The Framingham risk models and pooled cohort equations (PCE) are widely used and advocated in guidelines for predicting 10-year risk of developing coronary heart disease (CHD) and cardiovascular ...disease (CVD) in the general population. Over the past few decades, these models have been extensively validated within different populations, which provided mounting evidence that local tailoring is often necessary to obtain accurate predictions. The objective is to systematically review and summarize the predictive performance of three widely advocated cardiovascular risk prediction models (Framingham Wilson 1998, Framingham ATP III 2002 and PCE 2013) in men and women separately, to assess the generalizability of performance across different subgroups and geographical regions, and to determine sources of heterogeneity in the findings across studies.
A search was performed in October 2017 to identify studies investigating the predictive performance of the aforementioned models. Studies were included if they externally validated one or more of the original models in the general population for the same outcome as the original model. We assessed risk of bias for each validation and extracted data on population characteristics and model performance. Performance estimates (observed versus expected (OE) ratio and c-statistic) were summarized using a random effects models and sources of heterogeneity were explored with meta-regression.
The search identified 1585 studies, of which 38 were included, describing a total of 112 external validations. Results indicate that, on average, all models overestimate the 10-year risk of CHD and CVD (pooled OE ratio ranged from 0.58 (95% CI 0.43-0.73; Wilson men) to 0.79 (95% CI 0.60-0.97; ATP III women)). Overestimation was most pronounced for high-risk individuals and European populations. Further, discriminative performance was better in women for all models. There was considerable heterogeneity in the c-statistic between studies, likely due to differences in population characteristics.
The Framingham Wilson, ATP III and PCE discriminate comparably well but all overestimate the risk of developing CVD, especially in higher risk populations. Because the extent of miscalibration substantially varied across settings, we highly recommend that researchers further explore reasons for overprediction and that the models be updated for specific populations.
Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte ...macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic "crazy paving" pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.
Idiopathic pulmonary alveolar proteinosis is presumed to be an autoimmune disorder that may lead to pulmonary insufficiency. However, steroids do not appear to be effective and the standard of ...therapy is whole-lung lavage. We report the first case of successful therapy with rituximab, which addresses the pathogenic mechanism of pulmonary alveolar proteinosis.
To determine whether findings from lung ultrasound and chest high-resolution computed tomography (HRCT) correlate when evaluating COVID-19 pulmonary involvement.
The present prospective single-centre ...study included consecutive symptomatic patients with reverse transcription polymerase chain reaction (RT-PCR)-proven COVID-19 who were not in the intensive care unit. All patients were assessed using HRCT and ultrasound of the lungs by distinct operators blinded to each other's findings. The number of areas (0–12) with B-lines and/or consolidations was evaluated using ultrasound and compared to the percentage and classification (absent or limited, <10%; moderate, 10–25%; extensive, 25–50%; severe, 50–75%; critical, >75%) of lung involvement on chest HRCT.
Data were analysed for 21 patients with COVID-19 (median range age 65 37–90 years, 76% male) and excellent correlation was found between the ultrasound score for B-lines and the classification (p<0.01) and percentage of lung involvement on chest HRCT (r=0.935, p<0.001). In addition, the ultrasound score correlated positively with supplemental oxygen therapy (r=0.45, p=0.041) and negatively with minimal oxygen saturation at ambient air (r=–0.652, p<0.01).
The present study suggests that among COVID-19 patients, lung ultrasound and HRCT findings agree in quantifying lung involvement and oxygen parameters. In the context of the COVID-19 pandemic, lung ultrasound could be a relevant alternative to chest HRCT.
•Ultrasonography is correlated with chest CT in COVID-19 patients.•Lung ultrasonography could be a relevant alternative to chest CT.•Lung ultrasonography is correlated with oxygen parameters.
La pandémie actuelle liée à l’émergence du SARSCoV-2 en 2019 a considérablement modifié la perception des médecins de l’impact des virus respiratoires et de leur rôle dans les pneumonies aiguës ...communautaires (PAC). Alors que plus de 25 % des tableaux de PAC chez l’adulte étaient d’origine virale, les virus respiratoires étaient souvent perçus comme des agents pathogènes peu graves. Devant le défi que représente encore à nos jours la documentation microbiologique d’une PAC, l’instauration d’un traitement empirique par antibiotiques est souvent réalisée aux urgences. La pandémie de COVID-19 a surtout mis en exergue le rôle déterminant de la biologie moléculaire et du scanner thoracique dans l’algorithme diagnostique de la PAC. En effet, un diagnostic rapide et fiable est la clé pour améliorer les mesures de précaution et réduire la prescription inutile d’antibiotiques. Du fait de prises en charges très différentes, il est nécessaire de distinguer l’étiologie virale de la bactérienne d’une PAC.
