bluuebunny/crossref_metadata_2025 huggingface dataset:
β-Elimination as major side reaction in periodate-oxidation of cellulosic model mono- and disaccharides
Authors: Sasaki Jumpei , Kosma Paul
Published: December 2023

To structurally characterize periodate-oxidized cellulosic substrates, methyl 4-O-methyl β-d-glucopyranoside and methyl 4’-O-methyl-cellobioside were subjected to periodate treatment at pH 4.8–5.0. Oxidation of the monosaccharide using two molar equivalents of oxidant produced 3-methoxy-2,5-dihydro-2-furanol as main product. To confirm its structure and mode of formation, 6-O-bisdeuteromethyl 4-O-methyl-β-d-glucopyranoside and methyl 4-O-trisdeuteromethyl-β-d-glucopyranoside were synthesized and oxidized to generate 3-methoxy-5-deutero-2-hydro-2-furanol in the former case and 3-trisdeuteromethoxy-2,5-dihydro-2-furanol in the latter case. Oxidation using one molar equivalent of periodate led to preferential formation of hemialdal products and (E)-4-hydroxy-2-methoxy-2-butenal. The latter product was also formed upon end-wise oxidation of methyl 4’-O-methyl-cellobioside, wherein the reducing unit was released as non-oxidized methyl β-d-glucopyranoside. This data indicate that periodate oxidation of cellulosic model substrates might be accompanied by peeling reactions and formation of β-elimination products even under slightly acidic conditions.

Graphical abstract
Distalization of perianal fistulas after loose silicone seton drainage is a myth
Authors: Verkade Carolien , van Tilborg G. Fiek A. J. B. , Stijns Jasper , Wasowicz Daria K. , Zimmerman David D. E.
Published: December 2023

Background

It is often stated that loose seton drainage results in distal migration of a fistula tract in perianal fistula. The aim of the present study was to assess this distalization of trans- and suprasphincteric perianal fistulas after a silicone seton has been inserted.

Methods

Consecutive patients who underwent loose seton placement for the management of a transsphincteric or suprasphincteric fistula between January 2016 and December 2021 with a pre- and postoperative magnetic resonance imaging (MRI) were included in the present retrospective study. The height of the external anal sphincter (EAS) and the level of penetration of perianal fistula through the EAS or puborectal muscle (PRM) were determined on MRI. Primary outcome was migration of the fistula tract through the EAS and PRM.

Results

Thirty-eight patients with perianal fistulas were included. Median height of the EAS was 28 (IQR 25–34) mm before seton placement and 27 (IQR 24–33) mm afterward. Median level of perforation was 32 (IQR 17–40) mm before seton placement and 28 (IQR 17–40) mm afterward (p = 0.37). One fistula (3%) was downgraded from mid to low transsphincteric and was laid open after 14.9 months of loose seton drainage.

Conclusions

No statistically significant distalization of complex fistula tracts after loose silicone seton drainage was found. Some complex fistulas may downgrade to a less complex fistula after long-term seton drainage. However, loose silicone seton drainage should not be offered to patients as a treatment option to downgrade a complex fistula to a simple one or even have the hope to heal it.
Temporally extended goal recognition in fully observable non-deterministic domain models
Authors: Pereira Ramon Fraga , Fuggitti Francesco , Meneguzzi Felipe , De Giacomo Giuseppe
Published: December 2023

Goal Recognitionis the task of discerning the intended goal that an agent aims to achieve, given a set of goal hypotheses, a domain model, and a sequence of observations (i.e., a sample of the plan executed in the environment). Existing approaches assume that goal hypotheses comprise a single conjunctive formula over a single final state and that the environment dynamics are deterministic, preventing the recognition of temporally extended goals in more complex settings. In this paper, we expand goal recognition totemporally extended goalsinFully Observable Non-Deterministic(fond) planning domain models, focusing on goals on finite traces expressed inLinear Temporal Logic(ltl$$_f$$f) andPure-Past Linear Temporal Logic(ppltl). We develop the first approach capable of recognizing goals in such settings and evaluate it using differentltl$$_f$$fandppltlgoals over sixfondplanning domain models. Empirical results show that our approach is accurate in recognizing temporally extended goals in different recognition settings.
Role of La2O3 in enhancement the properties of the BaO–B2O3 glass system: optical and radiation shielding study
Authors: Zenhom Kamilia , Ebrahem Nasra M. , Mohammad S. S. , Saudi H. A.
Published: December 2023

This work aims to prepare modified glassy barriers of the composition (70 − x) mol% B2O3 + 20 mol% Na2O + 10 mol% BaO + x mol% La2O3 for use as radiation shielding materials. The cooling method has been considered for the sample’s preparation process. The structural properties were investigated using density and Infrared Spectroscopy. The hardness of the prepared glasses was studied. The optical transmittance and absorbance of the prepared glasses was measured using optical spectra measurements. The prepared samples were exposed to a parallel beam of gamma rays emitted from different radioactive sources. Moreover, the shielding properties were evaluated experimentally and theoretically. The resulting value of the proposed programs is largely in line with the experimental values. The results prove that the studied glass has a largely shielding behavior for gamma rays by increasing lanthanum and vice versa for neutrons. In addition, it has been observed that the absorbance of glass samples and hardness values increase with increasing lanthanum content.
Symbiosexuality: A Review of Discourses of Attraction to the “Third Force” Created by People in Relationships
Authors: Johnston Sally W.
Published: December 2023

