OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

INTRODUCTION: Takayasu arteritis is the most common large-vessel vasculitis in childhood, but there is a lack of literature regarding childhood-onset Takayasu arteritis (c-TAK) in Southeast Asia. We aim to describe a c-TAK cohort in Singapore and highlight a unique subset that first presents with Kawasaki-like disease (KD). METHOD: A single-centre cohort study in Singapore of consecutive children diagnosed with c-TAK between 2002 and 2023 was performed. Demographic and clinical features, laboratory and angiographic findings, treatment, and outcomes were summarised. Disease activity was evaluated using the Paediatric Vasculitis Disease Activity Score and inflammatory markers. RESULTS: Twenty-three patients, fulfilling both the EULAR/ PRINTO/PReS and ACR/EULAR 2022 criteria, were recruited. The most common clinical features at diagnosis were fever (15, 65%) and neurological symptoms (11, 48%, half of which presented with stroke), while the most prevalent angiographic pattern by Hata's classification was Type V (21, 91%). Eight children (35%) initially presented with refractory KD, and these patients were significantly younger, more male-predominant, and had higher inflammatory markers at diagnosis; all of them had coronary artery involvement, but none had intracranial vascular findings. Of the entire cohort, 16 (70%) achieved inactive disease on medications with a median duration of 6 months (interquartile range [IQR]: 4-11), and 8 (35%) achieved remission off medications with a median duration of 43 months (IQR 35-60). CONCLUSION Our c-TAK cohort has high proportions of neurological involvement and stroke. This is also the first cohort study to describe a distinct group of patients who first presented with refractory KD.
Humans ; Takayasu Arteritis/complications* ; Singapore/epidemiology* ; Male ; Female ; Child ; Adolescent ; Age of Onset ; Mucocutaneous Lymph Node Syndrome/diagnosis* ; Cohort Studies ; Child, Preschool ; Fever/etiology* ; Stroke/epidemiology* ; Retrospective Studies

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

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.

Objective:To explore the association between lifestyle-related factors and colorectal adenoma.Methods:Based on the Screening Project of Early Diagnosis and Treatment of Colorectal Cancer in Jiashan county Zhejiang province, from August 2012 to March 2018, information gathered through records on questionnaire and colonoscopic diagnosis were collected from participants with positive results during the primary screening stage. According to the findings of colonoscopy, 11 232 controls without any colorectal diseases and 3 895 cases with colorectal adenoma were included in the study. Multivariate logistic regression models were used to analyze the association between lifestyle-related factors and colorectal adenoma.Results:After adjusting for possible confounding factors, results from multivariate logistic regression analysis showed that smoking, alcohol drinking and obesity were positively related to the risk of colorectal adenoma, with ORs (95 %CIs) as 1.38 (1.24-1.54), 1.37 (1.24-1.51) and 1.38 (1.20-1.59) respectively. However, regular aspirin intake was negatively related with the risk of colorectal adenoma ( OR=0.65, 95 %CI: 0.53-0.80). After stratified by sex and age, data showed that the associations between smoking, alcohol drinking and colorectal adenoma were statistically significant in males, and the association between regular aspirin intake and colorectal adenoma was also statistically significant in older participants (aged 60 years and older). Conclusion:Smoking, alcohol drinking, regular aspirin intake and obesity were associated with colorectal adenoma.

Objective By analyzing the perioperative management in our hospital to explore the clinical effect and safety of single kidney transplantation from deceased juveniles' donors.Methods We retrospectively analyze 86 cases of kidney transplantations from deceased juveniles' donors in our hospital from 2007 December to 2015 August.Results The success rate of the operations was 100％.The postoperative complications occurred as fellows:7 cases of acute rejection (8.14％);10 cases of drug intoxication (11.62％);21 cases of DGF (24.44％),4 cases of leakage of urine (4.65％),7 cases of lung infection (8.14％).Two cases (2.32％) died after the operation because of serious lung infection,and by corresponding treatment 47 cases recovered after 2-4 weeks.The creatinine level in 37 cases without any complications was 131.88 ± 44.20 μmol/L during discharge.Conclusion With strict selection,the organ from a deceased juvenile donor is safe and practicable.

Objective To observe the curative effect of imatinib mesylate combined with myeloablative allogeneic hematopoietic stem cell transplantation for treatment of chronic myeloid leukemia advanced phase. Methods To retrospectively analyze clinical effect of 6 patients with chronic myeloid leukemia advanced phase were treated with imatinib mesylate combined with myeloablative allogeneic hematopoietic stem cell transplantation from July 2005 to April 2009, and literature review. Results The disease-free survival and the survival rate of 4 patients were 66.67 %. 2 patients died (one case die for Chemotherapy pretreatment in the third transplantation after two years, the other case die for Chemotherapy pretreatment in the second transplantation after six months ). Conclusion The clinical cure rate of chronic myeloid leukemia advanced phase may be improved with the treatment of imatinib mesylate combined with myeloablative allogeneic hematopoietic stem cell transplantation.

Objective To compare the clinical effect, hematopoietic reconstitution, and adverse effects of compatriots HLA in the same period with haploidentical allogeneic hematopoietic stem cell transplantation among relatives for treatment of haematological malignancies. Methods 9 patients of compatriots HLA and 9 patients of haptoidentical allogeneic were recruited. The clinical effect, hematopoietic reconstitution, and transplant-related adverse effects of the observation groups were retrospectively analyzed. Results There was no statistical difference between the clinical effect in two groups, hematopoietic reconstitution, pretreatment-related toxicity and acute and chronic GVHD. The infusion volume of blood products, CMV infection and fungal infection in haploidentical transplant group was higher than that in compatriots HLA group. Conclusion HLA haploidentical family donor transplantation is a good way to increase the source of donor for the treatment of haematological malignancies.