Piperine as a Potential Nutraceutical Agent for Managing Diabetes and Its Complications: A Literature Review.

The global prevalence of diabetes and its related complications has increased drastically and is currently a worldwide health challenge. There is still an urgent need for safe and effective natural products and supplements as alternative and/or adjunctive therapeutic interventions. Nowadays, people pay more and more attention to the nutritional and medicinal value of food ingredients. As one of the most widely employed spices in cooking, pepper also has novel medicinal values attributed to its main component, piperine (Pip). Pip is an amide alkaloid with pleiotropic properties such as anti-inflammatory, antioxidant, anti-cancer, and other related activities. Recently, Pip has received increasing scientific attention due to its antidiabetic and related complication properties. However, the values of existing studies are limited due to being scattered and unsystematic. The present study reviewed the therapeutic potential and possible mechanisms of Pip in diabetes and related complications, with the aim of providing promising candidates for the development of novel and effective alternative and/or adjunctive nutraceutical agents for the management of diabetes.

Resistin targets TAZ to promote osteogenic differentiation through PI3K/AKT/mTOR pathway.

Osteogenic differentiation (OD) of bone marrow mesenchymal stem cells (BMSCs) contributes significantly to the regeneration of bone defects. Resistin, an adipose tissue-specific secretory factor, has been shown to involve many different functions, including metabolism, inflammation, cancer, and bone remodeling. However, the effects and mechanisms of resistin on OD of BMSCs remain unclear. Herein, we demonstrated that resistin was highly expressed in BMSCs with OD. Upregulation of resistin contributed to the progression of OD of BMSCs by activating PI3K/AKT/mTOR signaling pathway. In addition, resistin facilitated OD by targeting transcriptional co-activator with PDZ-binding motif (TAZ). In a rat femoral condyle bone defect model, local injection of resistin significantly promoted bone repair and improved bone formation. This work contributes to better understanding the mechanism of resistin directly involved in the OD and might provide a new therapeutic strategy for bone defect regeneration.

Low albumin-to-fibrinogen ratio predicts adverse clinical outcomes after primary total joint arthroplasty: A retrospective observational investigation.

Nutritional markers for adverse clinical outcomes following total joint arthroplasty (TJA) remain controversial. This study attempted to explore the validity of the albumin-to-fibrinogen ratio (AFR) in nutritional assessment and assess its predictive value for adverse postoperative outcomes in patients receiving TJA. 2137 patients who underwent primary TJA between January 2016 and June 2021 were screened. We performed receiver operating characteristic curves and area under the curve (AUC) to assess predictive value and establish optimal thresholds. Multivariate regression models were then used to assess potential associations between AFR and adverse postoperative outcomes. AFR might predict postoperative deep surgical site infections (AUC = 0.699, P = .023). The optimal threshold for wound complications, determined by the Youden index, was 12.96. Compared with patients with reduced AFR, patients with high AFR exhibited an enhanced risk of adverse postoperative outcomes (adjusted OR: 4.010-8.832, all P < .05). Using multivariate Cox regression analysis, we further confirmed a higher risk of adverse postoperative outcomes in patients with low AFR (adjusted HR: 3.733-7.335, all P < .05). Reduced preoperative AFR markedly enhanced adverse postoperative outcomes. Hence, AFR may serve as a potential biomarker for nutritional assessment, and may predict postoperative wound complications following primary TJA.

Cost-effectiveness of camrelizumab plus chemotherapy versus chemotherapy alone as first-line therapy in advanced or metastatic esophageal squamous cell carcinoma.

