Publications by authors named "Ana Margarida Pereira"

40 Publications

Anaphylaxis in children and adolescents: the Portuguese Anaphylaxis Registry.

Pediatr Allergy Immunol 2021 Mar 27. Epub 2021 Mar 27.

Immunoallergy Department, Hospital Santa Maria, Centro Hospitalar Lisboa Norte, Portugal.

Background: Anaphylaxis is increasing at pediatric age; however, its characterization is hampered by underdiagnosis and underreporting. The aim of this study was to identify the causes of anaphylaxis in children and adolescents in Portugal, thus contributing to a better knowledge of its etiology, clinical manifestations and management.

Methods: During a 10-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 533 patients under 18 years of age with anaphylaxis were included.

Results: Mean age was 8.5±4.9 years, 61% were male; 45% had asthma. Mean age at the first anaphylaxis episode was 5.3±4.7 years (ranging from 1 month to 17 years of age), 63% at preschool age. Most reactions occurred at home (57%). Food-induced anaphylaxis was the leading cause (77%). The main culprit foods were cow's milk (32%), tree nuts (16%), shellfish (13%), egg (12%), fresh fruits (11%), fish (8%) and peanut (8%). Other causes included drugs (11%), insect-sting (5%), cold-induced anaphylaxis (4%), exercise-induced (2%), latex (1%) and idiopathic anaphylaxis (1%). Most patients (83%) were admitted to the emergency department; only 46% received adrenaline treatment. Recurrence of anaphylaxis occurred in 41% of the patients (3 or more episodes in 21%). An adrenaline autoinjector was used in 9% of the patients.

Conclusions: In the Portuguese pediatric population, food is the leading cause of anaphylaxis. Undertreatment with adrenaline and high recurrence of anaphylaxis highlight the need to improve both the diagnosis and the therapeutic management of this life-threatening entity.
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http://dx.doi.org/10.1111/pai.13511DOI Listing
March 2021

Profiling Persistent Asthma Phenotypes in Adolescents: A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies.

Int J Environ Res Public Health 2021 Jan 24;18(3). Epub 2021 Jan 24.

Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal.

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included ( = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact ( = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 ( = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 ( = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms ( < 0.001). Class 3 ( = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month ( = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.
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http://dx.doi.org/10.3390/ijerph18031015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908090PMC
January 2021

[ARIA 2019: An Integrated Care Pathway for Allergic Rhinitis in Portugal].

Acta Med Port 2021 Feb 4;34(2):144-157. Epub 2020 Dec 4.

MACVIA-France. Fondation Partenariale FMC VIA-LR. Centre Hospitalier Arnaud de Villeneuve. Montpellier. INSERM U 1168. Université Versailles St-Quentin-en-Yvelines. Montigny le Bretonneux. France. Charité. Universitätsmedizin Berlin. Humboldt-Universität zu Berlin. Berlin. Alemanha.

The Allergic Rhinitis and Its Impact on Asthma (ARIA) initiative started more than 20 years ago and has developed and disseminated evidence-based guidelines and projects in the field of allergic rhinitis. This initiative is currently focused on providing patient-centred guidelines that contribute to an integrated care pathway between the various levels of care and take advantage of digital solutions, and the introduction of integrated care pathways in clinical practice has been recommended. In this article we describe the adaptation for Portugal of the ARIA Integrated Care Pathways document. After a brief review of the epidemiology and impact of allergic rhinitis in Portugal and the activities carried out in Portugal within the ARIA initiative, we describe the broad knowledge base used for the development of recommendations for the pharmacological treatment of allergic rhinitis, and these recommendations are based on the GRADE methodology, real world evidence acquired by mobile technology (mHealth) and resulting from allergenic exposure chamber studies. What follows is a summary of integrated care pathways for allergen immunotherapy produced in 2019. Allergen immunotherapy is considered an example of precision medicine where the use of mHealth technologies will improve stratification for patient selection and response monitoring. These recommendations were considered as best practices of integrated patient-centred care supported by digital systems from Directorate General for Health and Food Safety of the European Union (DG Santé) and represent the ARIA Phase 4 Change Management strategy.
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http://dx.doi.org/10.20344/amp.13777DOI Listing
February 2021

A school-based intervention for a better future: study protocol of Sintra Grows Healthy.

BMC Public Health 2020 Oct 27;20(1):1615. Epub 2020 Oct 27.

Agrupamento de Centros de Saúde de Sintra, Estrada de Mem Martins 247 - 6° andar, 2725-391, Mem Martins, Portugal.

