ObjectiveTo investigate the recent development of Acinetobacter baumannii infection and its drug-resistance.MethodsThe Acinetobacter baumannii infections of inpatients during the year 2001 to June,2005 were analyzed retrospectively. ResultsThe infection of Acinetobacter baumannii increased from 15 strains in 2001 to 68 strains in the first half of 2005.The rate of high drug-resistance strains also raised from 20% to 77%.ConclusionThe incident of infection of Acinetobacter baumannii continuously increased in the past 5 years and became more difficult to treat.

ObjectiveTo investigate the clinical features of chronic lung diseases patients combined with lung fungal infection.MethodsThe data of 216 hospitalized cases with chronic lung diseases were retrospectively analyzed.ResultsThe rate of lung fungal infection of chronic lung diseases patients was 28.1%, and the main pathologic fungal was Candida albicans, about 67.2 %.ConclusionThe chronic lung diseases patient has a higher rate of lung fungal infections compared with other diseases. The measures of preventing, diagnosing and treating lung fungal infection at early stage should be taken.

Objective To compare the ROSCO disk diffusion method with broth microdilution method (CLSI, M27-A) for antimicrobial susceptibility test of Candida species isolated from patients with lung cancer. Methods Danish ROSCO company disk diffusion testing method and bio Merieux ATB FUNGUR2 were applied to test 5-flucytosine, fluconazole, itraconazole and amphotericin B antimicrobial susceptibility for 78 Candida species strains isolated from patients with lung cancer. Results Through evaluating the susceptibility to 5-flucytosine, amphotericin B, fluconazole and itraconazole by disk diffusion method, the Kappa value was 0.89. The sensitive strains detected by one method did not show resistance in another method. The sensitive rates of 78 strains of Candida species to 5-flucytosine, amphotericin B, fluconazole and itraconazole were 88.20 %, 89.17 %, 56.34 % and 52.12 %. The susceptibility of C.albicans, C.tropicalis, C.glabrata and C.krusei to four kinds of antifungal agents was 90.95 %, 85.71 %, 67.50 % and 41.67 %respectively. Conclusions Results of disk diffusion method coincide well with broth microdilution method. It can be chosen as a clinical routine method for antimicrobial susceptibility test.

Corpus Callosum infarction is relatively rare in clinical practice, of which the pathogenesis is still unclear. The artical reports a patient with bilateral corpus callosum infarction associated with Moyamoya syndrome, discussing the etiology from the perspective of vascular anatomy and risk factors. With the review of relevant clinical cases home and abroad nearly a decade, we analyzed and summarized the vascular features of corpus callosum infarction and the main etiology, in order to contribute to clinical diagnosis and treatment.

Objective:To analyze the predictive factors of autogenous arteriovenous fistula (AVF) maturation and tentatively discuss the intervention timing of assisted maturation.Methods:It was a retrospective study. The data of patients with newly established AVF and regular follow-up in Haidian Hospital, the Third Hospital of Peking University from August 1, 2018 to March 31, 2022 were analyzed. The patients were divided into mature group and immature group based on whether they met clinical maturity or ultrasonic maturity criteria 3 months after AVF establishment.The general data, preoperative laboratory examination and postoperative ultrasonic examination parameters were compared between the two groups. Logistic regression analysis model was used to analyze the related factors of AVF maturation, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of each factor for AVF maturation and intervention timing.Results:A total of 568 patients were included, with age of (56.86±13.82) years old, 339 males (59.68%), and 229 females (40.32%). There were 380 patients in the maturation group and 188 patients in the immature group. The total rate of AVF maturation was 66.90% (380/568). The anastomosis diameter ( t=9.732, P < 0.001), ln(anastomosis artery diameter)( t=10.116, P < 0.001), anastomosis vein diameter ( t=13.961, P < 0.001), ln(brachial artery diameter)( t=9.362, P < 0.001) and brachial artery blood flow ( t=16.542, P < 0.001) of postoperation one month, and anastomosis diameter ( t=7.356, P < 0.001), anastomosis artery diameter ( t=11.117, P < 0.001), anastomosis vein diameter ( t=12.332, P < 0.001), ln(brachial artery diameter) ( t=7.956, P < 0.001) and brachial artery blood flow ( t=13.803, P < 0.001) of postoperation three months in the mature group were significantly higher than those in the immature group. Logistic regression analysis models showed anastomosis vein diameter at 1 month after surgery ( OR=0.577, 95% CI 0.342-0.975, P=0.040), brachial arterial blood flow at 1 month after surgery ( OR=0.988, 95% CI 0.996-1.000, P=0.043) and brachial arterial blood flow at 3 months after surgery ( OR=0.997, 95% CI 0.995-0.999, P=0.002) were the independent relevant factors of AVF maturation. When the anastomosis vein diameter ≥ 3.90 mm at 1 month after AVF surgery ( AUC=0.842, 95% CI 0.809-0.871, P < 0.001), the blood flow of brachial artery ≥ 446.90 ml/min at 1 month after AVF surgery ( AUC=0.880, 95% CI 0.850-0.906, P < 0.001), the critical value of the combined index of anastomotic vein diameter and blood flow of brachial artery at 1 month after fitting ≥ 0.44 ( AUC=0.889, 95% CI 0.860-0.914, P < 0.001) and brachial arterial blood flow ≥ 595.00 ml/min ( AUC=0.857, 95% CI 0.822-0.888, P < 0.001), the unassisted maturation of AVF could be predicted. Conclusions:The anastomosis vein diameter ≥ 3.90 mm at 1 month after AVF surgery, and the blood flow of brachial artery ≥ 446.90 ml/min at 3 months after AVF surgery, or the critical value of combined index of both after fitting ≥ 0.44 can predict the unassisted maturation of AVF, and one month after surgery may be the opportunity for early intervention to promote maturation.

