bluuebunny/crossref_metadata_2025 huggingface dataset:
PP52 Will Joint European Health Technology Assessment Provide Additional Benefits Over Individual Country-wise Assessments?
Authors: Arora Rhythm , Gonzalez Ignacio Garcia , Delaitre-Bonnin Caroline
Published: December 2023

Introduction

In December 2021 the European Union (EU) Health Technology Assessment (HTA) Regulation, a key pillar of the EU Pharmaceutical Strategy, was adopted by the Council and the European Parliament. The focus areas of Joint HTA Cooperation include Joint Clinical Assessments (JCA), Joint Scientific Consultations (JSC), and joint early-stage horizon scanning. The European HTA regulation will be adopted in a stepwise approach and from 2030 onwards, all products (drugs, high-risk medical devices, and in vitro diagnostics) approved in all indications will be subjected to JCA in EU.

Methods

A targeted literature research was performed for policies and the European Network for HTA (EUnetHTA) methodological guidelines describing the HTA methods including scoping process, comparators, endpoints, the applicability of evidence, and validity of clinical studies. Additionally, the anticipated opportunities and challenges were also summarized with respect to these methods.

Results

EUnetHTA put forward a timeline for different activities over the next three years as part of the new EU HTA Regulation, including key deadlines for ongoing EUnetHTA consultations on the processes and methods. EUnetHTA will set up a new ecosystem across the EU as it aims to reduce duplication and time to access by supplementing multiple national clinical assessments with a joint central assessment. In any case, assessment of added value and pricing and reimbursement decisions will still occur at the national level.

Additionally, EU HTA may promote harmonization of processes, standards, and evidence requirements, which will increase predictability and simplify evidence requirements. However, differences in clinical practice, standard of care, and national priorities may lead to assessments that are not generalizable to all Member States.

Conclusions

The joint EU HTA cooperation will benefit countries which have less developed or do not have established HTA expertise or infrastructure. However, the JCA process could result in increased requirements for clinical evidence generation as relative effectiveness and relevance of outcomes to patients gain further importance for products to successfully gain access across countries.
PP55 Citizens’ General Needs Assessment In SOTERIA Project: ‘User-friendly Digital Secured Personal Data And Privacy Platform’
Authors: Arana-arri Eunate , Imaz-Ayo Natale , del Burgo Ainara Velez , Idoyaga Eneko , Barasoain Maitane , Orcajo Janire , Lazar Iuliana , Van Thuy Luyen , Keba Varvara , Galariotis Emilios , Oliveira Tiago
Published: December 2023

Introduction

During the COVID-19 pandemic, the use of e-services increased, bringing a better choice of technologies and services. Nevertheless, these services require the use of sensitive personal data, which increased the level of risk because of potential privacy and security breaches. As a result, citizens are more concerned about their privacy, security, and personal data protection. The SOTERIA project aims to provide a secure and user-driven solution. This study aims to identify barriers and key points related to citizens when using digital systems for data interoperability.

Methods

Both qualitative and quantitative approaches were applied in order to identify and measure citizens’ general needs regarding the tool to be developed within the context of SOTERIA. The questionnaire was distributed throughout the three European countries under study: Austria, Romania, and Spain, with 400 responses collected in each country. The distribution of sex, age, occupation and educational level was representative in the entire sample.

Results

This study corroborates the critical role of perceived security in the intention to adopt new technologies. In addition, to trust and being consistent with the extant literature on technology adoption/acceptance, perceived benefits and usefulness also play a crucial role in driving attitudes and behavioral intention to adopt digital data wallet (DDW). Our findings show that perceived ease of use, the user’s belief of having no difficulty using the technology (i.e., DDW), is a significant predictor of consumers’ intentions to use DDW. Our qualitative data from both the in-depth interviews and focus groups also revealed convenience, being comfortable, and/or less time and energy needed to use DDW in comparison to one’s current situation, to be a determinant of perceived benefits. Transparency, which provides consumers with knowledge of how firms manage their personal information, was also viewed as important among our participants in both in-depth interviews and focus groups. Our findings corroborate previous studies that report the control of privacy concerns, or the extent to which consumers believe they can manage the flow of information, feel comfortable and enhance their perceived view of privacy or lower privacy concerns.

Conclusions

Our qualitative studies confirmed that trust, or consumers’ expectation of how data will be handled in the future plays an important role in influencing the intention of DDW adoption.
PP71 Hospitalization Costs Associated With Advanced Non-Small Cell Lung Cancer In China: Real World Evidence From Jiangsu
Authors: Xia Yu , Yang Yi , Chen Yingyao
Published: December 2023

Introduction

Non-small cell lung cancer (NSCLC) constitutes 85 percent of lung cancer diagnoses and poses an economic threat to the sustainability of healthcare services. This study was conducted to estimate hospitalization costs associated with advanced NSCLC without sensitizing EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase) alterations in China and explore the potential predictors.

Methods

Data linked with patients with advanced NSCLC (stage IIIB–IV) without sensitizing EGFR and ALK alterations were obtained from the electronic medical record system of one general hospital and one cancer hospital in Jiangsu province, China, ranging from January 2017 to December 2020. We excluded patients with lung metastases from tumors elsewhere in the body. The socio-demographic characteristics, disease-related characteristics, and hospitalization cost of eligible patients were extracted. We used the generalized linear model (GLM) to assess the potential influencing factors of hospitalization cost.