Background: Preventing childhood obesity is a public health challenge of the twenty-first century and it must be a priority. Governments play a major role in creating and supporting a healthy school environment and should prioritise actions to improve children's health. Sintra Grows Healthy aims to promote healthy lifestyles to prevent childhood obesity and improve children's health-related quality of life and social and emotional skills, through the development of a school evidence-based and sustainable model.

Methods: This protocol describes a quasi-experimental design and community-based participatory research. The participants included in the study are the school community of Portuguese public primary schools from the municipality of Sintra. Data will be collected on demographic and socio-economic characterization, nutritional status, eating habits and behaviours, physical activity, sedentary behaviours and sleep, health-related quality of life, and social and emotional skills.

Discussion: There is evidence to support interventions in school settings as strategies for obesity prevention. Up-to-date homogeneous and community-based interventions for preventing childhood obesity are lacking, therefore Sintra Grows Healthy intends to fill this gap. Furthermore, Sintra Grows Healthy aims to contribute with relevant scientific findings that will allow the development of better strategies for policymakers and society to manage this major public health problem.
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http://dx.doi.org/10.1186/s12889-020-09715-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590451PMC
October 2020

Supplemental selenium source on gut health: insights on fecal microbiome and fermentation products of growing puppies.

FEMS Microbiol Ecol 2020 Oct;96(11)

LAQV, REQUIMTE, ICBAS, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.

Selenium is an essential trace element that can modulate the gut microbiome with an impact on host health. The present study aimed to evaluate the effects of organic (selenium-enriched yeast) vs inorganic (sodium selenite) selenium source on fecal end-fermentation products and gut microbiome of puppies from 20 to 52 weeks of age. Alpha and beta diversity of the gut bacterial community were affected by age but not by gender or selenium source. The relative abundance of taxa was differently affected by age, and the DNA concentration of all selected bacterial groups increased with age, although total volatile fatty acids (VFA), acetate, propionate, caproate and lactate concentrations decreased. Organic selenium was associated with a higher concentration of total VFA, propionate and butyrate, a higher number of DNA copies of Lactobacillus, and a trend to lower DNA copies of Escherichia coli. Effects on fecal microbiome during growth differed with selenium source. Females had higher fecal end-fermentation products related to protein degradation, whereas males had higher DNA concentration of Bifidobacterium. Organic selenium might be beneficial over inorganic for dog food supplementation due to the positive modulation of the gut microbiome observed in puppies.
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http://dx.doi.org/10.1093/femsec/fiaa212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580910PMC
October 2020

Nutrition Information in Oncology - Extending the Electronic Patient-Record Data Set.

J Med Syst 2020 Sep 28;44(11):191. Epub 2020 Sep 28.

Faculty of Medicine, Center for Research in Health Technologies and Information Systems (CINTESIS), University of Porto, Porto, Portugal.

Electronic health records (EHRs) present extensive patient information and may be used as a tool to improve health care. However, the oncology context presents a complex content that increases the difficulties of EHR application. This study aimed at developing openEHR-archetypes representing clinical concepts in cancer nutrition-care, as well as to develop an openEHR-template including the aforementioned archetypes. The study involved the following stages: 1) a thorough literature review, followed by an expert's (nutrition guideline authors) survey, aiming to identify the main statements of published clinical guidelines on nutrition in cancer patients that were not included on the Clinical Knowledge Manager (CKM) repository; 2) modelling of the archetypes using the Ocean Archetype Software and submission to the CKM repository; 3) creating an example template with Template Designer; and 4) automatic conversion of the openEHR-template into a readily usable EHR using VCIntegrator. The clinical concepts (among 17 clinical concepts not yet available in the CKM repository) chosen for further development were: body composition, diet plan, dietary nutrients, dietary supplements, dietary intake assessment, and Malnutrition Screening Tool (MST). So far, four archetypes were accepted for review in the CKM repository and a template was created and converted into an EHR. This study designed new openEHR-archetypes for nutrition management in cancer patients. These archetypes can be included in EHR. Future studies are needed to assess their applicability in other areas and their practical impact on data quality, system interoperability and, ultimately, on clinical practice and research.
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http://dx.doi.org/10.1007/s10916-020-01649-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520877PMC
September 2020

Identifying Indicators to Assess and Monitor Data Integration Engines Systems.

Stud Health Technol Inform 2020 Jun;270:1315-1316

Center for Health and Technology and Services Research - CINTESIS, University of Porto, Portugal.

We aimed to identify relevant indicators for end-users in integration engines for healthcare systems.

Methods: The study was performed in two steps, including interviews and the identification of additional indicators from the literature.

Results: 10 interviews were performed and 90 indicators identified.

