Efficacy and safety of rivaroxaban in different doses for the treatment of isolated distal deep vein thrombosis / 中华普通外科杂志

Objective:To evaluate the efficacy and safety of of rivaroxaban for different doses in the treatment of isolated distal deep vein thrombosis.Methods:The clinical data of 853 patients of isolated distal deep vein thrombosis attending Nanjing Drum Tower Hospital from Jan 2018 to Dec 2020 was retrospectively analyzed.Results:Thrombotic recurrence rate increased with increasing follow-up in the standard and low dose groups, and it was significantly lower in the standard dose group than in the low dose group (HR=0.44, 95% CI: 0.25-0.78, P=0.005) with most thrombosis occurring within the first year of follow-up. There was no statistical difference between the two groups in terms of major bleeding events (HR=1.70,95%CI 0.56-5.14, P=0.530) and the incidence of clinically relevant non-major bleeding events was significantly higher in the standard dose group than in the low dose group (HR=2.36, 95%CI 1.26-4.44, P=0.020). Subgroup analysis on anticoagulation duration found when anticoagulation duration was longer than 1.5 months, the risk of thrombosis was lower in the standard dose group than the low dose group (1.5-3 months:HR=0.11, 95%CI 0.01-0.87, >3 months: HR=0.19, 95%CI 0.04-0.95), there was an interaction between anticoagulation duration and dose ( P=0.007). Conclusions:Based on the risk of thrombosis recurrence and bleeding events, the standard dose of rivaroxaban (20 mg qd) is recommended for patients with isolated distal deep vein thrombosis, and the anticoagulant duration should be maintained for 1.5 months or more.

Application status and prospects of topical drug therapy in oral mucosal diseases / 口腔疾病防治

@#Oral mucosal disease is a general term for a type of disease that mainly affects the oral mucosa and surrounding soft tissues. In the treatment of oral mucosal diseases, due to the particularity of the anatomical location, the use of topical administration is relatively simple and convenient; drugs can easily accumulate in the lesions, and at the same time, they can also avoid adverse reactions caused by systemic drug delivery. Topical administration has become an important and even preferred option for the treatment of oral mucosal diseases. There are various types of topically used drugs for oral mucosal diseases, such as glucocorticoids (triamcinolone acetonide), immunomodulatory drugs (tacrolimus), antiseptic drugs (chlorhexidine), pain relievers (lidocaine) and proprietary Chinese medicines (aloe vera gel). Among these drugs, although the most widely used liquid formulations such as gargles and sprays are easy to use, they are not conducive to local retention of drugs due to the particularity of the oral environment and function. Based on this, researchers have continuously improved the dosage form of the drug, and developed a series of semi-solid pharmaceutical preparations such as gels and ointments, some of which have exerted good curative effects in clinical work. In addition, although films, patches and other solid oral mucosal topical pharmaceutical preparations have few clinical applications, they have also been widely researched and described and are expected to become the mainstream dosage form in the future. In general, with the improvement of dosage forms, topical administration is playing an increasingly important role in the treatment of oral mucosal diseases. Therefore, combined with basic research and clinical reports, this article reviews the application of topical drug delivery in the treatment of oral mucosal diseases

Efficacy of different doses of apatinib combined with chemotherapy in the treatment of advanced gastric cancer and its effect on prognosis / 中国基层医药

