bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD36 Scoping Of Interventions Of The Philippines' Most Burdensome Diseases
Authors: Haw Nel Jason , Wong John , Lim Abigail , Co Stephanie Anne 
Published: January 2019

Introduction:In 2016, Global Burden of Disease (GBD) data was used to identify the top twenty percent of disease causes in the Philippines, which happened to account for eighty percent of the burden, following the Pareto principle. This study follows from that initial work, aimed at creating a list of cost-effective interventions recommended for priority-setting to achieve universal health coverage (UHC).Methods:A comprehensive literature review search was done, from global sources such as the Disease Control Priorities (DCP) for Developing Countries Project and World Health Organization's (WHO) Choosing Interventions that are Cost-Effective (CHOICE), and local sources such as clinical practice guidelines (CPGs). Forty-seven local experts from thirty-eight medical societies were also consulted on the applicability, appropriateness, adaptability, feasibility of implementation, ability to maintain fidelity, ease of dissemination, and sustainability of selected interventions in the Philippine setting. Resource requirements were then derived using the WHO OneHealth Tool, CPGs, and key informant interviews.Results:A list of 745 interventions categorized by life stages and by level of intervention with estimates of cost-effectiveness was produced. From these, fifty seven percent had cost-effectiveness studies. Primary interventions were found to be the least costly for the pregnant women, newborn, infant, adolescents, adults, and elderly life stages, while tertiary interventions were found to be the least costly for children.Conclusions:The interventions are potential targets for inclusion by policymakers. Additional factors to consider include the appropriateness of the context in which the cost-effectiveness study was conducted, the feasibility of conducting primary HTA locally, the local costs of the intervention, and the need to act quickly before the policy window closes.
PD48 OTL38, A Tumour-Specific Agent In Surgery For Ovarian Cancer
Authors: Polo-Desantos Mar , Luengo-Matos Setefilla , Orrego Juan Pablo Chalco , Sánchez-Gómez Luis María 
Published: January 2019

Introduction:Ovarian cancer (OC) has the highest mortality rate of all gynecologic malignancies. Completeness of cytoreductive surgery is a key prognostic factor for survival. To differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is difficult and can lead to incomplete tumour removal. OTL38 is a folate analogue conjugated to a near-infrared fluorescent dye which has high specificity and affinity for folate receptor alpha (FRα) expressed in OC. OTL38 together with a specific imaging system can help the surgeon to visualize diseased tissue. The objective of this work is to know the effectiveness and safety of OTL38 in of OC surgery.Methods:Early assessment of OTL38 identified through the early-awareness and alert-system, “SINTESIS-new technologies”, of AETS-ISCIII. The searched databases were: PubMed, WOS, Tripdatabase, Dynamed, Cochrane Library and ICTRP. Clinical studies using the OTL38 in cytoreductive surgery in OC published until September 2017 were reviewed.Results:Only one publication, supported by industry, was retrieved. The study assesses the pharmacokinetics and tolerability of OLT38 in 30 healthy people randomized into 4 groups with different doses and a control group. The study also analyses the percentage of cytoreduction in 12 OC patients. Infusion of 0.025, 0.05, and 0.1 mg/kg OTL38 doses was associated with mild adverse events which did not require intervention. The 0.2 mg/kg dose was associated to adverse events of moderate severity. In OC patients, 0.0125 mg/kg dose was considered the optimal dose with mild adverse events. OTL38 accumulated in FRα-positive tumours and metastases allowed the surgeon to resect an additional 29 percent of malignant lesions which were not detected using standard inspection and palpation methods.Conclusions:The OTL38 is an emergent health technology, which could help in cytoreductive surgery for ovarian cancer. However, the evidence is scarce and it would be necessary to continue further studies.
PD50 Helping Innovators Navigate Policy And Regulatory Processes
Authors: MacNeil Maggie , Koch Melissa , Juzwishin Don , Stole Paul 
Published: January 2019

