New hope for hepatitis C virus:Summary of global epidemiologic changes and novel innovations over 20 years

Hepatitis C virus(HCV)is a global health concern associated with significant morbidity and mortality.Before the approval of second-generation direct-acting antiviral agents(DAAs),interferon therapy and liver transplantation constituted the mainstay of treatment.The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95%cure rates.The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs.Despite the unparallel efficacy observed among these novel therapies,pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally.To reduce the burden of disease worldwide,essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies.Through transparent negotiations with the pharmaceutical industry,the consideration for compassionate release of medications to promote equitable division of care is paramount.Here we provide a literature review of HCV,changes in epidemiologic trends,access issues for current therapies,and global inequities in disease burden.

Fixed-effect and random-effects models in meta-analysis

A systematic review synthesizes evidence addressing a structured clinical question using systematic and explicit methods to search,identify,screen,critically appraise,and extract and analyze data from relevant studies.[1]A meta-analysis,on the other hand,is a statistical method that combines the quantitative results of available primary studies addressing the same question to generate a pooled summary estimate and confidence interval(CI).[2]Meta-analyses can increase statistical power,enhance precision,and answer questions that single trials are underpowered to address.Although there are systematic reviews where meta-analyses are not appropriate,when they are well-conducted and reported,systematic reviews combined with meta-analyses provide valuable information for clinicians,researchers,and policymakers.

A 12-month follow-up study of discharged patients with acute pancreatitis:An acute condition with prolonged sequela

To the Editor:Acute pancreatitis(AP)is the most common gastrointestinal condition that leads to acute hospitalization.[1]The incidence of AP has increased in recent decades,with a current global incidence of 34/100,000,probably due to a rising trend of obesity and gallstone disease.AP is associated with remarkable pain,reduced quality of life(QoL),and even death,thus posing a heavy socioeconomic burden.In addition,approximately 22%of AP patients experience recurrent AP(RAP)and 10%of AP patients progress to chronic pancreatitis.[2]Petrov and Yadav[3]have,therefore,argued that AP should not be considered as an acute and self-limiting disease.Treatment and long-term care after AP have drawn widespread attention,which has improved patients’physical and mental health.

Evidence-based medicine and precision medicine:complementary approaches to clinical decision-making

Evidence-based medicine is widely promoted for decision-making in health care and is associated with improved patient outcomes.Critics have suggested that evidence-based medicine focuses primarily on groups of patients rather than individuals,but often fail to consider subgroup analyses,N-of-1 trials,and the incorporation of patient values and preferences.Precision medicine has been promoted as an approach to individualize diagnosis and treatment of diseases through genetic,biomarker,phenotypic,and psychosocial characteristics.However,there are often high costs associated with personalized medicine,and high-quality evidence is lacking for effectiveness in many applications.For the potential of personalized medicine to be realized,it must adhere to the principles of evidencebased medicine:(1)evidence in isolation is not sufficient to make clinical decisions—patient’s values and preferences as well as resource implications must be considered,and(2)there is a hierarchy of evidence to guide clinical decision-making and studies at lower risk of bias are likely to provide more trustworthy findings.

Application of artificial intelligence in clinical diagnosis and treatment:an overview of systematic reviews

Objective This study aimed to summarize the characteristics and methodological quality of systematic reviews on the application of artificial intelligence(AI)in clinical diagnosis and treatment.Methods We systematically searched seven English-and Chinese-language literature databases to identify sys-tematic reviews on the application of AI,deep learning,or machine learning in the diagnosis and treatment of any disease published in 2020.We evaluated the methodological quality of the included systematic reviews using“A Measurement tool for the assessment of multiple systematic reviews”(AMSTAR).We also conducted meta-analyses on the diagnostic accuracy of AI on selected disease categories with a large number of included studies and low clinical heterogeneity.Results A total of 40 systematic reviews reporting 1,083 original studies were included,covering 31 diseases from 11 groups of diseases.Eleven systematic reviews were related to neoplasms and nine were systematic reviews related to diseases of the digestive system.We selected digestive system diseases for the meta-analysis.The pooled sensitivities(with 95%confidence interval(CI))of AI to assist the diagnosis of helicobacter pylori,gastrointestinal ulcers,hemorrhage,esophageal tumors,gastric tumors,and intestinal tumors(with 95%CI)were 0.91(0.83-0.95),0.99(0.76-1.00),0.95(0.83-0.99),0.90(0.85-0.93),0.90(0.82-0.95),and 0.93(0.88-0.96),respectively,and the pooled specificities were 0.82(0.77-0.87),0.97(0.86-1.00),1.00(0.99-1.00),0.80(0.71-0.87),0.93(0.87-0.97),and 0.89(0.85-0.92),respectively.The AMSTAR items“the list of included studies”(n=39,97.5%)and“the characteristics of the included studies”(n=39,97.5%)had the highest compliance among the reviews;the compliance was relatively low to the items“the consideration of publication status”(n=1,2.5%),“the consideration of scientific quality”(n=19,47.5%),“data synthesis methods”(n=18,45.0%),and“the evaluation of publication bias”(n=13,32.5%).Conclusions The main subjects of systematic reviews on AI applications in clinical diagnosis and treatment pub-lished in 2020 were diseases of the digestive system and neoplasms.The methodological quality of the systematic reviews on AI needs to be improved,paying particular attention to publication bias and the rigorous evaluation of the quality of the included studies.

