Drug-induced dysphagia risk in elder people——A pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) database / 中国临床药理学与治疗学

AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c

Pharmacokinetic Characteristics of Siponimod in Healthy Volunteers and Patients With Multiple Sclerosis: Analyses of Published Clinical Trials.

Objectives: This study aimed to investigate the pharmacokinetic characteristics of siponimod in healthy volunteers and patients with MS based on aggregated data from published clinical trials, and to explore the factors influencing siponimod exposure. Methods: A total of 476 siponimod plasma concentrations aggregated from 28 dosage groups (corresponding to 294 healthy volunteers and 207 patients with MS) were collected from published clinical trials. Population pharmacokinetic (PPK) analysis was performed using a nonlinear, mixed-effect modeling approach. The pharmacokinetic properties of siponimod in healthy volunteers and patients with MS were compared, and the influence of covariates on siponimod exposure was evaluated using both PPK analysis and noncompartmental analysis (NCA). Results: A one-compartment model with first-order absorption and elimination adequately described siponimod pharmacokinetics. The typical population parameter estimates of clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (ka) were 3.17 L/h, 112.70 L, and 0.38 h-1, respectively. An 11.85% lower siponimod clearance was estimated for patients with MS relative to healthy volunteers. Subgroup analyses using NCA assessments revealed that siponimod presented an accumulation index of approximately 2 after multiple administration. Compared with nonobese participants, obese participants had a relatively lower dose-corrected area under the concentration-time curve (AUC0-∞/D) (0.31 vs. 0.42 h/L) and V/F (120.95 vs. 133.75 L), and a relatively higher CL/F (3.25 vs. 3.21 L/h). Participants with CYP2C9*2/*3, *1/*3, and *3/*3 genotypes experienced an increased (1.3- and 3.4-fold, respectively) AUC0-∞/D and a decreased (0.7- and 0.3-fold, respectively) CL/F compared with those in participants with the CYP2C9*1/*1, *1*2, and *2*2 genotypes. Fluconazole combination led to a decrease in CL/F (approximately 0.5 times) and an increase in AUC0-∞/D (approximately 1.3 times). Conclusion: Siponimod pharmacokinetic properties in healthy volunteers and patients with MS were explored using complementary model-based meta-analysis (MBMA) and NCA approaches. A slightly lower siponimod clearance was observed in patients with MS than in healthy volunteers. The dosage regimen, body mass index, CYP2C9 genetic polymorphism and fluconazole combination may had influences on siponimod pharmacokinetics. Such model paves the road to more population-based analyses in different patient populations with MS to quantify the effect of any influencing factors on siponimod pharmacokinetics.

Cobalamin metabolism and the clinical application in its different forms / 中华实用儿科临床杂志

Cobalamin, also known as Vitamin B 12, is the most complex vitamin in nature, and also one of essential vitamins in human body, which involved in many physiological activities, including homocysteine metabolism and translation of methylmalonyl-CoA to succinyl-CoA as a biological coenzyme.As a higher organism, human cannot synthesize cobalamin by themselves, so cobalamin needs to be supplemented by diet or medicine.At present, there are various forms of cobalamin, including cyanocobalamin (a common form of Vitamin B 12), hydroxylcobalamin, mecoba-lamin and 5′-adenosylcobalamin.These different forms of cobalamin are similar in structures and physiochemical pro-perties, but have some differences in the pharmacokinetics of absorption, distribution, metabolism and elimination, as well as clinical application and therapeutic efficacy.Among them, cyanocobalamin and hydroxycobalamin are widely used in Europe and the United States.Mecobalamin is more commonly used in Asia.5′-adenosylcobalamin has been approved in China, but less widely used in the world.Cyanocobalamin and mecobalamin are mainly used for the treatment of diseases caused by peripheral neuropathy and cobalamin deficiency.Hydroxycobalamin has been approved as an antidote to cyanide and has shown some potential in the treatment of methylmalonic acidemia in recent years.Now, the chemical structures, physiochemical properties, pharmacokinetic characteristics and clinical applications of the four cobalamins were compared and distinguished, so as to provide references for clinicians in clinical rational drug use and to avoid confusion.