Objective: To explore the efficacies of regimens of three-drug induction therapy (ATRA+ATO+anthracyclines) versus two-drug induction therapy (ATRA+ATO) in patients with acute promyelocytic leukemia (APL). Methods: Of 184 patients diagnosed with APL from January 2009 to March 2016, 58 patients underwent three-drug induction therapy, while the rest were treated with two-drug induction therapy. Three-drug induction therapy was of ATRA (20 mg·m^-2·d^-1, d_1-28) + ATO (0.16 mg·kg^-1·d^-1, d_1-28) + Idarubicin (8 mg·m^-2·d^-1, d_3-5) /daunorubicin (40 mg·m^-2·d^-1, d_3-5) , while two-drug induction therapy ATRA+ATO with the same doses and methods as above. Of 184 cases, 69 cases accompanied with WBC counts>10×10⁹/L, 115 cases with WBC counts≤10×10⁹/L at onset. Results: ①Short-term efficacy: After one cycle induction therapy, the rates of hematologic remission, genetic remission, molecular remission and induced differentiation syndrome (DS) in three-drug regimen group were 98.3%, 87.9%, 72.4% and 0 respectively, while those in two-drug regimen group were 87.3%, 65.9%, 51.6% and 12.7% respectively. In patients with WBC >10×10⁹/L, DS rate and early mortality in three-drug regimen group were lower than in two-drug regimen group (0 vs 15.6%, 4.2% vs 15.6%, respectively). In patients with WBC≤10×10⁹/L, DS rate in three-drug regimen group was also lower than in two-drug regimen group (0 vs 12.3%) , but there were no statistical differences in terms of relapse and early mortality. ② Long-term efficacy: The relapse rate, overall survival (OS) and disease free survival (DFS) in three-drug regimen group were 0, 98.5%, 96.6% respectively, while those in two-drug regimen group were 8.6%, 86.5% and 84.1% respectively; the advantages of three-drug over two-drug regimen, especially in cases of WBC >10×10⁹/L were observed. ③ Side effects: the incidences of gastrointestinal reaction, liver dysfunction, myocardial damage and headache in three-drug regimen group hardly increased. Conclusion The efficacies of three-drug induction therapy were superior to two-drug one.