Symbiosexuality, the individual experience of attraction to people in relationships, has not been examined as a lived experience. Lack of recognition and examination of symbiosexuality is surprising when one considers studies of romantic and sexual desires and behaviors associated with more than two people. Also evident in the existence of the sexual identity label known as the unicorn and easily found in essays, memoirs, and dating apps, this attraction proves salient. Further, we find evidence of symbiosexuality outside Western discourses on desire and sexuality. Dominant conceptions and assumptions about sexuality and desire including mononormativity, respectability politics within polyamorous communities, and current conceptions of desire within western discourse contribute to symbiosexual invisibility. This invisibility harms several sexual minority groups, especially women and gender minorities within these groups. The purpose of this review is to describe and provide evidence of the phenomenon of symbiosexuality. Through a queer-feminist lens, I argue that recognition of symbiosexuality will fill a knowledge gap in the field of sexuality studies on the nature and shape of human sexual attractions and may be validating and/or empowering to those experiencing these types of attractions.
Fiscal Policy and Child Poverty in Ethiopia
Authors: Ambel Alemayehu A. , Belete Getachew Yirga , Fiala Oliver
Published: December 2023

This study investigates the effects of public transfers and taxes on the wellbeing of children in Ethiopia. It applies the Commitment to Equity for Children (CEQ4C) methodology to examine the burdens of taxation and the benefits from government transfers and spending, and their differential wellbeing impacts on children. The study integrates data from the Ethiopia Socioeconomic Survey 2018/19, which also collected data on taxes and transfers, with administrative data. Measuring its distribution by child monetary and multidimensional wellbeing, the study finds, on average, a progressive, poverty-reducing and equalizing fiscal system. However, there are important differences in the distribution of some of its elements. Indirect taxes, comprising of VAT and excise taxes, are regressive. Similarly, primary education spending, the largest of in-kind transfers, is only progressive in urban areas. With regards to poverty and inequality, the fiscal system reduced the monetary child poverty headcount by 21% and the poverty gap by 33%. The effect is stronger for girls and children in rural areas than for boys and children in urban areas, therefore reducing inequalities in poverty rates. However, this is only the case when in-kind transfers for education and health are considered. Without the inclusion of in-kind transfers, the study finds that the fiscal system is not well calibrated to reduce poverty. This highlights the essential role of public services, not only in delivering fundamental child rights, but also in reducing poverty amongst children.
A transboundary agenda for nature-based solutions across sectors, scales and disciplines: Insights from carbon projects in Southeast Asia
Authors: Miller Michelle Ann , Taylor David
Published: December 2023

Nature-based Solutions (NbS) are integral to efforts to keep global warming below 2°C in accordance with the United Nations’ 2015 Paris Agreement on Climate Change. Yet the transboundary governance dimensions of NbS remain unclear and largely undocumented. In Southeast Asia, NbS have emphasised the conservation and/ or sustainable commodification of carbon sinks found in terrestrial and mangrove forests, seagrass meadows, peatlands and agricultural soils. Mostly project-driven and fixed-term, these “solutions” have often failed to meet their social and ecological objectives. Increasingly, they have added to cross-border problems of: (1) displaced carbon emissions; and (2) economic migration and societal dispossession. This perspective paper delineates a transboundary governance research agenda to mitigate these trade-offs and enhance the co-benefits of NbS in carbon sinks. Building on NbS literature, it identifies cross-sector, multi-scalar and interdisciplinary pathways to improve transboundary cooperation, inclusion and equity in carbon sink governance in varying Southeast Asian contexts.
A New Eyeless Species of Micranops Cameron 1913 from Bolivia (Coleoptera: Staphylinidae: Paederinae)
Authors: Guzman Yoan Camilo , Żyła Dagmara
Published: December 2023

This work adds a new eyeless species of the genusMicranopsCameron, 1913 (Staphylinidae, Paederinae, Scopaeina) to the endogean Coleoptera of the Bolivian fauna. The loss of eyes is usually associated with adaptations to subterranean habitats, althoughM. bolivianusGuzman & Żyłasp. nov.was collected from leaf litter. We also report new occurrences for the genus west of the Andes mountain range. Our work increases the number of known NeotropicalMicranopsspecies to seven and extends the known distribution range for the genus in South America.
Extended analysis of benchmarks for gas phase appearance in low-permeable rocks
Authors: Grunwald Norbert , Nagel Thomas , Pitz Michael , Kolditz Olaf
Published: December 2023