Introduction and interpretation of the screening tool of older persons prescriptions in frail adults with limited life expectancy / 中华老年医学杂志

Screening Tool of Older Person's Prescriptions(STOPP)in Frail old patients(STOPP Frail)with limited life expectancy is a list of explicit criteria for potentially inappropriate medication (PIM)using in frail older adults.STOPP Frail criteria were initially created by the experts from Cork university hospital based on the clinical experience and literature appraisal and released in 2017 by an expert panel of Cork university hospital,Ireland.Using Delphi consensus methodology,the panelists ranked their agreement with each criterion on a 5-point Likert scale and provided a written feedback.Twenty-seven criteria with a median Likert response of 4/5 (agree/strongly agree)and a 25th centile of ≥4 scores were included in the final list.STOPP Frail may assist physicians in deprescribing medications to reduce the PIM use in frail older adults.

Interpretation of the list of alternative medications for high-risk medications in the elderly and potentially harmful drug-disease interactions based on the Beers criteria / 中华老年医学杂志

The National Committee for Quality Assurance(NCQA)and the Pharmacy Quality Alliance(PQA)used the American Geriatrics Society(AGS)Beers Criteria to establish the quality measure system of high-risk medications and potentially harmful drug-disease interactions in the elderly.Medications included may be harmful to elderly adults,and negatively affect health care plans' quality ratings.AGS experts conducted a comprehensive literature review and prepared a list of drug-therapy alternatives with supporting references.NCQA,PQA,the 2015 AGS Beers Criteria panel,and the Executive Committee of the AGS reviewed the drug therapy alternatives and nonpharmacological approaches.Prescribers,pharmacists,patients,and health care plans may benefit from this list.

Absence of ethnic differences in the pharmacokinetics of moxifloxacin, simvastatin, and meloxicam among three East Asian populations and Caucasians.

AIM: To examine whether strict control of clinical trial conditions could reduce apparent differences of pharmacokinetic (PK) parameters among ethnic groups. METHODS: Open-label, single dose PK studies of moxifloxacin, simvastatin and meloxicam were conducted in healthy male subjects from three East Asian populations (Japanese, Chinese and Koreans) and one Caucasian population as a control. These three drugs were selected because differences in PK parameters have been reported, even though the backgrounds of these East Asian populations are similar. Moxifloxacin (400 mg) was administered orally to 20 subjects, and plasma and urine levels of moxifloxacin and its metabolite (M2) were measured. Simvastatin (20 mg) was given to 40 subjects, and plasma levels of simvastatin and simvastatin acid were measured. Meloxicam (7.5 mg) was given to 30 subjects and its plasma concentration was determined. Intrinsic factors (polymorphism of UGT1A1 for moxifloxacin, SLCO1B1 for simvastatin, and CYP2C9 for meloxicam) were also examined. RESULTS: AUCinf values for moxifloxacin, simvastatin and meloxicam showed no significant differences among the East Asian groups. Cmax values of moxifloxacin and simvastatin, but not meloxicam, showed significant differences. There were no significant differences of data for M2 or simvastatin acid. Genetic analysis identified significant differences in the frequencies of relevant polymorphisms, but these differences did not affect the PK parameters observed. CONCLUSIONS: Although there were some differences in PK parameters among the three East Asian groups, the present study performed under strictly controlled conditions did not reproduce the major ethnic differences observed in previous studies.

Application of three-dimensional computerised tomography reconstruction and image processing technology in individual operation design of developmental dysplasia of the hip patients.

