With the perspective of evidence-based medicine, this review aims to investigate the effectiveness and safety of off-label drug use of bevacizumab for eye disease, and explore the barriers to further study. And then, suggestions for the supported evidence and clinical use of off-label drug use will be provided based on this case.
ObjectiveTo summarize the progress of the researches about nano-carbon tattoo in targeted lymph node dissection of breast cancer. MethodThe relevant studies on the application of nano-carbon tattoo to target lymph nodes in the breast cancer at home and abroad were searched and the feasibility and shortcomings of this method were summarized. ResultFrom the studies reported, the nano-carbon tattoo method had a high detection rate (64.0%–100%) and coincidence rate (55.0%–100%), as well as a lower false negative rate (0.0%–9.1%) in the labeling of breast cancer targeted lymph nodes. ConclusionsThe nano-carbon tattoo method is a useful, simple, and safe in the labeling of targeted lymph nodes in breast cancer. But the specific implementation scheme of this method, such as the optimal labeling dosage, the number of labeled lymph nodes, and the improvement of patients’ quality of life are still unclear, which still needs more large-scale prospective research to verify.
A multi-label based level set model for multiple sclerosis lesion segmentation is proposed based on the shape, position and other information of lesions from magnetic resonance image. First, fuzzy c-means model is applied to extract the initial lesion region. Second, an intensity prior information term and a label fusion term are constructed using intensity information of the initial lesion region, the above two terms are integrated into a region-based level set model. The final lesion segmentation is achieved by evolving the level set contour. The experimental results show that the proposed method can accurately and robustly extract brain lesions from magnetic resonance images. The proposed method helps to reduce the work of radiologists significantly, which is useful in clinical application.
ObjectiveTo understand the situation of off-label use of aspirin among outpatients in Sun Yatsen Memorial Hospital, so as to provide baseline data for developing off-label drug use policy. MethodsA stratified random sampling method was used to collected prescription data of aspirin among outpatients in 2013. The incidence rates between different types of off-label use of aspirin were determined by chi-square test, and the influence factors of off-label drug use were analyzed by logistic regression model. ResultsA total of 5 023 prescriptions with aspirin were collected and analyzed, with incidence rate of off-label use up to 17.7%. The major category of off-label use was no indication (94.38%). The top 3 no indications were recurrent abortion, infertility and systemic lupus erythematosus. Drug specification, gender, age and prescribed department were the risk factors of off-label use. ConclusionAspirin off-label use is common among outpatients in Sun Yat-sen Memorial Hospital in 2013, especially in obstetrics and gynecology department and assisted reproductive center. The results suggest that more clinical studies about aspirin for reproduction are needed to provide more evidence of drug use, so as to ensure the safety of drug use in special populations and avoid potential medical risk.
Objective To explore the method of radiolabeling anti-Aspergillus monoclonal antibody (WF-AF-1)with 99mTc,and evaluate the in vitro and in vivo characteristics of 99mTc labeled WF-AF-1 (99mTc-WF-AF-1). Methods 99mTc-WF-AF-1 was prepared with indirect-labeling method.The labeled product was identified using thin layer chromatography.Suspensions of Aspergillus fumigatus,Staphylococcus aureus and Candida albicans were incubated with 99mTc-WF-AF-1 to evaluate the specificity of the labeled antibody.Mice were injected with 3.7MBq of labeled product.The biodistribution was measured at 40min,2h,4h and 7h after injection. Results The labeling efficiency of 99mTc-WF-AF-1 was over 95%,and the labeled product was stable in serum and phosphate buffer solution.In vitro binding of 99mTc-WF-AF-1 revealed that the labeled Mab-WF-AF-1 preferentially binds to Aspergillus fumigatus. Biodistrbution data showed that the labeled antibody was deposited mainly in liver,kidneys and spleen.The radioactivity uptake in blood at 40min and 7h was (2.51±0.23)%ID/g and (0.53±0.13)%ID/g,respectively. Conclusions The labeling efficiency and stability of 99mTc-WF-AF-1 are high.The labeled antibody is excreted mainly through the liver and kidneys with fast clearance in blood in normal mice.
