Objective To investigate the regulations and implementation effect for high-risk drugs of the FDA and MHRA on the basis of natalizumab, and to provide references for the risk regulation of the innovative drugs and high-risk drugs of China. Methods We searched MEDLINE, EMBASE.com, the official website of Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for the marketing/withdrawal and risk regulation information of natalizumab as well as the relevant information of drug marketing/withdrawal and approval track. Results (1) Natalizumab was initially approved by the FDA through accelerated approval in November, 2004 with the phase three clinical trial still being conducted. But in February 2005, it was withdrawn after 3 patients developed PML. FDA resumed its marketing under a specially restricted distribution program called the Touch Prescribing Program in March, 2006. (2) Natalizumab was marketed in the European Union in April 2006. No cases of PML have been reported in the UK for this drug. (3) To speed the development of drugs that treat serious diseases, the FDA developed 3 distinct and successful approaches to make such drugs available as rapidly as possible: Priority Review, Accelerated Approval, and Fast Track. The proportion of new molecular entity and new biologic approved by fast tract were 45% and 74%, respectively between 2002 and 2009. (4) Drug regulation of MHRA contained: Yellow Card Scheme, Black Triangle products, Download Drug Analysis Prints (DAPs), and Defective Medicines Report Centre (DMRC). Self-reporting and monitoring system were fairly perfect, thus they can fulfill the close monitoring for high-risk drugs under the existing conditions and then realize the risk-minimization. Conclusion (1) The risk-minimization program of FDA for high-risk drugs is effective, and plays a role in the policy support for the researching and marketing of irreplaceable innovative drugs. (2) The risk regulation for high-risk drugs of MHRA is integrated into drug regulation program and enforces hierarchical management, and acquires risk-minimization effect. (3) We should learn from the policy and operational experience for the international new molecular entity and new biologic on the re-evaluation for innovative drugs and high-risk drugs. Combined with drug specific characteristics, evaluation indicators and criteria are developed base on evidence, risk management system and mechanism for innovative drugs are established and improved, and policy and administration security for the safety application of innovative drugs and high-risk drugs are provided.
ObjectiveTo observe the children with idiopathic epilepsy who received AED therapy and seizure-free, withdrawal at least 1 year, and analyze the risk factors of seizure recurrence. In order to give better instructions for AED withdrawal of children with idiopathic epilepsy in pediatric department. MethodsChildren with idiopathic epilepsy who were seizure-free and had stopped AED treatment at least 1 year before the deadline of observation were collected from pediatric outpatient and inpatient department of the First Affiliated Hospital of Guangxi Medical University from January 2011 to January 2014. The following variables, derived from the case records were analyzed: sex, age at seizure onset, type of seizure, time period between the onset of the first seizure and start of treatment, number of seizures in the time period between the start of AED therapy and the last seizure, number of AEDs before remission, time period between the start of AED therapy and the last seizure, time period between the last seizure and withdrawal of AED treatment (seizure-free period, timing of AED withdrawal), time period between the start of AED withdrawal and total discontinuation(speed of withdrawal), EEG registered at the time of diagnosis, before AED withdrawal, during and after AED withdrawal, and the condition of recurrence, data analysed by multi-variate step-wise Cox regression model analysis. ResultsA total of 16(12.8%) children relapsed in a total number of 125 children with idiopathic epilepsy we collected; date evaluated by multi-variable analysis showed that the children suffering from seizure type of focal seizure, starting withdrawal after a seizure-free period of less than 3 years and with abnormal post-withdrawal EEG recording was associated with a higher risk of seizure recurrence. ConclusionsChildren with idiopathic epilepsy have a low risk of recurrence after AED withdrawal. Those who suffer from seizure type of focal seizure, start withdrawal after a seizure-free period of less than 3 years and with abnormal post-withdrawal EEG recording are associated with a higher risk of seizure recurrence.