PURPOSE: Acetabular coverage deficiency displays individual difference among patients with developmental dysplasia of the hip (DDH). Therefore, the correct direction and degree of the acetabular fragment is patient-specific during Bernese periacetabular osteotomy (PAO). This paper introduces a feasible method using 3D computed tomography (CT) and computer image processing technology for customised surgical planning. METHODS: CT data of 96 hips in 60 DDH patients (male 15, female 45; average age/range 30 ± 8/14-49 years) and 53 normal hips (male 13, female 37; average age/range 52 ± 13/16-69 years) were reconstructed using commercially available software Mimics and Imageware. Geometric parameters of each hip were measured in relation to the anterior pelvic plane after correcting for pelvic tilt and rotation. Deficiency types and degrees of acetabular dysplasia in patients with DDH were determined by comparison with normal hips, and improvement in femoral-head coverage was analysed again after virtual PAO. A customised surgery programme for each DDH patient was designed and provided the reference for the actual operation. RESULTS: We produced a 3D pelvic model using image processing software, doing precise measurement and with close approximation to the actual PAO. Lateral centre-edge angle (LCEA), anterior centre-edge angle (ACEA), acetabular anteversion angle (AAVA), anterior acetabular sector angle (AASA) and posterior acetabular sector angle (PASA) of normal hips in the control group were 35.128 ± 6.337, 57.052 ± 6.853, 19.215 ± 5.504, 61.537 ± 7.291 and 99.434 ± 8.372°, respectively. Angles of hips with DDH before surgery were 11.46 ± 11.19, 35.79 ± 13.75, 22.77 ± 6.13, 43.58 ± 9.15 and 88.46 ± 8.24, which were corrected to 33.81 ± 2.36, 55.38 ± 2.09, 20.16 ± 2.18, 58.29 ± 7.60, and 4.71 ± 7.75°, respectively, after surgery. After virtual Bernese PAO, LCEA, ACEA, AAVA, AASA and PASA were corrected significantly (p < 0.01). There was no statistically significant differences between LCEA, ACEA and AAVA after virtual Bernese PAO and normal hips (p = 0.06, p = 0.23, p = 0.06°, respectively). AASA improved significantly (p = 0.002) post-operatively at the cost of reducing posterior coverage represented by PASA, which is significantly smaller than in normal and pre-operative hips of DDH patients (p < 0.01). CONCLUSIONS: The geometric feature of the pelvis for patients with DDH can be assessed comprehensively by using 3D-CT reconstruction and image processing technology. Based on this method, surgeons can design individualised treatment scheme and improve the effect of PAO.

Preliminary results of treatment of complex hip dysplasia with combined periacetabular and intertrochanteric osteotomies / 中华骨科杂志

Objective To detect the preliminary results of combined periacetabular and intertrochanteric osteotomies for complex hip dysplasia.Methods From January 2006 to August 2011,23 patients (25 hips) with complex hip dysplasia were treated with combined periacetabular and intertrochanteric osteotomies (ITO).Valgus ITO was performed on 2 hips and varus ITO on others.The averagc age of patients at the time of index procedure was 20.5± 3.9 years (range:15 to 26).The hip pain period before surgery varied from 5 to 24 months (mean 11±4.7 months).The Shenton's line was broken in every hip and the mean preoperative lateral central edge angle (LCEA) was 5.6°±4.6°.The average preoperative fenoral neck-shaft (CCD) angles were 158°±3.2° and 110° in 23 valgus hips and both of two varus hips respectively.The preoperative Harris hip score was 76.7±3.7.According to T(o)nnis osteoarthritis grades,there were 7 hips at grade 0,12 hips at grade Ⅰ and 6 hips at grade Ⅱ.Results The mean followup period was 40±18 months (range:12 to 78).The CCD angle (130°±2.1°),LCEA (28.6°±2.9°) and Harris hip score (90.8±3.3)were all improved postoperatively,whereas no progression was found in preoperative T(o)nnis grades.The postoperative Harris hip scores were excellent in 17 hips and good in 8 hips.The T(o)nnis osteoarthritis grades were grade 0 in 6 hips,grade Ⅰ in 11 hips and grade Ⅱ in 8 hips.There wcre six cases with lateral femoral cutaneous nerve injury,three cases with limp and two cases with broken Shenton's line.Neither femoral head necrosis nor bone nonunion was found in this study.Conclusion Satisfactory preliminary results could be obtained through combined periacetabular and intertrochanteric osteotomies among patients with complex hip dysplasia.The risk of femoral head necrosis and bone nonunion was low.

