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OBJECTIVE: The association between thyroid function, coagulation and venous thromboembolism (VTE) has been reported in observational studies with conflicting findings. This study aimed to elucidate the causal effects of thyroid function on coagulation and VTE from a genetic perspective. METHODS: Two sample Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies in a European population. Coagulation status was associated with nine coagulation-related factors (F VIII, F IX, F XI, Fibrinogen, Antithrombin-III, Thrombomodulin, Plasminogen activator inhibitor-1, Protein C and Protein S). Inverse variance weighting with random effect method was used as the main analytic approach with MR-Egger, weighted median, simple mode and weighted mode methods serving as complements. Sensitivity analyses including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis were conducted to further assess the reliability of results. RESULTS: No genetic causal effects of thyroid function on VTE (including pulmonary embolism and deep venous thrombosis) were found. Genetically, hyperthyroidism was suggestively related to decreased Antithrombin-III (ß: -0.04 [95% CI: -0.06 to - 0.01], p = 0.010) and Protein C (ß: -0.03 [95% CI: -0.06 to 0.00], p = 0.045). No notable associations were observed between other thyroid function parameters and coagulation-related factors. CONCLUSION: We provide suggestive genetic evidence supporting the causal effect of hyperthyroidism on decreased level of anticoagulant factors including Antithrombin-III and Protein C. However, whether this genetic causality could lead to clinically significant hypercoagulable state and increased risk of VTE in hyperthyroid population needs to be further addressed.
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OBJECTIVES: Comprehensive data using Next-Generation Sequence (NGS) and fluorescence in situ hybridization (FISH) for detecting MET amplification is limited in Chinese patients, we evaluating NGS performance both in tissue and plasma samples using FISH as reference. We also sought to find optimal thresholds value for NGS in detecting MET amplification via bioinformatics methods. METHOD: Patients progressed after 1st-, 2nd-, or 3rd-generation (G) EGFR-TKIs were enrolled. Tissue biopsy samples were performed for MET amplification detection via both NGS and FISH. Paired plasma samples were collected for MET amplification detection by NGS. The sensitivity, specificity and agreement were analyzed between NGS and FISH. RESULTS: 116 eligible patients were analyzed. 44 patients were male. 82 patients were after 3rd generation EGFR-TKI. MET amplification was detected in 43 (37.1 %) patients by FISH, including 19 (16.4 %) polysomy and 24 (20.7 %) focal amplification. The positive rate of MET amplification in post 3rd generation EGFR-TKI and post 1st/2ndgeneration EGFR-TKI resistant patients was 42.7 % (35/82), and 23.5 % (8/34). The sensitivity, specificity and agreement of detecting MET amplification by NGS in tissue were 39.5 % (17/43), 98.6 % (72/73) and 76.7 % (89/116), respectively, 66.7 % (16/24), 98.6 % (72/73) and 90.7 % (88/97) for focal MET amplification in tissue and 29.2 % (7/24), 94.5 % (69/73), 78.4 % (76/97) for focal amplification in plasma. Results were shown in the table below. CONCLUSION: NGS is an alternative method for MET focal amplification detection in tissue. While the sensitivity of NGS testing in plasma needs further improvement to maximize identification of patients with potential benefit from dual-targeted therapy.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Drug Resistance, Neoplasm , ErbB Receptors , Gene Amplification , High-Throughput Nucleotide Sequencing , In Situ Hybridization, Fluorescence , Lung Neoplasms , Protein Kinase Inhibitors , Proto-Oncogene Proteins c-met , Humans , In Situ Hybridization, Fluorescence/methods , Male , Female , Proto-Oncogene Proteins c-met/genetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/diagnosis , ErbB Receptors/genetics , Protein Kinase Inhibitors/therapeutic use , Drug Resistance, Neoplasm/genetics , Middle Aged , Aged , High-Throughput Nucleotide Sequencing/methods , Lung Neoplasms/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Prospective Studies , China/epidemiology , Adult , Aged, 80 and overABSTRACT
