Public involvement in chronic respiratory diseases research: A qualitative study of patients', carers' and citizens' perspectives.

INTRODUCTION: Patient and public involvement (PPI) initiatives involving patients with chronic respiratory disease (CRD) are rare. Therefore, this study aimed to explore the perspectives of patients with CRD, carers and interested citizens regarding the relevance and need for a PPI network and suggestions for its implementation. METHODS: A qualitative study based on focus groups was conducted. Recruitment occurred through invitations on social media platforms and to patients who have participated in previous asthma studies of the team. Three focus groups were conducted, via video conference, using a semi-structured guide. Thematic analysis was performed by two independent researchers and discussed with the extended team. RESULTS: Fifteen patients with CRD, one carer and one interested citizen (13 females, median 36 (range: 18-72) years) participated. All participants acknowledged the importance of implementing a collaborative network and demonstrated interest in being integrated. Participants acknowledged the importance of their involvement in several phases of the research cycle. The main aim identified for this network was to facilitate communication between patients and researchers. Participants regarded the integration of patients, carers, researchers and healthcare professionals from different scientific areas as relevant. The use of digital platforms to attract members and support the work, together with group dynamics and regular meetings, were some of the most relevant practical considerations for implementing the network. The identified facilitators for their engagement were sharing experiences, researchers' and healthcare professionals' support and feedback and schedule flexibility. The identified barriers included the amount of time dedicated, low health/digital literacy and the potential detachment of nondiagnosed patients or those with low symptom impact in daily life. CONCLUSION: Patients, carers and citizens acknowledged the relevance of implementing a collaborative network and demonstrated interest in active participation in every stage of the health research cycle. A deeper knowledge of the barriers and facilitators identified in this study could support implementing these initiatives in Portugal. PATIENT OR PUBLIC CONTRIBUTION: This study was designed by a research team that included one patient with asthma and one carer. They were specifically involved in building the study protocol and the interview guide. They also gave feedback regarding the electronic consent form and the short sociodemographic questionnaire created, namely by removing noncontributing words or phrases and rewording expressions. The lay summary was written by another patient with asthma. All participants of this study were invited to implement and integrate the ConectAR network-a collaborative network of research in respiratory health. PUBLIC SUMMARY: In Portugal, chronic respiratory patients do not have an active role as 'coinvestigators'. This study aimed to acknowledge if patients and citizens considered a patient and public involvement network useful, whose main purpose would be to facilitate communication between patients and researchers. A study based on online group interviews was carried out with patients with chronic respiratory diseases and interested citizens, both recruited on social media platforms. Participants considered that bringing together patients, carers, researchers and healthcare professionals is valuable because sharing different experiences and perspectives may help patients to improve their daily lives and increase research quality. In conclusion, patients agree that implementing a collaborative network with researchers and healthcare professionals and participating in the health research cycle is quite preponderant. Acknowledging what can help and deter this network may be beneficial to implementing this type of initiative in Portugal.

Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health.

OBJECTIVE: Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. DESIGN: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes. RESULTS: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion. CONCLUSION: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.

Risk Factors and Outcomes of Tetralogy of Fallot: From Fetal to Neonatal Life.

Tetralogy of Fallot (ToF) is the most prevalent cyanotic congenital heart disease. Genetic syndromes are present in up to one quarter of patients with this condition, leading to increased morbidity and mortality. Our aim in this work is to characterize our population, evaluate ToF based on the presence of genotype anomalies, and investigate early intervention predictors and outcomes. A retrospective study was performed on neonates with ToF born between August 1, 2008, and August 31, 2018, and admitted to a level III neonatal intensive care unit (NICU). Patients were categorized based on the presence of genotype anomalies and timing of intervention. Thirty-nine neonates were included. The overall mortality during the follow-up period was 5.1% (n = 2). Threatened preterm labor/preterm labor was more prevalent in patients with associated genotype anomalies (p = 0.015). Multivariate analysis showed an association between an abnormal amount of amniotic fluid and ToF with altered genotype, adjusted for smoking, maternal age, gestational age and birth weight [OR = 29.92, 95% CI (1.35-662.44), p = 0.032]. We also found an association between cesarean delivery and neonatal procedures (p = 0.006). Mortality was significantly higher in neonates who underwent early intervention (p = 0.038). Our results indicate that an abnormal amount of amniotic fluid is an independent predictive factor for ToF with genotype alterations. This finding could ultimately have an impact on both prenatal and neonatal counseling and management.

