Safety Profiles of Tripterygium wilfordii Hook F: A Systematic Review and Meta-Analysis.
ABSTRACT: Objective:Tripterygium wilfordii Hook F (TwHF) is a widely used and effective treatment for inflammatory diseases. There have been concerns about its toxicity but no adequate synthesis of the evidence for adverse events (AEs). We aimed to undertake a clinically informative, systematic safety profile of TwHF. Methods: We undertook a systematic review and meta-analysis of experimental studies and observational studies. We searched electronic databases and conference abstracts. Safety outcomes were rates of common AEs. Results: We screened 4137 abstracts for eligibility and included 594 studies in the analysis. The overall incidence of AEs was 26.7% (95% CI 24.8%, 28.8%) in 23,256 TwHF users. The estimates did vary markedly when stratified by specific study types. The incidence of gastrointestinal symptoms, adverse reproductive outcomes, adverse skin reactions, hematologic events and cardiovascular events were 13.3% (95% CI 11.9%, 14.9%), 11.7% (95% CI 10.3%, 13.3%), 7.8% (95% CI 6.3-9.5%), 6.5% (95% CI 5.7-7.4 %) and 4.9% (95% CI 1.6 %, 14.3 %), respectively. The prevalence of irregular menstruation (IM) was increased in patients taking TwHF compared with those given control (odds ratio [OR] 4.65, 95% CI 3.08 to 7.03). TwHF use has lower risk of weight gain (OR 0.12 [95% CI 0.04 to 0.39]) and hair loss (OR 0.37 [95% CI 0.18 to 0.78]). Furthermore, long-term aspirin use (>6 months) has a higher AEs incidence (31.0% [95% CI 24.5%-38.5%]). Conclusion: Our findings suggest that more than one in four patients who were taking TwHF had experienced AEs. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to improve patients' tolerance for TwHF.
Project description:The first-line agents comprising antihistamines for chronic urticaria, are not completely satisfactory. Tripterygium wilfordii Hook F (TwHF), a Chinese herb, has been developed into several Tripterygium agents and have definite effects on autoimmune and inflammatory diseases. In chronic urticaria, however, their values of practical application remain unclear. The aim of this study was to investigate the efficacy and safety of TwHF in patients with chronic urticaria.Several databases were systematically searched including PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, Chinese Scientific Journals Database, Wan Fang Database, and Chinese Biomedicine. Randomized controlled trials comparing antihistamines with TwHF or Tripterygium agents in combination with antihistamines were included. Revman5.3 was utilized to calculate risk ratios (RR) with 95% confidence intervals (CI). This study was registered with PROSPERO, number CRD42018091595.Twenty-one trials with 2565 participants were included in this analysis. Meta-analysis showed that, when antihistamines were combined with TwHF and Tripterygium agents, the curative effect in cases of chronic urticaria was superior to that of antihistamines alone (RR: 1.40; 95% CI: 1.33-1.46). The incidence rates of gastrointestinal disorder (RR: 2.91; 95% CI: 1.70-4.99) and menstrual disorder (RR: 6.00; 95% CI: 1.79-20.13) in drug combination groups were higher than those in controls, while other adverse events were similar between the two groups. After treatment, Dermatology Life Quality Index (RR: 1.23; 95% CI: 1.09-1.40), quality of sleep (RR: 1.50; 95% CI: 1.07-2.12), and daily activity (RR: 1.49; 95% CI: 1.25-1.78) were all improved. Furthermore, drug combination groups demonstrated less relapse (RR: 0.34; 95% CI: 0.25-0.45).TwHF and Tripterygium agents, in combination with antihistamines, appear to be more effective than antihistamines alone. Nevertheless, adverse events cannot be ignored. Large sample, multi-center, high-quality clinical studies are needed to verify the exact effects and safety of TwHF and Tripterygium agents in treatment of chronic urticaria.
