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Computed tomography (CT) imaging of the thorax is widely used for the detection and monitoring of pulmonary embolism (PE). However, CT images can contain artifacts due to the acquisition or the processes involved in image reconstruction. Radiologists often have to distinguish between such artifacts and actual PEs. We provide a proof of concept in the form of a scalable hypothesis testing method for CT, to enable quantifying uncertainty of possible PEs. In particular, we introduce a Bayesian Framework to quantify the uncertainty of an observed compact structure that can be identified as a PE. We assess the ability of the method to operate under high-noise environments and with insufficient data.
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Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory-approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory-approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches.
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BACKGROUND: The world symposium on pulmonary hypertension (PH) has proposed that PH be defined as a mean pulmonary artery pressure (mPAP) > 20 mmHg as assessed by right heart catheterisation (RHC). Transthoracic echocardiography (TTE) is an established screening tool used for suspected PH. International guidelines recommend a multi-parameter assessment of the TTE PH probability although effectiveness has not been established using real world data. STUDY AIMS: To determine accuracy of the European Society of Cardiology (ESC) and British Society of Echocardiography (BSE) TTE probability algorithm in detecting PH in patients attending a UK PH centre. To identify echocardiographic markers and revised algorithms to improve the detection of PH in those with low/intermediate BSE/ESC TTE PH probability. METHODS: TTE followed by RHC (within 4 months after) was undertaken in patients for suspected but previously unconfirmed PH. BSE/ESC PH TTE probabilities were calculated alongside additional markers of right ventricular (RV) longitudinal and radial function, and RV diastolic function. A refined IMPULSE algorithm was devised and evaluated in patients with low and/or intermediate ESC/BSE TTE PH probability. RESULTS: Of 310 patients assessed, 236 (76%) had RHC-confirmed PH (average mPAP 42.8 ± 11.7). Sensitivity and specificity for detecting PH using the BSE/ESC recommendations was 89% and 68%, respectively. 36% of those with low BSE/ESC TTE probability had RHC-confirmed PH and BSE/ESC PH probability parameters did not differ amongst those with and without PH in the low probability group. Conversely, RV free wall longitudinal strain (RVFWLS) was lower in patients with vs. without PH in low BSE/ESC probability group (- 20.6 ± 4.1% vs - 23.8 ± 3.9%) (P < 0.02). Incorporating RVFWLS and TTE features of RV radial and diastolic function (RVFAC and IVRT) within the IMPULSE algorithm reduced false negatives in patients with low BSE/ESC PH probability by 29%. The IMPULSE algorithm had excellent specificity and positive predictive value in those with low (93%/80%, respectively) or intermediate (82%/86%, respectively) PH probability. CONCLUSION: Existing TTE PH probability guidelines lack sensitivity to detect patients with milder haemodynamic forms of PH. Combining additional TTE makers assessing RV radial, longitudinal and diastolic function enhance identification of milder forms of PH, particularly in those who have a low BSE/ESC TTE PH probability.
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BACKGROUND: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. METHODS: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. FINDINGS: Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57-0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. INTERPRETATION: Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19. FUNDING: Sponsored by the University of Dundee and supported through an Investigator Initiated Research award from Insmed, Bridgewater, NJ; STOP-COVID19 trial.
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Tratamento Farmacológico da COVID-19 , Catepsina C , Humanos , Método Duplo-Cego , Serina Proteases , Resultado do Tratamento , Catepsina C/antagonistas & inibidoresRESUMO
Introduction and objectivesThe ongoing respiratory sequelae of COVID-19 pneumonia remain unclear, and the ideal follow-up of these patients is still a work in progress. We describe our experience of using a pre-follow-up multidisciplinary team (MDT) to decide the follow-up stream in patients hospitalised for COVID-19 pneumonia. METHODS: We reviewed all patients with a clinico-radiological diagnosis of COVID-19 admitted to hospital during a 3-month period and assigned a follow-up stream based on British Thoracic Society guidance. RESULTS: We changed the follow-up pathway in 71% (277/392) and refined the pathway in 67% (261/392) of indeterminate cases. We also created an automated process for the general practitioner to book follow-up imaging and will use this process going forward. CONCLUSION: These findings highlight the importance of the MDT review of cases with suspected COVID-19 pneumonia prior to clinic attendance to ensure appropriate patients are followed up and to optimise utilisation of outpatient imaging and clinics.
