Search

Additional file 2. The flow of three-round Delphi survey.

Additional file 3. Available registration examples of good reporting of TCM clinical trials.

Additional file 1. S1. Search strategy and flow chart of the literature review. S2. Available published examples of reporting moxibustion SRs.

Additional file 1. Description of 42 participants in the Delphi survey.

With the introduction and development of evidence-based medicine in China, it has been spread rapidly in the area of integrative medicine (IM) and has become a new unique discipline. During almost 20 years, as one of the most important parts of evidence-based IM, systematic review (SR)/meta-analysis (MA) of IM have shown a good development momentum in the aspects of quantity, depth, breadth and influence, but also face the harsh situation of the uncontrolled quantity and quality, especially for SRs in Chinese. Therefore, how to supervise and standardize this area effectively becomes a problem to be solved. Based on the experience both at home and abroad, the authors put forward several kinds of solutions for laying the foundation for further development such as promoting the registration system of SR/MA of IM, effectively setting up the regulatory platform of quality and quantity, launching professional training for SR/MA reviewers, forming qualification registration, developing the data transfer and sharing platform to realize the transparency of evidence process.

Editors' Note: This article is the simplified Chinese version of the CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. (Cheng C, Wu T, Shang H, Li, Y, Altman D, Moher D; CONSORT-CHM Formulas 2017 Group. CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. Ann Intern Med. 2017;167:112-21. [Epub 27 June 2017]. doi:10.7326/M16-2977).

Because of its mechanism of action, the starch content of a diet might alter the hypoglycemic effect of acarbose.We aimed to determine whether differences in this hypoglycemic effect existed between individuals consuming Eastern and Western diets with significantly different starch contents, a systematic meta-analysis of studies comparing acarbose with placebo or other hypoglycemic agents in patients with type 2 diabetes mellitus (T2DM) was performed.Records were retrieved from the Cochrane clinical controlled trials, MEDLINE, EMBASE, Wanfang, Chinese Technical Periodicals, and ongoing trials databases, and full texts and reference lists were screened. Because no study has directly compared patients consuming different types of diet, fixed- and random-effect models were used to indirectly compare the hypoglycemic effect of acarbose monotherapy with that of placebo and/or comparator drugs in patients with T2DM consuming an Eastern (Eastern Asia) or Western (including Europe and North America) diet.A total of 46 studies were included in the meta-analysis. The results revealed that, compared with placebo, hemoglobin A1c (HbA1c) levels were reduced to a significantly greater extent (1.02%) in the Eastern diet (mean [SD], 1.54% [2.00%]) than in the Western diet (mean [SD], 0.52% [1.20%]) P0.00001). The ability of acarbose to reduce HbA1c levels in the Eastern (P = 0.20) and Western (P = 0.10) diet groups was similar to that of sulfonylureas, and HbA1c levels were reduced significantly more (0.39%; P0.00001) in the Eastern than in the Western diet group. The ability of acarbose to reduce HbA1c levels was similar to those of metformin and nateglinide/repaglinide, but a comparison of its efficacy with different diets was difficult because of the inclusion of few studies in these categories. Analysis of all included studies revealed that acarbose achieved a greater absolute reduction of HbA1c levels in the Eastern diet (mean [SD], 1.26% [1.20%]) than in the Western diet (mean [SD], 0.62% [1.28%]; P0.00001) group. However, the poor quality of Eastern diet trials may have affected the outcomes of the meta-analysis.The hypoglycemic effect of acarbose is superior in patients with T2DM consuming an Eastern diet than in those consuming a Western diet and is similar to that of sulfonylureas, metformin, and glinide drugs.

The association between vascular endothelial growth factor (VEGF) +936 C/T gene polymorphisms and gastric cancer risk is still controversial and ambiguous. The objective of our study was to investigate this association. The Medline and Embase databases were searched by two investigators. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to test the association between VEGF +936 C/T polymorphisms and gastric cancer risk. Our meta-analysis comprised seven case-control studies, which included 1,893 gastric cancer cases and 2,245 controls. The combined results showed that there was no relationship between VEGF +936 C/T gene polymorphisms and gastric cancer risk (cc: OR 0.97, 95% CI 0.85, 1.11; CT: OR 1.01, 95% CI 0.88, 1.16; TT: OR 1.10, 95% CI 0.79, 1.55). Subgroup analysis by ethnicity and stage, location, and Lauren classification of gastric cancer did not change the results. This meta-analysis suggests that there is no association between VEGF +936 C/T polymorphisms and gastric cancer risk. Further studies should pay attention to other potentially functional SNPs.

Studies investigating the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 10 case-control studies, which included 1161 gastric cancer cases and 2847 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR) = 1.14, 95% confidence interval (CI) = 0.91, 1.44; AG (OR=0.82, 95% CI = 0.66, 1.03); GG (OR = 1.11, 95% CI = 0.55, 2.24)] between gastric cancer and non-cancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly higher frequency of AA (OR = 1.53, 95% CI = 1.14, 2.06) and lower frequency of AG (OR = 0.70, 95% CI = 0.55, 0.89) than non-cancer patients among Caucasians. When stratifying by the location and Lauren’s classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the GSTP1 codon 105 polymorphism may be associated with gastric cancer among Caucasians.