Project description:Combining immune checkpoint inhibitors has shown its efficacy compared to monotherapy in advanced malignancies. We conducted this meta-analysis to provide latest evidence on the objective response rate (ORR) and incidence of treatment-related high-grade adverse events (AEs) during nivolumab and ipilimumab combination treatment and further explore from different drug dose level. PubMed and the 2019 American Society of Clinical Oncology (ASCO) annual meeting abstracts were searched for qualified clinical trials up to June 2019. Of the 23 clinical trials (13 from publications and 11 from ASCO abstracts) included, 2,114 and 2,674 patients were eligible for efficacy and safety analysis, respectively. Pooled analysis suggested that the overall ORR was achieved in 34.5% [95% confidence interval (CI), 29.1-40.4%] of patients. There was no significant difference between nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks (N3I1-Q3W) and nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (N1I3-Q3W) arms in ORR [30.8% vs 41%; odds ratio (OR), 0.72; 95% CI, 0.39-1.30; P = 0.275]. Grade 3-4 AEs related to combination therapy occurred in 39.9% (95% CI, 33.5-46.7%) of patients; the most commonly reported grade 3-4 treatment-related AEs were diarrhea (5.28%), colitis (3.96%) and increased alanine aminotransferase (3.51%). Incidence of grade 3-4 AEs were significant lower in N3I1-Q3W arm than in N1I3-Q3W arm (31.3% vs 55.9%; OR 0.52; 95% CI, 0.32-0.87; P = 0.012). Treatment-related death was rare and occurred in 2.0% (95% CI, 1.5-2.7%) of patients. Our comprehensive study provides more precise data on the incidence of treatment-related high-grade AEs and ORR among patients receiving nivolumab and ipilimumab combination regimens. Patients on the N3I1-Q3W arm had comparable ORR and significantly occurred less grade 3-4 AEs than patients on the N1I3-Q3W arm. Our finding is of great importance in assisting clinical trial design and clinical medication choice.
Project description:Objective:To assess the safety of abatacept treatment in rheumatoid arthritis (RA) using integrated data from multiple clinical trials. Methods:Data from nine double-blind, placebo-controlled studies of abatacept treatment (seven intravenous, two subcutaneous) in patients with RA were pooled, focusing on safety events in the double-blind treatment period of each study. Incidence rates (IRs) of adverse events (AEs) per 100 patient-years of exposure were calculated for abatacept- and placebo-treated patients. AEs in abatacept-treated patients were combined regardless of dose and formulation. Results:In total, 2653 patients received abatacept and 1485 received placebo, with 2357 and 1254 patient-years of exposure, respectively. The mean (SD) durations of exposure in the abatacept and placebo groups were 10.8 (3.3) and 10.3 (3.5) months, respectively. The IRs (95% confidence interval [CI]) for serious AEs were 14.8 (13.3, 16.5) and 14.6 (12.5, 17.0) in the abatacept and placebo groups, respectively. Death occurred in 12 (0.5%) and 12 (0.8%) patients in the abatacept and placebo groups, respectively, and was most commonly caused by cardiac disorders. Malignancies were observed in 31 patients (1.2%) treated with abatacept (IR: 1.32 [95% CI: 0.90, 1.87]) versus 14 (0.9%; IR: 1.12 [0.61, 1.88]) who received placebo. Solid organ tumor was the most frequent malignancy reported in both groups (abatacept: 1.0%; IR: 1.11 [95% CI: 0.72, 1.62]; placebo: 0.8%; 0.96 [0.50, 1.67]). Conclusion:In this integrated analysis, the IRs of safety events in the abatacept and placebo groups were similar with no new safety concerns identified.