OBJECTIVE: Camrelizumab combination therapy for advanced or metastatic esophageal squamous cell carcinoma (ESCC) has considerable survival benefits. This study investigated the cost-effectiveness of camrelizumab combination therapy versus chemotherapy alone as a first-line treatment for patients with ESCC from the perspective of the Chinese healthcare system. METHODS: A three-state partitioned survival model was developed to estimate total costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) over a 20-year time horizon. Sensitivity and scenario analyses were also performed. RESULTS: Camrelizumab plus chemotherapy increased QALYs by 0.30 (0.43 LYs), with an incremental cost of $9,272. The ICERs for camrelizumab plus chemotherapy vs chemotherapy alone was $31,062/QALY ($21,599/LY), and the INHB was 0.05 QALY at the cost-effective threshold of $37,653/QALY (3 times China's GDP per capita). One-way sensitivity analyses showed that the ICER was the most sensitive to utility values in the PFS state. Probabilistic sensitivity analyses suggested that camrelizumab combination therapy had a probability of 74.04% cost-effectiveness at a threshold of $37,653/QALY. Scenario analyses confirmed that the findings were robust. CONCLUSIONS: Camrelizumab combination therapy is likely to have a cost-effectiveness advantage over chemotherapy alone for previously untreated advanced or metastatic ESCC in China.

Effect of pharmacist intervention on antibiotic prophylaxis in orthopedic internal fixation: A retrospective study.

BACKGROUND: Despite the availability of guidelines and official policies, antibiotic prophylaxis in clean surgery remains suboptimal. OBJECTIVE: The aim of this study was to evaluate the clinical effects and cost-effectiveness of pharmacist-led intervention in the perioperative anti-infection prophylaxis of patients undergoing orthopedic internal fixation. METHODS: We performed a retrospective analysis based on the medical records of internal fixation surgery in a tertiary hospital from July 2019 to June 2020. Data were divided into two groups based on whether a full-time pharmacist participated in the treatment. The research parameters included use of antibiotics, rationality of medication, postoperative complications, and related cost. To deal with selection bias, propensity score matching method was employed at a ratio of 1:1. Meanwhile, a cost-effectiveness analysis was used to evaluate the impact of pharmacist intervention on antibiotic prevention in internal fixation surgery. RESULTS: A total of 537 participants were included in this study. After matching, 236 patients were comparable in each group. During the pharmacist intervention period, less pharmacologic prophylaxis (96.6% vs 100.0%, p = 0.007) and shorter prophylaxis duration (1.60 vs 2.28 days, p < 0.001) were observed. The reasonable rate increased dramatically in usage and dosage (96.6% vs 83.9%, p < 0.001), timing of administration (94.5% vs 78.4%, p < 0.001) and medication duration (64.4% vs 37.7%, p < 0.001). In addition, pharmacist intervention yielded net economic benefits. A remarkable reduction was observed in average length of stay (10.43 vs 11.14 days, p = 0.012), drug cost ($610.57 vs $706.60, p = 0.001) and defined daily doses (2.31 vs 3.27, p < 0.001). The cost-effectiveness ratios, divided drug cost savings by cost of pharmacist time, were 28:1 for drug and 2:1 for antibiotics, respectively. CONCLUSION: Pharmacist-driven antibiotic stewardship for orthopedic internal fixation patients improved compliance with peri-procedure antibiotic prophylaxis, and reduced the cost and utilization of antibiotics. This helped to bring significant clinical and economic benefits.

Nutritional Risk Screening 2002 predicts surgical outcomes in 1532 patients undergoing total joint arthroplasty: A retrospective cohort study.

BACKGROUND: Limited information exists about the predictive effect of Nutritional Risk Screening (NRS) 2002 on orthopedic surgery. The aim of the present study is to explore the role of NRS 2002 in postoperative complications and resource utilization in patients with total joint arthroplasty (TJA). METHODS: We retrospectively collected the demographics and surgical results of nearly 2000 TJA patients admitted from 2016 to 2020 and assessed the differences in short- and long-term complications and resource utilization parameters. Multivariate linear, logistic regression, and subgroup analysis were subsequently used to control for potential confounders. Survival analysis was performed to further verify the cumulative incidence of postoperative complications. RESULTS: We identified 1532 patients receiving TJA, 8.7% of which were at nutrition risk (NRS 2002 score ≥3 out of 7). Preoperative nutrition risk was associated with an increased risk of systemic complications, incisional complications, surgical site infection (SSI), incisional SSI, periprosthetic joint infection, dislocation, and periprosthetic fracture after TJA (odds ratio [OR], 3.62-31.99; all P < 0.05). Preoperative nutrition risk was further associated with an increased risk of cardiac complications, respiratory complications, urinary complications, and arthroplasty-related reoperation (OR, 3.16-12.29; all P < 0.01). Moreover, preoperative nutrition risk was associated with increased costs and length of stay, and increased risk of unplanned intensive care unit admission, arthroplasty-related readmission, infection-related readmission, and SSI-related readmission. CONCLUSIONS: NRS 2002 is associated with an elevated risk of postoperative complications and increased resource utilization, following TJA. Thus, routine screening is recommended to identify nutrition risk statuses of patients undergoing elective TJA.