Results

Patients with advanced NSCLC (n=7,260) were included in this study. The median hospitalization cost of advanced NSCLC was USD11,540.47. The median hospitalization examination and test costs were USD1,539.46, and the median hospitalization drug cost was USD6,351.47. GLM results showed that patients aged 60 or older (95% Confidence Interval [CI]: -1019.1,128.6), who had no gene driver (95%CI: -1,681.6,-233.6) were more likely to have relatively lower hospitalization costs for advanced NSCLC. Patients treated in cancer hospital (95%CI: 1,329.1,2,620.0) and with non-squamous carcinoma (95%CI: 171.3, 1,235.4) may have higher hospitalization costs. Compared with Urban Employee Basic Medical Insurance, patients with free medical services (95%CI: 1,248.4,6,298.7) were associated with higher hospitalization costs. Patients with higher hospitalization frequency and longer length of hospital stay (p < 0.05) were linked to higher hospitalization costs.

Conclusions

The hospitalization costs linked to advanced NSCLC is considerable for patients, with drug costs accounting for the largest. More efforts still need to be made to alleviate the direct medical burden.
PP79 Publication Trends Of Network Meta-analyses In Europe And Asia: A Focus On Cardiovascular Disease
Authors: Ng Alvin , Choi Min Hee , Evans Jennifer S
Published: December 2023

Introduction

The objective of this research was to compare trends in publications of network meta-analyses (NMAs) in cardiovascular diseases (CVDs) in Asia-Pacific (APAC; China, Japan, Singapore, South Korea, Thailand) and Europe (United Kingdom [UK], Germany, France, Spain, Italy), with a focus on volume, collaborations and methods.

Methods

Freely available NMAs assessing pharmacological or surgical interventions for CVD in terms of mortality or major adverse cardiovascular events, published in 2012 or later, by authors affiliated with institutions in the target countries were identified via MEDLINE and Embase. CVDs were grouped using the International Classification of Diseases, Tenth Edition (ICD-10).

Results

Across the 193 publications identified, heart diseases such as atrial fibrillation, aortic stenosis and heart failure (ICD-10 I30-I52) were the most common indications reported (38%). The majority of publications involved authors in APAC countries (63%) and 40% from Europe. Cumulative numbers of publications from APAC surpassed those from Europe from 2018 onwards. Authors were largely affiliated with institutions in China (50%), the UK (20%) and Italy (20%). One hundred and forty-five publications were by authors affiliated with institutions in a single country; 91 percent of publications from APAC and 44 percent from Europe, indicating different patterns of collaboration within these regions. In terms of reporting methodologies, 39 percent of included publications did not specify whether a frequentist or Bayesian framework was used (43% in APAC, 34% in Europe). Among those that reported, the Bayesian framework was more commonly used.

Conclusions

Whilst there is a growing trend in NMA publication counts generally, the rate of increase in APAC was higher than Europe, particularly in the years following adoption of health technology assessment (HTA) procedures in APAC. The volume of publications not reporting the framework used was substantial, despite requirements for this in reporting guidelines e.g., PRISMA. Where reported, the Bayesian framework may have been favored due to its advocacy by some health technology assessment bodies.
PP90 Artificial Intelligence To Detect Ischemic Heart Disease In Non-traumatic Chest Pain At The Emergency Department – SmartHeart Study
Authors: Arana-arri Eunate , de Vicuña Aitor García , Carbajo Silvia , de Benito Sobrado Sara , Carreras Magdalena , Arrieta Irma , Bayon-Yusta Juan Carlos
Published: December 2023

Introduction

An estimated 17.9 million people died from cardiovascular diseases (CVDs) in 2019, which is 32 percent of all global deaths and 85 percent were due to heart attack and stroke. Chest pain is one of the most common reasons for presenting to the emergency department (ED). It is increasingly recognized that artificial intelligence (AI) will have a significant impact on the practice of medicine in the near future and may help with diagnosis and risk stratification. We aim to estimate a diagnostic prediction of acute myocardial infarction by the development and validation of an AI model.

Methods

Data on 134 variables of 3,986 consecutive patients who presented to the ED with non-traumatic chest pain were included in the analysis. Using AI tools, a neural network model was developed to establish the risk of acute myocardial infarction (AMI) to achieve n=150 patients over 18 years of age attending the ED.

Results

The mean age was 65.5 (±13.7) years and 63.6 percent were male. Most (60.1%) patients were admitted to hospital, with only 20.3 percent diagnosed at hospital discharge with ischemic heart disease (IHD). All patients were followed up for two months, and 6.3 percent were readmitted to the ED, but none presented with an episode of IHD. In the data analysis of the entire sample we obtained a probability of diagnosing IHD by the SmartHeart model (S=93.1%, E=47.3%, PPV=31.0%, and NPV=96.4%). When we analyzed the sample of patients with no history of IHD (n=104), the diagnosis accuracy was as follows (S=100%, E=77.5%, PPV=42.8%, and NPV=100%).

