Properties of Test Scores
Authors: von Davier Matthias , Cho Youngmi , Pan Tianshu
Published: January 2019

This paper provides results on a form of adaptive testing that is used frequently in intelligence testing. In these tests, items are presented in order of increasing difficulty. The presentation of items is adaptive in the sense that a session is discontinued once a test taker produces a certain number of incorrect responses in sequence, with subsequent (not observed) responses commonly scored as wrong. The Stanford-Binet Intelligence Scales (SB5; Riverside Publishing Company, 2003) and the Kaufman Assessment Battery for Children (KABC-II; Kaufman and Kaufman, 2004), the Kaufman Adolescent and Adult Intelligence Test (Kaufman and Kaufman 2014) and the Universal Nonverbal Intelligence Test (2nd ed.) (Bracken and McCallum 2015) are some of the many examples using this rule. He and Wolfe (Educ Psychol Meas 72(5):808–826, 2012. https://doi.org/10.1177/0013164412441937) compared different ability estimation methods in a simulation study for this discontinue rule adaptation of test length. However, there has been no study, to our knowledge, of the underlying distributional properties based on analytic arguments drawing on probability theory, of what these authors call stochastic censoring of responses. The study results obtained by He and Wolfe (Educ Psychol Meas 72(5):808–826, 2012. https://doi.org/10.1177/0013164412441937) agree with results presented by DeAyala et al. (J Educ Meas 38:213–234, 2001) as well as Rose et al. (Modeling non-ignorable missing data with item response theory (IRT; ETS RR-10-11), Educational Testing Service, Princeton, 2010) and Rose et al. (Psychometrika 82:795–819, 2017. https://doi.org/10.1007/s11336-016-9544-7) in that ability estimates are biased most when scoring the not observed responses as wrong. This scoring is used operationally, so more research is needed in order to improve practice in this field. The paper extends existing research on adaptivity by discontinue rules in intelligence tests in multiple ways: First, an analytical study of the distributional properties of discontinue rule scored items is presented. Second, a simulation is presented that includes additional scoring rules and uses ability estimators that may be suitable to reduce bias for discontinue rule scored intelligence tests.
Theoretical Aspects of Spinodal Decomposition in Fe-C
Authors: Kim B. , Sietsma J. , Santofimia M. J.
Published: January 2019

Carbon redistribution is known to occur during room temperature aging of Fe-C martensite. One of the proposed mechanisms in the literature by which carbon redistributes is spinodal decomposition, a thermodynamically driven reaction in which the alloy undergoes separation into carbon-rich and carbon-poor regions, giving rise to modulations in carbon concentration. Despite the substantial experimental evidence supporting the occurrence of spinodal decomposition in Fe-C, its theoretical formulation requires attention. In the present study, a theoretical framework based on the regular solution model is built for evaluating the thermodynamics of the Fe-C system, with particular emphasis on the interstitial nature of carbon atoms within the ferrite lattice. Assuming a defect-free lattice, the model explains a miscibility gap in the Fe-C system. The limitations of the current model are critically evaluated.
Educational Disparities in Adult Mortality Across U.S. States: How Do They Differ, and Have They Changed Since the Mid-1980s?
Authors: Montez Jennifer Karas , Zajacova Anna , Hayward Mark D. , Woolf Steven H. , Chapman Derek , Beckfield Jason
Published: January 2019

Adult mortality varies greatly by educational attainment. Explanations have focused on actions and choices made by individuals, neglecting contextual factors such as economic and policy environments. This study takes an important step toward explaining educational disparities in U.S. adult mortality and their growth since the mid-1980s by examining them across U.S. states. We analyzed data on adults aged 45–89 in the 1985–2011 National Health Interview Survey Linked Mortality File (721,448 adults; 225,592 deaths). We compared educational disparities in mortality in the early twenty-first century (1999–2011) with those of the late twentieth century (1985–1998) for 36 large-sample states, accounting for demographic covariates and birth state. We found that disparities vary considerably by state: in the early twenty-first century, the greater risk of death associated with lacking a high school credential, compared with having completed at least one year of college, ranged from 40 % in Arizona to 104 % in Maryland. The size of the disparities varies across states primarily because mortality associated with low education varies. Between the two periods, higher-educated adult mortality declined to similar levels across most states, but lower-educated adult mortality decreased, increased, or changed little, depending on the state. Consequently, educational disparities in mortality grew over time in many, but not all, states, with growth most common in the South and Midwest. The findings provide new insights into the troubling trends and disparities in U.S. adult mortality.
Investigation on tool wear and tool life prediction in micro-milling of Ti-6Al-4V
Authors: Dadgari Amin , Huo Dehong , Swailes David
Published: January 2019