Evaluating outcome is the primary means by which different medical modalities can be compared with regard to effectiveness. In traditional Chinese medicine (TCM), this focus has prompted practitioners to search for outcome measures that can objectively verify the effectiveness of TCM interventions, especially in the context of randomized controlled trials (RCTs). Commonly used indexes for outcome assessment in RCTs of TCM can be categorized into two types: TCM-specific outcomes such as tongue and pulse characteristics, and Western medicine (WM)-specific outcomes such as blood test and X-ray examination results. Some studies include both types of indicators. During the trial design, it is necessary to consider the rationales of selecting outcome assessments, the purpose and study approach, balance between objective and subjective indexes, standardization of outcome assessment, and standardized outcome indexes. We recommend to report the outcome assessment in RCTs of TCM in the following format: 1) identifying the primary and secondary outcomes based on the purpose and hypothesis of the trial; 2) defining the primary and secondary outcomes clearly; 3) presenting the rationale of selection; 4) presenting the method with aims to standardize the assessment process; 5) presenting the method to improve the reliability of assessment; and 6) stating the termination criteria in the trial.

The Consolidated Standards of Reporting Trials (CONSORT) Statement was published in 1996, and first introduced to China in 2001. Although CONSORT has been widely accepted in high-quality international journals, we still need to have more investigation on how many Chinese journals have adopted the CONSORT Statement, and whether the quality of reporting has improved. A systematic search of the “Instructions to authors” in all Chinese medical journals in China Academic Journals (CAJ) Full-text Database was conducted up to February 2012 and only 7 journals officially listed the requirements of the CONSORT Statement. The research articles about randomized controlled trials (RCTs) published in 2002, 2004, 2006, 2008, and 2010 from journals which had specifically adopted the CONSORT Statement, and from 30 top journals based on the Chinese Science Citation Index (CSCI) 2011 as the control group, were identified. The quality of both cohorts of articles was assessed using the revised CONSORT Checklist and Jadad scale. A total of 1221 Chinese medical journals was identified. Only seven journals stated clearly in the “Instructions to authors” that authors should adopt the CONSORT requirement in the clinical trial paper. None of these journals is among the control group in the CSCI 2011. In the selected years, a total of 171 articles from 7 journals which had adopted CONSORT and 232 articles in the control were identified as including RCT trials. The average scores according to the revised CONSORT Checklist were 29.47 for the CONSORT-adopting journals and 25.57 for the control group; while the average scores based on the Jadad scale were 2.53 for CONSORT-adopting journals and 1.97 for the control group. Few journals among Chinese medical journals have adopted the CONSORT Statement. The overall quality of RCT reports in the 7 journals which have adopted CONSORT was better than those in the top 30 journals which have not adopteded CONSORT. The quality of RCT reports in Chinese journals needs further improvement, and the CONSORT Statement could be a very helpful guideline.

Objective: To discuss the quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) with respect to design and methodology and provide suggestions for further improvement in future clinical trials. Methods; A search of the Cochrane Library was conducted to identify RCTs of CHM on line in July 2005. Quality of the RCTs was assessed using a 11-item checklist modified from the revised CONSORT statement, with 2 items specific to CHM (i.e. herb preparation form and quality control of herbs). Results; The search yielded 167 RCTs that were selected for assessment. All trials included statements about the interventions, objectives, primary outcome design statistical methods, and herb preparation form. Although 163 (97.6%) trials reported inclusion criteria, exclusion criteria were only reported in 26 (15.6%) trials. Fewer than 10% of trials clearly stated the random allocation sequence generation methods, and only 2.4% mentioned allocation concealment. The vast majority (86.8%) of trials were open-label. while only 13.2% used blinding. Almost half (45.5%) administered the CHM intervention as a tea or decoction. Only one trial (0.6%) reported a sample size calculation, and a single trial (0.6%) discussed quality control of the CHM intervention. Conclusion: The overall methodologic quality of RCTs in CHM was poor. It is essential to improve the design of future RCTs in this clinical area. Recommendations: (1) Investigator conducting RCTs should have formal training about clinical trial design; (2) A flow chart is recommended to ensure that all essential steps of clinical trial design are included. (3) Conducting pilot studies prior to RCTs may help improve their design; (4) Registration of clinical trials and publishing their protocols prior to enrolment may reduce publication bias and solicit peer reviews of the proposed design; (5) Collaboration between CHM investigators and traditional medicine academic research centers interested in integrative medicine may lead to quality improvement of RCTs of CHM.

Objective: To discuss the types of control groups in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM), and to provide suggestions for improving the design of control group in future clinical studies in this therapeutic area. Methods: A search of the Cochrane Library was conducted in July 2005 to identify RCTs of CHM. and 66 RCTs with CHM for type 2 diabetes mellitus were obtained as the basis for further analysis. Results: Of 66 RCTs with OHM for type 2 diabetes mellitus, 61 (92.4%) trials had both a treatment group and a control group. Twenty-seven (40.9%) RCTs compared CHM plus conventional drug vs conventional drug, 24 (36.4%) compared CHM vs conventional drug 5 (7.6%) compared CHM vs placebo. 3 (4.5%) compared CHM plus conventional drug vs conventional drug plus placebo. 3 (4.5%) compared CHM plus conventional drug vs other CHM, 1 (1.5%) compared CHM vs no treatment. 1 (1.5%) compared CHM plus placebo vs conventional drug plus placebo. 1 (1.5%) compared CHM vs CHM plus conventional drug vs conventional drug vs placebo. and 1 (1.5%) compared CHM vs conventional drug vs CHM plus conventional drug. Conclusion: A variety of control groups were used in RCTs of CHM for type 2 diabetes mellitus, including placebo, active, and no treatment control groups. Justification for selecting particular types of control groups were not provided in the trials reviewed in this study. Different control groups may be appropriate according to the study objectives, and several factors should be considered prior to selecting control groups in future RCTs of CHM. Recommendations: (1) Investigators of CHM who design clinical trials should understand the rationale for selecting different types of control groups; (2) Control groups for RCTs should be selected according to study objectives; (3) Active control groups should select interventions for comparisons that have the strongest evidence of efficacy and prescribe them as recommended; (4) Placebo control groups should select a placebo that mimics the physical characteristics of test intervention as closely as possible and is completely inert; (5) No treatment control groups should only be used when withholding treatment is ethical and objectives outcomes will not be subject to bias due to absent blinding; (6) Crossover control groups may be appropriate in chronic and stable conditions.

