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The risk factors of high trait anger of juvenile offenders were explored through questionnaire study in a youth correctional facility of Hubei province, China. A total of 1090 juvenile offenders in Hubei province were investigated by self-compiled social-demographic questionnaire, Childhood Trauma Questionnaire (CTQ), and State-Trait Anger Expression Inventory-II (STAXI-II). The risk factors were analyzed by chi-square tests, correlation analysis, and binary logistic regression analysis with SPSS 19.0. A total of 1082 copies of valid questionnaires were collected. High trait anger group ( n=316) was defined as those who scored in the upper 27th percentile of STAXI-II trait anger scale (TAS), and the rest were defined as low trait anger group ( n=766). The risk factors associated with high level of trait anger included: childhood emotional abuse, childhood sexual abuse, step family, frequent drug abuse, and frequent internet using ( P<0.05 or P<0.01). Birth sequence, number of sibling, ranking in the family, identity of the main care-taker, the education level of care-taker, educational style of care-taker, family income, relationship between parents, social atmosphere of local area, frequent drinking, and frequent smoking did not predict to high level of trait anger ( P>0.05). It was suggested that traumatic experience in childhood and unhealthy life style may significantly increase the level of trait anger in adulthood. The risk factors of high trait anger and their effects should be taken into consideration seriously. [ABSTRACT FROM AUTHOR]

Inhibition of vascular epithelial growth factor (VEGF) signaling pathways has proven to be an effective strategy for the treatment of several common solid tumors, but its role in the management of advanced gastric cancer (AGC) is yet to be defined. We performed a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of anti-VEGF agents in the treatment of AGC. Several databases were searched, including PubMed, Embase, and Cochrane databases. The endpoints were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events (AEs). The pooled hazard ratio (HR) or relative risk (RR) and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Seven RCTs which involved 2,340 patients were ultimately identified. The pooled analysis demonstrated that anti-VEGF therapy significantly improved OS (HR 0.74, 95 % CI 0.61-0.91, p = 0.003), PFS (HR 0.59, 95 % CI 0.44-0.78, p < 0.001), and ORR (RR 1.43, 95 % CI 1.14-1.79, p = 0.002) when compared to non-anti-VEGF therapy. Sensitivity analysis further confirmed this association. Additionally, more incidences of grade 3 or 4 thrombocytopenia, diarrhea, and hypertension were observed in anti-VEGF therapy. The anti-VEGF therapy offers a significant survival benefit in patients with AGC, especially for those previously treated patients, when compared to non-anti-VEGF therapy. With the present available data from randomized clinical trials, we could not clearly set the role of specific anti-VEGF agents in the treatment of AGC. Further studies are recommended to identify patients who could derive greater benefits from specific anti-VEGF agents. [ABSTRACT FROM AUTHOR]

Background: The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event. Materials and methods: We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. Results: A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95 % CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR 3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78-20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036). Conclusions: Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: Aflibercept, a fully humanized vascular endothelial growth factor (VEGF)-targeted agent, has emerged as an effective therapy in the treatment of various solid tumors. We carried out an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in cancer patients treated with aflibercept. Methods: We searched databases such as PubMed and Web of Science, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings for records up to August 2013 to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating aflibercept in cancer patients with adequate data on FAEs. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95 % confidence intervals (CIs) by using either random effects or fixed-effect models according to the heterogeneity of included studies. Results: A total of 3,060 patients with a variety of solid tumors from ten clinical trials were included in our analysis. The overall incidence of FAEs associated with aflibercept was 5.1 % (95%CI: 3.8-6.8 %). The use of aflibercept significantly increased the risk of FAEs compared to patients treated with control medication (OR 1.81, 95 % CI: 1.20-2.72, p = 0.004). Additionally, the most common causes of FAEs were infection (38.8 %), hemorrhage (5.9 %) and GI perforation (5.9 %), respectively. Conclusions: With available evidence, the use of aflibercept is associated with an increased risk of FAEs compared to controls. Further studies are still needed to investigate this association. In the appropriate clinical scenario, the use of aflibercept remains justified in its approved indications. