FDA“治疗等效性评价供企业用指导原则”（草案）介绍

美国食品药品管理局（FDA）于2022年7月发布了"治疗等效性评价供企业用指导原则"（草案）。该指导原则阐明了FDA治疗等效性的标准以及治疗等效性编码系统，目的是准确评价仿制药与参比制剂的治疗等效性并通过治疗等效性代码，在"橙皮书"中迅速检索到治疗等效的仿制药。而中国目前尚无类似的指导原则，详细介绍FDA该指导原则主要内容，期望对中国加强仿制药的治疗等效性评价和加速完善和实施符合国情的治疗等效性编码系统有所帮助。     

Process evaluation of implementation strategies to reduce potentially inappropriate medication prescribing in older population: A scoping review

ObjectivesSeveral implementation strategies can reduce potentially inappropriate medication (PIM) prescribing. Although use of PIMs has declined in recent years, it remains prevalent. Various strategies exist to improve the appropriateness of medication use. However, little is known about the processes of these different implementation strategies. This scoping review aims to investigate how the process evaluation of implementation strategies for reducing PIM prescribing in the older population has been studied.MethodsWe searched for process evaluations of implementation strategies for reducing PIM prescribing in PUBMED, SCOPUS and Web of Science published between January 2000 and November 2019 in English. We applied the following inclusion criteria: patients aged ≥65 years, validated PIM criteria, and implementation process evaluated. The review focuses on decision support for health care professionals. We described the findings of the process evaluations, and compared the authors’ concepts of process evaluation of the included publications to those of Proctor et al.( 2010).ResultOf 9131 publications screened, 29 met our inclusion criteria. Different process evaluation conceptualizations were identified. Most process evaluations took place in the initial stages of the process (acceptability, adoption, appropriateness, and feasibility) and sustainability and implementation costs were seldom evaluated. None of the included publications evaluated fidelity.Multifaceted interventions were the most studied implementation strategies. Medication review was more common in acceptability evaluations, multidisciplinary interventions in adoption evaluations, and computerized systems and educational interventions in feasibility evaluations. Process evaluations were studied from the health care professionals’ viewpoint in most of the included publications, but the management viewpoint was missing.DiscussionThe conceptualization of process evaluation in the field of PIM prescribing is indeterminate. There is also a current gap in the knowledge of sustainability and implementation costs. Clarifying the conceptualization of implementation process evaluation is essential in order to effectively translate research knowledge into practice.     

Trans-lesional fractional flow reserve gradient as derived from coronary CT improves patient management: ADVANCE registry

BackgroundThe role of change in fractional flow reserve derived from CT (FFR_CT) across coronary stenoses (ΔFFR_CT) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown.ObjectivesTo investigate the incremental value of ΔFFR_CT in predicting early revascularization and improving efficiency of catheter laboratory utilization.MaterialsPatients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR_CT was measured 2 ?cm distal to stenosis. ΔFFR_CT was manually measured as the difference of FFR_CT across visible stenosis.ResultsOf 4730 patients (66 ?± ?10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR_CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26–1.35]; p ?< ?0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR_CT. Among the 3 models (model 1: risk factors ?+ ?stenosis type and location ?+ ?CAD-RADS; model 2: model 1 ?+ ?FFR_CT; model 3: model 2 ?+ ?ΔFFR_CT), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86–0.88] vs 0.85 [0.84–0.86]; p ?< ?0.001), with the greatest incremental value for FFR_CT 0.71–0.80. ΔFFR_CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR_CT ≤0.8, a diagnostic strategy incorporating ΔFFR_CT >0.13, would potentially reduce ICA by 32.2% (1638–1110, p ?< ?0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%.ConclusionsΔFFR_CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR_CT, particularly for those with FFR_CT 0.71–0.80. ΔFFR_CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization.     