Background: Genital warts are a common sexually transmitted disease caused by human papillomaviruses. Podophyllotoxin 0.5%, approved for patient self-administration, has been used most extensively in the treatment of genital warts. Imiquimod, a novel immune response modifier capable of inducing interferon-α and a variety of cytokines, has been examined as a potential treatment for genital warts. But 0.5% podophyllotoxin and 5% imiquimod have not been compared in any extensive and formal studies, although they are the common topical agents for genital warts. Objective: To evaluate the efficacy and safety of topical 5% imiquimod and 0.5% podophyllotoxin in the treatment of genital warts. Methods: We searched Medline (1966 to June 2005), Embase (1974 to June 2005) and the Cochrane Controlled Trials Register (issue 3, 2005). Randomized controlled trials of 5% imiquimod or 0.5% podophyllotoxin in the treatment of genital warts were collected. Two reviewers extracted the data and independently assessed the quality of the included medical literature. Then, meta-analysis was conducted. Results: Twelve studies including 3 placebo-controlled trials of imiquimod and 9 placebo-controlled trials of podophyllotoxin were included. The clinical cure rates of imiquimod and podophyllotoxin were 50.34 and 56.41%, respectively, without statistically significant differences between the two (p > 0.05). A combined analysis of the 3 studies on imiquimod showed a statistically significant difference to the placebo group [pooled odds ratio (OR) 11.65, 95% confidence interval (CI) 6.05–22.44], as did a combined analysis of the 9 studies on podophyllotoxin (pooled OR 16.70, 95% CI 7.06–39.48). The most common adverse events of imiquimod were erythema, erosion, excoriation, itching and burning; those of podophyllotoxin were burning, pain, erosion, itching and inflammation. Conclusion: Imiquimod and podophyllotoxin possess similar curative effects on condylomata acuminata but podophyllotoxin has more serious adverse effects.

No abstract.

Importance Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures The primary outcome was live birth. Secondary outcomes included adverse events. Results Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene ( P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, −0.6%; 95% CI, −5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration clinicaltrials.gov Identifier:NCT01573858

Editors' Note: This article is the simplified Chinese version of the CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. (Cheng C, Wu T, Shang H, Li, Y, Altman D, Moher D; CONSORT-CHM Formulas 2017 Group. CONSORT Extension for Chinese Herbal Medicine Formulas 2017: Recommendations, Explanation, and Elaboration. Ann Intern Med. 2017;167:112-21. [Epub 27 June 2017]. doi:10.7326/M16-2977).

To systematically assess the efficacy of different programs regarding the selenium supplementation formulae used for prevention and treatment of Kaschin-Beck disease (KBD) in children.PubMed, EMBASE, Cochrane Library, SCI expanded, CNKI (Chinese National Knowledge Infrastructure), VIP (Chinese Science and Technique Journals Database), CBM (The Chinese Biomedical Database), Wanfang Database, CSCD (Chinese Science Citation Database) had been electronically searched. All the searching processes were up-dated to Dec 2012 to identify randomized trials (RCTs) and non-RCTs to compare the selenium supplementation formulae with placebo or with no intervention. Two reviewers assessed the methodological quality of the study design, including RCTs or non-RCTs according to Cochrane Handbook for Systematic Reviews of Interventions 5.1 or a checklist described by Deeks JJ, et al, respectively. Data was extracted independently.There were 14 RCTs and 12 non-RCTs papers included, but showing low methodological quality. Data from Meta analysis showed that selenium supplementation had caused the following progresses: radiologic improvement (RR = 3.28, 95%CI: 2.06 - 5.22), higher hair selenium (SMD = 2.05, 95%CI: 1.00 - 3.11) lower new radiologic lesions (OR = 0.18, 95%CI: 0.09 - 0.36) than in the placebo or with no treatment groups. Both selenium and vitamin C supplementation did not show differences in radiologic improvement of metaphysis (RR = 1.01, 95%CI: 0.84 - 1.22). Combination of selenium and vitamin E supplementation showed higher radiologic improvement than the placebo group. Combination of selenium and vitamin C supplementation had no influence on the difference in radiologic improvement or hair selenium than selenium supplementation. Selenium-enriched yeast showed higher radiologic improvement than sodium selenite (70.83% vs. 48.84%, P0.05). Selenium fertilization showed higher radiologic improvement than the non-treatment group (RR = 3.98, 95%CI: 2.25 - 7.05). Comprehensive intervention program and 'grain drying approach' also showed certain effects.Selenium supplementation could lead to better radiologic improvement and hair selenium, with lower new radiologic lesions. Current evidence supported its benefits on prevention and treatment of KBD. Large sample sized and well-designed trials together with the reporting on adverse outcome remained necessary.

