| 1. |
- Bousquet, Jean, et al.
(author)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Journal article (peer-reviewed)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 2. |
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| 3. |
- Menditto, Enrica, et al.
(author)
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Adherence to treatment in allergic rhinitis using mobile technology : The MASK Study
- 2019
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In: Clinical and Experimental Allergy. - : WILEY. - 0954-7894 .- 1365-2222. ; 49:4, s. 442-460
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Journal article (peer-reviewed)abstract
- Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC <= 1.25), 51 (4.23%) were partly adherent (MPR >= 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR <70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. Conclusion and clinical relevance: Adherence to treatment is low. The relative efficacy of continuous vs on-demand treatment for allergic rhinitis symptoms is still a matter of debate. This study shows an approach for measuring retrospective adherence based on a mobile app. This also represents a novel approach for analysing medication-taking behaviour in a real-world setting.
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| 4. |
- Abrahamsson, B., et al.
(author)
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Six years of progress in the oral biopharmaceutics area - A summary from the IMI OrBiTo project
- 2020
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In: European journal of pharmaceutics and biopharmaceutics. - : ELSEVIER. - 0939-6411 .- 1873-3441. ; 152, s. 236-247
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Journal article (peer-reviewed)abstract
- OrBiTo was a precompetitive collaboration focused on the development of the next generation of Oral Biopharmaceutics Tools. The consortium included world leading scientists from nine universities, one regulatory agency, one non-profit research organisation, three small/medium sized specialist technology companies together with thirteen pharmaceutical companies. The goal of the OrBiTo project was to deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This goal was achieved through novel prospective investigations to define new methodologies or refinement of existing tools. Extensive validation has been performed of novel and existing biopharmaceutics tools using historical datasets supplied by industry partners as well as laboratory ring studies. A combination of high quality in vitro and in vivo characterizations of active drugs and formulations have been integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of gastrointestinal drug absorption and some of the best practices has been highlighted. This approach has given an unparalleled opportunity to deliver transformational change in European industrial research and development towards model based pharmaceutical product development in accordance with the vision of model-informed drug development.
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| 7. |
- Darwich, Adam S., et al.
(author)
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IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
- 2017
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 626-642
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Journal article (peer-reviewed)abstract
- Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
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| 8. |
- Grandadam, M., et al.
(author)
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Electronic spectral function in the fractionalized pair density wave scenario
- 2020
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In: Physical Review B. - : AMER PHYSICAL SOC. - 2469-9950 .- 2469-9969. ; 102:12
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Journal article (peer-reviewed)abstract
- Studies of the electronic spectral function in cuprates by angle-resolved photoemission spectroscopy (ARPES) reveal unusual features in the pseudogap phase that persist in the superconducting phase. Here we address these observations based on the recently proposed idea that the pseudogap is due to the fractionalization of modulated particle-particle pairs (a pair density wave) into uniform particle-particle and modulated particle-hole pairs. The constraint that appears between these two types of pairs can be seen has an amplitude for the pseudogap energy scale. This constraint directly modifies the electronic spectral function in the pseudogap phase. We derive a self-consistent equation for the pseudogap amplitude and show that it leads to the formation of Fermi arcs. The band dispersion obtained in the antinodal region is in good agreement with experimental ARPES observations in Pb0.55Bi1.5Sr1.6La0.4CuO6+delta (Bi2201) and present a back-bending that goes to the Fermi level as we go away from the antinodal region. We also discuss the temperature dependence of the ARPES spectrum in the pseudogap and in the superconducting state.
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| 9. |
- Lennernäs, Hans, et al.
(author)
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Oral biopharmaceutics tools - Time for a new initiative - An introduction to the IMI project OrBiTo
- 2014
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57:SI, s. 292-299
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Research review (peer-reviewed)abstract
- OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organization, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using active pharmaceutical ingredient (API), formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silica biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and modified-release formulations, as well as allowing optimization of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
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| 10. |
- Margolskee, Alison, et al.
(author)
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IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2 : An introduction to the simulation exercise and overview of results
- 2017
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In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 610-625
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Journal article (peer-reviewed)abstract
- Orally administered drugs are subject to a number of barriers impacting bioavailability (F-oral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp (R), and GastroPlus (TM)) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exercise may not be representative of prospective modelling in industry, as API information was limited to sparse details. 43 active pharmaceutical ingredients (APIs) from the OrBiTo database were selected for the exercise. Over 4000 simulation output files were generated, representing over 2550 study arm-institution-software combinations and approximately 600 human clinical study arms simulated with overlap. 84% of the simulated study arms represented administration of immediate release formulations, 11% prolonged or delayed release, and 5% intravenous (i.v.). Higher percentages of i.v. predicted area under the curve (AUC) were within two-fold of observed (52.9%) compared to per oral (p.o.) (37.2%), however, F-oral and relative AUC (F-rel) between p.o. formulations and solutions were generally well predicted (64.7% and 75.0%). Predictive performance declined progressing from i.v. to solution and immediate release tablet, indicating the compounding error with each layer of complexity. Overall performance was comparable to previous large-scale evaluations. A general overprediction of AUC was observed with average fold error (AFE) of 1.56 over all simulations. AFE ranged from 0.0361 to 64.0 across the 43 APIs, with 25 showing overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms.
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| 11. |
- You, Q. L., et al.
(author)
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Recent frontiers of climate changes in East Asia at global warming of 1.5 degrees C and 2 degrees C
- 2022
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In: npj Climate and Atmospheric Science. - : Springer Science and Business Media LLC. - 2397-3722. ; 5:1
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Journal article (peer-reviewed)abstract
- East Asia is undergoing significant climate changes and these changes are likely to grow in the future. It is urgent to characterize both the mechanisms controlling climate and the response of the East Asian climate system at global warming of 1.5 and 2 degrees C above pre-industrial levels (GW1.5 and GW2 hereafter). This study reviews recent studies on East Asian climate change at GW1.5 and GW2. The intensity and variability of the East Asian summer monsoon are expected to increase modestly, accompanied by an enhancement of water vapor transport. Other expected changes include the intensification of the Western Pacific Subtropical High and an intensified and southward shift of the East Asian jet, while the intensity of the East Asian winter monsoon is projected to reduce with high uncertainty. Meanwhile, the frequency of ENSO may increase in a warming world with great uncertainty. Significant warming and wetting occur in East Asia, with more pronounced intensity, frequency, and duration of climate extremes at GW2 than that at GW1.5. The fine structure of regional climate changes and the presence and location of various warming hotspots, however, show substantial divergence among different model simulations. Furthermore, the Asian climate responses can differ substantially between the transient and stabilized GW1.5 and GW2, which has important implications for emission policies. Thus, to better plan effective mitigation and adaptation activities, further research including an in-depth exploration of the divergent responses in transient versus stabilized scenarios, the quantification of future projection uncertainties, and improvements of the methods to reduce model uncertainties are required.
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