Targeting of non-apoptotic cancer cell death mechanisms by quercetin: Implications in cancer therapy.

The ultimate goal of cancer treatment is to kill cancer cells, based on the use of various therapeutic agents, such as chemotherapy, radiotherapy, or targeted therapy drugs. Most drugs exert their therapeutic effects on cancer by targeting apoptosis. However, alterations in apoptosis-related molecules and thus assisting cells to evade death, eventually lead to tumor cell resistance to therapeutic drugs. The increased incidence of non-apoptotic cell death modes such as induced autophagy, mitotic catastrophe, senescence, and necrosis is beneficial to overcoming multidrug resistance mediated by apoptosis resistance in tumor cells. Therefore, investigating the function and mechanism of drug-induced non-apoptotic cell death modes has positive implications for the development of new anti-cancer drugs and therapeutic strategies. Phytochemicals show strong potential as an alternative or complementary medicine for alleviating various types of cancer. Quercetin is a flavonoid compound widely found in the daily diet that demonstrates a significant role in inhibiting numerous human cancers. In addition to direct pro-tumor cell apoptosis, both in vivo and in vitro experiments have shown that quercetin exerts anti-tumor properties by triggering diverse non-apoptotic cell death modes. This review summarized the current status of research on the molecular mechanisms and targets through which quercetin-mediated non-apoptotic mode of cancer cell death, including autophagic cell death, senescence, mitotic catastrophe, ferroptosis, necroptosis, etc.

A multifunctional non-viral vector for the delivery of MTH1-targeted CRISPR/Cas9 system for non-small cell lung cancer therapy.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system adapted from bacteria is a programmable nuclease-based genome editing tool. The long-lasting effect of gene silencing or correction is beneficial in cancer treatment. Considering the need to broaden the practical application of this technology, highly efficient non-viral vectors are urgently required. We prepared a multifunctional non-viral vector that could actively target tumor cells and deliver CRISPR/Cas9 plasmids into nuclei of cancer cells. Protamine sulfate (PS) which contains nuclear localization sequence was utilized to condense plasmid DNA and facilitate nuclei-targeted delivery. Liposome-coated protein/DNA complex avoided the degradation of nuclease in blood circulation. The obtained PS@Lip/pCas9 was further modified with distearoyl phosphoethanolamine-polyethylene glycol-hyaluronic acid (HA) to endow the vector ability to actively target tumor cell. Results suggested that PS@HA-Lip could deliver CRISPR/Cas9 plasmids into nuclei of tumor cells and induce genome editing effect. With the disruption of MTH1 (mutT homolog1) gene, the growth of non-small cell lung cancer was inhibited. Moreover, cell apoptosis in tumor tissue was promoted, and liver metastasis of non-small cell lung cancer (NSCLC) was reduced. Our study has provided a therapeutic strategy targeting MTH1 gene for NSCLC therapy. STATEMENT OF SIGNIFICANCE: CRISPR/Cas9 as a powerful tool for genome editing has drawn much attention. The long-lasting effect possesses unique advantage in cancer treatment. Non-viral vectors have high loading capacity, high safety and low immunogenicity, playing an important role in CRISPR/Cas9 delivery. In our study, a multifunctional non-viral vector for the efficient delivery of CRISPR/Cas9 plasmid was constructed. With the active targeting ligand and nuclei-targeting component, the cargo was efficiently delivered into cell nuclei and exerted genome editing effect. By using this vector, we successfully inhibited the growth and induced the apoptosis of non-small cell lung cancer by disrupting MTH1 expression with good safety. Our work provided an efficient non-vial vector for CRISPR/Cas9 delivery and explored the possibility for cancer treatment.

