Blended teaching mode based on small private online course and case-based learning in analgesia and sedation education in China: a comparison with an offline mode.

BACKGROUND: Standardized training for pain, agitation-sedation, and delirium (PAD) management is urgently needed for Chinese intensivists' continuing education. Since 2020, because of the COVID-19 pandemic, the Chinese Analgesia and Sedation Education and Research (CASER) group has used an online blended teaching mode based on a small private online course (SPOC) and case-based learning (CBL). This study evaluated whether an online blended teaching mode has similar effects on PAD management training when an offline mode cannot be used. MATERIALS AND METHODS: Since 2020, the CASER group has provided offline training and online SPOC&CBL training three times each, targeting intensivists and ICU nurses in China. All participants were divided into an offline group and SPOC&CBL group. A final examination was offered in each training session to assess the students' mastery of professional knowledge. Teachers' and students' perceptions regarding the online SPOC&CBL mode were evaluated through questionnaires. RESULTS: Of all participants (n = 117), 106 completed all examinations and questionnaires. Most participants were aged 31-40 years (53, 50.0%), had an academic degree (60, 56.6%), and worked in a tertiary hospital (100, 94.34%). We assessed the learning effect on participants from two aspects: theory and clinical practice. There was no significant difference between the SPOC&CBL and offline groups in terms of theoretical, case analysis, and total scores (p > 0.05). In terms of the participants' perceptions regarding the SPOC&CBL mode, 91.5% considered the online mode to be a useful and accessible alternative to improve knowledge and skills. A total of 95.7% of the participants believed that they could interact well with group members, and 87.2% believed that they had a good degree of participation. Of these participants, 76.6% believed that they had received valuable learning resources. All instructors believed that the SPOC&CBL mode was more flexible than the offline mode in terms of teaching time and location, and they were all willing to carry out training with the SPOC&CBL mode. CONCLUSION: Compared to the offline mode, the SPOC&CBL mode can also enhance participants' knowledge and skills and meets their expectations. Therefore, an online mode can be considered a potential method in PAD management education in China.

Glycyrrhiza polysaccharides inhibits PRRSV replication.

Glycyrrhiza polysaccharide (GCP) is a natural plant active polysaccharide extracted from traditional Chinese medicine licorice. In this research, we studied the antiviral activity of glycyrrhiza polysaccharide against porcine reproductive and respiratory syndrome virus (PRRSV), a virus of the Arteriviridae family, with a high rate of variation and has caused huge economic losses to the pig industry in various countries since its discovery. Our results show that GCP can inhibit PRRSV replication in a dose-dependent manner. Furthermore, GCP could inhibit the mRNA expression of receptor genes CD163 and NF-κB p65 and promote the mRNA expression of the SLA-7 gene. Because of these results, GCP can be used as a candidate drug to prevent and treat PRRS.

Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units.

BACKGROUND: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. METHODS: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors. RESULTS: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 µg/mL in the HD group, which was higher than in the SD group (0,21 µg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. CONCLUSIONS: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Association Between Glycemic Gap and Mortality in Critically Ill Patients with Diabetes.

OBJECTIVES: Dysglycemia is associated with poor outcomes in critically ill patients,which is uncertain in patients with diabetes regarding to the situation of glucose control before hospitalization. This study was aimed to investigate the effect of the difference between the level of blood glucose during ICU stay and before admission to ICU upon the outcomes of critically ill patients with diabetes. METHOD: Patients with diabetes expected to stay for more than 24hs were enrolled, HbA1c was converted to A1C-derived average glucose (ADAG) by the equation: ADAG = [ (HbA1c * 28.7) - 46.7 ] * 18-1, blood glucose were measured four times a day during the first 7 days after admission, the mean glucose level(MGL) and SOFA (within 3, 5, and 7days) were calculated for each person, GAPadm and GAPmean was calculated as admission blood glucose and MGL minus ADAG, the incidence of moderate hypoglycemia(MH), severe hypoglycemia (SH), total dosage of glucocorticoids and average daily dosage of insulin, duration of renal replacement therapy(RRT), ventilator-free hours, and non-ICU days were also collected. Patients were divided into survival group and nonsurvival group according to survival or not at 28-day, the relationship between GAP and mortality were analyzed. RESULTS: 431 patients were divided into survival group and nonsurvival group. The two groups had a comparable level of HbA1c, the nonsurvivors had greater APACHE II, SOFA, GAPadm, GAPmean-3, GAPmean-5, GAPmean-7 and higher MH and SH incidences. Less duration of ventilator-free, non-ICU stay and longer duration of RRT were recorded in the nonsurvival group. GAPmean-5 had the greatest predictive power with an AUC of 0.807(95%CI: 0.762-0.851), the cut-off value was 3.6 mmol/L (sensitivity 77.7% and specificity 76.6%). The AUC was increased to 0.852(95%CI: 0.814-0.889) incorporated with SOFA5 (NRI = 11.34%). CONCLUSION: Glycemic GAP between the MGL within 5 days and ADAG was independently associated with 28-day mortality of critically ill patients with diabetes. The predictive power was optimized with addition of SOFA5.