Discussion: Several of the indicators are difficult to calculate, nevertheless, they have the potential to improve data quality and processes in healthcare institutions and should be further explored in future studies.
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http://dx.doi.org/10.3233/SHTI200419DOI Listing
June 2020

Flow-Based Dynamic Approach to Assess Bioaccessible Zinc in Dry Dog Food Samples.

Molecules 2020 Mar 15;25(6). Epub 2020 Mar 15.

LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n 228, 4050-313 Porto, Portugal.

This work proposes a simple and easy-to-use flow-through system for the implementation of dynamic extractions, aiming at the evaluation of bioaccessible zinc and the characterization of leaching kinetics in dry dog food samples. The kinetic profile of Zn extraction was determined by flame atomic absorption spectroscopy and the results were fitted in an exponential function (R > 0.960) compatible with a two first-order reactions model. Values of fast leachable Zn ranged from 83 ± 1 to 313 ± 5 mg of Zn per kg of sample, with associated rate constants ranging from 0.162 ± 0.004 to 0.290 ± 0.014 min. Similar results were observed compared to the static batch extraction. The percentage of bioaccessible Zn ranged from 49.0 to 70.0%, with an average value of 58.2% in relation to total Zn content. Principal component analysis regarding the variables fast leachable Zn, associated rate constant, total Zn, and market segment, has shown that 84.6% of variance is explained by two components, where the second component (24.0%) presented loadings only for the fast leachable Zn and associated rate constant. The proposed method is suitable for the fast evaluation (<1 h) of leaching kinetics and bioaccessibility in dry dog food.
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http://dx.doi.org/10.3390/molecules25061333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144096PMC
March 2020

Elastins-Based Antimicrobial Particles for Delivery of Bioactive Compounds.

Methods Mol Biol 2020 ;2118:29-43

CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Braga, Portugal.

In the development of drug delivery systems, researchers pursue multifunctionality to target more complex problems, while maintaining biocompatibility and high encapsulation efficiency. Herein, we describe the preparation of noncytotoxic particles with intrinsic antimicrobial properties able to entrap bioactive compounds. The particles are composed of a recombinantly produced elastin-like recombinamer functionalized with an antimicrobial peptide, and are spontaneously formed in mild conditions by exploiting the thermoresponsiveness of the elastin-like portion. This chapter provides advice and methods for the preparation of the self-assembled antimicrobial particles, the evaluation of antimicrobial activity and cytotoxicity, and the basis to set up the methodology for the encapsulation of bioactive compounds.
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http://dx.doi.org/10.1007/978-1-0716-0319-2_3DOI Listing
January 2021

Effect of Zinc Source and Exogenous Enzymes Supplementation on Zinc Status in Dogs Fed High Phytate Diets.

Animals (Basel) 2020 Feb 29;10(3). Epub 2020 Feb 29.

LAQV, REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, R. Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal.

Zinc is an essential element, a cofactor of many enzymes, and performs catalytic, structural and regulatory functions. Once in the gastrointestinal tract, zinc can interact with food constituents. Phytic acid, the major phosphorus storage in plants, limits zinc availability from animal feeds due to the formation of insoluble complexes with phytates. This study tested the effect of supplemental zinc source (zinc sulfate and a chelate zinc proteinate) and the addition of exogenous enzymes from a solid-state fermentation product of to a high phytate diet. The study was designed according to three Latin Squares 4 × 4 with a 2 × 2 factorial arrangement of treatments, with four periods, four diets, and 12 young adult Beagles. Periods lasted 5 weeks each. Diets were supplemented with 75 mg/kg of zinc sulfate (IZ) or zinc proteinate (OZ), and without or with 200 mg/kg of exogenous enzymes (IZ+, OZ+). Results showed that zinc proteinate increased the bioavailability of phosphorus, yet the zinc biomarkers remained unaffected by the zinc source, with the exception of lymphocyte subsets that benefit from zinc proteinate. The use of exogenous enzymes did not affect zinc availability nor nutrient and energy digestibility.
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http://dx.doi.org/10.3390/ani10030400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142709PMC
February 2020

Penicillin Allergy Testing Is Cost-Saving: An Economic Evaluation Study.

Clin Infect Dis 2021 Mar;72(6):924-938

Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal.

Background: Having a penicillin allergy label is associated with the use of less appropriate and more expensive antibiotics and increased healthcare utilization. Penicillin allergy testing results in delabeling most allergy claimants and may be cost-saving. This study aimed to project whether penicillin allergy testing in patients reporting a penicillin allergy is cost-saving.

