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Impact of treatment adherence and inhalation technique on asthma outcomes of pediatric patients: a longitudinal study
(2024-03-13) Lizano Barrantes, Catalina; Garin, Olatz; Mayoral, Karina; Dima, Alexandra Lelia; Pont, Angels; Caballero Rabasco, María Araceli; Praena Crespo, Manuel; Valdesoiro Navarrete, Laura; Teresa Guerra, María; Bercedo Sanz, Alberto; Ferrer, Montse; ARCA Group
Introduction: We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroidbased maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma. Methods: Participants (6–14 years old) from the ARCA (Asthma Research in Children and Adolescents) cohort—a prospective, multicenter, observational study (NCT04480242)—were followed for a period from 6 months to 5 years via computer-assisted telephone interviews and a smartphone application. The Medication Intake Survey–Asthma (MIS-A) was administered to assess the implementation stage of adherence, and the Inhalation Technique Questionnaire (InTeQ) was used to assess the five key steps when using an inhaler. Symptom control was measured with the Asthma Control Questionnaire (ACQ), and HRQL was measured with the EQ-5D and the Patient-Reported Outcomes Measurement Information System–Pediatric Asthma Impact Scale (PROMIS-PAIS). Multilevel longitudinal mixed models were constructed separately with symptom control, exacerbation occurrence, EQ-5D, and PROMIS-PAIS as the dependent variables. Results: Of the 360 participants enrolled, 303 (1,203 interviews) were included in the symptom control and exacerbation analyses, 265 (732) in the EQ-5D, and 215 (617) in the PROMIS-PAIS. Around 60% of participants were male subjects, and most of them underwent maintenance treatment with inhaled corticosteroids plus longacting β-agonists in a fixed dose (73.3%). Within-person variability was 83.6% for asthma control, 98.6% for exacerbations, 36.4% for EQ-5D, and 49.1% for PROMISPAIS. At the within-person level, patients with higher adherence had better symptom control (p = 0.002) and HRQoL over time (p = 0.016). Patients with a better inhalation technique reported worse HRQoL simultaneously (p = 0.012), but they showed better HRQoL in future assessments (p = 0.012). The frequency of reliever use was associated with symptom control (p < 0.001), exacerbation occurrence (p < 0.001), and HRQoL (p = 0.042); and boys were more likely to present better symptom control and HRQoL than girls. Conclusion: Our results confirm longitudinal associations at the within-person level of the two indicators of quality use of inhalers: for adherence to maintenance treatment with symptom control and HRQoL, and for the inhalation technique with HRQoL. Although treatment adherence was shown to be excellent, a third of the participants reported a suboptimal inhalation technique, highlighting the need for actions for improving asthma management of the pediatric population.
Systematic review of the needs and health‑related quality of life domains relevant to people surviving cancer in Europe
(2025-01-23) Amat Fernandez, Clara; Garin, Olatz; Luer Aguila, Ricardo; Pardo Cladellas, Yolanda; Briseño, Renata; Lizano Barrantes, Catalina; Rojas Concha, Leslye; Thong, Melissa S. Y.; Apolone, Giovanni; Brunelli, Cinzia; Caraceni, Augusto; Couespel, Norbert; Bos, Nanne; Groenvold, Mogens; Kaasa, Stein; Ciliberto, Gennaro; Lombardo, Claudio; Pietrobon, Ricardo; Pravettoni, Gabriella; Sirven, Aude; Vachon, Hugo; Gilbert, Alexandra; Velikova, Galina; Ferrer, Montse; the EUonQoL Working Group
Purpose To systematically review qualitative studies on outcomes, needs, experiences, preferences, concerns and healthrelated quality of life (HRQoL) of people surviving cancer in Europe in the last decade. Methods Protocol registered (https://www.crd.york.ac.uk/PROSPERO, ID575065). Inclusion criteria: studies with qualitative methods, constructs related to HRQoL, and adults surviving cancer in Europe. The search was conducted in PubMed and Scopus since 2013. Abstracts and full text were revised, data extracted and study risk of bias assessed independently by two researchers. The primary outcomes were the themes arising from each study. A thematic analysis stratified according to the study objective was undertaken by grouping themes into categories. Results Of 18,256 articles identified, 43 fulfilled the inclusion criteria: 16 studies with a generic objective and 27 with specific objectives. Seven categories (57 themes) emerged from the studies with a generic focus: Clinical Management (n=16), Symptoms and Physical Function (n=5), Psychological Function (n=21), Social Function (n=18), HRQoL (n=3), Life Disruption (n=6), and Individual Factors (n=1). The 12 studies focused on treatment and care experiences stand out among those with specific objectives, with most themes fitting into the same seven categories. Conclusions Results clearly showed the predominance of the social and psychological function domains over physical domains among people surviving cancer, additionally identifying specific needs in clinical management, such as information and communication, and relationship with and support from professionals. Therefore, these aspects should be incorporated into the evaluation of patient-centred initiatives for people surviving cancer. Limitations: only two databases were searched, and most European countries were not represented.