Objective:To investigate the efficacy of different doses of apatinib combined with chemotherapy in the treatment of advanced gastric cancer and its effect on prognosis.Methods:Sixty-nine patients with advanced gastric cancer who received treatment in Lishui City People's Hospital from January 2015 to February 2019 were retrospectively analyzed. All patients received apatinib combined with teggio chemotherapy. These patients were divided into groups A, B and C according to the different dosages of apatinib used: 250 mg/d ( n = 21, group A), 500 mg/d ( n = 23, group B) and 850 mg/d ( n = 23, group C). The control rate of gastric cancer, serum levels of carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4), toxic and side effects, and survival within 1 year after surgery were determined among the three groups. Results:By the end of follow-up, one patient from group A was lost, one patient from group B interrupted medication because of personal reasons, and two patients from group C withdrew from the treatment due to serious discomfort caused by drugs. After treatment, disease control rate in group C was significantly higher than that in group A [91.30% (21/23) vs. 60.00% (12/20), χ2 = 6.484, P < 0.05]. Serum levels of carcinoembryonic, CA19-9 and CA72-4 in group C were (27.51 ± 2.21) μg/L, (101.46 ± 8.02) g/L, (46.34 ± 6.15) U/mL, respectively, which were significantly lower than those in group B [(29.33 ± 2.17) μg/L, (106.67 ± 8.10) g/L, (50.67 ± 6.20) U/mL, t = 2.786, 2.168, 2.352, all P < 0.05]. Serum levels of carcinoembryonic, CA19-9 and CA72-4 in group B were significantly lower than those in group A [(31.63 ± 2.92) μg/L, (112.12 ± 8.38) g/L, (55.12 ± 6.48) U/mL, t = 2.915, 2.142, 2.274, all P < 0.05]. The incidences of hand foot syndrome and gastrointestinal discomfort in group C were (34.78% (8/23) and (39.13% (9/23), respectively, which were significantly higher than those in group A [15.00% (3/23) and 25.00% (5/20), χ2 = 5.734, 4.769, both P < 0.05]. After 1-year follow-up,1-year survival rate in group C was significantly higher than that in group A [39.13% (9/23) vs. 10.00% (2/20), log-Rank χ2 = 6.600, P < 0.05]. Conclusion:High-dose apatinib combined with chemotherapy in the treatment of advanced gastric cancer has a high disease control rate and a high 1-year survival rate, but it has serious adverse drug reactions.

Effects of a loading dose of clopidogrel hydrogen sulfate on hemorheology and neurological function in patients with acute progressive cerebral infarction / 中国基层医药

Objective:To investigate the effects of a loading dose of clopidogrel hydrogen sulfate on hemorheology and neurological function in patients with acute progressive cerebral infarction.Methods:A total of 110 patients with acute progressive cerebral infarction who received treatment between January 2018 and January 2019 in the Affiliated Hospital of Shaoxing University, China were included in this study. They were randomly assigned to receive either conventional treatment (control group, n = 55) or treatment with a loading dose of clopidogrel hydrogen sulfate based on conventional treatment (study group, n = 55) for 2 weeks. Hemorheological parameters, National Institute Health of Stroke Scale (NIHSS) scores and adverse reactions were compared between the study and control groups. Results:After treatment, the levels of hemorheological parameters in both groups were obviously decreased. Plasma viscosity, high-shear whole blood viscosity, low-shear whole blood viscosity, fibrinogen level and hematocrit in the study group were (1.01± 0.37) mPa/s, (4.23 ± 0.35) mPa/s, (8.36 ± 1.64) mPa/s, (1.23 ± 0.28) g/L, (40.08 ± 5.04) %, respectively, which were significantly lower than those in the control group [(1.84 ± 0.52) mPa/s, (5.44 ± 0.39) mPa/s, (10.54 ± 1.79) mPa/s, (2.30 ± 0.37) g/L, (44.36 ± 5.12) %, t = 5.485, 8.594, 9.523, 7.789, 11.236, P = 0.019, 0.006, 0.004, 0.007, 0.001]. After treatment, NIHSS scores in the study group were significantly lower than those in the control group [(3.11 ± 1.17) points vs. (6.43 ± 2.25) points, t = 10.416, P = 0.003). There was no significant difference in the incidence of adverse reactions between study and control groups [5.45% (3/55) vs. 9.09% (5/55), χ2 = 0.539, P = 0.463). Conclusion:The loading dose of clopidogrel hydrogen sulfate is highly effective in the treatment of acute progressive cerebral infarction and it can greatly improve hemorheological parameters and neurological function.

