OBJECTIVE: With the increasing prevalence of osteoarthritis of the hip and knee, total joint replacement, the end-stage treatment, provides pain relief and restoration of function, but is often associated with massive blood loss. Tranexamic acid (TXA) has been reported to reduce perioperative blood loss in hip or knee arthroplasty. However, the optimal dose of TXA administration remains controversial. Therefore, we performed a meta-analysis combining data from 5 trials comparing the efficacy and safety of one fixed dose of 1 g intravenously administered TXA with two doses of 1 g each administered intravenously for hip or knee arthroplasty.
METHODS: PubMed, Medline, Embase, Web of Science, and The Cochrane Library were searched from January 2000 to February 2023. Our meta-analysis included randomized controlled trials and cohort studies comparing the efficacy and safety of different doses of intravenous TXA (IV-TXA) for THA or TKA. The observation endpoints included total blood loss, postoperative hemoglobin drop, blood transfusion rate, length of hospital stay, incidence of deep venous thrombosis (DVT), and incidence of pulmonary embolism (PE). Meta-analysis was performed according to Cochrane\'s guidelines and PRISMA statement. The Danish RevMan5.3 software was used for data merging.
RESULTS: Five cohort studies involving 5542 patients met the inclusion criteria. Our meta-analysis showed that the two groups were significantly higher in total blood loss (mean difference (MD) = - 65.60, 95% confidence interval (CI) [- 131.46, 0.26], P = 0.05); blood transfusion rate (risk difference (RD) = 0.00, 95% CI [- 0.01, 0.02], P = 0.55); postoperative hemoglobin (MD = 0.02, 95% CI [- 0.09, 0.13], P = 0.31); postoperative hospital stay days (MD = - 0.13), 95% CI [- 0.35, 0.09], P = 0.25); DVT (RD = 0.00, 95% CI [- 0.00, 0.01], P = 0.67); PE (RD = 0.00, 95% CI [- 0.01, 0.00], P = 0.79). There was some inherent heterogeneity due to variance in sample size across each major study.
CONCLUSIONS: 1 dose of 1 g and 2 doses of 1 g IV-TXA each time have similar effects on reducing blood loss, blood transfusion rate, postoperative hemoglobin level, and postoperative hospital stay after TKA or THA, without increasing the risk of postoperative complications risk. For patients at high risk of thromboembolic events, one dose of 1 g TXA throughout surgery may be preferred. However, higher-quality RCT is needed to explore the optimal protocol dose to recommend the widespread use of TXA in total joint arthroplasty. Trial registration We conducted literature selection, eligibility criteria evaluation, data extraction and analysis on the research program registered in Prospero (CRD42023405387) on March 16, 2023.

The purpose of the study is to determine the efficacy and safety of postoperative single-dose anticoagulant treatment in preventing venous thromboembolism (VTE) after revision THA, in comparison with a multiple-dose chemoprophylaxis protocol.
We retrospectively compared 295 patients undergoing revision THA who received multiple-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once and oral rivaroxaban for 10 days) or single-dose chemoprophylaxis protocol (40 mg low-molecular-weight heparin once) for VTE. The patients in both groups performed active lower limb exercises. Each group was further stratified into subgroups based on the aetiology of revision. The incidence of VTE, wound complications within three months, hidden blood loss (HBL), transfusion rate, and surgical drainage duration were recorded.
The incidence rates of VTE (P = 0.870) did not differ between the two prophylaxis protocols. However, significant differences were observed in wound complications within three months (P = 0.002), HBL (P = 0.015), transfusion rate (P = 0.028). Surgical drainage duration was also shorter in the single-dose chemoprophylaxis group (P = 0.0023). In the subgroup analysis, the use of single-dose chemoprophylaxis protocol cannot significantly reduce HBL and transfusion rate after septic revision THA. The use of multiple-dose chemoprophylaxis protocol (OR = 2.89, P = 0.002) and high BMI (OR = 1.09, P = 0.037) were independent risk factors of wound complications.
Single-dose chemoprophylaxis protocol effectively and safely prevented VTE after revision THA compared with multiple-dose chemoprophylaxis protocol. The effect in reducing HBL and postoperative transfusion rate was limited in septic revision.

