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Background Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to... more
Background Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class. Methods Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset. Results A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means cluster...
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Among drug-eluting stents (DESs), the durable polymer everolimus-eluting stent (EES) and resolute zotarolimus-eluting stent (R-ZES) are widely used in clinical practice and have contributed to improve the outcomes of patients undergoing... more
Among drug-eluting stents (DESs), the durable polymer everolimus-eluting stent (EES) and resolute zotarolimus-eluting stent (R-ZES) are widely used in clinical practice and have contributed to improve the outcomes of patients undergoing percutaneous coronary intervention (PCI). Few studies addressed their long-term comparative performance in patients with acute coronary syndrome (ACS). We aimed to investigate the 5 year comparative efficacy of EES and R-ZES in ACS. We queried ACTION-ACS, a large-scale database of ACS patients undergoing PCI. The treatment groups were analyzed using propensity score matching. The primary endpoint was a composite of mortality, myocardial infarction (MI), stroke, repeat PCI, and definite or probable stent thrombosis, which was addressed at the five-year follow-up. A total of 3497 matched patients were analyzed. Compared with R-ZES, a significant reduction in the primary endpoint at 5 years was observed in patients treated with EES (hazard ratio (HR) [9...
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Background Corticoid therapy has been recommended in the treatment of critically ill patients with COVID-19, yet its efficacy is currently still under evaluation. We investigated the effect of corticosteroid treatment on 90-day mortality... more
Background Corticoid therapy has been recommended in the treatment of critically ill patients with COVID-19, yet its efficacy is currently still under evaluation. We investigated the effect of corticosteroid treatment on 90-day mortality and SARS-CoV-2 RNA clearance in severe patients with COVID-19. Methods 294 critically ill patients with COVID-19 were recruited between December 30, 2019 and February 19, 2020. Logistic regression, Cox proportional-hazards model and marginal structural modeling (MSM) were applied to evaluate the associations between corticosteroid use and corresponding outcome variables. Results Out of the 294 critically ill patients affected by COVID-19, 183 (62.2%) received corticosteroids, with methylprednisolone as the most frequently administered corticosteroid (175 accounting for 96%). Of those treated with corticosteroids, 69.4% received corticosteroid prior to ICU admission. When adjustments and subgroup analysis were not performed, no significant associatio...
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Background: Many severity scores are widely used for clinical outcome prediction for critically ill patients in the intensive care unit (ICU). However, for patients identified by sepsis-3 criteria, none of these have been developed. This... more
Background: Many severity scores are widely used for clinical outcome prediction for critically ill patients in the intensive care unit (ICU). However, for patients identified by sepsis-3 criteria, none of these have been developed. This study aimed to develop and validate a risk stratification score for mortality prediction in sepsis-3 patients.Methods: In this retrospective cohort study, we employed the Medical Information Mart for Intensive Care III (MIMIC III) database for model development and the eICU database for external validation. We identified septic patients by sepsis-3 criteria on day 1 of ICU entry. The Least Absolute Shrinkage and Selection Operator (LASSO) technique was performed to select predictive variables. We also developed a sepsis mortality prediction model and associated risk stratification score. We then compared model discrimination and calibration with other traditional severity scores.Results: For model development, we enrolled a total of 5,443 patients f...
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Fluid strategy is the key to the successful management of patients with sepsis. However, previous studies failed to consider individualized treatment strategy, and clinical trials typically included patients with sepsis as a homogeneous... more
Fluid strategy is the key to the successful management of patients with sepsis. However, previous studies failed to consider individualized treatment strategy, and clinical trials typically included patients with sepsis as a homogeneous study population. We aimed to develop sequential decision rules for managing fluid intake in patients with sepsis by using the dynamic treatment regimen (DTR) model. A retrospective analysis of the eICU Collaborative Research Database comprising highly granular data collected from 335 units at 208 hospitals was performed. The DTR model used a backward induction algorithm to estimate the sequence of optimal rules. 22,868 patients who had sepsis according to the Acute Physiology and Chronic Health Evaluation (APACHE) IV diagnosis group were included. Optimal fluid management (liberal [> 40 ml/kg/d] versus restricted [
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Background and objectivesDelayed patient admission to the intensive care unit (ICU) from the ED is common in China. Patients with severe sepsis or septic shock requiring ICU admission are in need of specialised monitoring and tailored... more
Background and objectivesDelayed patient admission to the intensive care unit (ICU) from the ED is common in China. Patients with severe sepsis or septic shock requiring ICU admission are in need of specialised monitoring and tailored treatment. Delayed admission to the ICU might be associated with adverse clinical outcomes for patients with sepsis.MethodsPatients with sepsis admitted to the ICU from the ED from January 2010 to April 2018 were retrospectively identified from a clinical data warehouse. The primary endpoint was in-hospital mortality. Length of stay in ED (EDLOS) was compared between survivors and non-survivors. A multivariable regression model was employed to adjust for potential confounding due to patient clinical condition.ResultsA total of 1997 patients, including 473 non-survivors and 1524 survivors, were included. The crude mortality rate for patients with EDLOS <6 hours was 21.4%, which was significantly lower than patients with EDLOS of 12–24 hours (31.9%), ...