Position statement from the Brazilian Society of Nephrology regarding chloroquine and hydroxychloroquine drug dose adjustment according to renal function / Nota da Sociedade Brasileira de Nefrologia em relação ao ajuste das drogas cloroquina e hidroxicloroquina pela função renal

ABSTRACT Chloroquine and hydroxychloroquine have shown promising preliminary results and have been discussed as therapeutic options for patients with Covid-19. Despite the lack of robust evidence demonstrating the benefits and justifying the use of one of these drugs, the final decision is the responsibility of the attending physician and should be individualized and shared, whenever possible. This position statement recommends dosage adjustment for these drugs in the context of renal impairment.

RESUMO Em razão de resultados preliminares promissores, a hidroxicloroquina e a cloroquina têm sido discutidas como opção terapêutica para pacientes com Covid-19. Apesar da ausência de estudos robustos que evidenciem o benefício e justifiquem o uso de uma dessas drogas, a decisão final compete ao médico assistente, devendo ser individualizada e, sempre que possível, compartilhada. A presente nota pretende orientar o ajuste posológico dessas drogas no contexto da disfunção renal.

Association Research between CYP3A5，CYP3A4，ABCB1 and POR*28 Genetic Polymorphisms and Individualized Use of Tacrolimus in Lung Transplant Recipients after One Year of Tacrolimus Administration / 中国药房

ABSTRACT OBJECTIVE：To study the association between CYP3A5，CYP3A4，ABCB1 and POR*28 genetic polymorphisms and drug dosage（D）and steady blood concentration/dosage（c0/D）of tacrolimus in lung transplant recipients after one year of tacrolimus administration. METHODS：By retrospective analysis，a total of 46 recipients who underwent lung transplantation in China-Japan Friendship Hospital during May 2017-May 2018 were selected. The c0 and D of tacrolimus were measured and collected after one year of tacrolimus administration，and c0/D was calculated. Recipients’genotypes of CYP3A5（rs776746）， CYP3A4（rs2242480，rs28371759），ABCB1（rs1045642，rs2032582，rs1128503）and POR*28（rs1057868）were collected. The relationship between genetic polymorphism and D，c0/D was analyzed statistically. RESULTS：The genotype frequency in this study were all in accordance with Hardy-Weinberg equilibrium （P＞0.05）. While maintaining tacrolimus c0 within therapeutic range， genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）influenced D and c0/D of tacrolimus significantly（P＜ 0.05）. There was no statistical significance in D or c0/D among different genotypes of other sites（P＞0.05）. There was statistical significance in D or c0/D among extensive metabolism type recipients with CYP3A5（rs776746）*1 and CYP3A4（rs2242480）*1G alleles，normal metabolism type recipients with only CYP3A5 （rs776746） *1 or CYP3A4 （rs2242480） *1G alleles and poor metabolism type recipients without CYP3A5（rs776746）*1 and CYP3A4（rs2242480）* 1G alleles（P＜0.05）. D of tacrolimus was the highest in extensive metabolism type recipient and the lowest in poor metabolism type recipient. CONCLUSIONS：The detection of genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）has guiding significance for individualized medication of tacrolimus after one year of tacrolimus administration.

Estimation of Aminophylline effectiveness at Neonatal Intensive Care Unit (NICU) using Artificial Intelligence

@#Introduction: The estimation of drug competence using Artificial Intelligence is presented in various literature for the adult population, but it is still new for drug dosage optimization in neonates. Aminophylline, a methylxanthine is administered as central nervous system stimulant for reducing Apnea episodes in neonates. Methods: The paper describes comparative evaluation of Support Vector Machine (SVM), K Nearest Neighbour (KNN), Decision Tree (DT) and Artificial Neural Network (ANN) for predicting drug effectiveness of Aminophylline. The models were evaluated using 100 Aminophylline cases based on various metrics such as sensitivity, specificity, and accuracy. The data used for the analysis was collected from the population pharmacokinetic study conducted at Kasturba Medical College, Neonatal Intensive Care Unit (NICU). Results: The evaluation result seemed to favour Multi-Layer Perceptron (MLP) with accuracy of 0.92 Area Under the Curve (AUC) followed by 0.85 (AUC) for Support Vector Machine (SVM). The input parameters in particular maternal, pharmacokinetics, demographic and physiological that were identified in literature as predictor variable played an important role in estimating effectiveness of Aminophylline regimens. Conclusion: Artificial Intelligence approach was potentially helpful in analysing drug dosage of Aminophylline and its effectiveness in diagnosing neonatal Apnea.