基于CiteSpace的足三里穴研究可视化分析＊

目的 围绕足三里穴（ST36）进行文献可视化分析，探索近20年来有关足三里穴的研究进程、热点以及未来发展趋势。方法 以中国知网（CNKI）为数据来源，利用citespace软件对检索出的2000年1月至2021年11月收录的基础研究和临床研究文献分别进行可视化分析，绘制关键词、作者、机构相关图谱。结果 基础研究纳入1030篇文献，得到9个关键词聚类，电针中心度最高（0.53），发文量最多的作者是胡森（22篇），发文量最大的机构是北京中医药大学针灸推拿学院（23篇）。临床研究纳入2067篇文献，得到9个关键词聚类，穴位注射和针刺中心度最高（0.27），发文量最多的作者是张波（7篇），发文量最大的机构是浙江中医药大学附属第一医院（8篇）。结论 足三里穴在基础和临床的研究重点、热点和趋势不一致。并且在基础研究和临床研究之间，针刺镇痛、电针疗法、胃肠功能这三个内容是同步的，而关于代谢组学、穴位注射、温针灸和揿针的内容则是脱节的。     

Renal sympathetic denervation in resistant hypertension: The association between vitamin D and positive early response in systolic blood pressure

Aims and objectivesVitamin D deficiency is a common finding and there is a suggested association with hypertension. Resistant hypertension is a clinical problem observed in 5–30% of hypertensive patients. Renal denervation (RDN) has been used for patients with resistant hypertension and has proven to lower blood pressure. Our primary goal was to assess the vitamin D serum concentration as a predictor of blood pressure response to RDN in highly selected patients.MethodsThis prospective, nonrandomized, single-center study included 24 patients treated with RDN. Based on their one-year response after RDN, patients were classified as responders or non-responders at six months or at 12 months.ResultsThe median follow-up was 52 months (range, 14-91 months). After RDN, 17 patients (70.8%) had a reduction >5 mmHg in the mean systolic blood pressure, at the first six months of follow-up. At 12 months, 20 patients (83.3%) were responders. Vitamin D levels at baseline (15.1±4.8 vs. 24.2±8.8 ng/ml) and at six months (16.6±7.2 vs. 25±9.2 ng/ml) were lower in early non-responders compared to early responders (p=0.008), without significant variation during follow-up. Even though Vitamin D levels were lower in the total responder's group, no statistically significant differences were found (p=ns).ConclusionIn patients with resistant hypertension, low vitamin D concentrations were associated with an absence of early response to RDN.     

NEMA NU 2-2018标准在PET/CT系统性能测试中的作用评价

目的 评价美国国家电器制造协会(National Electrical Manufactures Association, NEMA)最新标准(NU 2-2018)在正电子发射型计算机断层显像/电子计算机断层显像(positron emission tomography/computed tomography, PET/CT)设备性能检测中的作用。 方法 依据最新的NEMA NU 2-2018标准,检测西门子Biograph Vision PET/CT的空间分辨率、灵敏度、散射分数、计数丢失、随机符合、飞行时间分辨率、计数丢失率和随机符合校正精度、图像质量、衰减和散射校正精度及PET与CT配准精度指标。 结果 距视野中心1 cm处横向和轴向空间分辨率分别为3.75 mm和3.76 mm;在视野中心和轴向10 cm处的灵敏度分别为16.83 kcps/MBq和16.67 kcps/MBq;放射性浓度为27.37 kBq/mL时,最大等效噪声计数率为258.26 kcps,散射分数为38.58%;系统时间分辨率为209.82 ps;图像质量模型的对比度恢复系数范围为88.9%~96.2%,背景变异系数范围为2.05%~6.80%,平均肺插件残余误差为2.43%;计数丢失和随机符合校正最大误差为3.9%;距离床板末端 5 cm 和 100 cm处,在距视野中心Y轴1 cm处,PET和CT的配准精度分别为0.46 mm和1.07 mm,在距视野中心X轴20 cm处,PET和CT的配准精度分别为1.06 mm和1.45 mm,在距视野中心Y轴20 cm处PET和CT的配准精度分别为0.85 mm和1.15 mm。 结论 NEMA NU 2-2018标准检测条件更加接近临床,能更好地反映PET/CT设备的系统性能。     