Short tool life and rapid tool wear in micromachining of hard-to-machine materials remain a barrier to the process being economically viable. In this study, standard procedures and conditions set by the ISO for tool life testing in milling were used to analyze the wear of tungsten carbide micro-end-milling tools through slot milling conducted on titanium alloy Ti-6Al-4V. Tool wear was characterized by flank wear rate, cutting-edge radius change, and tool volumetric change. The effect of machining parameters, such as cutting speed and feedrate, on tool wear was investigated with reference to surface roughness and geometric accuracy of the finished workpiece. Experimental data indicate different modes of tool wear throughout machining, where nonuniform flank wear and abrasive wear are the dominant wear modes. High cutting speed and low feedrate can reduce the tool wear rate and improve the tool life during micromachining. However, the low feedrate enhances the plowing effect on the cutting zone, resulting in reduced surface quality and leading to burr formation and premature tool failure. This study concludes with a proposal of tool rejection criteria for micro-milling of Ti-6Al-4V.
Vaccination Data When the Outbreak Happens: A Qualitative Evaluation of Oregon’s Rapid Response Tool
Authors: Osborn Andrew W. , Peters Lee R.
Published: January 2019

Objective

Immunization data are vital to support responses to vaccine-preventable disease outbreaks. The Oregon Immunization Program developed a unique prototype instrument—the Rapid Response Tool (RRT)—that provides population data to local responders within 2 hours of a request. Data outputs include vaccination coverage by age group and zip code; percentages of students with nonmedical exemptions to vaccination requirements, by school; and current, comprehensive lists of local vaccination providers.

Methods

The RRT was demonstrated to staff at 7 Oregon counties and feedback was solicited via comments and a structured survey.

Results

The RRT received strong support. Attendees identified several uses for RRT data, including outbreak response and ongoing intervention efforts, and they pointed to areas for further development.

Conclusions

The success of the RRT demonstrations illustrates that a well-populated immunization information system can contribute to preparedness work well beyond current standards. (Disaster Med Public Health Preparedness. 2019;13:682–685)
Reaction to Severe Stress and Adjustment Disorders After the September 2017 Earthquakes in a Psychiatric Emergency Department in Mexico City
Authors: Fresán Ana , Robles-García Rebeca , Becerra-Palars Claudia , Muñoz-Suárez Manuel Alejandro , Rangel-Cupa Omar , Monroy-Cortés Brisa Gissel , Molina-Lopez Alejandro
Published: January 2019

Objective

Earthquakes may lead to a reaction to severe stress and adjustment disorders (RSSAD). On September 7, 19, and 23, 2017, Mexico was struck by many severe earthquakes. The aim of this study was to examine whether there was an increase in the number of consultations and RSSAD in a psychiatric emergency department in Mexico City after these earthquakes.

Methods

We studied retrospectively the diagnosis and triage assessment from a Mexican psychiatric emergency department database from September 1 to November 30, 2017, and analyzed RSSAD and the number of consultations after the earthquakes.

Results

A total of 1,811 psychiatric emergency consultations were registered from the period of study. A total of 141 consultations represented RSSAD. There was a significant increase of RSSAD after the September 23, 2017, earthquake. The triage assessment revealed that the urgency of the consultations was higher immediately after the earthquakes.