Project description:<h4>Background</h4>Benralizumab, a humanized, anti-interleukin-5 (anti-IL-5) receptor ? monoclonal antibody that directly and rapidly depletes eosinophils, has shown significant efficacy in reducing asthma exacerbations and improving lung function in moderate to severe eosinophilic asthma patients. However, there is some controversy regarding the adverse events (AEs) of benralizumab and a comprehensive analysis of these AEs has not been performed. This study aimed to assess the incidence of these AEs in published randomized controlled trials (RCTs).<h4>Methods</h4>We searched for RCTs in the Embase, PubMed and Cochrane databases that compared benralizumab with placebo in moderate to severe eosinophilic asthma patients. The outcome was the incidence of AEs during the observation period.<h4>Results</h4>Eight RCTs were analyzed in this study. Patients treated with benralizumab had a lower risk of overall AEs (risk ratio (RR) 0.94; 95% confidence interval (CI) 0.90-0.98), serious adverse events (SAEs) (RR 0.82; 95% CI 0.68-0.98), asthma exacerbation (RR 0.72, 95% CI 0.61-0.85), bronchitis (RR 0.76, 95% CI 0.59-0.96) and sinusitis (RR 0.64, 95% CI 0.48-0.85), but had a higher risk of headache (RR 1.42, 95% CI 1.07-1.87) and pyrexia (RR 2.26, 95% CI 1.32-3.87) than patients treated with placebo. No increased incidence of death, hypersensitivity, injection-site reactions, nasopharyngitis, rhinitis, upper respiratory tract infection, influenza, cough, nausea, back pain or arthralgia was observed with benralizumab compared with placebo.<h4>Conclusions</h4>Benralizumab reduced the risk of SAEs, asthma exacerbation, bronchitis and sinusitis, and aggravated the risk of headache and pyrexia. Other AEs were comparable between the benralizumab group and placebo group. Therefore, benralizumab is a relatively safe drug, but vigilance regarding AEs is imperative during long-term treatment.
Project description:Background: Aclidinium bromide, an M3-receptor-selective, twice-daily (BID), long-acting muscarinic antagonist, is rapidly hydrolyzed in human plasma, resulting in low systemic exposure and urinary excretion. We evaluated the overall and cardiovascular (CV) safety of aclidinium in patients with moderate to severe chronic obstructive pulmonary disease (COPD) by pooling data from 6 randomized, double-blind, placebo-controlled, parallel-group studies of ?1 month's duration. METHODS:Patients were current/former smokers aged ?40 years with no history of clinically significant CV conditions. Treatment was administered (morning and evening) via GenuairTM/Pressair.®a Adverse events (AEs), major adverse CV events (MACE), cardiac and cerebrovascular AEs, and serious AEs (SAEs) were analyzed. Results: The pooled population included 2781 patients (aclidinium: n=1529; placebo: n=1252). The incidence of AEs was similar with aclidinium (53.5%) and placebo (55.4%), as was the incidence of cardiac (aclidinium: 5.0%; placebo: 4.4%) and cerebrovascular (aclidinium: 0.4%; placebo: 0.5%) events. The incidence of MACE was low (AEs: 0.7%; SAEs: 0.5%) and comparable between groups. The incidence of cardiac and cerebrovascular events was similar for patients with CV risk factors with aclidinium and placebo (rate ratio [RR] [95 %confidence interval (CI)]=1.01[.074, 1.39]). In patients with mild to severe renal impairment, the incidence of cardiac events was similar between groups (RR [95% CI]=0.87 [0.56, 1.36]). Conclusion: Aclidinium 400µg BID has a good safety profile and this pooled analysis found no evidence of increased CV or cerebrovascular risk compared with placebo in patients with moderate to severe COPD. Further studies are needed in high-risk patients.