Ancient Literatures of Classical Famous Prescription Dihuang Yinzi / 中国实验方剂学杂志

Classical famous prescription Dihuang Yinzi is widely used in modern clinical practice，and can treat many kinds of diseases，especially the diseases of nervous system in internal medicine. Its clinical effect is accurate，but it has not been converted into Chinese patent medicine preparations. Therefore，the authors have collected ancient traditional Chinese medicine（TCM） literatures of Dihuang Yinzi by the methods of bibliometrics，and selected and sorted out 254 pieces of effective data， involving 144 ancient books of TCM，and systematically summarized and analyzed the historical development origin，main treatment syndrome，formula making principle，dosage，preparation method，decoction method and medicine taking method of Dihuang Yinzi，in order to provide the ancient literary evidence support for the development and clinical application of classic famous prescriptions. It is found that Dihuang Yinzi was from Xuanming Lunfang written by LIU He-jian，a doctor of Jin dynasty. It was composed of 12 kinds of herbs，namely Rehmanniae Radix Praeparata，Morindae Officinalis Radix，Corni Fructus，Cistanches Herba，Dendrobii Caulis，Aconm Lateralis Radix Praeparaia，Schisandrae Chinensis Fructus，Cinnamomi Ramulus，Poria，maimendong，Acori Calami Rhizoma and Polygalae Radix, and mainly used for the treatment of Yinfei. The later records of Dihuang Yinzi mostly followed the prescription composition and main treatment set forth in Xuanming Lunfang，and its clinical application was expanded. In the 199 articles with the indications for disease treatment，Yinfei was the most commonest indication, and took up about half of the total，which was followed by stroke，taking up about two fifths of the total. It was also used for the treatment of sudden aphonia，flaccidity syndrome，vertigo，enuresis. Dihuang Yinzi has a wide range of treatment，but the pathogenes is always belongs to "the deficiency of water and fire in the kidney". The recipe of Dihuang Yinzi was unique，and can be used to treat both the upper and lower parts of the body，as well as both the outward symptoms and root causes of an illness at the same time， in particular，it mainly focuses on the treatment of the lower and the root. Among the 56 literatures with drug dosage records，about one third of them inherited the records of Xuanming Lunfang: "Equal division，the top is the end，3 qian for each dose." The dosage was generally light. The preparations are mostly decoction and boiled powder. In the decocting and taking methods，it was suggested that "turbid medicine shall be boiled for a short time，and taken after several boilings，with no limit to time."

Preformulation of a liquid dosage formulation of captopril for pediatric use: drug-excipient compatibility and stability studies

Currently, medications used in children are typically modified from pharmaceutical dosage forms designed for adults. Captopril is widely adapted to liquid formulations for use in hospitals. Its stability in the aqueous medium is reduced since it undergoes oxidation producing captopril disulfide (its main metabolite). The aim of this formulation study was to suggest favorable conditions for the development of a stable captopril formulation. The compatibility between the drug and excipients was evaluated by differential scanning calorimetry analysis (DSC). For studies in solution, different formulations were prepared according to a factorial design varying EDTA concentration, water purity and pH. The resultant formulations were stored at 60°C and analyzed over a twelve-day period using HPLC. The DSC curves obtained suggested, although not conclusive to elucidation, interactions of captopril with citric acid and sucralose. The stability study of these solutions revealed that the variables significantly influenced captopril content, which degraded at zero order kinetics and rates differing by a factor of up to 7 times, where pH proved the most influential factor. Interactions between variables were observed. Therefore, development of a stable captopril formulation is feasible provided EDTA and a buffering agent is used at suitable concentrations (0.08% and pH 3.85).