Molecular mechanism of Ginkgo biloba in treating type 2 diabetes mellitus combined with non-alcoholic fatty liver disease based on network pharmacology, molecular docking, and experimental evaluations.

Ginkgo biloba has gained increasing attention owing to its remarkable effects against cardiovascular disease. However, the role of G. biloba in hepatic lipid metabolism disorders in type 2 diabetes mellitus (T2DM) combined with non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms have not been elucidated. Here, the effective ingredients and mechanisms of action of G. biloba in T2DM combined with NAFLD were investigated via an integrated strategy of network pharmacology and molecular docking. Thirty-four core targets for the alleviation of T2DM combined with NAFLD were identified and retrieved from multiple open-source databases, after validating the ameliorative effect of G. biloba on lipid accumulation in vitro. The targets IL6, IL1B, VEGFA, PTGS2, and CCL2, among others, with high network association values, were screened using Cytoscape. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that 34 compounds derived from G. biloba may exert therapeutic effects via response to molecule of bacterial origin, cellular response to lipid, and response to the hormone. In addition, the AGE-RAGE and IL-17 signaling pathways were predicted to be most significantly affected. Meanwhile, the outcomes of the molecular docking experiment showed that the most effective ingredients in G. biloba showed a strong binding affinity to the potential target active sites. Findings from further in vitro experiments confirmed that G. biloba treatment decreased the level of IL6, IL1B, and VEGFA protein. In conclusion, our findings provided novel insights into the mechanisms underlying the therapeutic effect of G. biloba in T2DM combined with NAFLD. PRACTICAL APPLICATIONS: As a medicinal food plant, G. biloba has been shown to exert benefits in cardiovascular diseases. However, the pharmacological material basis and complex mechanism of action in G. biloba in T2DM combined with NAFLD remain unknown. Here, the mechanism by which G. biloba could ameliorate T2DM combined with NAFLD was investigated, and the potential target and molecular mechanism were explored, through a comprehensive strategy combining network pharmacology and molecular docking. Our findings indicate that G. biloba exerts synergistic effects in treating T2DM combined with NAFLD through multi-ingredients, multi-targets, and multi-pathways; the findings also elucidate the nutritional and therapeutic potential of G. biloba in preventing and treating T2DM combined with NAFLD and provides robust evidence for its clinical application.

Hesperetin, a Promising Treatment Option for Diabetes and Related Complications: A Literature Review.

The morbidity and mortality of diabetes have increased dramatically in recent decades. Novel strategies for treating diabetes and its complications with minimal side effects are in urgent need. New monomeric molecules extracted from herbal medicine, which is a form of alternative medicine, are being sought as drug candidates for the treatment of diabetes and its complications. Hesperetin (Hst), a citrus flavonoid, is of increasing interest in scientific studies recently due to its properties in combating diabetes and its complications, whereas existing studies are scattered and unsystematic. Here, we summarized the literature studies over the last 10 years to review the potential therapeutic role of Hst in the prevention and mitigation of diabetes and its complications, intending to provide promising strategies for the clinical management of diabetes and its complications.

Cost-Effectiveness of Tislelizumab Versus Docetaxel for Previously Treated Advanced Non-Small-Cell Lung Cancer in China.