Project description:OBJECTIVES:Preventing adverse events (AEs) after orthopaedic surgery is a field with great room for improvement. A Swedish instrument for measuring AEs after hip arthroplasty based on administrative data from the national patient register is used by both the Swedish Hip Arthroplasty Register and the Swedish Association of Local Authorities and Regions. It has never been validated and its accuracy is unknown. The aim of this study was to validate the instrument's ability to detect AEs, and to calculate the incidence of AEs following primary hip arthroplasties. DESIGN:Retrospective cohort study using retrospective record review with Global Trigger Tool methodology in combination with register data. SETTING:24 different hospitals in four major regions of Sweden. PARTICIPANTS:2000 patients with either total or hemi-hip arthroplasty were recruited from the SHAR. We included both acute and elective patients. PRIMARY AND SECONDARY OUTCOME MEASURES:The sensitivity and specificity of the instrument. Adjusted cumulative incidence and incidence rate. RESULTS:The sensitivity for all identified AEs was 5.7% (95% CI: 4.9% to 6.7%) for 30 days and 14.8% (95% CI: 8.2 to 24.3) for 90 days, and the specificity was 95.2% (95% CI: 93.5% to 96.6%) for 30 days and 92.1% (95% CI: 89.9% to 93.8%) for 90 days. The adjusted cumulative incidence for all AEs was 28.4% (95% CI: 25.0% to 32.3%) for 30 days and 29.5% (95% CI: 26.0% to 33.8%) for 90 days. The incidence rate was 0.43 AEs per person-month (95% CI: 0.39 to 0.47). CONCLUSIONS:The AE incidence was high, and most AEs occurred within the first 30 days. The instrument sensitivity for AEs was very low for both 30 and 90 days, but the specificity was high for both 30 and 90 days. The studied instrument is insufficient for valid measurements of AEs after hip arthroplasty.
Project description:BACKGROUND: Adverse events (AEs) are adverse outcomes caused by medical care. Several studies have indicated that a substantial number of patients experience AEs before or during hospitalization. However, few data describe AEs after hospital discharge. We determined the incidence, severity, preventability and ameliorability of AEs in patients discharged from the general internal medicine service of a Canadian hospital. METHODS: At a multisite Canadian teaching hospital, we prospectively studied patients who were consecutively discharged home or to a seniors' residence from the general internal medicine service during a 14-week interval in 2002. We used telephone interview and chart review to identify outcomes after discharge. Two physicians independently reviewed each outcome to determine if the patient experienced an AE. The severity, preventability and ameliorability of all AEs were classified. RESULTS: During the study period, outcomes were determined for 328 of the 361 eligible patients, who averaged 71 years of age (interquartile range 54-81 years). After discharge, 76 of the 328 patients experienced at least 1 AE (overall incidence 23%, 95% confidence interval [CI] 19%-28%). The AE severity ranged from symptoms only (68% of the AEs) or symptoms associated with a nonpermanent disability (25%) to permanent disability (3%) or death (3%). The most common AEs were adverse drug events (72%), therapeutic errors (16%) and nosocomial infections (11%). Of the 76 patients, 38 had an AE that was either preventable or ameliorable (overall incidence 12%, 95% CI 9%-16%). INTERPRETATION: Approximately one-quarter of patients in our study had an AE after hospital discharge, and half of the AEs were preventable or ameliorable.
Project description:Objective:The use of early colonoscopy in the management of acute lower gastrointestinal bleeding (LGIB) is controversial, with disparate evidence. We aim to formally characterize the utility of early colonoscopy (within 24 h) in managing acute LGIB. Design:A systematic literature search to August 2016 identified fully published and abstracts of randomized controlled trials (RCTs) and observational studies assessing early colonoscopy in acute LGIB. Single-arm studies were also included to define incidence. Primary outcomes were overall rebleeding rates and time to rebleeding. Secondary outcomes included mortality, surgery, length of stay (LOS), definite cause of bleeding and adverse events (AEs). Odds ratios (OR) and weighted mean differences (WMD) were calculated. Results:Of 897 citations, 10 single-arm, 9 observational studies, and 2 RCTS were included (25,781 patients). Rebleeding was no different between patients undergoing early colonoscopy and controls (seven studies, OR = 0.89, 95% CI 0.49-1.62), or RCT data only (OR = 1.00, 95% CI 0.52-1.62). Early colonoscopy detected more definitive sources of bleeding (OR = 4.12, 95% CI 2.00-8.49), and was associated with shorter LOS colonoscopy (WMD = -1.52, 95% CI -2.54 to -0.50 days). No other differences were noted between early and late colonoscopy. AEs occurred in 4.0%, (95% CI 2.9%; 5.4%) of early colonoscopies. Included studies were of low quality, with significant heterogeneity for some outcomes. Conclusion:Early colonoscopy in acute LGIB does not decrease rebleeding, mortality or need for surgery, but is associated with increased detection of definitive sources of bleeding, shorter LOS, with low complication incidence. However, the quality of evidence is low, highlighting the need for additional high-level studies.