ObjectiveTo determine the outcome of antiepileptic drugs (AEDs) withdrawal in patients who had been seizure-free for more than two years. MethodsPatients with epilepsy who had been seizure-free for at least two years and decided to stop AEDs therapy gradually were checked on every two months for seizure relapse. The inclusion criteria were:①diagnosis of epilepsy, defined as at least two unprovoked seizures at least 24 hours apart; ②patients remained seizure-free for at least 24 consecutive months during AEDs therapy; ③patients expressed a desire to discontinue AEDs therapy gradually and agreed to return for regular follow-ups; and④electroencephalogram (EEG) showed no epileptic discharge. The time to a seizure relapse and predictive factors were analyzed by survival methods, including sex; age at seizure onset; number of episodes; seizure-free period before AEDs withdrawal; duration of follow-up after AEDs withdrawal; AEDs tapering off period (taper period); results from brain MRI; EEG before seizure-free; EEG before drug withdrawal; seizure type (classified as generalized, partial, or multiple types based on history); the number of AEDs administered for long-term seizure control. A log-rank test was used for univariate analysis, and a Cox proportional hazard model was used for multivariate analysis. ResultsSixty-eight patients (39 male, 29 female) were admithed. The relapsed rate was 23.5%. Univariate analysis and multivariate Cox regression analysis indicated that multiple AEDs, hippocampal sclerosis and withdrawal time were significantly correlated with seizure recurrence and those were significant independent predictive factors, with hazard ratio were 0.861, 2.223 and 2.137 respectively. ConclusionsThe relapsed rate in our study was similar to other studies. Distinguishing variables, such as multiple AEDs, hippocampal sclerosis and withdrawal time, need to be considered when decide to withdraw. Therefore, our recommendation is that after two years of being seizure-free, patients could consider withdrawal unless they are hippocampal sclerosis patients.
ObjectiveTo explore the effect of motivation interview skill on the improvement of withdrawal motivation of amphetamine abusers. MethodsSeventy amphetamine abusers were divided into the experimental group and the control group randomly by random number table between January and July 2013. Both groups had 35 subjects. Amphetamine abusers in the control group received conventional medical treatment and nursing, while the amphetamine abusers in the experimental group were treated with motivation interview skill therapy in addition to conventional medical treatment and nursing. The questionnaires on withdrawal motivation were used to evaluate the effects for the improvement of withdrawal motivation of both groups in the first week and third week respectively. ResultsScores of the questionnaire on withdrawal motivation of the two groups showed significant differences after hospital treatment compared with before (P<0.05), but the experimental group was much better than the control group (P<0.05). ConclusionMotivation interview skill therapy has a remarkable therapeutic effect for the improvement of withdrawal motivation of amphetamine abusers.
ObjectiveTo systematically evaluate the efficacy of different interventions in preventing rocuroniuminduced injection pain or withdrawal movements, so as to provide references for preventing adverse reactions induced by rocuronium injection in clinical practice. MethodsWe electronically searched PubMed, EMbase, The Cochrane Library (Issue 3, 2014), CBM, and CNKI databases to collect randomized controlled trials (RCTs) about the prevention of rocuronium-induced injection pain or withdrawal movements from inception to March 2014. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2.8 software. ResultsA total of 43 RCTs involving 6 034 patients were include. The results of meta-analysis showed that compared with the placebo/blank group, lidocaine pretreatment with venous occlusion (RR=0.37, 95%CI 0.29 to 0.48, P<0.000 01), opioid drug pretreatment with venous occlusion (RR=0.77, 95%CI 0.68 to 0.87, P<0.000 1), lidocaine pretreatment with venous injection (RR=0.51, 95%CI 0.44 to 0.59, P<0.000 01), opioid drug pretreatment with venous injection (OR=0.03, 95%CI 0.02 to 0.05, P<0.000 01), ketamine pretreatment with venous injection (RR=0.36, 95%CI 0.23 to 0.54, P<0.000 01), mixing sodium bicarbonate (NaHCO3) with rocuronium (OR=0.02, 95%CI 0.01 to 0.04, P<0.000 01) and local heating (RR=0.74, 95%CI 0.63 to 0.88, P=0.000 6) were all effective in decreasing the incidence of rocuronium-induced injection pain or withdrawal movements. ConclusionThe intravenous injection of opioid drugs was effective in preventing rocuronium-induced injection pain or withdrawal movements, while local heating needs further research. Due to the limited quantity and quality of the induced studies, the above conclusion still needs to be verified by more high quality studies.