Background: Tislelizumab, a new high-affinity programmed cell death protein-1 (PD-1) inhibitor, significantly prolonged the overall survival in pretreated non-small-cell lung cancer (NSCLC). This study aimed to assess the cost-effectiveness of tislelizumab versus docetaxel for this population in China. Methods: A three-state partitioned survival model was developed to simulate advanced NSCLC. Efficacy and safety data were based on a global phase 3 clinical trial (RATIONALE 303). Utilities were mainly extracted from previously published resources. Costs were calculated from the Chinese healthcare system's perspective, and only direct medical costs were covered. The main outcomes included total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were carried to test the uncertainty of the modeling results. In addition, several scenarios including tislelizumab price before negotiation, different docetaxel price calculation, 50-year time horizon, and alternative utility values were assessed. Results: The model predicted an average gain of 0.62 LYs and 0.51 QALY for tislelizumab vs. docetaxel, at the additional cost of $9,219. The resulting ICER was $15,033.92/LY and $18,122.04/QALY, both below the cost-effective threshold (CET) of three times gross domestic product (GDP) per capita in China. Sensitivity analyses showed that the results are robust over a plausible range for majority of inputs. Utility of progression-free survival (PFS), followed by the price of tislelizumab, had the greatest impact on the ICER. The probability of being cost-effective for tislelizumab was 96.79% at the CET we set. Conclusion: Tislelizumab improves survival, increases QALYs, and can be considered a cost-effective option at current price compared with docetaxel for pretreated advanced NSCLC in China.

Body mass index and pharmacodynamics of target-controlled infusion of propofol: A prospective non-randomized controlled study.

WHAT IS KNOWN AND OBJECTIVE: In our preliminary study, there were large individual variations at sedation levels during propofol target-controlled infusion (TCI). The present study aimed to assess the effects of body mass index (BMI) on the pharmacodynamic index of propofol TCI. METHODS: This prospective, non-randomized controlled trial evaluated 175 female patients undergoing breast lumpectomy. Anesthesia was induced with propofol using the TCI system embedded Schnider model. The effect compartment concentration was set to 3 µg/ml, and the start time of infusion was recorded. When the target concentration reached 3 µg/ml, the patient could not be awakened (Ramsay sedation score ≥4), and when the Bispectral Index (BIS) was <60, the infusion was discontinued, and the time point was recorded. The observation end-point was set at the Observer's Assessment of Alertness/Sedation (OAA/S) score of <4. The correlation between the BMI and the pharmacodynamic index of propofol was evaluated. RESULTS AND DISCUSSION: Propofol induction time was significantly correlated with the BMI (p < 0.001). The induction time of the underweight subjects was 10.14 ± 2.19 min, which was remarkably higher than that of normal weight (6.48 ± 3.44 min) and overweight (4.75 ± 2.53 min) individuals (p < 0.001). There were still significant differences after multivariable-adjusted regressions (p < 0.001). There were no significant differences in recovery time and sedative effect indicators, such as Ramsay score, BIS value, and effect compartment concentration, between the three groups (p > 0.05 for all). WHAT IS NEW AND CONCLUSION: These results suggest that the BMI is one of the critical factors affecting the pharmacodynamic index of propofol TCI, and the induction time decreased progressively with increasing BMI. The Schnider model might underpredict doses of propofol for underweight individuals.

Impact of antibiotic prophylaxis courses on postoperative complications following total joint arthroplasty: Finding from Chinese population.

WHAT IS KNOWN AND OBJECTIVE: Prolonged antibiotic prophylaxis after total joint arthroplasty (TJA) may not assist in minimizing postoperative complications, however, data based on the Chinese population have been limited. The purpose of this study is to investigate the effect of antibiotic prophylaxis on postoperative complications after TJA in Chinese patients. METHODS: We retrospectively reviewed 990 patients undergoing elective primary TJA surgery from January 2016 to June 2019. Patients who received a short course (≤3 days) of antibiotic prophylaxis were compared with those who received a longer course (>3 days). Logistic regression analysis and subgroup analysis were performed to control for potential confounders. Beyond that, survival analysis was used to determine the cumulative incidence of postoperative complications. RESULTS AND DISCUSSION: Follow-up to 12 months after surgery, the prevalence of system complications in the longer course group and the short course group were 5.1% and 3.9%, respectively (p = 0.451). Similarly, no statistical differences in incisional complications (1.5% vs. 1.8%, p > 0.999) and periprosthetic joint infection (PJI) (1.0% vs. 1.0%, p > 0.999) were observed between the two groups. After performing logistic regression analysis and survival analysis, no potential association was found between the course of antibiotic prophylaxis and postoperative complications. In addition, prolonged antibiotic prophylaxis conferred no benefit for high-risk obese patients. WHAT IS NEW AND CONCLUSION: Extended antibiotic prophylaxis did not result in a statistically significant and clinically meaningful reduction in postoperative complications. Therefore, we recommended that the duration of antibiotic prophylaxis in TJA should be shortened to 3 days or less in the Chinese population.