Conclusion

Natural disasters, such as earthquakes, may trigger diverse RSSAD leading to increased emergency consultations, especially when those disasters are repetitive. Mental health professionals should be adequately trained and sensitized for possible acute disaster victims. (Disaster Med Public Health Preparedness. 2019;13:686–690).
Multiple Patients With Burn Injury Induced by a Chemical Explosion Managed by Physician-Staffed Helicopters
Authors: Kondo Akihiko , Jitsuiki Kei , Osaka Hiromichi , Takeuchi Ikuto , Ishikawa Kouhei , Omori Kazuhiko , Yanagawa Youichi
Published: January 2019

On December 1, 2017, the Fuji factory of Arakawa Chemical Industries exploded. Dust that formed as a byproduct from the crushing and packing process of the resin for ink exploded at the facility. The Fuji City Fire Department requested the dispatch of 2 physician-staffed helicopters (known as a doctor helicopter [DH] in Japan). The first party of emergency services established a headquarters and first-aid station. However, this area was feared to be at risk of a second explosion. Physicians performed re-triage for all 11 burned patients. Three severely injured patients were transported to emergency medical service centers either by ground ambulance or the DH without undergoing any decontamination. The physician who escorted the patient by ground ambulance complained of a headache. One of the severely injured patients was treated at a local hospital and then transported to an emergency medical service center after undergoing decontamination and intubation. Fortunately, all patients who were transported to medical facilities obtained a survival outcome. Chemical, biological, radiological, nuclear, and explosive incidents are rare but can be fatal for responders to these types of disaster. Therefore, all who work in these settings should be prepared and trained adequately to ensure that they have the knowledge and skill to both manage patients and protect themselves from harm. (Disaster Med Public Health Preparedness.2019;13:799–805)
Serum 25-hydroxyvitamin D fluctuations in military personnel during 6-month summer operational deployments in Afghanistan
Authors: Fallowfield Joanne L. , Delves Simon K. , Hill Neil E. , Lanham-New Susan A. , Shaw Anneliese M. , Brown Pieter E. H. , Bentley Conor , Wilson Duncan R. , Allsopp Adrian J.
Published: January 2019

Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P<0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P<0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P<0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P<0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.
Critique des systèmes et antimathématisme au XVIIIesiècle
Authors: FERRARO ANGELA
Published: January 2019

Cet article est consacré au rapport que, dans la France du XVIIIesiècle, la réflexion sur l’utilité et la légitimité des systèmes entretient avec le débat sur le statut et l’usage des mathématiques. En retraçant une double ligne d’opposition — entre Formey et Condillac, d’une part, et entre d’Alembert et le couple Diderot-Buffon, d’autre part — on s’attache à décrire l’émergence d’un partage significatif à l’intérieur du front newtonien; partage qui reflète des changements profonds s’opérant dans le panorama philosophique et scientifique de l’époque. À la fin de ce parcours, une question supplémentaire se pose au sujet du destin réservé aux mathématiques et aux systèmes après 1750.
Radical View of Freedom: An Interview with Dread Scott
Authors: ORR JOEY
Published: January 2019

In 2019, US-based African American artist Dread Scott will present his new performative work, Slave Rebellion Reenactment, just outside the city of New Orleans, Louisiana, USA. It will be a re-performance of the German Coast uprising of 1811, one of the largest rebellions of enslaved people in US history. It is the most recent installment in a slowly growing historical body of knowledge about this little-known history. The story is about a radical idea of freedom that Scott seeks to enliven through recruiting the performers. The potential for organizing and future networks is at the heart of this effort. This text is based upon Joey Orr's interview with Dread Scott on Thursday 12 May 2016, at the Museum of Contemporary Art Chicago.
Interpreting Paul Oliver
Authors: Horn David
Published: January 2019