Diet-induced metabolic changes of the human gut microbiome: importance of short-chain fatty acids, methylamines and indoles.

The human gut is a home for more than 100 trillion bacteria, far more than all other microbial populations resident on the body's surface. The human gut microbiome is considered as a microbial organ symbiotically operating within the host. It is a collection of different cell lineages that are capable of communicating with each other and the host and has an ability to undergo self-replication for its repair and maintenance. As the gut microbiota is involved in many host processes including growth and development, an imbalance in its ecological composition may lead to disease and dysfunction in the human. Gut microbial degradation of nutrients produces bioactive metabolites that bind target receptors, activating signalling cascades, and modulating host metabolism. This review covers current findings on the nutritional and pharmacological roles of selective gut microbial metabolites, short-chain fatty acids, methylamines and indoles, as well as discussing nutritional interventions to modulate the microbiome.

MWASTools: an R/bioconductor package for metabolome-wide association studies.

Summary: MWASTools is an R package designed to provide an integrated pipeline to analyse metabonomic data in large-scale epidemiological studies. Key functionalities of our package include: quality control analysis; metabolome-wide association analysis using various models (partial correlations, generalized linear models); visualization of statistical outcomes; metabolite assignment using statistical total correlation spectroscopy (STOCSY); and biological interpretation of metabolome-wide association studies results. Availability and implementation: The MWASTools R package is implemented in R (version > =3.4) and is available from Bioconductor: https://bioconductor.org/packages/MWASTools/. Contact: m.dumas@imperial.ac.uk. Supplementary information: Supplementary data are available at Bioinformatics online.

Compressed perovskite aqueous mixtures near their phase transitions show very high permittivities: New prospects for high-field MRI dielectric shimming.

PURPOSE: Perovskites are greatly used nowadays in many technological applications because of their high permittivity, more specifically in the form of aqueous solutions, for MRI dielectric shimming. In this study, full dielectric characterizations of highly concentrated CaTiO3 /BaTiO3 water mixtures were carried out and new permittivity maxima was reached. METHODS: Permittivity measurements were done on aqueous solutions from 0%v/v to dry powder. The permittivity dependence with pressure was investigated. Scanning electron microscopy images were performed on a few representative solutions. BaTiO3 pressed pads of different thicknesses, permittivities, and distances to the head were compared in a 7T MRI scanner. RESULTS: Perovskite aqueous mixtures undergo a pressure-dependent phase transition in terms of permittivity, with increasing water content. A new relative permittivity maximum of 475 was achieved. Microscopic images revealed structural differences between phases. A B1+ improvement in the temporal lobe was obtained with thin, high permittivity BaTiO3 head. CONCLUSIONS: This new preparation method allows improved pad geometry and placement, as a result of the high relative permittivity values achieved. This method has great significance for medical applications of MRI dielectric shimming, being easy to replicate and implement on a large scale. Magn Reson Med 79:1753-1765, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

J-Resolved 1H NMR 1D-Projections for Large-Scale Metabolic Phenotyping Studies: Application to Blood Plasma Analysis.

1H nuclear magnetic resonance (NMR) spectroscopy-based metabolic phenotyping is now widely used for large-scale epidemiological applications. To minimize signal overlap present in 1D 1H NMR spectra, we have investigated the use of 2D J-resolved (JRES) 1H NMR spectroscopy for large-scale phenotyping studies. In particular, we have evaluated the use of the 1D projections of the 2D JRES spectra (pJRES), which provide single peaks for each of the J-coupled multiplets, using 705 human plasma samples from the FGENTCARD cohort. On the basis of the assessment of several objective analytical criteria (spectral dispersion, attenuation of macromolecular signals, cross-spectral correlation with GC-MS metabolites, analytical reproducibility and biomarker discovery potential), we concluded that the pJRES approach exhibits suitable properties for implementation in large-scale molecular epidemiology workflows.

MetaboSignal: a network-based approach for topological analysis of metabotype regulation via metabolic and signaling pathways.