Conclusions

Our AI model provides information to predict patients who are suffering from acute IHD. AI has been reported to outperform emergency physicians and current risk stratification tools to diagnose IHD, but has rarely been integrated into practice. This study highlights the diagnostic applicability and accuracy of this type of tool and that is why studies should be implemented to see its effectiveness in routine practice in EDs.
PP97 How Health Technology Agencies Estimate Target Population Size For Medical Devices: The Example Of Spinal Cord Stimulation
Authors: Ade Apolline , Hallas Natalie , Vancauwenberghe Lydie , Vogt-Humberg Ilona , Holm Astrid , Lundsby Mette , Borgman Benny , Pellicer Beatriz , Borghetti Francesca , Strachan Liesl
Published: December 2023

Introduction

Spinal cord stimulation (SCS) is an effective and safe option for patients with refractory neuropathic pain, with positive health technology assessment (HTA) recommendations across Western Europe, yet SCS uptake remains low. Estimating target patient populations within HTAs may impact upon medical device uptake, pricing and access. However, there is a dearth of information on how this is typically conducted. This study aimed to compare the approaches of Western Europe HTA agencies for estimating the target population for SCS.

Methods

A survey was conducted among members of the Health Economics and Reimbursement function from Western Europe to collect country-specific information on how HTA agencies assess the target population of medical devices (MD). The estimations of the target population for SCS were extracted from HTA publications and compared.

Results

Eight Health Economics and Reimbursement (HER) Analysts from France, Germany, the United Kingdom (UK), Belgium, Spain, Italy, Sweden and Norway completed the survey. HTA Agencies in France, UK and Belgium routinely ask for epidemiological data in the manufacturer submission, whereas in Germany, Sweden and Norway the request is dependent on the type of HTA submission. All HTA agencies, except NICE (UK), perform an independent estimation of the target population. HTA agencies in Germany and UK typically use epidemiological data from industry. In all countries, the estimation of the target population may indirectly impact the price of the MD, especially when budget impact analysis indicates a potential high use of healthcare resources. Only France, Belgium and UK have published HTA recommendations about SCS, however the estimated target population, nor the number of patients with refractory neuropathic pain, is not always included. Only the French and UK HTA agencies publish an approximation of the target population for SCS using the number of patients implanted every year.

Conclusions

This study showed there is a lack of harmonization between Western European HTA agencies’ guidelines on the inclusion and estimation of target patient populations. The new EU HTA Regulation should help to address this situation.
PP99 Positron Emission Tomography Combined With Computed Tomography (PET/CT) Using 11-C Methionine (11C-MET)
Authors: Akhmetova Makpal , Aimanova Tansolpan , Okesh Makhabbat , Avdeyev Andrey , Albayev Rustam , Saduakassova Aigul , Lyugay Yekaterina , Tleulessova Indira , Turar Olzhas , Bariyeva Gulzada , Shanazarov Nasrulla
Published: December 2023

Introduction

Positron emission tomography combined with computed tomography (PET/CT) using 11C-methionine (11C-MET) is used to detect astrocytomas and low-grade brain tumors, in the primary detection of all malignant and benign neoplasms of the central nervous system (CNS), and in order to monitor staging and evaluate the results of treatment.

Methods

To assess the clinical and economic effectiveness of PET/CT with the use of radiopharmaceutical drugs (RFLP) based on 11C-MET in the diagnosis of CNS neoplasms, a systematic review of literature by keywords in the Pubmed/MEDLINE database was conducted. The search result was 218 publications. The analysis included 21 publications that met the search criteria, including three meta-analyses and six systematic literature reviews.

Results

Diagnostic efficacy in distinguishing gliomas of high and low malignancy has moderate diagnostic accuracy (combined sensitivity and specificity were 80% and 72%, respectively), but higher sensitivity compared to Fludeoxyglucose F18 (18F-FDG). PET/CT with 11C-MET demonstrated good diagnostic value in detecting brain tumor recurrence (combined sensitivity and specificity of 92% and 87%, respectively) compared with 18F-FDG.

Conclusions

PET/CT diagnostics of CNS neoplasms using the drug 11C-MET is an innovative technology with greater specificity and sensitivity than 18F-FDG, positively influences the subsequent surgery plan and identifies tumors previously undetermined by magnetic resonance imaging (MRI), CT or PET/CT with 18F-FDG.
PP103 Budget Impact Analysis Of Utilization Of WavelinQ Endo-arteriovenous Fistula System For Hemodialysis Patients: An Australian Hospital Perspective
Authors: Delaney Christopher , Agresta Blaise , Gupta Ritu , Papadopoulos George
Published: December 2023

Introduction

A high proportion of patients with end-stage kidney disease (ESKD) are treated with hemodialysis (HD). To lower morbidity and maintain overall cost control in patients with ESKD, it is crucial for health systems to establish and maintain durable hemodialysis (HD) access. Our objective was to assess the budget impact of utilizing the ‘WavelinQ Endo Arteriovenous Fistula (AVF) system’ (WavelinQ) for HD patients.

Methods

A one-year economic model from the Hospital (Flinders Medical Centre, FMC) perspective was developed with Australian epidemiological and costing data. Clinical data were collected from real-world sources. The incident (n=50) and prevalent (n=250) cohorts were based on FMC utilization patterns. The current standard of care was surgical AVF (sAVF) and/or central venous catheters (CVC). With introduction of WavelinQ into practice, the substitution rate was set at 50 percent in new patients and ten percent amongst existing patients. Index procedure and reinterventions costs for the patient were based on the weighted average cost using National Efficient Price Determination 2020 to 21. Total costs preWavelinQ introduction were compared to post WavelinQ substitution to determine the budget impact.

