Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasi...Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.展开更多
Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases an...Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.展开更多
Objective:To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia(P.daemia) against anti-tuberculosis drugs(ATDs) induced liver injury.Methods:Wistar albino rats were divided into seven groups...Objective:To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia(P.daemia) against anti-tuberculosis drugs(ATDs) induced liver injury.Methods:Wistar albino rats were divided into seven groups of six animal in each.The ATDs and P.daemia extract(100,200 and 400 mg/kg,p.o.) were conjointly administered for 8 weeks and various biochemical,histoarchitectural,ultrastructural studies were performed.Results:Administration of ATDs significantly increased aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,triglycerides,cholesterol,bilirubin and decreased glucose and albumin level.Increased lipid peroxidation and reduction in glutathione,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase and glucose-6-phosphate dehydrogenase were found after ATDs exposure.Administration of P.daemia extract maintained serum biochemical indices as well as antioxidant status similar to control and diminished oxidative stress in dose dependent manner.Histological and ultra-structural observations substantiated biochemical findings.Conclusions:P.daemia has therapeutic potential against ATDs induced liver injury and may be of clinical significance after extensive studies.展开更多
Background/objective: A nationwide survey on the resistance to first line anti-tuberculosis (anti-TB) drugs was conducted in Ghana from 2007-2008 by Noguchi Memorial Institute for Medical Research in collaboration wit...Background/objective: A nationwide survey on the resistance to first line anti-tuberculosis (anti-TB) drugs was conducted in Ghana from 2007-2008 by Noguchi Memorial Institute for Medical Research in collaboration with the National Tuberculosis Control Programme. We aimed to characterize mycobacterial species causing pulmonary tuberculosis (PTB) and determine the resistance pattern to first line anti-TB drugs among newly diagnosed and previously treated PTB patients in Ghana. Methods: Two sputum samples from consented new smear positive PTB patients who had never been treated for TB or had been on anti-TB treatment for less than a month and patients who had been treated for TB previously for more than a month in selected diagnostic centres nationwide were collected for culture, identification and drug susceptibility test. Culture positive isolates were tested against streptomycin (S), isoniazid (H), rifampicin (R) and ethambutol (E) using the simplified proportion method and line probe assay (LPA). The LPA was performed in mid-2017. Results: Among 410 samples, 345 positive cultures were obtained and identified as Mycobacterium tuberculosis complex (MTBC). Of the 345 isolates, 133 were further differentiated by GenoType MTBC®as M. tuberculosis, 126 (94.7%) and M. africanum 7 (5.3%). The overall drug resistance patterns were as follows: 43/345 (12.5%), 6/345 (1.7%), 9/345 (2.6%) and 71/345 (20.6%) were resistant to H, R, E and S respectively and 5/345 (1.4%) were multi-drug resistant (MDR). Conclusion: The results indicate high levels of resistance to S and H among new and previously treated TB patients. We recommend adequate surveillance systems including periodic national anti-TB drug resistance surveys.展开更多
The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combination...The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.展开更多
BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis...BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.展开更多
Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of im...Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.展开更多
Some bacteria have the ability to co-exist, proliferate and survive in a multicellular community, biofilm. Each participating bacteria can form its colonies and encases itself by a self-produced insoluble extracellula...Some bacteria have the ability to co-exist, proliferate and survive in a multicellular community, biofilm. Each participating bacteria can form its colonies and encases itself by a self-produced insoluble extracellular matrix substance (EPS). Microcolonies within biofilm are held together by interactions and bonding of the substances present in the EPS with their separation from the water channels. Similar to insoluble EPS, bacterial microcolonies release soluble exofactors that have direct impacts on the survivability, growth and antibacterial resistivity of other microcolonies made of single- or multi-species bacteria in the same biofilm. How the exofactors of microcolonies of one-type bacteria impact on microcolonies of other-type bacteria is still unclear. We studied about the role of exofactors released from Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are common biofilm-forming pathogenic bacteria. Exofactors facilitate to transform the microenvironment where bacteria can acquire alternative lifestyle with a long survival period and resistivity to certain antimicrobial drugs.展开更多