To assess the diagnostic value of glycosylated hemoglobin A1c (HbA1c) ≥ 6.5% for diabetes in Chinese adults with oral glucose tolerance test (OGTT) as the reference standard.Major databases were searched to get all diagnostic tests with HbA1c ≥ 6.5% for diabetes in Chinese adults. QUADAS items were used to evaluate the quality of the eligible studies. Meta-disc software was used to perform comprehensive quantitative assessment for all included studies and summary ROC (SROC) curve were drawn.A total of 11 studies were included. The outcomes of the diagnostic value with HbA1c ≥ 6.5% were as the following: pooled sensitivity 0.62 (95%CI: 0.60 - 0.64), pooled specificity 0.96 (95%CI: 0.95 - 0.96), diagnostic odds ratio (DOR) 40.25 (95%CI: 20.79 - 77.95) and AUCSROC 0.7702 (sx = 0.0636).The diagnostic specificity is pretty high for the diagnostic test with HbA1c ≥ 6.5%, while sensitivity is low. Combination of HbA1c and glucose tests is needed to reduce the missed diagnosis rate.

Objectives: To assess the effects of long-term beta blockers in patients with stable angina. Methods: We reviewed the literature up to June 2010 from CENTRAL, MEDLINE, EMBASE, CBM, and CNKI for randomized controlled trials. The appropriate data were meta-analysed using Revman 5.0. Results: Twenty-six trials including 6108 patients were identified. The treatment with beta blockers has significantly decreased all-cause mortality when compared with no control (OR 0.40, 95% CI 0.20 to 0.79), but has had no statistically differences when compared with placebo (OR 0.92, 95% CI 0.62 to 1.38) and with calcium-channel blocker (CCB) (OR 0.84, 95% CI 0.49 to 1.44). This was similar in patients with fatal and non-fatal acute myocardial infarction when compared with placebo (OR 0.82, 95% CI 0.57 to 1.17) or CCB (OR 1.08, 95% CI 0.71 to 1.66); on revascularization and quality of life. The beta blockers reduced the incident of unstable angina compared to no treatment (OR 0.14, 95% CI 0.07 to 0.29), but increased unstable angina compared to placebo (OR 3.32, 95% CI 1.50 to 7.36). There was a significant reduction of nitrate consumption when beta blockers were compared with CCBs (OR −1.18, 95% CI −1.54 to −0.82), but not with placebo and trimetazidine. There was no significant difference in angina attack between each group. Side effects in beta blocker were similar with ones in controls. Conclusions: Beta blockers may decrease the death and unstable angina when compared with no treatment, but no more effective than other anti-anginal agents on prophylaxis of myocardial ischaemia in stable angina patients.

Many patients with chronic hepatitis B (CHB) seek help from traditional Chinese medicine (TCM). TCM treatment is based on syndrome differentiation. This study aimed to investigate the syndrome distribution in populations of CHB patients. The pre-specific search strategy was set, and 93 studies (20,106 participants) were identified by electronic and hand searches. The methodological quality of included studies was assessed. Data on syndrome distribution and correlations between syndromes and severity of CHB, were extracted and analyzed. Forty-seven syndromes were identified under 24 different syndrome diagnosis systems for CHB. The majority of included studies reported Liver Depression and Spleen Deficiency (LDSD) (52.54% of studies) or Liver-Gallbladder Dampness Heat (LGDH)/Dampness-Heat Obstructing Middle Energizer (DHME) (32.20%) as the major syndromes in CHB patients without cirrhosis. Pooled analysis revealed that LDSD and LGDH/DHME accounted for 61.19% of participants without cirrhosis. In addition, Liver-Kidney Yin Deficiency (LKYinD) (40.99%) and Spleen-Kidney Yang Deficiency (SKYangD) (40.43%) syndromes were common in patients with severe CHB. The percentage of patients with Blood Stasis syndrome increased as the disease progressed to cirrhosis (32.09%). To conclude, LDSD and LGDH/DHME syndromes are found in a significant majority of CHB patients, particularly in the early stages. LKYinD, SKYangD and Blood Stasis dominate in patients at more advanced stages. More epidemiological studies of high methodological quality on syndrome distribution in CHB and standardization of syndrome differentiation for CHB are required to confirm the trends indicated by the studies reviewed here; confirming these trends can increase the efficacy of treatment and give guidance to doctors.

Background & Aims The chemopreventive effects of Allium vegetables (onions, garlic, shallots, leeks, chives, and so forth) have been studied extensively, although their effect on gastric cancer risk is controversial. We performed a meta-analysis of cohort and case-control studies to analyze this association. Methods We searched MEDLINE for studies of Allium vegetable consumption and gastric cancer that were published in any language, from January 1, 1966, to September 1, 2010. We analyzed 19 case-control and 2 cohort studies, of 543,220 subjects. We pooled the relative risks from individual studies using a random-effects model and performed dose-response, heterogeneity, and publication bias analyses. Results In a pooled analysis of all studies, consumption of large amounts of Allium vegetables (in a comparison of the highest and lowest consumption groups) reduced the risk for gastric cancer (odds ratio, 0.54; 95% confidence interval, 0.43–0.65). Specific analyses for onion, garlic, leek, Chinese chive, scallion, garlic stalk, and Welsh onion yielded similar results, except for onion leaf. The estimated summary odds ratio for an increment of 20 g/day of Allium vegetables consumed (approximately the average weight of 1 garlic bulb) was 0.91 (95% confidence interval, 0.88–0.94), based on case-control studies from the dose-response meta-analysis. Conclusions In a meta-analysis, consumption of high levels of Allium vegetables reduced the risk for gastric cancer risk. Because of potential confounding factors and exposure misclassification, further studies are required to establish this association.