Results

Based on FMC expected patient cohort and WavelinQ substitution rates, the mean annual cost savings per incident and prevalent patient were AUD26,873 and AUD3,549, respectively, which lead to overall mean annual cost savings per patient of AUD7,437. The calculated per patient additional upfront cost of AUD7,010 with the WavelinQ index procedure versus sAVF was more than offset by the savings due to less post-procedure reinterventions. Overall, at the assumed substitution rates with WavelinQ, the model predicted a cost saving of approximately AUD2.2 million dollars for FMC.

Conclusions

The use of WavelinQ is expected to lead to cost savings of AUD2.2 million dollars from the FMC perspective. Hospitals should consider not just the increase in upfront costs but also potential savings from less reintervention procedures. There is a need for continued research on the budget impact of different HD modalities across multiple settings.
PP105 Efficacy, Effectiveness And Safety Of Letermovir For Prophylaxis Of Cytomegalovirus Infection And Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Muniz Júnior Roberto Lúcio , do Nascimento Martins Álex Brunno , Alvernaz dos Santos Bárbara Rodrigues , Ferreira Bambirra Eduardo Henrique , Prata Luana Oliveira , Araújo Maiara Silva , Borin Marcus Carvalho , de Assis Acurcio Francisco , Alvares-Teodoro Juliana , Guerra Júnior Augusto Afonso
Published: December 2023

Introduction

Clinically significant cytomegalovirus infection (CSI-CMV) is an important factor associated with mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). It is estimated that the incidence of CSI-CMV in the post-HSCT period is 30 percent to 70 percent in transplanted individuals. Therefore, CSI-CMV is considered a complication in allogeneic HSCT, which can trigger Cytomegalovirus disease (CMVD). Letermovir is an antiviral agent indicated especially for the prophylaxis of CMVD post-HSCT. The objective of this work was to evaluate the efficacy, effectiveness and safety of letermovir, comparing it with placebo or other existing prophylactic treatments.

Methods

A systematic review was carried out according to PRISMA 2020. A strategy was developed for searching electronic bibliographic databases. Retrieved publications were selected by a pair of reviewers. The same pair performed the data extraction. A qualitative assessment of the efficacy, effectiveness and safety of letermovir was performed.

Results

Eighteen studies were included, being experimental and observational. Overall, the pivotal RCT demonstrates the efficacy of letermovir in reducing the incidence of CSI-CMV. However, there was no statistically significant difference in all-cause mortality and letermovir-related overall survival, events of graft versus host disease, neutropenia, acute kidney disease and 48-week mortality. Observational studies, in general, present results similar to those found in the pivotal RCT. The main adverse events associated with letermovir were peripheral edema (14.5%), vomiting (18.5%), headache (13.9%), cough (14.2%), abdominal pain (11.8%) and fatigue (13.4%).

Conclusions

The prophylactic use of letermovir in CMV-R+ patients after allogeneic HSCT demonstrates beneficial results in the prevention of CSI-CMV. However, there were no identified improvements for other outcomes. As for safety, it was observed that there is still little information about adverse events related to the drug, and studies assessing this aspect are needed for better comprehension.
PP122 The Feasibility Assessment For Domestic Introduction Of Newborn Pulse Oximetry Screening For Critical Congenital Heart Disease
Authors: Choi Miyoung , Kim Jimin , Choi Byung Min , Shin Jeonghee , Park Chanmi , Ha Gisu , Shin Hong Joo , Choi Eui Kyung
Published: December 2023

Introduction

Critical congenital heart disease (CCHD) refers to a group of heart defects that cause serious, life-threatening symptoms in the neonatal period and requires timely surgical or catheter interventions. We reviewed evidence for incorporating a mandatory neonatal CCHD screening test as a national public health project for all neonates born in Korea by analyzing the validity and cost-effectiveness of neonatal CCHD screening using pulse oximetry in Korea.

Methods

We performed a rapid literature review to establish models for the diagnostic accuracy and economic evaluation of pulse oximetry. Also, we analyzed the prevalence, mortality, and medical expenditure for different types of CCHD using the national health insurance (NHI) data. We analyzed the cost-effectiveness of pulse oximetry by comparing the group of neonates who received a combination of a physical examination and pulse oximetry, and group of neonates who only received a physical examination. For the cost-effectiveness analysis for the CCHD screening test in this study, we used a duration of one year, diagnostic accuracy as the clinical endpoint, and Life Year Gain (LYG) as the effectiveness indicator.

Results

We used recent systematic review he pooled sensitivity can be enhanced from 76.5 percent (pulse oximetry alone) to 92 percent (combined with physical examination). We used a total of 2,334 neonates with CCHD data for the economic model. Our analysis revealed that adding pulse oximetry to the routine neonatal physical examination leads to 2.34 of LYG and a cost difference of USD1,080,602, showing a ICER of KRW610,063,240 (USD461,857)/LYG.