This manuscript presents a comprehensive study on the numerical simulation of gas transport in clay rock using the finite-element method, with a specific focus on the transition of the transport regime from single-phase to two-phase conditions. Our code demonstrates the capability to cover this transition seamlessly, without relying on common approaches such as the use of persistent primary variables or the switching of primary variables. In our simulations, the primary variables are gas pressure, capillary pressure, temperature, and displacement of the solid phase. To validate our approach, two benchmark tests were conducted. The first benchmark replicates a well-known scenario in the field of radioactive waste disposal, where gas injection induces a transition from single-phase to two-phase flow. The second benchmark simulates a core drilling experiment, where the mechanical unloading of a fully saturated domain results in the appearance of a gas phase. In addition to analyzing primary quantities, a comprehensive set of secondary variables was introduced to gain deeper insights into the model’s operation and enhance understanding of the underlying processes. By plotting these secondary variables alongside the primary quantities, a comprehensive understanding of the system’s behavior during the transition of flow regimes was obtained. The primary objective of this work is to improve our understanding and confidence in the model used for simulating large repository systems, particularly in the context of nuclear waste disposal and CO$$_2$$

2

storage. By successfully capturing the transition from single-phase to two-phase gas transport, our study provides valuable insights into the behavior of gas in clay rock. This enhanced understanding lays the groundwork for utilizing the model effectively in large-scale repository simulations, contributing to the advancement of the field of gas transport in clay rock.
CBT-Based and eHealth-Supported Case Management for Patients with Panic Disorder or Depression in Primary Care: Results of a Proof of Concept
Authors: Lukaschek K , Lezius S , van den Akker M , Hanf M , Zapf A , Heider D , König H H , Gensichen J ,   for the PREMA-study group
Published: December 2023

Evaluation of a team-based intervention in primary care that includes cognitive behavioural therapy elements and case management and was supported by eHealth components in patients with panic disorder with or without agoraphobia (PD ± AG) and/or depression. In a two-armed cluster-randomised controlled trial (cRCT), mental health conditions were assessed by the Mental Health Index (MHI-5), Patient Health Questionnaire (PHQ-9), Overall Anxiety Severity and Impairment Scale (OASIS), Panic and Agoraphobia Scale (PAS), Mobility Inventory for Agoraphobia (MIA), and Patient Assessment of Chronic Illness Care (PACIC) at baseline (T0), after 6 months (T1), and after 12 months (T2). Scores were analysed as differences from baseline using a mixed linear model with general practitioner (GP) as a random intercept and treatment, time point, and respective baseline value as fixed factors. The majority of participants (mean age 54 years, SD 12.8 years) were women (n = 40, 67.8%). We found consistent mean effects in favour of the intervention group (MHI-5 index, 6.66 [−7.38; 20.70]; PACIC, 15.92 [4.58; 27.26]; PHQ-9, −3.43 [−5.71; −1.14]; OASIS, −2.89 [−5.41; −0.37]). A cautious interpretation indicates promising effects of the intervention. Obstacles to recruitment included the workload for GPs and medical assistants (MAs), potential reservations regarding eHealth, and the onset of the COVID-19 pandemic.

Trial registration:

The study was registered at the German Clinical Trials Register (DRKS00016622) on February 22nd, 2019. https://drks.de/search/de/trial/DRKS00016622.
Comorbid Eating Disorders and Obsessive-Compulsive Disorder
Authors: DiLossi Jenna , Harrison Melissa
Published: December 2023

Numerous studies have shown that individuals with eating disorders (EDs) have statistically higher rates of OCD and vice versa, yet there has been no comprehensive book dedicated to their comorbidity. This clinical guide fills that gap and provides a tool for health professionals working with patients presenting with both diagnoses. This book reviews the existing literature on the comorbidity of these disorders, and the perspectives of the authors' clinical practice working with OCD and EDs. Chapters cover clinical pitfalls, assessment, and suggested treatments, detailing the overlap between both illnesses and how comorbidity changes the overall presentations. The authors provide evidence-informed clinical suggestions for existing treatments, in addition to several case study examples, to highlight ways in which to better improve care for patients. A must-read for clinicians who have either experience with or want to expand their knowledge on how to assess and treat the co-occurrence of OCD and EDs.
Live birth rate of gonadotropin-releasing hormone antagonist versus luteal phase gonadotropin-releasing hormone agonist protocol in IVF/ICSI: a systematic review and meta-analysis
Authors: Liu Chenhong , Tian Tian , Lou Yanru , Li Jia , Liu Ping , Li Rong , Qiao Jie , Wang Yuanyuan , Yang Rui
Published: December 2023

In vitro fertilization (IVF) and embryo transfer and intracytoplasmic sperm injection (ICSI) have allowed millions of infertile couples to achieve pregnancy. As an essential part of IVF/ICSI enabling the retrieval of a high number of oocytes in one cycle, controlled ovarian stimulation (COS) treatment mainly composes of the standard long gonadotrophin-releasing hormone agonist (GnRH-a) protocol and the gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol. However, the effectiveness of GnRH-ant protocol is still debated because of inconsistent conclusions and insufficient subgroup analyses. This systematic review and meta-analysis included a total of 52 studies, encompassing 5193 participants in the GnRH-ant group and 4757 in the GnRH-a group. The findings of this study revealed that the GnRH-ant protocol is comparable with the long GnRH-a protocol when considering live birth as the primary outcome, and it is a favourable protocol with evidence reducing the incidence of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI, especially in women with polycystic ovary syndrome. Further research is needed to compare the subsequent cumulative live birth rate between the two protocols among the general and poor ovarian response patients since those patients have a lower clinical pregnancy rate, fewer oocytes retrieved or fewer high-grade embryos in the GnRH-ant protocol.
Are You Talking to Me? How Ideological and Gender Characteristics Moderate the Effect of Legitimizing Rhetoric on SCOTUS Legitimacy
Authors: Williams Ryan J. , Christiani Leah
Published: December 2023

