Papers by Zhongheng Zhang
Critical Care
Background Septic shock comprises a heterogeneous population, and individualized resuscitation st... 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...
Journal of Clinical Medicine
Among drug-eluting stents (DESs), the durable polymer everolimus-eluting stent (EES) and resolute... 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...
Critical Care
Background Corticoid therapy has been recommended in the treatment of critically ill patients wit... 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...
Frontiers in Medicine
Background: Many severity scores are widely used for clinical outcome prediction for critically i... 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...
Journal of Emergency and Critical Care Medicine
Scientific Reports
Fluid strategy is the key to the successful management of patients with sepsis. However, previous... 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 [
Frontiers in Medicine
Background: Lung mechanics during invasive mechanical ventilation (IMV) for both prognostic and t... more Background: Lung mechanics during invasive mechanical ventilation (IMV) for both prognostic and therapeutic implications; however, the full trajectory lung mechanics has never been described for novel coronavirus disease 2019 (COVID-19) patients requiring IMV. The study aimed to describe the full trajectory of lung mechanics of mechanically ventilated COVID-19 patients. The clinical and ventilator setting that can influence patient-ventilator asynchrony (PVA) and compliance were explored. Post-extubation spirometry test was performed to assess the pulmonary function after COVID-19 induced ARDS. Methods: This was a retrospective study conducted in a tertiary care hospital. All patients with IMV due to COVID-19 induced ARDS were included. High-granularity ventilator waveforms were analyzed with deep learning algorithm to obtain PVAs. Asynchrony index (AI) was calculated as the number of asynchronous events divided by the number of ventilator cycles and wasted efforts. Mortality was recorded as the vital status on hospital discharge. Results: A total of 3,923,450 respiratory cycles in 2,778 h were analyzed (average: 24 cycles/min) for seven patients. Higher plateau pressure (Coefficient: -0.90; 95% CI: -1.02 to -0.78) and neuromuscular blockades (Coefficient: -6.54; 95% CI: -9.92 to -3.16) were associated with lower AI. Survivors showed increasing compliance over time, whereas non-survivors showed persistently low compliance. Recruitment maneuver was not able to improve lung compliance. Patients were on supine position in 1,422 h (51%), followed by prone positioning (499 h, 18%), left positioning (453 h, 16%), and right positioning (404 h, 15%). As compared with supine positioning, prone positioning was associated with 2.31 ml/cmH 2 O (95% CI: 1.75 to 2.86; p < 0.001) increase in lung compliance. Spirometry tests showed that pulmonary functions were reduced to one third of the predicted values after extubation. Ge et al. Conclusions: The study for the first time described full trajectory of lung mechanics of patients with COVID-19. The result showed that prone positioning was associated with improved compliance; higher plateau pressure and use of neuromuscular blockades were associated with lower risk of AI.
Critical Care
Background: The aim of this study is to assess the prevalence of abnormal urine analysis and kidn... more Background: The aim of this study is to assess the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 patients and to determine the association of acute kidney injury (AKI) with the severity and prognosis of COVID-19 patients. Methods: The electronic database of Embase and PubMed were searched for relevant studies. A meta-analysis of eligible studies that reported the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 was performed. The incidences of AKI were compared between severe versus non-severe patients and survivors versus non-survivors. Results: A total of 24 studies involving 4963 confirmed COVID-19 patients were included. The proportions of patients with elevation of sCr and BUN levels were 9.6% (95% CI 5.7-13.5%) and 13.7% (95% CI 5.5-21.9%), respectively. Of all patients, 57.2% (95% CI 40.6-73.8%) had proteinuria, 38.8% (95% CI 26.3-51.3%) had proteinuria +, and 10.6% (95% CI 7.9-13.3%) had proteinuria ++ or +++. The overall incidence of AKI in all COVID-19 patients was 4.5% (95% CI 3.0-6.0%), while the incidence of AKI was 1.3% (95% CI 0.2-2.4%), 2.8% (95% CI 1.4-4.2%), and 36.4% (95% CI 14.6-58.3%) in mild or moderate cases, severe cases, and critical cases, respectively. Meanwhile, the incidence of AKI was 52.9%(95% CI 34.5-71.4%), 0.7% (95% CI − 0.3-1.8%) in non-survivors and survivors, respectively. Continuous renal replacement therapy (CRRT) was required in 5.6% (95% CI 2.6-8.6%) severe patients, 0.1% (95% CI − 0.1-0.2%) non-severe patients and 15.6% (95% CI 10.8-20.5%) non-survivors and 0.4% (95% CI − 0.2-1.0%) survivors, respectively. Conclusion: The incidence of abnormal urine analysis and kidney dysfunction in COVID-19 was high and AKI is closely associated with the severity and prognosis of COVID-19 patients. Therefore, it is important to increase awareness of kidney dysfunction in COVID-19 patients.