Trends of Antibiotic Use and Expenditure After an Intensified Antimicrobial Stewardship Policy at a 2,200-Bed Teaching Hospital in China.

Objective: This study aimed to evaluate the effects of intensified Chinese special rectification activity on clinical antibiotic use (CSRA) policy on a tertiary-care teaching hospital. Methods: A 48-month longitudinal dataset involving inpatients, outpatients, and emergency patients were collected. Study period included pre-intervention stage (adopting soft measures like systemic training) and post-intervention stage (applying antibiotic control system to intensify CSRA policy). Antibiotic use was evaluated by antibiotic use rate (AUR) or antibiotic use density (AUD). Economic indicator was evaluated by antibiotic cost in prescription or antibiotic expenditure in hospitalization. Data was analyzed by interrupted time series (ITS) analysis. Results: The medical quality indicators remained stable or improved during the study period. AUR of inpatients (AURI) declined 0.553% per month (P = 0.025) before the intervention and declined 0.354% per month (P = 0.471) after the intensified CSRA policy was implemented. AUD, expressed as defined daily doses per 100 patients per day (DDDs/100PD), decreased by 1.102 DDDs/100PD per month (P = 0.021) before and decreased by 0.597 DDDs/100PD per month (P = 0.323) thereafter. The ratio of antibiotic expenditure to medication expenditure (AE/ME) decreased by 0.510% per month (P = 0.000) before and fell by 0.096% (P = 0.000) per month thereafter. AE per patient decreased by 25.309 yuan per month (P = 0.002) before and decreased by 7.987 yuan per month (P = 0.053) thereafter. AUR of outpatient (AURO) decreased by 0.065% per month before (P = 0.550) and decreased by 0.066% per month (P = 0.994) thereafter. The ratio of antibiotic cost to prescription cost in outpatient (ACO/PCO) decreased by 0.182% per month (P = 0.506) before and decreased by 0.216% per month (P = 0.906) thereafter. AUR of emergency patient (AURE) decreased by 0.400% per month (P = 0.044) before and decreased by 0.092% per month (P = 0.164) thereafter. The ratio of antibiotic cost to prescription cost in emergency patient (ACE/PCE) decreased by 0.616% per month (P < 0.001) before and decreased by 0.151% per month (P < 0.001) thereafter. Conclusions: Implementation of CSRA policy was associated with declining antibiotic use and antibiotic expenditure in inpatients, outpatients, and emergency patients. However, it is also important to note that the declining trend of antibiotic consumption slowed due to the limited capacity for decline in the later stages of CSRA intervention.

Cost-Effectiveness Analysis of Anlotinib as Third- or Further-Line Treatment for Relapsed Small Cell Lung Cancer (SCLC) in China.

INTRODUCTION: The survival of patients with relapsed small cell lung cancer (SCLC) has achieved little progress in the last several decades. ALTER1202 confirmed the efficacy and safety of anlotinib as a third- or further-line option for relapsed SCLC. This study aimed to assess the cost-effectiveness of anlotinib compared with placebo as third- or further-line treatment for advanced SCLC in China. METHODS: A Markov model was developed to simulate the process of advanced SCLC and estimate the incremental cost-effectiveness ratio (ICER) of anlotinib versus placebo. The health outcomes and utilities were derived from the ALTER1202 (NCT03059797) and published sources, respectively. Total costs were calculated from the perspective of Chinese society. One-way and probabilistic sensitivity analyses (PSA) were conducted to explore the model uncertainties. RESULTS: Anlotinib was estimated to result in an additional 0.12 quality-adjusted life-years (QALYs) at an incremental cost of $2131.32, resulting in an ICER of $17,741.94/QALY. The ICER did not exceed the willingness-to-pay (WTP) threshold of $30,833 per QALY, which was three times the gross domestic product (GDP) per capita of China in 2019. One-way sensitivity analysis showed that the cost of anlotinib exerted the maximum influence on the result of the model, followed by the utility of progression-free survival (PFS) state in the anlotinib group and median overall survival (mOS) in the anlotinib group. In PSA, the probability of anlotinib being cost-effective was 26.6% and 78.5% when the WTP threshold was one and three times the GDP per capita, respectively. CONCLUSION: Anlotinib is likely to be a cost-effective option compared with placebo for patients with relapsed SCLC who experience failure of at least two lines of chemotherapy in China.