Possessing neither purse nor sword, the unelected US Supreme Court relies on sustained public confidence in its institutional credibility to give force to its decisions. Previous research shows that Supreme Court justices are increasingly making public appearances to engage in a course of institutional maintenance to preserve its legitimacy. Amid a potential legitimacy crisis, justices seek to shore up the Court’s public support in these public appearances by emphasizing the apolitical nature of the Court and its decision making. The question for a growing body of literature is whether these attempts at institutional maintenance do, in fact, lead to higher support for the Court. Using an original survey experiment where we manipulate the identity of the justice giving legitimizing rhetoric, we find that respondents’ ideological preferences and female respondents’ level of gender identity do impact the effectiveness of such rhetoric. These results build on previous work by demonstrating the importance of justice identity in conditioning how different ideologues respond to the Court’s elite signals.
Exploring Litigation, Court Rulings, and Legal Mobilization in Response to Death and Suicide from Overwork: Implications for Labor Law Reform Policy Making in Japan
Authors: Sala Adrienne
Published: December 2023

This article analyzes how litigation, court rulings, and legal mobilization have influenced law and policy making related to death from overwork (karōshi) and suicide from overwork (karōjisatsu) in Japan over the course of half a century. It highlights the gradual, but substantial, impact of litigation and court rulings on different levels of governmental measures. By taking a longer-term perspective to assess the political effects of different stages of the judicialization process and focusing on the actors of legal mobilization—particularly, cause lawyers—this study provides a more accurate depiction of the overall process of social and legal changes observed in the recent Japanese labor law reform.
Migrants’ access to healthcare services: evidence from fieldwork in Turkey
Authors: Genç H. Deniz , Elitsoy Z. Aslı
Published: December 2023

This study builds on an analytical framework of access to healthcare and, using notes from interviews conducted with 110 migrants of different categories, it discusses the fit between migrant patients and Turkish health services. There is an overall mediocre fit between migrant patients and the Turkish healthcare system, which varies for different migrant groups, and is influenced by the dimensions of awareness, availability, affordability, and accommodation. Migrants’ social capital and socio-economic statuses affect the degree of fit, while irregularities in their legal statuses do not necessarily create a misfit. The existence of many private healthcare institutions offering various services to patients with different incomes and operating in informal ways has improved accessibility, availability, affordability, and accommodation and thus affects the fit positively. Therefore, the health reforms that paved the way for privatization, marketization, and commodification of health services in Turkey in the early 2000s also help explain the degree of fit. Migrants suffer most from language barriers in the health system, and there is an alarming decline in acceptability especially for Syrian refugees, who have reported facing discrimination while seeking healthcare.
OP09 Developing A Patient And Consumer Training Tool Explaining Health Technology Assessment And Patient/Consumer Participation: The French Experience
Authors: Low Eunice , André-Vert Joëlle , Guerrier Marc , Fanelli Gaëlle , Galbraith Margaret
Published: December 2023

Introduction

The French National Authority for Health’s (HAS) 2019-2024 strategic workplan called for “making public involvement a priority.” This project was designed within the roadmap validated in 2021; “Strengthening public involvement in health technology assessment (HTA) at the HAS”, including an action of building a means of training patient organizations for their contribution. The project’s overall objective was to develop with patients and consumers a first training tool, representing an online knowledge base targeting French patients and consumers to explain the HAS HTA process and assist their participation in these assessments.

Methods

Three stages were designed to meet this objective. Firstly, an international benchmark was performed of available online HTA training tools for patients and consumers, notably those used by HTA bodies and European and international patient and consumer groups (PCGs). Secondly, an internal HAS search for e-learning tools, was conducted to identify whether they could meet the training needs of French patients and consumers. Finally, the training tool was developed via a working group composed of patients and HAS scientific officers.

Results

The benchmark identified 82 online training tools selected according to the specified inclusion criteria. Sixteen international HTA agencies, nine European and international PCGs and 13 other bodies provided online HTA training tools for patients and consumers during the research period, but no journal articles identified such tools. Eleven formats and 12 key themes, divided into two main categories were identified: important content related to HTA, and important content related to public involvement in HTA. The HAS search for e-learning tools resulted in internal e-learning tools offered for clinical experts not meeting the needs and preferences of patients and consumers. Finally, HAS based its training tool development on these preferences and needs to create a PowerPoint in two blocks of modules covering the two main categories above (six modules in total).