Summary: MetaboSignal is an R package that allows merging metabolic and signaling pathways reported in the Kyoto Encyclopaedia of Genes and Genomes (KEGG). It is a network-based approach designed to navigate through topological relationships between genes (signaling- or metabolic-genes) and metabolites, representing a powerful tool to investigate the genetic landscape of metabolic phenotypes. Availability and Implementation: MetaboSignal is available from Bioconductor: https://bioconductor.org/packages/MetaboSignal/. Contact: m.dumas@imperial.ac.uk . Supplementary information: Supplementary data are available at Bioinformatics online.

The Utility of Brain Natriuretic Peptide in Pediatric Cardiology: A Review.

OBJECTIVE: The aim of this article is to evaluate the clinical utility of brain natriuretic peptide in pediatric patients, examining the diagnostic value, management, and prognostic relevance, by critical assessment of the literature. DATA SOURCES: In December 2015, a literature search was performed (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/) and included these Medical Subject Headings and text terms for the key words: "brain natriuretic peptide," "amino-terminal pro-brain natriuretic peptide," "children," "neonate/s," "newborn/s," "infant/s," and "echocardiography." STUDY SELECTION: Each article title and abstract was screened to identify relevant studies. The search strategy was limited to published studies in English language concerning brain natriuretic peptide/amino-terminal pro-brain natriuretic peptide in pediatric patients. DATA EXTRACTION: Data on age, gender, type of clinical condition, brain natriuretic peptide assay method, cardiac function variables evaluated by echocardiography, and prognosis were extracted. DATA SYNTHESIS: Brain natriuretic peptide reference values in healthy newborns, infants, and children are presented. Brain natriuretic peptide diagnostic accuracy in newborns, infants, and children suspected to have congenital heart defects is discussed, and brain natriuretic peptide prognostic value reviewed. The data suggest that the determination of brain natriuretic peptide levels improves the diagnostic accuracy in the assessment of heart disease in the pediatric population. Brain natriuretic peptide assay may increase the accuracy of neonatal screening programs for diagnosing congenital heart defects. Echocardiographic variables correlated to brain natriuretic peptide levels. Additionally, brain natriuretic peptide levels predicted adverse outcomes in the postoperative period. CONCLUSIONS: Brain natriuretic peptide assessment is a reliable test to diagnose significant structural or functional cardiovascular disease in children. In the integrated follow-up of these cases, several physiologic and clinical variables must be considered; brain natriuretic peptide may be an additional helpful marker. Nevertheless, larger prospective studies are warranted to elucidate the true prognostic value of brain natriuretic peptide in pediatric patients.

Cardiac injury biomarkers in paediatric age: Are we there yet?

The aim of this article is to evaluate the clinical utility of cardiac injury biomarkers in paediatric age. In December 2015, a literature search was performed (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included the following medical subject headings and text terms for the key words: "cardiac injury biomarkers", "creatine kinase-MB", "myoglobin", "troponin", "children", "neonate/s", "newborn/s", "infant/s" and echocardiography. In the paediatric population, troponins show a good correlation with the extent of myocardial damage following cardiac surgery and cardiotoxic medication and can be used as predictors of subsequent cardiac recovery and mortality. Elevation of cardiac injury biomarkers may also have diagnostic value in cases when cardiac contusion or pericarditis is suspected. Cardiac injury biomarkers are very sensitive markers for the detection of myocardial injury and have been studied in healthy newborns, after tocolysis, intrauterine growth restriction, respiratory distress and asphyxia. The proportion of newborns with elevated troponin was higher than that in ill infants, children, and adolescents and in healthy adults, suggesting that myocardial injury, although clinically occult, is common in this young age group. Results suggest that significant elevation of cord troponin is an excellent early predictor of severity of hypoxic-ischaemic encephalopathy and mortality in term infants. Cardiac biomarkers may also benefit centres without on-site echocardiography with evidence showing good correlation with echo-derived markers of myocardial function. Further studies are needed to better clarify the role of cardiac biomarkers in paediatric age and their correlation with echocardiographic parameters.

Facilitators, barriers and expectations in the self-management of type 2 diabetes--a qualitative study from Portugal.