Introduction for clinical trials of aogliptin / 中国生化药物杂志

Alogliptin is a class of highly selective dipeptidyl peptidase-IV (DPP-IV) inhibitors.It can reduce the glucose level mainly through inhibiting the decomposition of dipeptidyl peptidase of glucagon peptide-1 (GLP-1), therefor promote insulin secretion.A large number of clinical trials have been conducted before and after algliptin get approved by Food and Drug Administration form different countries , which proves that alogliptin can remarkably reduce blood glucose without causing any serious risks.This article is mean to introduce most of the important clinical trials that has been conducted, from Phase I to Phase IV.

Applying Stoppa approach in acetabular fractures / 中华骨科杂志

ObjectiveTo report the preliminary results and surgical technique of Stoppa approach used in treatment of acetabular fracture.MethodsFrom May 2005 to May 2010,23 patients with acetabular fracture were treated using modified Stoppa approach.The mean age was 37 years old(range,21-71years old).According to Letournel classification,there were 7 cases in anterior column fracture,6 cases in anterior column with posterior hemitransverse fracture,6 cases in transverse fracture,4 cases in associated with both column fractures.All patients in the study were operated under general anesthesia on a radiolucent table in a supine position and underwent Stoppa approach.Fracture reduction was evaluated by Matta's score system.The clinical outcome was judged by modified Merle d' Aubigne and Postel score system.Four cases of associated both column fractures,4 cases of anterior column with posterior hemitransverse fracture required the use of the lateral window.ResultsThe mean surgical time was 166 min (range,110-320 min).The mean blood lose was 647 ml (range,300-2500 ml).Blood transfusion was 3.3 unites (0-12 unites).All the factures healed in 3 months.The fracture reduction was evaluated according to the Matta's score system:an excellent reduction was obtained in 15 patients(65％),a good reduction was obtained in 5 patients (22％),and three(13％) were considered poor.Clinical results were excellent in 11 patients(48％),good in 7 patients (30％),fair in 3 patient (13％),and poor in 2 patients (9％).Superficial wound infection happened in 1 case.It healed after debridment.One patient noted to have significant weakness of the hip adductors (obturator nerve palsy) after surgery.It reached grade Ⅳone year later.No sciatic nerve,femoral nerve and vascular injury happened in this study.ConclusionFor the selected acetabualar fracture,Stoppa approach can get satisfied exposure and fixation of the fracture,especially in the patient with central dislocation of the femoral head as well as medial displacement of quadrilateral plate.

Differentiation of bone marrow mesenchymal stem cells into fibrochondrocyte phenotype / 中国组织工程研究

