When do confounding by indication and inadequate risk adjustment bias critical care studies? A simulation study

Abstract Introduction In critical care observational studies, when clinicians administer different treatments to sicker patients, any treatment comparisons will be confounded by differences in severity of illness between patients. We sought to investigate the extent that observational studies assessing treatments are at risk of incorrectly concluding such treatments are ineffective or even harmful due to inadequate risk adjustment. Methods We performed Monte Carlo simulations of observational studies evaluating the effect of a hypothetical treatment on mortality in critically ill patients. We set the treatment to have either no association with mortality or to have a truly beneficial effect, but more often administered to sicker patients. We varied the strength of the treatment’s true effect, strength of confounding, study size, patient population, and accuracy of the severity of illness risk-adjustment (area under the receiver operator characteristics curve, AUROC). We measured rates in which studies made inaccurate conclusions about the treatment’s true effect due to confounding, and the measured odds ratios for mortality for such false associations. Results Simulated observational studies employing adequate risk-adjustment were generally able to measure a treatment’s true effect. As risk-adjustment worsened, rates of studies incorrectly concluding the treatment provided no benefit or harm increased, especially when sample size was large (n = 10,000). Even in scenarios of only low confounding, studies using the lower accuracy risk-adjustors (AUROC < 0.66) falsely concluded that a beneficial treatment was harmful. Measured odds ratios for mortality of 1.4 or higher were possible when the treatment’s true beneficial effect was an odds ratio for mortality of 0.6 or 0.8. Conclusions Large observational studies confounded by severity of illness have a high likelihood of obtaining incorrect results even after employing conventionally “acceptable” levels of risk-adjustment, with large effect sizes that may be construed as true associations. Reporting the AUROC of the risk-adjustment used in the analysis may facilitate an evaluation of a study’s risk for confounding.http://deepblue.lib.umich.edu/bitstream/2027.42/111639/1/13054_2015_Article_923.pd

Contrastive Latent Space Reconstruction Learning for Audio-Text Retrieval

Cross-modal retrieval (CMR) has been extensively applied in various domains, such as multimedia search engines and recommendation systems. Most existing CMR methods focus on image-to-text retrieval, whereas audio-to-text retrieval, a less explored domain, has posed a great challenge due to the difficulty to uncover discriminative features from audio clips and texts. Existing studies are restricted in the following two ways: 1) Most researchers utilize contrastive learning to construct a common subspace where similarities among data can be measured. However, they considers only cross-modal transformation, neglecting the intra-modal separability. Besides, the temperature parameter is not adaptively adjusted along with semantic guidance, which degrades the performance. 2) These methods do not take latent representation reconstruction into account, which is essential for semantic alignment. This paper introduces a novel audio-text oriented CMR approach, termed Contrastive Latent Space Reconstruction Learning (CLSR). CLSR improves contrastive representation learning by taking intra-modal separability into account and adopting an adaptive temperature control strategy. Moreover, the latent representation reconstruction modules are embedded into the CMR framework, which improves modal interaction. Experiments in comparison with some state-of-the-art methods on two audio-text datasets have validated the superiority of CLSR.Comment: Accepted by The 35th IEEE International Conference on Tools with Artificial Intelligence. (ICTAI 2023

The predictive values of monocyte–lymphocyte ratio in postoperative acute kidney injury and prognosis of patients with Stanford type A aortic dissection

ObjectivesPostoperative acute kidney injury (pAKI) is a serious complication of Stanford type A aortic dissection (TAAD) surgery, which is significantly associated with the inflammatory response. This study aimed to explore the relationship between blood count-derived inflammatory markers (BCDIMs) and pAKI and to construct a predictive model for pAKI.MethodsPatients who underwent TAAD surgery were obtained from our center and the Medical Information Mart for Intensive Care (MIMIC)-IV database. The differences in preoperative BCDIMs and clinical outcomes of patients with and without pAKI were analyzed. Logistic regression was used to construct predictive models based on preoperative BCDIMs or white cell counts (WCCs). The performance of the BCDIMs and WCCs models was evaluated and compared using the receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), Hosmer–Lemeshow test, calibration plot, net reclassification index (NRI), integrated discrimination improvement index (IDI), and decision curve analysis (DCA). The Kaplan–Meier curves were applied to compare the survival rate between different groups.ResultsThe overall incidence of pAKI in patients who underwent TAAD surgery from our center was 48.63% (124/255). The presence of pAKI was associated with longer ventilation time, higher incidence of cerebral complications and postoperative hepatic dysfunction, and higher in-hospital mortality. The results of the logistic regression indicated that the monocyte–lymphocyte ratio (MLR) was an independent risk factor for pAKI. The BCDIMs model had good discriminating ability, predictive ability, and clinical utility. In addition, the performance of the BCDIMs model was significantly better than that of the WCCs model. Analysis of data from the MIMIC-IV database validated that MLR was an independent risk factor for pAKI and had predictive value for pAKI. Finally, data from the MIMIC-IV database demonstrated that patients with a high MLR had a significantly poor 28-day survival rate when compared to patients with a low MLR.ConclusionOur study suggested that the MLR is an independent risk factor for pAKI. A predictive model based on BCDIMs had good discriminating ability, predictive ability, and clinical utility. Moreover, the performance of the BCDIMs model was significantly better than that of the WCCs model. Finally, a high MLR was significantly associated with poor short-term survival of patients who underwent TAAD surgery