Methods: In this economic evaluation study, we built decision models to project the economic impact of 2 strategies for a patient with a penicillin allergy label: (1) perform diagnostic testing (drug challenges, with or without skin tests); and (2) do not perform diagnostic testing. The health service perspective was adopted, considering costs with penicillin allergy tests, and with hospital bed-days/outpatient visits, antibiotic use, and diagnostic testing. Twenty-four base case decision models were built, accounting for differences in the diagnostic workup, setting (inpatient vs outpatient) and geographic region. Uncertainty was explored via probabilistic sensitivity analyses.

Results: Penicillin allergy testing was cost-saving in all decision models built. For models assessing the performance of both skin tests and drug challenges, allergy testing resulted in average savings (in United States [US] dollars) of $657 for inpatients (US: $1444; Europe: $489) and $2746 for outpatients (US: $256; Europe: $6045). 75% of simulations obtained through probabilistic sensitivity analysis identified testing as the less costly option.

Conclusions: Penicillin allergy testing was projected to be cost-saving across different scenarios. These results are devised to inform guidelines, supporting the adoption of policies promoting widespread testing of patients with a penicillin allergy label.
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http://dx.doi.org/10.1093/cid/ciaa194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958749PMC
March 2021

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

Allergy 2020 07 11;75(7):1659-1671. Epub 2020 May 11.

Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe.

Objective: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa.

Methods: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility.

Results: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days).

Conclusion: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.
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http://dx.doi.org/10.1111/all.14153DOI Listing
July 2020

Urinary tract infection in patients with spinal cord injury after urodynamics under fosfomycin prophylaxis: a retrospective analysis.

Porto Biomed J 2019 Nov-Dec;4(6):e56. Epub 2019 Nov 26.

Centro de Reabilitação do Norte, Valadares, Portugal.

Background: Urinary tract infection (UTI) is a common complication of spinal cord injury (SCI). Urodynamic testing is widely used for characterization of vesico-sphincteric dysfunction and for therapeutic orientation. As an invasive procedure, the risk of UTI is increased so, in some medical centers, antibiotic prophylaxis is instituted. Fosfomycin is one of the antibiotics used.

Objective: The aim of this study was to evaluate the incidence of UTI after urodynamics in patients with SCI, under fosfomycin prophylaxis.

Methods: Retrospective analysis was performed on patients with SCI, admitted to a rehabilitation center between January 2016 and June 2017, who underwent urodynamics studies under fosfomycin prophylaxis. Demographic data, risk factors for UTI-bacteriuria before urodynamics, high residual volume (>100 mL), bladder emptying method, vesico-sphincteric dyssynergia, and detrusor hyperactivity were analyzed. The incidence of UTI after urodynamics was evaluated.

Results: The study included 84 patients, predominantly men 55 (65.5%). The mean age of the patients was 55.6 (18.9). Eleven (22.5%) had vesico-sphincteric dyssynergia, 32 (65.3%) detrusor hyperactivity and 22 (44.9%) had a high residual volume. Thirty-seven (44.1%) had asymptomatic bacteriuria before the urodynamics. Urinary complaints suggestive of UTI after urodynamics were observed in 2(2.4%) of patients, without significant bacteriuria and identification of bacterial agent.

Conclusions: The incidence of UTI after invasive procedures is reported between 3% and 20% in the literature, so antibiotic prophylaxis has been instituted, although controversial. In the study, in none of the patients the diagnosis of UTI was confirmed. Fosfomycin prophylaxis may have been important in reducing the incidence of UTI.
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http://dx.doi.org/10.1097/j.pbj.0000000000000056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819542PMC
November 2019

Smoking in Portugal: Where do we stand today?

Rev Port Cardiol 2019 08 6;38(8):595-597. Epub 2019 Nov 6.

CINTESIS, Center for Health Technology and Services Research, Faculty of Medicine, University of Porto, Portugal; Allergy Unit, CUF-Porto Instituto & Hospital, Porto, Portugal; MEDCIDS-Department of Community Medicine, Information, and Health Sciences, Faculty of Medicine, University of Porto, Porto, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.repc.2019.09.002DOI Listing
August 2019

Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts.

BMJ Open 2019 11 7;9(11):e031732. Epub 2019 Nov 7.

Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto (FMUP), Porto, Portugal

Objective: We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.

Design: Baseline data from two prospective multicentre observational studies.

Setting: 29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal.

Participants: 395 patients (≥13 years old) with persistent asthma.

Measures: Data on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0-50; medium 51-80; high 81-100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients' and physicians' VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation.

Results: High inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65-95) mm; 53% VAS>80) and by physicians (84 (68-95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (r=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R=44%).

Conclusion: Although both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.
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http://dx.doi.org/10.1136/bmjopen-2019-031732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858182PMC
November 2019

Can openEHR Represent the Clinical Concepts of an Obstetric-Specific EHR - ObsCare Software?

