BackgroundImmune checkpoint inhibitors (ICIs) have been identified as validated medications in non-small cell lung cancer (NSCLC). However, they are often associated with immune-related adverse events (irAEs) including liver dysfunction. Therefore, we conducted a systematic review of the literature and performed a meta-analysis to ascertain overall incidence and risk of immune mediated liver dysfunction in NSCLC patients.MethodsPubMed, the Cochrane Library, Embase and ClinicalTrials.gov (http://clinicaltrials.gov/) were searched from inception to December 2019. Studies regarding all grade (1–5), high grade (3–5) hepatitis and ALT or AST elevation were included.ResultsA total of 11 clinical trials including 7086 patients were selected for further assessment. The overall incidence of ALT elevation, AST elevation and hepatitis for the application of ICIs was 6.18%, 4.99% and 1.09%, respectively. Compared with chemotherapy group, treatment with ICIs had a significantly higher risk of all grade (RR: 7.27, p = 0.001) and high grade (RR: 6.70, p = 0.003) hepatitis. When ICIs combined with chemotherapy, the relative risk of all grade hepatitis was higher than monotherapy group (RR: 7.89, p = 0.044 vs RR: 6.94, p = 0.008).ConclusionThe application of ICIs could result in a higher incidence and relative risk of all grade immune-induced liver dysfunction. Moreover, immunotherapy combined with chemotherapy may also increase relative risk of all grade hepatic AEs when compared with monotherapy. Prompt recognition and proper administration is required for clinicians to prevent potentially hepatic deterioration. 相似文献
ObjectivesAssess the efficacy and safety of Broncho-Vaxom in pediatric recurrent respiratory tract infections (RRTIs).MethodsPublished randomized controlled trials (RCTs) of Broncho-Vaxom for pediatric RRTI were searched using PubMed, Embase, Cochrane Library, CBM, CNKI, WanFang Data, and VIP databases up to January 2017. Risk of bias was evaluated in accordance to the guidelines of the Cochrane collaboration and the level of evidence was graded according to the GRADE.Results53 RCTs involving 4851 pediatric patients were included in this meta-analysis. It showed that Broncho-Vaxom was positively correlated with a reduction in the frequency of respiratory infection [MD = − 2.33, 95% CI (− 2.75, − 1.90), P < 0.00001] compared to the control group. The Broncho-Vaxom group was more effective than control groups in relation to the duration of antibiotics course, infections, fever, cough, and wheezing, increasing serum immunoglobulin levels (IgG, IgA or IgM), and T-lymphocytes subtype (CD3 +, CD4 +, or CD8 +). However, Broncho-Vaxom had higher adverse event rates [RR = 1.39, 95% CI (1.02, 1.88), P = 0.04]; these were not serious and did not influence the treatment course.ConclusionBroncho-Vaxom shows a good efficacy for pediatric RRTIs on the basis of routine therapy (e.g. anti-infection and antiviral therapy). However, the level of evidence was low and more international multicenter clinical trials are needed to explore the efficacy and safety of Broncho-Vaxom. 相似文献
PurposePrimary (PID) and secondary immune deficiencies (SID) represent diverse groups of diagnoses, yet both can be effectively treated with intravenous immunoglobulin (IVIG) replacement therapy. Guidelines for the use of IVIG in SID vary due to the paucity of data. The objective was to analyze available IVIG Privigen® (IgPro10, CSL Behring, Bern, Switzerland) data on Efficiency Index (EI) and pharmacokinetic (PK) parameters in patients with PID and SID.MethodsThree Privigen® studies (NCT00168025, NCT00322556, and the observational study IgPro10_5001) were used to identify patients with PID and SID meeting the qualifying criteria for the PK analysis. PK properties of IVIG were estimated using a population PK model based on a standard two-compartment PK model. Immunoglobulin G (IgG) EI was calculated as the gain in serum IgG level per unit external IgG dose.ResultsA similar IVIG dose-serum IgG concentration relationship was observed in patients with PID (N = 90) and SID (N = 91). IgG EI was inversely proportional to the endogenous IgG concentration and comparable in PID (slope = −1.079) and SID (slope = −2.12).ConclusionsThese findings indicate that the disposition of Privigen® is similar during IgG replacement therapy in PID and SID. The results contribute to the understanding of IVIG treatment of SID and may support an evidence-based approach for the use of IVIG in SID in the future. 相似文献