Cardiovascular mortality by cancer risk stratification in patients with localized prostate cancer: a SEER-based study

PurposeThe risk of cardiovascular disease (CVD) mortality in patients with localized prostate cancer (PCa) by risk stratification remains unclear. The aim of this study was to determine the risk of CVD death in patients with localized PCa by risk stratification.Patients and methodsPopulation-based study of 340,806 cases in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed with localized PCa between 2004 and 2016. The proportion of deaths identifies the primary cause of death, the competing risk model identifies the interaction between CVD and PCa, and the standardized mortality rate (SMR) quantifies the risk of CVD death in patients with PCa.ResultsCVD-related death was the leading cause of death in patients with localized PCa, and cumulative CVD-related death also surpassed PCa almost as soon as PCa was diagnosed in the low- and intermediate-risk groups. However, in the high-risk group, CVD surpassed PCa approximately 90 months later. Patients with localized PCa have a higher risk of CVD-related death compared to the general population and the risk increases steadily with survival (SMR = 4.8, 95% CI 4.6–5.1 to SMR = 13.6, 95% CI 12.8–14.5).ConclusionsCVD-related death is a major competing risk in patients with localized PCa, and cumulative CVD mortality increases steadily with survival time and exceeds PCa in all three stratifications (low, intermediate, and high risk). Patients with localized PCa have a higher CVD-related death than the general population. Management of patients with localized PCa requires attention to both the primary cancer and CVD

Metastatic patterns and prognosis of patients with primary malignant cardiac tumor

BackgroundDistant metastases are independent negative prognostic factors for patients with primary malignant cardiac tumors (PMCT). This study aims to further investigate metastatic patterns and their prognostic effects in patients with PMCT.Materials and methodsThis multicenter retrospective study included 218 patients with PMCT diagnosed between 2010 and 2017 from Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was utilized to identify metastatic risk factors. A Chi-square test was performed to assess the metastatic rate. Kaplan–Meier methods and Cox regression analysis were used to analyze the prognostic effects of metastatic patterns.ResultsSarcoma (p = 0.002) and tumor size¿4 cm (p = 0.006) were independent risk factors of distant metastases in patients with PMCT. Single lung metastasis (about 34%) was the most common of all metastatic patterns, and lung metastases occurred more frequently (17.9%) than bone, liver, and brain. Brain metastases had worst overall survival (OS) and cancer-specific survival (CSS) among other metastases, like lung, bone, liver, and brain (OS: HR = 3.20, 95% CI: 1.02–10.00, p = 0.046; CSS: HR = 3.53, 95% CI: 1.09–11.47, p = 0.036).ConclusionPatients with PMCT who had sarcoma or a tumor larger than 4 cm had a higher risk of distant metastases. Lung was the most common metastatic site, and brain metastases had worst survival among others, such as lung, bone, liver, and brain. The results of this study provide insight for early detection, diagnosis, and treatment of distant metastases associated with PMCT

Acute kidney injury in hospitalized patients with coronavirus disease 2019 (COVID-19): A meta-analysis

10.1016/j.jinf.2020.05.009JOURNAL OF INFECTION814661-66

Salicylic Acid Enhances Cadmium Tolerance and Reduces Its Shoot Accumulation in <i>Fagopyrum tataricum</i> Seedlings by Promoting Root Cadmium Retention and Mitigating Oxidative Stress

