Jinfang Xu

Maintenance Therapy With Continuous or Switch Strategy in Advanced Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis

BACKGROUND Maintenance therapy for patients with non-small cell lung cancer (NSCLC) has gained extensive interest. Varying results for this treatment underpin the need for a synthesis of evidence. METHODS Trials investigating maintenance therapy with either a continuous or a switch strategy for patients with nonprogressing NSCLC compared with placebo or observation were identified. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS) and toxicity. RESULTS Eight trials of 3,736 patients were included in the analysis. Switch maintenance therapy substantially improved OS compared with placebo or observation (hazard ratio [HR], 0.85; 95% CI, 0.79-0.92; P < .001). A similar trend of improved OS was found in continuous maintenance therapy, despite lacking statistical significance (HR, 0.88; 95% CI, 0.74-1.04; P = .124). The interaction test suggested that the difference in OS between the two maintenance strategies was not statistically significant (P = .777). Clinically substantial and statistically significant improvement in PFS was found with both maintenance strategies (switch maintenance therapy HR, 0.67; 95% CI, 0.57-0.78; continuous maintenance therapy HR, 0.53; 95% CI, 0.43-0.65; interaction P = .128). Subgroup analyses revealed no statistically significant differences in OS or PFS between switch maintenance therapy with cytotoxic agents and that with tyrosine kinase inhibitor agents. Toxicity was greater in maintenance therapy. CONCLUSIONS Maintenance therapy with either a continuous or a switch strategy significantly increases OS and PFS compared with placebo or observation. However, the benefits must be balanced against toxicity.

Effect of anti-obesity drug on cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials.

Background Anti-obesity drugs are widely used to prevent the complications of obesity, however, the effects of anti-obesity drugs on cardiovascular risk factors are unclear at the present time. We carried out a comprehensively systematic review and meta-analysis to assess the effects of anti-obesity drugs on cardiovascular risk factors. Methodology and Principal Findings We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles and proceedings of major meetings for relevant literatures. We included randomized placebo-controlled trials that reported the effects of anti-obesity drugs on cardiovascular risk factors compared to placebo. Overall, orlistat produced a reduction of 2.39 kg (95%CI-3.34 to −1.45) for weight, a reduction of 0.27 mmol/L (95%CI: −0.36 to −0.17) for total cholesterol, a reduction of 0.21 mmol/L (95%CI: −0.30 to −0.12) for LDL, a reduction of 0.12 mmol/L (95%CI: −0.20 to −0.04) for fasting glucose, 1.85 mmHg reduction (95%CI: −3.30 to −0.40) for SBP, and a reduction of 1.49 mmHg (95%CI: −2.39 to −0.58) for DBP. Sibutramine only showed effects on weight loss and triglycerides reduction with statistical significances. Rimonabant was associated with statistically significant effects on weight loss, SBP reduction and DBP reduction. No other significantly different effects were identified between anti-obesity therapy and placebo. Conclusion/Significance We identified that anti-obesity therapy was associated with a decrease of weight regardless of the type of the drug. Orlistat and rimonabant could lead to an improvement on cardiovascular risk factors. However, Sibutramine may have a direct effect on cardiovascular risk factors.

P16 gene hypermethylation and hepatocellular carcinoma: A systematic review and meta-analysis

AIM To quantitatively investigate the effect of p16 hypermethylation on hepatocellular carcinoma (HCC) and hepatocirrhosis using a meta-analysis of available case-control studies. METHODS Previous studies have primarily evaluated the incidence of p16 hypermethylation in HCC and corresponding control groups, and compared the incidence of p16 hypermethylation in tumor tissues, pericancer liver tissues, normal liver tissues and non-tumor liver tissues with that in other diseases. Data regarding publication information, study characteristics, and incidence of p16 hypermethylation in both groups were collected from these studies and summarized. RESULTS Fifteen studies, including 744 cases of HCC and 645 non-tumor cases, were identified for meta-analysis. Statistically significant odds ratios (ORs) of p16 hypermethylation were obtained from tumor tissues and non-tumorous liver tissues of HCC patients (OR 7.04, 95% CI: 3.87%-12.78%, P < 0.0001), tumor tissues of HCC patients and healthy liver tissues of patients with other diseases (OR 12.17, 95% CI: 6.64%-22.31%, P < 0.0001), tumor tissues of HCC patients and liver tissues of patients with non-tumorous liver diseases (OR 6.82, 95% CI: 4.31%-10.79%, P < 0.0001), and cirrhotic liver tissues and non-cirrhotic liver tissues (OR 4.96, 95% CI: 1.45%-16.96%, P = 0.01). The pooled analysis showed significantly increased ORs of p16 hypermethylation (OR 6.98, 95% CI: 4.64%-10.49%, P < 0.001) from HCC tissues and cirrhotic tissues. CONCLUSION P16 hypermethylation induces the inactivation of p16 gene, plays an important role in hepatocarcinogenesis, and is associated with an increased risk of HCC and liver cirrhosis.