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to gain a better understanding of the overall incidence and risk of osteonecrosis of the jaw (ONJ) in cancer patients receiving denosumab. Methods: We performed a meta-analysis of relevant randomized controlled trials identified in Pubmed, Embase, and Cochrane databases. Abstracts presented at the conferences were also searched. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: A total of 8963 patients with a variety of solid tumors from 7 randomized controlled trials (RCTs) were included for the meta-analysis. The overall incidence of ONJ in cancer patients receiving denosumab was 1.7 % [95 % CI: 0.9-3.1 %]. Also, the use of denosumab was associated with significantly increased risk of ONJ in comparison with bisphosphonates (BPs)/placebo treatment (RR 1.61, 95 % CI: 1.05-2.48, P = 0.029). Subgroup analysis based on controlled therapies demonstrated an increased risk of ONJ in denosumab therapy, when compared with BPs (RR 1.48, 95 % CI: 0.96-2.29, P = 0.078) or placebo (RR 16.28, 95 % CI: 1.68-158.05, P = 0.017). Similar results were observed in prostate cancer (RR 3.358, 95 % CI: 1.573-7.166, P = 0.002) while there was a non-significantly increased risk of denosumab-related osteonecrosis of the jaw (DONJ) in non-prostate cancers (RR 1.142, 95 % CI: 0.678-1.921, P = 0.618). Conclusions: The use of denosumab is associated with an increased risk of developing ONJ when compared with BP treatment or placebo, although the increased risk was not statistically significant between denosumab and BP treatment. Further studies are still needed to establish guidelines for the prevention and effective treatment of ONJ. [ABSTRACT FROM AUTHOR]

Background: Aflibercept is currently approved as second-line treatment for patients with metastatic colorectal cancer, and its application in other types of tumors is undergoing clinical evaluation. Hypertension is one of its major adverse effects with a substantial variation in the reported incidences and has not been systematically investigated. Methods: We searched PubMed, EMBASE, and Cochrane Library databases from January 2000 to August 2013 and abstracts presented at annual meetings from 2004 to 2013 to identify relevant studies. Eligible studies were phase II and III prospective clinical trials of aflibercept in patients with any type of cancer describing events of hypertension. Summary incidence rates, odds ratios (OR), and 95 % confidence intervals (CIs) were calculated employing fixed- or random-effects models depending on the heterogeneity of the included trials. Results: A total of 15 trials with 4,451 patients were included for the meta-analysis. The summary incidences of all-grade and high-grade hypertension were 42.4 % (95 % CI 35.0-50.3) and 17.4 % (95 % CI 13.7-21.9), respectively. The use of aflibercept in cancer patients was associated with a significantly increased risk of all-grade (OR 4.47, 95 % CI 3.84-5.22, p < 0.001) and high-grade (OR 4.97, 95 % CI 3.95-6.27, p < 0.001) hypertension. The risk of developing hypertension with aflibercept was significantly higher than that of bevacizumab (all-grade: OR 1.93, 95 % CI 1.61-2.32, p < 0.001; high-grade: OR 2.06, 95 % CI 1.79-2.37, p < 0.001). Conclusions: The use of aflibercept is associated with a significantly increased risk of developing all-grade and high-grade hypertension compared with control. Close monitoring and adequate managements are highly recommended to decrease cardiovascular complication. [ABSTRACT FROM AUTHOR]

Purposes: To gain a better understanding of the overall incidence and risk of hypertension in cancer patients who receive pazopanib and to compare the differences in incidence among sorafenib, sunitinib, and pazopanib. Methods: Several databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned single drug pazopanib 800 mg/day with data on hypertension available. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials. Results: A total of 1,651 patients with a variety of solid tumors from 13 clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade hypertension in cancer patients were 35.9 % (95 % CI 31.5-40.6 %) and 6.5 % (95 % CI 5.2-8.0 %), respectively. The use of pazopanib was associated with an increased risk of developing all-grade (RR 4.97, 95 % CI 3.38-7.30, p < 0.001) and high-grade hypertension (RR 2.87, 95 % CI 1.16-7.12, p = 0.023). Additionally, there was no significant difference in the incidence of all-grade (RR 1.21, 95 % CI 0.96-1.53, p = 0.11) and high-grade hypertension (RR 1.29, 95 % CI 0.80-2.07, p = 0.30) between RCC and non-RCC patients. Interestingly, the risk of all-grade hypertension with pazopanib was substantially higher than sorafenib (RR 1.99; 95 % CI 1.73-2.29, p = 0.00) and sunitinib (RR 2.20; 95 % CI 1.92-2.52, p = 0.00), while the risk of pazopanib-induced high-grade hypertension was similar to sorafenib (RR 0.98; 95 % CI 0.75-1.30, p = 0.90) and sunitinib (RR 0.81; 95 % CI 0.62-1.06, p = 0.12). Conclusions: The use of pazopanib is associated with a significantly increased risk of developing hypertension. Close monitoring and appropriate managements are recommended during the therapy. Future studies are still needed to investigate the risk reduction and possible use of pazopanib in selected patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy of doublet versus single third-generation cytotoxic agent as first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC). Methods: Several databases including PubMed, Embase, and Cochrane databases were searched. The endpoints were overall survival (OS), time to progression (TTP), 1-year survival rate (1-year SR), overall response rate (ORR), and grade 3 or 4 adverse event (AE). We performed a meta-analysis of the randomized controlled trials using a fixed-effects model and an additional random-effects model when applicable. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95 % confidence intervals (95 % CI). A subgroup meta-analysis was performed based on chemotherapy regimens. Results: Ten eligible trials involving 2,510 patients were identified. The intention-to-treatment (ITT) analysis demonstrated that doublet therapy was superior to single agent in terms of OS (HR = 0.84, 95 % CI = 0.71-1.00, p = 0.053), TTP (HR = 0.76, 95 % CI = 0.60-0.96, p = 0.022), 1-year SR (RR = 1.17, 95 % CI = 1.02-1.35, p = 0.03), and ORR (RR = 1.54, 95 % CI = 1.36-1.73, p = 0.000). Subgroup analysis also favored platinum-based doublet therapy in terms of 1-year SR (RR = 1.40, 95 % CI = 1.09-1.81, p = 0.009) and ORR (RR = 1.64, 95 % CI = 1.38-1.96, p = 0.000). Though gemcitabine-based doublet significantly increased ORR compared with single agent (RR = 1.45, 95 % CI = 1.23-1.71, p = 0.000), it did not translate into an increase in survival benefits. In addition, more incidences of grade 3 or 4 anemia, thrombocytopenia, and neurotoxicity were observed in the doublet combination group. With respect to grade 3 or 4 neutropenia and nonhematologic toxicities such as diarrhea, fatigue, nausea, and vomiting, equivalent frequencies were found between the two groups. Conclusions: Our results indicated that doublet therapy was superior to a single third-generation cytotoxic agent for elderly patients with advanced NSCLC. The optimal dosage and schedule of platinum-based doublet should be investigated in future prospective clinical trials. Gemcitabine-based doublet could be considered for elderly patients who were not suitable for platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the feasibility and efficacy of pirarubicin (THP)-cisplatin (DDP) chemotherapy for refractory and recurrent high-grade osteosarcoma. Between 2008 and 2010, 23 patients with refractory and recurrent high-grade osteosarcoma were included in this analysis. THP was given at a dose of 50 mg/m i.v. d1 and DDP 100-120 mg/m i.v. d2-3 every 3 weeks. Treatment was continued until evidence of disease progression or unacceptable toxicity. Tumor response was usually evaluated every two chemotherapy cycles by CT/MRI scan. The primary end point was overall response rate, secondary endpoint including progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities. A total of 68 cycles were given, median 2 per patient (range 2-7). Overall response rate was 13% and disease control rate was 34.5%, with 3 partial responses and 5 stable diseases. Median time to progression and overall survival time were 2 (95%CI 2-11) and 10 months (95%CI 6-23), respectively. Major severe toxicities were grade 3 or 4 leucopenia occurred 12 times (17.7%) in total cycles; Mild toxicities included grade 1 or 2 nausea and vomiting (80.9%), leucopenia (61.8%), fatigue (50.0%), and alopecia (79.4%). THP-DDP regimen chemotherapy represents an active and well-tolerated treatment for Chinese refractory and recurrent high-grade osteosarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. [ABSTRACT FROM AUTHOR]