PURPOSE: To investigate the impact of obstructive sleep apnea (OSA) on postoperative delirium (PD), and evaluate the effectiveness of positive airway pressure (PAP) therapy on PD among OSA patients. METHODS: We systematically searched Embase, Cochrane Library and PubMed databases from their establishment to November 27, 2022. A random-effects approach was employed to determine aggregated results. Subgroup and sensitivity analyses were carried out to investigate heterogeneity. RESULTS: Sixteen eligible studies were included in the analysis. Thirteen studies revealed that OSA significantly elevated the likelihood of developing PD (OR = 1.71; 95%CI = 1.17 to 2.49; p = 0.005). Subgroup analysis according to delirium assessment scales showed that OSA did not exhibit an association with the incidence of PD assessed by the Confusion Assessment Method-Intensive Care Unit (OR = 1.14; 95%CI = 0.77 to 1.67; p = 0.51) but enhanced the likelihood of developing PD evaluated with other measurement scales (OR = 2.15; 95%CI = 1.44 to 3.19; p = 0.0002). Three additional studies explored the impact of PAP treatment on PD among OSA individuals, indicating no significant reduction in PD incidence with PAP use (OR = 0.58; 95%CI = 0.13 to 2.47; p = 0.46). CONCLUSIONS: OSA may not be a risk factor for PD in critically ill patients in the intensive care unit, but may increase the likelihood of developing PD among individuals receiving regular care in the ward postoperatively. The efficacy of PAP therapy in decreasing PD incidence among OSA patients remains debatable.
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BACKGROUND: There is no individualized prediction model for intensive care unit (ICU) admission on patients with community-acquired pneumonia (CAP) and connective tissue disease (CTD) so far. In this study, we aimed to establish a machine learning-based model for predicting the need for ICU admission among those patients. METHODS: This was a retrospective study on patients admitted into a University Hospital in China between November 2008 and November 2021. Patients were included if they were diagnosed with CAP and CTD during admission and hospitalization. Data related to demographics, CTD types, comorbidities, vital signs and laboratory results during the first 24 h of hospitalization were collected. The baseline variables were screened to identify potential predictors via three methods, including univariate analysis, least absolute shrinkage and selection operator (Lasso) regression and Boruta algorithm. Nine supervised machine learning algorithms were used to build prediction models. We evaluated the performances of differentiation, calibration, and clinical utility of all models to determine the optimal model. The Shapley Additive Explanations (SHAP) and Local Interpretable Model-Agnostic Explanations (LIME) techniques were performed to interpret the optimal model. RESULTS: The included patients were randomly divided into the training set (1070 patients) and the testing set (459 patients) at a ratio of 70:30. The intersection results of three feature selection approaches yielded 16 predictors. The eXtreme gradient boosting (XGBoost) model achieved the highest area under the receiver operating characteristic curve (AUC) (0.941) and accuracy (0.913) among various models. The calibration curve and decision curve analysis (DCA) both suggested that the XGBoost model outperformed other models. The SHAP summary plots illustrated the top 6 features with the greatest importance, including higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), lower level of CD4 + T cell, lymphocyte and serum sodium, and positive serum (1,3)-ß-D-glucan test (G test). CONCLUSION: We successfully developed, evaluated and explained a machine learning-based model for predicting ICU admission in patients with CAP and CTD. The XGBoost model could be clinical referenced after external validation and improvement.