Conclusions

Considering the benefit of LYG and cost of reducing the complications and after effects of newborns with CCHD who survived early diagnosis, it is considered to be worthwhile in Korea for a mandatory screening test.
PP124 Patisiran For Patients With Hereditary Transthyretin Amyloidosis (hATTR) With Stage 2 Polyneuropathy Or Who Have An Inadequate Response To Tafamidis
Authors: Borin Marcus , Martins Álex Brunno , Alvernaz Bárbara , Gargano Ludmila , Júnior Roberto , Magalhães Wagner , Acúrcio Francisco , Alvares-Teodoro Juliana , Guerra Augusto
Published: December 2023

Introduction

Hereditary Transthyretin amyloidosis (hATTR) is a rare autosomal dominant, multisystemic, progressive, and potentially fatal genetic disease. Currently, the only drug made available in the Brazilian National Health System to treat hATTR is tafamidis meglumine, indicated for symptomatic adult patients in early stage (stage 1) and not undergoing liver transplantation for amyloidosis associated with hATTR.

Methods

A systematic review was conducted in the databases MEDLINE via Pubmed, Embase, The Cochrane Library, and LILACS addressing the question “Is patisiran treatment effective and safe for patients diagnosed with ATTRh amyloidosis with stage 2 polyneuropathy or who have an inadequate response to tafamidis?”

Results

The 13 studies included in the review demonstrate the efficacy of patisiran in reducing the neuropathic progression of the disease, as evidenced by decreased mNIS+7 scale scores following 18-month use of the drug. Improvements in the quality of life of patients taking patisiran have been reported, as measured by reduced scores on the Norfolk-QoL-DN scale. Patisiran has also been shown to be effective in reducing NT-proBNP, a marker related to cardiac stress. Improvements in the nutritional status of patients taking patisiran were demonstrated by increasing modified body mass index (BMI). Good tolerability of patisiran was observed by patients using it. Most adverse events were classified as mild or moderate. The studies indicated that the occurrence of deaths is similar between the patisiran and placebo groups. Most deaths were related to cardiac events and were not associated with the use of patisiran.

Conclusions

The use of patisiran in patients with hATTR demonstrated efficacy in reducing the neuropathic progression of the disease, evidenced by decreased mNIS+7 scale scores, improvements in quality of life as measured by reduced Norfolk-QoL-D scale scores, and reduced NT-proBNP. The drug patisiran was well tolerated, with most adverse events rated as mild and moderate.
PP127 Early Health Technology Assessment (HTA) Of Medical Technologies To Inform Subsidy Decision-making In Singapore
Authors: Batcagan-Abueg Ada PM , Soon Swee Sung , Ju Hong , Ng Kwong
Published: December 2023

Introduction

Medical technologies are evolving rapidly, with many new and expensive technologies entering the market constantly, challenging the sustainability of the public healthcare system. Early health technology assessment (HTA) to inform subsidy decision for innovative medical technologies, before they diffuse into the public healthcare system, may drive appropriate early adoption or curtail inappropriate use. This abstract describes the Agency for Care Effectiveness (ACE)’s experience in conducting early HTAs and key challenges faced.

Methods

During ACE’s 2021 topic prioritization exercise, ACE took a proactive approach by considering medical technologies identified from horizon scanning (HS) for subsidy evaluation. Two topics were shortlisted from HS. Standard HTA evaluation framework and local clinician consultation were used to define the evaluation scope and clinical pathways. Literature search and appraisal were conducted for safety, effectiveness, and economic evidence. Budget impact estimations and organizational feasibility assessment were additional domains considered for subsidy decision-making by the Ministry of Health Medical Technology Advisory Committee (MTAC).

Results

MTAC did not recommend subsidy for the two technologies due to weak evidence base, largely due to a lack of comparative evidence, small samples, short-term follow-ups, or heterogeneity of population. Additional considerations included potentially high budget impact or organizational feasibility issues such as substantial capital and maintenance cost and infrastructure reconfiguration required. During the evaluation, key challenges of assessing such technologies in their early diffusion within the healthcare system were: (i) differing clinical opinions on whether the technology meets an unmet need; (ii) uncertain place in the clinical management algorithm for the relevant indications; (iii) sparse and weak evidence; (iv) uncertain financial implications to the healthcare system due to a lack of available local costs.

Conclusions

Early HTA on medical technologies identified from HS can be a useful tool to guide subsidy decisions; however, several challenges exist. Careful selection of technologies and timing of evaluation are critical. Seeking stakeholder inputs earlier would ensure shortlisting appropriate technologies with greater clinical need for HTA.
PP138 Awareness Of Health Technology Assessment And Its Predictors Among Medical Students In Public Universities In Klang Valley, Malaysia
Authors: Mohamad Nur Farhana , Mansor Zawiah , Mahmud Aidalina , Ismail Suriani , Mohamed Ghazali Izzuna Mudla , Sarimin Roza
Published: December 2023

Introduction

Lack of awareness has been recognized as one of the most important barriers in the implementation of health technology assessment (HTA) across numerous countries. Medical students have been identified as a vital target group to instill an awareness, basic knowledge, and positive attitude towards HTA from the beginning of their medical career. Presently, there was no study found conducted on HTA awareness in medical students in Malaysia. This study aims to determine the level of awareness of HTA, and its predictors among clinical year medical students in public universities in Klang Valley, Malaysia.

Methods

A cross-sectional study using the stratified random sampling method was conducted among clinical year medical students in four public universities in Klang Valley, Malaysia. The data on level of awareness of HTA and its associated factors were collected using a self-administered online questionnaire. Data were analyzed using IBM SPSS version 27 to determine the level of awareness of HTA, its associated factors and predictors.

