Helicobacter pylori "test and treat" or endoscopy for managing dyspepsia: an individual patient data meta-analysis

BACKGROUND & AIMS: Helicobacter pylori "test and treat" has been recommended for the management of young dyspeptic patients without alarm symptoms, and trials have suggested that it is as effective as endoscopy. However, none of these trials have had sufficient sample size to confirm that "test and treat" costs less or to detect small differences in effect. A collaborative group has prospectively registered trials comparing prompt endoscopy with a "test and treat" approach, with the aim of performing an individual patient data meta-analysis of both effect and resource utilization data. METHODS: Researchers provided data for meta-analysis, pooling effects of interventions on individual dyspepsia symptoms. Standardized unit costs were applied to resource utilization, and net benefit was calculated at patient level. Effects, costs, and net benefit were then pooled at study level. RESULTS: Five trials were identified, containing 1924 patients (946 endoscopy [mean age, 40 years], 978 "test and treat" [mean age, 41 years]). The relative risk (RR) of remaining symptomatic after 1 year was reduced with endoscopy compared with "test and treat" (RR = 0.95; 95% confidence interval [CI]: 0.92-0.99). "Test and treat" cost 389 dollars less per patient (95% CI: 275-502 dollars). Using the net benefit approach, at no realistic level of willingness to pay per patient symptom-free did prompt endoscopy become cost-effective. CONCLUSIONS: Prompt endoscopy confers a small benefit in terms of cure of dyspepsia but costs more than "test and treat" and is not a cost-effective strategy for the initial management of dyspepsia.     

A systematic review on the effect of aspirin in the prevention of post-operative arterial thrombosis in patients undergoing total hip and total knee arthroplasty

Introduction

Major surgery is associated with increased risk of venous thromboembolism (VTE), which is decreased by anticoagulant drugs. Evidence is growing that major surgery is associated with increased risk of arterial thrombosis (AT). With the aim of testing aspirin ability in reducing the risk of post-operative AT, we performed a systematic review of studies in which acetylsalicylic acid (ASA) was compared to anticoagulant drugs in VTE prophylaxis of patients undergoing total hip replacement (THR) or total knee replacement (TKR).

Materials and Methods

Studies were identified by reviewing the reference of the ACCP guidelines and by electronic search of MEDLINE database from January 2012 to December 2013 and of the web database www.trialresultscenter.org.

Results

We analyzed 5 of the 78 studies that were identified by our search strategy; they included 5179 patients; the median follow-up was 90 days. The incidence of post-operative AT tended to be lower in ASA-treated patients, compared to anticoagulant-treated patients, although the difference did not reach statistical significance (OR 0.56, 95%CI 0.23-1.35). In contrast, the incidence of post-operative VTE tended to be higher in ASA-treated patients, compared to anticoagulant-treated patients (1.48, 95% CI 0.93-2.36).

Conclusions

Due to the heterogeneity and low quality of the studies, which do not allow firm conclusions, it is uncertain whether aspirin is effective in reducing the incidence of postoperative AT. Our results do emphasize the need for developing specifically designed studies to test the safety and efficacy of ASA in the prevention of post-operative AT.     

The attitudes of 1066 patients with cancer towards participation in randomised clinical trials

Background:

Barriers to randomised clinical trial (RCT) recruitment include failure to identify eligible patients, reluctance of staff to approach them and attitudes of some health-care professionals and patients. As part of a larger UK prospective study examining the communication and involvement in RCTs of 22 multidisciplinary teams in Wales, we also assessed the attitudes of patients they treat towards trials.

Methods:

Out of 1146 patients attending outpatient departments who were approached, 1146 (93%) completed the seven-item Attitudes to Randomised Trials Questionnaire (ARTQ), probing their general attitudes towards medical research and likely participation in a hypothetical two-arm RCT.

Results:

Randomisation initially deterred many patients from endorsing a willingness to participate. However, if information about the trial logic, voluntary nature and rights to withdraw were provided, together with further treatment details, 83% (886 out of 1066) would potentially participate. Other variables associated with a positive inclination towards participation included previous trial experience (P<0.01), male gender (P<0.01) and younger age, with patients ⩾70 years less likely to consider trial entry (P<0.01).

Conclusion:

The majority of patients were receptive to RCT participation. Many of those initially disinclined because of randomisation would consider joining if given further details that form part of standard GCP consent guidelines. These data show the importance and need for clear communication and information to encourage RCT participation. Evidence-based training courses are available to assist with this.     