Subject(s)
Community-Acquired Infections , Connective Tissue Diseases , Intensive Care Units , Machine Learning , Patient Admission , Pneumonia , Humans , Community-Acquired Infections/diagnosis , Community-Acquired Infections/epidemiology , Male , Connective Tissue Diseases/diagnosis , Connective Tissue Diseases/epidemiology , Female , Middle Aged , Retrospective Studies , Intensive Care Units/trends , Aged , Patient Admission/trends , Pneumonia/diagnosis , Pneumonia/epidemiology , Predictive Value of Tests , China/epidemiology , AdultABSTRACT
STUDY OBJECTIVES: To determine the clinical impact of sleep apnea-related hypoxic burden in pregnant women and neonates. METHODS: This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b) study. Hypoxia burden was calculated from the home sleep apnea test (HSAT) and defined as the total area under respiratory events. Logistic regression analysis assessed the relationship between hypoxia burden and pregnancy/neonatal outcomes. RESULTS: A total of 3006 subjects in the early term, and 2326 subjects in the middle term of pregnancy, had HSAT. A hypoxic burden greater than 6.8%min was present in 1740 at early term and associated with a higher risk of preeclampsia (odds ratio 1.297, 95 % confidence interval 1.032-1.630, p: 0.026) after adjusted by obstructive sleep apnea (OSA) severity. In the middle term, 1058 subjects had a hypoxia burden more than 11.8%min, which was a predictor for higher incidence of gestational diabetes (OR 1.795, 95 % CI 1.097-2.938, p: 0.020) and an Apgar <7 at 1 min (OR 1.446, 95 % CI 1.079-1.939, p: 0.012) after adjusted by obstructive sleep apnea (OSA) severity. After adjusted by oxygenation disturbance index, HB was not related with Apgar <7 at 1 min (p:0.565). CONCLUSIONS: The hypoxic burden is an independent predictor for preeclampsia and gestational diabetes and an Apgar <7 at 1 min.
Subject(s)
Hypoxia , Pre-Eclampsia , Pregnancy Outcome , Humans , Pregnancy , Female , Hypoxia/complications , Adult , Infant, Newborn , Pregnancy Outcome/epidemiology , Pre-Eclampsia/epidemiology , Pregnancy Complications/epidemiology , Diabetes, Gestational/epidemiology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Risk Factors , Sleep Apnea Syndromes/complications , Sleep Apnea Syndromes/epidemiologyABSTRACT
BACKGROUND: The effect of sleep apnea treatment on reducing cardiovascular disease risk remains inconclusive. This study aims to assess if the effective apnea hypopnea index (eAHI), a measure of residual sleep apnea burden post-treatment, is a factor in determining blood pressure (BP) response to continuous positive airway pressure therapy. The eAHI integrates time on therapy, residual apnea, and % of sleep time untreated. METHODS: A secondary analysis of the Heart Biomarker Evaluation in Apnea Treatment (HeartBEAT) study, a randomized, controlled, parallel group assessment of continuous positive airway pressure (CPAP), oxygen and sleep hygiene. The Delta-AHI (â²AHI) was defined as the difference between baseline AHI and effective AHI at 12 weeks. Logistic and linear regression models estimated the predictors for nocturnal systolic BP change following sleep apnea therapy. RESULTS: One hundred and sixty-nine subjects with a mean age of 62.82 ± 6.99 years were included in the final analysis. Fifty subjects had â²AHI ≤8/hour of sleep and 119 subjects were higher. After adjustment, baseline mean nighttime systolic blood pressure (OR 1.036, 95% CI 1.015-1.058, p: 0.001) and â²AHI ≥8/hour (OR 2.406, 95% CI 1.116-5.185, p:0.025) were independent predictors for mean nighttime systolic blood pressure change >3 mm Hg. The higher effective AHI was negatively related with BNP (ß: -2.564, SE: 1.167, p: 0.029) and positively related with troponin change (ß: 0.703, SE: 0.256, p: 0.007). CONCLUSION: The â²AHI was an independent predictor of the blood pressure response to sleep apnea treatment. REGISTER NUMBER: NCT01086800.
Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Obstructive , Humans , Middle Aged , Aged , Blood Pressure/physiology , Continuous Positive Airway Pressure , Sleep Apnea Syndromes/therapy , Sleep Apnea Syndromes/complications , OxygenABSTRACT
Background: There is no predictive tool developed for pneumonia-associated acute respiratory distress syndrome (ARDS) specifically so far, and the clinical risk classification of these patients is not well defined. Our study aims to construct an early prediction model for hospital mortality in patients with pneumonia-associated ARDS. Methods: In this single-center retrospective study, consecutive patients with pneumonia-associated ARDS admitted into intensive care units (ICUs) in West China Hospital of Sichuan University in China between January 2012 and December 2018 were enrolled. The least absolute shrinkage and selection operator (LASSO) regression and then multivariate logistic regression analysis were used to identify independent predictors which were used to develop a nomogram. We evaluated the performance of differentiation, calibration, and clinical utility of the nomogram. Results: The included patients were divided into the training cohort (442 patients) and the testing cohort (190 patients) with comparable baseline characteristics. The independent predictors for hospital mortality included age (OR: 1.04; 95% CI: 1.02, 1.05), chronic cardiovascular diseases (OR: 2.62; 95% CI: 1.54, 4.45), chronic respiratory diseases (OR: 1.87; 95% CI: 1.02, 3.43), lymphocytes (OR: 0.56; 95% CI: 0.39, 0.81), albumin (OR: 0.94; 95% CI: 0.90, 1.00), creatinine (OR: 1.00; 95% CI: 1.00, 1.01), D-dimer (OR: 1.06; 95% CI: 1.03, 1.09) and procalcitonin (OR: 1.14; 95% CI: 1.07, 1.22). A web-based dynamic nomogram (https://h1234.shinyapps.io/dynnomapp/) was constructed based on these factors. The concordance index (C index) of the nomogram was 0.798 (95% CI: 0.756, 0.840) in the training cohort and 0.808 (95% CI: 0.747, 0.870) in testing cohort. The precision-recall (PR) curves, calibration curves, decision curve analyses (DCA) and clinical impact curves showed that the nomogram has good predictive value and clinical utility. Conclusion: We developed and evaluated a convenient nomogram consisting of 8 clinical characteristics for predicting mortality in patients with pneumonia-associated ARDS.
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The objective of this study was to assess the associations of asthma control with hypertension, cardiovascular disease, and mortality in obese individuals. We used data from the National Health and Nutrition Examination Survey (NHANES), 2001-2018. Weighted logistic regression analyses and Cox proportional hazard models were performed to evaluate the influence of asthma control on hypertension, cardiovascular disease, and mortality. A total of 2744 obese participants were included. Of them, 937 participants had poorly controlled asthma, 873 had well-controlled asthma, and 934 did not have asthma. We found that poorly controlled asthma was associated with an increased risk of angina pectoris, congestive heart failure (CHF), stroke, and all-cause mortality in obese participants, while well-controlled asthma was associated with an increased risk of CHF and all-cause mortality. Compared with patients with poorly controlled asthma, patients with well-controlled asthma were at low risk of angina pectoris (OR [odds ratio], 0.49; 95% CI [confidence interval], 0.29-0.81), heart attack (OR, 0.54; 95% CI 0.34-0.87), CHF (OR, 0.62; 95% CI 0.39-0.99), and stroke (OR, 0.45; 95% CI 0.27-0.73). The present study suggested that obese individuals with poorly controlled asthma were associated with increased risks of angina pectoris, CHF, stroke, and all-cause mortality. Well-controlled asthma had fewer negative health effects than poorly controlled asthma in obese individuals.
