Severe cerebral edema induced by watershed shift after bypass in a patient with chronic steno-occlusive disease: a case report and short literature review.

BACKGROUND: Carotid occlusive disease is a type of progressive disease resulting in ischemic stroke. Extracranial-intracranial bypass surgery represents a valid therapeutic option when medical treatment does not make effects. The appearance of cerebral edema following bypass is common during acute stage. Additionally, there are many causes of mild cerebral edema, such as hemodynamic changes, venous congestion and others. However, severe edema involving large brain tissue, which presents as reversible aphasia and hemiplegia, remains to be elucidated. CASE PRESENTATION: A 55-year-old man was admitted to the neurosurgery department for repeated dizziness for over a year and sudden onset of syncope 1 month prior, and he was diagnosed with carotid occlusive disease. After surgical contraindications were excluded, dual bypass and encephalo-duro-myo-synangiosis were performed. Although blood pressure and fluid management were strictly under control promptly after surgery, massive cerebral edema involving the left anterior cerebral artery and middle cerebral artery territories occurred from the 6th day after surgery. Additionally, no discernible cerebral infarction or hemorrhage occurred. Moreover, the cerebral blood flow of the middle cerebral artery displayed an early decrease followed by delayed elevation on the left side. Without restricting the spreading of cerebral edema, life-threatening cerebral herniation could develop at any time. Mannitol and furosemide were administered for impending cerebral herniation. The amelioration of symptoms was noticed on the 16th day after surgery. The patient felt relief on the 21st day after surgery. Digital subtraction angiography performed on the 180th day after surgery demonstrated the patency of dual anastomosed vessels, and the patient recovered without any permanent neurological deficit. CONCLUSION: Based on changes in cerebral blood flow and reversible symptoms, the "watershed shift" phenomenon could explain such a severe deficit. However, this deficit was not the same as the classical presentation of the "watershed shift", which involves a moderate amount of brain tissue and presents significant increases in cerebral blood flow. In addition to the "watershed shift", a swollen temporal muscle may also participate in the progression of focal edema.

Involvement of PML-I in reformation of PML nuclear bodies in acute promyelocytic leukemia cells by leptomycin B.

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation between chromosomes 15 and 17, t(15;17), resulting in the expression of PML-RARα fusion protein, which disrupts the normal PML nuclear bodies (PML-NBs) to micro-speckled pattern, leading to loss of their original functions. Moreover, reformation of PML-NBs in APL by arsenic is considered as one of the important step for APL treatment. Leptomycin B (LMB), a nuclear export inhibitor, is commonly used to inhibit the proteins exporting from the nucleus to the cytoplasm. In the present study, we found that LMB could induce the reformation of PML-NBs in leukemia NB4 cells as well as in APL blast cells from the patients, implying that nuclear shuttle proteins might be involved in the reformation of PML-NBs. Herein, we further found that LMB totally lost the ability to induce PML-NBs reformation when the endogenous PML gene was knocked out, indicating that endogenous PML protein is probably involved in the reformation of PML-NBs. More interestingly, among all PML isoforms (i.e., seven isoforms), reformation of PML-NBs was only observed when co-transfection of PML-RARα with PML-I after LMB treatment. Similarly, deletion of nuclear export signal (NES) of PML-I could also reform PML-NBs, suggesting that the protein level of endogenous PML-I in nucleus is important for the reformation of PML-NBs that interfered by PML-RARα fusion protein. Additionally, LMB has synergistic effect with iAsIII on enhancing PML-RARα fusion protein degradation, and it might provide new insight into APL treatment at clinical level in the near future.

Novel multimodal analgesia regimen improves post-TACE pain in patients with hepatocellular carcinoma.