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COVID-19 , Instituições de Assistência Ambulatorial , Seguimentos , Hospitalização , Humanos , SARS-CoV-2RESUMO
BACKGROUND: Inflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling. METHODS: We conducted a phase 2 open-label study of intravenous tocilizumab (8â mg·kg-1) over 6â months in patients with group 1 PAH. Co-primary end-points were safety, defined by incidence and severity of adverse events, and change in pulmonary vascular resistance. Separately, a mendelian randomisation study was undertaken on 11â744 individuals with European ancestry including 2085 patients with idiopathic/heritable disease for the IL-6 receptor (IL6R) variant (rs7529229), known to associate with circulating IL-6R levels. RESULTS: We recruited 29 patients (male/female 10/19; mean±sd age 54.9±11.4â years). Of these, 19 had heritable/idiopathic PAH and 10 had connective tissue disease-associated PAH. Six were withdrawn prior to drug administration; 23 patients received at least one dose of tocilizumab. Tocilizumab was discontinued in four patients owing to serious adverse events. There were no deaths. Despite evidence of target engagement in plasma IL-6 and C-reactive protein levels, both intention-to-treat and modified intention-to-treat analyses demonstrated no change in pulmonary vascular resistance. Inflammatory markers did not predict treatment response. Mendelian randomisation did not support an effect of the lead IL6R variant on risk of PAH (OR 0.99, p=0.88). CONCLUSION: Adverse events were consistent with the known safety profile of tocilizumab. Tocilizumab did not show any consistent treatment effect.
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Pesquisa Biomédica , Hipertensão Arterial Pulmonar , Adulto , Idoso , Hipertensão Pulmonar Primária Familiar , Feminino , Humanos , Interleucina-6 , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Pulmonary arterial hypertension is an unmet clinical need. Imatinib, a tyrosine kinase inhibitor, 200 to 400 mg daily reduces pulmonary artery pressure and increases functional capacity in this patient group, but is generally poorly tolerated at the higher dose. We have designed an open-label, single-arm clinical study to investigate whether there is a tolerated dose of imatinib that can be better targeted to patients who will benefit. The study consists of two parts. Part 1 seeks to identify the best tolerated dose of Imatinib in the range from 100 and up to 400 mg using a Bayesian Continuous Reassessment Method. Part 2 will measure efficacy after 24 weeks treatment with the best tolerated dose using a Simon's two-stage design. The primary efficacy endpoint is a binary variable. For patients with a baseline pulmonary vascular resistance (PVR) >1000 dynes · s · cm-5, success is defined by an absolute reduction in PVR of ≥300 dynes · s · cm-5 at 24 weeks. For patients with a baseline PVR ≤1000 dynes · s · cm-5, success is a 30% reduction in PVR at 24 weeks. PVR will also be evaluated as a continuous variable by genotype as an exploratory analysis. Evaluating the response to that dose by genotype may inform a prospective biomarker-driven study.