Subject(s)
Asthma , Cardiovascular Diseases , Hypertension , Nutrition Surveys , Obesity , Humans , Male , Female , Obesity/complications , Middle Aged , Asthma/complications , Asthma/mortality , Cardiovascular Diseases/mortality , Hypertension/complications , Hypertension/mortality , Adult , Aged , Proportional Hazards Models , Risk FactorsABSTRACT
Background: There are limited published data on mortality trends in pulmonary hypertension (PH) worldwide. The objective of this study was to assess the PH-related mortality and time trends in the general population over the past 20 years. Material and methods: We used country-level PH mortality data from the World Health Organization (WHO) mortality database (2000-19), using the International Classification of Diseases, tenth revision (ICD-10) codes (I27.0, I27.2, I27.8, or I27.9). The average annual percentage changes (AAPCs) were calculated to describe mortality trends. Results: Fifty-four countries were included in this study. Between 2017 and 2019, the average age-standardized death rates (per 100,000) were 0.80 and 0.87 for males and females, respectively. Joinpoint analyses revealed a decreasing PH mortality trend for the overall population from 2000 to 2019 (AAPC -3.2 [95% confidence interval (CI) -4.1 to -2.4]), which was consistent between males and females (males: AAPC -5.3 [95% CI -6.2 to -4.4], females: AAPC -1.7 [95% CI -2.4 to -0.9]). When the estimates were stratified by etiology, we found that the mortality rates from idiopathic pulmonary arterial hypertension (I27.0) and pulmonary heart disease (unspecified, I27.9) had decreased significantly, while the mortality rates in other secondary PH (I27.2) and other specified pulmonary heart diseases (I27.8) had significantly increased. In addition, there were substantial differences in mortality rates and time trends across countries. Conclusion: Although an overall decrease in PH mortality trends over the past two decades, there were substantial differences across countries. For countries with high or rising mortality rates, more efforts are needed to reduce the mortality.
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BACKGROUND: Severe community-acquired pneumonia is one of the most lethal forms of CAP with high mortality. For rapid and accurate decisions, we developed a mortality prediction model specifically tailored for elderly SCAP patients. METHODS: The retrospective study included 2365 elderly patients. To construct and validate the nomogram, we randomly divided the patients into training and testing cohorts in a 70% versus 30% ratio. The primary outcome was in-hospital mortality. Univariate and multivariate logistic regression analyses were used in the training cohort to identify independent risk factors. The robustness of this model was assessed using the C index, ROC and AUC. DCA was employed to evaluate the predictive accuracy of the model. RESULTS: Six factors were used as independent risk factors for in-hospital mortality to construct the prediction model, including age, the use of vasopressor, chronic renal disease, neutrophil, platelet, and BUN. The C index was 0.743 (95% CI 0.719-0.768) in the training cohort and 0.731 (95% CI 0.694-0.768) in the testing cohort. The ROC curves and AUC for the training cohort and testing cohort (AUC = 0.742 vs. 0.728) indicated a robust discrimination. And the calibration plots showed a consistency between the prediction model probabilities and observed probabilities. Then, the DCA demonstrated great clinical practicality. CONCLUSIONS: The nomogram incorporated six risk factors, including age, the use of vasopressor, chronic renal disease, neutrophil, platelet and BUN, which had great predictive accuracy and robustness, while also demonstrating clinical practicality at ICU admission.
Subject(s)
Community-Acquired Infections , Kidney Failure, Chronic , Pneumonia , Renal Insufficiency, Chronic , Aged , Humans , Hospital Mortality , Nomograms , Retrospective Studies , Gemfibrozil , Risk Factors , Vasoconstrictor AgentsABSTRACT
OBJECTIVE: The meta-analysis aimed to evaluate the efficacy of mandibular advancement device (MAD) for the treatment of obstructive sleep apnea (OSA) and explore the effect of different positions on MAD for OSA. METHODS: The Embase, PubMed, Medline, and Cochrane Library databases were searched for relevant studies evaluating the effect of MAD on the treatment of OSA from database inception to November 2022. The Bayesian random-effects mode was used to calculate the pooled outcome. Subgroup analysis and sensitivity analysis were applied to investigate the heterogeneity. RESULTS: A total of 6 studies enrolling 643 patients were eligible for further analysis. MAD treatment led to improvements in total apnea-hypopnea index (AHI) for both positional OSA(POSA) and Non-POSA groups, but there was no significant difference in the effect of MAD on Non-POSA and POSA (MD = -1.46,95%CI [-4.89,1.97], P = 0.40). In the supine position, AHI improvement after MAD treatment in POSA group was more than that in Non-POSA group by 15 events/hour in average (MD = 14.82, 95%CI [11.43,18.22], Pï¼0.00001), while in the non-supine position, the change of AHI in Non-POSA group was significantly better than that in POSA group by approximately 8 events/hour (MD = -7.55,95%CI[-10.73,-4.38],p < 0.00001). CONCLUSION: MAD is more suitable for POSA compared to Non-POSA in patients with habitual sleep in the supine or supine predominant position. While for patients with habitual sleep in the non-supine position, MAD is an effective treatment option for Non-POSA.