To assess the effectiveness of dapoxetine in the treatment of premature ejaculation.Both English and Chinese studies involving men with prematrue ejaculation who were treated with dapoxetine from the Cochrane Library, MEDLINE, EMBASE and CNKI, CBM, VIP between 1979 and 2009.were included in the randomized controlled trials (RCTs) and the data processed by RevMan.Five RCTs involving 4433 patients were included in the Meta analysis, of which 3 were of grade A and 2 were of grade B according to the quality evaluation of methodology. Intravaginal ejaculatory latency time (IELT), patient-reported global impression of change (PGI), satisfaction with sexual intercourse (SWSI), perceived control over ejaculation (PCOE), personal distress related to ejaculation (PDRE) were used for assessment. Meta analysis based on included studies of patients having been treated with dapoxetine for 9-24 weeks showed that: (1) the difference of the patients' IELT between treatment group and control group was statistically significant [P0.001, WMD (95%CI) was 1.38 (1.21,1.55)]; (2) the difference of the PGI of development in premature ejaculation between treatment group and control group was statistically significant [P0.001, OR (95%CI) was 3.56 (2.60,4.88)]; (3) the difference of the patients' SWSI between treatment group and control group was statistically significant [P0.001, OR (95%CI) was 3.85 (2.08,7.10)]; the difference of the patients' score of SWSI between treatment group and control group was statistically significant [P0.001, WMD (95%CI) was 0.55 (0.48,0.62)]; (4) the difference of the patients' change of PCOE between treatment group and control group was statistically significant [P0.001, OR (95%CI) was 2.87(2.30,3.58)]; the difference of the patients' score of PCOE between treatment group and control group was statistically significant [P0.001, WMD (95%CI) was 0.63(0.49,0.78)]; (5) after being treated with dapoxetine for 9-24 weeks, the difference of the patients' change of PDRE between treatment group and control group was statistically significant [P0.001, OR (95%CI) was 2.02 (1.69,2.42)]. All the RCTs reported the side effects of dapoxetine, but the results showed that there were no serious side effects of dapoxetine during the treatment period.The available evidence indicates that dapoxetine would improve the symptoms of premature ejaculation, prolong IELT over 9-24 weeks in men from a wide range of cultural backgrounds, and significantly improve all patients' reported outcomes and the patients' clinical global impressions of premature ejaculation, including more control, greater satisfaction, and less distress.

Public confidence in clinical trials has been eroded by data suppression, misrepresentation and manipulation. Although various attempts have been made to achieve universal trial registration- e.g., Declaration of Helsinki, WHO clinical Trial Registry Platform (WHO ICTRP), the International Committee of Medical Journal Editors requirement- they have not succeeded, probably because they lack the enough power of enforcement. Legislation appears to be the most efficient and effective means to ensure that all researchers register their trials and disseminate their data accurately and in a timely manner. We propose that a global network be established. This could be accomplished in two steps. The first step is to legislate about trial registration and data transparency, such as USA's FDAAA Act 2007; and the second step to establish a global network to ensure uniform, international consistency in policy and enforcement of trial registration and data transparency.

To assess the association of male infertility with CAG repeat polymorphism of the androgen receptor (AR) gene by meta-analysis.We identified the case-control studies on the relationship of male infertility with CAG repeats of the AR gene by searching Medline/PubMed and CBM databases, and conducted meta-analysis on the data obtained with the RevMan 4.2 software.Thirty-two eligible articles were selected in this study, including 3,153 idiopathic infertile men and 2,314 controls. The combined data statistics showed that all the infertile men had a significantly higher mean of CAG repeats than the controls (SMD = 0.27, 95% CI: 0.17-0.37, P0.01). The specific SMD between the infertile patients and controls was 0.29, 95% CI: 0.08-0.50 for the azoospermic men, 0.27, 95% CI: 0.13-0.41 for the moderate oligozoospermic men, and 0.18, 95% CI: 0.02-0.33 for the severe oligozoospermic cases. The results of sensitivity analyses were consistent with those mentioned above.The increased length of CAG repeats in the AR gene may be correlated with the risk of the impairment of spermatogenesis.

The Glutathione S-transferases (GSTs) play multiple roles in the pathogenesis and treatment of cancer. Studies investigating the association between Glutathione S-transferase M1 (GSTM1) null genotype and gastric cancer risk report conflicting results. The purpose of this study was to quantitatively summarize the evidence for such a relationship.This meta-analysis included 35 studies, which included 4,505 gastric cancer cases and 9,062 controls. The combined results based on all studies showed that the GSTM1 null genotype was associated with an increased risk of gastric cancer (OR = 1.15, 95% confidence interval [CI] = 1.02, 1.29). When stratifying for race, results were similar among Asians (OR = 1.24, 95% CI = 1.07, 1.44) except Caucasians (OR = 1.04, 95% CI = 0.88, 1.24). When stratifying by the location, stage, Lauren's classification, histological differentiation, lymph node metastasis, smoking, and Helicobacter pylori infection of gastric cancer, we observed that patients with diffuse classification had a significantly higher frequency null genotype (OR = 4.80, 95% CI = 1.65,13.94) than those with intestinal classification among Caucasians.This meta-analysis suggests that the GSTM1 null genotype may be associated with gastric cancer among Asians.