Investigation and evaluation of randomized controlled trials for interventions involving artificial intelligence

Objective Complete and transparent reporting is of critical importance for randomized controlled trials(RCTs).The present study aimed to determine the reporting quality and methodological quality of RCTs for interventions involving artificial intelligence(AI)and their protocols.Methods We searched MEDLINE(via PubMed),Embase,Web of Science,CBMdisc,Wanfang Data,and CNKI from January 1,2016,to November 11,2020,to collect RCTs involving AI.We also extracted the protocol of each included RCT if it could be obtained.CONSORT-AI(Consolidated Standards of Reporting Trials-Artificial Intelligence)statement and Cochrane Collaboration’s tool for assessing risk of bias(ROB)were used to evaluate the reporting quality and methodological quality,respectively,and SPIRIT-AI(The Standard Protocol Items:Recommendations for Interventional Trials-Artificial Intelligence)statement was used to evaluate the reporting quality of the protocols.The associations of the reporting rate of CONSORT-AI with the publication year,journal’s impact factor(IF),number of authors,sample size,and first author’s country were analyzed univariately using Pearson’s chi-squared test,or Fisher’s exact test if the expected values in any of the cells were below 5.The compliance of the retrieved protocols to SPIRIT-AI was presented descriptively.Results Overall,29 RCTs and three protocols were considered eligible.The CONSORT-AI items“title and abstract”and“interpretation of results”were reported by all RCTs,with the items with the lowest reporting rates being“funding”(0),“implementation”(3.5%),and“harms”(3.5%).The risk of bias was high in 13(44.8%)RCTs and not clear in 15(51.7%)RCTs.Only one RCT(3.5%)had a low risk of bias.The compliance was not significantly different in terms of the publication year,journal’s IF,number of authors,sample size,or first author’s country.Ten of the 35 SPIRIT-AI items(funding,participant timeline,allocation concealment mechanism,implementation,data management,auditing,declaration of interests,access to data,informed consent materials and biological specimens)were not reported by any of the three protocols.Conclusions The reporting and methodological quality of RCTs involving AI need to be improved.Because of the limited availability of protocols,their quality could not be fully judged.Following the CONSORT-AI and SPIRIT-AI statements and with appropriate guidance on the risk of bias when designing and reporting AI-related RCTs can promote standardization and transparency.

Discriminating endoscopic features of sessile serrated lesions

To the Editor:Colorectal cancer(CRC)remains a leading cause of cancer-related death worldwide.[1]In addition to the classical adenoma-to-carcinoma model of colorectal carcinogenesis,the serrated neoplastic pathway accounts for 20%–30%of CRCs.Sessile serrated lesions(SSLs),the most common premalignant serrated polyp subtype,share many of the genomic characteristics of post-colonoscopy CRCs and are thus recognized as their precursor lesions.However,SSLs can be easily missed due to their flat shape and subtle endoscopic features.Sometimes they can also be difficult to distinguish from other types of polyps,especially hyperplastic polyps(HPs),which are believed to have no malignant potential.[2]Approximately 10%of polyps initially diagnosed as HPs endoscopically are reclassified as SSLs after histopathological examination,reflecting diagnostic difficulties in colonoscopy.[3,4]Current guidelines recommend“diagnose-and-leave”and“resect-and-discard”strategies for diminutive polyps,which might lead to SSLs being left in situ or diagnoses being missed,[5]raising the risk of recurrence and post-colonoscopy cancers.Furthermore,it remains debatable in the gastrointestinal community whether the risks of resecting SSLs outweigh the reduction in cancer risk.Any strategy that improves the diagnostic accuracy of SSLs could have a meaningful clinical impact.

Persistent depression is a predictor of quality of life in stroke survivors: results from a 5-year follow-up study of a Chinese cohort

Background:Whether the time course of post-stroke depression (PSD) can be used to predict the quality of life (QoL) of patients with late-stage stroke remains unclear,this study investigated whether persistent depression at 1 year after stroke predicts QoL at 5 years following stroke.Methods:We analyzed the demographic and clinical data of patients with stroke in 56 hospitals across China that participated in the Prospective Cohort Study on the Incidence and Outcome of Patients with PSD in China Study.Follow-up assessments were performed at the following time points after stroke:in person,2 weeks,3 months,6 months,and 1 year;by telephone,5 years.National Institutes of Health Stroke Scale (NIHSS) score on admission,recurrence,disability,depression,QoL,and chronic complications were recorded.Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders.QoL was measured using short form-12 (SF-12).Multivariable ordinal logistic regression analysis was used to identify factors that independently affected the physical component summary (PCS) and mental component summary (MCS) scores of the SF-12.Results:Of the 801 patients evaluated in this study,80 had persistent depression.The multivariable regression analysis of data obtained at 5 years showed that persistent depression at 1 year (odds ratio [OR]:0.48;95% confidence interval [CI]:0.29-0.81) and disability at 5 years (OR:0.34;95% CI:0.23-0.49) were associated with poor MCS scores at 5 years.Old age,a high NIHSS score on admission,disability at 5 years,and stroke recurrence within 5 years were associated with poor PCS scores at the 5-year follow-up.Conclusions:Persistent depression at the 1-year follow-up could predict poor MCS scores at the 5-year follow-up.The development of interventional strategies targeting post-stroke patients with persistent depression is warranted.