Annals of Translational Medicine
BMC Anesthesiology
Background: Postoperative hypoxemia is quite common in patients with acute aortic dissection (AAD... more Background: Postoperative hypoxemia is quite common in patients with acute aortic dissection (AAD) and is associated with poor clinical outcomes. However, there is no method to predict this potentially life-threatening complication. The study aimed to develop a regression model in patients with AAD to predict postoperative hypoxemia, and to validate it in an independent dataset. Methods: All patients diagnosed with AAD from December 2012 to December 2017 were retrospectively screened for potential eligibility. Preoperative and intraoperative variables were included for analysis. Logistic regression model was fit by using purposeful selection procedure. The original dataset was split into training and validating datasets by 4:1 ratio. Discrimination and calibration of the model was assessed in the validating dataset. A nomogram was drawn for clinical utility. Results: A total of 211 patients, involving 168 in non-hypoxemia and 43 in hypoxemia group, were included during the study period (incidence: 20.4%). Duration of mechanical ventilation (MV) was significantly longer in the hypoxemia than non-hypoxemia group (41(10.5140) vs. 12(3.75,70.25) hours; p = 0.002). There was no difference in the hospital mortality rate between the two groups. The purposeful selection procedure identified 8 variables including hematocrit (odds ratio [OR]: 0.89, 95% confidence interval [CI]: 0.80 to 0.98, p = 0.011), PaO 2 /FiO 2 ratio (OR: 0.99, 95% CI: 0.99 to 1.00, p = 0.011), white blood cell count (OR: 1.21, 95% CI: 1.06 to 1.40, p = 0.008), body mass index (OR: 1.32, 95% CI: 1.15 to 1.54; p = 0.000), Stanford type (OR: 0.22, 95% CI: 0.06 to 0.66; p = 0.011), pH (OR: 0.0002, 95% CI: 2*10 − 8 to 0. 74; p = 0.048), cardiopulmonary bypass time (OR: 0.99, 95% CI: 0.98 to 1.00; p = 0.031) and age (OR: 1.03, 95% CI: 0.99 to 1.08; p = 0.128) to be included in the model. In an independent dataset, the area under curve (AUC) of the prediction model was 0.869 (95% CI: 0.802 to 0.936). The calibration was good by visual inspection. Conclusions: The study developed a model for the prediction of postoperative hypoxemia in patients undergoing operation for AAD. The model showed good discrimination and calibration in an independent dataset that was not used for model training.
Journal of Investigative Surgery
Dexmedetomidine has been widely used in the intensive care unit (ICU), with the primary aim to ke... more Dexmedetomidine has been widely used in the intensive care unit (ICU), with the primary aim to keep patients on an appropriate level of sedation. Both observational and randomized controlled trials have observed that the use of dexmedetomidine is associated with improved outcomes for mechanically ventilated patients [1]. In ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to other sedatives in maintaining sedation level, but was associated with shortened MV duration and improved ability to communicate pain [2]. MV is an important factor for delirium and dexmedetomidine was found to be associated with lower risk of delirium [3, 4]. Prophylactic low-dose dexmedetomidine is able to reduce the occurrence of delirium during the first 7 days after surgery for patients aged over 65 years who are admitted to the ICU after surgery [4]. Thus, the beneficial effect of might be explained by the reduction of delirium in the treated group. In fact, delirium can be considered as a type of acute organ dysfunction mediated via inflammatory response. There has been evidence that inflammatory biomarkers such as C-reactive protein was positively correlated with the occurrence of delirium [5].