When the English blues scholar Paul Oliver, who died in 2017 aged 90, was interviewed for a special issue of Popular Music in his honour, on the occasion of his 80th birthday (issue 26/1, January 2007), it was striking how much of the conversation revolved around a recurring flow of ideas for future research, to be undertaken by him or by anyone else who came with credentials appropriate to the enterprise (such as musicology, a discipline that he never considered himself well enough versed in to allow engagement). It didn't enter his mind that he might become a research subject himself. Now, with Christian O'Connell's book, he has; and it is his own methods that are under scrutiny, not, or not directly, the blues that he spent a long adult lifetime investigating (and for which he was such a knowledgeable and, for many who read his books or heard him speak live or on air, inspiring advocate), nor the social and economic life of the African American working class who created the music that continued to fascinate him. What is under the microscope is how he depicted both of those things.
OP03 Optimizing The Use Of RWE In HTA: Lessons From The ICER Summit
Authors: Hampson Grace , Henshall Chris , Towse Adrian , Dreitlein Bill , Pearson Steven
Published: January 2019

Introduction:

Real world evidence (RWE) is changing the overall data landscape and it has potential to advance the evaluation of real world performance (comparative effectiveness) of healthcare technologies by providing a greater quantity and quality of evidence. However, many are concerned that non-randomized RWE may be substituted for RCT data and thus increase uncertainty about effectiveness. This presentation sets out the opportunities and challenges for use of RWE by payers and HTA bodies to evaluate health care technologies.

Methods:

Current uses, opportunities and challenges were identified via a literature review and interviews with nine experts. Interim results were discussed at the 2017 ICER Policy Summit, which brought together leaders from payer and life sciences organizations, to develop specific and actionable recommendations for the use of RWE in drug coverage and policy decision-making.

Results:

RWE is utilized for multiple purposes in the US and globally, including: aiding design of drug development pathways; supporting regulatory approval decisions; monitoring safety; and informing HTA assessments and payer coverage decisions. Some stakeholders see great value in RWE and want to make greater use of these data sources, including for: drug effectiveness evaluations (including supplementing network meta-analyses); innovative study designs (including pragmatic trials); real time patient monitoring; and adaptive pathways or coverage with evidence development. However, others see numerous challenges, many of which are related to the quality and reliability of RWE sources. Acceptance of an expanded future role for RWE is not universal, and payers and developers must work together to find mutually beneficial strategies for progressing the development and use of RWE.

Conclusions:

Specific and actionable recommendations will be presented which highlight the role that each stakeholder group can play in overcoming the challenges and realizing the potential for RWE.
OP40 Effect Of Advanced Nursing Practice On Hospital Use For The Elderly
Authors: Trepanier Marc-Olivier , Wassef Maggy , Beauchamp Sylvie
Published: January 2019

Introduction:

Within the local context in Montréal, the elderly population makes up more than 50% of patient hours in emergency department. To meet ministerial targets for length of stay, our health technology assessment unit was requested to conduct an umbrella review to evaluate interventions aimed at reducing health care services use for this population. Within that context, our unit was asked to further evaluate the efficacy of advance practice nurse (APN)-led interventions. The objective of this rapid response was to summarize the scientific literature for APN-led interventions on hospital services use.

Methods:

An umbrella review using the PRISMA statement was conducted to review the scientific literature. Systematic searches were conducted in five databases, along with a grey literature search. Two reviewers performed the study selection, quality assessment using the ROBIS, and data extraction. The primary studies within the selected systematic reviews were extracted by two reviewers and a meta-analysis was conducted to analyze the efficacy of APN-involved in discharge planning and transitional care.

Results:

From the twenty-seven systematic reviews identified in the literature search, four reported data on APN-led interventions. In all, sixteen primary studies were included in the four systematic reviews. While most studies focused on transitional care, there was heterogeneity in the components of the interventions implemented. At six months post-discharge, a reduction of forty-one percent in relative risk of readmission was observed with APN-led discharge planning and transitional care with patient education, follow-up and services coordination. Studies with fewer components reported less significant results than studies with comprehensive discharge planning and transitional care. The few APN-led primary care studies identified in the systematic reviews reported inconsistent results.