With the real-world study (RWS) becoming a hotspot for clinical research, health data collected from routine clinical practice have gained increasing attention worldwide, particularly the data related to the off-label use of drugs, which have been at the forefront of clinical research in recent years. The guidance from the National Medical Products Administration has proposed that real-world evidence (RWE) can be an important consideration in supporting label expansions where randomized controlled trials are unfeasible. Nevertheless, how to use the RWE to support the approval of new or expanded indications remains unclear. This study aims to explore the structured process for the use of RWE in supporting label expansions of approved drugs, and to discuss the key considerations in such process by reviewing the documents from relevant regulatory agencies and publications from public databases, which can inform future directions for studies in this area.
Objective lt;brgt;To investigate the feasibility of labeling iris pigment epithelial（IPE）cells of rabbits with 5（and 6）carboxyfluorescein diacetate succinimidyl ester（CFSE）. lt;brgt; lt;brgt;Methods lt;brgt;Enzyme-assisted microdissection was used to isolate the cultured rabbitprime;s IPE cells.The third or forth subcultured IPE cells were incubated with 2.5，5，10，20，and 40 mu;mol/L of CFSE for 1，5，and10min respectively.The fluorescence intensity was detected by flow cytometry，and the leakage of CFSE and its dyeing were observed by fluorescence antibody labeling. lt;brgt;Results lt;brgt;Incubation with 20 mu;mol/L CFSE under 37℃for1minute was the most optimal condition for IPE cells labeling.The coloration of IPE cells stained by CFSE lasted 4 weeks.There was no leakage of dye from labeled rabbit IPE cells to non-labeled human IPE cells in mixed culture process. lt;brgt; lt;brgt;Conclusion lt;brgt;With the advantages of high rate of dyeing，long time of tracing，safety and convenience，CFSE can be used as a new method to label the rabbitprime;s IPE cells. lt;brgt; lt;brgt;(Chin J Ocul Fundus Dis, 2006, 22: 261-264)
【Abstract】 Objective To explore the optimal dosage, timing and cytotoxicity of bromodeoxyuridine (BrdU) labelling for rabbit adipose-derived stromal stem cells (ADSCs) in vitro so as to confirm its feasibil ity for stem cells labell ing and tracer means. Methods Six rabbits were used in this experiment, aged 8-12 weeks, weighing 1.5-2.0 kg and neglecting their gender. 1-2 mL fat was removed, the ADSCs were isolated and cultured using the adherence method in vitro . The 3rd passage of ADSCs was incubated with BrdU at 5, 10, 15 and 20 μg/mL (groups A, B, C and D）for 12, 24, 48 and 72 hours to identify the optimal BrdU concentration and incubating time for cell labell ing. Immunohistochemistry and trypanblau strain were performed respectively to calculate the labell ing index (positive rate) and the cells’ activity for different time after BrdU labell ing. The ADSCs without BrdU labell ing were used as control (Group E）. Results The main appearance of primary ADSCs was short fusiform shape, and of the 3rd passage ADSCs long fusiform shape. The 3rd passage of ADSCs could differentiate into osteoblastsand adipocytes under corresponding inductive medium. The ADSCs’ nucleus show green fluor under fluorescence microscope after labeled by the BrdU. The labell ing ratio increased in groups A, B, C and D after incubating 12 hours, the mean labell ing ratio were 30.6％ ±2.3％，32.4％ ±1.9％，45.8％ ±1.8％，50.8％ ±3.1％ , respectively, and the labell ing ratio of Group E was 0. There were significant differences between groups C, D and Group A (P lt; 0.01). The labell ing ratio of groups A, B, C and D were 45.9％ ±2.0％，87.9％ ±3.3％，90.6％ ±2.9％，91.7％ ±3.2％，respectively after 24 hours and the labell ing ratio of Group E was 0. There were significant differences between groups B, C, D and Group A (P lt; 0.01). The results of all groups after incubating48 hours and 72 h ours were similar to that after incubating 24 hours. The cell counting of groups A, B, C and D were better than that of Group E, but showing no siginificant differences（P gt; 0.05）. Conclusion The most appropriate time for BrdU labell ing ADSCs is 48 hours, the most appropriate concentration is 10 μg/mL. The labell ing rate is high and cytotoxicity is l ittle.