Adverse Drug Reactions of Spontaneous Reports in Shanghai Pediatric Population

Background Knowledge of drug safety in the pediatric population of China is limited. This study was designed to evaluate ADRs in children reported to the spontaneous reporting system (SRS) of Shanghai in 2009. Methodology and Principal Findings Crude ADR reports submitted to Shanghai SRS in 2009 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to age, gender, category of ADR (System Organ Class [SOC]), the severity of reports and type of reporter. Results A male overrepresentation was observed regarding the total number of reports. The most frequently reported group of drugs were vaccines (42.15%). Skin rash and fever were the commonest symptoms reported in the total pediatric dataset. The proportion of children that suffered from a serious ADR was 2.16% and that for drug related deaths was 0.34%. And we found that the multiple drug exposure experienced a high proportion of serious ADRs compared with the single drug use (χ2 = 15.99, P<0.0001). Sixty-five percent of ADRs were for children less than 6 years of age. And more than half of reports were from doctors. Conclusions In our study, consumers were more likely to report new ADRs though they appear to contribute a relatively small percentage of total reports. We propose that patients would take an active role in reporting ADRs. More researches are needed in order to achieve better understanding the characteristics of ADRs in pediatric population of China.

Exploration of the association rules mining technique for the signal detection of adverse drug events in spontaneous reporting systems.

Background The detection of signals of adverse drug events (ADEs) has increased because of the use of data mining algorithms in spontaneous reporting systems (SRSs). However, different data mining algorithms have different traits and conditions for application. The objective of our study was to explore the application of association rule (AR) mining in ADE signal detection and to compare its performance with that of other algorithms. Methodology/Principal Findings Monte Carlo simulation was applied to generate drug-ADE reports randomly according to the characteristics of SRS datasets. Thousand simulated datasets were mined by AR and other algorithms. On average, 108,337 reports were generated by the Monte Carlo simulation. Based on the predefined criterion that 10% of the drug-ADE combinations were true signals, with RR equaling to 10, 4.9, 1.5, and 1.2, AR detected, on average, 284 suspected associations with a minimum support of 3 and a minimum lift of 1.2. The area under the receiver operating characteristic (ROC) curve of the AR was 0.788, which was equivalent to that shown for other algorithms. Additionally, AR was applied to reports submitted to the Shanghai SRS in 2009. Five hundred seventy combinations were detected using AR from 24,297 SRS reports, and they were compared with recognized ADEs identified by clinical experts and various other sources. Conclusions/Significance AR appears to be an effective method for ADE signal detection, both in simulated and real SRS datasets. The limitations of this method exposed in our study, i.e., a non-uniform thresholds setting and redundant rules, require further research.

Misuse of Statistical Methods in 10 Leading Chinese Medical Journals in 1998 and 2008

Statistical methods are vital to biomedical research. Our aim was to find out whether progress has been made in the last decade in the use of statistical methods in Chinese medical research. We reviewed 10 leading Chinese medical journals published in 1998 and in 2008. Regarding statistical methods, using a multiple t-test for multiple group comparison was the most common error in the t-test in both years, which significantly decreased in 2008. In contingency tables, no significant level adjustment for multiple comparison significantly decreased in 2008. In ANOVA, over a quarter of articles misused the method of multiple pair-wise comparison in both years, and no significant difference was seen between the two years. In the rank transformation nonparametric test, the error of using multiple pair-wise comparison for multiple group comparison became less common. Many mistakes were found in the randomised controlled trial (56.3% in 1998; 67.9% in 2008), non- randomised clinical trial (57.3%; 58.6%), basic science study (72.9%; 65.5%), case study or case series study (48.4%; 47.2%), and cross-sectional study (57.1%; 44.2%). Progress has been made in the use of statistical methods in Chinese medical journals, but much is yet to be done.