Developing evidence-based immunization recommendations and GRADE

The Strategic Group of Advisory Experts (SAGE) on immunization is an independent advisory committee with a mandate to advise the World Health Organization (WHO) on the development of vaccine and immunization related policies. SAGE working groups are established on a time-limited basis to review and provide evidence-based recommendations, together with their implications, for open deliberation and decision-making by SAGE. In making its recommendations, SAGE takes into consideration: the epidemiologic and clinical characteristics of the disease; vaccine and immunization characteristics; economic analysis; health system considerations; the existence of and interaction with other intervention and control strategies; costing and social impacts; and legal and ethical concerns. Since 1998, WHO has produced evidence-based vaccine position papers for use primarily by national public health officials and immunization programme managers. Since April 2006 all new or updated position papers have been based on SAGE recommendations. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach has been adopted by WHO and, since 2008, GRADE tables that rate the quality of evidence have been produced in support of key recommendations. SAGE previously expressed concern that GRADE was not ideally suited to many immunization-specific issues such as the vaccine population level effect and the inclusion of surveillance system data, particularly for vaccine safety. Extensive productive interactions with various advisory groups including the US Advisory Committee on Immunization Practices, the European Centres for Disease Control, the German Standing Committee on Vaccination (STIKO), WHO's Global Advisory Committee on Vaccine Safety and the GRADE working group resulted in key enhancements to accommodate vaccine-relevant evidence. This facilitated integration and acceptability of the GRADE approach in the development of immunization related SAGE and WHO recommendations. Ongoing utilisation should result in further fine-tuning of the approach to ensure that recommendations are based on the full range of appropriate evidence.     

Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines

Ethnopharmacological relevance

While there is an increasing number of toxicity report cases and toxicological studies on Chinese herbal medicines, the guidelines for toxicity evaluation and scheduling of Chinese herbal medicines are lacking.

Aim

The aim of this study was to review the current literature on potentially toxic Chinese herbal medicines, and to develop a scheduling platform which will inform an evidence-based regulatory framework for these medicines in the community.

Materials and methods

The Australian and Chinese regulations were used as a starting point to compile a list of potentially toxic herbs. Systematic literature searches of botanical and pharmaceutical Latin name, English and Chinese names and suspected toxic chemicals were conducted on Medline, PubMed and Chinese CNKI databases.

Results

Seventy-four Chinese herbal medicines were identified and five of them were selected for detailed study. Preclinical and clinical data were summarised at six levels. Based on the evaluation criteria, which included risk–benefit analysis, severity of toxic effects and clinical and preclinical data, four regulatory classes were proposed: Prohibited for medicinal usage, which are those with high toxicity and can lead to injury or death, e.g., aristolochia; Restricted for medicinal usage, e.g., aconite, asarum, and ephedra; Required warning label, e.g., coltsfoot; and Over-the-counter herbs for those herbs with a safe toxicity profile.

Conclusion

Chinese herbal medicines should be scheduled based on a set of evaluation criteria, to ensure their safe use and to satisfy the need for access to the herbs. The current Chinese and Australian regulation of Chinese herbal medicines should be updated to restrict the access of some potentially toxic herbs to Chinese medicine practitioners who are qualified through registration.     

Antibiotic prophylaxis is not protective in severe acute pancreatitis: a systematic review and meta-analysis

Background

The use of prophylactic systemic antibiotics to prevent infection and reduce mortality in severe acute pancreatitis (SAP) remains a contentious issue. We assessed the clinical outcome of patients with SAP treated with prophylactic antibiotics compared with that of patients not treated with antibiotics.

Methods

We performed a systematic search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, using PubMed, Google Scholar, and Ovid as search engines without language restriction until the end of May 2008. We also manually searched the references of original/review articles and evaluated symposia proceedings, poster presentations, and abstracts from major gastrointestinal and surgical meetings. Relative risks were calculated for individual trials and data were pooled using a fixed-effects model. Relative risk (RR) reduction, absolute risk reduction, and number needed to treat were calculated and are reported with 95% confidence intervals.

Results

Results were subjected to sensitivity analysis to determine heterogeneity among studies. We pooled 502 patients from 8 studies. Patient age ranged from 43 to 59 years, and length of stay ranged from 18 to 95 days. There were 253 patients with SAP who received prophylactic antibiotics, and 249 patients were randomized to the placebo arm. Overall, there was no protective effect of antibiotic treatment with respect to mortality (RR, .76; 95% confidence interval [CI], .49-1.16). With respect to morbidity, antibiotic prophylaxis did not protect against infected necrosis (RR, .79; 95% CI, .56-1.11) or surgical intervention (RR, .88; 95% CI, .65-1.20). There was, however, an apparent benefit in regards to nonpancreatic infections (RR, .60; 95% CI, .44-.82), with a RR reduction of 40% (95% CI, 18%-56%), absolute risk reduction of 15% (95% CI, 6%-23%), and number needed to treat of 7 (95% CI, 4-17).

Conclusions

Antibiotic prophylaxis of SAP does not reduce mortality or protect against infected necrosis, or frequency of surgical intervention.     