The variations in human orphan G protein-coupled receptor QRFPR affect PI3K-AKT-mTOR signaling.

BACKGROUND: QRFPR is a recently identified member of the G protein-coupled receptor and is an orphan receptor for 26Rfa, which plays important role in the regulation of many physiological functions. METHODS: Here, we employed whole exome sequencing (WES) to examine the patients with intellectual disability (ID) and difficulty in feeding. We performed SIFT and PolyPhen2 predictions for the variants. The structure model was built from scratch by I-TASSER. Here, results derived from a number of cell-based functional assays, including shRNA experiment, intracellular Ca2+ measurement, the expression of PI3 K-AKT-mTOR, and phosphorylation. The functional effect of QRFPR variants on PI3K-AKT-mTOR signaling was evaluated in vitro transfection experiments. RESULT: Here, we identified two QRFPR variants at c.202 T>C (p.Y68H) and c.1111C>T (p.R371W) in 2 unrelated individuals. Structural analysis revealed that p.Y68H and p.R371W variants may affect the side chain structure of adjacent amino acids causing reduced binding of QRFPR to 26Rfa. The results show that QRFPR stimulated by 26Rfa leading to the transient rise of intracellular Ca2+ . The QRFPR variations p.Y68H and p.R371 W can reduce the mobilization of intracellular Ca2+ . The phosphorylation levels of the PI3K, Akt, and mTOR were significantly up- or downregulated by QRFPR overexpression or silencing, respectively. The QRFPR variations inhibited PI3K-AKT-mTOR signaling, resulting in downregulation of p-mTOR. CONCLUSIONS: Our findings suggest that QRFPR acts as important role in neurodevelopment, and the effects of QRFPR are likely to be mediated by the Ca2+ -dependent PI3K-AKT-mTOR pathways. Importantly, these findings provide a foundation for future elucidation of GPCR-mediated signaling and the physiological implications.

[Association between glucose variability and poor prognosis in critically ill patients].

OBJECTIVE: To explore the association between glucose variability and poor prognosis in critically ill patients. METHODS: This prospective study was undertaken in a 24-bed intensive care unit (ICU). A total of 145 patients staying for over 24 hours in ICU were enrolled. Their arterial levels of blood glucose were measured four times daily routinely. And the mean glucose level (MGL), standard deviation (SD) and coefficient of variation (CV) were calculated. The incidence of moderate hypoglycemia (MH), severe hypoglycemia (SH), total dosage of hormone, average daily dosage of insulin, duration of renal replacement- therapy (RRT), mechanical ventilation and ICU free days were also recorded. They were divided into survival (n = 85) and nonsurvival (n = 60) groups according to survival or not at 28 days. And CV was compared between two groups and the relationship of CV and mortality examined. RESULTS: The nonsurvival group had higher CV value accompanied by higher RRT proportion, higher incidences of MH and SH, shorter free mechanical ventilation time and free ICU stay. The higher CV value was found in surviving nondiabetics. However, no significant difference existed in diabetes group. CONCLUSION: Critically ill patients have higher CV of glucose variability especially in non-diabetic patients. Blood glucose fluctuations denote a worse prognosis. And hypoglycemia should raise a high alert. Frequent blood glucose monitoring is beneficial to detecting the changes of condition and adjusting treatment regimens accordingly.

Exploration of teaching practice of analgesia and sedation in mainland China: CASER experience.