Would integrated Western and traditional Chinese medicine have more benefits for stroke rehabilitation? A systematic review and meta-analysis

Background Stroke is a major cause of death or long-term disability worldwide.Many patients with stroke receive integrative therapy consisting of Western medicine(WM)and routine rehabilitation in conjunction with Chinese medicine(CM),such as acupuncture and Chinese herbal medicine.However,there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation.Aims The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only.Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed.MEDLINE,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI)were searched.The included outcomes were dependency,motor function,depression and swallowing function.Subgroup analysis was performed,and publication bias was assessed using funnel plots.Summary of review 58 studies and 6339 patients were included in the meta-analysis.Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone.Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found.Conclusions Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone.However,most studies were short in duration(2 to 4 weeks)and prone to different types of biases,which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias.So,more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined.

Providing Timely,Trustworthy Guidance to Frontline Clinicians during a Pandemic

When the unexpected happens,such as a pandemic caused by a novel virus,governmental agencies,organizations,and experts in the field are rightly concerned that the paucity of available evidence may trigger unsubstantiated or erroneous recommendations.The harms of which can be exacerbated with today’s massive spread of misinformation through unregulated social media or other trusted information sites,inevitably influencing frontline clinicians’and healthcare workers’behavior and practices.However,recommendations for clinical practices are essential for the prevention,detection,treatment,and management during a global crisis.In response to the COVID-19 pandemic,clinical and research experts,government agencies,and specialty societies immediately took action to provide guidance to their constituents on how to manage all aspect of the pandemic.

血浆置换和糖皮质激素治疗抗中性粒细胞胞质抗体相关性血管炎:临床实践指南

对于抗中性粒细胞胞质抗体(antineutrophil cytoplasmic antibody,ANCA)相关性血管炎(ANCA-associated vasculitis,AAV)患者,血浆置换的作用是什么?接受治疗前6个月糖皮质激素的最佳剂量是多少?一项新发表的随机对照试验(randomised controlled trial,RCT)引起本次指南的制订。

观点为中国生产可靠的真实世界数据和证据

中国是一个人口大国,并一直有致力于推进全民健康的雄心壮志。但目前面临的一个重大挑战是缺乏本土适用、可靠的临床研究证据。生产这些证据已成为中国医疗卫生研究者的一项重要使命。

肠促胰素类药物治疗与2型糖尿病患者的死亡风险：系统性综述和meta分析

目的评价2型糖尿病患者使用肠促胰素类药物治疗对全因死亡的影响。设计随机对照试验（RCT）的系统性综述和meta分析。数据来源来自Medline、Embase、the Cochrane Central Register of Controlled Trials（CENTRAL）、Clinical Trials．gov。纳入标准2型糖尿病患者使用胰高血糖素样肽-1（GLP-1）受体激动剂或二肽基肽酶-4（DPP-4）抑制剂与使用安慰剂或其他降糖药物治疗相比的RCT。数据收集和分析2名研究者独立筛选文献，评价纳入研究的偏倚风险，并提取数据。采用Peto法作为合并来自RCT效应估计的主要方法，采用其他统计方法进行敏感性分析，针对6种预先设定的假设开展meta回归来探索异质性。使用GRADE方法评价证据质量。结果纳入189个RCT（n=155145），偏倚风险为低至中等。其中77个RCT报告零死亡事件，112个RCT报告在151614例患者中发生3888例死亡事件。meta分析结果显示：肠促胰素类药物与对照组相比，死亡风险在组间差异无统计学意义f1925／84136比1963／67478；比值比（OR）=0．96，95％可信区间（CI）：0．90-1．02，I^2=0％；率差（RD）=比对照低3／1000，95％C1（比对照低7／1000～比对照高1／1090）／5年·1000例患者；中等质量证据1。亚组分析结果提示：GLP-1受体激动剂可能降低死亡风险，但DPP-4抑制剂未发现类似结果；该亚组效应的可信度较低。敏感性分析结果未发现明显差异。结论当前证据不支持肠促胰素类药物增加2型糖尿病患者死亡风险的假设。需进一步研究证实GLP-1受体激动剂与DPP．4抑制剂两类肠促胰素类药物之间是否存在差异。

钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南

临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。