保肝药物预防化疗所致药物性肝损伤的Meta 分析

目的评价预防性使用常用保肝药物对改善肿瘤化疗所致药物性肝损伤的效果。方法在Pubmed、Cochrane Library、Embase、Web of Science、中国知网、万方、维普等数据库中检索在进行抗肿瘤化疗的同时,以异甘草酸镁或双环醇或谷胱甘肽作为预防性保肝药物的临床随机对照研究,检索时间均为从数据库建库至2019年8月。对搜集到的文献进行筛选和数据提取,采用RevMan 5.3软件进行Meta分析。结果本研究共纳入12个随机对照研究,共计2230例研究对象。研究结果显示,预防性使用保肝药物可降低药物性肝损伤率(RR=0.43,95%CI:0.30~0.61,P<0.01),尤其是Ⅲ-Ⅳ度肝损伤的患者(RR=0.33,95%CI:0.25-0.43,P<0.01),并降低ALT水平(MD=-32.03,95%CI:-47.11~-16.95,P<0.01)、AST水平(MD=-25.61,95%CI:-38.15~-13.07,P<0.01)及TBIL水平(MD=-3.82,95%CI:-5.97~-1.67,P<0.01),但对ALP水平(MD=-19.90,95%CI:-54.86~15.06,P=0.26)和DBIL水平(MD=-2.09,95%CI:-5.12~0.95,P=0.18)无明显影响。结论保肝药物可能对预防化疗所致药物性肝损伤产生影响。     

伊曲康唑治疗口腔念珠菌病安全性与有效性的系统评价#br#

摘要：目的 系统评价伊曲康唑与其他抗真菌药(克霉唑、氟康唑、酮康唑及特比萘芬)相比治疗口腔念珠菌病的临床疗效与安全性,以期为临床提供循证参考。方法 计算机检索PubMed、EMbase、Medline、the Cochrane Library、中国生物医学文献数据库、中国知网、维普数据库和万方数据库。检索时间均从建库到2017年6月。搜集伊曲康唑治疗口腔念珠菌病的随机对照试验(randomized controlled trials, RCTs),采用RevMan 5.3统计软件进行Meta分析。结果 共纳入8项RCT,共计892例患者。Meta分析结果显示：(1)临床治愈率：伊曲康唑组与氟康唑组[RR=0.82, 95%CI(0.62, 1.10), P=0.19]、克霉唑组[RR=1.05, 95%CI(0.87, 1.26), P=0.63]相比临床治愈率差异均无统计学意义;但伊曲康唑组临床治愈率(65.9%)显著高于特比萘芬组(33.3%)。(2)真菌学治愈率：伊曲康唑组与氟康唑组相比,真菌学治愈率差异无统计学意义[RR=0.87, 95%CI(0.75, 1.01), P=0.07]。(3)复发率：伊曲康唑组与氟康唑组相比,复发率差异无统计学意义[RR=0.85, 95%CI(0.51, 1.40), P=0.52]。(4)不良反应发生率：伊曲康唑并不会增加主要胃肠道不良反应[RR=1.10, 95%CI(0.59, 2.05), P=0.77],其他不良反应发生率差异亦无统计学意义。结论 伊曲康唑治疗口腔念珠菌病的有效性和安全性与其他抗真菌药物无显著差异。然而,由于纳入文献质量偏低,提供的信息有限,尚需大规模和高质量的RCT进一步验证。     

清开灵注射液治疗急性缺血性中风的系统评价

目的：系统评价清开灵注射液治疗急性缺血性中风的临床疗效及安全性。方法：全面系统检索文献数据库中清开灵注射液治疗急性缺血性中风的随机对照试验,采用Cochrane风险评价表评价其研究质量,提取资料并通过RevMan5.2进行Meta分析。结果：共纳入8篇文献,共计受试者633例,仅1篇文献采用随机数字表法。Meta分析结果显示,清开灵注射液联合西医常规疗法治疗缺血性中风具有很好的疗效,可以提高总有效率[RR=1.28, 95%CI (1.18,1.39), P<0.000 01],降低死亡率[RR=0.32, 95%CI (0.11,0.91), P=0.03],降低神经功能缺损评分[MD=-5.61, 95%CI (-8.51,-2.72), P=0.000 1,抑制肿瘤坏死因子（TNF-α）[MD=-5.56, 95%CI (-9.23,-1.90), P=0.003]和白介素-6（IL-6）的产生,降低全血黏度[MD=-0.75, 95%CI (-1.47,-0.03), P=0.04],抑制血小板胞浆内-α颗粒膜上糖蛋白CD62P的表达[MD=-2.07, 95%CI (-2.53,-1.61), P<0.000 01]等。有4篇研究表明确无不良反应,1篇研究报道了共8例不良事件,其中治疗组3例,无重大不良反应,其他文献均未对安全性做出说明。结论：临床治疗缺血性中风过程中,在常规治疗的基础上,加用清开灵注射液可以提高疗效,且较为安全,但仍需更多设计严谨的、大样本的随机双盲对照试验作进一步的评价。