Varespladib (LY315920) inhibits neuromuscular blockade induced by Oxyuranus scutellatus venom in a nerve-muscle preparation
(2020-08) Oliveira, Isadora Caruso Fontana; Gutiérrez, José María; Lewin, Matthew R.; Oshima Franco, Yoko
The phospholipase A2 (PLA2) inhibitors varespladib (LY315920) and its orally available derivative methyl-varespladib (LY333013) have been proposed as potential therapies for the treatment of snakebite envenomings in which toxicity depends on the action of PLA2s. In this study, the ability of LY315920 to abrogate the effect of the potent neurotoxic venom of Oxyuranus scutellatus (taipan) was assessed using the mouse phrenic nerve-diaphragm preparation. LY315920 inhibited the venom when (a) incubated with venom before addition to the medium; (b) added to the medium before addition of venom, and; (c) added to the medium within 30 min after addition of venom, and even after the onset of decline in twitch response. This contrasts with previous results with antivenom using the same experimental model, in which the window of time when antibodies are effective is shorter than 10 min. It is proposed that such differences may depend either on the higher affinity of the inhibitor for PLA2s or on the possibility that LY315920 reaches the cytosol of the nerve terminals, inhibiting neurotoxins that have been internalized. Our findings bear implications on the therapeutic potential of varespladib in neurotoxic snakebite envenomings mediated by presynaptically-acting PLA2s.
Citrate inhibition of snake venom proteases
(1998-12) Odell, George V.; Fenton, Aron; Decker, Lilli; Rick, Cowell; Ownby, Charlotte Ledbetter; Gutierrez, José María; Ferry, P. C.; Vick, L. M.
Thirty snake venoms had a citrate content of 2.3 to 12.9%, dry basis, by an aconitase–isocitric dehydrogenase coupled enzyme assay. This is a venom concentration range of approximately 30 to 150 mM citrate assuming 25% venom solids content. Inhibition of snake venom protease activity by the addition of exogenous citrate was obtained using azure blue hide powder and azocasein as substrates. Protease inhibitions of 7.5% for Crotalus atrox venom to 78% for Bothrops picadoi venom were observed with citrate. Complete inhibition of snake venom protease activity by citrate was not observed. Bothrops asper (Pacifico) venom showed a 41% protease inhibition by citrate with azocasein as the substrate and 46% inhibition of Bothrops asper (Alantico) venom protease with azure blue hide power as a substrate. Trypsin was not inhibited in this system. Citrate may inhibit some venom protease activity by forming a complex with the zinc of zinc-dependent enzymes.
Bothrops snakebite envenomings in the amazon region
(2020-03-23) Resiere, Dabor; Monteiro, Wuelton Marcelo; Houcke, Stephanie; Pujo, Jean Marc; Mathien, Cyrille; Mayence, Claire; Neviere, Rémi; Hommel, Didier; Sachett, Jacqueline de Almeida Gonçalves; Mehdaoui, Hossein; Gutiérrez, José María; Kallel, Hatem
The present review summarizes the main aspects of envenomings by Bothrops sp. snakes in the Amazonia, including the epidemiology, pathophysiology, clinical manifestations, and therapy of envenomings. In a context of global efforts to reduce the impact of snakebite envenomings, there is a need for international cooperative efforts by public health authorities and civil society in these countries.