Introduction:As part of a national aging and technology network, AGE-WELL, one work group aims to promote the understanding of potential policy and regulatory hurdles among innovators and decision-makers. This study describes the development of resources to help innovators to navigate policy and regulatory systems to have their technologies adopted.Methods:A policy primer was created that highlights considerations for innovators during the innovation process (from development to implementation). The content of the policy primer was developed by identifying resources through the Canadian Agency for Drugs and Technology in Health Grey Matters search tool, and in consultation with legal and regulatory consultants. By surveying AGE-WELL technology-developing projects (n=15) we characterized the technologies being developed within the network. Survey questions included: intended end-user/purchaser of the technology and past/anticipated facilitators/barriers in their innovation process. The policy primer and survey data were combined to create tailored innovation maps with considerations for each technology being developed within the network. These materials were used to develop a beta website where users can receive information relevant to various innovation stages, as it pertains to their technology. We gained feedback about our materials via surveys and interviews with AGE-WELL technology developers.Results:The tailored innovation maps and website were seen as helpful resources for understanding policy and regulatory processes required for technology adoption. Technology developers expressed interest in gaining further access to these resources. Innovators desired additional resources about demonstrating value and measuring technology effectiveness.Conclusions:Resources were developed to help guide technology innovators through policy and regulatory processes; preliminary feedback suggests these were valued by innovators. Next steps include refining the website and releasing these resources to innovators beyond the AGE-WELL Network.
PD56 Economic Evaluation Of Dalbavancin In European Countries
Authors: Viti Raffaella , Marcellusi Andrea , Sarmati Loredana , Streinu-Cercel Adrian , Pana Adrian , Espín Jaime , Gallego Juan Pablo Horcajada , Favato Giampiero , Andreoni Massimo , Mennini Francesco Saverio 
Published: January 2019

Introduction:Dalbavancin is a new innovative long-acting antimicrobial treatment that allows clinicians to endorse an early discharge program for patients suffering from acute bacterial skin and skin structure Infections (ABSSSI). The aim of this study was to develop a spending predictor model for evaluating the direct costs associated with the management of ABSSSI from the National Health Service (NHS) perspective of Italy, Spain, and Romania. The main purpose is to compare the hospitalization and drug costs due to the treatment of ABSSSI patients treated with standard antibiotics therapy or innovative long-acting treatment dalbavancin.Methods:A decision-analytic model was performed to evaluate the diagnostic and clinical pathways of ABSSSI patients in the hospital, based on clinicians’ expert opinion. The standard of care scenario was compared with the dalbavancin scenario. The epidemiological and cost parameters were extrapolated from national administrative databases (hospital information system) and from a systematic literature review for each country. Only direct costs in the national payer's perspective were considered. Probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OSA) were performed to check the robustness of the model assumptions.Results:Overall, the model estimated an average annual number of patients with ABSSSI equal to around 50,000 in Italy, Spain, and Romania. The introduction of dalbavancin reduced the length of stay of, on average, 3.3 days per ABSSSI patient. From the economic point of view, dalbavancin did not incur any additional cost from the NHS perspective with homogenous results between countries. The PSA and OSA demonstrated the robustness of the results.Conclusions:The preliminary results highlight that the introduction of dalbavancin could generate a significant reduction in term of length of stay with no incremental cost from the NHS perspective. This model could represent a good tool for policymakers to provide information on the early discharge approach in the ABSSSI management.
PD66 Indirect Comparison Of Treatments For Metastatic Melanoma
Authors: Aleman Alicia , Pedrosa Daniel , Irisarri Magdalena , Alonso Rafael , Galán Ana Perez , Guzman Regina 
Published: January 2019