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OBJECTIVES: To undertake the first systematic review examining the performance of artificial intelligence (AI) applied to cross-sectional imaging for the diagnosis of acquired pulmonary arterial hypertension (PAH). METHODS: Searches of Medline, Embase and Web of Science were undertaken on 1 July 2020. Original publications studying AI applied to cross-sectional imaging for the diagnosis of acquired PAH in adults were identified through two-staged double-blinded review. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies and Checklist for Artificial Intelligence in Medicine frameworks. Narrative synthesis was undertaken following Synthesis Without Meta-Analysis guidelines. This review received no funding and was registered in the International Prospective Register of Systematic Reviews (ID:CRD42020196295). RESULTS: Searches returned 476 citations. Three retrospective observational studies, published between 2016 and 2020, were selected for data-extraction. Two methods applied to cardiac-MRI demonstrated high diagnostic accuracy, with the best model achieving AUC=0.90 (95% CI: 0.85-0.93), 89% sensitivity and 81% specificity. Stronger results were achieved using cardiac-MRI for classification of idiopathic PAH, achieving AUC=0.97 (95% CI: 0.89-1.0), 96% sensitivity and 87% specificity. One study reporting CT-based AI demonstrated lower accuracy, with 64.6% sensitivity and 97.0% specificity. CONCLUSIONS: Automated methods for identifying PAH on cardiac-MRI are emerging with high diagnostic accuracy. AI applied to cross-sectional imaging may provide non-invasive support to reduce diagnostic delay in PAH. This would be helped by stronger solutions in other modalities. ADVANCES IN KNOWLEDGE: There is a significant shortage of research in this important area. Early detection of PAH would be supported by further research advances on the promising emerging technologies identified.
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Inteligência Artificial , Hipertensão Pulmonar/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To assess the feasibility and reliability of the use of artificial intelligence post-processing to calculate the RV:LV diameter ratio on computed tomography pulmonary angiography (CTPA) and to investigate its prognostic value in patients with acute PE. METHODS: Single-centre, retrospective study of 101 consecutive patients with CTPA-proven acute PE. RV and LV volumes were segmented on 1-mm contrast-enhanced axial slices and maximal ventricular diameters were derived for RV:LV ratio using automated post-processing software (IMBIO LLC, USA) and compared to manual analysis in two observers, via intraclass coefficient correlation analysis. Each CTPA report was analysed for mention of the RV:LV ratio and compared to the automated RV:LV ratio. Thirty-day all-cause mortality post-CTPA was recorded. RESULTS: Automated RV:LV analysis was feasible in 87% (n = 88). RV:LV ratios ranged from 0.67 to 2.43, with 64% (n = 65) > 1.0. There was very strong agreement between manual and automated RV:LV ratios (ICC = 0.83, 0.77-0.88). The use of automated analysis led to a change in risk stratification in 45% of patients (n = 40). The AUC of the automated measurement for the prediction of all-cause 30-day mortality was 0.77 (95% CI: 0.62-0.99). CONCLUSION: The RV:LV ratio on CTPA can be reliably measured automatically in the majority of real-world cases of acute PE, with perfect reproducibility. The routine use of this automated analysis in clinical practice would add important prognostic information in patients with acute PE. KEY POINTS: ⢠Automated calculation of the right ventricle to left ventricle ratio was feasible in the majority of patients and demonstrated perfect intraobserver variability. ⢠Automated analysis would have added important prognostic information and altered risk stratification in the majority of patients. ⢠The optimal cut-off value for the automated right ventricle to left ventricle ratio was 1.18, with a sensitivity of 100% and specificity of 54% for the prediction of 30-day mortality.
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Embolia Pulmonar , Disfunção Ventricular Direita , Doença Aguda , Inteligência Artificial , Ventrículos do Coração/diagnóstico por imagem , Humanos , Embolia Pulmonar/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Tomografia Computadorizada por Raios X , Disfunção Ventricular Direita/diagnóstico por imagemRESUMO
Computed tomography (CT) is a valuable tool in the workup of patients under investigation for pulmonary hypertension (PH) and may be the first test to suggest the diagnosis. CT parenchymal lung changes can help to differentiate the aetiology of PH. CT can demonstrate interstitial lung disease, emphysema associated with chronic obstructive pulmonary disease, features of left heart failure (including interstitial oedema), and changes secondary to miscellaneous conditions such as sarcoidosis. CT also demonstrates parenchymal changes secondary to chronic thromboembolic disease and venous diseases such as pulmonary venous occlusive disease (PVOD) and pulmonary capillary haemangiomatosis (PCH). It is important for the radiologist to be aware of the various manifestations of PH in the lung, to help facilitate an accurate and timely diagnosis. This pictorial review illustrates the parenchymal lung changes that can be seen in the various conditions causing PH.