Subject(s)
Occlusal Splints , Sleep Apnea, Obstructive , Humans , Bayes Theorem , Polysomnography , Sleep Apnea, Obstructive/therapy , Supine PositionABSTRACT
OBJECTIVE: This study aimed to determine whether the C-reactive protein-to-albumin ratio (CAR) can serve as a prognostic marker in patients with sepsis. METHODS: Chinese and English databases were searched to retrieve the included literature. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) with their 95% confidence interval (CI) were calculated using the bivariate model. Moreover, the hazard ratio (HR) and 95% CI were calculated using the random effect model. RESULTS: Nine articles comprising 3224 patients with sepsis were included in the meta-analysis. The pooled SEN was 0.73 (95% CI 0.65-0.80), the pooled SPE was 0.78 (95% CI 0.69-0.84), the pooled PLR was 3.29 (95% CI 2.15-5.03), the pooled NLR was 0.35 (95% CI 0.24-0.49), and the pooled DOR was 9.50 (95% CI 4.38-20.59). The AUC under the SROC was 0.82 (95% CI 0.78-0.85) for the prognostic meta-analysis. The pooled HR was 1.10 (95% CI 1.02-1.18). CONCLUSIONS: This meta-analysis suggests that a high CAR level is associated with increased mortality and a poor prognosis.
Subject(s)
C-Reactive Protein , Sepsis , Humans , Prognosis , Albumins , Sepsis/diagnosis , Area Under CurveABSTRACT
BACKGROUND: Diaphragmatic dysfunction is known to be associated with difficulties weaning from invasive mechanical ventilation and is related to worse patient outcomes yet our understanding of how to prevent diaphragmatic dysfunction remains incomplete. We examined potentially modifiable risk factors for diaphragmatic dysfunction and attempted to estimate benefits attributable to altering these modifiable risk factors. METHODS: This prospective multicenter observational study was undertaken in the general ICUs of two tertiary care teaching hospitals. Critically ill adults expected to receive invasive mechanical ventilation for at least 48 h were enrolled. Diaphragm function was assessed by ultrasound each study day, with dysfunction defined as thickening fraction less than 20%. RESULTS: From January to December 2019, 856 patients were screened and 126 patients were enrolled. Overall, 40.5% (51/126) of patients experienced diaphragmatic dysfunction during invasive mechanical ventilation. Patients with diaphragmatic dysfunction were more likely to develop ventilator associated pneumonia (risk difference [RD] + 12.9%, 95% Confidence Interval [CI] 1.4 to 24.4%, P = 0.028), were more likely to experience extubation failure (RD + 8.5%, 95% CI 0.4 to 16.6%, P = 0.039) and required a longer duration of invasive mechanical ventilation (RD + 1.3 days, 95% CI 0.1 to 2.5 days, P = 0.035). They also required a longer hospital stay (RD + 1.2 days, 95% CI 0.04 to 2.4 days, P = 0.041) and were more likely to die before hospital discharge (RD + 18.1%, 95% CI 3.7 to 32.5%, P = 0.014). Multivariable analysis considered the impact of age, sex, pre-existing nutritional status, caloric intake, amino acid intake, acute disease severity, modes of mechanical ventilation, measures of respiratory status, sedation, pain control and baseline diaphragm thickness. Only SOFA score (P = 0.008) and early amino acid intake (P = 0.001) remained significant independent risk factors for the onset of diaphragmatic dysfunction. Causal path modeling suggested early amino acid intake may significantly reduce diaphragmatic dysfunction (RRR 29%, 95% CI 10% to 48%, P = 0.003) and may also reduce mortality (RRR 49%, 95% CI 25% to 73%, P < 0.0001). CONCLUSIONS: Amino acid intake during the first 24 h of ICU stay may represent an important, modifiable risk factor for diaphragmatic dysfunction and may have a direct causal effect on mortality. We recommend additional research on this topic.