Background: To compared pemetrexed-based doublet with single-agent pemetrexed as second-line treatment for advanced non-small-cell lung cancer Methods: We systematically searched for randomized clinical trials that compared pemetrexed-based doublet with single-agent pemetrexed in patients with histologically proven non-small-cell lung cancer. The primary end point was overall survival. Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by 2 independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, Texas, USA). Results: Five randomized clinical trials (totally 1,186 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (HR 0.82, 95% CI 0.71-0.95, P = 0.007) and overall response rate (OR 2.39, 95% CI 1.58-3.62, P = 0.000) in pemetrexed-based doublet group, compared with pemetrexed alone, though the pooled HR for overall survival (HR 0.89, 95% CI 0.76-1.04; P = 0.129) showed no significant difference between the two groups. However, there were more incidences of grade 3 or 4 neutropenia (OR 2.3, 95% CI 1.4-3.77, P = 0.001), thrombocytopenia (OR 6.41, 95% CI 2.57-16.0, P = 0.000), and leucopenia (OR 2.45, 95% CI 1.13-5.34, P = 0.024) in pemetrexed-based doublet group. With regard to the risk of grade 3 or 4 anemia (OR 0.71, 95% CI 0.17-2.91, P = 0.629) and fatigue (OR 1.47, 95% CI 0.92-2.35, P = 0.104), there was no significant difference between the two groups. Conclusion: Pemetrexed-based doublet therapy didn't gain any benefit in survival but significantly improved PFS and better ORR compared with single-agent pemetrexed as second-line therapy for advanced non-small-cell lung cancer. However, more incidences of grade 3 or 4 neutropenia, thrombocytopenia, and leucopenia were observed in pemetrexed-based doublet group. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess the efficacy and toxicity of vandetanib in the second-line treatment for advanced non-small cell lung cancer (NSCLC). Methods: We systematically searched for randomized clinical trials that compared therapy with vandetanib versus standard second-line treatment, including docetaxel, pemetrexed, erlotinib, or gefitinib, as second-line treatment for patients with histologically proven non-small-cell lung cancer. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival, overall response rate, and grade 3 or 4 toxicity. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, TX, USA). Results: Four randomized clinical trials ( N = 3,292 patients) were eligible. Meta-analysis showed that there was significant improvement in PFS (hazards ration (HR), 0.91; 95% confidence interval (CI), 0.83−1.00; P = 0.039) and overall response rate (relative risk (RR), 1.49; 95% CI, 1.04−2.14; P = 0.03) in therapy with vandetanib group compared with standard second-line therapy group, although the pooled HR for overall survival (HR, 0.95; 95% CI, 0.88−1.03; P = 0.191) showed no significant difference between the two groups. In addition, there were less incidences of grade 3 or 4 anemia (RR, 0.39; 95% CI, 0.22−0.67; P = 0.001) in therapy with vandetanib group. With regard to the risk of grade 3 or 4 neutropenia (RR, 1.19; 95% CI, 1.0-1.43; P = 0.054), diarrhea (RR, 1.38; 95% CI, 1.0−1.94; P = 0.059), nausea and vomiting (RR, 0.77; 95% CI, 0.48−1.26; P = 0.308), rash (RR, 2.83; 95% CI, 0.73−10.9; P = 0.131), cough (RR, 1.19; 95% CI, 1.0−1.43; P = 0.054), and fatigue (RR, 1.0; 95% CI, 0.747−1.35; P = 0.971), there was no significant difference between the two groups. Conclusions: Therapy with vandetanib offered a clinically meaningful and statistically significant improvement in PFS and ORR in patients with advanced NSCLC but did not benefit overall survival. Therapy with vandetanib regimens might be suggested as second-line treatment for advanced NSCLC based on a similar toxicity profile compared with standard second-line therapy. [ABSTRACT FROM AUTHOR]

Background: The aim of this meta-analysis was to gather current data and evaluate not only the risk of gastrointestinal (GI) perforation with bevacizumab, but also the potential risk factors for this adverse event. Materials and methods: We carried out a literature search in PubMed for randomized controlled trials (RCTs) reported from January 2000 to December 2013. Summary incidence, relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of the included studies. Results: A total of 26,833 patients from 33 RCTs were included in the meta-analysis. Bevacizumab-containing therapy significantly increased the risk of developing all-grade (RR 3.35, 95 % CI 2.35-4.79, P < 0.001) and fatal GI perforation (RR 3.08, 95%CI: 1.04-9.08, P = 0.042). On subgroup analysis, no significant risk differences were found based on bevacizumab dosage, treatment duration, treatment line, type of clinical trial and median age. When stratified by tumor types, a significantly increased risk of GI perforation with bevacizumab was observed in colorectal cancer (RR 2.84, 95% CI 1.43-5.61, P = 0.003), gynecologic cancer (RR 3.37, 95% CI 1.71-6.62, P < 0.001) and prostate cancer (RR 6.01, 95% CI 1.78-20.28, P = 0.004). Additionally, the use of bevacizumab significantly increased the risk of GI perforation when used in conjunction with taxanes (RR 3.09, 95% CI 1.92-4.96, P < 0.001) or oxaliplatin (RR 2.85, 95% CI 1.07-7.57, P = 0.036). Conclusions: Bevacizumab treatment is associated with a significantly increased risk of developing GI perforation, and clinicians should be aware of the risks of GI perforation with the administration of this drug in cancer patients. [ABSTRACT FROM AUTHOR]