Stud Health Technol Inform 2019 Aug;264:773-777

Center for Health and Technology and Services Research - CINTESIS, University of Porto, Portugal.

ObsCare is an obstetric-specific Electronic Health Record in use in nine Portuguese obstetric departments. Like other EHRs, it faces major challenges related to semantic interoperability and data quality. openEHR is proposed to address those needs. This study aimed to describe a summary representation of Obscare workflow and to validate whether archetypes in the openEHR Clinical Knowledge Manager repository can represent ObsCare clinical concepts. The study included the phases: a) ObsCare form selection; b) Description of the workflow care process; c) Detailed data extraction; and d) CKM models analysis. 379 variables were analyzed: 219 were fully represented in CKM repository; 99 were partially represented and needed archetype modification; and 61 were not represented and need new archetypes. To conclude, our study showed that the openEHR CKM repository requires further enhancements to be able to fully answer to the needs of an obstetric-specific EHR, the ObsCare software.
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http://dx.doi.org/10.3233/SHTI190328DOI Listing
August 2019

Lipidomics in autoimmune diseases with main focus on systemic lupus erythematosus.

J Pharm Biomed Anal 2019 Sep 6;174:386-395. Epub 2019 Jun 6.

Mass Spectrometry Center & QOPNA, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; Departament of Chemistry & CESAM & ECOMARE, University of Aveiro, Campus Universitário de Santiago 3810-193 Aveiro, Portugal. Electronic address:

Autoimmune diseases (AID) are a heterogeneous group of disorders that have in common a chronic inflammation and dysregulation of the immune system. Systemic lupus erythematosus (SLE) is one of the most frequent systemic autoimmune diseases characterized by autoimmune phenomena in multiple organs. The tests used for evolution and prognosis assessment are either non-specific or non-sensitive, impairing an adequate therapeutics. To face this drawback, lipidomics is being used to provide more knowledge and insights regarding autoimmune disorders. Through lipidomic approaches using MS, it is possible to identify and quantify the level of lipid molecular species in the biological system and this could be useful to identify biomarkers and to better understand the pathophysiology of autoimmune diseases. There are some evidence that lipids and oxidized lipids can play a key role in AID pathogenesis. Although this field has been scarcely explored, there are some studies that reported variations on the lipid profile at a molecular level using lipidomic approaches based on MS in SLE. The results gathered herein showed changes mainly in the level of phospholipids, with decrease of some plasmenyl lipids, fatty acids, with reduction of PUFA, and sphingolipids, with changes in fatty acyl chain composition. These changes may be the result of lipids` modifications due to oxidation and increase of ROS. Some alterations can be associated with changes in membrane of lymphocytes and with the deregulation of the immune system. Thus, exploring the knowledge from modern lipidomic approaches in the study of the role of lipids and oxidized lipids, in oxidative stress and in inflammatory diseases, could contribute for the identification of new lipid biomarkers. Lipid biomarkers are promising tools to prognosis and treatment monitoring, tailored for the best therapeutic response and highest safety to ensure better patient care and to be used for personalized medicine.
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http://dx.doi.org/10.1016/j.jpba.2019.06.005DOI Listing
September 2019

Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study.

J Allergy Clin Immunol 2019 07 3;144(1):135-143.e6. Epub 2019 Apr 3.

MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France; University Hospital, Montpellier, France; INSERM U 1168, VIMA: Ageing and chronic diseases Epidemiological and Public Health Approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, Montigny le Bretonneux, and Euforea, Brussels, Belgium. Electronic address:

Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control.

Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR.

Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-antihistamines were studied.

Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-antihistamines were found.

Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible.
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http://dx.doi.org/10.1016/j.jaci.2019.01.053DOI Listing
July 2019

From ObsCare Software to an OpenEHR Platform: Modelling Obstetric Archetypes.

Stud Health Technol Inform 2019 ;258:153-157

Center for Health and Technology and Services Research - CINTESIS, University of Porto, Portugal.

Introduction And Aims: Electronic health records (EHRs) are important tools to facilitate communication between care providers and to improve clinical research. In obstetrics they became essential. The ObsCare software was created to answer to the need for an EHR with specific obstetric features. The present study aimed to develop openEHR-archetypes capable of representing an ObsCare® EHR form and to create an openEHR-template using the developed archetypes.

Methods: The study was performed in four phases: 1) selection and description of the ObsCare form; 2) Clinical Knowledge Manager (CKM) analysis; 3) modelling of the archetypes; 4) creation and testing of the template.

Results: One openEHR-archetype - Newborn summary - was modelled to assemble the following three clinical concepts that were not represented in CKM: hours of life, "Examination of newborn movements" and "Examination of reflexes". Finally, an openEHR-template was built and automatically converted into an EHR by VCIntegrator.