Conclusions:

APN-led comprehensive discharge planning and transitional care can reduce hospital readmission rate. Several components were identified and should be considered in the discharge planning and transitional care.
OP45 HTA Of A Pediatric Biplanar Low-Dose X-Ray Imaging System
Authors: Andellini Martina , Faggiano Francesco , di Mauro Roxana , Derrico Pietro , Ritrovato Matteo
Published: January 2019

Introduction:

Patients with adolescent idiopathic scoliosis frequently receive X-ray imaging at diagnosis and subsequent follow monitoring. To achieve the ALARA concept of radiation dose, a biplanar low-dose X-ray system (BLDS) has been proposed. The aim of the study is to gather evidence on safety, accuracy and overall effectiveness of a BLDS compared with CT scanning, in a pediatric population, in order to support the final decision on possible acquisition of such innovative diagnostic system.

Methods:

The new method Decision-oriented HTA (DoHTA) was applied to carefully assess the diagnostic technology. It was developed starting from the EUnetHTA Core Model® integrated with the analytic hierarchy process in order to identify all the relevant assessment aspects of the technology involved, identified from scientific literature, experts’ judgments and specific context analysis of Bambino Gesù Children's Hospital. A weight was associated to each assessment element and the alternatives’ ranking was defined.

Results:

This innovative system provides orthopedic images in standing or sitting position, being able to examine the spine and lower limbs under normal weight-bearing conditions. This system is recommended for particular clinical indications as scoliosis and other congenital deformities of the spine. It is able to acquire simultaneous posteroanterior and lateral images in a single scan without vertical distortion and with lower radiation exposure than CT scanning. 2D images acquired can be combined to obtain a 3D reconstruction scanning based on a semi-automated statistical model.

Conclusions:

The major advantages of BLDS are the relatively low dose of radiation and the possibility of obtaining a 3D reconstruction of the bones. Our preliminary results show that data on the clinical effectiveness are limited but the technical advancements of BLDS appear promising in terms of patient management and patient health outcomes associated with its use.
OP56 Rehabilitation Of Memory In Brain Injury: A Cost-Utility Analysis
Authors: Harris Shaun , Fitzsimmons Deborah , das Nair Roshan , Bradshaw Lucy
Published: January 2019

Introduction:

People with traumatic brain injuries (TBIs) commonly report memory impairments which are persistent, debilitating, and reduce quality of life. As part of the Rehabilitation of Memory in Brain Injury trial, a cost-effectiveness analysis was undertaken to examine the comparative costs and effects of a group memory rehabilitation program for people with TBI.

Methods:

Individual-level cost and outcome data were collected. Patients were randomized to usual care (n=157) or usual care plus memory rehabilitation (n=171). The primary outcome for the economic analysis was the EuroQol-5D quality of life score at 12 months. A UK NHS costing perspective was used. Missing data was addressed by multiple imputation. One-way sensitivity analyses examined the impact of varying different parameters, and the impact of available cases, on base case findings whilst non-parametric bootstrapping examined joint uncertainty.

Results:

At 12 months, the intervention was GBP 26.89 (USD 35.76) (SE 249.15) cheaper than usual care; but this difference was statistically non-significant (p=0.914). At 12 months, a QALY loss of −0.007 was observed in the intervention group confidence interval (95% CI: −0.025–0.012) and a QALY gain seen in the usual care group 0.004 (95% CI: -0.017–0.025). This difference was not statistically significant (p=0.442). The base case analysis gave an ICER of GBP 2,445 (USD 3,252) reflecting that the intervention was less effective and less costly compared to usual care. Sensitivity analyses illustrated considerable uncertainty. When joint uncertainty was examined, the probability of the intervention being cost-effective at a willingness-to-pay threshold of GBP 20,000 per QALY gain was 29 percent and 24 percent at GBP 30,000.

Conclusions:

Our cost-utility analysis indicates that memory rehabilitation was cheaper but less effective than usual care but these findings must be interpreted in the light of small statistically non–significant differences and considerable uncertainty was evident. The ReMemBrIn intervention is unlikely to be considered cost-effective for people with TBI.
OP65 Genomics: From Horizon Scanning To National Health Policy
Authors: Fennessy Paul , Kearney Brendon , Mundy Linda , Howard Margaret
Published: January 2019

Introduction:

Technology advances have resulted in cheaper and quicker genomic sequencing (panels, exomes, whole genomes). Uptake into clinical practice has been rapid despite limited consideration of workforce, patient safety, consent, practice standards, guidelines and cost benefit. AUD 150M (USD 113M) has been independently allocated to genomic initiatives by Australian state and federal governments that don't reflect a national approach to genomics.