BACKGROUD: Transarterial chemoembolization (TACE) is the primary palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it is often accompanied by postoperative pain which hinder patient recovery. This study was to examine whether preemptive parecoxib and sufentanil-based patient controlled analgesia (PCA) could improve the pain management in patients receiving TACE for inoperable HCC. METHODS: From June to December 2016, 84 HCC patients undergoing TACE procedure were enrolled. Because of the willingness of the individuals, it is difficult to randomize the patients to different groups. We matched the patients' age, gender and pain scores, and divided the patients into the multimodal group (n = 42) and control group (n = 42). Patients in the multimodal group received 40 mg of parecoxib, 30 min before TACE, followed by 48 h of sufentanil-based PCA. Patients in the control group received a routine analgesic regimen, i.e., 5 mg of dezocine during operation, and 100 mg of tramadol or equivalent intravenous opioid according to patient's complaints and pain intensity. Postoperative pain intensity, percentage of patients as per the pain category, adverse reaction, duration of hospital stay, cost-effectiveness, and patient's satisfaction were all taken into consideration when evaluated. RESULTS: Compared to the control group, the visual analogue scale scores for pain intensity was significantly lower at 2, 4, 6, and 12 h (all P < 0.05) in the multimodal group and a noticeably lower prevalence of post-operative nausea and vomiting in the multimodal group (31.0% vs. 59.5%). Patient's satisfaction in the multimodal group was also significantly higher than that in the control group (95.2% vs. 69.0%). No significant difference was observed in the duration of hospital stay between the two groups. CONCLUSION: Preemptive parecoxib and sufentanil-based multimodal analgesia regime is a safe, efficient and cost-effective regimen for postoperative pain control in HCC patients undergoing TACE.

Epirubicin-loaded superparamagnetic iron-oxide nanoparticles for transdermal delivery: cancer therapy by circumventing the skin barrier.

The transdermal administration of chemotherapeutic agents is a persistent challenge for tumor treatments. A model anticancer agent, epirubicin (EPI), is attached to functionalized superparamagnetic iron-oxide nanoparticles (SPION). The covalent modification of the SPION results in EPI-SPION, a potential drug delivery vector that uses magnetism for the targeted transdermal chemotherapy of skin tumors. The spherical EPI-SPION composite exhibits excellent magnetic responsiveness with a saturation magnetization intensity of 77.8 emu g(-1) . They feature specific pH-sensitive drug release, targeting the acidic microenvironment typical in common tumor tissues or endosomes/lysosomes. Cellular uptake studies using human keratinocyte HaCaT cells and melanoma WM266 cells demonstrate that SPION have good biocompatibility. After conjugation with EPI, the nanoparticles can inhibit WM266 cell proliferation; its inhibitory effect on tumor proliferation is determined to be dose-dependent. In vitro transdermal studies demonstrate that the EPI-SPION composites can penetrate deep inside the skin driven by an external magnetic field. The magnetic-field-assisted SPION transdermal vector can circumvent the stratum corneum via follicular pathways. The study indicates the potential of a SPION-based vector for feasible transdermal therapy of skin cancer.

Effect of statins on the mortality and mechanical ventilation duration of acute lung injury patients: a meta-analysis of five randomized controlled trials.

BACKGROUND: Statins have been reported to exert anti-inflammatory effects, but the association between statins and acute lung injury (ALI) remains controversial. Thus, we performed a meta-analysis of all published randomized controlled trials (RCTs) aiming to summarize and evaluate the current evidence about the potential use of statins in ALI patients. METHOD: We searched for articles that focused on the association between statins and ALI-related outcomes through electronic databases until December 10th, 2014. The inclusion of articles, quality appraisal of included studies, and data extraction were performed by two investigators. Eligible articles were analyzed by Review manager 5.2 and STATA 12.0 software. RESULTS: Data from 1,778 patients in five randomized controlled clinical trials were analyzed. No differences in intensive care unit (ICU) mortality (RR=0.88, 95% CI=0.63-1.22, p=0.44), hospital mortality (RR=1.00, 95% CI=0.85-1.17, p=0.97) and mechanical ventilation duration (MD=-0.40, 95% CI=-1.52-0.71, p=0.48) were observed between the experimental and control groups. CONCLUSIONS: According to large and high-quality published clinical trials as also summarized by the present meta-analysis, there is insufficient evidence to support the use of statins in ALI patients.

Efficacy and safety of thrombolysis for stroke of unknown onset time: a meta-analysis.

