Is bivalirudin an alternative anticoagulant for extracorporeal membrane oxygenation (ECMO) patients? A systematic review and meta-analysis.

BACKGROUND: Anticoagulation is important for extracorporeal membrane oxygenation (ECMO). Heparin is widely used; however, in some cases, it is not suitable for patients. Bivalirudin has been recently proposed for ECMO patients, and there is no evidence regarding its effectiveness and safety. OBJECTIVE: We aimed to systematically review the effectiveness and safety of bivalirudin in ECMO patients. STUDY DESIGN AND METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE were searched to find relevant research on the use of bivalirudin versus heparin for anticoagulation in ECMO patients. Outcomes included in-hospital mortality, ECMO duration, major bleeding events, thrombosis events and circuit intervention events. Types of studies included randomized control trials (RCTs), cohort studies, and case-control studies. Case reports, studies lacking comparison with heparin, and where patients transitioned between heparin and bivalirudin, were excluded. Publication bias was evaluated when the number of included studies was more than ten. Sensitivity analysis was performed to examine the stability of the results. RESULTS: Ten articles were selected, and nine articles were included in the meta-analysis. The results of the meta-analysis showed hospital mortality [OR = 0.65, 95%CI (0.44, 0.95), P = 0.03] and thrombosis events decreased (OR = 0.55, 95%CI [0.37, 0.83], P = 0.004) in bivalirudin group compared with heparin in adult patients. Major bleeding events (OR = 0.66, 95%CI [0.17, 2.55], P = 0.55), ECMO duration (MD = 18.92, 95%CI [-29.33, 67.17], P = 0.44) and circuit intervention events (OR = 1.67, 95%CI [0.54, 5.18], P = 0.37) in the bivalirudin group was not statistically significant compared with the heparin group. CONCLUSION: Bivalirudin may provide survival benefits and reduce thrombosis in adult patients on ECMO compared with heparin. There is no difference in treating major bleeding events between bivalirudin and heparin group. However, because all included studies were retrospective observational studies, the evidence level of this systematic review is low and heterogeneity could not be avoided. More high-quality clinical studies are urgently needed to confirm these benefits.

Evaluating machine learning models for sepsis prediction: A systematic review of methodologies.

Studies for sepsis prediction using machine learning are developing rapidly in medical science recently. In this review, we propose a set of new evaluation criteria and reporting standards to assess 21 qualified machine learning models for quality analysis based on PRISMA. Our assessment shows that (1.) the definition of sepsis is not consistent among the studies; (2.) data sources and data preprocessing methods, machine learning models, feature engineering, and inclusion types vary widely among the studies; (3.) the closer to the onset of sepsis, the higher the value of AUROC is; (4.) the improvement in AUROC is primarily due to using machine learning as a feature engineering tool; (5.) deep neural networks coupled with Sepsis-3 diagnostic criteria tend to yield better results on the time series data collected from patients with sepsis. The new evaluation criteria and reporting standards will facilitate the development of improved machine learning models for clinical applications.

Efficacy of intravenous vitamin C intervention for septic patients: A systematic review and meta-analysis based on randomized controlled trials.

BACKGROUND: The role of vitamin C in sepsis is still controversial, we aimed to systematically review the efficacy of intravenous vitamin C supplementation in the treatment of sepsis. METHODS: MEDLINE, EmBase, Web of Science, WanFang Data and CNKI were comprehensively searched to collect randomized controlled trails (RCTs) of vitamin C supplementation for patients with sepsis or sepsis shock from January 2000 to March 2021. Two researchers independently screened the literature, extracted the data and accessed the risk of bias in the included studies; meta-analysis was then performed by using Revman 5.4 software. RESULTS: A total of 10 RCTs involving 1400 participants were included. The results of meta-analysis showed that intravenous vitamin C supplementation can improve SOFA (ΔSOFA) within 72 h [RR = 1.32,95% CI(0.80,1.85), P < 0.0001] of septic patients. There were no difference on short term mortality (28-30d)[RR = 0.83,95% CI(0.65,1.05), P = 0.11], long term mortality (90d) [RR = 1.16,95% CI(0.82,1.66), P = 0.40], hospital LOS[RR = 0.15,95% CI(-0.73,1.03), P = 0.55], ventilator-free days[RR = 0.09,95% CI(-0.24,0.42), P = 0.60], ICU-LOS[RR = 0.22,95% CI(-0.13,0.57), P = 0.22], between two groups. The results of Subgroup analysis showed that intravenous vitamin C alone can reduce the risk of short term mortality (28-30d) [RR = 0.61,95% CI(0.47,0.79), P = 0.0002]of sepsis patients. CONCLUSION: Based on current RCTs, our work indicated that mono-intravenous vitamin C therapy may reduce short-term mortality of sepsis patients, and it may protect organ functions. Due to the limitation of the quantity and quality of included studies, the above conclusions need to be verified by more large scale and high quality randomized control trials.