Conclusions: Considering the potential to improve clinical research, we believe that more obstetric-gynecologic clinical statements should be modelled into openEHR.
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August 2019

The Impact of Electronic Obstetric Records Using the ObsCare Software on Scientific Production.

Stud Health Technol Inform 2019 ;258:55-59

Center for Health and Technology and Services Research - CINTESIS, University of Porto, Portugal.

Aims: To compare the characteristics of scientific publications performed in hospitals that used with those that didn't use an obstetric electronic health record (EHR).

Methods: This study included two reviews (A and B). Review A was an exploratory analysis of all 100 abstracts presented at the Scientific Meeting of the Portuguese Society of Obstetrics and Maternal-Fetal Medicine, in November 2017. Review B was a systematic review of studies in obstetrics, performed in Portugal and published between 2016-18 and indexed in PubMed. In both reviews, the included papers/abstracts were divided into two groups: from hospitals that used ObsCare® (ObsCare group) and from hospitals without a specific obstetric EHR or that didn't use ObsCare (sObsCare group).

Results: In both reviews, the sample size was significantly higher in hospitals from the ObsCare group. In review B, the length of the study period was also significantly longer in ObsCare group; no significant difference was found in review A.

Conclusion: Publications from hospitals that used an obstetric specific EHR (ObsCare), included a higher number of patients and longer study periods.
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August 2019

The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies.

Biomed Res Int 2018 21;2018:1495039. Epub 2018 Nov 21.

Pulmonology Department, Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE, Vila Real, Portugal.

The Portuguese Severe Asthma Registry ( RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at . It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.
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http://dx.doi.org/10.1155/2018/1495039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280304PMC
April 2019

How the Smartphone Is Changing Allergy Diagnostics.

Curr Allergy Asthma Rep 2018 10 25;18(12):69. Epub 2018 Oct 25.

Allergy Unit, Instituto and Hospital CUF, Porto, Portugal.

Purpose Of Review: Evidence-based clinical diagnosis of allergic disorders is increasingly challenging. Clinical decision support systems implemented in mobile applications (apps) are being developed to assist clinicians in diagnostic decisions at the point of care. We reviewed apps for allergic diseases general diagnosis, diagnostic refinement and diagnostic personalisation. Apps designed for specific medical devices are not addressed.

Recent Findings: Apps with potential usefulness in the initial diagnosis and diagnostic refinement of respiratory, food, skin and drug allergies are described. Apps to support diagnostic personalisation are not yet available. There is an urgent need to increase the scientific evidence on the real usefulness of these apps, as well as to develop new scientifically grounded apps designed and validated to support all allergic diseases and diagnostic levels. Apps have the potential to change the diagnosis of allergic diseases becoming part of the routine diagnostics toolset, but its usefulness needs to be established.
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http://dx.doi.org/10.1007/s11882-018-0824-4DOI Listing
October 2018

Adult Asthma Scores-Development and Validation of Multivariable Scores to Identify Asthma in Surveys.

J Allergy Clin Immunol Pract 2019 01 18;7(1):183-190.e6. Epub 2018 Jul 18.

CINTESIS-Center for Health Technology and Services Research, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; MEDCIDS-Department of Community Medicine, Information, and Health Sciences, Faculdade de Medicina, Universidade do Porto, Porto, Portugal; Allergy Unit, Instituto & Hospital CUF Porto, Porto, Portugal. Electronic address:

Background: One of the questions in epidemiology is the identification of adult asthma in studies.

Objective: To develop and validate multivariable scores for adult asthma identification in epidemiological studies and to explore cutoffs to rule in/rule out asthma, compared with asthma diagnosed by a physician after clinical examination and diagnostic tests, blinded to the self-administered questions.

Methods: We analyzed data (n = 711 adults) from a nationwide population-based study. The predictors were self-administered questions identified in a literature review (the Adult Asthma Epidemiological Score [A2 score]) and from the Global Allergy and Asthma Network of Excellence (GA2LEN) questionnaire (the GA2LEN Asthma Epidemiological Score [GA2LEN score]). Scores were developed using exploratory factor analysis. Internal consistency, discriminative power, and diagnostic accuracy were assessed.