Current stroke treatment guidelines exclude unknown onset stroke (UOS) patients from thrombolytic therapy even though several studies have reported significant treatment efficacy and safety. We performed a meta-analysis of relevant studies retrieved by systematic searches of the PubMed, Embase, and Cochrane databases up to December 31, 2013. Dichotomized modified Rankin Scale (mRS) scores 0-1 at 90 days, mRS 0-2 at 90 days, overall mortality, and symptomatic intracranial hemorrhage (sICH) incidence were collected as primary outcome measures. Fixed effects meta-analytical models were used, and between-study heterogeneity was assessed. Eleven studies encompassing 1,832 patients were included. In case-control studies of UOS patients, thrombolysis was associated with a significant increase in the proportion of patients with mRS scores of 0-1 (OR 2.37; 95% CI 1.20-4.69; P = 0.013) and 0-2 (OR 2.03; 95% CI 1.26-3.30; P = 0.004) without increased mortality or sICH incidence. In studies comparing thrombolysis-treated UOS to thrombolysis-treated known onset stroke, however, fewer UOS patients had mRS scores of 0-1 (OR 0.70; 95% CI 0.51-0.97; P = 0.033) with no change in mortality, sICH incidence, or patients with mRS of 0-2. Subgroup analysis based on imaging criteria and time window of thrombolysis indicated that UOS patients treated within 3 h after first found abnormal and those with early ischemic changes restricted to <1/3 of the middle cerebral artery territory gained more benefit from thrombolysis treatment than the whole UOS population. Randomized controlled trials are warranted to confirm the efficacy of thrombolysis in this UOS subgroup.

Impact of pharmacist antimicrobial dosing adjustments in septic patients on continuous renal replacement therapy in an intensive care unit.

BACKGROUND: Correct dosing of antimicrobial drugs in septic patients receiving continuous renal replacement therapy (CRRT) is complex. This study aimed to evaluate the effects of dosing adjustments performed by pharmacists on the length of intensive care unit (ICU) stay, ICU cost, and antimicrobial adverse drug events (ADEs). METHODS: A single-center, 2-phase (pre-/post-intervention) study was performed in an ICU of a university-affiliated hospital. Septic patients receiving CRRT in the post-intervention phase received a specialized antimicrobial dosing service from critical care pharmacists, whereas patients in the pre-intervention phase received routine medical care without involving pharmacists. The 2 phases were compared to evaluate the outcomes of pharmacist interventions. RESULTS: Pharmacists made 183 antimicrobial dosing adjustment recommendations for septic patients receiving CRRT. Changes in CRRT-related variables (116, 63.4%) were the most common risk factors for dosing errors, and ß-lactams (101, 55.2%) were the antimicrobials most commonly associated with dosing errors. Dosing adjustments were related to a reduced length of ICU stay from 10.7 ± 11.1 days to 7.7 ± 8.3 days (p = 0.037) in the intervention group, and to cost savings of $3525 (13,463 ± 12,045 vs. 9938 ± 8811, p = 0.038) per septic patient receiving CRRT in the ICU. Suspected antimicrobial adverse drug events in the intervention group were significantly fewer than in the pre-intervention group (19 events vs. 8 events, p = 0.048). CONCLUSIONS: The involvement of pharmacists in antimicrobial dosing adjustments in septic patients receiving CRRT is associated with a reduced length of ICU stay, lower ICU costs, and fewer ADEs. Hospitals may consider employing clinical pharmacists in ICUs.

Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage.

Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1ß, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

Dimethyl fumarate attenuates lipopolysaccharide-induced mitochondrial injury by activating Nrf2 pathway in cardiomyocytes.

AIMS: To determine whether dimethyl fumarate (DMF) can protect against lipopolysaccharide (LPS) -induced myocardial injury. MAIN METHODS: H9c2 cells pretreated with or without DMF were stimulated with LPS. Cell viability and apoptosis were evaluated. Nrf2 and HO-1 expression were detected using Western blotting. Mitochondrial morphology, mitochondrial superoxide production were observed using confocal microscope. Mitochondrial respiration function was measured using Seahorse bioanalyzer. KEY FINDINGS: (1) The cell viability decreased, LDH release and apoptosis increased in LPS- challenged H9c2 cells. DMF pretreatment brought a higher cell viability, and a lower LDH leakage and apoptosis than those of LPS group (P < 0.01). (2) DMF pretreatment resulted in an increased Nrf2 and HO-1 expression, and enhanced nuclear Nrf2 level in LPS-challenged cells (P < 0.01). (3) Nrf2-siRNA could inhibit DMF-induced enhancement of HO-1 expression and cell viability, and partly abolish DMF-induced reduction of LDH leakage and apoptosis. (4) ERK1/2 inhibitor PD98059 could not only prevent the DMF-induced enhancement of nuclear Nrf2 and HO-1, but also inhibit DMF-induced increase in cell viability. (5) Compared with LPS-challenged cells, DMF pretreatment caused a lower production of mitochondrial superoxide and a higher mitochondrial membrane potential, which could be abolished by Nrf2-siRNA. (6) DMF could attenuate LPS-induced mitochondrial fragmentation and improve mitochondrial respiration function by enhancement of the oxygen consumption rate of basal respiration and ATP production in LPS-challenged cells (P < 0.01). SIGNIFICANCE: DMF protects cardiomyocytes against LPS-induced damage. ERK1/2-dependent activation of Nrf2/HO-1 pathway is responsible for DMF-induced cardioprotection via reduction of oxidative stress, improvement of mitochondrial morphology and energy metabolism.