Introduction:Vemurafenib plus cobimetinib (VC) for the treatment of metastatic melanoma was requested to be included in the National Formulary in Uruguay. The standard of care for metastatic melanoma in Uruguay is dacarbazine. There is no published head-to-head trial assessing the effects of VC versus dacarbazine. The objective of this study was to perform an indirect comparison of the effects of dacarbazine, compared with VC, based on the results of trials that included both treatments versus the same comparator (vemurafenib alone).Methods:We searched Pubmed and The Cochrane Library for trials comparing either VC or dacarbazine with vemurafenib. Trials were assessed in terms of risk of bias, similarity of interventions and inclusion and exclusion criteria, and comparability of characteristics of patients in the vemurafenib arm. We performed an indirect comparison using the Bucher method.Results:From the literature search we retrieved two studies that met the inclusion criteria: a randomized clinical trial that assessed VC versus vemurafenib or placebo and another assessing dacarbazine versus vemurafenib. Both studies were similar in terms of methodological quality, inclusion and exclusion criteria, and comparability of the vemurafenib arms. However, the comparison of overall survival and progression-free survival curves for the vemurafenib arms were quite different between the two trials. At 9 months, overall survival was eighty-one percent and fifty-five percent and progression-free survival was thirty percent and fifteen percent, respectively. The indirect comparison provided the following hazard ratios: 0.24 (95% confidence interval [CI]: 0.14–0.48) for overall survival; 0.13 (95% CI: 0.09–0.19) for progression-free survival; and 0.15 (95% CI: 0.02–1.29) for grade 4 adverse events.Conclusions:Treatment with VC increased overall survival and progression-free survival, compared with dacarbazine. Severe adverse events were less frequent with the combined therapy. However, the differences in the vemurafenib survival curves increases doubts about the accuracy of the indirect estimators of overall survival and progression-free survival.
PD67 Strengthening And Accelerating Health Technology Assessments Through Artificial Intelligence
Authors: Goebel Randy , Kim Mi-Young , Jonsson Egon , Wolfaardt Ulli 
Published: January 2019

Introduction:Rising costs and the rapidly increasing volume of findings from research in health care are driving the demand for comprehensive information to inform the allocation of resources. Health technology assessment (HTA) applies rigorous processes to provide high-quality synthesized information to policymakers and healthcare payers. HTA involves combining large amounts of research publications to systematically evaluate the properties, effects, and impacts on a topic of interest.Methods:The time and resources required to complete a full HTA are often demanding. There is an opportunity to apply high-performance computing (inclusive of artificial intelligence and machine learning disciplines) to HTA. This project applied high-computing technology to create a research synthesis tool to support HTA and then developed a service that integrates as much relevant data as possible to strengthen HTA. This was a joint project that combined expertise from the areas of health technology, machine learning, information technology, and innovation.Results:The information gathered for this phased project from HTA subject matter experts and other stakeholders was collated to inform a research synthesis tool and a broader concept of the project.Conclusions:The results of this study will inform the design of a research synthesis tool that covers the entire HTA process (literature search, screening titles and abstracts, data extraction, quality assessment, and analysis). The collaborators included Alberta Innovates, the Alberta Machine Intelligence Institute, the University of Alberta, Cybera, and PolicyWise. Alberta Innovates, which is an accelerator and innovator of research in the province of Alberta, Canada, was the primary source of funding for this project.
VP36 Benefit Cost Analysis Of Electronic Claims Processing System In Ghana
Authors: Addo Rebecca , Nonvignon Justice , Wang Huihui 
Published: January 2019