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Hipertensão Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Humanos , Pulmão/diagnóstico por imagemRESUMO
Background - Approximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics. Methods - We analyzed 13,037 participants enrolled in the NIHR BioResource - Rare Diseases (NBR) study, of which 1,148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension (PH), we used the Bayesian rare-variant association method BeviMed. Results - Heterozygous, high impact, likely loss-of-function variants in the Kinase Insert Domain Receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (KCO, posterior probability (PP)=0.989) and older age at diagnosis (PP=0.912). We also provide evidence for familial segregation of a rare nonsense KDR variant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the five patients harboring these predicted deleterious variants in KDR. Four additional PAH cases with rare likely loss-of-function variants in KDR were independently identified in the US PAH Biobank cohort with similar phenotypic characteristics. Conclusions - The Bayesian inference approach allowed us to independently validate KDR, which encodes for the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence for KDR being a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.
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INTRODUCTION: The purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for outpatient management of pulmonary embolism in the UK, together with measurable markers of good practice. Quality statements are based on the British Thoracic Society (BTS) Guideline for the Initial Outpatient Management of Pulmonary Embolism. METHODS: Development of BTS Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards. RESULTS: Six quality statements have been developed, each describing a standard of care for the outpatient management of pulmonary embolism in the UK, together with measurable markers of good practice. DISCUSSION: BTS Quality Standards for Outpatient Management of Pulmonary Embolism form a key part of the range of supporting materials that the society produces to assist in the dissemination and implementation of a guideline's recommendations.
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Guias de Prática Clínica como Assunto , Embolia Pulmonar/terapia , Gerenciamento Clínico , Humanos , Pacientes Ambulatoriais , Garantia da Qualidade dos Cuidados de Saúde , Sociedades Médicas , Reino UnidoRESUMO
While traffic and air pollution exposure is associated with increased mortality in numerous diseases, its association with disease severity and outcomes in pulmonary arterial hypertension (PAH) remains unknown.Exposure to particulate matter with a 50% cut-off aerodynamic diameter ≤2.5â µm (PM2.5), nitrogen dioxide (NO2) and indirect measures of traffic-related air pollution (distance to main road and length of roads within buffer zones surrounding residential addresses) were estimated for 301 patients with idiopathic/heritable PAH recruited in the UK National Cohort Study of Idiopathic and Heritable PAH. Associations with transplant-free survival and pulmonary haemodynamic severity at baseline were assessed, adjusting for confounding variables defined a prioriHigher estimated exposure to PM2.5 was associated with higher risk of death or lung transplant (unadjusted hazard ratio (HR) 2.68 (95% CI 1.11-6.47) per 3â µg·m-3; p=0.028). This association remained similar when adjusted for potential confounding variables (HR 4.38 (95% CI 1.44-13.36) per 3â µg·m-3; p=0.009). No associations were found between NO2 exposure or other traffic pollution indicators and transplant-free survival. Conversely, indirect measures of exposure to traffic-related air pollution within the 500-1000â m buffer zones correlated with the European Society of Cardiology/European Respiratory Society risk categories as well as pulmonary haemodynamics at baseline. This association was strongest for pulmonary vascular resistance.In idiopathic/heritable PAH, indirect measures of exposure to traffic-related air pollution were associated with disease severity at baseline, whereas higher PM2.5 exposure may independently predict shorter transplant-free survival.