Enhancement of oral bioavailability of salmon calcitonin through chitosan-modified, dual drug-loaded nanoparticles.

Because numerous challenges limit the effective oral delivery of protein and peptide drugs, we developed promising chitosan (CS)-modified, dual drug-loaded nanoparticles (NPs) simultaneously containing salmon calcitonin (sCT) and puerarin (PR) (CS-sCT/PR-NPs), and to explore the potential of PR as a protease inhibitor. This oral delivery system showed efficient encapsulation of sCT (75.7%) and PR (50.9%), protection of encapsulated sCT and PR from premature release in simulated gastric fluid (SGJ, pH 1.2), and sustained-release behavior in phosphate buffer saline (PBS, pH 7.4). CS-sCT/PR-NPs were capable of sequential drug-release in which PR was partially released prior to sCT, allowing PR to play a role of enzyme inhibitor before sCT release. Compared with CS-sCT-NPs, CS-sCT/PR-NPs were more stable in simulated intestinal fluid containing pancreatinum. The internalization of fluorescein isothiocyanate-labeled sCT (FITC-sCT) by Caco-2 cells increased when incorporated into NPs compared with free sCT. In vivo, the oral absolute bioavailability of sCT in CS-sCT/PR-NPs was 12.52 ±â€¯1.83%, approximately 1.74-fold higher than that of the NPs not co-loaded with PR. In conclusion, the CS-based NPs and introduction of PR as a protease inhibitor improved the oral bioavailability of sCT and had potential to be developed as an oral delivery system of peptide drug.

Irreversibility of arsenic trioxide induced PML/RARα fusion protein solubility changes.

Arsenic trioxide (As2O3) is one of the most effective drugs for the treatment of acute promyelocytic leukemia (APL), and induces the degradation of chimeric oncoprotein PML/RARα (P/R) and APL cell differentiation. Recent evidence has suggested that P/R fusion protein degradation by arsenic occurs through two steps, namely, rapid solubility change/shift of the P/R fusion protein following arsenic treatment (i.e., transfer of P/R protein from the soluble fraction to the insoluble pellet fraction), and subsequent degradation of these insoluble proteins. However, there is little information regarding the reversibility of arsenic induced P/R fusion protein solubility change as well as protein degradation in the insoluble fraction after removing arsenic. In this study, we used APL cell line NB4 or P/R and PML over-expressed 293T cells as well as HeLa cells to reveal the solubility change of P/R and PML by arsenic exposure, and further determined the fate of these insoluble proteins after the removal of arsenic. Here, for the first time, we found that arsenic induced P/R or PML protein solubility change is an irreversible process. Once arsenic induces a P/R or PML protein solubility change, these insoluble proteins could be degraded by the proteasomal pathway even without continuous arsenic treatment. However, PML and P/R proteins can be newly synthesized after the removal of arsenic, suggesting that great caution should be taken in the clinical therapy of APL patients before ending arsenic treatment.

Integrity of zinc finger motifs in PML protein is necessary for inducing its degradation by antimony.