Subject(s)
Diaphragm , Ventilators, Mechanical , Adult , Humans , Diaphragm/diagnostic imaging , Prospective Studies , Risk Factors , Amino AcidsABSTRACT
PURPOSE: The causal relationships between circulating adipokines and idiopathic pulmonary fibrosis (IPF) are yet to be established. We performed a two-sample Mendelian randomization (MR) study to investigate the causal roles of adipokines on IPF risk. METHODS: We analyzed the summary data from genome-wide association studies (GWAS), including adiponectin, leptin, resistin and monocyte chemoattractant protein-1 (MCP-1) and IPF. The inverse-variance weighted (IVW) method was considered as the major method and the MR-Egger, weighted median, simple mode and weighted mode were utilized as complementary methods. We also performed the sensitivity analyses, including heterogeneity test, horizontal pleiotropy test and leave-one-out analysis. RESULTS: The selected number of single nucleotide polymorphisms (SNPs) was 13 for adiponectin, 6 for leptin,12 for resistin, and 6 for MCP-1, respectively. The results showed a causal effect of the circulating adiponectin levels on the risk of IPF (OR 0.645, 95% CI 0.457-0.911, P = 0.013). However, we did not observe significant associations of genetic changes in serum leptin (OR 1.018, 95% CI 0.442-2.346, P = 0.967), resistin (OR 1.002, 95% CI 0.712-1.408, P = 0.993), and MCP-1 (OR 1.358, 95% CI 0.891-2.068, P = 0.155) with risk of developing IPF. There was no evidence of heterogeneity or horizontal pleiotropy. The sensitivity analyses confirmed that our results were stable and reliable. CONCLUSIONS: The increase in serum adiponectin was associated causally with a decreased risk of developing IPF. There is no evidence to support a causal association between leptin, resistin or MCP-1 with risk of IPF. Further studies are needed to confirm our findings.
Subject(s)
Adipokines , Idiopathic Pulmonary Fibrosis , Humans , Resistin/genetics , Leptin/genetics , Adiponectin/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Idiopathic Pulmonary Fibrosis/genetics , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: The diagnosis of Pneumocystis jirovecii pneumonia (PCP) in patients presenting with severe pneumonia is challenging and delays in treatment were associated with worse prognosis. This study aimed to develop a rapid, easily available, noninvasive machine learning diagnostic model for PCP among patients with severe pneumonia. METHODS: A retrospective study was performed in West China Hospital among consecutive patients with severe pneumonia who had undergone bronchoalveolar lavage for etiological evaluation between October 2010 and April 2021. Factors associated with PCP were identified and four diagnostic models were established using machine learning algorithms including Logistic Regression, eXtreme Gradient Boosting, Random Forest (RF) and LightGBM. The performance of these models were evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: Ultimately, 704 patients were enrolled and randomly divided into a training set (n = 564) and a testing set (n = 140). Four factors were ultimately selected to establish the model including neutrophil, globulin, ß-D-glucan and ground glass opacity. The RF model exhibited the greatest diagnostic performance with an AUC of 0.907. The calibration curve and decision curve analysis also demonstrated its accuracy and applicability. CONCLUSIONS: We constructed a PCP diagnostic model in patients with severe pneumonia using four easily available and noninvasive clinical indicators. With satisfying diagnostic performance and good clinical practicability, this model may help clinicians to make early diagnosis of PCP, reduce the delays of treatment and improve the prognosis among these patients.