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ObjectiveAlthough sodium bicarbonate (SB) solution has been widely used in clinical practice, its effect on mortality when administered to a large population of patients with acidosis is not known. The study aimed to investigate the... more
ObjectiveAlthough sodium bicarbonate (SB) solution has been widely used in clinical practice, its effect on mortality when administered to a large population of patients with acidosis is not known. The study aimed to investigate the effectiveness of SB infusion in septic patients with metabolic acidosis.MethodsSeptic patients with metabolic acidosis were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) was used to account for the baseline differences in the probability to receive SB or not. The marginal structural Cox model (MSCM) was employed to adjust for both baseline and time-varying confounding factors.Main resultsA total of 1718 septic patients with metabolic acidosis were enrolled in the study, including 500 in the SB group and 1218 in the non-SB group. Both pH [7.16 (standard deviation (SD): 0.10) vs. 7.22 (SD: 0.07); p < 0.001] and bicarbonate concentration (BC) [11.84 (SD: 3.63) vs. 14.88 (SD: 3.36) mmol/l; p < 0.001] were significantly lower in the SB than that in the non-SB group. While there was no significant mortality effect in the overall population [hazard ratio (HR): 1.04; 95% CI 0.86–1.26; p = 0.67], SB was observed to be beneficial in patients with acute kidney injury (AKI) stage 2 or 3 and pH < 7.2 (HR 0.74; 95% CI 0.51–0.86; p = 0.021). Similar results were replicated with the MSCM.ConclusionOur study observed that SB infusion was not associated with improved outcome in septic patients with metabolic acidosis, but it was associated with improved survival in septic patients with AKI stage 2 or 3 and severe acidosis. The results need to be verified in randomized controlled trials.
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Artificial neural networks (ANNs) are powerful tools for data analysis and are particularly suitable for modeling relationships between variables for best prediction of an outcome. While these models can be used to answer many important... more
Artificial neural networks (ANNs) are powerful tools for data analysis and are particularly suitable for modeling relationships between variables for best prediction of an outcome. While these models can be used to answer many important research questions, their utility has been critically limited because the interpretation of the "black box" model is difficult. Clinical investigators usually employ ANN models to predict the clinical outcomes or to make a diagnosis; the model however is difficult to interpret for clinicians. To address this important shortcoming of neural network modeling methods, we describe several methods to help subject-matter audiences (e.g., clinicians, medical policy makers) understand neural network models. Garson's algorithm describes the relative magnitude of the importance of a descriptor (predictor) in its connection with outcome variables by dissecting the model weights. The Lek's profile method explores the relationship of the outcome...
It is common that data format extracted from clinical database does not meet the purpose of statistical analysis. In clinical research, variables are frequently measured repeatedly over the follow-up period. Such data can be displayed... more
It is common that data format extracted from clinical database does not meet the purpose of statistical analysis. In clinical research, variables are frequently measured repeatedly over the follow-up period. Such data can be displayed either in wide or long format. Transformation between these 2 forms can be challenging by hand. Fortunately, there are sophisticated packages in R environment. Data frame should firstly be melted and then casted to format that you want. Aggregation over unique combination of id variables is also allowable. Additionally, the article also introduces 2 functions colsplit() and funstofun() that can be useful in some circumstances.
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Enteral nutrition (EN) feeding protocol was proposed to have positive impact on critically ill patients. However, current studies showed conflicting results. The present study aimed to investigate whether enteral feeding protocol was able... more
Enteral nutrition (EN) feeding protocol was proposed to have positive impact on critically ill patients. However, current studies showed conflicting results. The present study aimed to investigate whether enteral feeding protocol was able to improve clinical outcomes in critically ill patients. A before (stage 1) and after (stage 2) interventional study was performed in 10 tertiary care hospitals. All patients expected to stay in the intensive care unit (ICU) for over three days were potentially eligible. Clinical outcomes such as 28-day mortality, ICU length of stay, duration of mechanical ventilation (MV), and nosocomial infection were compared between the two stages. A total of 410 patients were enrolled during the study period, including 236 in stage 1 and 174 in stage 2. EN feeding protocol was able to increase the proportion of EN in day 2 (41.8±22.3 vs. 50.0±28.3%; p = 0.006) and day 6 (70.3±25.2 vs. 77.6±25.8%; p = 0.006). EN percentages tended to be higher in stage 1 than t...