5-Fluorouracil (5FUra) is the third most popular chemotherapeutic component employed to treat solid tumors. In the present study, we aimed to appraise the silymarin (SM) and silymarin nanoemulsion (SMN) effect on 5FUra-induced gastrointestinal toxicity in adult male rats. A total of 30 male Wistar rats were divided into 6 groups including the control (Crl) group, and groups treated with SMN (5 mg.kg−1), SM (5 mg.kg−1), 5FUra + SMN (5 mg.kg−1), and 5FUra + SM (5 mg.kg−1) by IP injection for 14 days. And gastrointestinal toxicity was induced by a single intraperitoneal (IP) injection of 5FUra (100 mg.kg−1) for the last group in the study. Treating rats with SM and SMN diminished elevating malondialdehyde (MDA) levels, and improved total antioxidant capacity (TAC) levels. Also, the intensity of mRNA expression of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) caused by 5FUra in the gastrointestinal tissue tract, and macroscopic oral ulcerations decreased, ass well as weight loss was prevented, particularly in the SMN group. Moreover, in the microscopic scope, there were significant improvements in the levels of hyperemia, hyaline, and inflammatory cell infiltration in the tongue, esophagus, and intestinal tissues in the FUra + SMN and FUra + SM groups compared to 5FUra. Hence, treatment with SM and SMN reduced oxidative stress, histopathological degeneration, and gene expression of inflammatory markers in the gastrointestinal tract. According to the results, treatment with SM and SMN markedly decreases the gastrointestinal toxicity caused by 5FUra. 相似文献
ABSTRACTBackground: Lorcaserin is a novel, selective 5-hydroxytryptamine 2C serotonin receptor agonist, approved for the treatment of obesity. Several phase 3 randomized controlled trials (RCTs) trials have shown a significant reduction in body weight with lorcaserin.Research design and methods: We systematically searched the database of PubMed, Embase, The Cochrane Library and ClinicalTrials.gov up to 31 July 2019 and retrieved all the studies conducted with lorcaserin for ≥1 year that have explicitly reported the efficacy and safety outcomes versus placebo. Subsequently, we studied the effect of lorcaserin on weight reduction, FDA-defined valvulopathy, depression and suicidal risks in RCTs.Results: The meta-analysis of four RCTs (N = 16,856) demonstrated a significant decrease in body weight (mean ? ?3.076 Kg; 95% CI, ?3.49 to ?2.66; P < 0.00001), compared to placebo. No significant difference in FDA-defined valvulopathy (RR 1.20; 95% CI, 0.89 to 1.63; P = 0.24), depression (RR 1.07; 95% CI, 0.80 to 1.43; P = 0.67) or suicidal risk (RR 1.43; 95% CI, 0.96 to 2.15; P = 0.08) has been observed with lorcaserin compared to placebo.Conclusions: Lorcaserin reduces body weight modestly, with no obvious serious adverse side effects. The common adverse events noted with lorcaserin include nausea, dizziness, and transient headache. 相似文献
Introduction: To compare common side effects of mood stabilizers (MSs) and antipsychotics in pediatric and adult bipolar disorder (BD).
Area covered: MEDLINE, EMBASE, PsycINFO was searched for randomized, double-blind, placebo-controlled trials (RCTs) in the treatment of pediatric and adult BD. Twelve RCTs for pediatric patients and 30 for adult patients were included. The risk for the discontinuation due to adverse events, ≥7% weight gain, somnolence, akathisia, nausea and vomiting from a medication relative to placebo was estimated with absolute risk increase and the number needed to harm. The relative risk of these measures in pediatric and adult patients was compared.