BACKGROUND: Patients with type 2 diabetes mellitus (DM) have a central role in managing their disease, but the effective adoption of self-management behaviours is often challenging. OBJECTIVES: The main objective of this study was to assess the facilitators, barriers and expectations in the self-management of type 2 DM, as perceived by patients. METHODS: Patients with type 2 DM were recruited at the Portuguese Diabetes Association outpatient clinic, using a convenient sampling technique. Qualitative data was obtained using video-recorded focus groups. Each session had a moderator and an observer, and followed a pre-tested questioning route. Two independent researchers transcribed and analysed the focus groups. RESULTS: Three major themes were identified: diet, physical exercise, and glycaemic control. Difficulties in changing dietary habits were grouped in four main categories: decisional, food quality, food quantity, and dietary schedule. Barriers related to physical exercise also included decisional aspects, as well as fatigue, muscle and joint pain, and other co-morbidities. Information and knowledge translation, as well as family and social ties, were commonly explored aspects across the three themes and were regarded as facilitators in some situations and as barriers in others. CONCLUSION: This study provided new insight on the barriers, facilitators and expectations in type 2 DM self-management, pointing out the importance of tailored guidance. Future research should explore interventions designed to promote and facilitate behaviour change in this population.

The influence of social networking sites on health behavior change: a systematic review and meta-analysis.

OBJECTIVE: Our aim was to evaluate the use and effectiveness of interventions using social networking sites (SNSs) to change health behaviors. MATERIALS AND METHODS: Five databases were scanned using a predefined search strategy. Studies were included if they focused on patients/consumers, involved an SNS intervention, had an outcome related to health behavior change, and were prospective. Studies were screened by independent investigators, and assessed using Cochrane's 'risk of bias' tool. Randomized controlled trials were pooled in a meta-analysis. RESULTS: The database search retrieved 4656 citations; 12 studies (7411 participants) met the inclusion criteria. Facebook was the most utilized SNS, followed by health-specific SNSs, and Twitter. Eight randomized controlled trials were combined in a meta-analysis. A positive effect of SNS interventions on health behavior outcomes was found (Hedges' g 0.24; 95% CI 0.04 to 0.43). There was considerable heterogeneity (I(2) = 84.0%; T(2) = 0.058) and no evidence of publication bias. DISCUSSION: To the best of our knowledge, this is the first meta-analysis evaluating the effectiveness of SNS interventions in changing health-related behaviors. Most studies evaluated multi-component interventions, posing problems in isolating the specific effect of the SNS. Health behavior change theories were seldom mentioned in the included articles, but two particularly innovative studies used 'network alteration', showing a positive effect. Overall, SNS interventions appeared to be effective in promoting changes in health-related behaviors, and further research regarding the application of these promising tools is warranted. CONCLUSIONS: Our study showed a positive effect of SNS interventions on health behavior-related outcomes, but there was considerable heterogeneity. Protocol registration The protocol for this systematic review is registered at http://www.crd.york.ac.uk/PROSPERO with the number CRD42013004140.

Lipid-heparin infusion suppresses the IL-10 response to trauma in subcutaneous adipose tissue in humans.

An imbalance between pro- and anti-inflammatory cytokine productions in adipose tissue is thought to contribute to chronic, systemic, low-grade inflammation and consequently to an increased risk of cardiovascular complications in obese and type 2 diabetic patients. Nonesterified fatty acids (NEFA), whose serum levels are elevated in such patients, have been shown to interfere with cytokine production in vitro. In order to evaluate the effects of elevated NEFA levels on cytokine production in adipose tissue in vivo we used an 18-gauge open-flow microperfusion (OFM) catheter to induce local inflammation in the subcutaneous adipose tissue (SAT) of healthy volunteers and to sample interstitial fluid (IF) specifically from the inflamed tissue. In two crossover studies, nine subjects received either an intravenous lipid-heparin infusion to elevate circulating NEFA levels or saline over a period of 28 h. The former increased the circulating levels of triglycerides (TGs), NEFA, glucose, and insulin over the study period. NEFA effects on locally induced inflammation were estimated by measuring the levels of a panel adipokines in the OFM probe effluent. Interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) levels increased during the study period but were not affected by lipid-heparin infusion. In contrast, the level of IL-10, an anti-inflammatory cytokine, was significantly reduced during the final hour of lipid-heparin infusion (saline: 449.2 ± 105.9 vs. lipid-heparin: 65.4 ± 15.4 pg/ml; P = 0.02). These data provide the first in vivo evidence that elevated NEFA can modulate cytokine production by adipose tissue.