Introduction:Since the inception of the Ghana National Health Insurance Scheme (NHIS), it has been pursuing a number of provider payment mechanisms that could not only control the continuous escalating costs of claims payout, but also facilitate the claims processing time. In lieu of this, electronic processing of claims (E-claims) was introduced in 2013 as part of the World Bank supported Health Insurance project that sought to facilitate the financial and operational management of the NHIS. It was piloted in 29 health facilities up to March 2014. They reported cost savings made by the NHIS using E-claims, creating interest in scaling it up. However, the comparative effectiveness and cost effectiveness of E-claims to the health system compared to manual claims processing is unknown. Therefore, to provide decision makers with the appropriate information to choose between manual and E-claims processing, this study sought to evaluate the cost-benefit of E-claims.Methods:A benefit-cost analysis was used to evaluate the efficiency of E-claims from the perspective of the health system. Health providers and the purchaser (NHIS claims processing center) were the study population. Resource use and costs were obtained from the study population. The volumes and values of claims reimbursed and the claims rejection rate were used as the benefits of claims processing. The incremental benefit-cost ratio (IBCR) was estimated for the provider, purchaser and the entire health system. Analysis was conducted in Microsoft Excel.Results:The total cost per claim for providers were USD 1,177.04 and USD 1,240.65 for E-claims and paper claims respectively. The total cost per E-claims and paper claims for the purchaser were 592.17 and 502.19 respectively. Total benefit per E-claim and paper claim processing for the providers were USD 8,562.90 and USD 8,888.37 respectively while that for the purchaser was USD 11,037.62 and USD 8,737.60 respectively. Processing claims electronically led to incremental gains by both providers and purchasers. Providers gained additional USD 2008.51 while the purchaser gained USD 2,300.02. The IBCR was estimated at −19.75, 25.56 and 5.10 for all providers, purchaser and both providers and purchaser of the health system respectively. Thus the IBCR was less than 1for the providers and more than 1 for purchaser and both purchaser and providers.Conclusions:The electronic processing of claims is more efficient compared to manual processing in the Ghana NHIS. This provides decision makers with evidence for scaling it up to all the facilities in Ghana.
Novel application of discrete choice experiment methodology to understand how clinicians around the world triage palliative care needs: A research protocol
Authors: Russell Bethany , Vogrin Sara , Philip Jennifer , Hennessy-Anderson Nicole , Collins Anna , Burchell Jodie , Le Brian , Brand Caroline , Hudson Peter , Sundararajan Vijaya 
Published: January 2019

AbstractObjectiveAs referrals to specialist palliative care (PC) grow in volume and diversity, an evidence-based triage method is needed to enable services to manage waiting lists in a transparent, efficient, and equitable manner. Discrete choice experiments (DCEs) have not to date been used among PC clinicians, but may serve as a rigorous and efficient method to explore and inform the complex decision-making involved in PC triage. This article presents the protocol for a novel application of an international DCE as part of a mixed-method research program, ultimately aiming to develop a clinical decision-making tool for PC triage.MethodFive stages of protocol development were undertaken: (1) identification of attributes of interest; (2) creation and (3) execution of a pilot DCE; and (4) refinement and (5) planned execution of the final DCE.ResultSix attributes of interest to PC triage were identified and included in a DCE that was piloted with 10 palliative care practitioners. The pilot was found to be feasible, with an acceptable cognitive burden, but refinements were made, including the creation of an additional attribute to allow independent analysis of concepts involved. Strategies for recruitment, data collection, analysis, and modeling were confirmed for the final planned DCE.Significance of resultsThis DCE protocol serves as an example of how the sophisticated DCE methodology can be applied to health services research in PC. Discussion of key elements that improved the utility, integrity, and feasibility of the DCE provide valuable insights.
Separating the North and South Pacific Meridional Modes Contributions to ENSO and Tropical Decadal Variability
Authors: Liguori Giovanni , Di Lorenzo Emanuele 
Published: January 2019

AbstractNorth and South Pacific Meridional Modes (NPMM and SPMM) are known precursors of El Niño–Southern Oscillation (ENSO) and Tropical Pacific decadal variability (TPDV). However, the relative importance of these precursors and the timescale on which they impact the tropics remain unclear. Using a 30‐member ensemble of the Community Earth System Model as the control climate, we generate two additional members where the NPMM and SPMM are selectively suppressed. We find that both meridional modes energize the tropical variance independently on different timescales. The absence of NPMM leads to a significant reduction of the tropical interannual variability (~35%), while the absence of the SPMM has no appreciable impact on ENSO but significantly reduces the TPDV (~30%). While the relative importance of the NPMM and SPMM may be model dependent, the stochastic atmospheric variability in the extratropics that energizes the meridional modes emerges as a key source of TPDV.
Estimation of the Variation in Specific Discharge Over Large Depth Using Distributed Temperature Sensing (DTS) Measurements of the Heat Pulse Response
Authors: des Tombe Bas F. , Bakker Mark , Smits Frank , Schaars Frans , van der Made Kees‐Jan 
Published: January 2019

