Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations

IntroductionThe potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice.MethodsA panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach.ResultsAccording to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence).DiscussionThis review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values.Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.     

PARP-inhibitors for BRCA1/2-related advanced HER2-negative breast cancer: A meta-analysis and GRADE recommendations by the Italian Association of Medical Oncology

BackgroundApproximately 5–10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials.MethodsThe panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC.ResultsTwo studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration.ConclusionsThe Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology.     

The efficacy of moxibustion and acupuncture therapy for ankylosing spondylitis: A protocol for an overview of systematic reviews and meta-analysis

Background:Ankylosing spondylitis is a complex and progressive autoimmune inflammatory disease with a worldwide prevalence ranging up to 0.9%. Several systematic reviews and meta-analyses of traditional Chinese medicine alternative therapies, such as acupuncture or moxibustion, have demonstrated the effectiveness of moxibustion and acupuncture in the treatment of ankylosing spondylitis. However, there is no relevant literature to comprehensively evaluate the evidence. The purpose of this overview is to synthesize and evaluate the reliability of evidence generated in the systematic review (SR) and meta-analysis of moxibustion and acupuncture as a primary or complementary therapy for patients with ankylosing spondylitis.Methods:PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database were searched for systematic reviews and meta-analysis that review the efficacy of acupuncture or moxibustion as the primary treatment for patients with Ankylosing Spondylitis. The literature published before August 2020 will be selected. Additionally, the relevant SRs and meta-analyses that unpublished or ongoing will be searched in PROSPERO and INPLASY. The methodological guidelines for overviews will be used to review and extract data by 2 reviewers, and their will do it independently. Methodology quality will be analyzed by the assessment of multiple systematic reviews-2and the risk of bias by POBIS. For the included studies, we will adopt the following results as primary evaluation indicators: effective rate, visual analogue scale and bath AS disease activity index. Reviewers will assess the certainty of evidence by Grading of Recommendations Assessment, Development and Evaluation.Results:The results will be published in a peer-reviewed journal.Conclusion:This overview will provide comprehensive evidence of moxibustion and acupuncture for patients with Ankylosing Spondylitis.     

Empirically Supported Treatment: Recommendations for a New Model

Over the 20 years since the criteria for empirically supported treatments (ESTs) were published, standards for synthesizing evidence have evolved and more systematic approaches to reviewing the findings from intervention trials have emerged. Currently, the APA is planning the development of treatment guidelines, a process that will likely take many years. As an intermediate step, we recommend a revised set of criteria for ESTs that will utilize existing systematic reviews of all of the available literature, and recommendations that address the methodological quality, outcomes, populations, and treatment settings included in the literature.     

Effects of orthopaedic manual therapy in knee osteoarthritis: a systematic review and meta-analysis

Objective

This systematic review to aimed to evaluate the effects of orthopaedic manual therapy (OMT) on pain, improving function, and physical performance in patients with knee osteoarthritis (OA).

消栓肠溶胶囊治疗急性脑梗死的Meta-分析和GRADE评价

目的 系统评价消栓肠溶胶囊治疗急性脑梗死的临床疗效和安全性。方法 系统检索中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和维普中文期刊全文数据库（VIP）、万方数据库、Pub Med、CochraneLibrary和Web of science数据库,收集从建库至2020年5月消栓肠溶胶囊治疗急性脑梗死的临床随机对照试验（RCTs）,应用RevMan 5.3软件进行Meta-分析,最后采用GRADE系统对重要结局指标进行证据质量的评价并形成推荐意见。结果 纳入14项RCTs,共1 093例患者。Meta-分析结果显示：在改善临床总有效率方面,消栓肠溶胶囊+常规治疗组优于常规治疗组[RR=1.23,95% CI=（1.15,1.32）,P<0.000 01]和安慰剂+常规治疗组[RR=1.52,95% CI=（1.14,2.02）,P=0.004];在改善神经功能缺损评分方面,消栓肠溶胶囊+常规治疗组优于常规治疗组[MD_NIHSS=-2.70,95% CI=（-3.80,-1.59）,P<0.000 01;MD_NDS=-3.87,95% CI=（-4.64,-3.09）,P<0.000 01]和安慰剂+常规治疗组[MD_NIHSS=-1.87,95% CI=（-3.27,-0.47）,P=0.009];在改善日常生活能力评分方面,消栓肠溶胶囊+常规治疗组优于常规治疗组[MD=14.60,95% CI=（6.17,23.02）,P=0.000 7]和安慰剂+常规治疗组[MD=36.11,95% CI=（27.04,45.18）,P<0.000 01];在不良事件发生率方面,消栓肠溶胶囊+常规治疗组与常规治疗组比较差异无统计学意义[RR=0.86,95% CI=（0.29,2.58）,P=0.79]。GRADE系统评价临床总有效率、神经功能缺损评分、日常生活能力评分,显示证据等级为低或极低,推荐强度均为弱推荐。结论 消栓肠溶胶囊在改善急性脑梗死患者临床总有效率、神经功能缺损程度及日常生活质量方面具有一定的疗效,且安全性较好。但因纳入研究的文献质量不高,证据等级较低,故需要样本量更大、质量更高、设计更严格的随机对照试验作进一步论证。     

EAACI Biologicals Guidelines—dupilumab for children and adults with moderate-to-severe atopic dermatitis

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.     

中药注射剂治疗心律失常的系统评价再评价

目的：对中药注射剂治疗心律失常的Meta分析或系统评价进行再评价。方法：计算机检索PubMed、EMbase、the Cochrane Library、知网、万方、维普、CBMdisc等中英文数据库,检索中药注射剂治疗心律失常的系统评价,时间为建库至2019年6月。2位评价者独立进行文献筛选以及资料提取工作,应用AMSTAR2量表以及GRADE评估工具进行评价。结果：最终纳入7篇Meta分析或系统评价,包含25个结局指标,涉及4种中药注射剂。AMSTAR2量表评价结果中"是否提供前期设计方案"、"是否提供排除文献清单"、"纳入标准中是否考虑发表文献,如灰色文献"、"是否说明相关利益冲突"4项为导致方法学质量降低的主要因素。GRADE评估工具的评价结局中,纳入系统评价的局限性以及发表偏倚为引起结局指标证据质量降低的原因。对纳入文献再进行Meta分析显示,中药注射剂治疗心律失常,可提高治疗总有效率[Z=10.99,RR=1.45,95% CI （1.36,1.55）,P<0.01]、血管再通率[Z=2.29,OR=1.34,95% CI （1.04,1.72）,P=0.02],改善心率[Z=21.52,MD=4.80,95% CI （10.12,12.15）,P<0.01],降低心律失常发生率[Z=4.38,RR=0.53,95% CI （0.40,0.70）,P<0.01]、病死率[Z=5.94,RR=0.49,95% CI （0.39,0.62）,P<0.01]。结论：中药注射剂在治疗心律失常中发挥重要作用,但现今关于中药注射剂治疗心律失常的Meta分析或系统评价的评价方法尚不规范,证据质量偏低,对此次评价结论可靠性产生了影响。