Subject(s)
Pneumocystis carinii , Pneumonia, Pneumocystis , beta-Glucans , Humans , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/diagnosis , Retrospective Studies , Bronchoalveolar LavageABSTRACT
BACKGROUND: The risk factors for depression in asthma are still unclear. The objective of this study was to identify the risk factors associated with depression in asthmatic individuals. METHODS: We used data from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Univariate analysis and multivariate logistic regression analyses were used to identify risk factors for depression and calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 5,379 asthmatic participants were included. Of these subjects, 767 individuals had depression, and 4,612 individuals had no depression. Univariate analysis and multivariate analyses suggested that asthmatic individuals with smoking (OR 1.98, 95% CI 1.19-3.29), hypertension (OR 2.73, 95% CI 1.48-5.04), and arthritis (OR 2.83, 95% CI 1.53-5.22) were more likely to have depression. Asthmatic individuals who had more than a high school education had lower depression risk than those with less than a high school education (OR 0.55, 95% CI 0.30-0.99). Increasing age was also associated with decreased depression risk (OR 0.97, 95% CI 0.95-0.99). CONCLUSIONS: Depression was more likely in asthmatic individuals with smoking, hypertension, and arthritis and less likely in individuals with higher education and increasing age. These findings could improve the identification of target populations for effective interventions to improve the mental health of asthmatic individuals.
Subject(s)
Arthritis , Asthma , Hypertension , Humans , Nutrition Surveys , Risk Factors , Asthma/complications , Asthma/epidemiology , Arthritis/complications , Arthritis/epidemiology , Hypertension/complications , Hypertension/epidemiologyABSTRACT
PURPOSE: ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study. METHODS: Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0-2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety. RESULTS: A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53-0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1-12.5) and 13.9 months (95% CI 13.1-15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively. CONCLUSION: Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified. CLINICAL TRIAL NUMBER: NCT02474355.
Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Adult , Humans , Aniline Compounds/adverse effects , Antineoplastic Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , East Asian People , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Protein Kinase Inhibitors/adverse effectsABSTRACT
Background: The physiological effects of HFNC devices are closely related to temperature and humidity. HFNC devices from different manufacturers may have varied performances. It is unclear whether there are differences in the humidification performance of different HFNC devices and the degree of differences. Methods: Four integrated HFNC devices (AIRVO 2, Fisher & Paykel Healthcare, Auckland, New Zealand; TNI softFlow 50, TNI Medical AG, Würzburg, Germany; HUMID-BH, RESPIRACARE, Shenyang, China; OH-70C, Micomme, Hunan, China) and a ventilator with an HFNC module (bellavista 1000, Imtmedical, Buchs, Switzerland) were evaluated using their matching circuits. The dew point temperature was set at 31, 34, and 37°C (set-DP). In MR850, it was set to non-invasive mode (34°C/-3°C) and invasive mode (40°C/-3°C), respectively. At each level of set-DP, the flow was set from 20 L/min up to its maximum set limit at a gradient of 5 L/min or 10 L/min. After stabilization, the dew point temperature, temperature, relative humidity, and flow rate of the delivered gas from the cannulas were recorded. Results: There were significant differences in actual-DP among these devices at any set-DP (p < 0.001). The actual-DP of OH-70C and TNI softFlow 50 was lower than set-DP, and the difference between the actual-DP and the set-DP of these two devices increased with the increase of set-DP. AIRVO 2, bellavista 1000 (MR850), and HUMID-BH can provide the nominal humidity at 37°C. The actual-DP increased with the increase of set-flow under each set-DP in AIRVO 2, TNI softFlow 50 and bellavista 1000 (MR850), but decreased when the set-flow was greater than 60 L/min. The actual-T of the delivered gas was higher than actual-DP in all devices and was higher than set-DP in AIRVO 2 and HUMID-BH. Conclusion: Set-flow, set-DP, and types of devices will affect the actual temperature and humidity of the delivered gas. AIRVO 2, bellavista 1000 (MR850), and HUMID-BH can provide the nominal humidity at 37°C and may be more suitable for tracheotomy patients. The flow rate over 60 L/min should be set with caution.