Studies investigating the association between interleukin10 (IL10) -592 promoter polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship.Two investigators independently searched the MEDLINE and Embase databases. This meta-analysis included ten case-control studies, which included 1,715 gastric cancer cases and 2,783 controls.The combined results based on all studies showed that there was no significant difference in genotype distribution (AA odds ratio [OR] = 0.88, 95% confidence interval [CI] = 0.66, 1.18; AC OR = 1.09, 95% CI = 0.95, 1.24; CC OR = 1.03, 95% CI = 0.89, 1.18) between gastric cancer and noncancer patients. When stratifying for race, the results were similar, except that patients with gastric cancer had a significantly lower frequency of AA (OR = 0.67, 95% CI = 0.52, 0.87) and a higher frequency of AC (OR = 1.34, 95% CI = 1.07, 1.68) than noncancer patients among Asians. When stratifying by the location of gastric cancer, we found that patients with cardia gastric cancer had a significantly lower frequency of AA (OR = 0.41, 95% CI = 0.20, 0.84) than those with noncardia gastric cancer among Caucasians. When stratifying by Lauren's classification of gastric cancer, we found that patients with diffuse gastric cancer had a significantly higher frequency of AA (OR = 1.91, 95% CI = 1.07, 3.41) than those with intestinal gastric cancer among Caucasians.This meta-analysis suggests that the IL10 -592 promoter polymorphism may be associated with gastric cancer among Asians, and that differences in genotype distribution may be associated with the location and Lauren's classification of gastric cancer.

To evaluate and compare the postoperative implant-related complications after treatment of intertrochanteric fracture by gamma nail or by sliding hip screw.Literatures on randomized controlled trials (RCTs) of the postoperative implant-related complications after treatment of intertrochanteric fracture by gamma nail or by sliding hip screw published before the end of June 2007 were retrieved from Cochrane library, Medline, Embase databank, and Chinese Biomedical Database. Relevant articles were handsearched in several Chinese journals. Methodology quality of the trials was critically assessed and data on postoperative implant-related complications were extracted. The software RevMan4.2.10 provided by the Cochrane Collaboration was used for meta-analysis.10 RCTs and 3 quasi-RCTs involving 1857 cases were included. The results of meta-analysis showed that gamma nailing significantly increased the rate of postoperative femoral shaft fractures [RR = 3.75, 95%CI (1.47, 9.55), P = 0.006]. However, there were no statistic differences in the rates of lag screw cut-out and total mechanical complications between gamma nail and sliding hip screw treatment.Compared with sliding hip screw for intertrochanteric fractures, gamma nailing can lead to higher incidence of postoperative femoral shaft fractures. Fracture stability may influence the rate of postoperative implant-related complications. Further large sample and high quality RCTs based on fracture stability are required in order to provide more sufficient and reliable evidence.

Although all Chinese materia medica (CMM) come from nature, CMM interventions have both therapeutic effects and adverse effects (AEs). Normally, AEs in randomized controlled trial (RCT) with traditional Chinese medicine (TCM) could be divided into five types as follows: 1) AEs under proper TCM principles and guidelines, such as the toxicity (acute and chronic) and allergy; 2) AEs due to improper usage without following TCM principles, involving without following the TCM therapeutic principles, over-dosage, improper processing and preparation methods, improper formula strategy, etc; 3) AEs due to contamination in CMM, such as heavy metal and pesticides contaminations in Chinese herbal medicine interventions, and intentional or unintentional contamination with drug(s); 4) AEs due to replacement of CMMs; 5) AEs due to drug-herb interaction. AEs of TCM should be treated properly. Overestimation or underestimation about AEs of TCM intervention will bring a wrong message to patients and health care providers. In order to give readers a more comprehensive understanding about the safety issue of study intervention, Consolidated Standards of Reporting Trials (CONSORT) for TCM should involve the background information on side effects of each CMM constituents and/or the study intervention, specific outcome assessment on AEs, the details of reported AEs and the interpretation of the AEs occurrence in a structural RCT report.

Traditional Chinese medicine (TCM) intervention should be concisely and precisely reported in randomized controlled trials (RCTs). Based on State Food and Drug Administration s categories, we recommend reporting the interventions as follows: (1) Single Chinese herbal medicine-based/formula-based/extraction-based intervention includes 1) Name, dosage format and registration; 2) The composition and quality of intervention; 3) Pharmaceutical processing and quality control; 4) Stability of final product and quality control: 5) Function and safety description; 6) Dosage and treatment course; 7) Control group. (2) Active compound-based TOM drug intervention includes 1) Name of active compound(s); 2) Original source of active compound(s): 3) The brief process obtaining active compound(s); 4) Percentage of active compound(s) in final product; 5) Added materials and its quality and quantity control. Besides. the detailed information of intervention can be published as an online supplement in web site.