Antimony (Sb) belongs to the same group as arsenic (As) in the periodic table, and both share similar characteristics. However, Sb2O3 (SbIII) has no methylation capacity, unlike arsenic trioxide (As2O3). In the present study, we determined the effect of SbIII on NB4 cells and found that antimony could induce PML-RARα fusion protein degradation, reorganization of PML-NBs, and NB4 cell differentiation with low cytotoxicity. On the other hand, zinc finger motifs in PML protein are considered to be a key target binding site for arsenic-induced PML-RARα protein degradation. Interestingly, antimony and arsenic lost their ability to degrade PML-RARα fusion protein in NB4 cells following pretreatment with phenanthroline (i.e., chelator of zinc ions), indicating that the integrity of zinc finger motifs in PML-RARα fusion protein is a fundamental condition for inducing the protein's degradation by antimony and arsenic. Moreover, we found that SbIII could not induce mutant PML (e.g., A126V and L218P) solubility change and degradation, similar to As2O3. In contrast, we found that the organic antimony compound phenylstibine oxide (PSO) could induce mutant PML protein degradation. In conclusion, our results indicate that SbIII might also be a promising agent to treat acute promyelocytic leukemia, in the same manner as As2O3.

Tocopherol polyethylene glycol succinate-modified hollow silver nanoparticles for combating bacteria-resistance.

Multiple drug resistance and the increase in the appearance of superbugs together with the exceedingly scant development of new potent antibiotic drugs pose an urgent global medical threat and imminent public security crisis. In the present study, we fabricated well-dispersed tocopherol polyethylene glycol succinate (TPGS)-capped silver nanoparticles (AgNPs) of about 10 nm in size. The hollow structure of the TPGS-capped AgNPs (TPGS/AgNPs) was confirmed and applied to load antibiotics. The TPGS/AgNPs proved to be able to cross the bacterial cell wall and penetrate into bacteria, thereby delivering more of the antibiotic to the interior of bacteria and thus enhancing the in vitro antibacterial effect of the antibiotic, even overcoming the drug-resistance in drug-resistant E. coli and Acinetobacter baumannii. It was found that the TPGS modification in the TPGS/AgNPs could decrease the activity of the efflux pumps AdeABC and AdeIJK in drug-resistant Acinetobacter baumannii via inhibiting the efflux pump genes adeB and adeJ, thus increasing the accumulation of the delivered antibiotic and overcoming the drug-resistance. Tigecycline delivered by TPGS/AgNPs could effectively antagonize drug-resistance in an acute peritonitis model mice, thereby increasing the survival rate and alleviating the inflammatory response. TPGS/AgNPs were developed as a novel and effective antibiotic delivery system and TPGS was demonstrated to have great potential as a pharmaceutical excipient for use in drug-resistant infection therapy.

Effectiveness of the Chronic Care Model in Type 2 Diabetes Management in a Community Health Service Center in China: A Group Randomized Experimental Study.

OBJECTIVE: The Chronic Care Model, based on core elements of team-centered care in chronic diseases, has widely been accepted. This study was aimed at evaluating the effectiveness of the Chronic Care Model in type 2 diabetes management. METHODS: A group randomized experimental study was conducted. Twelve communities of the Zhaohui Community Health Service Center in Hangzhou, China, were randomly assigned into an intervention group (n = 6) receiving the Chronic Care Model-based intervention and a control group (n = 6) receiving conventional care. A total of three hundred patients, twenty-five for each community, aged ≥18 years with type 2 diabetes for at least 1-year duration, were recruited. Data of health behaviors, clinical outcomes, and health-related quality of life (Short-Form 36-item questionnaire) were collected before and after a 9-month intervention and analyzed using descriptive statistics, t-test, chi-square test, binary logistic regression, and linear mixed regression. A total of 258 patients (134 in intervention and 124 in control) who completed the baseline and follow-up evaluations and the entire intervention were included in the final analyses. RESULTS: Health behaviors such as drinking habit (OR = 0.07, 95% CI: 0.01, 0.75), physical activity (OR = 2.92, 95% CI: 1.18, 7.25), and diet habit (OR = 4.30, 95% CI: 1.49, 12.43) were improved. The intervention group had a remarkable reduction in glycated hemoglobin (from 7.17% to 6.60%, P < 0.001). The quality of life score changes of the role limitation due to physical problems (mean = 9.97, 95% CI: 3.33, 16.60), social functioning (mean = 6.50, 95% CI: 2.37, 10.64), role limitation due to emotional problems (mean = 8.06, 95% CI: 2.15, 13.96), and physical component summary score (mean = 3.31, 95% CI: 1.22, 5.39) were improved in the intervention group compared to the control group. CONCLUSION: The Chronic Care Model-based intervention helped improve some health behaviors, clinical outcomes, and quality of life of type 2 diabetes patients in China in a short term.