Investigation and Analysis of Antibiotics Management in Hospitals of Anhui Province at Different Levels / 中国药房

OBJECTIVE:To provide reference for promoting the management of antibiotics in the hospitals. METHODS:Each 3 hospitals from county second grade class A general hospitals,municipal third grade class A general hospitals and provincial third grade hospitals(including 2 third grade class A general hospitals and one third grade special hospital)in Anhui province were select-ed and respectively included into group A,B,and C. By on-site survey mode,questionnaires were used to investigate and score the situation of antibiotics management in hospitals of 3 groups,and then analyzed statistically. RESULTS:Scoring rate (SR) of overall situation on antibiotics management were 65.33%,89.34% and 86.67% in group A,B and C respectively;group A was statistically significantly lower than group B and C (P0.05). SR of development indicator of antibiotics management were 58.33%,88.90% and 86.10%,respectively in group A,B and C;group A was significantly lower than group B and C (P<0.001). SR of information construction indicator of antibiotics management were 50.00%,83.33% and 77.79% respectively in group A,B and C;group A was significantly lower than group B and C (P≤0.001). SR of information construction indicator of antibiotics management in 3 groups were all signifi-cantly lower than SR of basic situation indicator(P<0.05). SR of development indicator of antibiotics management in group A and C were all significantly lower than SR of basic situation indicator(P<0.05). CONCLUSIONS:The antibiotics management of mu-nicipal third grade class A general hospital is equal to that of provincial third grade hospital,and that of county second grade class A general hospital is in relatively low level. Different levels of hospitals should further strengthen the related antibiotics manage-ment work and information construction,especially for county second grade class A general hospitals.

[Establishment and evaluation of a dynamic in vitro intestinal absorption model of lipid formulations].

A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.

Influence of silica on intestinal absorption of solid self-microemulsifying drug delivery systems / 药学学报

Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.

Optimization of novel self-microemulsifying mouth dissolving films by response surface methodology / 药学学报

This paper report the development of a new dosage form - self-microemulsifying mouth dissolving films, which can improve the oral bioavailability of water insoluble drugs and have good compliance. A three factor, three-level Box-Behnken design was used for optimizing formulation, investigated the effect of amounts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose on the weight, disintegration time, cumulative release of indomethacin after 2 min, microemulsified particle size and stretchability. Optimized self-microemulsifying mouth dissolving films could fast disintegrate in (17.09 +/- 0.72) s; obtain microemulsified particle size at (28.81 +/- 3.26) nm; and release in vitro at 2 min to (66.18 +/- 1.94)%. Self-microemulsifying mouth dissolving films with broad application prospects have good compliance, strong tensile and can be released rapidly in the mouth through fast self-microemulsifying.

Influence of silica on intestinal absorption of solid self-microemulsifying drug delivery systems / 药学学报

Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.

Optimization of novel self-microemulsifying mouth dissolving films by response surface methodology / 药学学报

This paper report the development of a new dosage form - self-microemulsifying mouth dissolving films, which can improve the oral bioavailability of water insoluble drugs and have good compliance. A three factor, three-level Box-Behnken design was used for optimizing formulation, investigated the effect of amounts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose on the weight, disintegration time, cumulative release of indomethacin after 2 min, microemulsified particle size and stretchability. Optimized self-microemulsifying mouth dissolving films could fast disintegrate in (17.09 +/- 0.72) s; obtain microemulsified particle size at (28.81 +/- 3.26) nm; and release in vitro at 2 min to (66.18 +/- 1.94)%. Self-microemulsifying mouth dissolving films with broad application prospects have good compliance, strong tensile and can be released rapidly in the mouth through fast self-microemulsifying.

Use of an in vitro lipolysis model to evaluate type I lipid formulations / 药学学报

The distribution fate and solubilization behavior of indomethacin through the intestinal tract were investigated with in vitro lipolysis model, by comparing the Capmul MCM and Labrafil M 1944 CS type I lipid formulations. The results showed that the more favorable solubilization was in the aqueous digestion phase from each lipid formulations for indomethacin. The lipolysis rate and extent were decided with chemical constitution of the lipid excipients, which meant that less indomethacin was transferred from the long chain polar oil lipid solution into the aqueous digestion phase. Increasing the concentration of indomethacin in the lipid formualitons from a solution to a suspension led to a linear increase in the concentration of indomethacin attained in the aqueous digestion phase from lipid formulations. This study also implied that adverse effects of the lipolysis rate and extent on drug absorption were could be taken into consideration when screening lipid formulations. Lipid suspensions likely had better enhancement of drug absorption. Last, this study demonstrated that a potential basis for optimizing and assessing type I lipid formulations and also researching in vivo-in vitro correlations of lipid formulations were provided by an in vitro lipolysis model.

Use of an in vitro lipolysis model to evaluate type I lipid formulations / 药学学报

The distribution fate and solubilization behavior of indomethacin through the intestinal tract were investigated with in vitro lipolysis model, by comparing the Capmul MCM and Labrafil M 1944 CS type I lipid formulations. The results showed that the more favorable solubilization was in the aqueous digestion phase from each lipid formulations for indomethacin. The lipolysis rate and extent were decided with chemical constitution of the lipid excipients, which meant that less indomethacin was transferred from the long chain polar oil lipid solution into the aqueous digestion phase. Increasing the concentration of indomethacin in the lipid formualitons from a solution to a suspension led to a linear increase in the concentration of indomethacin attained in the aqueous digestion phase from lipid formulations. This study also implied that adverse effects of the lipolysis rate and extent on drug absorption were could be taken into consideration when screening lipid formulations. Lipid suspensions likely had better enhancement of drug absorption. Last, this study demonstrated that a potential basis for optimizing and assessing type I lipid formulations and also researching in vivo-in vitro correlations of lipid formulations were provided by an in vitro lipolysis model.