Results

The total number of study participants was 323 and the response rate was 90 percent. The analysis showed that 69 percent of respondents had low level of awareness of HTA while 31 percent had high level of awareness of HTA. Factors associated with the level of awareness of HTA was attitude towards HTA (p < 0.001). The predictors of level of awareness of HTA were attitude towards HTA (Adjusted Odds Ratio (AOR) = 7.417, 95% confidence interval [CI]: 3.491, 15.758), peer interaction on HTA (AOR = 0.320, 95% CI: 0.115, 0.888), and previous training on HTA (AOR = 4.849, 95% CI: 1.096, 21.444).

Conclusions

The majority of clinical year medical students in public university have low awareness of HTA which can be predicted by the level of attitude, peer interaction and training of HTA. Therefore, it is important to increase awareness among these future medical practitioners to encourage evidence-based decision-making. Early exposure and introduction of HTA in the current university curriculum in collaboration with a local HTA agency can be recommended to increase awareness as well as to improve students’ attitude towards HTA.
POST-CAROLINGIAN GEOGRAPHIES OF NORTH AND WEST IN RODULFUS GLABER
Authors: WOLEVER ERIC
Published: December 2023

This article evaluates the geographical consciousness of north and west found in the Five Books of the Histories by the eleventh-century Burgundian monk Rodulfus Glaber. In contrast with dominant approaches to medieval geography that have informed prior commentators, who have focused on ideas of Europe or the opposition of east and west, it argues that we must situate Glaber's spatial consciousness first and foremost in the lineage of Carolingian and post-Carolingian conceptions of the north. Focusing especially on the climactic episode of the first book, a vision of the crucifixion that prophesies the rise of Christianity in the northern and western regions of the world, it seeks to contextualize this around the wider geography within Glaber's text. First, the unusual place of the Riphaean mountains and Raetia Secunda in Glaber's descriptions of Gaul and Germania are compared with early medieval textual geographies and eleventh- to twelfth-century cartography to show the shifting and ambiguous place of the north as an expansive and immediate frontier of the Christian world. Then, with this background in place, Glaber's conception of the west is considered through its use alongside a range of signs and portents, most notably the whale sighting at the beginning of the second book. These considerations reveal a messier and more local, Frankish conception of west that is interconnected with the north as a site of violence and disorder. This not only highlights important tensions in Glaber's text itself, but also a geographical vision that remained influential well into the twelfth century.
“MEMBERS OF THE COVENANT OF THE GUIDE”: READING MAIMONIDES IN CHRISTIAN TOLEDO
Authors: PICK LUCY K.
Published: December 2023

This article argues that Moses Maimonides's Guide of the Perplexed first became known to a Latin Christian audience in Toledo before 1220, and that the section of it translated as the Liber de parabolis et de mandatis in 1223–24 (Guide III.29–49) is the work of Samuel ibn Tibbon and Michael Scot. Moreover, the introduction to exegesis that prefaces the translation reflects the work of ibn Tibbon. The article considers the impact early contact with the Guide had, first in Toledo, and then in Paris and Provence. The Guide presented a God who worked through the principles of Aristotelian physics, and offered an incentive to translate and study those works of Aristotle and his interpreters that illuminated these questions. Texts translated in Toledo under the inspiration of the Guide became core texts for Paris scholastics. William of Auvergne, the first Parisian scholar to use the translation, would play a key role in the trial of the Talmud. And Cardinal Romanus, to whom the Liber de parabolis et de mandatis was dedicated, is implicated in the controversy of the Guide itself among Jews at Montpellier.
Beavers Have Engineered Ecosystems in the Tetons for Millennia
Authors: van Deelen Grace
Published: December 2023

Analysis of lake sediment in Grand Teton National Park is helping piece together ecosystem history, with helpful implications for land managers today.
Asymmetric Dipole Trends in Geodynamo Models and the Paleomagnetic Field
Authors: Buffett B. A.
Published: December 2023

Temporal trends in the paleomagnetic dipole moment exhibit the property of positive skewness. On average, positive trends are larger and occur less frequently than negative trends over timescales of several tens of kyr. We explore the origin of this property using numerical geodynamo models. A suite of models reveals that skewness arises for a restricted set of boundary conditions. Models driven by heat flow at the top and bottom boundaries exhibit very little skewness, whereas models driven solely by heat flow on the lower boundary produce significant positive skewness. Further increases in skewness occur in the presence of thermal stratification at the top of the core. The level of skewness in the geodynamo models is correlated with estimates of upwelling near the core‐mantle boundary. Sustained upwelling is expected to increase magnetic‐flux expulsion, contributing to higher levels of skewness. Similar behavior is recovered from stochastic models in which the dipole is generated by a random series of cyclonic convection events. Skewness in the stochastic models is quantitatively similar to estimates from the geodynamo models when the average recurrence time of the convection events is 100 years. Extending the stochastic models to the paleomagnetic field implies a longer recurrence time of 1,000 years or more. We interpret this recurrence time in terms of the timing of flux‐expulsion events rather than individual convective events. Abrupt increases in the dipole moment from flux expulsion can produce skewed trends on timescales of tens of kyr.
Thermochemical Structure and Melting Distribution of the Upper Mantle Beneath Intraplate Volcanic Areas in Eastern South China Block
Authors: Zhang Anqi , Guo Zhen , Dai Hongkun , Yang Yingjie
Published: December 2023