Effective targeted therapy for drug-resistant infection by ICAM-1 antibody-conjugated TPGS modified ß-Ga2O3:Cr3+ nanoparticles.

The prevalence of antibiotic resistance and lack of alternative drugs have posed an increasing threat to public health. Here, we prepared ß-Ga2O3:Cr3+ nanoparticles modified with ICAM1-antibody-conjugated TPGS (I-TPGS/Ga2O3) as a novel antibiotic carrier for the treatment of drug-resistant infections. Methods: I-TPGS/Ga2O3 were firstly characterized by measuring particle size, morphology, crystal structure, drug loading capacity, and in vitro drug release behaviors. The in vitro antibacterial activities of I-TPGS/Ga2O3/TIG were evaluated using standard and drug-resistant bacteria. The internalization of I-TPGS/Ga2O3 was observed by fluorescence confocal imaging, and the expression levels of the efflux pump genes of TRKP were analyzed by real-time RT-PCR. In vitro cellular uptake and in vivo biodistribution study were performed to investigate the targeting specificity of I-TPGS/Ga2O3 using HUEVC and acute pneumonia mice, respectively. The in vivo anti-infective efficacy and biosafety of I-TPGS/Ga2O3/TIG were finally evaluated using acute pneumonia mice. Results: It was found that TPGS could down-regulate the over-expression of the efflux pump genes, thus decreasing the efflux pump activity of bacteria. I-TPGS/Ga2O3 with small particle size and uniform distribution facilitated their internalization in bacteria, and the TPGS modification resulted in a significant reduction in the efflux of loaded antibiotics. These properties rendered the encapsulated tigecycline to exert a stronger antibacterial activity both in vitro and in vivo. Additionally, targeted delivery of I-TPGS/Ga2O3 mediated by ICAM1 antibodies contributed to a safe and effective therapy. Conclusion: It is of great value to apply I-TPGS/Ga2O3 as a novel and effective antibiotic delivery system for the treatment of drug-resistant infections.

Off-label prescriptions in intensive care unit: the Chinese experience.

BACKGROUND AND PURPOSE: Off-label prescriptions for critically ill patients pose several ethical and legal dilemmas for intensive care unit (ICU) clinicians. Yet, few data are available on the prevalence of this practice in critical care environment in China. This nationwide survey was performed to evaluate the conditions of off-label prescriptions in ICU within China. METHODS: The survey was performed at the scene of the national ICU conferences in 2016. ICU clinicians attending the congress from 23 provinces across the country were invited. The features of the clinician's off-label prescription practice were investigated and analyzed. RESULTS: A total of 1,318 ICU clinicians completed the anonymous questionnaire. Of these, 76.2% prescribed off-label in clinical practice. A significant difference (p<0.005) was observed between the ICU clinicians with different years of working experience and professional levels, respectively. For 69.2% of the ICU clinicians, the proportion of off-label prescriptions did not exceed 10%, while for fewer prescribers (2.9%), the proportion exceeded 25%. The main reasons for off-label prescriptions were life-threatening or terminal medical condition without other substitutes (48.3%), new treatments with strong scientific evidence (38.1%), and limited indications of drug labels (22.7%). Of the ICU clinicians surveyed, 87.5% worried about causing medical disputes, and 26.5% encountered medical disputes caused by off-label prescriptions. The risk of medical disputes was positively associated with the proportion of off-label prescriptions (p=0.009). Among the ICU clinicians, 92.5% expected the national policy for off-label prescriptions in future. Gastrointestinal and respiratory drug classes were noted to have the highest prevalence of off-label use. CONCLUSION: Off-label prescriptions have been commonly practiced by ICU clinicians in China. A concerted effort should be made to develop a practical and explicit guidance for off-label prescriptions.

Effectiveness of continuous improvement by a clinical pharmacist-led guidance team on the prophylactic antibiotics usage rationality in intervention procedure at a Chinese tertiary teaching hospital.