Conclusions

French patients and consumers preferences and needs for a HTA training tool were inspired by the international benchmark, dividing key themes into two main categories: important content related to HTA, and important content related to public involvement in HTA. This resulted in HAS development of two blocks of modules in PowerPoint format covering these two categories.
OP10 Standardized Multilingual Reporting Of Health Technology Assessment And Stakeholder Involvement
Authors: Nunn Jack , Mason Gillian
Published: December 2023

Introduction

There is currently no standardized way to share information about health technology assessment (HTA). Standardised Data on Initiatives (STARDIT) addresses current limitations and inconsistencies in sharing data about HTA processes by providing a way to report these data, including which stakeholders have been involved, their tasks, what methods and data sources were used, and any impacts or outcomes observed.

Methods

STARDIT development began in 2019 and was guided by participatory action research paradigms. A multidisciplinary international team of over 100 citizens, experts, and data users was involved in co-creating STARDIT. These co-creators include cancer patients, people affected by rare diseases, Indigenous peoples from multiple countries, representatives involved in HTA processes, health researchers, environmental researchers, economists, librarians, and academic publishers. Methods of involving people included public events, online discussions, and a public consultation process. STARDIT is free to use, and data can be submitted by anyone. Report authors can be verified to improve trust and transparency, and data can be checked for quality.

Results

STARDIT can help create high-quality standardized information about HTA processes that can be accessed and edited by anyone. STARDIT enables data reporting at all stages of the HTA process and works in multiple languages. This allows stakeholders involved in or affected by HTA processes (including patients, the public, Indigenous peoples, and people from industry) to appraise and edit information and to self-identify the labels and terminology used to describe them. Organizations such as the Cochrane Collaboration, Australian Genomics, and multiple universities have created STARDIT reports. A link to the working beta version can be found at scienceforall.world/STARDIT.

Conclusions

STARDIT offers those conducting HTA access to standardized information that enables well-founded comparisons of the effectiveness of different HTA methods, including the most effective methods of involving stakeholders. STARDIT allows anyone to access data about HTA processes, which can support participatory ways of working and help improve the equity and quality of HTA processes worldwide.
OP21 Patient Values Project (PVP): Patient Preferences For Cancer Treatments To Inform A Framework Incorporating Patient Values Into Health Technology Assessment
Authors: Marshall Deborah A , MacDonald Karen V , Stein Barry
Published: December 2023

Introduction

The methodology for explicitly incorporating patient preferences by expert committees engaged in deliberative health technology assessment (HTA) processes for drug reimbursement recommendations is a relatively unexplored area despite the growing emphasis on patient-reported outcomes and patient engagement. The Patient Values Project (PVP) aims to improve patient input to expert review committees and promote a better understanding of the patient perspective using quantitative data to support the rationale in assessing new cancer drugs. Using colorectal cancer as a starting point, the PVP aims to develop a framework to objectively incorporate quantitative patient values and preferences into Canada’s cancer drug HTA decision-making process. We report on results from the first phase.

Methods

In the first phase, we developed a bilingual survey informed by qualitative focus groups, literature review and feedback from clinicians, patients and experts. The survey includes background questions, general and cancer specific quality-of-life tools, two discrete choice experiments (DCE) and a best worst scaling (BWS) experiment. After pre-testing and pilot testing, the survey was administered across Canada to metastatic and non-metastatic colorectal cancer patients and caregivers, in addition to adults from the general population. In the next phases, we will use vignettes to explore how patient preferences could be incorporated explicitly into decision-making, and what approach to use in HTA submissions.

Results

DCE1 survey results (˜n=1,000) reflect trade-offs between health-related quality-of-life and survival; DCE2 results reflect trade-offs between treatment regimens, side effects and survival/risk of recurrence; BWS results ranked and weighted the tolerability of 25 possible side effects of treatment. We observed differences in preferences amongst the general population, patients with metastatic cancer, non-metastatic cancer and caregivers.

Conclusions

Patients have unique perspectives and preferences about what is important and of value to them, which may impact patient adherence to treatment. In the next phases, we will explore how this evidence from patient preferences can be translated into values that could potentially be incorporated as an explicit element of the deliberative process for HTA decision-making.
OP23 Early Detection Tools For Emotional Distress In Adult Cancer Patients In Spain: A Health Technology Assessment Report
Authors: Gomez-Salgado Patricia , Triñanes Yolanda , Casal-Acción Beatriz , Faraldo-Vallés María José
Published: December 2023

Introduction

Patient-reported outcome measures are being increasingly considered both in clinical practice and in the field of health technology assessment. Although emotional distress is currently recognized as the sixth vital sign in cancer care, its early detection and screening is not yet included in routine clinical practice in Spain. The main objective of this study was to assess the psychometric properties and diagnostic accuracy of validated tools for the early detection of distress among adults with cancer in the Spanish context, at the request of the Spanish National Health System (NHS) Cancer Strategy.

Methods

A systematic review was carried out to analyze development and validation studies. The Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) was used for the risk of bias assessment, and a multicriteria global assessment was used for the tests. Ethical and organizational aspects were also addressed.