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Poluição do Ar/efeitos adversos , Hipertensão Arterial Pulmonar/epidemiologia , Poluição Relacionada com o Tráfego/efeitos adversos , Adulto , Idoso , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Dióxido de Nitrogênio/efeitos adversos , Dióxido de Nitrogênio/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Estudos Prospectivos , Hipertensão Arterial Pulmonar/etiologia , Poluição Relacionada com o Tráfego/análise , Reino Unido/epidemiologiaRESUMO
BACKGROUND: In pulmonary arterial hypertension (PAH), pathological changes in pulmonary arterioles progressively raise pulmonary artery pressure and increase pulmonary vascular resistance, leading to right heart failure and high mortality rates. Recently, the first potassium channelopathy in PAH, because of mutations in KCNK3, was identified as a genetic cause and pharmacological target. METHODS: Exome sequencing was performed to identify novel genes in a cohort of 99 pediatric and 134 adult-onset group I PAH patients. Novel rare variants in the gene identified were independently identified in a cohort of 680 adult-onset patients. Variants were expressed in COS cells and function assessed by patch-clamp and rubidium flux analysis. RESULTS: We identified a de novo novel heterozygous predicted deleterious missense variant c.G2873A (p.R958H) in ABCC8 in a child with idiopathic PAH. We then evaluated all individuals in the original and a second cohort for rare or novel variants in ABCC8 and identified 11 additional heterozygous predicted damaging ABCC8 variants. ABCC8 encodes SUR1 (sulfonylurea receptor 1)-a regulatory subunit of the ATP-sensitive potassium channel. We observed loss of ATP-sensitive potassium channel function for all ABCC8 variants evaluated and pharmacological rescue of all channel currents in vitro by the SUR1 activator, diazoxide. CONCLUSIONS: Novel and rare missense variants in ABCC8 are associated with PAH. Identified ABCC8 mutations decreased ATP-sensitive potassium channel function, which was pharmacologically recovered.
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Exoma , Hipertensão Pulmonar Primária Familiar/genética , Mutação de Sentido Incorreto , Receptores de Sulfonilureias/genética , Adulto , Substituição de Aminoácidos , Criança , Análise Mutacional de DNA , Hipertensão Pulmonar Primária Familiar/tratamento farmacológico , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with an emerging genetic basis. Heterozygous mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2) are the commonest genetic cause of PAH, whereas biallelic mutations in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Here, we determine the frequency of these mutations and define the genotype-phenotype characteristics in a large cohort of patients diagnosed clinically with PAH. METHODS: Whole-genome sequencing was performed on DNA from patients with idiopathic and heritable PAH and with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis recruited to the National Institute of Health Research BioResource-Rare Diseases study. Heterozygous variants in BMPR2 and biallelic EIF2AK4 variants with a minor allele frequency of <1:10 000 in control data sets and predicted to be deleterious (by combined annotation-dependent depletion, PolyPhen-2, and sorting intolerant from tolerant predictions) were identified as potentially causal. Phenotype data from the time of diagnosis were also captured. RESULTS: Eight hundred sixty-four patients with idiopathic or heritable PAH and 16 with pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis were recruited. Mutations in BMPR2 were identified in 130 patients (14.8%). Biallelic mutations in EIF2AK4 were identified in 5 patients with a clinical diagnosis of pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. Furthermore, 9 patients with a clinical diagnosis of PAH carried biallelic EIF2AK4 mutations. These patients had a reduced transfer coefficient for carbon monoxide (Kco; 33% [interquartile range, 30%-35%] predicted) and younger age at diagnosis (29 years; interquartile range, 23-38 years) and more interlobular septal thickening and mediastinal lymphadenopathy on computed tomography of the chest compared with patients with PAH without EIF2AK4 mutations. However, radiological assessment alone could not accurately identify biallelic EIF2AK4 mutation carriers. Patients with PAH with biallelic EIF2AK4 mutations had a shorter survival. CONCLUSIONS: Biallelic EIF2AK4 mutations are found in patients classified clinically as having idiopathic and heritable PAH. These patients cannot be identified reliably by computed tomography, but a low Kco and a young age at diagnosis suggests the underlying molecular diagnosis. Genetic testing can identify these misclassified patients, allowing appropriate management and early referral for lung transplantation.
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Pressão Arterial/genética , Hipertensão Pulmonar/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Artéria Pulmonar/fisiopatologia , Adulto , Idoso , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Análise Mutacional de DNA , Europa (Continente) , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Hereditariedade , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
INTRODUCTION: The purpose of the quality standards document is to provide healthcare professionals, commissioners, service providers and patients with a guide to standards of care that should be met for home oxygen provision in the UK, together with measurable markers of good practice. Quality statements are based on the British Thoracic Society (BTS) Guideline for Home Oxygen Use in Adults. METHODS: Development of BTS Quality Standards follows the BTS process of quality standard production based on the National Institute for Health and Care Excellence process manual for the development of quality standards. RESULTS: 10 quality statements have been developed, each describing a key marker of high-quality, cost-effective care for home oxygen use, and each statement is supported by quality measures that aim to improve the structure, process and outcomes of healthcare. DISCUSSION: BTS Quality Standards for home oxygen use in adults form a key part of the range of supporting materials that the society produces to assist in the dissemination and implementation of a guideline's recommendations.