Objective To evaluate the related laws, regulations and guidelines about off-label drug use in several countries, so as to provide evidence for regulating off-label drug use in China. Methods The following 3 Chinese databases as CBM, CNKI and VIP, 11 foreign databases including EMbase, PubMed and so on, 15 countries’ official websites of pharmaceutical administration department or academic organization, and WHO website were searched to obtain the related laws, regulations and guidelines about off-label drug use. By adopting the system evaluation method and self-defined index evaluation, the quality of the included literatures was evaluated in three aspects: literatures’ type, content relevance and timeliness. Seven researchers independently extracted data by Excel which included basic information of literatures, preconditions of off-label drug use, medicines categories that could be off-labelly used, regulations and legal responsibility in off-label drug use. And finally the descriptive analysis was conducted. Results A total of 4 735 literatures were retrieved, 104 of which were finally included, including 89 at grade A quality level (85.58%) and 15 was at grade B (14.42%). The analysis showed that, a) Seven countries had laws related to off-label drug use: America, Germany, Italy, Netherland, New Zealand, India and Japan. Except India, the rational off-label drug use was allowed in the other 6 countries. The right to prescribe off-label drug was defined in Britain and Ireland; b) Medical staff had to take the responsibility of off-label drug use in the country where the duty regulations were formulated; and c) Ten countries published guidelines or statements related to off label drug use by their official departments and academic organizations. And the regulation included the following procedures: firstly, to obtain the relative information and evidence; secondly, to get the informed consent; thirdly, to be approved by the ethics committee and/or pharmacy administration committee; fourthly, to record the reasons and effectiveness of off-label use; fifthly, to monitor the adverse reactions of off-label drug use. Besides monitoring the medical institutes, the pharmaceutical companies had also be monitored which included the following 3 aspects: a) to require companies to train specialized staffs to answer the questions related to off-label drug use; b) to open the contact information of medical departments of companies; and c) to prohibit preaching and advertising the off-label drug use. Conclusion Off-label drug use has its rationality and necessity. To protect the safety of patients, avoid the risk for hospitals and medical staffs, it requires formulating relative regulations soon in order to manage the off-label drug use in China. As a developing country, China is different from the developed countries in health care system. Therefore, when formulating the regulations, it is necessary to perform evidence-based evaluation on each country’s laws, regulations and guidelines about off-label drug use, with Chinese national conditions and experts’ opinions in combination. After a regulation is preliminarily drawn up, it needs to be put into pilot practice, and then revised and spread to the whole country.
Cardiac three-dimensional electrophysiological labeling technology is the prerequisite and foundation of atrial fibrillation (AF) ablation surgery, and invasive labeling is the current clinical method, but there are many shortcomings such as large trauma, long procedure duration, and low success rate. In recent years, because of its non-invasive and convenient characteristics, ex vivo labeling has become a new direction for the development of electrophysiological labeling technology. With the rapid development of computer hardware and software as well as the accumulation of clinical database, the application of deep learning technology in electrocardiogram (ECG) data is becoming more extensive and has made great progress, which provides new ideas for the research of ex vivo cardiac mapping and intelligent labeling of AF substrates. This paper reviewed the research progress in the fields of ECG forward problem, ECG inverse problem, and the application of deep learning in AF labeling, discussed the problems of ex vivo intelligent labeling of AF substrates and the possible approaches to solve them, prospected the challenges and future directions for ex vivo cardiac electrophysiology labeling.