The current pandemic linked to the emergence of SARS-CoV-2 in 2019 has considerably changed the perception of doctors of the impact of respiratory viruses and their role in community-acquired acute pneumonia (CAP). While more than 25% of CAP in adults were of viral origin, respiratory viruses were often perceived as harmless pathogens. Faced with the challenge that the microbiological documentation of a CAP still represents today, the establishment of empirical antibiotic treatment is often carried out in the emergency room. The COVID-19 pandemic has primarily highlighted the decisive role of molecular biology and chest CT in the diagnostic algorithm of CAP. Indeed, a rapid and reliable diagnosis is the key to improve isolation decisions and reducing the unnecessary prescription of antibiotics. Due to significantly different treatments, it is necessary to distinguish the viral etiology from the bacterial of a CAP.
Objective: Interstitial lung disease (ILD) is a common feature of connective tissue disease (CTD). The diagnosis of CTD-ILD can be challenging and is important for therapeutic decisions. In this ...study, we aimed to determine whether a systematic rheumatological assessment could help pulmonologists in the diagnosis and care of ILD patients.
Method: We conducted an observational single-centre study of patients with ILD. All patients underwent standardized pulmonary and rheumatological evaluations, including clinical evaluation (pulmonary symptoms and musculoskeletal signs), immunological screening, chest high-resolution computed tomography, pulmonary function tests, and ultrasonography (US) of joints and major salivary glands.
Results: We included 100 consecutive ILD patients (47% women, mean ± sd age 67 ± 14 years); 15 patients already had CTD. The main extrapulmonary symptoms were joint pain (n = 52), joint swelling (n = 26), and sicca syndrome (n = 33). US of joints revealed synovitis, bone erosion, and tenosynovitis in 37, 17, and 13 patients, respectively. US of major salivary glands detected features associated with Sjögren's syndrome in 13 patients. After rheumatological evaluation, CTD-ILD was confidently diagnosed in 39 patients; diseases were mainly rheumatoid arthritis (n = 20), primary Sjögren's syndrome (n = 17), and inflammatory myopathies (n = 7). The diagnosis of CTD-ILD was associated with the presence of musculoskeletal symptoms and immunological and US abnormalities. The CTD diagnosis led to a therapeutic change in 21 patients.
Conclusion: Our findings suggest that musculoskeletal symptoms are frequent in ILD patients, which supports multidisciplinary management, involving the rheumatologist, for evaluating patients with ILD.
Individual participant data (IPD) from multiple sources allows external validation of a prognostic model across multiple populations. Often this reveals poor calibration, potentially causing poor ...predictive performance in some populations. However, rather than discarding the model outright, it may be possible to modify the model to improve performance using recalibration techniques. We use IPD meta‐analysis to identify the simplest method to achieve good model performance. We examine four options for recalibrating an existing time‐to‐event model across multiple populations: (i) shifting the baseline hazard by a constant, (ii) re‐estimating the shape of the baseline hazard, (iii) adjusting the prognostic index as a whole, and (iv) adjusting individual predictor effects. For each strategy, IPD meta‐analysis examines (heterogeneity in) model performance across populations. Additionally, the probability of achieving good performance in a new population can be calculated allowing ranking of recalibration methods. In an applied example, IPD meta‐analysis reveals that the existing model had poor calibration in some populations, and large heterogeneity across populations. However, re‐estimation of the intercept substantially improved the expected calibration in new populations, and reduced between‐population heterogeneity. Comparing recalibration strategies showed that re‐estimating both the magnitude and shape of the baseline hazard gave the highest predicted probability of good performance in a new population. In conclusion, IPD meta‐analysis allows a prognostic model to be externally validated in multiple settings, and enables recalibration strategies to be compared and ranked to decide on the least aggressive recalibration strategy to achieve acceptable external model performance without discarding existing model information.
Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the ...strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA.
Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls.
Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval CI, 2.8 to 5.2; P=9.7×10
). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7×10
) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3×10
). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4×10
), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5×10
). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone.
We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Société Française de Rhumatologie and others.).
PDF