[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and ...[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.展开更多
Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incide...Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.展开更多
Background:Alcohol and illicit drugs(AID)continue to be a major global health concern.Although preventable,AID is linked to millions of deaths annually worldwide.The situation is particularly grave for young people,wi...Background:Alcohol and illicit drugs(AID)continue to be a major global health concern.Although preventable,AID is linked to millions of deaths annually worldwide.The situation is particularly grave for young people,with AID being a major direct risk factor for disability-adjusted youth life-years lost and death.It further contributes to assaults,road crashes,accidental poisoning,and suicide,leading to long-term issues and public health concerns.Objective:This study aimed at disclosing current AID prevalence data for Argentinian,Bulgarian,Chilean and Romanian youth.It shed light on the predictors of AID in young people from those countries.Method:The study used an online survey to gather data from people aged 18 to 25(n=1,297).The survey was underpinned by the theory of planned behaviour(TPB).Predictors were investigated separately for drinking alcohol and using illicit drugs.Results:Our data revealed that across the four target countries,49%to 90%of the participants drank alcohol,and 8%to 35%used illicit drugs in the past three months.Between 20%and 91%of them intended to drink,and between 8%and 31%intended to use illicit drugs in the following three months.Our TPB model predicted statistically significant(P<0.001)amounts of variance in drinking alcohol(between 61%and 72%)and using illicit drugs(between 20.3%and 74.4%).Intention was consistent in significantly predicting both behaviours.Evidence around the predictive validity of self-efficacy,age and gender was mixed across the investigated countries.Conclusion:This research provided an update on the scarce AID epidemiological data.It also supplied evidence about what theoretically-informed measures might be useful targets of interventions in the case of Argentina,Bulgaria,Chile and Romania.This new knowledge of understanding substance abuse determinants and prevalence may help researchers and practitioners better meet young people's health prevention needs.展开更多
Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no prop...Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.展开更多
Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common ...Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.展开更多
Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between m...Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between men and women.Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects.Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions,to maximize therapeutic effectiveness and to provide personalized management of care.展开更多
Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune chec...Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.展开更多
BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review an...BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.展开更多
Objective To analyze the reimbursement policies of innovative drugs in some developed countries,and to provide reference for future reimbursement management in China.Methods Literature research method was used to stud...Objective To analyze the reimbursement policies of innovative drugs in some developed countries,and to provide reference for future reimbursement management in China.Methods Literature research method was used to study the policies related to the reimbursement management of innovative drugs in Germany,France and Japan,and their successful experience was summarized.Results and Conclusion China should establish an open and transparent value evaluation standard to improve the medical insurance reimbursement management of innovative drugs.Besides,the value of innovative drugs should be taken as an important basis for reimbursement decisions,and an independent third-party value evaluation agency must be established.展开更多
Objective To identify technical risks in the process of innovative drug development,and to provide reference for technical risk management so as to reduce the uncertainties and improve the efficiency of research and d...Objective To identify technical risks in the process of innovative drug development,and to provide reference for technical risk management so as to reduce the uncertainties and improve the efficiency of research and development.Methods The initial risk index was investigated by literature research.Then,the Likert scale was used to design a questionnaire,and the experts’opinion was used to analyze the risk factors affecting the different stages of the development of innovative drugs in China.Results and Conclusion Based on the analysis of questionnaire,31 risk indicators of five key stages in the development of innovative drugs from drug discovery to marketing authorization were established.The key risk indicators constructed in this study can provide reference for technology-related risk management in the process of innovative drug development.展开更多
Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involv...Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.展开更多
文摘Introduction: Multi-drug resistant tuberculosis (MDR-TB) that is the tuberculosis that is resistant to at least 2 of the first line anti-tuberculosis drugs is fatal infectious disease. Cases of MDR-TB are now increasing with 30,000 cases of MDR-TB reported in 2013 by national TB programme. Rapid diagnosis of MDR-TB is extremely important for rapid treatment of patient and to prevent spread of MDR-TB to other. BACTEC 960 system helps in rapid diagnosis but purchase of expensive instrument for the same is the limitation. However, the same purpose can be solved by use of semi-automated MGIT system. Aims and Objectives: Aim of this study is to do drug sensitivity testing of the first line anti-tuberculosis drugs with the use of semi-automated MGIT systems. 350 newly registered and suspected cases of tuberculosis in tertiary care hospital were included. Samples were processed for digestion and decontamination and inoculated in MGIT tubes and also on LJ medium. Reading was taken using semi-automated MGIT system. Positive tubes were confirmed by rapid test for M. tuberculosis and then drug sensitivity was performed. Result: Out of 350 samples, 62% were sputum;33% were pleural fluid and rest 5% were lymph node, Ascetic fluid, CSF, pus. Average day of positivity by MGIT was 13 - 20 days as compared to 25 - 37 days by solid medium, which was statistically significant with p value Conclusion: Manual MGIT System is a simple, efficient, safe to use diagnostic system. It does not require any expensive/special instrumentation other than the UV lamp for detection of fluorescence. The rapidity by which mycobacteria are detected is the most important advantage of the Manual MGIT. In areas with limited resources where purchase of expensive instruments such as the MGIT960 is out of scope, the use of manual MGIT for rapid susceptibility testing for MDR-TB could be a possibility.
文摘Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.
基金Financial assistance from University Grants Commission,New Delhi(UGC-MRP,F.42-520/2013 SR)Guru Ghasidas University,Bilaspur for providing laboratory facility
文摘Objective:To evaluate therapeutic potential of hydroethanolic extract of Pergularia daemia(P.daemia) against anti-tuberculosis drugs(ATDs) induced liver injury.Methods:Wistar albino rats were divided into seven groups of six animal in each.The ATDs and P.daemia extract(100,200 and 400 mg/kg,p.o.) were conjointly administered for 8 weeks and various biochemical,histoarchitectural,ultrastructural studies were performed.Results:Administration of ATDs significantly increased aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase,triglycerides,cholesterol,bilirubin and decreased glucose and albumin level.Increased lipid peroxidation and reduction in glutathione,superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase and glucose-6-phosphate dehydrogenase were found after ATDs exposure.Administration of P.daemia extract maintained serum biochemical indices as well as antioxidant status similar to control and diminished oxidative stress in dose dependent manner.Histological and ultra-structural observations substantiated biochemical findings.Conclusions:P.daemia has therapeutic potential against ATDs induced liver injury and may be of clinical significance after extensive studies.
文摘Background/objective: A nationwide survey on the resistance to first line anti-tuberculosis (anti-TB) drugs was conducted in Ghana from 2007-2008 by Noguchi Memorial Institute for Medical Research in collaboration with the National Tuberculosis Control Programme. We aimed to characterize mycobacterial species causing pulmonary tuberculosis (PTB) and determine the resistance pattern to first line anti-TB drugs among newly diagnosed and previously treated PTB patients in Ghana. Methods: Two sputum samples from consented new smear positive PTB patients who had never been treated for TB or had been on anti-TB treatment for less than a month and patients who had been treated for TB previously for more than a month in selected diagnostic centres nationwide were collected for culture, identification and drug susceptibility test. Culture positive isolates were tested against streptomycin (S), isoniazid (H), rifampicin (R) and ethambutol (E) using the simplified proportion method and line probe assay (LPA). The LPA was performed in mid-2017. Results: Among 410 samples, 345 positive cultures were obtained and identified as Mycobacterium tuberculosis complex (MTBC). Of the 345 isolates, 133 were further differentiated by GenoType MTBC®as M. tuberculosis, 126 (94.7%) and M. africanum 7 (5.3%). The overall drug resistance patterns were as follows: 43/345 (12.5%), 6/345 (1.7%), 9/345 (2.6%) and 71/345 (20.6%) were resistant to H, R, E and S respectively and 5/345 (1.4%) were multi-drug resistant (MDR). Conclusion: The results indicate high levels of resistance to S and H among new and previously treated TB patients. We recommend adequate surveillance systems including periodic national anti-TB drug resistance surveys.
