What drug dosage range is appropriate for treatment? What drug dosage range can maximally reduce the incidence of adverse drug reaction (ADR)? The gold zone method as a new method of evidence-based medical research was proposed to study those two blind areas of drug dosage in this article. Studying the dose-effect relationship, taking gold zone as the middle range and dividing empirical range into 3 sections were the key to study design. The evidence-based survey with extremely large sample showed a U-shaped rule existing between the antibiotics’ dosage and the incidence of ADR; and the dosage in gold zone appeared at the bottom of U-shaped curve. The gold zone method for determining dosage is a special breakthrough currently for solving those two blind areas of drug dosage
This article aims to review the recall of refecoxib which increases the incidence of cardiovascular and cerebrovascular diseases and to find the methods to solve problems in post marked monitoring of drug safety.
Objective
To investigate the effects of antiepileptic drugs (AEDs) with warfarin functions and blood coagulation system, to provide the reference for clinicians of the selection of AEDs under the combination therapy with warfarin.
Methods
Analyse the clinical data of the patient with symptomatic epilepsy from the Second Clinical Medical College of Guiyang University of Chinese Medicine on April 1, 2017, whom taking AEDs and warfarin at the same time, clear the drug adverse reactions, and analysed related literature.
Results
After the treatment with valproate, abnormal blood coagulation, a danger and emergency data appeared, so we stopped using warfarin immediately, and reduce the dosage of valproate gradually, insteadly, we used levetiracetam as antiepileptic therapy. Monitoring blood coagulation function, when it returned to normal, restart warfarin anticoagulant therapy.
Conclusions
When start antiepileptic treatment in relevant basic diseases of symptomatic epilepsy, for a variety of combination reactions, AEDs can affect the anticoagulant effect of warfarin, so we need to consider the interaction between drugs and avoid adverse reactions.
Objective
To investigate the efficacy and safety of neo-adjuvant chemotherapy for stage ⅠB2-ⅡB cervical cancer.
Methods
From June 2012 to December 2014, 66 patients with stage ⅠB2-ⅡB cervical cancer were selected and treated by PT (cisplatin/ carboplatin and taxol/docetaxel) as neo-adjuvant chemotherapy prior to surgery. Neo-adjuvant chemotherapy response and toxicity were collected and analyzed.
Results
The extinctive condition of tumor by neo-adjuvant chemotherapy: the complete remission rate was 10.6% (7/66), partial remission rate was 59.1% (39/66), and the total effective rate was 69.7%. The main toxicities were myelosuppression (59.1%, 39/66) and gastrointestinal reactions (33.3%, 22/66). The toxicities could be tolerated or relieved by prevention and treatment. The effective rate of chemotherapy for cervical squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma was 72.6%, 33.3% and 0%, respectively, with significant differences among the three types (P<0.05). The effective rate of chemotherapy for high, medium and low differentiated cervical cancer was 100.0%, 77.3% and 55.9%, respectively, with significant differences among the three degrees (P<0.05).
Conclusions
Neo-adjuvant chemotherapy is proved to be a safe and effective complementary treatment for most patients with locally advanced cervical cancer. Due to the limitation of sample size, the correlations between therapeutic effect and tumor differentiation degree and between therapeutic effect and pathological type need further study.
ObjectiveTo analyze the clinical efficacy of decitabine contained chemotherapy regimens in the treatment of relapsed or refractory acute myeloid leukemia (AML) patients.MethodsA total of 101 patients with relapsed or refractory AML from May 2014 to December 2017 were collected retrospectively. Three schemes with a relatively larger number of users were included: 15 cases were treated with decitabine monotherapy (DAC regime); 37 cases were treated with decitabine, anthracycline antibiotic, and cytarabine (D-DA regime); and 49 cases were treated with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulatingfactor (G-CSF) (D-CAG regimen). The remission rate, blood products support strength, degree and duration of bone marrow suppression, adverse reaction, and survival time were compared.ResultsThe complete remission (CR) rates of DAC, D-DA and D-CAG regimen group were 40.0%, 48.6%, and 71.4%, respectively; the overall respond rates (ORR) were 46.7%, 54.1%, and 79.6%, respectively. The ORR in D-CAG regimen group was higher than those in the other two groups (P<0.017). The dosage of G-CSF in D-CAG regimen group were lower than those in DAC regimen group [ (1 363.0±1 037.9) vs. (2 517.0±1 163.4) μg, P<0.05]; the mean number of erythrocyte transfusion and the dosage of G-CSF were lower than those in D-DA regimen group [(6.7±4.0) vs. (14.8±10.1) U, P<0.05; (1 363.0±1 037.9) vs. (2 786.0±1474.0) μg, P<0.05]; the time to the suppression of hemoglobin and platelet in D-CAG regimen group were later than those in D-DA regimen group [(11.5±2.6) vs. (8.8±2.5) days, P=0.007; (10.9±2.6) vs. (7.6±2.5) days, P=0.002]; the time to the suppression of platelet was later than that in DAC regimen group [(10.9±2.6) vs. (7.6±1.6) days, P=0.003]. There was no statistically significant difference in the incidence of adverse reations among the three group (P>0.05). The median overall survival of D-CAG regimen group was longer than that in DAC regimen group (11.6 vs. 8.8 months, P=0.013).ConclusionAmong the three chemotherapy regimens containing decitabine, the CR and ORR of D-CAG regimen are higher, the tolerance is better, and further promotion can be attempted in qualified medical institutions.