ObjectivesTo systematically review the prophylactic efficacy of lidocaine administrated intravenously in advance on rocuronium associated injection pain/withdrawal movement in patients under general anesthesia.MethodsPubMed, The Cochrane Library, Web of Science, EMbase, CNKI, WanFang Data and VIP databases were electronically searched to collect relevant randomized controlled trials (RCTs) on pretreatment with lidocaine intravenously to prevent injection pain /withdraw movement from rocuronium from inception to September 30th, 2018. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies; then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 30 RCTs involving 2 518 patients were included. The results of meta-analysis showed that, compared to the control group, pretreating with intravenous lidocaine could significantly reduced the occurrence of total pain/withdrawal movement associated with rocuronium injection (RR=0.43, 95%CI 0.36 to 0.51, P<0.000 01), and whether with (RR=0.39, 95%CI 0.29 to 0.52, P<0.000 01) or without (RR=0.45, 95%CI 0.36 to 0.57, P<0.000 01) occluding the vein, intravenous lidocaine could prevent pain/withdrawal movement associated with rocuronium injection. In addition, the incidence of lidocaine group igniting moderate (RR=0.38, 95%CI 0.31 to 0.46, P<0.000 01) or severe (RR=0.23, 95%CI 0.18 to 0.30, P<0.000 01) pain/ withdrawal movement were less likely to occur. However, there was no difference between the lidocaine and control group in the incidence of mild injection pain/withdrawal movement induced by rocuronium (RR=0.89, 95%CI 0.75 to 1.06, P=0.19).ConclusionsCurrent evidence shows that pre-intravenous lidocaine can reduce the occurrence of injection pain/withdrawal movement associated with rocuronium injection patients, especially in the prevention of moderate and severe injection pain/withdrawal movement.
ObjectiveThe risk factors of relapse in 133 epileptic children after withdrawal were analyzed retrospectively and provide reference for clinical withdrawal.MethodsFrom January 2017 to March 2019, 133 children with withdrawal epilepsy were selected as the study object. According to whether there was recurrence during the follow-up period, the children with epilepsy were divided into recurrence group (42 cases) and non recurrence group (91 cases). The gender, age of onset, history of trauma, frequency of seizure before treatment, EEG before drug reduction, imaging, type of medication, family history, time of reaching control, course of disease before treatment, comorbidity, multiple attack types, withdrawal speed and EEG before treatment were observed and compared between the two groups. ResultsThere were significant differences in EEG (χ2 =7.621), medication type (χ2=8.760), time to control (χ2=6.618), course before treatment (χ2=6.435), multiple seizure types (χ2=5.443) and epilepsy comorbidity (χ2=42.795) between the two groups (P < 0.05). The results of Logistic multiple regression analysis showed that the recurrence of epileptic children after drug reduction / withdrawal was correlated with abnormal EEG before drug reduction [OR=9.268, 95%CI (2.255, 38.092)], combined drug treatment [OR=3.205, 95%CI (1.159, 8.866)] and course of disease > 1 year before treatment [OR=5.363, 95%CI (1.781, 16.150)] (P < 0.05).ConclusionsIn order to reduce the possibility of recurrence of epileptic children, the treatment time of epileptic children with abnormal EEG, combined medication and long course before treatment should be prolonged properly.
ObjectiveTo analyze the current situation of day surgery patients’ withdrawal from hospitalization, and put forward reasonable and effective measures and suggestions.MethodsDescriptive statistical analysis and trend chi-square test were conducted on the hospitalization withdrawal rate of day surgery in the Day Surgery Ward of the Second Affiliated Hospital Zhejiang University School of Medicine from 2012 to 2020. The reasons for hospitalization withdrawal and the operation methods of withdrawn cases from 2019 to 2020 were descriptively analyzed.ResultsFrom 2012 to 2020, the hospitalization withdrawal rate of day surgery decreased from 4.48% to 2.19%, with a significant decrease and a linear downward trend (χ2trend=138.500, P<0.001). From 2019 to 2020, patient factor was the most important reason for hospitalization withdrawal of day surgery, accounting for 79.72%; secondly, long waiting time for surgery, abnormal examination results, inadequate preoperative evaluation, medical insurance reimbursement, epidemic situation in 2020 and other reasons had affected the patients’ hospitalization withdrawal of day surgery to varying degrees. Endoscopic lithotripsy accounted for the largest proportion (210 cases, accounting for 20.87%) in the withdrawn procedures from 2019 to 2020, followed by minimally invasive rotary resection for breast lesions (126 cases, accounting for 12.52%).ConclusionImproving preoperative evaluation, strengthening preoperative communication, implementing efficient medical treatment, and shortening the waiting time for surgery can reduce the rate of hospitalization withdrawal of day surgery.