基金sponsored by the National Research Foundation of Korea(NRF)Grant funded by the Korean government(MSIT)(Grant No.:2018R1A5A2021242).
文摘The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.
基金Supported by Science and Technology Plan Project of Shaoyang City,No.2022GX4139.
文摘BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.
基金supported by grants from the National Natural Science Foundation of China (Grant No. U20A20369)GuangDong Basic and Applied Basic Research Foundation (Grant No. 2022B1515120085)。
文摘Cancer immunotherapy has emerged as a promising approach in cancer treatment and is considered a major advancement after surgical interventions, radiotherapy, chemotherapy, and targeted therapy. The clinical use of immunotherapeutic drugs, particularly antibody-based drugs that target immune checkpoints, has notably increased~1.
文摘Some bacteria have the ability to co-exist, proliferate and survive in a multicellular community, biofilm. Each participating bacteria can form its colonies and encases itself by a self-produced insoluble extracellular matrix substance (EPS). Microcolonies within biofilm are held together by interactions and bonding of the substances present in the EPS with their separation from the water channels. Similar to insoluble EPS, bacterial microcolonies release soluble exofactors that have direct impacts on the survivability, growth and antibacterial resistivity of other microcolonies made of single- or multi-species bacteria in the same biofilm. How the exofactors of microcolonies of one-type bacteria impact on microcolonies of other-type bacteria is still unclear. We studied about the role of exofactors released from Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are common biofilm-forming pathogenic bacteria. Exofactors facilitate to transform the microenvironment where bacteria can acquire alternative lifestyle with a long survival period and resistivity to certain antimicrobial drugs.
基金Supported by Science and Technology Innovation Plan for Medical Workers in Shandong Province(SDYWZGKCJH2023095)Clinical Pharmacy Research Project of Shandong Provincial Medical Association(YXH2022ZX010)+1 种基金Traditional Chinese Medicine Science and Technology Development Project of Shandong Province(2019-0400&2021Q097)Traditional Chinese Medicine Research Program of Qingdao City(2020-zyy031)Medical Research Guidance Plan of Qingdao City(2020-WJZD087).
文摘[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
基金This work was supported by grants from the National Natural Science Foundation of China(81902484)China Postdoctoral Science Foundation(2020M670864)+2 种基金Youth Support Project of Jilin Association for Science and Technology(202028)Jilin Provincial Health Special Project(2020SCZT039)Jilin Health and Healthy Youth Science and Technology Training Plan(2020Q017).
文摘Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:Literature search was conducted in PubMed,MEDLINE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://www.chictr.org.cn/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.
文摘Background:Alcohol and illicit drugs(AID)continue to be a major global health concern.Although preventable,AID is linked to millions of deaths annually worldwide.The situation is particularly grave for young people,with AID being a major direct risk factor for disability-adjusted youth life-years lost and death.It further contributes to assaults,road crashes,accidental poisoning,and suicide,leading to long-term issues and public health concerns.Objective:This study aimed at disclosing current AID prevalence data for Argentinian,Bulgarian,Chilean and Romanian youth.It shed light on the predictors of AID in young people from those countries.Method:The study used an online survey to gather data from people aged 18 to 25(n=1,297).The survey was underpinned by the theory of planned behaviour(TPB).Predictors were investigated separately for drinking alcohol and using illicit drugs.Results:Our data revealed that across the four target countries,49%to 90%of the participants drank alcohol,and 8%to 35%used illicit drugs in the past three months.Between 20%and 91%of them intended to drink,and between 8%and 31%intended to use illicit drugs in the following three months.Our TPB model predicted statistically significant(P<0.001)amounts of variance in drinking alcohol(between 61%and 72%)and using illicit drugs(between 20.3%and 74.4%).Intention was consistent in significantly predicting both behaviours.Evidence around the predictive validity of self-efficacy,age and gender was mixed across the investigated countries.Conclusion:This research provided an update on the scarce AID epidemiological data.It also supplied evidence about what theoretically-informed measures might be useful targets of interventions in the case of Argentina,Bulgaria,Chile and Romania.This new knowledge of understanding substance abuse determinants and prevalence may help researchers and practitioners better meet young people's health prevention needs.