Methods:

Modified horizon scanning (HS) methodology identified issues around genomic sequencing to be considered by governments regarding their support, or otherwise, before appropriate implementation and diffusion into local healthcare systems. A national jurisdictional advisory group was subsequently established that undertook extensive stakeholder consultation across Australia, including written submissions, over a four-month period.

Results:

HS identified that genomic sequencing is diffusing rapidly through the health system and flagged issues of pressing concern, including: workforce requirements; education, training and literacy for the medical workforce and community; infrastructure; data; and ethical, legal and social implications (ELSI). HealthPACT recommended a national coordinated approach to policy development across jurisdictional boundaries to ensure appropriate adoption of genomics. Stakeholder consultation confirmed overwhelming support for greater national coordination of the application of genomic knowledge in healthcare. Five strategic priorities were developed to support appropriate integration of genomics into health care for Australians: person-centered approach; workforce; financing; services; and, data. Three principles underpin strategic priorities: i) application of genomic knowledge is ethically, legally and socially responsible and community trust is promoted; ii) access and equity are promoted for vulnerable populations; and, iii) application of genomic knowledge to health care is supported and informed by evidence and research.

Conclusions:

HS identified significant policy, workforce, funding and sustainability issues already facing state and territory governments that would, in time, face the federal government. The National Health Genomics Policy Framework outlines an agreed high-level national approach to policy, regulatory and investment decision-making for genomics and was approved by all Australian health Ministers in November 2017.
OP72 Added Value Of Using Individual Patient Data Meta-analysis
Authors: Guo Bing , Moga Carmen
Published: January 2019

Introduction:

Although individual patient data meta-analysis (IPD MA) is considered the gold standard of systematic reviews (SRs), a recent International Network of Agencies for Health Technology Assessment survey indicates that IPD MA is not frequently included in a health technology assessment (HTA), or conducted by HTA researchers. The objective of this presentation is to describe our first experience with including an IPD MA in a HTA report, discuss the added value for an evidence-based decision-making process, and advocate for expanding work in this field.

Methods:

An overview of SRs on endovascular therapy for acute ischemic stroke included one IPD MA and six study-level SRs/MAs. Methodological quality was appraised by two reviewers independently using the tool recommended by the Cochrane IPD MA working group for the IPD MA, and the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) for the study-level reviews. Pooled results from subgroup analyses based on access to primary patient data were compared to those reported in SRs that conducted subgroup analyses based on the published data to identify patients or clinical factors that would impact clinical outcomes.

Results:

The overall findings were similar between the IPD MA and other SRs/MAs. However, when compared to aggregated data used in study-level SRs/MAs, subgroup analyses based on patient data allowed for adjustment of confounders, multiple categories within a subgroup, standardization of outcomes across trials, and detailed data checking. Larger sample sizes of each pre-defined subgroup permitted for more precise estimates of treatment effects. A number of methodological issues in the IPD MA were identified; particularly, no assessment of risk of bias of included trials was conducted.

Conclusions:

Access to original patient data is demanding and conducting IPD MA requires extensive resources. The advantages of having an improved quality analysis, an appropriate quantification of the effects in the analyzed subgroups, and precision of results may justify additional efforts, and may increase confidence in the decision-making process.
OP75 Tailoring Review Methods: Scope, Timescale And Needs Of Commissioners
Authors: Cooper Katy , Harnan Susan , Preston Louise , Campbell Fiona , Chatters Robin , Kaltenthaler Eva , Pandor Abdullah
Published: January 2019

Introduction:

Commissioners of systematic reviews have differing requirements in terms of breadth of scope, level of analysis required, and timescales available. Planning a review requires consideration of the trade-off between these elements. This applies to both “rapid” reviews and “traditional” reviews with a broad or complex scope.

Methods:

Approaches for tailoring review methods to commissioner requirements are described. These will be illustrated via case studies of reviews conducted for the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) and Health Services & Delivery Research (HS&DR) programs and other organizations.