ObjectiveTo systematically review the efficacy of exercise intervention on smoking cessation. MethodsCNKI, WanFang Data, VIP, Web of Science, PubMed and EMbase databases were electronically searched to collect randomized controlled trials (RCTs) and randomized cross controlled trials (RCDs) on exercise intervention for smoking cessation from inception to September 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Then, meta-analysis was performed using Stata 12.0 software. ResultsA total of 47 studies (35 RCTs and 12 RCDs) involving 5 130 subjects were included. The results of meta-analysis showed that acute exercise could significantly reduce the quitters’ desire to smoke (P<0.05), alleviate most of the withdrawal symptoms, and the effect of acute exercise was maintained for at least 30 minutes. Periodic exercise significantly reduced 7-day point abstinence and sustained abstinence rates in ex-smokers (P<0.05), and the effect of periodic exercise was maintained for at least 12 weeks, however, depression and stress were not found to be effectively relieved, and mood was not found to be significantly improved (P>0.05). ConclusionExercise intervention to quit smoking has a positive effect, however, more high-quality studies are needed to verify the above conclusion.
Objective Exploring the correlation between intravesical pressure (IP) and diaphragm excursion (DE) in patients with severe acute pancreatitis (SAP) and acute respiratory distress syndrome (ARDS), and evaluating its predictive value for weaning outcomes. Methods A retrospective analysis was conducted on the clinical data of 144 SAP patients with ARDS admitted between 2020 and 2023. By collecting the outcome of weaning, collect data on gender, age, acute physiology and chronic health score II (APACHE II), oxygenation index, and IP and DE before weaning and extubation for all patients. Based on weaning outcomes, divide patients into successful and failed groups, and compare the differences in various indicators between the two groups; Use binary logistic regression to analyze whether IP and DE are risk factors affecting weaning in SAP patients with ARDS, and use Pearson correlation analysis to examine the correlation between IP and DE; Use receiver operating characteristic curve (ROC curve) to analyze the predictive value of IP and DE on weaning outcomes in SAP patients with ARDS. ResultsA total of 144 SAP patients with ARDS were included, of which 108 were successfully weaned and 36 were unsuccessful. There were no statistically significant differences in gender, age, and APACHE II scores between the successful and failed groups (males: 62.96% (68/108) compared to 69.44% (25/36), age (years): 41.91 ± 8.14 compared to 42.42 ± 6.22, APACHE II score (points): 18.28 ± 2.22 compared to 18.97 ± 1.83, P>0.05). The IP of the successful group was significantly lower than that of the failed group, and the DE was significantly higher than that of the failed group [IP (mmHg): 18.45 ± 3.76 compared to 23.92 ± 5.65, DE (mm): 16.18 ± 4.23 compared to 12.28 ± 4.44, all P<0.05]. All patients showed a significant negative correlation between IP and DE (r=–0.457, P<0.001). ROC curve analysis showed that the area under the curve (AUC) of IP predicting the withdrawal outcome of SAP patients with ARDS was 0.805, with a 95% confidence interval (95%CI) of 0.724-0.885 and P<0.001. When the cutoff value was 19.5 mmHg, the sensitivity was 91.57% and the specificity was 47.54%; The AUC for predicting the withdrawal outcome of SAP patients with ARDS by DE was 0.738, with a 95%CI of 0.641-0.834 and P<0.001. When the cutoff value was 11.5 points, the sensitivity was 84.82% and the specificity was 59.38%. Conclusions There is a significant negative correlation between IP and DE in SAP combined with ARDS patients, and both have certain predictive value for weaning outcomes.