ObjectiveKetogenic diet (KD) has shown promising efficacy in the treatment of super-refractory status epilepticus (SRSE); however, its adverse effects have not been systematically evaluated. This study aimed to analyze the safety profile of adjunctive KD therapy for SRSE and explore potential risk factors. MethodsProspective data from 13 SRSE patients (3 adolescents, 10 adults; mean age 34.6±18.4 years) at Xuanwu Hospital, Capital Medical University (July 2020–December 2024) who received KD adjunctive therapy after failing conventional treatments were collected. Adverse reactions were observed, and a systematic literature review (up to March 2025) was conducted for meta-analysis. ResultsIn the single-center cohort of 13 patients, common adverse events included gastrointestinal intolerance (53.8%), hematologic and metabolic abnormalities such as thrombocytosis (84.6%), hyperammonemia (76.9%), dyslipidemia (69.2%), and hypocalcemia (69.2%), as well as nutritional deficits including hypoalbuminemia (61.5%), anemia (53.8%), and transient weight loss (61.5%). Most adverse events were transient and reversible with timely adjustments to the KD regimen. The meta-analysis (25 studies, 251 cases; mean age 16.1±19.0 years) revealed a spectrum of major adverse events, including gastrointestinal intolerance (26.7%), hypoglycemia (19.1%), acidosis (17.5%), and hyperlipidemia (12.0%). ConclusionsThe ketogenic diet as adjunctive therapy for super-refractory status epilepticus demonstrates a manageable safety profile. Reported adverse events are primarily confined to gastrointestinal intolerance, metabolic derangements, and nutritional deficits, with notable occurrences of thrombocytosis and hyperammonemia requiring timely clinical management. This study provides critical evidence-based support for KD implementation in SRSE treatment protocols.
Objective To analyze the withdrawal reason of natalizumab in depth based on the serious adverse reaction reports and approval channel, and to provide decision references for more safe and effective report method of other biologicals. Methods We searched MEDLINE, EMbase, and the official websites of Food and Drug Administration (FDA) for case reports, approval channel, and the relevant information of drug marketing or withdrawal. Results Four case reports and fourteen official reports were included. Three cases of progressive multifocal leukoencephalopathy (PML) were reported in the clinical trials after natalizumab’s initially approval with two dead and one disabled, which could be retrieved by hemodialysis (2 cases hitherto). Consequently, multiple sclerosis (MS) patients were willing to bear the risk. Two cases of natalizumab-related PML (0.06‰) were confirmed in 32 000 patients without death report after two years of its remarketing, in July 2008. Another PML patient was reported in October 2008. Because of its non-substitutability for treating MS and Crohn disease (CD), FDA announced that patients could still use natalizumab under the close monitoring. Conclusion (1) The most serious adverse reaction of treating MS and CD with natalizumab is PML, but it can be preventable and curable now. The monitoring findings of efficacy and adverse reaction during the postmarketing indicate that the review system is perfect and practicable relatively, and can give references for other high-risk drugs on the fast or standard approval channel, for example, Chinese medicine injection can draw lessons from it. (2) The remarketing of natalizumab not only provide significant risk management precedent for other drug-development firms, but also brings hope to the remarketing or relaunching clinical trials for the suspected sideeffect drugs. (3) Because of the fast-track reviewing of natalizumab and the overlap between the research of Good Clinical Practice (GCP) and the post-marketing evaluation, we should continue to track the information and provide new evidence.