Results: The A2 score comprises 8 questions (including "Did a physician confirm you had asthma?") and the GA2LEN score comprises 6 questions (including "Have you ever had asthma?"). Both had high Cronbach α (0.89 and 0.85, respectively, for the A2 score and the GA2LEN score) and good area under the receiver-operating characteristic curve (90.4% and 89.0%). The scoring is the sum of positive answers. Asthma is present (rule in) for scores of 4 or more (specificity, 99.2%; PPV, 93.3% and 91.7%; accuracy, 89.4% and 87.4%, respectively, for the A2 score and the GA2LEN score). Asthma is excluded (rule out) for A2 scores of 0 to 1 and a GA2LEN score of 0 (sensitivity, 93.1%; NPV, 98.2% and 98.0%; accuracy 89.4% and 82.8%, respectively, for the A2 score and the GA2LEN score).

Conclusions: These practical scores can be used to rule in/rule out asthma in epidemiological studies and clinical screening/triage settings. They may help physicians in primary care or other specialties to screen patients with asthma using a simple score with a high level of discrimination and to identify the best candidates to be referred for a diagnostic workup. Moreover, their use may contribute to reducing the inconsistencies of operational definitions of asthma across studies and surveys.
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http://dx.doi.org/10.1016/j.jaip.2018.06.024DOI Listing
January 2019

Mineral Composition of Dry Dog Foods: Impact on Nutrition and Potential Toxicity.

J Agric Food Chem 2018 Jul 11;66(29):7822-7830. Epub 2018 Jul 11.

LAQV, REQUIMTE, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) , Universidade do Porto , Rua de Jorge Viterbo Ferreira no. 228 , 4050-313 Porto , Portugal.

Detailed mineral profile of a selection of commercially available complete dry dog foods was determined using ICP-MS (Se, Cu, Mn, Zn, and nonessential trace elements), flame photometry (Na and K) and atomic and molecular spectrophotometry (Ca, P, Mg, and Fe). The contribution of ingredients to the mineral composition was correlated to the food market segment. Results showed an oversupply of essential elements due to the energy density effect on feed intake. Additives contributed from 40.8 to 55.1% to the total trace elements contents. With the exception of Se, all trace elements were supplied above the nutritional requirements of adult dogs. Legal limits of Cu, Se, and Zn were surpassed. The content of nonessential trace elements included values in the range of nanograms to micrograms per kg, without surpassing safe upper limits. This work brings awareness to the need to find supplementation strategies that ensure nutritional adequacy and avoid waste.
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http://dx.doi.org/10.1021/acs.jafc.8b02552DOI Listing
July 2018

Asthma costs and social impact.

Asthma Res Pract 2017 6;3. Epub 2017 Jan 6.

Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal.

In recent decades, both asthma prevalence and incidence have been increasing worldwide, not only due to the genetic background, but mainly because of the effect of a wide number of environmental and lifestyle risk factors. In many countries noncommunicable diseases, like asthma, are not yet considered a healthcare priority. This review will analyze and discuss disparities in asthma management in several countries and regions, such as access to healthcare human resources and medications, due to limited financial capacity to develop strategies to control and prevent this chronic disease. This review tries to explore the social and economic burden of asthma impact on society. Although asthma is generally accepted as a costly illness, the total costs to society (direct, indirect and intangible asthma costs) are difficult to estimate, mainly due to different disease definitions and characterizations but also to the use of different methodologies to assess the asthma socio-economic impact in different societies. The asthma costs are very variables from country to country, however we can estimate that a mean cost per patient per year, including all asthmatics (intermittent, mild, moderate and severe asthma) in Europe is $USD 1,900, which seems lower than USA, estimated mean $USD 3,100.
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http://dx.doi.org/10.1186/s40733-016-0029-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5219738PMC
January 2017

Corrigendum to "Silk-based biomaterials functionalized with fibronectin type II promotes cell adhesion" [Acta Biomater. 47 (2017) 50-59].

Acta Biomater 2017 02 11;49:604. Epub 2016 Nov 11.

CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Electronic address:

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http://dx.doi.org/10.1016/j.actbio.2016.11.008DOI Listing
February 2017

Silk-based biomaterials functionalized with fibronectin type II promotes cell adhesion.

Acta Biomater 2017 01 3;47:50-59. Epub 2016 Oct 3.

CBMA (Centre of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal. Electronic address:

The objective of this work was to exploit the fibronectin type II (FNII) module from human matrix metalloproteinase-2 as a functional domain for the development of silk-based biopolymer blends that display enhanced cell adhesion properties. The DNA sequence of spider dragline silk protein (6mer) was genetically fused with the FNII coding sequence and expressed in Escherichia coli. The chimeric protein 6mer+FNII was purified by non-chromatographic methods. Films prepared from 6mer+FNII by solvent casting promoted only limited cell adhesion of human skin fibroblasts. However, the performance of the material in terms of cell adhesion was significantly improved when 6mer+FNII was combined with a silk-elastin-like protein in a concentration-dependent behavior. With this work we describe a novel class of biopolymer that promote cell adhesion and potentially useful as biomaterials for tissue engineering and regenerative medicine.