BACKGROUND: The meniscus has limited ability in repairing itself after being injured. However, tissue engineering provides a new way to meniscus repair after injury. Bone marrow mesenchymal stem cells (BMSCs), which possess the potential of multi-directional differentiations, can be ideal seed cells in meniscus tissue engineering. OBJECTIVE: To investigate the feasibility of differentiation of in vitro cultured porcine BMSCs into fibrochondrocyte phenotypes in inductive medium. METHODS: BMSCs were isolated with whole bone marrow culture method. Then, BMSCs of the third passage were digested and incubated in a medium containing transforming growth factor-β1, insulin-like growth factor-Ⅰ, dexamethasone and ascorbic acid in a 24-well plate at a density of 2.0×10~4/cm~2 in the experimental group. While in the control group, the DMEM-LG complete culture medium containing no inductive factor were used instead. At day 7, 14 and 21 after induction respectively, Toluidine blue staining and immunocytochemical staining were performed to detect differentiation. MAIN OUTCOME MEASURES: ①Population double time (PDT) of BMSCs; ②Morphological changes of BMSCs under light microscope;③Proteoglycan expression;④Collagen type Ⅰ and type Ⅱ expression. RESULTS AND CONCLUSION: ① The PDT of the second passage BMSCs was 2 days, which was the shortest. The PDT prolonged relatively after the fourth passage, which were 5 to 9 days. ② The BMSCs changed from a spindle-like appearance into a polygonal shape after induction. ③ In the experimental group, toluidine blue staining resulted in hyacinthine-stained cytoplasm and the blue was even deeper in the area where cells were dense; The degree of staining increased with the increasing induction time. While in the control group, only nucleus of BMSCs were stained blue. ④ Collagen type Ⅰ immunocytochemical staining was positive in both the experimental and the control group and there was no difference of significance between various induction time. No collagen type Ⅱwas seen expressed in the control group, while in the experimental group it was seen to be expressed steadily after 14 days of induction. It is indicated tlat BMSCs can be induced to synthesize fibrochondrocyte-characterized extracellular matrixes in vitro, which suggests that BMSCs are available as seed cells in meniscus tissue engineering.

Establishment of Standard Medication History in China / 中国药房

OBJECTIVE: To explore the way to establish standard medication history in China. METHODS: To establish Chinese standard medication history by referring to other medication history pattern abroad, considering three factors - patients, physicians and pharmacists centered on the pharmaceutical care, and taking a case of diabetes mellitus patient as example to explain it clearly. RESULTS: The medication history was established by combining tables and descriptions, which consisted of four parts: First page, Record chart, Procedure and Summary. CONCLUSION: This medication history is concise, comprehensive, and legible, and it highlights the characteristics of pharmacists' job and meets the needs of clinical pharmacy practice.

Pharmacokinetics of penciclovir injection in Chinese healthy volunteers / 中国临床药理学与治疗学

AIM:To study the pharmacokinetics of penciclovir injection in Chinese healthy volunteers.METHODS:10 healthy volunteers were infused a single dose of 10 mg/kg of penciclovir.The concentrations of penciclovir in plasma and urine were determined by HPLC-FLD.Pharmacokinetic parameters were conformed to a non-compartment model analyzed by WinNonLin program.RESULTS:The main pharmacokinetic parameters were as follows:the ke was(0.37?0.05)/h;the t1/2 was(1.91?0.26)h;the Cmax was(9.8?1.6)mg/L;the AUC0-t was(19.1?2.8)mg?L-1?h;the AUC0-∞ was(19.6?2.9)mg?L-1?h;the Vd was(1.4?0.4)L/kg;the CL was(0.52?0.08)L?h?kg-1.About 70% of penciclovir was excreted into urine within 12 h.CONCLUSION:Penciclovir is widely distributed and rapidly excreted,predominantly by the kidney.

Concentration Determination of Sodium Valproate in Human Serum by HPLC-Fluorescence Detection Method / 中国药房

OBJECTIVE:To establish a method for the determination of sodium valproiate in human serum and to study the bioequivalence of steady state concentration C ssm in of the domestic and imported sodium valproiate sustained-release compound tablets.METHODS:Two periods of multi-oral administration of domestic and imported sodium valproiate sustained-release compound tablets were conducted alternately at random on20healthy male volunteers;the trough concentration of sodium valproate in human serum was determined by HPLC-fluorescence detection and the data were analyzed by3p97pro?gram.RESULTS:The blood concentration was steady after3d oral administration of both the domestic and imported sodium valproate sustained-release compound tablets.The C ssm in of domestic and imported products were(38.17?9.36)、(35.48?9.44)mg/L respectively.C ss min of domestic and imported sodium valproate sustained-release compound tablets were of bioe?quivalence either single or multi-oral administration.CONCLUSION:This HPLC-fluorescence method is quick,sensitive and economical,which can be used to monitor the concentration of sodium valproate in human serum.