Project description:Objective:To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults. Methods:Multiple electronic databases were searched to find randomized controlled trials (RCTs) on paroxetine and panic disorder. The primary efficacy outcomes were: the mean change compared to the baseline in the total number of full panic attacks, Clinical Global Impression-Severity of Illness (CGI-S) score, and the proportion of participants with zero full panic attacks and with a 50% or greater reduction in the number of full panic attacks. The tolerability outcomes included withdrawal rate and the incidence of adverse events (AEs). Results:13RCTs were included. The pooled analyses showed patients who received paroxetine experienced greater improvements in the number of full panic attacks (total: MD=-1.96, 95%CI -3.45 to -0.47, P=0.010; ?50% reduction: OR=1.66, 95%CI 1.08 to 2.55, P=0.02; zero full panic attacks: OR=1.70, 95%CI 1.42 to 2.03, P < 0.00001) and CGI-S (MD=-0.37, 95%CI -0.74 to -0.01, P=0.05) than placebo. There was no evident difference in the total withdrawal rate (OR=0.91, 95%CI 0.76 to 1.08, P=0.26) and withdrawal rate due to AEs (OR=1.29, 95%CI 0.97 to 1.72, P=0.07) between the two groups. Withdrawal rate due to lack of efficacy or relapse (OR=0.44, 95%CI 0.31 to 0.63, P < 0.00001) and the incidence of serious AEs (OR=0.42, 95%CI 0.23 to 0.79, P=0.007) in the paroxetine group was lower than the placebo group. Meanwhile, the incidence of any treatment-emergent adverse events (TEAEs) (OR=1.32, 95%CI 1.05 to 1.64, P=0.02) in the paroxetine group was higher in comparison with the placebo. Conclusions:Paroxetine is an effective and well-tolerated short-term treatment for adults with panic disorder.
Project description:Cardiovascular or arteriothrombotic adverse events (CV- or AT-AEs) are reported in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). The incidence and characteristics across different TKI have not been systematically analyzed. We analyzed 531 patients treated with frontline TKIs in different prospective trials: imatinib 400 mg (n = 71) and 800 mg (n = 203), nilotinib (n = 108), dasatinib (n = 106), and ponatinib (n = 43). Characteristics and incidence of new-onset CV-AEs and AT-AEs were analyzed. Poisson regression models assessed factors associated with AE incidence. Median follow-up was 94 months (range, 2-195). Overall, 237 patients (45%) developed CV-AEs and 46 (9%) developed AT-AEs. Hypertension was the most common AE seen in 175 patients (33%; grade 3/4 in 17%). CV-AE and AT-AE incidence ratios (IRs) with 95% confidence intervals (CIs) were 8.6 (7.6-9.8) and 1.7 (1.2-2.2) per 100 person-years. Among the TKIs, ponatinib showed the highest IR (95% CI) for CV-AEs and AT-AEs at 40.7 (27.9-59.4) and 9.0 (4.1-20.1). In multivariate analysis, ponatinib therapy was associated with increased incidence rate ratio (IRR) for CV-AEs (4.62; 95% CI, 2.7-7.7; P < .0001) and AT-AEs (6.38; 95% CI, 1.8-21.8; P < .0001) compared with imatinib 400. In summary, there is an increased risk of CV-AEs (except hypertension) and AT-AEs in CML patients treated with newer TKIs, particularly with ponatinib. Patients on TKIs must be informed and closely monitored for vascular AEs. These studies were registered at www.clinicaltrials.gov as #NCT00048672, #NCT00038649, #NCT00050531, #NCT00254423, #NCT00129740, and #NCT01570868.