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OBJECTIVES: Psychological difficulties are a common complication among patients with respiratory disease, and are associated with poorer health outcomes and increased use of healthcare. As prevalence studies typically sample patients from community settings, this study aimed to explore the extent and nature of psychological difficulties during acute hospital admission. METHODS: A case example of an acute respiratory ward is presented. In total, 41 acute respiratory inpatients completed standardised measures of depression, anxiety, and health anxiety. RESULTS: Rates of clinically significant depression, anxiety, and health anxiety were 71%, 40%, and 21%, respectively, with 76% of participants showing clinically significant scores on at least one measure. Comparison to existing literature suggests depression rates may be elevated in the acute inpatient context. The difficulties experienced encompassed both contextual factors related to being in hospital and broader health concerns. CONCLUSION: We suggest that psychological distress may be particularly prevalent in inpatient settings and that larger-scale studies are warranted.
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The introduction of pulmonary hypertension (PH)-specific drugs has allowed certain forms of PH to become more treatable. However, patients with these diseases can present to a number of medical specialties and can be challenging to identify, particularly in a non-specialist setting. This article provides guidance on who should be investigated and referred on to a specialist centre, highlighting the potential pitfalls during assessment.
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Hipertensão Pulmonar , Encaminhamento e Consulta , Humanos , Hipertensão Pulmonar/classificação , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Reino UnidoRESUMO
The ability to provide oxygen in a patient's home can offer enormous benefits, including improvements in life expectancy when given in the appropriate setting. Confusingly, however, home oxygen is available in many forms, including long-term oxygen therapy (LTOT), ambulatory oxygen therapy (AOT), palliative oxygen therapy (POT) and short-burst oxygen therapy (SBOT)-each with varying degrees of supporting evidence. The British Thoracic Society (BTS) has recently published new guidance on home oxygen therapy, after collating the available evidence. This article aims to summarise those guidelines, focusing on who should and should not be considered for oxygen therapy. Although the BTS guidelines target a UK audience, many of the principles covered below are applicable internationally, even if the availability of certain oxygen modalities and supporting service arrangements may vary between different healthcare systems.
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Dispneia/terapia , Tolerância ao Exercício , Serviços de Assistência Domiciliar , Oxigenoterapia/métodos , Guias de Prática Clínica como Assunto , Doença Pulmonar Obstrutiva Crônica/terapia , Dispneia/fisiopatologia , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Reino Unido , Capacidade VitalRESUMO
The British Thoracic Society (BTS) Home Oxygen Guideline provides detailed evidence-based guidance for the use of home oxygen for patients out of hospital. Although the majority of evidence comes from the use of oxygen in patients with chronic obstructive pulmonary disease, the scope of the guidance includes patients with a variety of long-term respiratory illnesses and other groups in whom oxygen is currently ordered, such as those with cardiac failure, cancer and end-stage cardiorespiratory disease, terminal illness or cluster headache. It explores the evidence base for the use of different modalities of oxygen therapy and patient-related outcomes such as mortality, symptoms and quality of life. The guideline also makes recommendations for assessment and follow-up protocols, and risk assessments, particularly in the clinically challenging area of home oxygen users who smoke. The guideline development group is aware of the potential for confusion sometimes caused by the current nomenclature for different types of home oxygen, and rather than renaming them, has adopted the approach of clarifying those definitions, and in particular emphasising what is meant by long-term oxygen therapy and palliative oxygen therapy. The home oxygen guideline provides expert consensus opinion in areas where clinical evidence is lacking, and seeks to deliver improved prescribing practice, leading to improved compliance and improved patient outcomes, with consequent increased value to the health service.