Objective: Analgesia and sedation assessments vary widely in clinical performance. This study investigated the cognition of intensivist and the importance of training for analgesia and sedation through the Chinese Analgesia and Sedation Education & Research (CASER) group training program. Methods: A total of 107 participants studied the training courses on the "Sedation, Analgesia and Consciousness Assessment of Critically Ill Patients" held by CASER from June 2020 to June 2021. Ninety-eight valid questionnaires were recovered. The content of the questionnaire included the preface, general information of the trainees, students' awareness of the importance of analgesia and sedation evaluation and related guidelines, and professional test questions. Results: All respondents were senior professionals engaged in the ICU. A total of 92.86% believed that analgesia and sedation treatment were very important parts of the ICU, and 76.5% believed that they had mastered relevant professional knowledge. However, when evaluating the relevant professional theory and practice of the respondents from an objective point of view, it can be seen that only 28.57% of the respondents could reach the passing line in the specific case analysis scenario. Before participating in the training, 42.86% of the medical staff believed that analgesia and sedation treatment should be evaluated in the daily work of the ICU; after participating in the training, 62.24% of the medical staff believed that the evaluation was necessary and believed that they had improved after the training. Moreover, 69.4% of the respondents affirmed the necessity and significance of jointly undertaking the task of analgesia and sedation in Chinese ICUs. Conclusion: This study revealed that the assessment of analgesia and sedation is not standardized in the ICU in mainland China. The importance and significance of standardized training for analgesia and sedation are presented. The CASER working group thus established has a long way to go in its future work.

Vancomycin therapeutic drug monitoring in patients on continuous renal replacement therapy: a retrospective study.

OBJECTIVES: This study aimed to investigate vancomycin therapeutic drug monitoring (TDM) in patients on continuous renal replacement therapy (CRRT) and explore the risk factors for exceeding the target concentration. METHODS: This retrospective study enrolled patients aged ≥18 years who were admitted to the intensive care unit and treated with ≥3 intravenous vancomycin doses during CRRT, and who underwent vancomycin TDM. Demographic and other information were collected. Multivariate logistic regression was used assess the risk factors for exceeding the target concentration. RESULTS: Sixty-nine patients were included, and 40.6% patients underwent TDM. Additionally, 14.5% of patients reached the optimal concentration, and 87.5% of patients who exceeded the target received a daily dose adjustment. The cumulative dose of vancomycin and serum albumin were risk factors for exceeding the target concentration in patients on CRRT. CONCLUSIONS: Patients on CRRT did not meet the optimal vancomycin management; <50% of the patients routinely received vancomycin TDM, and <15% achieved the optimal concentration. Fewer patients in the subtherapeutic group received a daily dose adjustment than those who exceeded the target concentration. Cumulative vancomycin and serum albumin doses before TDM were the risk factors for exceeding the target concentration in CRRT patients.

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU.

Purpose: Tigecycline is an agent for carbapenemase-producing Klebsiella pneumonia (KPC-KP), given its penetration into lung tissues. Our study focused on the molecular and clinical efficacy of tigecycline for hospital-acquired pneumonia (HAP) in the ICU. Patients and Methods: A retrospective cohort study of 52 adult KPC-KP HAP patients by searching hospital medical records from January 2018 to December 2020 was established to investigate the epidemiology of KPC-KP infections for tigecycline treatment and the associated clinical efficacy of tigecycline. The KPC-KP isolates underwent multilocus sequence typing. Molecular typing, antimicrobial resistance, and virulence profiling were also analyzed by whole-genome sequencing of KPC-KP. Results: Among 52 patients with KPC-KP, the ICU mortality rate was 14/52 (27%), and there was no significant statistical difference in mortality between the effective group and failure group (p = 0.754). However, the duration of tigecycline was statistically different between the two groups of patients (14.4 vs 10 days, p=0.046). The total bacterial clearance rate was 6/52 (11.5%). There was no significant statistical difference in both groups (p=0.416). Antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were negatively correlated with clinical efficacy (p = 0.011, OR = 1.237). Conclusions: Blakpc was the main carbapenemase in all K. pneumoniae strains. ST11-KL64 KPC-KP was the most common virulence factors in KPC-KP isolates. This study suggested that antibiotic resistance genes (aac3iia) and virulence gene (AREO-iutA, Capsule-wzc) were independent mortality risk factors for patients with Klebsiella pneumoniae carbapenemase-2 producing K. pneumoniae infections, when during the tigecycline treatment. Molecular analysis of K. pneumoniae may provide an option when choosing the antimicrobial treatment.

Effect of glycemic gap upon mortality in critically ill patients with diabetes.