This randomized, parallel-group study evaluated the plasma pharmacokinetic profile of safinamide in 24 healthy Chinese men and women, randomly assigned to receive 50 or 100 mg of safinamide as a single dose, followed, after a 7-day washout, by multiple doses once daily for 7 days. Plasma safinamide was determined up to 96 h after the first single dose (day 1) and the last multiple dose (day 14), and up to 24 h after the first multiple dose (day 8). Following single- and multiple-dose administration, peak concentrations were achieved at a median time of 1.5-2 h. Plasma exposure increased in a dose-proportional manner. After single dose, mean half-life was 23-24 h. Area under the concentration-time curve (AUC) from time zero extrapolated to infinity was only slightly higher than AUC from time zero to the last quantifiable concentration, corresponding for the 2 parameters, respectively, to 12,380 and 11,560 ng • h/mL for the 50 mg and to 22,030 and 20,790 ng • h/mL for the 100-mg dose. AUC in the dosing interval at steady state was 13,150 and 23,100 ng • h/mL for 50 and 100 mg of safinamide. Steady state was reached in 6 days, accumulation was approximately twofold, and the pharmacokinetics were time independent. The plasma safinamide pharmacokinetic profile observed in this study is in line with the published results in both Chinese and non-Asian populations.

Desvenlafaxine succinate is a selective serotonin-norepinephrine reuptake inhibitor for the treatment of major depressive disorder. The pharmacokinetic profile of desvenlafaxine succinate at the clinically recommended dose of 50 mg in Chinese healthy subjects has been reported rarely. The objective of this study was to evaluate the pharmacokinetics and bioequivalence of desvenlafaxine succinate in Chinese healthy subjects. A single-dose, open-label, randomized, two-way crossover study with a 7-day washout period was conducted. A total of 88 individuals were incorporated to show bioequivalence of a generic and a reference drug, with 48 individuals in the fasting state and 40 receiving a high-fat diet. Finally, 46 and 38 individuals completed the fasting and the fed study, respectively. The 90% confidence intervals of the adjusted geometric mean ratios for maximum plasma concentration, area under the concentration-time curve from time zero to the last measurable concentration, and area under the concentration-time curve from time zero to infinity all fell in the bioequivalent interval of 80%-125% in both the fasting and fed states. A total of 33 adverse events were reported, and all were mild or moderate in severity. In summary, the generic and reference formulations were bioequivalent, with no observable safety differences in the fasting/fed state.

Pseudorabies (PR) is an important infectious disease of swine that causes enormous economic losses to the swine industry in China. Immunization with vaccines is a routine practice to control this disease. PRV inactivated vaccines usually require a booster vaccination to provide complete immune protection. Therefore, Astragalus saponins (AST) have been added as an immunopotentiator to improve the immune efficacy and reduce the immunization times for the PRV inactivated vaccine. The results in mice have shown that a single dose of AST-adjuvanted PRV inactivated vaccine promoted higher production of gB-specific IgG, IgG1, and IgG2a and neutralizing antibody, secretion of Th1-type (IFN-γ) and Th2-type (IL-4) cytokines, and lymphocyte proliferation than mice immunized without AST. Compared to mice immunized without AST, a single dose of the AST-adjuvanted PRV inactivated vaccine improved the survival percentage of mice and reduced the PRV viral loads in the lungs and brains after lethal challenge. In summary, AST was an effective immunopotentiator to improve the immune efficacy of a single dose PRV inactivated vaccine.

