中医体质研究40年回顾与展望

文章回顾中医体质研究40年来在6大理论创新、3大技术创新、4大转化应用、2大学术平台方面取得的辉煌成就。展望未来，中医体质研究将积极策应国家需求，进一步发挥其原创优势、深化理论研究、完善技术方法、加快平台建设、提升服务能力，为实施“健康中国”战略作贡献。     

Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.     

Differences in Evidentiary Requirements Between European Medicines Agency and European Health Technology Assessment of Oncology Drugs—Can Alignment Be Enhanced?

ObjectivesNational health technology assessments (HTAs) across Europe show differences in evidentiary requirements from assessments by the European Medicines Agency (EMA), affecting time to patient access for drugs after marketing authorization. This article analyzes the differences between EMA and HTA bodies’ evidentiary requirements for oncology drugs and provides recommendations on potential further alignment to minimize and optimally manage the remaining differences.MethodsInterviews were performed with representatives and drug assessment experts from EMA and HTA bodies to identify evidentiary requirements for several subdomains and collect recommendations for potentially more efficiently addressing differences. A comparative analysis of acceptability of the evidence by EMA and the HTA bodies and for potential further alignment between both authorities was conducted.ResultsAcceptability of available evidence was higher for EMA than HTA bodies. HTA bodies and EMA were aligned on evidentiary requirements in most cases. The subdomains showing notable differences concerned the acceptance of limitation of the target population and extrapolation of target populations, progression-free survival and (other) surrogate endpoints as outcomes, cross-over designs, short trial duration, and clinical relevance of the effect size. Recommendations for reducing or optimally managing differences included joint early dialogues, joint relative effectiveness assessments, and the use of managed entry agreements.ConclusionsDifferences between assessments of EMA and HTA bodies were identified in important areas of evidentiary requirements. Increased alignment between EMA and HTA bodies is suggested and recommendations for realization are discussed.     

中医药治疗慢性前列腺炎研究概况

综述近年中医药治疗慢性前列腺炎的临床研究,认为本病病因病机之核心在于脾肾亏虚为本,湿热、痰浊、瘀毒为标,病久则伤及脾肾,由实转虚。中医内治法主要以辨证论治、辨病论治或单方验方为主,外治法以中药洗浴、中药灌肠、肛门给药、针灸为主。中医药治疗本病优势明显。应继续完善对中医药作用机制的认识,制订统一的辨证论治及疗效评价标准,针对效果显著的名方开展研究。     

Prevalence of Apical Periodontitis and Conventional Nonsurgical Root Canal Treatment in General Adult Population: An Updated Systematic Review and Meta-analysis of Cross-sectional Studies Published between 2012 and 2020

IntroductionThis study aimed to summarize data on apical periodontitis (AP) and nonsurgical root canal treatment (NSRCT) prevalence and risk factors related to age, gender, and quality of restorative and endodontic treatment in the general population from cross-sectional studies published between 2012 and 2020.MethodsAn electronic search was performed in the following databases: Web of Science, Scopus, and PubMed. The conducted literature search covered studies published between 2012 and 2020, without restrictions on language. The STROBE and NOS tools were used for quality assessment of the included studies.ResultsSixteen articles were included in the review. In total, 200,041 teeth were examined. On average, 6.3% of teeth had AP, and 7.4% had NSRCT. Forty-one percent of RCT teeth had AP, and 3.5% of untreated teeth had AP. Female patients were less prone to AP in endodontically treated teeth only, compared with male patients (P < .001). Variable stratification of age subgroups among included studies prevented us from conducting a meta-analysis. An increase in AP frequency was found in teeth with inadequate restorative and endodontic treatment (P < .001 and P < .001, respectively). Because of high heterogeneity, these results should be taken with caution.ConclusionsThere is an increased AP prevalence in the adult general population compared with data from 2012 (6.3% versus 5.4%) in both endodontically treated (41.3% versus 35.9%) and untreated teeth (3.5% versus 2.1%). In addition, AP developed less frequently in female patients with endodontically treated teeth and in teeth with inadequate compared with adequate restorative and endodontic treatment.