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Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis... more
Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on sepsis, we conducted a systematic review of all randomized controlled EGDT trials. Focus was laid on the setting (emergency department versus ICU) where EGDT was carried out. Early recognition of sepsis, through clinical or automated systems for early alert, together with well-timed initiation of the recommended therapy bundles may improve patients' outcome. However, the original "EGDT" protocol by Rivers and coworkers has been largely modified in subsequent trials. Currently, many inv...
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Clinical researches usually collected numerous intermediate variables besides treatment and outcome. These variables are often incorrectly treated as confounding factors and are thus controlled using a variety of multivariable regression... more
Clinical researches usually collected numerous intermediate variables besides treatment and outcome. These variables are often incorrectly treated as confounding factors and are thus controlled using a variety of multivariable regression models depending on the types of outcome variable. However, these methods fail to disentangle underlying mediating processes. Causal mediation analysis (CMA) is a method to dissect total effect of a treatment into direct and indirect effect. The indirect effect is transmitted via mediator to the outcome. The mediation package is designed to perform CMA under the assumption of sequential ignorability. It reports average causal mediation effect (ACME), average direct effect (ADE) and total effect. Also, the package provides visualization tool for these estimated effects. Sensitivity analysis is designed to examine whether the results are robust to the violation of the sequential ignorability assumption since the assumption has been criticized to be to...
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Background and Aims: Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically... more
Background and Aims: Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality
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Conference Paper RapidMiner Wisdom 2015 https://rapidminer.com/rapidminer-wisdom/europe/
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Background Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese... more
Background Septic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown. Methods In a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1–0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients’ shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with the χ2 test, ...
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Congenital pulmonary agenesis is a rare condition with high mortality. Mechanical ventilation in these patients is challenging and there has no such case been reported in the literature. We reported a 61-year-old female with lung agenesis... more
Congenital pulmonary agenesis is a rare condition with high mortality. Mechanical ventilation in these patients is challenging and there has no such case been reported in the literature. We reported a 61-year-old female with lung agenesis who presented to our hospital with pneumonia and pelvic mass. In the past, she had undergone repairing of atrial septal defect and mitral valve forming surgery at 6-year-old. Thereafter she had remained asymptomatic until this time of hospital admission. The patient underwent operation for the pelvic mass with one-lung ventilation (OLV) under general anesthesia. We highlighted the use of protective ventilation (PV) strategy during OLV.
With the accumulation of large amounts of health related data, predictive analytics could stimulate the transformation of reactive medicine towards Predictive, Preventive and Personalized (PPPM) Medicine, ultimately affecting both cost... more
With the accumulation of large amounts of health related data, predictive analytics could stimulate the transformation of reactive medicine towards Predictive, Preventive and Personalized (PPPM) Medicine, ultimately affecting both cost and quality of care. However, high-dimensionality and high-complexity of the data involved, prevents data-driven methods from easy translation into clinically relevant models. Additionally, the application of cutting edge predictive methods and data manipulation require substantial programming skills, limiting its direct exploitation by medical domain experts. This leaves a gap between potential and actual data usage. In this study, the authors address this problem by focusing on open, visual environments, suited to be applied by the medical community. Moreover, we review code free applications of big data technologies. As a showcase, a framework was developed for the meaningful use of data from critical care patients by integrating the MIMIC-II database in a data mining environment (RapidMiner) supporting scalable predictive analytics using visual tools (RapidMiner&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Radoop extension). Guided by the CRoss-Industry Standard Process for Data Mining (CRISP-DM), the ETL process (Extract, Transform, Load) was initiated by retrieving data from the MIMIC-II tables of interest. As use case, correlation of platelet count and ICU survival was quantitatively assessed. Using visual tools for ETL on Hadoop and predictive modeling in RapidMiner, we developed robust processes for automatic building, parameter optimization and evaluation of various predictive models, under different feature selection schemes. Because these processes can be easily adopted in other projects, this environment is attractive for scalable predictive analytics in health research.