Volume de dipirona para via oral versus tipo de conta-gotas, temperatura e ângulos de gotejamento / The volume of dipyrone for oral use versus dropper type, temperature and drip angles / Volumen de dipirona (metamizol) para vía oral versus tipo cuentagotas, temperatura y ángulo de goteo

Objetivo: determinar as diferenças entre volume e número de gotas de dipirona (via oral) por mililitro controlando algumas variáveis. Método: trata-se de um estudo experimental, com abordagem quantitativa, que foi realizado a partir de dados obtidos em experimentos realizados em laboratório, com dois tipos de conta-gotas, temperaturas de 5o e 35o Celsius, além da temperatura ambiente (30o Celsius), de laboratório e os ângulos de 90°, 60° e 45° utilizados para dispensar dipirona. Resultados: com base nos dados coletados, considerou-se que o ângulo de maior confiança para atingir o volume de 20 gotas por cada ml é o ângulo de 90o com o conta-gotas de vidro; em relação à temperatura, a maior confiança no volume de gotas desejado foi alcançada no intervalo de 5o e 30oCelsius. Conclusão: os resultados indicam a necessidade de seguir rigorosamente as orientações do fabricante para que se possa atingir a dose certa na administração de medicamento.

Objective: to determine the differences between volume and number of drops of dipyrone (oral) per milliliter, while controlling some variables. Method: this study applied quantitative analysis to data obtained in laboratory experiments with two types of droppers, temperatures of 5o and 35o Celsius, in addition to ambient temperature (30o Celsius), and the 90°, 60° and 45° angles used to dispense dipyrone. Results: based on the data collected, it was considered that, with the glass dropper, the angle of greatest confidence to achieve the volume of 20 drops per ml is 90o. In relation to temperature, the highest confidence in the desired volume of drops was achieved in the 5o to 30o Celsius interval. Conclusion: the results indicate the need to follow manufacturer's guidelines strictly, so as to achieve the correct dose for drug administration.

Objetivo: determinar las diferencias entre volumen y número de gotas de dipirona (vía oral) por mililitro controlando algunas variables. Método: se trata de un estudio experimental, con enfoque cuantitativo realizado con datos obtenidos en experimentos realizados en laboratorio, con dos tipos de cuentagotas, temperaturas de 5o y 35o Celsius, temperatura ambiente (30° Celsius) de laboratorio y los ángulos de 90°, 60° y 45° para gotear dipirona. Resultados: con base en los datos recolectados, se consideró que el ángulo de mayor confianza para alcanzar el volumen de 20 gotas por cada ml es el ángulo de 90o con el cuentagotas de vidrio. Respecto a la temperatura, la mayor confianza en el volumen de gotas deseado fue alcanzada en el intervalo de 5o y 30o Celsius. Conclusión: los resultados indican la necesidad de seguir rigurosamente las orientaciones del fabricante para alcanzar la dosis correcta en la administración de medicamentos.

Comparison of effect and safety of different dosages of alteplase in the treatment of elderly patients with acute cerebral infarction / 中国基层医药

Objective To compare the effect of different dosages of alteplase in the treatment of elderly patients with acute cerebral infarction,as well to evaluate the safety.Methods From January 2016 to June 2017,82 patients with acute cerebral infarction in the Hospital of Changping District were chosen in this study.The patients were randomly divided into 2 groups according to the digital table:41 patients in study group (0.6 mg/kg alteplase) and 41 patients in control group (0.9mg/kg alteplase).The effective rate and incidence of hemorrhage were compared between the two groups.Results The effective rate of the study group was 95.13％ (39/41),which of the control group was 100.00％ (41/41),the difference was not statistically significant (Z =4.982,P ＞ 0.05).The incidence rate of hemorrhage in the study group was 7.32％ (3/41),which in the control group was 24.39％ (10/41),the difference was statistically significant (x2 =6.248,P ＜ 0.05).Conclusion The effect of different dosages of alteplase demonstrates no significant difference in the treatment of elderly patients,and the safety of low dose is more reliable.