BACKGROUND: Irrational prophylactic antibiotics usage (PAU) during intervention procedures is common in China. A clinical pharmacist-led guidance team (CPGT) was established and participated in medical teams to advise on the rational usage of antibiotics. OBJECTIVES: The objective of this study was to assess the effectiveness of CPGT intervention for the rationality of PAU during intervention procedures. METHOD: This was a retrospective cross-sectional study with three stages at a Chinese tertiary teaching hospital. Patients who received some specific intervention procedures in the first quarter of 2015 were enrolled as the preintervention group, while those who received the procedures in the second and third quarters of 2015 were enrolled as the postintervention group. CPGT established the criteria for the PAU and conducted the intervention. The pre- and postintervention groups were then compared to evaluate the effectiveness of CPGTs' sustained interventions. RESULTS: A total of 651 patients were enrolled, with 200 patients in the preintervention group, while 233 patients and 218 patients in the first- and second-intervention groups, respectively. With the implementation of CPGTs continuous intervention, the rationality of PAU was significantly improved, including the timing (91.98% vs 97.74%, P=0.015), duration (82.72% vs 98.31%, P<0.0001), and choice (81.48% vs 93.22%, P=0.001) of antibiotics administered during perioperative period. Moreover, the cost of total (US$34.89±80.96 vs US$9.81±26.31, P=0.025) and inappropriate PAU (US$28.75±73.27 vs US$3.57±14.62, P<0.0001) per patient was significantly reduced. CONCLUSION: CPGTs' continuous intervention significantly improved the rationality of PAU during intervention procedures, with a significant reduction in antibiotic cost.

High-performance liquid chromatography-mass spectrometric analysis of ramipril and its active metabolite ramiprilat in human serum: application to a pharmacokinetic study in the Chinese volunteers.

This study presents a rapid, specific and sensitive LC-MS/MS assay for the determination of ramipril and ramiprilat in human serum using enalapril as an internal standard (IS). A Waters Atlantis C18 column (2.1 mm x 100 mm, 3 microm) and a mobile phase consisting of 0.1% formic acid-methanol (25:75, v/v) were used for separation. The analysis was performed by the selected reaction monitoring (SRM) method, and the peak areas of the m/z 417.3-->234.3 and m/z 389.3-->206.2 transition for ramipril and ramiprilat, respectively, were measured versus that of the m/z 377.3-->234.2 for IS to generate the standard curves. The assay linearities of ramipril and ramiprilat were confirmed over the range 0.10-100 ngml(-1) and 0.25-100 ngml(-1), respectively, and limits of quantitation for them were 0.10 and 0.25 ngml(-1), respectively. The linear ranges correspond well with the serum concentrations of the analytes obtained in clinical pharmacokinetic studies. Intraday and interday relative standard deviations of ramipril and ramiprilat were 2.8-6.4% and 4.3-4.6%, 4.4-6.7% and 3.5-4.7%, respectively. The recoveries of ramipril and ramiprilat from serum were in the range of 81.0-98.2%. The developed LC-MS procedures were applied for the determination of the pharmacokinetic parameters of ramipril and ramiprilat following a single oral administration of 10mg ramipril tablets in 18 Chinese healthy male volunteers.

Pharmacokinetics of mycophenolic acid in Chinese kidney transplant patients.

To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients, the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chromatography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharmacokinetic parameters. The mean C(max), t(max), and AUC((0-12))were (21.88+/-10.52) microg/ml, (1.20+/-0.95) h, and (52.546+/-13.215) microg.h/ml, respectively. The level of AUC((0-12)) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC((0-12)) showed statistically significant difference according to the patient's gender.

[Study on determination of desloratadine in human serum and its pharmacokinetics by HPLC/MS].

OBJECTIVE: To study the determination of desloratadine in human serum and its pharmacokinetics in healthy volunteers. METHODS: A single oral dose of 10 mg desloratadine was given to 18 healthy volunteers. The serum concentrations of desloratadine were determined by HPLC-MS assay. The pharmacokinetics parameters of desloratadine tablets were calculated with program 3P97. RESULT: The main pharmacokinetics parameters of desloratadine tablets were as followsút(max)(1.611 +/-0.366)h, C(max) (4.455+/-1.990)microg x L(-1), AUC(0-t) (58.50+/-21.34)microg x L(-1) x h(-1), AUC(0-infinity) (60.59+/-22.32)microg x L(-1) x h(-1), t(1/2(ke)) (20.303+/-5.833)h, Ke (0.0372+/-0.0116)h(-1) and CL(0.1838+/-0.0563)L x h(-1). CONCLUSION: Desloratadine tablet is absorbed quicker in the 18 healthy volunteers than the reports and its peak blood concentration reached at 1.5 h after oral administration with t(1/2) 20 h.