Relationship between sample size and the definition of equivalence in non-inferiority drug studies

Statistical testing of clinical trial data leads to acceptance of a hypothesis if a test of the opposite (null) hypothesis (H0) fails to reach a critical probability value. The usual aim is to demonstrate that a new treatment is superior to a comparator, whence H0 is that the two treatments are the same. By contrast, in studies designed to show that a new treatment is equivalent to an existing therapy, the same principle is satisfied by an amended null hypothesis, that the treatments differ by more than a defined amount. This reversal entails subtle but important logical and practical problems which affect particularly the calculation of sample size. The choice of the limits used to define equivalence is critical to the calculation of sample size in a manner not previously discussed, and in the interpretation of data in relation to the probability of Type I and Type II errors. Investigators, regulatory bodies and institutional ethics committees must ensure that the range of values chosen to indicate equivalence is clinically appropriate and be aware of the effect of this decision on possible errors in accepting or rejecting H0.     

中晚期原发性肝癌患者TACE术后早期复发危险因素

目的观察中晚期原发性肝癌(HCC)患者TACE术后早期复发危险因素。方法对42例中晚期原发性HCC患者行TACE治疗,术后随访6个月,对比分析早期复发与未复发患者之间的差异。结果术后6个月中,23例HCC早期复发(复发组),19例未复发(无复发组)。复发组白蛋白35 g/L者占比低于未复发组(P0.05),甲胎蛋白(AFP)400 ng/ml者占比及谷氨酰基转移酶(ALT)水平均高于未复发组(P均0.05)。未复发组肿瘤病理分化程度较高(P0.05),复发组瘤灶相对较多、肿瘤最大径较大,ADC值和包膜完整比例低于未复发组(P均0.05)。多因素Logistic回归分析结果显示,AFP400 ng/ml者占比(OR=3.313,P=0.041)、肿瘤分化程度(OR=1.463,P=0.038)、瘤灶数量(OR=2.216,P=0.028)及肿瘤ADC值(OR=0.025,P=0.003)是TACE术后HCC早期复发的独立危险因素。结论 TACE术后中晚期HCC早期复发与AFP、肿瘤分化程度、瘤灶数量及ADC值独立相关。     

经动脉灌注化学治疗中晚期胃癌的临床效果

目的探讨经动脉灌注化学治疗(简称化疗)中晚期胃癌的临床效果。方法将80例中晚期胃癌患者随机分为观察组和对照组,每组40例。观察组给予DSA引导下经动脉灌注化疗,对照组采用常规SOX方案化疗,比较2组化疗3、6个周期后的疗效,并统计不良反应。绘制2组患者随访24个月时无进展生存时间曲线,比较无进展生存时间。结果3个周期化疗结束时,观察组治疗有效率69.44%(25/36),高于对照组的38.46%(15/39)(P=0.028);6个周期结束时,观察组治疗有效率58.82%(20/34),对照组为41.67%(15/36),组间差异无统计学意义(P=0.511)。6个周期化疗期间2组患者不良反应差异无统计学意义(P均>0.05)。随访24个月时,观察组、对照组中位无进展生存期分别为6.5、6.0个月,组间比较差异有统计学意义(P=0.041)。结论动脉置管持续灌注化疗对中晚期胃癌的短期疗效优于常规SOX化疗方案,并可延长患者无进展生存期,且较安全。     

Expression and clinical implications of leucine-rich repeat containing 15 (LRRC15) in osteosarcoma

Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor grade and aggression. Despite its known tumorigenicity, its roles within osteosarcoma are unknown, prompting us to evaluate its expression and clinical significance within this rare yet aggressive cancer. Western blots showed differential expression of LRRC15 in the osteosarcoma cell lines MNNG/HOS, KHOS, 143B, MG63, Saos-2, and U2OS. We additionally validated this positive expression, as well as sublocalization to the cell membrane, with immunofluorescence. A tissue microarray constructed from 69 osteosarcoma patient tissues was immunohistochemically stained for LRRC15 expression, stratified, and used for clinicopathological analysis. Publicly available databases on LRRC15 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2) were also analyzed. We found 63 of the 69 (91.3%) patient tissues exhibited some degree of LRRC15 immunostaining, including no staining (6 of 69, 8.7%), 1+ staining (12 of 69, 17.4%), 2+ staining (25 of 69, 36.2%), and 3+ staining (26 of 69, 37.7%). The patients with osteosarcomas having elevated LRRC15 expression demonstrated comparatively increased metastasis, chemoresistance, and shorter 5-year survival rates. Our analysis of the TARGET-OS and GENT2 databases also showed increased LRRC15 gene expression in osteosarcoma. Taken together, our study supports LRRC15 as a prognostic biomarker and emerging therapeutic target in osteosarcoma.     

The effects of preoperative chronic opioid use in total hip arthroplasty

BackgroundPerioperative opioid use is becoming an increasingly concerning topic in total joint arthroplasty (TJA). The current study aims to add to the paucity of prior studies that have detailed perioperative opioid use patterns and the effects of preoperative chronic opioid use among a cohort of total hip arthroplasty (THA) patients.MethodsA retrospective analysis of 256 consecutive patients who underwent a THA at our institution between February 2016 and June 2016 was performed. Two cohorts were compared: patients deemed 1) preoperative chronic opioid users, and 2) non-chronic users. Variables compared included baseline characteristics, quality metrics, and patients’ opioid use histories 3 months prior to surgery and 6 months following surgery.ResultsOf the 256 patients, 54 (21.1%) patients were identified as preoperative chronic opioid users. Baseline characteristics including age, gender, BMI, and ASA scores were similar between both cohorts. Discharge disposition, value-based purchasing (VBP) costs, length of stay (LOS), emergency room visits, and postoperative office visits were similar between the two cohorts. Readmission rates (30-day, 90-day, and 6-month) were significantly higher (p < 0.05) in the chronic opioid users cohort. By the 6-month postoperative time period, chronic opioid users were consuming approximately 100-times the morphine equivalents than non-chronic users.ConclusionsThe current study demonstrates that a substantial proportion of preoperative chronic opioid users continue to consume large amounts of opioids up to 6-months following THA surgery. Furthermore, preoperative chronic use is significantly associated with poorer quality outcomes, specifically with respect to readmission rates.Level of evidenceLevel II, Prognostic Study.