Analysis and Evaluation of Human Serum Albumin Use in 8 760 Inpatients / 中国药房

OBJECTIVE:To provide references for rational use of human serum albumin.METHODS:The inpatients receiving human serum albumin in the hospital during Jan.-Dec.2014 were investigated retrospectively and analyzed in respects of general information of patients,serum albumin level before medication,drug dosage,drug cost and reasons.RESULTS:Eight thousand seven hundred and sixty patients from top 8 departments in the list of the number of patients of human serum albumin were included in the study,accounting for 64％ of total.There were 5 244 male (59.9％) and 3 516 female (40.1％);patient's age mainly ranged ＞ 30-60 year-old (52.6％).The number of patients of albumin was the largest in general surgery department (2 588 cases) and cardio vascular surgery department (2 348 cases).Referring to domestic package inserts,8 210 patients (about 93.7％) were in accor dance with indications,and hypoproteinemia was the most common medication indication (35.6 ％).The drug dosage per capita of ICU was the highest (152.5 g);total drug cost was the highest in general surgery department (13 334 396.4 yuan);treatment course per capita of infection disease department was the longest (10.7 d).CONCLUSION:There is irrational use of human serum albumin in our hospital and difference of drug use among departments.It is necessary to strengthen human serum albumin use monitoring and establish rational medication evaluation system so as to promote standard drug use and realize rational distribution of medical resources.

Efficacy and safety of tacrolimus for patients with refractory IgA nephropathy / 第二军医大学学报

Objective To evaluate the efficacy and safety of tacrolimus (TAC) therapy in patients with refractory IgA nephropathy. Methods Nine IgA nephropathy patients were included in this study were treated from Jun. 2008 tc Sep. 2013 in Changzheng Hospital of Second Military Medical University. All patients received TAC therapy after the renin-angiotensin system (RAS) blockade therapy and steroid therapy failed. The main outcome was complete or partial remission. Secondary outcomes included the time required to remission, the frequency of recurrence, TAC dosage and adverse events. Results The initial dosage of TAC" was (1. 89 + 0. 33) mg/d. After treatment with TAC for 6 months, 6 patients achieved complete remission, 2 partial remission and 1 treatment resistance, and most of the remission patients achieved remission during the first 2 months of TAC therapy. The urine protein level of enrolled patients was significantly decreased ([3. 05 ± 1. 35] g/24 h vs [0. 85±1. 54] g/24 h. P<0. 05) and the serum album level of all patients was significantly improved ([27. 00±8. 37] g/L vs [37. 33±8. 08] g/L. P<0. 05). One patient receiving TAC" therapy presented worsened hypertension, and no other adverse event was observed in this study. Three of 8 proteinuria remission patients had relapses find achieved remission by adjusting the dosages of steroids and tacrolimus. Conclusion TAC ear improve proteinuria in patients with refractory IgA nephropathy, with less adverse reactions.

Summarize drug dosage forms in treatment of age-related macular degeneration disease / 中国中药杂志

In this review, the authors summarized the drugs in treatment of the age-related macular degeneration (AMD or ARMD), including the pathogenesis of the age-related macular degeneration at home and abroad, dosage forms used in the treatment, and the drugs research and development directions in the future. AMD disease is the third largest blinding diseases all over the world, with an incidence of 6.62%. The dosage form of the traditional medicine is mostly oral formulations, playing a role in body, while the newly dosage form is topical drug delivery formulation. Traditional Chinese medicine (TCM) has certain advantages in the treatment of AMD disease and the development of topical drug delivery preparations with newly preparation technologies would have a very bright prospect in the future.