Objective To assess the value of arsenious acid in treatment for metastatic liver cancer and inspect its adverse reaction through comparison between the therapeutic effect of arsenious acid-FOLFOX4 combined chemotherapy and that of single FOLFOX4 chemotherapy. Methods Twenty-six patients with metastatic liver cancer were selected from July 2006 to December 2007 in Huadong Hospital. All the cases were averagely divided into therapy group and control group randomly, arsenious acid combined FOLFOX4 chemotherapy was performed in therapy group and single FOLFOX4 chemotherapy in control group. Results The total of 26 cases completed at least 2 cycles of arsenious acid-FOLFOX4 combined chemotherapy or single FOLFOX4 chemotherapy. During 6-24 months follow-up (median 12.5 months), the average survival time of the therapy group was 242 d, the median survival time was 281 d, and the average survival time of the control group was 227 d, the median survival time was 246 d, there was no statistical difference between two groups (Pgt;0.05). Pain: There were 2 cases of complete remission (CR), 5 cases of partial remission (PR), 2 cases of stable disease (SD) in therapy group, the objective effect (CR+PR+SD) was 9 cases. There were 1 case of CR, 3 cases of PR, 2 cases of SD in control group, the objective effect (CR+PR+SD) was 6 cases. Objective efficacy: There were no CR cases in two groups. In therapy group, there were 5 cases of PR, 6 cases of NC, 2 cases of PD, the objective effect (CR+PR) was 5 cases, the benefit (CR+PR+NC) was 11 cases. In control group, there were 2 cases of PR, 4 cases of NC, 7 cases of PD, the objective effect (CR+PR) was 2 cases, the benefit (CR+PR+NC) was 6 cases. There was no significant difference of the objective effect between two groups (Pgt;0.05), but the benefit was significantly different (Plt;0.05). The major toxic reactions were digestive tract side effect, hepatic and hematological toxicity in two groups. Conclusions Arsenious acid-FOLFOX4 combined chemotherapy can lead to good therapeutic effect. Arsenious acid will not increase the adverse reaction of normal chemotherapy.
ObjectiveIn order to evaluate the efficacy, safety and tolerability of adjunctive perampanel in children with refractory epilepsy. MethodsThis study collected medical records of 34 children with refractory epilepsy, who were admitted to Children’s Hospital of Soochow University from January 2020 to January 2021. By comparing the baseline status with the status at 4, 8, 12, 24, 36, and 48 weeks of follow-up, the efficacy and adverse reactions of perampanel were evaluated. ResultsThe mean age of the patients treated with perampanel was 8.1±4.1 years. The male-to-female ratio was 1: 1. After the addition of perampanel, the average responder rate at the 4th, 8th, 12th, 24th, 36th, 48th weeks were 37.5%, 46.7%, 50.0%, 47.4%, 53.8%, 42.9%. The adverse events were reported by 32.4%, and the retention rate was 88.2%. ConclusionsPerampanel has good efficacy, safety and tolerability in the treatment of refractory epilepsy. Moreover, personalized treatment and better baseline seizure control may increase the effectiveness and retention rate of perampanel.
Objective To study the efficacy and adverse events of adjunctive perampanel in children with refractory epilepsy. Methods A prospective study was carried out in 45 children with refractory epilepsy, who were treated in our hospital from January 2020 to February 2021 using perampanel as an add-on treatment, with a criteria for enrollment and the starting dose of perampanel. Follow-up would be taken at once a month. Afte 3 months would check blood routine, liver function, kidney function and humoral immunity. The EEG was reviewed after 6 months. The initial dose of perampanel was 0.04 mg/(kg·d) (the maximum didn't exceed 2 mg/d), increasing by 0.04 mg/(kg·d) every two weeks, and the maximum maintenance dose didn't exceed 6 mg/d. The efficacy and adverse reactions of perampanel were evaluated by comparing the seizure frequency and EEG results before and after a 6-month add-on therapy.ResultsAmong the 45 children,complete seizure control was achieved in 7 cases after the therapy, and the seizure attacks were reduced in 26 cases, showing a total response rate of 73.3%. After the treatment, the epileptiform discharge of 28 children was reduced, and the effective rate was 62.22%. During the observation period, all the blood routine, liver function, kidney function,and humoral immunity of the children were normal.10 cases of adverse reactions occurred after the additional treatment of perampanel, and the adverse reaction rate was 22.22%. Conclusions Perampanel has good efficacy and safety in the add-on treatment of refractory epilepsy.