Expert opinion: Overall, the relative risk for ≥7% weight gain, somnolence, nausea, or vomiting was higher, and akathisia was lower in pediatric patients than in adults. The magnitude of difference among MSs and antipsychotics and between pediatrics and adults varied widely. The risk for pediatric patients could be underestimated because in most pediatric studies, doses of studied medications were lower and flexibly dosed, and titration speeds were slower than in adult studies. Clinicians should pay attention to differences in study designs to understand the risk for common side effects when prescribing a medication for BD. 相似文献
ContextAidi injection is one of the most commonly use antitumor Chinese medicine injections for advanced non-small cell lung cancer (NSCLC). It is made from the extraction of Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis.ObjectiveTo evaluate the efficacy and safety of Aidi injection in combination with gemcitabine-based chemotherapy (GBC) for advanced NSCLC.Materials and methodsPubMed, Embase, Cochrane Library, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and VIP were searched for relevant randomised controlled trials (RCTs) comparing Aidi injection plus GBC treatment with GBC alone in NSCLC, from inception up to October 2020. The primary outcomes were objective response rate (ORR), and disease control rate (DCR). Secondary outcomes were quality of life (QOL) and adverse drug reactions (ADRs). The quality of evidence was rated using the GRADE approach. This study was registered with PROSPERO: CRD42021221225.ResultsIn total, 54 RCTs involving 4318 NSCLC patients were included in this meta-analysis. Compared with GBC alone, Aidi injection plus GBC significantly improve ORR (risk ratios [RR] = 1.38, 95% confidence interval [CI] 1.29–1.48), DCR (RR = 1.15, 95% CI 1.12–1.19), QOL (RR = 1.71, 95% CI 1.54–1.89), and reduced the risk of gastrointestinal toxicity, thrombocytopenia, neutropenia, liver injury, renal injury, and anaemia. The evaluation results of the evidence ranged from moderate to low.ConclusionsCurrent moderate evidence revealed that Aidi injection as an adjunctive treatment to GBC was associated with superior benefits in patients with advanced NSCLC and alleviate toxicities. High-quality RCTs are needed to further confirm the results. 相似文献
ContextDesloratadine, an H1 receptor antagonist, is suggested as an effective first-line drug for chronic urticarial (CU). However, the efficacy of desloratadine alone is limited, and the recurrence rate of CU is relatively high.ObjectiveWe sought to evaluate the efficacy and clinical feasibility of desloratadine in combination with compound glycyrrhizin in the treatment of CU.Materials and methodsA systematic literature search was conducted in the databases of the China National Knowledge Infrastructure Database, VIP, WanFang, PubMed, and Web of Science using subject terms: “Chronic urticaria”, “Loratadine”, and “Compound glycyrrhizin”. Randomised controlled trials (RCTs) that compared the efficiency and safety of the combination treatment with desloratadine alone starting from January 1, 2014 until February 10, 2021 were selected by two co-first authors independently, and the extracted data were analysed using Rev Man 5.3 software.ResultsFourteen RCTs were included in our meta-analysis with a total of 1501 patients. The results showed that the combination treatment yielded a better treatment effect (total response rate: RR = 1.23, 95% CI: 1.17 to 1.29, p < 0.00001; cure rate: RR = 1.50, 95% CI: 1.30 to 1.73, p < 0.00001), lower recurrence rate as well as superior immune improvement than the treatment with desloratadine alone. In addition, there was no significant difference in the safety of the two treatments.Discussion and ConclusionThe combination of desloratadine and compound glycyrrhizin is a promising treatment for CU and is associated with decreased serum IgE level and improved proportions of CD4+ T and CD8+ T cells. 相似文献
目的 系统评价异甘草酸镁治疗抗结核药物所致肝损害的疗效和安全性。方法 检索PubMed、EMbase、Cochrane图书馆、Medline、中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库和维普数据库,收集国内外关于异甘草酸镁治疗抗结核药致肝损害的临床随机对照研究(RCTs),评价纳入研究的质量并提取数据,使用RevMan 5.3软件进行Meta-分析。结果 共纳入14篇RCTs,包括1 202名抗结核药致肝损害患者。Meta-分析结果显示:异甘草酸镁在治疗抗结核药致肝损害总有效率[RR=1.38,95% CI (1.24,1.54),P<0.000 01]、降低丙氨酸氨基转移酶(ALT)[MD=-25.98,95% CI (-34.68,-17.29),P<0.000 01]、天冬氨酸氨基转移酶(AST)[MD=-20.21,95% CI (-24.49,-15.93),P<0.000 01]、总胆红素(TB)[MD=-9.92,95% CI (-16.41,-3.43),P=0.003]、碱性磷酸酶(ALP)[MD=-13.91,95% CI (-26.03,-1.79),P=0.02]方面均优于对照组,差异有统计学意义,同时不良反应发生率低于对照组[RR=0.51,95% CI (0.27,0.96),P=0.04]。结论 异甘草酸镁治疗抗结核药致肝损害临床疗效较好,可显著降低患者血清ALT、AST、TB和ALP水平,同时具有较高安全性,但本研究纳入文献多为较低质量的小样本研究,尚需更多高质量、大样本的随机对照试验进一步支持。 相似文献
Introduction: Migraine is increasingly recognized as an extremely burdensome and disabling disorder in both children and adolescents. A proper treatment plan is needed to improve the quality of life of both children and families as well as to minimize the risk of disease progression.