Objective:To investigate the clinical features and associated influencing factors of cognitive impairment in middle-aged and elderly Chinese adult patients undergoing maintenance hemodialysis (HD).Methods:A cross-sectional study was conducted among HD patients from 11 centers in Beijing city from April 2017 to June 2017. A neuropsychological battery covering domains of attention/processing speed, executive function, memory, language, and visuospatial function was applied in cognitive function assessment. Patients were classified as normal cognitive function group and cognitive impairment group according to the fifth version of the diagnostic and statistical manual of mental disorders criteria (DSM-V). Multivariate binary logistic regression was used to analyze the independent influencing factors of cognitive impairment. Results:A total of 613 HD patients were included in the study, and the prevalence of cognitive impairment was 80.91% (496/613). Attention impairment (81.05%) and memory impairment (63.51%) were the most common impaired domains, and 79.23% was concomitant impairment across two or more cognitive domains among those with cognitive impairment. Compared with the patients in the normal cognitive function group, the patients in the cognitive impairment group had senior age, longer dialysis vintage, higher proportion of diabetes, hypertension, and stroke, higher level of serum intact parathyroid hormone (iPTH), lower education level, and lower urea clearance index (Kt/V) (all P<0.05). Factors were independently associated with cognitive impairment including increasing age ( OR=1.110, 95% CI 1.072-1.150, P<0.001), education time>12 years (with education time<6 years as reference, OR=0.323, 95% CI 0.115-0.909, P=0.032), history of diabetes ( OR=2.151, 95% CI 1.272-3.636, P=0.004), history of stroke ( OR=2.546, 95% CI 1.244-5.210, P=0.011), increased dialysis vintage ( OR=1.016, 95% CI 1.010-1.022, P<0.001), reduced Kt/V( OR=0.008, 95% CI 0.002-0.035, P<0.001), and increased iPTH level ( OR=1.002, 95% CI 1.002-1.003, P=0.012). Conclusions:The prevalence of cognitive impairment in middle-aged and elderly adult Chinese patients undergoing HD is high. Memory and attention are the most commonly impaired domains. Increasing age, low education level, history of diabetes and stroke, increased dialysis vintage, reduced Kt/V and increased serum iPTH are the independent influencing factors associated with cognitive impairment.

Objective:To investigate the association between cognitive impairment and all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis (HD).Methods:A prospective cohort study was conducted. Patients from 11 HD centers in Beijing between April and June 2017 were enrolled. Baseline data were collected, and a series of neuropsychological batteries covered 5 domains of cognitive function were applied for the assessment of cognitive function. The patients were then classified as normal and cognitive impairment groups according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-V) and followed-up until June 2018. The clinical characteristics of the two groups of patients were compared. Kaplan-Meier survival analysis was used to compare the difference in the cumulative survival rate between the two groups. Multivariate Cox regression model was used to analyze the independent influencing factors of all-cause mortality, to determine the relationship between cognitive impairment and different cognitive domain impairments and all-cause death.Results:A total of 613 patients were enrolled, of which 496(80.91%) patients had cognitive impairment. Compared with the normal cognitive function group, the patients in the cognitive impairment group tended to be older, longer dialysis vintage, a higher proportion of diabetes, hypertension, and stroke, increased serum iPTH level, and lower education level and urea clearance index (Kt/V) (all P<0.05). After (49.53±8.42) weeks of follow-up, Kaplan-Meier survival analysis showed that the cumulative survival rate of cognitive impairment group was significantly lower than that of cognitive normal group (Log-rank χ2=8.610, P=0.003). Multivariate Cox regression analysis showed that history of diabetes ( HR=2.742, 95% CI 1.598-4.723, P<0.001), coronary heart disease ( HR=1.906, 95% CI 1.169-3.108, P=0.010), dialysis vintage (every increase of 1 month, HR=1.007, 95% CI 1.003-1.011, P=0.001), serum level of albumin (every increase of 1 g/L, HR=0.859, 95% CI 0.809-0.912, P<0.001), cognitive impairment ( HR=2.719, 95% CI 1.088-6.194, P=0.032) were independently associated with all-cause mortality. Multivariate Cox regression analysis on different cognitive domains also indicated that memory impairment ( HR=2.571, 95% CI 1.442-4.584, P<0.001), executive function impairment ( HR=3.311, 95% CI 1.843-5.949, P=0.001) and three, four, five domains combined impairment ( HR=5.746, 95% CI 1.880-17.565, P=0.002; HR=12.420, 95% CI 3.690-41.802, P<0.001; HR=13.478, 95% CI 3.381-53.728, P<0.001) were independently related to all-cause mortality. Conclusions:Cognitive impairment is an independent risk factor of all-cause mortality in middle and elderly adult patients undergoing maintenance hemodialysis, and the risk is significantly increased in patients with the impairment of the domains of memory, executive function, or in the combination of three to five cognitive domains.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.