Studies investigating the association of polymorphisms in the 5′-untranslated regions (5′UTR) and 3′-untranslated regions (3′UTR) of thymidylate synthase with gastric cancer susceptibility and sensitivity to fluoropyrimidine-based chemotherapy report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. This meta-analysis included ten studies, which included 1,730 gastric cancer cases and 1,843 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution of 5′UTR or 3′UTR between gastric cancer and noncancer patients. When stratifying for race, we found that: (1) among Asians, patients with gastric cancer had significantly higher frequency of 2R/2R of 5′UTR than did noncancer patients, and (2) among Caucasians, patients with gastric cancer had significantly lower frequency of ins6/ins6 and higher frequency of ins6/del6 of 3′UTR than did noncancer patients. No significantly different response rate or survival of gastric cancer with fluoropyrimidine-based chemotherapy were observed with genotype distribution of 5′UTR or 3′UTR among Caucasians or Asians. This meta-analysis suggests that polymorphisms in the 5′UTR and 3′UTR of thymidylate synthase may be associated with gastric cancer susceptibility, but are not correlated with sensitivity of gastric cancer to fluoropyrimidine-based chemotherapy.

Studies investigating the association between interleukin-10 (IL-10) -1082 promoter polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 13 case-control studies, which included 2227 gastric cancer cases and 3538 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR) = 0.92, 95% confidence interval (CI) = 0.73, 1.14; AG (OR = 1.09, 95% CI = 0.87, 1.36); GG (OR = 1.03, 95% CI = 0.85, 1.25)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of AA (OR = 0.71, 95% CI = 0.52, 0.97) and higher frequency AG (OR = 1.53, 95% CI = 1.15, 2.03) than noncancer patients among Asians. When stratifying by the location of gastric cancer, we found that patients with cardia gastric cancer had a significantly lower frequency of AA (OR = 0.53, 95% CI = 0.34, 0.83) and higher frequency AG (OR = 1.50, 95% CI = 1.06, 2.11) than those with noncardia gastric cancer among Caucasians. When stratifying by the Lauren’s classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the IL-10 -1082 promoter polymorphism may be associated with gastric cancer among Asians, and that differences in genotype distribution may be associated with the location of gastric cancer.

Studies investigating the association between p53 codon 72 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 12 case-control studies, which included 1,665 gastric cancer cases and 2,358 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [Arg/Arg odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.79, 1.16; Pro/Pro (OR = 1.21, 95% CI = 0.92, 1.58); Pro/Arg (OR = 0.95, 95% CI = 0.79, 1.14)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of Arg/Arg (OR = 0.84, 95% CI = 0.72, 0.99) than noncancer patients among Asians. Stratified the various studies by the location, stage, Lauren's classification, and histological differentiation of gastric cancer, we found that (i) patients with cardia gastric cancer had a significantly higher frequency of Pro/Pro (OR = 3.20, 95% CI = 1.46,7.01) than those with noncardia gastric cancer among Asians; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.48, 95% CI = 1.01, 2.16) than those with early (stage I/II) gastric cancer among Asians; (iii) patients with poor differentiation had a significantly lower frequency of Pro/Pro (OR = 0.13, 95% CI = 0.03, 0.64) than those with well differentiation among Caucasians. This meta-analysis suggests that the p53 codon 72 polymorphism may be associated with gastric cancer among Asians, and that difference in genotype distribution may be associated with the location, stage, and histological differentiation of gastric cancer. © 2007 Wiley-Liss, Inc.

The number of randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) is increasing. However, there have been few systematic assessments of the quality of reporting of these trials.This study was undertaken to evaluate the quality of reporting of RCTs in TCM journals published in mainland China from 1999 to 2004.Thirteen TCM journals were randomly selected by stratified sampling of the approximately 100 TCM journals published in mainland China. All issues of the selected journals published from 1999 to 2004 were hand-searched according to guidelines from the Cochrane Centre. All reviewers underwent training in the evaluation of RCTs at the Chinese Centre of Evidence-based Medicine. A comprehensive quality assessment of each RCT was completed using a modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist (total of 30 items) and the Jadad scale. Disagreements were resolved by consensus.Seven thousand four hundred twenty-two RCTs were identified. The proportion of published RCTs relative to all types of published clinical trials increased significantly over the period studied, from 18.6% in 1999 to 35.9% in 2004 (P0.001). The mean (SD) Jadad score was 1.03 (0.61) overall. One RCT had a Jadad score of 5 points; 14 had a score of 4 points; and 102 had a score of 3 points. The mean (SD) Jadad score was 0.85 (0.53) in 1999 (746 RCTs) and 1.20 (0.62) in 2004 (1634 RCTs). Across all trials, 39.4% of the items on the modified CONSORT checklist were reported, which was equivalent to 11.82 (5.78) of the 30 items. Some important methodologic components of RCTs were incompletely reported, such as sample-size calculation (reported in 1.1% of RCTs), randomization sequence (7.9%), allocation concealment (0.3 %), implementation of the random-allocation sequence (0%), and analysis of intention to treat (0%).The findings of this study indicate that the quality of reporting of RCTs of TCM has improved, but remains poor.

To discuss quality control of Chinese herbal medicine (CHM) in randomized controlled trials (RCTs), and to provide suggestions for improving this aspect in future clinical study in this therapeutic area.A search of the Cochrane Library was conducted to identify RCTs of CHM. Quality control information reported in those RCTs was then assessed independently.The search yielded a total of 167 RCTs of CHM for a variety of conditions. A total of 11 CHM preparations were used in those RCTs. Only one trial discussed quality control of the CHM interventions used. Issues affecting the safety and efficacy of CHM products used in RCTs were discussed including standardization of raw herbal materials, processing methods, screening for product contamination, and effects of combination products.The overall quality of reporting of RCTs of CHM was poor, reflecting the need for improvements in reporting future clinical trials in this area.To improve quality control of CHM used in RCTs in future, we recommend developing and implementing guidelines such as Good Agricultural Practice (GAP) for Chinese crude drugs, and current Good Manufacturing Practice (GMP) specific to CHM products. Chemical analyses of individual herbs of CHM and combination products are also recommended to provide reference standards for quality control.