Impact of clinical pharmacist services on anticoagulation management of total joint arthroplasty: A retrospective observational study.

WHAT IS KNOWN AND OBJECTIVE: Even if total joint arthroplasty (TJA) patients have received conventional antithrombotic therapy, the incidence of thrombosis remains high. Clinical pharmacists have been involved in the multidisciplinary team of orthopaedics, but their roles and functions are not yet defined. The objective of this study was to assess the impact of clinical pharmacist services on the use of anticoagulant drugs, the rationality of medication and the incidence of thrombosis in patients with TJA. METHODS: This retrospective, observational cohort study was conducted for patients undergoing TJA procedures. Study variables were collected for a baseline period of 1 January 2016 to 30 June 2017 and an intervention period of 1 January 2018 to 30 June 2019, allowing for a 6-month run-in period. For demographic characteristics, the use of anticoagulant drugs and the incidence of thrombosis between the baseline and intervention periods, the data were statistically analysed. RESULTS AND DISCUSSION: During the 36-month study timeframe, a total of 591 TJA procedures were performed. A total of 577 participants were included in the study (240 in the baseline group and 377 in the intervention group). After clinical pharmacist participation, the prevention rate of anticoagulant drugs (p < 0.05), the proportion of oral anticoagulants (p = 0.000) and the course of preventive treatment (p = 0.004) increased significantly. The time of administration was shortened from after 24 h to within 24 h post-surgery (p = 0.000). Although the incidence of symptomatic DVT reduced in the intervention period, there was no statistical difference in either the hospital, 1-month follow-up, or 3-month follow-up after surgery (all p > 0.05). WHAT IS NEW AND CONCLUSION: Within the limitations of a retrospective study, clinical pharmacist intervention was associated with improvements in anticoagulation management of TJA procedures, likely conferring beneficial effects.

Dabigatran-induced chronic progressive immune hemolytic anemia: A case report.

Dabigatran is an orally active direct thrombin inhibitor, initially approved by FDA for the prophylaxis of stroke and systemic embolism in the setting of non-valvular atrial fibrillation (NVAF). Major bleeding is its most common adverse event which is of great concern. However, other types of adverse events such as esophagitis, esophageal ulcer, exanthem and pustular eruptions were reported increasingly in recent years. We present a case of immune hemolytic anemia (IHA) due to dabigatran use in a 72-year-old male with NVAF. This new and rare reported type of adverse event associated with dabigatran suggests that dabigatran may be a new cause of drug-induced immune hemolytic anemia (DIIHI).

Tirofiban for acute ischemic stroke: systematic review and meta-analysis.

