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INTRODUCTION: Adherence to controller medication is a major problem in asthma management, being difficult to assess and tackle. mHealth apps can be used to assess adherence. We aimed to assess the adherence to inhaled corticosteroids+long-acting ß2-agonists (ICS+LABA) in users of the MASK-air® app, comparing the adherence to ICS+formoterol (ICS+F) with that to ICS+other LABA. MATERIALS AND METHODS: We analysed complete weeks of MASK-air® data (2015-2022; 27 countries) from patients with self-reported asthma and ICS+LABA use. We compared patients reporting ICS+F versus ICS+other LABA on adherence levels, symptoms and symptom-medication scores. We built regression models to assess whether adherence to ICS+LABA was associated with asthma control or short-acting beta-agonist (SABA) use. Sensitivity analyses were performed considering the weeks with no more than one missing day. RESULTS: In 2598 ICS+LABA users, 621 (23.9%) reported 4824 complete weeks and 866 (33.3%) reported weeks with at most one missing day. Higher adherence (use of medication ≥80% of weekly days) was observed for ICS+other LABA (75.1%) when compared to ICS+F (59.3%), despite both groups displaying similar asthma control and work productivity. The ICS+other LABA group was associated with more days of SABA use than the ICS+F group (median=71.4% versus 57.1% days). Each additional weekly day of ICS+F use was associated with a 4.1% less risk in weekly SABA use (95%CI=-6.5;-1.6%;p=0.001). For ICS+other LABA, the percentage was 8.2 (95%CI=-11.6;-5.0%;p<0.001). CONCLUSIONS: In asthma patients adherent to the MASK-air app, adherence to ICS+LABA was high. ICS+F users reported lower adherence but also a lower SABA use and a similar level of control.
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BACKGROUND: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. METHODS: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. FINDINGS: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. INTERPRETATION: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.
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Asma , Aplicaciones Móviles , Rinitis Alérgica , Humanos , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/epidemiología , Asma/diagnóstico , Asma/epidemiología , Proyectos de InvestigaciónRESUMEN
Increased use and improved methodology of carbonate clumped isotope thermometry has greatly enhanced our ability to interrogate a suite of Earth-system processes. However, interlaboratory discrepancies in quantifying carbonate clumped isotope (Δ47) measurements persist, and their specific sources remain unclear. To address interlaboratory differences, we first provide consensus values from the clumped isotope community for four carbonate standards relative to heated and equilibrated gases with 1,819 individual analyses from 10 laboratories. Then we analyzed the four carbonate standards along with three additional standards, spanning a broad range of δ47 and Δ47 values, for a total of 5,329 analyses on 25 individual mass spectrometers from 22 different laboratories. Treating three of the materials as known standards and the other four as unknowns, we find that the use of carbonate reference materials is a robust method for standardization that yields interlaboratory discrepancies entirely consistent with intralaboratory analytical uncertainties. Carbonate reference materials, along with measurement and data processing practices described herein, provide the carbonate clumped isotope community with a robust approach to achieve interlaboratory agreement as we continue to use and improve this powerful geochemical tool. We propose that carbonate clumped isotope data normalized to the carbonate reference materials described in this publication should be reported as Δ47 (I-CDES) values for Intercarb-Carbon Dioxide Equilibrium Scale.
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PURPOSE: The recent repurposing of ketamine as treatment for pain and depression has increased the need for accurate population pharmacokinetic (PK) models to inform the design of new clinical trials. Therefore, the objectives of this study were to externally validate available PK models on (S)-(nor)ketamine concentrations with in-house data and to improve the best performing model when necessary. METHODS: Based on predefined criteria, five models were selected from literature. Data of two previously performed clinical trials on (S)-ketamine administration in healthy volunteers were available for validation. The predictive performances of the selected models were compared through visual predictive checks (VPCs) and calculation of the (root) mean (square) prediction errors (ME and RMSE). The available data was used to adapt the best performing model through alterations to the model structure and re-estimation of inter-individual variability (IIV). RESULTS: The model developed by Fanta et al. (Eur J Clin Pharmacol 71:441-447, 2015) performed best at predicting the (S)-ketamine concentration over time, but failed to capture the (S)-norketamine Cmax correctly. Other models with similar population demographics and study designs had estimated relatively small distribution volumes of (S)-ketamine and thus overpredicted concentrations after start of infusion, most likely due to the influence of circulatory dynamics and sampling methodology. Model predictions were improved through a reduction in complexity of the (S)-(nor)ketamine model and re-estimation of IIV. CONCLUSION: The modified model resulted in accurate predictions of both (S)-ketamine and (S)-norketamine and thereby provides a solid foundation for future simulation studies of (S)-(nor)ketamine PK in healthy volunteers after (S)-ketamine infusion.