注意缺陷多动障碍患儿血清25（OH）D及微量元素表达水平及临床意义

目的 探究注意缺陷多动障碍(ADHD)患儿血清25羟基维生素D[25(OH)D]、微量元素表达水平及临床意义。方法 选取2019年4月至2020年11月本院诊治的84例ADHD患儿进行研究(ADHD组),依据ADHD分型标准将患儿分为注意缺陷为主型组(28例)、多动为主型组(33例)、混合型组(23例),并选取同期84例体检健康儿童进行对照研究(对照组)。采用高效液相色谱-串联质谱法检测所有受试儿童血清25(OH)D水平；检测血清铁(Fe)、磷(P)、镁(Mg)、钙(Ca)、铜(Cu)、锌(Zn)、铅(Pb)水平；Pearson法分析ADHD患儿血清25(OH)D水平与Cu、Zn、Pb水平的相关性；Logistic回归分析ADHD发生的影响因素；受试者工作特征(ROC)曲线分析血清25(OH)D、Zn、Pb水平对ADHD的诊断价值。结果 ADHD组血清25(OH)D、Cu、Zn水平均显著低于对照组(P<0.05),Pb水平显著高于对照组(P<0.05)；注意缺陷为主型组、多动为主型组、混合型组患儿血清25(OH)D、Fe、P、Mg、Ca、Cu、Zn、Pb水平比较,差异无统计学意义(P>0.05)；ADHD患儿血清25(OH)D水平与Cu、Zn水平均呈正相关(P<0.05),与Pb水平呈负相关(P<0.05)；25(OH)D、Zn是影响ADHD发生的保护因素(P＜0.05),Pb是影响ADHD发生的危险因素(P＜0.05)；血清25(OH)D、Zn、Pb水平诊断ADHD的曲线下面积(AUC)分别为0.773、0.770、0.772,截断值分别为21.01 ng/mL、16.05 μmol/L、50.69 μg/L,相应灵敏度分别为82.1%、77.4%、63.1%,特异度分别为67.9%、71.4%、88.1%；三者联合诊断ADHD的AUC为0.883,其灵敏度、特异度分别为81.0%、81.0%。结论 ADHD患儿血清25(OH)D、Cu、Zn水平降低,Pb水平升高,25(OH)D、微量元素水平与ADHD患儿类型无关,25(OH)D、Zn、Pb联合有助于临床筛查ADHD患儿。     

Efficacy of Curcumin in Combination with Intralesional Dexamethasone with Hyaluronidase in the Treatment of Oral Submucous Fibrosis: A Randomized Controlled Trial

Objective: The objective of this study was to determine the efficacy of curcumin in combination with  intralesional dexamethasone with hyaluronidase in the treatment of oral submucous fibrosis (OSF). Methods: This randomized, double blind, parallel design, clinical trial was conducted at B.P. Koirala Institute of Health Sciences, Nepal. Thirty-four patients with clinically diagnosed OSF were randomized into two groups (17 participants in each) with baseline treatment of intralesional dexamethasone with hyaluronidase for 6 weeks for the both. Curcumin (2gm/day) was provided to Group A (Test) and Group B (Control) received placebo. Interincisal mouth opening, tongue protrusion, cheek flexibility and visual analogue scale (VAS) scoring of burning sensation of oral mucosa was recorded at baseline, 6, 8 and 12 weeks follow-up and independent t-test was used to compare the improvements in two groups. Results: On comparing the 6 weeks and baseline values, in Group A and B the mean difference in mouth opening was 8.82±1.33 mm and 5.53±1.17 mm respectively (p<0.001), in cheek flexibility was 2.94±1.02 mm and 1.94±1.24 mm respectively (p=0.02) and in tongue protrusion was 6.23±1.48 and 3.65±1.37 mm respectively (p<0.001). The findings were consistent in the 8 weeks follow-up. In 12 weeks follow-up, on comparing with the baseline values, in Group A and B, the mean difference in mouth opening was 8.71±1.16 mm and 5.35±1.22 mm respectively (<0.001), ), in cheek flexibility was 2.81±1.01 mm and 1.76±1.35 mm respectively (p=0.02) and in tongue protrusion was 6.06±1.48 and 3.35±1.50 mm respectively (p<0.001). Both the arms showed 100% improvement in burning sensation in 6, 8 and 12 weeks follow-up. Conclusion: Curcumin in combination with intralesional dexamethasone with hyaluronidase is efficacious in the treatment of OSF.