Statement Of Significance: This work reports the development of biocompatible silk-based composites with enhanced cell adhesion properties suitable for biomedical applications in regenerative medicine. The biocomposites were produced by combining a genetically engineered silk-elastin-like protein with a genetically engineered spider-silk-based polypeptide carrying the three domains of the fibronectin type II module from human metalloproteinase-2. These composites were processed into free-standing films by solvent casting and characterized for their biological behavior. To our knowledge this is the first report of the exploitation of all three FNII domains as a functional domain for the development of bioinspired materials with improved biological performance. The present study highlights the potential of using genetically engineered protein-based composites as a platform for the development of new bioinspired biomaterials.
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http://dx.doi.org/10.1016/j.actbio.2016.10.002DOI Listing
January 2017

[Approach and Registry of Anaphylaxis in Portugal].

Acta Med Port 2015 Nov-Dec;28(6):786-96. Epub 2015 Dec 31.

Centro de Alergia. Hospitais CUF Descobertas e CUF Infante Santo. Lisboa. Portugal. Centro de Investigação em Tecnologias e Serviços de Saúde. Faculdade de Medicina da Universidade do Porto. Porto Portugal. Sociedade Portuguesa de Alergologia e Imunologia Clínica. Lisboa. Portugal.

Anaphylaxis has a growing incidence, especially in children. It represents a medical emergency and its successful therapy depends on early and proper intervention. Intramuscular epinephrine, with dose adjustment according to weight and age, is the drug of choice for anaphylaxis treatment. After resolution of the acute reaction, the patient should be kept under clinical surveillance for 6 to 24 hours, due to possible biphasic reactions. Prescription of an epinephrine auto injectable device should be considered in all patients with diagnosed or suspected anaphylaxis; additionally these patients should always be referred to an Immunoallergy consultation, to perform adequate investigation and management in order to reduce future risk. All anaphylaxis episodes must be recorded in The Portuguese Catalogue of Allergies and other Adverse Reactions (Catálogo Português de Alergias e outras Reações Adversas, CPARA), which represents a fundamental tool to share clinical information within the Health System. The present manuscript intends to disclose the most recent Portuguese guidelines for the diagnosis and treatment of anaphylaxis, making its clinical approach more effective and homogeneous, and to promote the use of The Portuguese Catalogue of Allergies and other Adverse Reactions as an essential tool to register and share information on anaphylaxis in Portugal.
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March 2018

Circulating endothelial progenitor cells in obese children and adolescents.

J Pediatr (Rio J) 2015 Nov-Dec;91(6):560-6. Epub 2015 Aug 29.

Laboratório de Fisiologia, Instituto de Imagem Biomédica e Ciências da Vida, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.

Objective: This study aimed to investigate the relationship between circulating endothelial progenitor cell count and endothelial activation in a pediatric population with obesity.

Methods: Observational and transversal study, including 120 children and adolescents with primary obesity of both sexes, aged 6-17 years, who were recruited at this Cardiovascular Risk Clinic. The control group was made up of 41 children and adolescents with normal body mass index. The variables analyzed were: age, gender, body mass index, systolic and diastolic blood pressure, high-sensitivity C-reactive protein, lipid profile, leptin, adiponectin, homeostasis model assessment-insulin resistance, monocyte chemoattractant protein-1, E-selectin, asymmetric dimethylarginine and circulating progenitor endothelial cell count.

Results: Insulin resistance was correlated to asymmetric dimethylarginine (ρ=0.340; p=0.003), which was directly, but weakly correlated to E-selectin (ρ=0.252; p=0.046). High sensitivity C-reactive protein was not found to be correlated to markers of endothelial activation. Systolic blood pressure was directly correlated to body mass index (ρ=0.471; p<0.001) and the homeostasis model assessment-insulin resistance (ρ=0.230; p=0.012), and inversely correlated to adiponectin (ρ=-0.331; p<0.001) and high-density lipoprotein cholesterol (ρ=-0.319; p<0.001). Circulating endothelial progenitor cell count was directly, but weakly correlated, to body mass index (r=0.211; p=0.016), leptin (ρ=0.245; p=0.006), triglyceride levels (r=0.241; p=0.031), and E-selectin (ρ=0.297; p=0.004).

Conclusion: Circulating endothelial progenitor cell count is elevated in obese children and adolescents with evidence of endothelial activation, suggesting that, during infancy, endothelial repairing mechanisms are present in the context of endothelial activation.
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http://dx.doi.org/10.1016/j.jped.2015.01.011DOI Listing
July 2016