Results:

An initial step is to discuss with commissioners the trade-off between timescales/resource available, breadth of review scope, and level of analysis; for example, broad overview of many studies or in-depth analysis of a narrower set. Where the evidence base is unknown, one option is to undertake an initial mapping review to assess the volume and type of evidence available. This may assist in refining the selection criteria for the main review, to prioritize the most relevant evidence. In complex reviews, a further option is to develop a conceptual model (logic model) with input from commissioners and experts, to help identify factors which may influence outcomes. This can enable design of focused mini-reviews (not necessarily exhaustive) around each factor. These methodological approaches will be illustrated through three case studies including an HTA on cannabis cessation (trade-off of breadth versus depth); a review of yoga and health (initial mapping to refine selection criteria); and a rapid review of congenital heart disease services (conceptual model to identify areas for focused reviews).

Conclusions:

Different approaches may enable discussion with review commissioners around the trade-off between scope, methods and timescales, in order to tailor the review method to best meet commissioner requirements within the timescales available.
OP78 Code Of Ethics: Missing Cord In The Evidence-To-Action Connection?
Authors: Nyamadzawo Evidence
Published: January 2019

Introduction:

Ethics is a set of moral principles that guide our behavior when it affects others. HTAi acknowledges the fundamental values of “service, collaboration, professionalism and integrity, transparency, accountability”. Ethical conduct balances self-interest with consequences of that behavior for others. Unethical behavior has serious personal consequences and in the case of HTA practitioners it can damage stakeholder trust and thereby hinder implementation of evidence by policy makers. Compliance with regulation alone may not suffice in building stakeholder confidence. There is need for individuals and agencies to develop a ‘culture of integrity’ at all levels in the HTA process above and beyond compliance with the law. A strong ethical culture will foster trust of stakeholders, strengthen collaboration, improve implementation of recommendations and benefit society. This is the importance of developing a code of ethics to guide conduct and detail standards of professional practice expected of HTA practitioners affiliated to HTAi and related agencies.

Methods:

I will argue for the development of a detailed code of ethics for HTAi and related agencies. To do this, I will explain how the code of ethics gives guidance and informs the users (HTA practitioners), and how they can guide stakeholders in the HTA processes. The public relations benefits of a code of ethics will also be discussed. I will explain why having a mere list of seven words as “values” is not sufficient guidance to professionals with diverse backgrounds who are collaborating in a multidisciplinary team.

Results:

The role of a code of ethics in helping professionals to choose their actions well is an effective way to integrate ethics in HTA, safeguard the integrity of HTA processes, and improve evidence implementation by stakeholders.

Conclusions:

HTAi should develop a detailed code of ethics for its membership.
OP92 Non-Opioid Therapy For Pain Management – Health Technology Assessment In A Time Of Crisis
Authors: Mann Janice , Mulla Sohail , Pant Sirjana
Published: January 2019

Introduction:

North America is facing a public health epidemic – the opioid crisis – part of which is attributed to the inappropriate use of opioids in pain management. As such, the 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain recommends optimizing non-opioid pharmacotherapy or non-pharmacological therapy to treat chronic pain, before a trial of opioids. However, the Guideline itself is not designed to provide evidence on the effectiveness of these non-opioid alternatives, leaving a gap for those attempting to put the recommendation into practice.

Methods:

In collaboration with its partners, including clinicians and policymakers, the Canadian Agency for Drugs and Technologies (CADTH) identified the gaps in evidence, and developed an action plan to bridge the evidence gaps to support the optimization of non-opioid alternatives in pain management.

Results:

Since the release of the Guideline, CADTH produced over 20 Rapid Response reports that synthesize and appraise evidence on non-opioid alternatives in the management of a wide range of pain, both acute and chronic. Additionally, CADTH has also reviewed evidence on multidisciplinary pain treatment programs, and is developing environmental scan reports on the availability and access to non-pharmacological treatments for pain in Canada, and on drugs for emerging non-opioid pain. Further, CADTH developed knowledge mobilization tools based on the evidence reviews. The evidence reviews and tools are used as a resource by CADTH partners, including the Coalition of Safe and Effective Pain Management and McMaster University National Pain Center.