Results

Fifteen validation studies were included, corresponding to seven tests. The tools considered were the Distress Thermometer (DT), the Brief Symptom Inventory-18 (BSI-18), the Edmonton Symptom Assessment System-revised (ESAS-r), the Hospital Anxiety and Depression Scale (HADS), the Visual Analog Scale for Anxiety and Depression (VAS-AD), the Detection of Emotional Distress (DED) scale, and the Psychosocial and Spiritual Needs Evaluation (ENP-E) scale. Evidence of validity, reliability (internal consistency), and diagnostic accuracy (sensitivity, specificity, and area under the receiver operating characteristic curve) were summarized. Three scales were rated as poor (VAS-AD, BSI-18, and ESAS-r), the ENP-E scale was rated as acceptable, and three scales were rated as moderate (DT, DED, and HADS).

Conclusions

The DT (single-item measure) stands out as an appropriate tool for early detection of emotional distress in the Spanish NHS. The use of this scale could be considered a first stage, to be combined later with a longer scale to improve screening specificity. The HADS scale could be utilized for this purpose. The use of these tools should be framed within a structured screening program that ensures further evaluation and subsequent psychological care when needed.
OP51 Use Of Real-World Data In Cost-effectiveness Analysis Of Sequential Biologic Treatment For Rheumatoid Arthritis
Authors: Singh Janharpreet , Stevenson Matt , Hyrich Kimme , Gillies Clare , Abrams Keith , Bujkiewicz Sylwia
Published: December 2023

Introduction

In health technology assessment (HTA), economic evaluations assessing biologic drugs for rheumatoid arthritis (RA) involve modeling patients’ responses to multiple treatments given sequentially over a lifetime horizon. When data from randomized controlled trials (RCTs) are scarce, data from non-randomized studies (e.g., single-arm trials [SATs] and disease registries) can be used to supplement the evidence base. This research aimed to demonstrate meta-analytic methods for combining effectiveness data from randomized and non-randomized studies and their corresponding impact on cost-effectiveness estimates.

Methods

Data comparing patients receiving second-line rituximab with continued background non-biologic treatment were extracted from one RCT and six SATs identified in an HTA assessing second-line rituximab for RA, and from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis, by applying a target trial emulation approach. A binomial meta-analysis model was used to estimate the probabilities of achieving the European League against Rheumatism (EULAR) response criteria by pooling data from the RCT, SATs, and the registry. The probabilities were entered into a decision model from a previous HTA to derive incremental cost-effectiveness ratio (ICER) estimates for treatment strategies with and without biologic drugs.

Results

Compared with the original analysis, the estimated probability of at least a moderate EULAR response on rituximab from combined sources was substantially lower. For example, the probability obtained from an RCT was 0.68 (95% credible interval [CrI]: 0.345, 0.907), but only 0.29 (95% [CrI]: 0.242, 0.333) when using RCT plus registry data and 0.29 (95% CrI: 0.244, 0.336) for combined RCT, registry, and SAT data. In the cost-effectiveness analysis, the median ICERs were higher when including real-world
data.

Conclusions

Synthesis of all relevant data, including RWD, provides additional information regarding the variability in cost-effectiveness estimates and can be considered in sensitivity analyses for HTA decision-making.
OP54 Experiences With Out-Of-Hospital Drug Treatment For Systemic Lupus Erythematosus: A Thematic Synthesis
Authors: Portugal Clarice , Sacramento Adriana , de Souza Andrea Brigida , Almeida Andrija , Losco Luiza , Fonseca Mariana , Barros Melina , Canuto Vania
Published: December 2023

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects quality of life and sometimes requires the use of multiple drugs. Therefore, it is relevant to address the experiences of patients, family members, and caregivers in relation to out-of-hospital SLE drug treatment. This paper presents the results of a pilot project of a Qualitative Evidence Synthesis (QES) conducted by the National Committee for Health Technology Incorporation (Conitec) in the Brazilian public health system.

Methods

For this thematic synthesis, a structured search was conducted in the MEDLINE, CINAHL, and LILACS databases. Seventeen articles were included, and their quality was evaluated using the Critical Appraisal Skills Program criteria. Article content, which was extracted into a spreadsheet adapted from JBI SUMARI, underwent thematic content analysis. Confidence in the findings was evaluated using the GRADE Confidence in the Evidence from Reviews of Qualitative Research tool.

Results

Fifteen findings related to three central themes: self-image and appearance; SLE as a chronic disease (disease oscillation, recurrence of symptoms, fear of organ damage, expectation of cure or modification of the disease course, and frequency of medical appointments); and experience with drug therapy (belief in the need for drugs, skepticism, chronicity of treatment, financial difficulty, adverse effects as obstacles to adherence and a source of suffering, efficacy/effectiveness, large quantity and frequency of drugs, and multiple therapeutic attempts).