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The development of acute respiratory distress syndrome (ARDS) is associated with dys-regulated inflammation. Since corticosteroids are potent anti-inflammatory drugs, they are thought to be beneficial for ARDS patients. The study aimed to... more
The development of acute respiratory distress syndrome (ARDS) is associated with dys-regulated inflammation. Since corticosteroids are potent anti-inflammatory drugs, they are thought to be beneficial for ARDS patients. The study aimed to investigate the effectiveness of corticosteroids on mortality outcome in ARDS patients. The study was a secondary analysis of a prospective randomized controlled trial (NCT00979121). ARDS patients with invasive mechanical ventilation were enrolled. Corticosteroids use was defined as IV or PO administration of corticosteroids totaling more than 20 mg methylprednisolone equivalents during one calendar day. Missing data were handled using multiple imputation technique. Multivariable model was built to adjust for confounding covariates. A total of 745 patients were enrolled, including 540 survivors and 205 non-survivors. Patients in the non-survivor group were more likely to use corticosteroids (38% vs. 29.8%; p = 0.032). After adjustment for other pot...
Septic shock is an important contributor of mortality in the intensive care unit (ICU). Although strenuous effort has been made to improve its outcome, the mortality rate is only marginally decreased. The present study aimed to... more
Septic shock is an important contributor of mortality in the intensive care unit (ICU). Although strenuous effort has been made to improve its outcome, the mortality rate is only marginally decreased. The present study aimed to investigate the effectiveness of anisodamine in the treatment of septic shock, in the hope that the drug will provide alternatives to the treatment of septic shock. The study is a multi-center randomized controlled clinical trial. Study population will include critically ill patients with septic shock requiring vasopressor use. Blocked randomization was performed where anisodamine and control treatments were allocated at random in a ratio of 1:1 in blocks of sizes 2, 4, 6, 8, and 10 to 354 subjects. Interim analysis will be performed. The primary study end point is the hospital mortality, and other secondary study endpoints include ICU mortality, length of stay in ICU and hospital, organ failure free days. Adverse events including new onset psychosis, urinary...
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Ultrasonography (US) has found its way into the critical care and emergency settings for the evaluation of acute respiratory failure conditions in recent years. It is useful for the diagnosis of varieties of abnormalities involving pleura... more
Ultrasonography (US) has found its way into the critical care and emergency settings for the evaluation of acute respiratory failure conditions in recent years. It is useful for the diagnosis of varieties of abnormalities involving pleura and lung such as pleural effusion, alveolar interstitial syndrome, and pneumothorax (PTX). In addition to its reproducibility and timeliness, US has high sensitivity and specificity for the diagnosis of these conditions. The most widely used method for bedside evaluation of PTX is chest X-ray (CXR). However, the diagnostic sensitivity of CXR in detecting PTX is limited especially in occult PTX and when the patient is assumed supine position. Computed tomography (CT) is the gold standard in the evaluation of PTX, but is limited by its high radiation exposure and safety concerns in transporting critically ill patients. In this paper we review current advances in PTX diagnosis using US.
Acute Physiology and Chronic Health Evaluation (APACHE) III score has been widely used for prediction of clinical outcomes in mixed critically ill patients. However, it has not been validated in patients with sepsis-associated acute lung... more
Acute Physiology and Chronic Health Evaluation (APACHE) III score has been widely used for prediction of clinical outcomes in mixed critically ill patients. However, it has not been validated in patients with sepsis-associated acute lung injury (ALI). The aim of the study was to explore the calibration and predictive value of APACHE III in patients with sepsis-associated ALI. The study was a secondary analysis of a prospective randomized controlled trial investigating the efficacy of rosuvastatin in sepsis-associated ALI (Statins for Acutely Injured Lungs from Sepsis, SAILS). The study population was sepsis-related ALI patients. The primary outcome of the current study was the same as in the original trial, 60-day in-hospital mortality, defined as death before hospital discharge, censored 60 days after enrollment. Discrimination of APACHE III was assessed by calculating the area under the receiver operating characteristic (ROC) curve (AUC) with its 95% CI. Hosmer-Lemeshow goodness-o...
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To compare treatment based on either PiCCO-derived physiological values or central venous pressure (CVP) monitoring, we performed a prospective randomized controlled trial with group sequential analysis. Consecutive critically ill... more
To compare treatment based on either PiCCO-derived physiological values or central venous pressure (CVP) monitoring, we performed a prospective randomized controlled trial with group sequential analysis. Consecutive critically ill patients with septic shock and/or ARDS were included. The planned total sample size was 715. The primary outcome was 28-day mortality after randomization. Participants underwent stratified randomization according to the classification of ARDS and/or septic shock. Caregivers were not blinded to the intervention, but participants and outcome assessors were blinded to group assignment. The study was stopped early because of futility after enrollment of 350 patients including 168 in the PiCCO group and 182 in the control group. There was no loss to follow-up and data from all enrolled participants were analyzed. The result showed that treatment based on PiCCO-derived physiological values was not able to reduce the 28-day mortality risk (odds ratio 1.00, 95 % C...