BACKGROUND: The safety and efficacy of tirofiban for patients with acute ischemic stroke (AIS) remains controversial. We therefore conducted a systematic review and meta-analysis. METHODS: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and related international clinical trials registries through March 31, 2019, using the terms "tirofiban" and "stroke". All apparently unconfounded randomized controlled trials (RCTs) and cohort studies with two arms comparing treatment with and without tirofiban for AIS were included in this review. Primary outcomes included symptomatic intracranial hemorrhage (sICH), fatal ICH, mortality, and modified Rankin Scale (mRS 0-2) at 3 months. RESULTS: Seventeen studies including 2914 AIS patients were identified. Pooled results showed that tirofiban treatment in AIS did not increase the risk of sICH (OR, 0.95; 95% CI, 0.71-1.28; p = 0.75) or mortality (OR, 0.80; 95% CI; 0.64-1.02; p = 0.07). However, fatal ICH increased significantly in the tirofiban treatment group (OR, 2.84; 95% CI, 1.38-5.85; p = 0.005), and subgroup analysis showed that tirofiban via intra-arterial (IA) administration was associated with increased risk of fatal ICH (OR, 2.90; 95% CI, 1.12-7.55; p = 0.03), while intravenous (IV) administration was not (OR, 2.75; 95% CI, 0.92-8.20; p = 0.07). In addition, tirofiban showed no obvious improvement in functional outcome (mRS 0-2) (OR, 1.29; 95% CI, 0.97-1.71; p = 0.08). CONCLUSION: Tirofiban seems to be safe in systemic treatment and may represent a potential choice for management of AIS. However, intra-arterial administration requires further adequately controlled studies in order to develop an appropriate protocol, similar to that in cardiology.

Efficacy and safety of high-dose tigecycline for the treatment of infectious diseases: A meta-analysis.

BACKGROUND: High-dose (HD) tigecycline regimen is increasingly used in infectious diseases, however its efficacy and safety versus low-dose (LD) is still unclear. METHODS: A systematic review and meta-analysis was performed; PubMed, Embase, Cochrane Library, ScienceDirect, Web of Science, clinicalTrials.gov, Wanfang, VIP, and China National Knowledge Infrastructure (CNKI), were searched using terms "tigecycline" AND "dose" up to October 31, 2018. Eligible studies were randomized trials or cohort studies comparing mortality, clinical response, microbiological eradication and safety of different tigecycline dose regimens for any bacterial infection. The primary outcome was mortality, and the secondary outcomes were clinical response rate, microbiological eradiation rate and adverse events (AEs). Meta-analysis was done with random-effects model, with risk ratios (RR) and 95% confidence intervals (CI) calculated for all outcomes. RESULTS: Of 951 publications retrieved, 17 studies (n = 1041) were pooled in our meta-analysis. The primary outcome was available in 11 studies, and the RR for mortality was 0.67 (95% CI 0.53-0.84, P < .001). Clinical response (RR 1.46, 95% CI 1.30-1.65, P < .001) and microbiological eradication rate (RR 1.61, 95% CI 1.35-1.93, P < .001) were both higher in HD than in LD tigecycline regimen. However, non-Chinese study subgroup presented no statistical significance between HD and LD regimen, RR for mortality, clinical response and microbiological eradication were 0.79 (95% CI 0.56-1.14, P = .21), 1.35 (95% CI 0.96-1.92, P = .26), 1.00 (95% CI 0.22-4.43, P = 1.00), respectively. AEs did not differ between HD and LD tigecycline (RR 1.00, 95% CI 0.80-1.26, P = .97). CONCLUSION: HD tigecycline regimen reduced mortality meanwhile improved clinical efficacy and should be considered in serious infections caused by multidrug-resistant and extensively drug-resistant (MDR/XDR) bacteria.

An alternative lidocaine hydrochloride liposomal gel formulation: preparation, percutaneous permeation, and release kinetics.

Liposomal hydrogel formulations of lidocaine hydrochloride (LDH), suitable for topical application, were prepared, and drug percutaneous permeation and release properties were evaluated in vitro. Liposomes composed of lechitin and cholesterol, with LDH entrapped in the inner water compartment, were prepared by the reverse-phase evaporation technique. An optimal hydrogel formulation with carbopol as base included permeation enhancers polyethylene glycol (PEG-400), Azone, poloxamer, and propylene glycol, and this was screened in vitro. Percutaneous permeation kinetic models of LDH in three formulations, liposome solution, conventional gel, and liposomal gel, were studied. Results showed that the mean diameter of LDH liposomes was 88.31+/-6.82 nm and entrapment efficiency was 66.21+/-4.8%. The percutaneous permeation rate of LDH across skin from gel increased after LDH was entrapped in the water compartment of liposome compared with conventional gel, and the permeation kinetics of LDH across skin was not linear, but followed the Higuchi function.