Conclusions

The findings suggest that patients, family members, and caregivers have an ambivalent relationship with drug treatment. Even though they believe in the effectiveness of the drugs, they also distrust the need to keep using them, especially when SLE is controlled. The improvement of cosmetic manifestations and adverse effects also seem to be important outcomes. Furthermore, the high occurrence of adverse effects and the daily use of many drugs can make treatment adherence harder. In any case, there is an expectation of cure or more significant impact on the course of the disease through pharmacotherapy.
OP80 Diagnostic Molecular Sequencing Of DNA (Exomes And Genomes) Is Not Perfect: Implications For HTA
Authors: Schubert Camille , Goodall Stephen , Merlin Tracy
Published: December 2023

Introduction

The recent release of powerful next-generation sequencing platforms, which can provide whole exome sequencing (WES) or whole genome sequencing (WGS) in quicker timelines and at reduced costs, has resulted in proposals for these diagnostic testing methods to be routinely integrated into clinical practice in multiple settings. However, the complexities of these diagnostic approaches, and the minimal comparative evidence available on them, creates difficulties in the evaluation of their diagnostic performance. Novel approaches need to be developed to improve the health technology assessment (HTA) of WES and WGS.

Methods

Several HTAs on genetic testing and the use of WES or WGS in fetal medicine were reviewed. Information on factors associated with this diagnostic modality that affect typical test accuracy assessment (e.g., sensitivity and specificity) was extracted. The multiple steps required for completing a WES or WGS test, and the potential for the introduction of errors (type I or type II) at each of these steps, were mapped and examples provided. The clinical and economic implications associated with imperfect and uncertain test accuracy were described.

Results

Limited data on analytical and clinical validity were identified. WES and WGS are multistep processes and errors were found in sampling, molecular sequencing, bioinformatic filtering, and variant interpretation; therefore, the assumption that WES or WGS is 100 percent sensitive or specific is not reasonable. Although alternative evidence-based estimates are unlikely to be available, the inevitability of such errors, and their implications in terms of comparative effectiveness, safety, and cost effectiveness, should be described in HTAs.

Conclusions

While unknown diagnostic accuracy remains an issue with WES and WGS testing, formal sensitivity analysis of test performance characteristics should be conducted as part of HTAs. A checklist has been developed to assist those involved in HTA and policy to understand the potential for inaccurate test results in clinical practice, and the risk-benefit implications of these diagnostic errors for patients.
OP136 A Comparison Of Health Technology Assessment Recommendations In Australia, Canada, And England: Is There Opportunity For Further Alignment?
Authors: Wang Tina , Solar Belen , McAuslane Neil
Published: December 2023

Introduction

Over the past decade there have been increasing interactions between health technology assessment (HTA) agencies through international networks at the policy level and European joint actions at the product level. A pilot project is underway to explore collaboration beyond Europe between HTA agencies in Australia, Canada, and the UK. This study the compared HTA recommendations of new active substances (NAS) appraised by Australia’s Pharmaceutical Benefits Advisory Committee (PBAC), Canada’s CADTH, and England’s National Institute for Health and Care Excellence (NICE).

Methods

Using publicly available data and established benchmarking methodology, we examined 45 NAS appraised by PBAC, CADTH, and NICE between 2017 and 2021. Analysis was performed to assess rollout time from regulatory to HTA recommendation, and to the first HTA recommendation.

Results

Most products were submitted to the Europe Medicine Agency first (89%). However, 71 percent of NAS in Australia and 69 percent in Canada were submitted to HTA in parallel with regulatory review, which shortened overall rollout time. The median HTA submission gap among the three agencies was 140 days in Australia, 102 days in Canada, and 8 days in England. PBAC had the highest number of negative recommendations (51%), followed by CADTH (18%), and NICE (5%). The congruence of HTA decisions was highest between CADTH and NICE (56%), compared with PBAC and CADTH (11%), and PBAC and NICE (20%)

Conclusions

To achieve a more collaborative HTA process it is necessary to understand the rollout time in these jurisdictions. This study identified submission gaps among the regulatory agencies, but there may be more synergy in the future as regulators in the three jurisdictions work collaboratively through the Access Consortium. Currently, the submission gap for the three HTA agencies was mostly within six months, making collaboration on joint assessment possible. We observed divergences in HTA recommendations due to the methodology and decision criteria applied by each agency. Therefore, collaboration on assessment should build on the clinical aspects, although HTA decisions should be grounded in the local context.
OP147 Measuring Health Technology Assessment Impact On The Introduction Of Transcatheter Aortic Valve Replacement In A Private Healthcare System
Authors: Kelles Silvana , Pereira Camila , Martins Carina , Reis Daniel , Azevedo Ernesto , Ribeiro Geraldo , Zocrato Karina , Carvalho Lélia , Freitas Marcela , Horta Maria , Barbosa Mariana , Talim Mariza , Borin Marcus
Published: December 2023

Introduction

Aortic stenosis is an insidious disease that has a high mortality rate when it becomes symptomatic. Surgical valve replacement is the treatment of choice and has predictable risks. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to surgery, which is indicated for high-risk patients.