OBJECTIVE. Utilization and waste in diagnostic imaging have substantially increased worldwide. The purpose of this study was to highlight the utilization of contrast material and cost savings resulting from implementation of a multidose bulk IV contrast delivery system. MATERIALS AND METHODS. An observational study was conducted in October-November 2018 in eight hospitals in eight provinces in China. Contrast media specifications were 100-mL single-use IV contrast vials and 200-mL and 500-mL bulk packaging. Linear regression analysis was performed to identify the factors influencing contrast media use. Cost-minimization and sensitivity analyses were performed from patient and payer perspectives. RESULTS. A total of 1032 patients, some of whom underwent more than one CT examination, were enrolled in this study (100-mL package, 776 CT examinations; 200-mL package, 382 CT examinations). The mean injected volume of contrast medium was 75.46 mL. Number of scanned body parts, specification of amount of contrast medium (0, 100 mL; 1, 200 mL), whether the examination was CT angiography (CTA) (0, not CTA; 1, CTA), and patient weight all had a positive impact on the injected volume of contrast medium (p < 0.001 for all variables). Implementation of a multidose bulk IV contrast delivery system combined with different reimbursement units resulted in substantial waste reduction, estimated at US$5.59-6.04 per contrast-enhanced CT examination from the payer perspective, US$12.84-14.66 per examination from the patient perspective, and a total reduction of US$18.29-20.70 per examination. CONCLUSION. Use of multidose packaging of contrast media combined with reimbursement units for patients undergoing IV contrast-enhanced CT was found to be cost saving compared with use of single-dose packaging.

A rasagiline transdermal patch can be used to offer continuous rasagiline to patients with Parkinson\'s disease who cannot take their usual oral medications. This was the first study to investigate the pharmacokinetics, pharmacodynamics, and safety of the rasagiline transdermal patch in healthy Chinese subjects. Thirty subjects were randomized to 3 groups with 10 subjects in each group. The 10 subjects of group 1 received a single 1-mg dose of rasagiline as a tablet; the 20 subjects of groups 2 and 3 received a single transdermal patch (48-hour patch-on period) containing 1.25 mg and 2.5 mg rasagiline, respectively. After a 2-week washout period, the subjects of group 1 were assigned to receive 1 mg of rasagiline tablets every 24 hours for 7 days, and the subjects of group 2 were assigned to receive 1.25-mg rasagiline transdermal patches (48-hour patch-on period) every 72 hours for 5 time periods. The absorption of rasagiline from the transdermal patch was significantly improved, although the peak plasma concentration was obviously reduced. There was slight accumulation of rasagiline dose after multiple administrations. Inhibition of platelet monoamine oxidase-B (MAO-B) activity was dose dependent. The 80% inhibition maintained for at least 48 hours after multiple-dose administration of 1 mg tablets, and for 72 hours after multiple-dose administration of 1.25 mg/48 h patch. Compared with rasagiline tablets, the transdermal patch had a prolonged duration of 80% inhibition and increased maximal inhibition of MAO-B activity. These characteristics permitted an interval of 3 days of dosing, which was convenient for patients to use.