Reporting patterns of adverse drug reactions over recent years in China: analysis from publications

Purpose: The goal of this study was to clarify the reporting patterns of self-reported adverse drug reactions (ADRs) in China. Methods: A variety of sources were searched, including the official website of China FDA, the national center for ADR monitoring center, publications from PubMed, and so on. We retrieved the relevant information and made descriptive and comparative analysis from the year 2009 to 2013. Results: The ADR reporting numbers were 638,996, 692,904, 852,799, 1,200,000 and 1,317,000 from 2009 to 2013, respectively. Healthcare professionals contributed significantly, and their proportion always exceeded 80% before 2012. The average report per million inhabitants has increased from 479 to 983 from 2009 to 2013. However, the proportion of new or serious report was always below 25%. The reports mainly concern anti-infective agents and traditional Chinese medicine (TCM), especially TCM injection. The proportion of ADR reports in geriatric patients has increased for 4 consecutive years. Conclusions: ADR report numbers and reporting rates in China are on the rise. However, the proportion of new or serious reports as well as the proportion of reports contributed by consumers and pharmaceutical companies are still quite low. More attention should be paid to the elderly, anti-infective agents and TCM, especially TCM injections.

Pemetrexed plus platinum or gemcitabine plus platinum for advanced non-small cell lung cancer: final survival analysis from a multicentre randomized phase II trial in the East Asia region and a meta-analysis

Background and Objective:  Pemetrexed plus platinum has shown efficacy as a first‐line treatment for advanced non–small cell lung cancer (NSCLC), but little is known about its efficacy and safety in East Asian patients. We report the final analysis of overall survival (OS) from a multicentre, randomized, phase II trial in chemotherapy‐naive Chinese patients with advanced NSCLC. An additional meta‐analysis was performed to systematically evaluate pemetrexed/platinum as first‐line treatment for advanced NSCLC.

Combined EGFR and VEGFR versus Single EGFR Signaling Pathways Inhibition Therapy for NSCLC: A Systematic Review and Meta-Analysis

Background Lung cancer is a heterogeneous disease with multiple signaling pathways influencing tumor cell survival and proliferation, and it is likely that blocking only one of these pathways allows others to act as salvage or escape mechanisms for cancer cells. Whether combined inhibition therapy has greater anti-tumor activity than single inhibition therapy is a matter of debate. Hence, a meta-analysis comparing therapy inhibiting both VEGFR and EGFR signaling pathways with that inhibiting EGFR signaling pathway alone was performed. Methodology and Principal Findings We searched PubMed, EMBASE database and the proceedings of major conferences for relevant clinical trials. Outcomes analyzed were objective tumor response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity. Besides, subgroup analyses were performed to investigate whether the combined inhibition therapy is best performed using combination of selective agents or a single agent with multiple targets. Six trials recruiting 3,302 patients were included in the analysis. Combined inhibition therapy was associated with a 3% improvement in OS as compared with single-targeted therapy, but this difference was not statistically significant (HR, 0.97; 95% CI, 0.89–1.05; P = 0.472). Patients receiving combined inhibition therapy had significant longer PFS than the group with single-targeted therapy (HR, 0.80; 95% CI, 0.67–0.95; P = 0.011). There was no difference in the ORR between the groups (OR, 1.44; 95% CI, 0.95–2.18; P = 0.085). Subgroup analysis revealed that combined inhibition therapy using combination regimens was associated with statistically significant improvement in both ORR and PFS. Toxicity was greater in combined inhibition therapy. Conclusions There is no evidence to support the use of combined inhibition therapy in unselected patients with advanced NSCLC. However, given the significant advantage in ORR and PFS, combined inhibition therapy using combination regimens may be considered for further evaluation in subsets of patients who may benefit from this treatment.

Application of biclustering algorithm in adverse drug reaction monitoring system of China

Signal evaluation is considered to be a tedious process owing to the large number of disproportional signals detected. This study aimed to apply a biclustering algorithm in the spontaneous reporting system of China and to obtain the optimal parameters. The biclustering algorithm is expected to improve the efficiency of signal evaluation by identifying similar signal groups.