Retrospective analysis of the financial break-even point for intrathecal morphine pump use in Korea

BACKGROUND: The high cost of intrathecal morphine pump (ITMP) implantation may be the main obstacle to its use. Since July 2014, the Korean national health insurance (NHI) program began paying 50% of the ITMP implantation cost in select refractory chronic pain patients. The aims of this study were to investigate the financial break-even point and patients' satisfaction in patients with ITMP treatment after the initiation of the NHI reimbursement. METHODS: We collected data retrospectively or via direct phone calls to patients who underwent ITMP implantation at a single university-based tertiary hospital between July 2014 and May 2016. Pain severity, changes in the morphine equivalent daily dosage (MEDD), any adverse events, and patients' satisfaction were determined. We calculated the financial break-even point of ITMP implantation via investigating the patient's actual medical costs and insurance information. RESULTS: During the studied period, 23 patients received ITMP implantation, and 20 patients were included in our study. Scores on an 11-point numeric rating scale (NRS) for pain were significantly reduced compared to the baseline value (P < 0.001). The MEDD before ITMP implantation was 0.59 [IQR: 0.55–0.82]. The total MEDD increased steadily to 0.77 [IQR: 0.53–1.08] at 1 year, which was 126% of the baseline (P < 0.001). More than a half (60%) responded that the ITMP therapy was somewhat satisfying. The financial break-even point was 28 months for ITMP treatment after the NHI reimbursement policy. CONCLUSIONS: ITMP provided effective chronic pain management with improved satisfaction and reasonable financial break-even point of 28 months with 50% financial coverage by NHI program.

Risk factor analysis of additional administration of sedative agent and patient dissatisfaction in intravenous conscious sedation using midazolam for third molar extraction

OBJECTIVES: The primary purpose of this study was to investigate the factors related with additional administration of sedative agent during intravenous conscious sedation (IVS) using midazolam (MDZ). The secondary purpose was to analyze the factors affecting patient satisfaction. MATERIALS AND METHODS: Clinical data for 124 patients who had undergone surgical extraction of mandibular third molar under IVS using MDZ were retrospectively investigated in this case-control study. The initial dose of MDZ was determined by body mass index (BMI) and weight. In the case of insufficient sedation at the beginning of surgery, additional doses were injected. During surgery, peripheral oxygen saturation, bispectral index score (BIS), heart rate, and blood pressure were monitored and recorded. The predictor variables were sex, age, BMI, sleeping time ratio, dental anxiety, Pederson scale, and initial dose of MDZ. The outcome variables were additional administration of MDZ, observer's assessment of alertness/sedation, intraoperative amnesia, and patient satisfaction. Descriptive statistics were computed, and the P-value was set at 0.05. RESULTS: Most patients had an adequate level of sedation with only the initial dose of MDZ and were satisfied with the treatment under sedation; however, 19 patients needed additional administration, and 13 patients were unsatisfied. In multivariable logistic analysis, lower age (odds ratio [OR], 0.825; P=0.005) and higher dental anxiety (OR, 5.744; P=0.003) were related to additional administration; lower intraoperative amnesia (OR, 0.228; P=0.002) and higher BIS right before MDZ administration (OR, 1.379; P=0.029) had relevance to patient dissatisfaction. CONCLUSION: The preoperative consideration of age and dental anxiety is necessary for appropriate dose determination of MDZ in the minor oral surgery under IVS. The amnesia about the procedure affects patient satisfaction positively.

Serum levels of vancomycin: is there a prediction using doses in mg/kg/day or m2/day for neonates?

Abstract Coagulase-negative Staphylococcus has been identified as the main nosocomial agent of neonatal late-onset sepsis. However, based on the pharmacokinetics and erratic distribution of vancomycin, recommended empirical dose is not ideal, due to the inappropriate serum levels that have been measured in neonates. The aim of this study was to evaluate serum levels of vancomycin used in newborns and compare the prediction of adequate serum levels based on doses calculated according to mg/kg/day and m2/day. This is an observational reprospective cohort at a referral neonatal unit, from 2011 to 2013. Newborns treated with vancomycin for the first episode of late-onset sepsis were included. Total dose in mg/kg/day, dose/m2/day, age, weight, body surface and gestational age were identified as independent variables. For predictive analysis of adequate serum levels, multiple linear regressions were performed. The Receiver Operating Characteristic curve for proper serum vancomycin levels was also obtained. A total of 98 patients received 169 serum dosages of the drug, 41 (24.3%) of the doses had serum levels that were defined as appropriate. Doses prescribed in mg/kg/day and dose/m2/day predicted serum levels in only 9% and 4% of cases, respectively. Statistical significance was observed with higher doses when the serum levels were considered as appropriate (p < 0.001). A dose of 27 mg/kg/day had a sensitivity of 82.9% to achieve correct serum levels of vancomycin. Although vancomycin has erratic serum levels and empirical doses cannot properly predict the target levels, highest doses in mg/kg/day were associated with adequate serum levels.