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Ketamina/análogos & derivados , Ketamina/farmacocinética , Modelos Biológicos , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Using spin-polarized scanning tunneling microscopy and density functional theory, we have studied the magnetic properties of Pd/Fe atomic bilayers on Re(0001). Two kinds of magnetic ground states are discovered due to different types of stacking of the Pd adlayer on Fe/Re(0001). For fcc stacking of Pd on Fe/Re(0001), it is a spin spiral propagating along the close-packed (ΓK[over ¯]) direction with a period of about 0.9 nm, driven by frustrated exchange and Dzyaloshinskii-Moriya interactions. For the hcp stacking, the four-site four-spin interaction stabilizes an up-up-down-down state propagating perpendicular to the close-packed direction (along ΓM[over ¯]) with a period of about 1.0 nm. Our work shows how higher-order exchange interactions can be tuned at interfaces.
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Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , COVID-19 , Desensibilización Inmunológica , Humanos , SARS-CoV-2Asunto(s)
Productos Biológicos , Medicina , Pólipos Nasales , Anticuerpos Monoclonales Humanizados , HumanosAsunto(s)
Alérgenos/inmunología , Anafilaxia/diagnóstico , Asma/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Hipersensibilidad/diagnóstico , Polisorbatos/efectos adversos , Adulto , Alérgenos/uso terapéutico , Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/complicaciones , Femenino , Humanos , Omalizumab/efectos adversos , Omalizumab/uso terapéutico , Polisorbatos/uso terapéuticoRESUMEN
BACKGROUND: The association of acetylsalicylic acid (ASA) intolerance, chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, or chronic urticaria is known as NSAID-exacerbated respiratory disease (N-ERD). N-ERD patients often suffer from recurrent nasal polyps, severe asthma or also from urticaria. The aim of the present study was to retrospectively analyze the clinical efficacy of anti-IgE antibody treatment with omalizumab in patients with confirmed N-ERD. METHODS: In the open trial with patients receiving verum patients with CRSwNP, confirmed N-ERD by oral or nasal ASA challenges, asthma or chronic urticaria were included in the study. Rhinological and pulmonary parameters were evaluated before and after 3, 6 and 9 months of therapy by rhinological questionnaires (CRS VAS-scores and RSOM-31), nasal polyp (NP)-, ACT-scores and FEV1 values. Urticaria activity was monitored clinically. N-ERD patients with aspirin desensitization were included as control group (follow-up 9 months). RESULTS: In the omalizumab group 16 patients were included (10 female, 6 male, mean age 51 yrs). CRS symptoms, RSOM-31- and NP-score decreased significantly following omalizumab therapy compared to baseline. The ACT-score (MV 16.5 to 20.6) and FEV1values (MV 80 % to 89 %) improved significantly. No urticaria symptoms were reported after 3 months. Oral prednisolone therapy was required in one case and a repeated nasal sinus surgery in an additional case due to progression of NP. In the control group (8 female, 8 male, mean age 45 yrs) the NP-score was unchanged. CONCLUSIONS: Omalizumab is an effective therapy option in N-ERD patients in a 9 month study period.
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Antiinflamatorios no Esteroideos , Pólipos Nasales , Omalizumab , Rinitis , Sinusitis , Antiinflamatorios no Esteroideos/uso terapéutico , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/complicaciones , Pólipos Nasales/tratamiento farmacológico , Omalizumab/uso terapéutico , Estudios Retrospectivos , Rinitis/tratamiento farmacológico , Sinusitis/tratamiento farmacológicoRESUMEN
Betula pollen is frequently found in the atmosphere of central and northern Europe. Betula pollen are health relevant as they cause severe allergic reactions in the population. We developed models of thermal requirements to predict start, peak and end dates of the Betula main pollen season for Bavaria (Germany). Betula pollen data of one season from 19 locations were used to train the models. Estimated dates were compared with observed dates, and the errors were spatially represented. External validation was carried out with time series datasets of 3 different locations (36years in total). RESULTS: The temperature requirements to detonate the main pollen season proved non-linear. For the start date model (error of 8,75days during external validation), daily mean temperatures above a threshold of 10°C from 28th of February onwards were the most relevant. The peak model (error of 3.58days) takes into account mean daily temperatures accumulated since the first date of the main pollen season in which the daily average temperature exceeded 11°C. The end model (error of 3.75days) takes into account all temperatures accumulated since the start of the main pollen season. CONCLUSION: These models perform predictions that enable the allergic population to better manage their disease. With the established relationship between temperatures and pollen season dates, changes in the phenological behaviour of Betula species due to climate change can be also estimated in future studies by taking into account the different climate scenarios proposed by previous climate change studies.