Soil cadmium (Cd) contamination seriously reduces the production and product quality of Tartary buckwheat (Fagopyrum tataricum), and strategies are urgently needed to mitigate these adverse influences. Herein, we investigated the effect of salicylic acid (SA) on Tartary buckwheat seedlings grown in Cd-contaminated soil in terms of Cd tolerance and accumulation. The results showed that 75–100 µmol L−1 SA treatment enhanced the Cd tolerance of Tartary buckwheat, as reflected by the significant increase in plant height and root and shoot biomass, as well as largely mitigated oxidative stress. Moreover, 100 µmol L−1 SA considerably reduced the stem and leaf Cd concentration by 60% and 47%, respectively, which is a consequence of increased root biomass and root Cd retention with promoted Cd partitioning into cell wall and immobile chemical forms. Transcriptome analysis also revealed the upregulation of the genes responsible for cell wall biosynthesis and antioxidative activities in roots, especially secondary cell wall synthesis. The present study determines that 100 µmol L−1 is the best SA concentration for reducing Cd accumulation and toxicity in Tartary buckwheat and indicates the important role of root in Cd stress in this species

Enhancement of Palmarumycins C12 and C13 Production in Liquid Culture of Endophytic Fungus Berkleasmium sp. Dzf12 after Treatments with Metal Ions

The influences of eight metal ions (i.e., Na+, Ca2+, Ag+, Co2+, Cu2+, Al3+, Zn2+, and Mn4+) on mycelia growth and palmarumycins C12 and C13 production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12 were investigated. Three metal ions, Ca2+, Cu2+ and Al3+ were exhibited as the most effective to enhance mycelia growth and palmarumycin production. When calcium ion (Ca2+) was applied to the medium at 10.0 mmol/L on day 3, copper ion (Cu2+) to the medium at 1.0 mmol/L on day 3, aluminum ion (Al3+) to the medium at 2.0 mmol/L on day 6, the maximal yields of palmarumycins C12 plus C13 were obtained as 137.57 mg/L, 146.28 mg/L and 156.77 mg/L, which were 3.94-fold, 4.19-fold and 4.49-fold in comparison with that (34.91 mg/L) of the control, respectively. Al3+ favored palmarumycin C12 production when its concentration was higher than 4 mmol/L. Ca2+ had an improving effect on mycelia growth of Berkleasmium sp. Dzf12. The combination effects of Ca2+, Cu2+ and Al3+ on palmarumycin C13 production were further studied by employing a statistical method based on the central composite design (CCD) and response surface methodology (RSM). By solving the quadratic regression equation between palmarumycin C13 and three metal ions, the optimal concentrations of Ca2+, Cu2+ and Al3+ in medium for palmarumycin C13 production were determined as 7.58, 1.36 and 2.05 mmol/L, respectively. Under the optimum conditions, the predicted maximum palmarumycin C13 yield reached 208.49 mg/L. By optimizing the combination of Ca2+, Cu2+ and Al3+ in medium, palmarumycin C13 yield was increased to 203.85 mg/L, which was 6.00-fold in comparison with that (33.98 mg/L) in the original basal medium. The results indicate that appropriate metal ions (i.e., Ca2+, Cu2+ and Al3+) could enhance palmarumycin production. Application of the metal ions should be an effective strategy for palmarumycin production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12

Enhancement of Palmarumycins C12 and C13 Production in Liquid Culture of Endophytic Fungus Berkleasmium sp. Dzf12 after Treatments with Metal Ions

and Mn 4+) on mycelia growth and palmarumycins C12 and C13 production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12 were investigated. Three metal ions, Ca 2+, Cu 2+ and Al 3+ were exhibited as the most effective to enhance mycelia growth and palmarumycin production. When calcium ion (Ca 2+) was applied to the medium at 10.0 mmol/L on day 3, copper ion (Cu 2+) to the medium at 1.0 mmol/L on day 3, aluminum ion (Al 3+) to the medium at 2.0 mmol/L on day 6, the maximal yields of palmarumycins C12 plus C13 were obtained as 137.57 mg/L, 146.28 mg/L and 156.77 mg/L, which were 3.94-fold, 4.19-fold and 4.49-fold in comparison with that (34.91 mg/L) of the control, respectively. Al 3+ favored palmarumycin C12 production when its concentration was higher than 4 mmol/L. Ca 2+ had an improving effect on mycelia growth of Berkleasmium sp. Dzf12. The combination effects of Ca 2+, Cu 2+ and Al 3+ on palmarumycin C13 production were further studied by employing a statistical method based on the central composite design (CCD) and response surface methodology (RSM). By solving the quadratic regression equation between palmarumycin C13 and three metal ions, the optima