AbstractAn approach is presented to determine groundwater flow in unconsolidated aquifers with a heat pulse response test using a heating cable and a fiber‐optic cable. The cables are installed together using direct push so that the cables are in direct contact with the aquifer. The temperature response is measured for multiple days along the fiber‐optic cable with Distributed Temperature Sensing (DTS). The new approach fits a two‐dimensional analytical solution to the temperature measurements, so that the specific discharge can be estimated without knowledge of the position of the fiber‐optic cable relative to the heating cable. Two case studies are presented. The first case study is at a managed aquifer recharge system where fiber‐optic cables are inserted 15 m deep at various locations to test the fitting procedure. Similar and relatively large specific discharges are found at the different locations with little vertical variation (0.4–0.6 m/day). The second case study is at a polder, where the water level is maintained 2 m below the surrounding lakes, resulting in significant groundwater flow. The heating and fiber‐optic cables are inserted to a depth of 45 m. The specific discharge varies 0.07–0.1 m/day and is significantly larger in a thin layer at 30‐m depth. It is shown with numerical experiments that the estimated specific discharge is smoother than in reality due to vertical conduction, but the peak specific discharge is estimated correctly for layers thicker than ∼1.5 m.
Evolutionary constraints on species diversity in marine bacterioplankton communities
Authors: Lu Hsiao-Pei , Yeh Yi-Chun , Shiah Fuh-Kwo , Gong Gwo-Ching , Hsieh Chih-hao 
Published: January 2019

Abstract
Variation in microbial species diversity has typically been explained as the outcome of local ecological factors driving species coexistence, overlooking the roles of evolutionary constraints. Here, we argue that macro-evolutionary niche conservatism and unequal diversification rates among phylum-level lineages are strong determinants of diversity–environment relationships in bacterial systems. That is, apart from stochasticity, environmental effects operate most strongly on phylum composition, which in turn dictates the species diversity of bacterial communities. This concept is demonstrated using bacterioplankton in the surface seawaters of the East China Sea. Furthermore, we show that the species richness of a local bacterioplankton community can generally be estimated based on the relative abundances of phyla and their contributions of species numbers in the global seawater pool—highlighting the important influence of evolutionary constraints on local community diversity.
Molecular signatures of multiple myeloma progression through single cell RNA-Seq
Authors: Jang Jin Sung , Li Ying , Mitra Amit Kumar , Bi Lintao , Abyzov Alexej , van Wijnen Andre J. , Baughn Linda B. , Van Ness Brian , Rajkumar Vincent , Kumar Shaji , Jen Jin 
Published: January 2019

AbstractWe used single cell RNA-Seq to examine molecular heterogeneity in multiple myeloma (MM) in 597 CD138 positive cells from bone marrow aspirates of 15 patients at different stages of disease progression. 790 genes were selected by coefficient of variation (CV) method and organized cells into four groups (L1–L4) using unsupervised clustering. Plasma cells from each patient clustered into at least two groups based on gene expression signature. The L1 group contained cells from all MGUS patients having the lowest expression of genes involved in the oxidative phosphorylation, Myc targets, and mTORC1 signaling pathways (p < 1.2 × 10−14). In contrast, the expression level of these pathway genes increased progressively and were the highest in L4 group containing only cells from MM patients with t(4;14) translocations. A 44 genes signature of consistently overexpressed genes among the four groups was associated with poorer overall survival in MM patients (APEX trial, p < 0.0001; HR, 1.83; 95% CI, 1.33–2.52), particularly those treated with bortezomib (p < 0.0001; HR, 2.00; 95% CI, 1.39–2.89). Our study, using single cell RNA-Seq, identified the most significantly affected molecular pathways during MM progression and provided a novel signature predictive of patient prognosis and treatment stratification.