Areas covered: This review focuses on the current pharmacotherapy for acute migraine in pediatric populations, taking into account specific considerations for those drugs tested in randomized, placebo-controlled trials (RCTs).
Expert opinion: A large number of RCTs have documented the efficacy, tolerability, and safety of different compounds. Triptans appears more effective than placebo but results are variable and inconsistent. Almotriptan and rizatriptan are effective as oral formulations, as well as sumatriptan and zolmitriptan as both oral and nasal spray formulations. Adding non-steroidal anti-inflammatory drugs (NSAIDs) reinforces triptan’s effectiveness. Furthermore, small RCTs have documented both the efficacy of ibuprofen and the ineffectiveness of acetaminophen. Naproxen, ketoprofen, diclofenac, and indomethacin – NSAIDs effective in acute migraines in adults – should be tested also in pediatric subjects. Furthermore, the authors suggest that dopamine receptor antagonists should be considered in cases of severe migraines. Lastly, better designed RCTs are needed to fine-tune current therapeutic resources. 相似文献
Objective: Several biologic therapies are available for the treatment of mild-to-moderate Crohn’s disease (CD). This network meta-analysis (NMA) aimed to assess the comparative efficacy of ustekinumab, adalimumab, vedolizumab and infliximab in the maintenance of clinical response and remission after 1?year of treatment.
Methods: A systematic literature search was performed to identify relevant randomized controlled trials (RCTs). Key outcomes of interest were clinical response (CD activity index [CDAI] reduction of 100 points; CDAI-100) and remission (CDAI score under 150 points; CDAI < 150). A treatment sequence Bayesian NMA was conducted to account for the re-randomization of patients based on different clinical definitions, the lack of similarity of the common comparator for each trial and the full treatment pathway from the induction phase onwards.
Results: Thirteen RCTs were identified. Ustekinumab 90?mg q8w was associated with statistically significant improvement in clinical response relative to placebo and vedolizumab 300?mg. For clinical remission, ustekinumab 90?mg q8w was associated with statistically significant improvement relative to placebo and vedolizumab 300?mg q8w. Findings from sub-population analyses had similar results but were not statistically significant.
Conclusions: The NMA suggest that ustekinumab is associated with the highest likelihood of reaching response or remission at 1?year compared with placebo, adalimumab and vedolizumab. Results should be interpreted with caution because this is a novel methodology; however, the treatment sequence analysis may be the most methodologically sound analysis to derive estimates of comparative efficacy in CD in the absence of head-to-head evidence. 相似文献
Approximately 15% of US women currently smoke during pregnancy. An important step toward providing effective smoking cessation interventions during pregnancy is to identify individuals who are more likely to encounter difficulty quitting. Pregnant smokers frequently report smoking in response to intrapersonal factors (e.g., negative emotions), but successful cessation attempts can also be influenced by interpersonal factors (i.e., influence from close others). This study examined the association between emotion regulation difficulties, positive and negative social control (e.g., encouragement, criticism), and smoking cessation-related variables (i.e., smoking quantity, withdrawal symptoms) among pregnant smokers. Data were drawn from the pretreatment wave of a smoking cessation trial enrolling low-income pregnant women who self-reported smoking in response to negative affect (N = 73). Greater emotion regulation difficulties were related to greater smoking urges (b = 0.295, p = .042) and withdrawal symptoms (b = 0.085, p = .003). Additionally, more negative social control from close others was related to fewer smoking days (b = −0.614, p = .042) and higher smoking abstinence self-efficacy (b = 0.017, p = .002). More positive social control from close others interacted with negative affect smoking (b = −0.052, p = .043); the association between negative affect smoking and nicotine dependence (b = 0.812, p < .001) only occurred at low levels of positive social control. Findings suggest that emotion regulation difficulties may contribute to smoking during pregnancy by exacerbating women's negative experiences related to smoking cessation attempts. Negative social control was related to lower smoking frequency and greater confidence in quitting smoking, suggesting that it may assist pregnant smokers' cessation efforts. Positive social control buffered women from the effects of negative affect smoking on nicotine dependence.Trial registrationClinicalTrials.gov, NCT01163864 相似文献