Critical Care
Background and objective: Sepsis is a heterogeneous disease and identification of its subclasses ... more Background and objective: Sepsis is a heterogeneous disease and identification of its subclasses may facilitate and optimize clinical management. This study aimed to identify subclasses of sepsis and its responses to different amounts of fluid resuscitation. Methods: This was a retrospective study conducted in an intensive care unit at a large tertiary care hospital. The patients fulfilling the diagnostic criteria of sepsis from June 1, 2001 to October 31, 2012 were included. Clinical and laboratory variables were used to perform the latent profile analysis (LPA). A multivariable logistic regression model was used to explore the independent association of fluid input and mortality outcome. Results: In total, 14,993 patients were included in the study. The LPA identified four subclasses of sepsis: profile 1 was characterized by the lowest mortality rate and having the largest proportion and was considered the baseline type; profile 2 was characterized by respiratory dysfunction; profile 3 was characterized by multiple organ dysfunction (kidney, coagulation, liver, and shock), and profile 4 was characterized by neurological dysfunction. Profile 3 showed the highest mortality rate (45.4%), followed by profile 4 (27.4%), 2 (18.2%), and 1 (16.9%). Overall, the amount of fluid needed for resuscitation was the largest on day 1 (median 5115 mL, interquartile range (IQR) 2662 to 8800 mL) and decreased rapidly on day 2 (median 2140 mL, IQR 900 to 3872 mL). Higher cumulative fluid input in the first 48 h was associated with reduced risk of hospital mortality for profile 3 (odds ratio (OR) 0.89, 95% CI 0.83 to 0.95 for each 1000 mL increase in fluid input) and with increased risk of death for profile 4 (OR 1.20, 95% CI 1.11 to 1.30). The study identified four subphenotypes of sepsis, which showed different mortality outcomes and responses to fluid resuscitation. Prospective trials are needed to validate our findings.
Emergency Medicine Journal
Background and objectivesDelayed patient admission to the intensive care unit (ICU) from the ED i... 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%), ...
European Journal of Clinical Microbiology & Infectious Diseases
The World Health Organization (WHO) proposed a global priority pathogen list (PPL) of multidrug r... more The World Health Organization (WHO) proposed a global priority pathogen list (PPL) of multidrug resistant (MDR) bacteria. Our current objective was to provide global expert ranking of the most serious multi-drug resistant (MDR) bacteria present at intensive care units (ICU) that have become a threat in clinical practice. Methods: A proposal addressing a pathogens priority list (PPL) for ICU, arising from the WHO Global PPL was developed. Based on the supporting data, the pathogens were grouped in three priority tiers: Critical, high and medium. A multi-criteria decision analyses (MCDA) was used to identify the priority tiers. Results: After MCDA analysis, mortality, treatability and cost of therapy were of highest concern (scores of 19/20, 19/20 and 15/20, respectively) while dealing with PPL, followed by healthcare burden and resistance prevalence. Carbapenen-resistant (CR) Acinetobacter baumannii, Carbapenemaseexpressing Klebsiella pneumoniae (KPC) and MDR Pseudomonas aeruginosa were identified as critical organisms. High risk organisms were represented by CR Pseudomonas aeruginosa, Methicillinresistant Staphylococcus aureus, and Extended Spectrum Beta lactamase(ESBL) Enterobacteriaceae. Finally, ESBL Serratia marcescens, Vancomycin-resistant Enterococci and TMP-SMX resistant Stenotrophomonas maltophilia were identified as medium priority. Conclusions: We conclude that education, investigation, funding and development of new antimicrobials for ICU organisms should focus on Carbapenem-resistant Gram negative organisms.
Intensive Care Medicine
ObjectiveAlthough sodium bicarbonate (SB) solution has been widely used in clinical practice, its... 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.
Journal of Medical Artificial Intelligence
Annals of translational medicine, 2018
Artificial neural networks (ANNs) are powerful tools for data analysis and are particularly suita... 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...
Annals of translational medicine, 2016
It is common that data format extracted from clinical database does not meet the purpose of stati... 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.
Canadian respiratory journal, 2017
PloS one, 2017
Enteral nutrition (EN) feeding protocol was proposed to have positive impact on critically ill pa... 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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Papers by Zhongheng Zhang