Study on the Effects of Total Cost Prospective Payment System on the Consumption of Drugs / 中国药房

OBJECTIVE:To investigate the consumption of drugs after the inplementation of total cost prospective payment sys-tem(PPS),and to provide reference for hospital drug cost control. METHODS:The data of prescriptions collected from 9 hospital during 2007-2014 were divided into group A,B and C according to PPS,and then summarized statistically in respects of increase rate of total consumption sum,consumption sum ratio of major category;the drug cost per time of outpatient department,emergen-cy department and inpatient department were calculated as well as consumption sum ratio of self-paid drugs;the dosage per time of drugs in blood pressure and diabetes prescription were also calculated. RESULTS:The total consumption sum of drug increased slowly after the implementation of total cost PPS;the consumption sum ratio of major category kept stable,while that of anti-infec-tive agent decreased;the emergency drug cost per time achieved a negative growth,and outpatient and inpatient drug cost per time increased slightly. The proportion of self-paid drugs was relatively stable. The dosage per time of drugs in hypertension and diabetes prescriptions was stable,too. CONCLUSIONS:Total cost PPS is useful in controlling the rapid growth of drug costs,and promote the reasonable drug use. The consumption sum of self-paid drugs are well controlled. The increase of drug cost per time in outpa-tient and inpatient should arouse the attention of the relevant departments. In addition,it has no effect on drug dosage for the pa-tients with hypertension and diabetes.

Effects of serum level of TPOAb on Graves disease in patients using anti-thyroid drug treatment / 天津医药

Objective To analyse effects of the serum levels of thyroid peroxidase antibodies (TPOAb) on antithyroid drugs (ATD) treatment in patients with incipient Graves disease (GD). Methods A total of 121 patients with incipient GD, who were used anti thyroid drugs for 12 months, were included in this study. Patients were dvided into two groups:TPOAb negative group (TPOAb≤35 IU/mL, n=49) and TPOAb positive group (TPOAb>35 IU/mL, n=72). According to the degree of TPOAb drops the TPOAb positive group was sub-divided into low level positive group (35 IU/mL1 000 IU/mL, n=20). The ATD total dosage for 12 months and thyroid-stimulating hormone (TSH), which returned to normal rate after treatment of 3, 6 and 12 months, were compared between groups. Results ATD total dose was lower in TPOAb positive group (1 743.82±265.38) mg than that of negative group (1 889.18 ±125.51) mg. The ATD total dosages were (1 759.71±230.29) mg, (1 793.75±299.02) mg, (1 731.54± 236.44) mg and (1 710.00 ± 290.73) mg for low level TPOAb positive group, medium level TPOAb positive group, high level TPOAb positive group, and very high level TPOAb positive group respectively. The recovering ratio of TSH was significantly higher in TPOAb positive group than that of TPOAb negative group after 3-month treatment (P<0.05). Conclusion TPOAb positive serum can lead to shorten the course of ATD treatment and reduce the total amount of ATD treatment in GD patients.

Prospective validation of a novel dosing scheme for intravenous busulfan in adult patients undergoing hematopoietic stem cell transplantation

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW(0.5) mg daily) targeting an area under the concentration-time curve (AUC) of 5924 µM·min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC (AUC(PRED)). The accuracy and precision of the AUC(PRED) values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 µM·min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUCPRED were -5.8% and 20.6%, respectively, in the conventional dosing group and −2.1% and 14.0%, respectively, in the new dosing scheme group. These fi ndings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.