OBJECTIVE To discuss the quality of reporting in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM), and to provide suggestions for improving the reporting of future clinical studies in this therapeutic area. METHODS A search of the Cochrane Library was conducted to identify RCTs of CHM. A revised CONSORT checklist designed for CHM clinical studies was implemented. The revised CONSORT checklist contained 63 items, including the following new items added specifically for CHM: (1) "syndrome of disease" based on Chinese medicine theories; (2) rationale of CHM formula; (3) formula composition; (4) preparation form of CHM; (5) quality control of CHM. RESULTS The overall reporting quality of the RCTs as assessed with the revised CONSORT checklist varied between 19% and 44%, with a median score of 32% (standard deviation 8%). CONCLUSION The overall quality of reporting of RCTs of CHM evaluated with a revised CONSORT checklist was poor, reflecting the need for improvements in reporting future clinical trials in this area. RECOMMENDATIONS To improve the quality of reporting of RCTs of CHM, we recommend adopting a revised CONSORT checklist that includes items specific to CHM. We also recommend that editors of CHM journals require authors to use a structured approach to presenting their trials as a condition of publication.

To evaluate the effects of saponins from Chinese Buckeye Seed in the treatment of cerebral edema in patients with stroke or cerebral trauma, a metaanalysis of randomized controlled trials was conducted. Randomized trials that compare the effects of treatment with saponins from Chinese Buckeye Seed to placebo treatment, to lack of treatment, to non-specific treatment, or to mannitol treatment for cerebral edema were identified with electronic and manual searches. No blinding and language limitations were applied. The methodological quality of trials was assessed with the Jadad scale plus allocation concealment. The metaanalysis was performed where data were available. Forty-one randomized controlled trials involving 4066 patients were identified. The methodological quality of the trials was generally low. The combined results showed that intravenous administration of saponins from Chinese Buckeye Seed increased the total effective rate, reduced the mortality and the incidence of renal function impairment in comparison to control treatment. No serious adverse event was reported. Based on the metaanalysis, saponins from Chinese Buckeye Seed can reduce cerebral edema in patients with stroke or cerebral trauma. However, the evidence is not sufficient due to the generally low methodological quality of the studies. Further trials are needed with sufficiently numerous group size and rigorous design.

To evaluate the relationships between the viruses infections and the incidence of malignant lymphomas (ML) in Sichuan province.A hospital-based paired case-control study was designed with two controls per case. The case group comprised 97 cases diagnosed as ML by pathological examination; the control group A consisted of 194 subjects randomly selected from those with non-malignancies by matching on both gender and age in the corresponding period. Additionally, a control group B for Epstein-Barr virus(EBV), including 80 subjects, were chosen from other non-malignant diseases at the same time. Enzyme-linked immunosorbent assay(ELISA) was employed to test the serum antibodies and antigens of hepatitis C virus (HCV), human immunodeficiency virus (HIV), cytomegalovirus (CMV), and hepatitis B virus (HBV). The EBV was confirmed by the EBER in situ-hybridization (EBER-ISH) of pathological tissue.The positive rate of EBV in ML group was 70.1%(68/97) and that of control group was 7.5%(6/80). The difference between these two groups showed a statistical significance by conditional logistic regression analysis (OR = 6.58, 95% CI: 16.164-82.846, P = 0.0001). The differences in HCV, CMV and HBV infections between case group and control group demonstrated no statistical significance with P-values of 0.260, 0.258 and 0.399 respectively. We found no positive results of HIV antibody in case group and control group.The incidence of ML in Sichuan displayed a significant association with EBV infection. However, there were no relationships between the incidence of ML and the HCV, HBV, HIV, CMV infections in the area.

To assess the benefits and harms of artemisinin-type compounds for preventing schistosomiasis.The quality of included randomised controlled trials with the people at risk of contacting schistosomiasis were evaluated and Meta-analysis was conducted.We found ten randomised controlled trials relating to our question. Of them, four trials were multi-centre studies, others were single centre studies. Numbers of participants in the trials ranged from 318 to 5,098, total 12,829. The total OR of 0.11 (95% CI 0.06 to 0.21) indicated that those who were administrated artemisinin-type compounds were significantly less infected with Schistosoma japonica than those who were administrated placebo.Artemisinin-type compounds are effective drug for preventing Schistosomiasis japonica infection. Fifteen days interval schemes of artesunate and artemether be considered preferable to seven days interval scheme and were associated with very few side effects. More high quality controlled trials are required for assessing which scheme is the better. These studies should be large.

Constipation is a common gastrointestinal complaint in clinical practice, affecting an estimated 27% of the population. Many patients are disappointed by current conventional treatments and, therefore, seek help from complementary and alternative medicine (CAM). Traditional Chinese medicine, is the most important part of CAM and has been practiced for treating diseases and promoting the health of humans for thousands of years, and has become a popular alternative choice. Although there are many Chinese herbal medicine (CHM) interventions available, and some have been verified by clinical trials, their efficacy and safety are still questioned by both patients and health care providers worldwide. The purposes of this review are, first, to appraise the qualities of individual study designs in the new Cochrane approach. Second, the benefits of individual CHM interventions or individual types of CHM intervention for the treatment of functional constipation are analyzed. Finally, valid and comprehensive conclusions are drawn, if applicable, in order to make clinical recommendations.