Conclusions:

This presentation will discuss the role of HTA and CADTH to fill the gaps in evidence for a crucial clinical practice guideline recommendation in a time of public health crisis, and help put the evidence into action. It will present the evidence synthesized by CADTH on various non-opioid alternatives for pain management, while highlighting the remaining gaps in evidence. Understanding the evidence on non-opioid alternatives will inform clinical and policy decisions and potentially reduce inappropriate use of opioids in pain management.
OP105 Disinvestment Toolkit: Patients Involvement In Disinvestment Activities
Authors: Wale Janney , Bond Ken , Wortley Sally , Martin Janet , Godman Brian , Gutiérrez-Ibarluzea Iñaki
Published: January 2019

Introduction:

Patients are the people who, with their informed consent, receive medical interventions. It is important, therefore, that patients have an understanding of interventions and their potential as a treatment for their condition. Patients are becoming more informed about their health care and the treatments that are available to them. At a population level, the potential benefits and harms of treatments need to be regularly assessed. This is part of healthcare decision making at a policy level about what treatments are publically available. As technology develops and old methods are replaced by new and evidence-based interventions and procedures, healthcare payers look to streamline their payment schedules and disinvest in old technologies and procedures. Some users of health care are reluctant to let go of outmoded methods, so disinvestment is best achieved through transparent processes. Successful engagement with key stakeholders of health care, engaging with payers, health service administrators, clinicians and patients, can facilitate implementation of disinvestment processes.

Methods:

To assist in this process, Health Technology Assessment International (HTAi) Interest Groups and EuroScan have come together to develop the following key points to consider in the involvement and engagement of clinicians, patients, and the public in the disinvestment of services and technologies.

Results:

The best time to involve clinicians and patient representatives is right at the beginning of the process. Clinicians and patients can make valuable contributions as advisory committee members. The disinvestment processes may be led by clinicians, payers, or independent organizations. This will likely influence commitment of clinicians to the process.

Conclusions:

Broader consultation with clinicians, patients and the public in the development and consideration of draft reports and recommendations can increase the transparency of the disinvestment process. Consultation is an important means of obtaining buy in. Feedback needs to be seen as taken seriously, and explanations given for any changes made or not made to the report and its recommendations.
OP114 The Public's Role In Understanding The Value Of Health Technologies
Authors: Stafinski Tania , Street Jackie , Menon Devidas
Published: January 2019

Introduction:

Increasingly, health technology assessment (HTA) organizations have instituted mechanisms for involving patients in assessment and review processes. The reasons are obvious—to understand the “patient experience” with a disease and to ensure that patient perspectives are considered during deliberations about the value of new treatments. More recently there have been efforts to engage the public in HTAs and HTA-informed decision-making processes. However, the goals of these efforts have not been well articulated. This may be attributable to the lack of a shared definition of “the public”. The objective of this study was to develop a common understanding of the term “the public” within the context of HTA.

Methods:

The following were conducted: a survey of HTA organizations; a systematic review; consultation with Health Technology Assessment international's Special Interest Group on Patient and Citizen Involvement; and a workshop comprising representatives from patient organizations, industry, and HTA bodies in Canada.

Results:

In many HTA processes, the terms “public” and “patients” are synonymous. Definitions found in scholarly articles vary and depend on the rationale for involving the public in a particular issue. Through consultations it became clear that, in the context of HTA, the definition depends on understanding what is missing from current deliberations around the value of new health technologies. There was consensus among workshop participants that: (i) “patients” and “the public” are not the same; (ii) the role of the public may be to ensure societal values are reflected in HTAs and HTA-informed decision-making processes (e.g. serving an audit function); and (iii) a legitimate definition of “the public” could be: “A non-aligned community member with no commercial or professional interest in the HTA process who is not a patient or member of a stakeholder group”.

Conclusions:

Consensus on the use of the terms “patient” and “public” will support rigorous, evidence-based public and patient engagement in HTA. The proposed definition indicates a way forward in this debate.