The Eastern South China Block (SCB) has experienced complex Mesozoic‐Cenozoic tectonism and intraplate volcanism. However, due to a lack of exhaustive exploration of the upper mantle's thermochemical structure, it is difficult to determine the extent of the lithospheric modification and the mechanisms by which the volcanism generate. Here, we jointly invert Rayleigh wave dispersion, surface heat flow, geoid height, and elevation data to provide a comprehensive thermal and compositional structure of the upper mantle beneath eastern SCB and infer regions of partial melting. Our model reveals widespread lithospheric thinning in the eastern SCB and large variations of lithospheric composition with a more fertile eastern Lower Yangtze lithosphere than the lithosphere elsewhere, suggesting the lithosphere of the eastern Lower Yangtze is more severely modified than the rest of the SCB. Moreover, two high‐temperature anomalies are revealed: one beneath the eastern Lower Yangtze and the other beneath the Pearl River Delta region, associated with the Pacific plate subduction and Hainan plume, respectively. The high‐degree partial melting (∼6%) in the asthenosphere beneath the Lower Yangtze is responsible for the strong ongoing lithospheric modification and the young intraplate volcanism in the Nvshan and Subei areas. Small‐scale upper mantle convections triggered by the large mantle upwellings created a low value of ∼3% melts, possibly responsible for the intraplate volcanism in the coastal CB and less severe lithospheric modification. We demonstrate that the lithospheric thickness and its thermochemical state are the key factors that influence the composition and evolution of intraplate volcanism in the eastern SCB.
Long‐Term Landscape Evolution in Response to Climate Change, Ecosystem Dynamics, and Fire in a Basaltic Catchment on the Colorado Plateau
Authors: Staley Spencer E. , Fawcett Peter J. , Jiménez‐Moreno Gonzalo , Anderson R. Scott , Markgraf Vera , Brown Erik T.
Published: December 2023

Predicting responses of semi‐arid to montane landscapes in southwestern North America to ongoing anthropogenic changes requires understanding of past interplay among geomorphic, ecologic, and climatic factors. This study utilizes modern weathering and sediment transport processes to inform the interpretation of a 250‐kyr lacustrine sediment record of paleoecology, hydrology, and erosion from a small, closed basin, basaltic catchment on the southwestern edge of the Colorado Plateau. Geochemical and mineralogical analyses of bedrock, colluvium, and lake sediments indicate that clastic sediments in the basin are a mixture of local physical weathering products (albite and ilmenite) and eolian dust (quartz, illite, and zircon). Dust fractions increase during glacial periods coincident with lower overall sedimentation rates, suggesting this pattern results from decreased local erosion rates and not increased dust deposition. Titanium counts from X‐ray fluorescence core scanning, a proxy for ilmenite content, traces past local erosion rates. The highest erosion rates, inferred from the highest Ti counts, follow climatic transitions toward interglacial conditions (Marine Isotope Stage 5e, 3a, and the Holocene), periods characterized by vegetation changeover (observed in the core's palynology), higher temperatures (piñon‐juniper‐oak pollen abundance), lower effective precipitation (shallow lake facies), and increased wildfire activity (microscopic charcoal particle counts and sizes). While brief inferred episodes of erosion occur following abrupt transitions to cooler and wetter conditions, indicated by the abundance of subalpine tree (spruce and fir) pollen and deeper lake facies, landscapes appear more stable during glacial periods. This long‐term perspective suggests that aridification and resulting vegetation succession and increased wildfires will increase erosion rates in similar settings regionwide.
Analysis of Two Selected Solar Events in 2011 and 2015 With Mars Express Radio Occultation Data
Authors: Krishnan Ananya , Karatekin Ozgur , Verkercke Sebastien , Henry Gregoire , Sánchez‐Cano Beatriz , Witasse Olivier
Published: December 2023

The temporal behavior of the Martian ionosphere is highly variable due to various dynamic processes including space weather events. Here, we study the effect of solar flares and coronal mass ejections (CMEs) on the Martian ionosphere for two selected solar events in 2011 and 2015, using the publicly available Mars EXpress (MEX) radio occultation (RO) data (MaRS). We developed a data processing software that converts the calibrated Radio Occultation (RO) Doppler data to scientifically valuable atmospheric profiles. Using this software and previously unexplored MaRS observations, the variations in ionospheric parameters (electron density profiles and total electron content (TEC)) are calculated in order to evaluate the ionospheric changes due to solar flares and CMEs. The RO measurements mostly available 1–4 days apart from the peak events, showed no evident change in the TEC nor in the shape of electron density profiles except for a possible gradual decrease in altitude of M2 (main layer) peak density following the arrival of CMEs. To better quantify the effect of solar events on electron density profiles, RO observations near the time of arrival of solar flares and CMEs are crucial. This can be achieved by frequent RO measurements by various Mars orbiters including spacecraft‐to‐spacecraft measurements assisted by multi‐instrument monitoring of the ionosphere.
The emergence of obesity in type 1 diabetes
Authors: Kueh Martin T. W. , Chew Nicholas W. S. , Al-Ozairi Ebaa , le Roux Carel W.
Published: December 2023