Complications after TAVR include paravalvular leak, cerebrovascular events, and the need for pacemaker implantation. A health technology assessment report carried out by the Health Technology Assessment Unimed-BH group in 2018, two years before it became part of the National Supplementary Health Agency, recommended the introduction of TAVR with the following criteria: indications provided by a group of specialists; forwarding of a report with detailed clinical data; results of imaging exams; and follow-up results for up to one year after the procedure. After the introduction of TAVR with the agreed criteria, it was possible to access TAVR results from the private healthcare system of Unimed-BH.

Methods

Administrative data were collected from the Unimed-BH database. All patients who received a TAVR implant from 2013 to 2017 were included by virtue of a court injunction, and after 2018 by operator concession and within agreed criteria.

Results

From July 2013 to June 2019, 83 patients underwent TAVR implantation by Unimed BH. The median age of patients was 83.4 years (interquartile range 66.5 to 97.9), most of whom were women (56%). There was a predominance of patients in New York Heart Association classification III (50%) and IV (29%). There were 36 patients who underwent TAVR before 2018 and 47 patients within the agreed criteria. In the period prior to the agreed criteria, 28 percent needed a pacemaker, compared with 23 percent after 2018. During the follow-up period, 39 patients died: 18 (50%) before 2018 and 11 (23%) after 2018.

Conclusions

The agreement made with the providers, which included the obligation of having a team of specialists responsible for the indication and access to clinical data through the report, improved patient outcomes. This may be due to having a better indication for the procedure or to the greater experience of the professionals involved in its delivery.
OP151 Health Technology Assessment In Switzerland – Current And Future Challenges
Authors: Haasteren Goedele van , Finlayson Mark
Published: December 2023

Introduction

The Swiss Health Technology Assessment (HTA) program is a unique, innovative program that connects research with policy making. In 2017, a HTA unit was established within the Federal Office of Public Health following a decision by the Federal Council in 2015 to intensify efforts in HTA.

Methods

The legal basis of the HTA program is Article 32 of the Federal Health Insurance Act, which specifies that health technologies (i.e., all preventive, diagnostic, and therapeutic interventions in health care) covered by the compulsory health insurance must be effective (E), appropriate (A), and economically efficient (E).

Health technologies that do not meet the EAE criteria are not eligible for coverage. For health technologies that are already reimbursed, re-evaluation of the criteria can result in the removal of technologies from the catalog of benefits or limitations being placed on their reimbursement.

Results

The initial focus of the HTA program was the re-evaluation of controversial health technologies. This focus was later expanded to evaluating new and upcoming technologies through horizon scanning. Challenges encountered since the start of the program include:

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aligning the classic HTA domains with the EAE criteria;

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identifying suitable re-evaluation topics;

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tailoring HTA processes to regulation options and decision-making processes; and

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involving stakeholders in the HTA process without jeopardizing the quality and objectivity of the research.

Conclusions

Despite various initial challenges, the HTA program has become an acknowledged and appreciated actor within the Swiss reimbursement policy landscape. An outlook on the program’s future will also be shared.
OP152 Use of Real-world Evidence By The Brazilian Health Technology Assessment Committee (Conitec) For Monitoring Of Health Technologies
Authors: Lyrio Amanda Oliveira , Mega Tacila Pires , de Freitas Lopes Ana Carolina , Ferré Felipe , Santana Barreira Antônio Marcos , Portugal Clarice Moreira , de Carvalho Samara Helena , Neiva Pantuzza Laís Lessa , Schluckebier Bonan Luciene Fontes , Canuto Santos Vania Cristina
Published: December 2023

Introduction

In Brazil, the incorporation or disinvestment of health technologies into the Unified Health System (SUS) are advised by the National Committee for Health Technology Incorporation (Conitec). Despite the thorough evaluation carried out by Conitec, the results measured after implementation do not always reflect the economic and clinical impact expected from the incorporation. Thus, real-world evidence (RWE) is essential for monitoring health technologies. The aim of this study was to report how Brazil is using the RWE to obtain additional information about the incorporated technologies.

Methods

Actions related to the use of RWE for monitoring of technologies incorporated into the SUS were described. The period evaluated was between 2012 and 2022.

Results

The first Conitec recommendation in which the use of real-life data in the decision-making process was evidenced occurred in 2016. Administrative data from a cohort of patients identified that beta-interferons for Multiple Sclerosis were less effective than the other drugs used in the Brazilian public system. A further eight reports have been published assessing the performance of technologies using administrative data.

Another strategy for RWE generation was through the funding of primary studies, highlighting a study with 21 rare diseases and another one to evaluate Zolgensma gene therapy, acquired through court for Spinal Muscular Atrophy. Both studies are ongoing and aim to evaluate the effectiveness, safety, adherence, and cost of medications in the evaluated diseases. Conitec is also following studies in RWE financed by pharmaceutical companies to evaluate effectiveness for incorporated technologies subject to reassessment. Additionally, managed access arrangements have been promoted for generating RWE when there is uncertainty about outcomes.

Conclusions

Real-world evidence from administrative data and clinical research allows monitoring after the implementation of technologies in the Unified Health System in Brazil. This makes it possible to reallocate resources in health and contribute for the system sustainability, in addition to generating data that reduce the uncertainties assumed at the time of incorporation.