文摘Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.
文摘Endoscopic ultrasound(EUS)with fine needle aspiration or fine needle biopsy is the gold standard for sampling tissue to diagnose pancreatic cancer and auto-immune pancreatitis or to analyze cyst fluid.The most common reported adverse event of fine needle aspiration and/or fine needle biopsy is acute pancreatitis,which is likely induced by the same pathophysiological mechanisms as after en-doscopic retrograde cholangiopancreatography(ERCP).According to the current European Society of Gastrointestinal Endoscopy guideline,nonsteroidal anti-inflammatory drugs are administered prior to ERCP as a scientifically proven treatment to reduce post-ERCP pancreatitis incidence rate.A single suppository of diclofenac or indomethacin prior to EUS guided tissue acquisition(TA)is harm-less in healthy adults.Since it is associated with low costs and,most important,may prevent a dreadsome complication,we strongly recommend the adminis-tration of 100 mg diclofenac rectally prior to EUS-TA.We will explain this recom-mendation in more detail in this review as well as the risk and pathophysiology of post-EUS TA pancreatitis.
文摘Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between men and women.Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects.Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions,to maximize therapeutic effectiveness and to provide personalized management of care.
基金supported by the National Natural Science Foundation of China(Grant Nos.82203539 and 92259102)Provincial Cooperation Project of Science and Technology Department of Sichuan Province(Grant No.2023YFSY0043)the National Key Research and Development Program of China(Grant No.2023YFC3402100).
文摘Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.
基金Supported by the Science and Technology Plan Project of Jingmen Science and Technology Bureau,No.2018YFZD025。
文摘BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.
文摘Objective To analyze the reimbursement policies of innovative drugs in some developed countries,and to provide reference for future reimbursement management in China.Methods Literature research method was used to study the policies related to the reimbursement management of innovative drugs in Germany,France and Japan,and their successful experience was summarized.Results and Conclusion China should establish an open and transparent value evaluation standard to improve the medical insurance reimbursement management of innovative drugs.Besides,the value of innovative drugs should be taken as an important basis for reimbursement decisions,and an independent third-party value evaluation agency must be established.
文摘Objective To identify technical risks in the process of innovative drug development,and to provide reference for technical risk management so as to reduce the uncertainties and improve the efficiency of research and development.Methods The initial risk index was investigated by literature research.Then,the Likert scale was used to design a questionnaire,and the experts’opinion was used to analyze the risk factors affecting the different stages of the development of innovative drugs in China.Results and Conclusion Based on the analysis of questionnaire,31 risk indicators of five key stages in the development of innovative drugs from drug discovery to marketing authorization were established.The key risk indicators constructed in this study can provide reference for technology-related risk management in the process of innovative drug development.
基金Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Administration of Traditional Chinese Medicine(2021106)Beijing-Tianjin-Hebei Traditional Chinese Medicine Collaborative Development Specialty Alliance Construction Project(First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Qingxian County Traditional Chinese Medicine Hospital).
文摘Prostate cancer is a common male malignant tumor,and bone metastasis is one of the common complications in the late stage of prostate cancer.The mechanism of prostate cancer bone metastasis is a complex process involving multiple factors and steps.In recent years,with in-depth research on the mechanism of prostate cancer bone metastasis and the development of new drugs,important progress has been made in the treatment of prostate cancer bone metastasis.Based on this,this article introduces the mechanism of prostate cancer bone metastasis and the research progress of several bone-targeted drugs to provide reference and inspiration for future research.