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Alérgenos/análisis , Betula , Monitoreo del Ambiente , Polen , Cambio Climático , Alemania , Estaciones del Año , TemperaturaRESUMEN
mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.
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BACKGROUND: The use of allergen immunotherapy (AIT) for allergic rhinitis and its clinical efficacy in clinical trials depends on the effective determination of pollen allergen exposure time periods. We evaluate pollen data from Germany to examine the new definitions on pollen season and peak pollen period start and end as proposed by the European Academy of Allergy and Clinical Immunology (EAACI) in a recently published Position Paper. The aim was to demonstrate the ability of these definitions to mirror symptom loads for grass and birch pollen-induced allergic rhinitis based on real-life data. METHODS: Data coming from four pollen monitoring stations in the Berlin and Brandenburg area in Germany and for 3 years (2014-2016) were used to investigate the correlation of season definitions, birch and grass pollen counts and total nasal symptom and mediation scores as reported by patients in "Patients Hay fever Diaries" (PHDs). After the identification of pollen periods on the basis of the EACCI criteria, a statistical analysis was employed, followed by a detailed graphical investigation. RESULTS: The analysis revealed that the definitions of pollen season as well as peak pollen period start and end as proposed by the EAACI are correlated to symptom loads for grass and birch pollen-induced allergic rhinitis reported by patients in PHDs. CONCLUSION: Based on our analysis, the validity of the EAACI definitions on pollen season is confirmed. Their use is recommended in future clinical trials on AIT as well as in daily routine for optimal patient care.
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Alérgenos/inmunología , Betula/efectos adversos , Poaceae/efectos adversos , Polen/inmunología , Rinitis Alérgica/diagnóstico , Rinitis Alérgica/inmunología , Manejo de la Enfermedad , Femenino , Geografía , Alemania/epidemiología , Humanos , Masculino , Vigilancia en Salud Pública , Rinitis Alérgica/epidemiología , Rinitis Alérgica/terapia , Estaciones del AñoRESUMEN
BACKGROUND: Ambient air quality monitoring is a governmental duty that is widely carried out in order to detect non-biological ("chemical") components in ambient air, such as particles of < 10 µm (PM10, PM2.5), ozone, sulphur dioxide, and nitrogen oxides. These monitoring networks are publicly funded and air quality data are open to the public. The situation for biological particles that have detrimental effects on health, as is the case of pollen and fungal spores, is however very different. Most pollen and spore monitoring networks are not publicly funded and data are not freely available. The information regarding which biological particle is being monitored, where and by whom, is consequently often not known, even by aerobiologists themselves. This is a considerable problem, as local pollen data are an important tool for the prevention of allergic symptoms. OBJECTIVE: The aim of this study was to review pollen monitoring stations throughout the world and to create an interactive visualization of their distribution. METHODS: The method employed to collect information was based on: (a) a review of the recent and historical bibliography related to pollen and fungal spore monitoring, and (b) personal surveys of the managers of national and regional monitoring networks. The interactive application was developed using the R programming language. RESULTS: We have created an inventory of the active pollen and spore monitoring stations in the world. There are at least 879 active pollen monitoring stations in the world, most of which are in Europe (> 500). The prevalent monitoring method is based on the Hirst principle (> 600 stations). The inventory is visualised as an interactive and on-line map. It can be searched, its appearance can be adjusted to the users' needs and it is updated regularly, as new stations or changes to those that already exist can be submitted online. CONCLUSIONS: The map shows the current situation of pollen and spore monitoring and facilitates collaboration among those individuals who are interested in pollen and spore counts. It might also help to improve the monitoring of biological particles up to the current level employed for non-biological components.
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BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. METHODS: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. RESULTS: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.
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Hipersensibilidad/epidemiología , Aplicaciones Móviles , Multimorbilidad , Rinitis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación del Resultado de la Atención al Paciente , Prevalencia , Estudios Prospectivos , Proyectos de Investigación , Adulto JovenRESUMEN
BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.