BACKGROUND: Yogliptin is a novel xanthine dipeptidyl peptidase-4 (DPP-4) inhibitor targeting type 2 diabetes. After promising preclinical pharmacological studies, the first human trial of yogliptin was designed.
METHODS: A randomized, double-blind, parallel, placebo-controlled phase I single-dose escalation study was designed to evaluate the pharmacokinetics, pharmacodynamics, and tolerability after single oral doses of yogliptin in healthy Chinese subjects. Healthy subjects were assigned to nine cohorts, which received a single dose of yogliptin at 2.5, 5, 10, 25, 50, 100, 200, 400, or 600 mg. Two subjects in each cohort received placebo. Blood samples were collected before dosing and up to 192 h afterwards. Urine samples were collected until 120 h after dosing. Plasma and urine drug concentrations were determined using liquid chromatography coupled with tandem mass spectrometry, and DPP-4 activity was measured using a semi-quantitative, fluorescence-based kinetic assay.
RESULTS: A total of 104 subjects were enrolled, 103 of whom completed the study (mean age, 25.3 years; mean weight, 58.8 kg; mean BMI, 21.8 kg/m2). A total of 27 adverse events (AEs) occurred in 25 of 86 yogliptin subjects (29.1%), and 3 AEs occurred in 3 of 18 placebo subjects (16.7%). Yogliptin was absorbed with a median time of maximum observed concentration (Tmax) of 3.0 h and was eliminated slowly with a t1/2 of 25.45-43.84 h. The maximum observed concentration (Cmax) and area under the curve (AUC) varied slightly more than dose-proportionally over the dose range from 2.5 to 400 mg. The fraction of drug excreted in urine ranged from 8.39% to 24.77%. Mean DPP-4 inhibition at 24 h after dosing ranged from 97.7% to 99.5%, and DPP-4 inhibition was >80% for 72 h at doses from 25 to 400 mg. DPP-4 inhibition was >80% for 1 week in the group receiving 400 mg.
CONCLUSIONS: Yogliptin was well tolerated in healthy subjects, with no dose-limiting toxicity observed in the range from 2.5 to 600 mg. Yogliptin inhibited plasma DPP-4 activity for 72 h at single doses of 25-200 mg and for 1 week at 400 mg, suggesting that once-weekly dosing of yogliptin is possible in type 2 diabetes patients.
BACKGROUND: ChiCTR-IIR-17010311 (Chictr.org).

The objective of this trial was to investigate the safety, tolerability, and pharmacokinetics (PK) of benapenem administered by single or multiple intravenous infusions in healthy Chinese volunteers. The trial was divided into 3 parts. In part A, 94 subjects were enrolled in a double-blind, placebo-controlled, sequential-ascending-single-dose study. The subjects were randomly assigned to groups receiving placebo or benapenem for injection at doses of 62.5, 125, 250, 500, 1,000, 2,000, or 3,000 mg. The effects of intravenous infusion time on the subjects of 250-, 500-, and 1,000-mg groups were explored. In part B, 12 subjects were enrolled in a single-dose PK study under fasting conditions and received 250, 500, or 1,000 mg of benapenem for injection. In part C, 36 subjects were given 250, 500, and 1,000 mg of benapenem for injection once daily for 7 consecutive days. The results showed that benapenem for injection was well tolerated during the studies. The major observed adverse events were mild, and all were resolved spontaneously without any medical intervention. Benapenem was mainly excreted through the kidneys in the form of parent molecule and metabolites. The PK and safety profiles of benapenem in healthy Chinese volunteers support its once-daily dosing in future clinical investigations. (Part A, part B, and part C have been registered at ClinicalTrials.gov under identifiers NCT03588156, NCT03578588, and NCT03570970, respectively.).

BACKGROUND: Pregabalin (PGB) and gabapentin (GBP) are current and emerging drugs in the field of pre-emptive preoperative analgesia. However, the role of PGB or GBP in acute postoperative pain management still remains elusive.
METHODS: We conducted a comprehensive literature search of articles published by December 3, 2017. A total of 79 randomized controlled trials with 6,201 patients receiving single-dose premedication were included. Through a network meta-analysis (NMA), we validated the analgesic effect and incidence of adverse events by using various doses of PGB or GBP administration.
RESULTS: NMA results suggested that the analgesic effect may be dose related. For 24-hour opioid consumption, a consistent decrease was found with the increase in the dose of PGB or GBP. For 24-hour pain score at rest, a high dose (≥150 mg) of PGB was more effective in decreasing pain score than a dose of 75 mg, and a high dose (≥900 mg) of GBP reduced pain intensity than doses of 300 or 600 mg. Moreover, the incidence of adverse reactions varied with varying doses of PGB or GBP.
CONCLUSIONS: A dose-response relationship was detected in opioid consumption and postoperative pain for a single-dose preoperative administration of PGB and GBP. Making reasonable choice of drugs and dosage may prevent the occurrence of adverse reactions.