AIMS/INTRODUCTION: Hyperglycemia, hypoglycemia, and blood glucose fluctuation are associated with the outcome in critically ill patients, but the target of blood glucose control is debatable especially in patients with diabetes regarding the status of blood glucose control before admission to ICU. This study aimed to investigate the association between the glycemic gap which is calculated as the mean blood glucose level during the first 7 days after admission to ICU minus the A1C-derived average glucose and the outcome of critically ill patients with diabetes. METHOD: This study was undertaken in two intensive care units (ICUs) with a total of 30 beds. Patients with diabetes who were expected to stay for more than 24 h were enrolled, the HbA1c was tested within 3 days after admission and converted to the A1C-derived average glucose (ADAG) by the equation: ADAG = [(HbA1c * 28.7) - 46.7 ] * 18-1 , arterial blood glucose measurements were four per day routinely during the first 7 days after admission, the APACHE II score within the first 24 h, the mean blood glucose level (MGL), standard deviation (SD), and coefficient of variation (CV) during the first 7 days were calculated for each person, the GAPadm and GAPmean were calculated as the admission blood glucose and MGL minus the ADAG, respectively, the incidence of moderate hypoglycemia (MH) and severe hypoglycemia (SH), the total dosage of glucocorticoids and average daily dosage of insulin within 7 days, the duration of renal replacement therapy (RRT), ventilator-free hours, and non-ICU stay days within 28 days were also collected. The enrolled patients were divided into a survival group and a nonsurvival group according to survival or not at 28 days and 1 year after admission, and the relationship between parameters derived from blood glucose and mortality in the enrolled critically ill patients was explored. RESULTS: Five hundred and two patients were enrolled and divided into a survival group (n = 310) and a nonsurvival group (n = 192). It was shown that the two groups had a comparable level of HbA1c, the nonsurvivors had a greater APACHE II, MGL, SD, CV, GAPadm , GAPmean , and a higher incidence of hypoglycemia. A lesser duration of ventilator-free, non-ICU stay, and a longer duration of RRT were recorded in the nonsurvival group, who received a lower carbohydrate intake, a higher daily dosage of insulin and glucocorticoid. GAPmean had the greatest predictive power with an AUC of 0.820 (95%CI: 0.781-0.850), the cut-off value was 3.60 mmol/L (sensitivity 78.2% and specificity 77.3%). Patients with a low GAPmean tended to survive longer than the high GAPmean group 1 year after admission. CONCLUSIONS: Glycemic GAP between the mean level of blood glucose within the first 7 days after admission to ICU and the A1C-derived average glucose was independently associated with a 28 day mortality of critically ill patients with diabetes, the predictive power extended to 1 year. The incidence of hypoglycemia was associated with mortality either.

Effect of a quality improvement program on weaning from mechanical ventilation: a cluster randomized trial.

PURPOSE: To evaluate the efficacy of a quality improvement (QI) program for protocol-directed weaning from mechanical ventilation. METHODS: This was a prospective, cluster randomized controlled trial. The study consisted of a baseline phase and a QI phase. Fourteen intensive care units (ICUs) in Beijing, China, were randomized into the QI group and non-QI group. The QI group received a QI program to improve the compliance with protocol-directed weaning during the QI phase. RESULTS: A total of 444 patients were enrolled in the non-QI group (193 for the baseline, 251 for the QI phase) and 440 in the QI group (199 for the baseline, 241 for the QI phase). During the QI phase in the QI group, compared with the non-QI group, total duration of mechanical ventilation decreased from 7.0 to 3.0 days (p = 0.003), the time before the first weaning attempt decreased from 3.63 to 1.96 days (p = 0.003), length of ICU stay decreased from 10.0 to 6.0 days (p = 0.004), length of hospital stay decreased from 23.0 to 19.0 days (p < 0.001). These differences were also significant in the QI group when the QI phase was compared with the baseline phase. In addition, there was a significant reduction in the percentage of mechanical ventilation exceeding 21 days (p = 0.001) when the baseline phase was compared with the QI phase in the QI group. CONCLUSIONS: The QI program involving protocol-directed weaning is associated with beneficial clinical outcomes in mechanically ventilated patients.

Weaning critically ill patients from mechanical ventilation: A prospective cohort study.

PURPOSE: A proposal was made at the International Consensus Conference to classify weaning of patients in intensive care units from mechanical ventilation into simple, difficult, and prolonged weaning groups based on the difficulty and length of the weaning process. The objective of the present study was to determine the incidence and outcome of weaning according to these new categories. METHODS: We examined the weaning of patients in intensive care units from mechanical ventilation in a prospective multicenter cohort study. RESULTS: In total, 343 patients were included in the final analysis. Simple, difficult, and prolonged weaning occurred in 200 (58%), 99 (29%), and 44 (13%) patients, respectively. Hospital mortality rates were higher for patients in the prolonged weaning group than in the simple and difficult weaning groups. Multivariate analysis revealed that a lower Glasgow Coma Scale score (P < .014) and hypercapnia at the beginning of the first spontaneous breathing trial (P = .038) were independent predictors of prolonged weaning. CONCLUSIONS: Patients who experienced prolonged weaning had significantly higher mortality rates than patients who experienced either simple or difficult weaning. A lower Glasgow Coma Scale score and hypercapnia at the beginning of the weaning process were independent risk factors for prolonged weaning.