Obesity, a chronic low-grade inflammatory disease represented by multifactorial metabolic dysfunctions, is a significant global health threat for adults and children. The once-held belief that type 1 diabetes is a disease of people who are lean no longer holds. The mounting epidemiological data now establishes the connection between type 1 diabetes and the subsequent development of obesity, or vice versa. Beyond the consequences of the influx of an obesogenic environment, type 1 diabetes-specific biopsychosocial burden further exacerbates obesity. In the course of obesity management discussions, recurring challenges surfaced. The interplay between weight gain and escalating insulin dependence creates a vicious cycle from which patients struggle to break free. In the absence of weight management guidelines and regulatory approval for this population, healthcare professionals must navigate the delicate balance between benefits and risks. The gravity of this circumstance highlights the importance of bringing these topics to the forefront. In this Review, we discuss the changing trends and the biopsychosocial aspects of the intersection between type 1 diabetes and obesity. We highlight the evidence supporting the therapeutic means (i.e., exercise therapy, nutritional therapy, adjunct pharmacotherapy, and bariatric surgery) and directions for establishing a more robust and safer evidence-based approach.
Cotton microbiome profiling and Cotton Leaf Curl Disease (CLCuD) suppression through microbial consortia associated with Gossypium arboreum
Authors: Aqueel Rhea , Badar Ayesha , Roy Nazish , Mushtaq Qandeel , Ali Aimen Fatima , Bashir Aftab , Ijaz Umer Zeeshan , Malik Kauser Abdulla
Published: December 2023

The failure of breeding strategies has caused scientists to shift to other means where the new approach involves exploring the microbiome to modulate plant defense mechanisms against Cotton Leaf Curl Disease (CLCuD). The cotton microbiome of CLCuD-resistant varieties may harbor a multitude of bacterial genera that significantly contribute to disease resistance and provide information on metabolic pathways that differ between the susceptible and resistant varieties. The current study explores the microbiome of CLCuD-susceptible Gossypium hirsutum and CLCuD-resistant Gossypium arboreum using 16 S rRNA gene amplification for the leaf endophyte, leaf epiphyte, rhizosphere, and root endophyte of the two cotton species. This revealed that Pseudomonas inhabited the rhizosphere while Bacillus was predominantly found in the phyllosphere of CLCuV-resistant G. arboreum. Using salicylic acid-producing Serratia spp. and Fictibacillus spp. isolated from CLCuD-resistant G. arboreum, and guided by our analyses, we have successfully suppressed CLCuD in the susceptible G. hirsutum through pot assays. The applied strains exhibited less than 10% CLCuD incidence as compared to control group where it was 40% at 40 days post viral inoculation. Through detailed analytics, we have successfully demonstrated that the applied microbes serve as a biocontrol agent to suppress viral disease in Cotton.
Structures, functions and adaptations of the human LINE-1 ORF2 protein
Authors: Baldwin Eric T. , van Eeuwen Trevor , Hoyos David , Zalevsky Arthur , Tchesnokov Egor P. , Sánchez Roberto , Miller Bryant D. , Di Stefano Luciano H. , Ruiz Francesc Xavier , Hancock Matthew , Işik Esin , Mendez-Dorantes Carlos , Walpole Thomas , Nichols Charles , Wan Paul , Riento Kirsi , Halls-Kass Rowan , Augustin Martin , Lammens Alfred , Jestel Anja , Upla Paula , Xibinaku Kera , Congreve Samantha , Hennink Maximiliaan , Rogala Kacper B. , Schneider Anna M. , Fairman Jennifer E. , Christensen Shawn M. , Desrosiers Brian , Bisacchi Gregory S. , Saunders Oliver L. , Hafeez Nafeeza , Miao Wenyan , Kapeller Rosana , Zaller Dennis M. , Sali Andrej , Weichenrieder Oliver , Burns Kathleen H. , Götte Matthias , Rout Michael P. , Arnold Eddy , Greenbaum Benjamin D. , Romero Donna L. , LaCava John , Taylor Martin S.
Published: December 2023

The LINE-1 (L1) retrotransposon is an ancient genetic parasite that has written around one-third of the human genome through a ‘copy and paste’ mechanism catalysed by its multifunctional enzyme, open reading frame 2 protein (ORF2p)1. ORF2p reverse transcriptase (RT) and endonuclease activities have been implicated in the pathophysiology of cancer2,3, autoimmunity4,5 and ageing6,7, making ORF2p a potential therapeutic target. However, a lack of structural and mechanistic knowledge has hampered efforts to rationally exploit it. We report structures of the human ORF2p ‘core’ (residues 238–1061, including the RT domain) by X-ray crystallography and cryo-electron microscopy in several conformational states. Our analyses identified two previously undescribed folded domains, extensive contacts to RNA templates and associated adaptations that contribute to unique aspects of the L1 replication cycle. Computed integrative structural models of full-length ORF2p show a dynamic closed-ring conformation that appears to open during retrotransposition. We characterize ORF2p RT inhibition and reveal its underlying structural basis. Imaging and biochemistry show that non-canonical cytosolic ORF2p RT activity can produce RNA:DNA hybrids, activating innate immune signalling through cGAS/STING and resulting in interferon production6–8. In contrast to retroviral RTs, L1 RT is efficiently primed by short RNAs and hairpins, which probably explains cytosolic priming. Other biochemical activities including processivity, DNA-directed polymerization, non-templated base addition and template switching together allow us to propose a revised L1 insertion model. Finally, our evolutionary analysis demonstrates structural conservation between ORF2p and other RNA- and DNA-dependent polymerases. We therefore provide key mechanistic insights into L1 polymerization and insertion, shed light on the evolutionary history of L1 and enable rational drug development targeting L1.