Regulatory Issues of Propensity Score Methodology Application to Drug and Device Safety Studies

While randomized, well-controlled, clinical trials have been viewed as the gold standard in the evaluation of medical products, including drugs, biological products, and medical devices, it is not uncommon for safety assessment to be performed using observational studies, for ethical or practical reasons. In observational studies, various biases could be introduced in every stage and aspect of study, and consequently the resulting statistical inference may carry a lower level of scientific assurance, compared to randomized trials. To ensure the objectivity of study design and interpretability of the results, it is critical to address the challenges of such studies. In this paper, we share regulatory considerations on the prospective design of observational studies to address safety issues using propensity score methodology.     

辛芩颗粒联合盐酸氮卓斯汀治疗变应性鼻炎的临床研究

目的探讨辛芩颗粒联合盐酸氮卓斯汀治疗变应性鼻炎的临床疗效。方法选取2015年1月—2016年1月在商洛市中心医院接受治疗的变应性鼻炎患者176例为研究对象,随机分为对照组和治疗组,每组各88例。对照组鼻喷盐酸氮卓斯汀鼻喷剂,1喷/鼻孔,2次/d。治疗组在对照组基础上口服辛芩颗粒,5 g/次,3次/d。两组均连续用药28 d。观察两组的临床疗效,比较两组的症状评分、RQLQ评分和血清学指标。结果治疗后,对照组和治疗组的总有效率分别为85.23%、94.32%,两组比较差异有统计学意义(P0.05)。治疗后,两组鼻塞、鼻痒、喷嚏和流涕评分及总评分均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的下降程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组日常活动、睡眠、非鼻–结膜炎症、相关行为、鼻部症状、眼部症状和情感反应评分均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的下降程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组白细胞介素-4(IL-4)、白细胞介素-5(IL-5)、转化生长因子-α(TGF-α)和免疫球蛋白E(Ig E)均明显升高,而白细胞介素-12(IL-12)和γ-干扰素(IFN-γ)均明显降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论辛芩颗粒联合盐酸氮卓斯汀治疗变应性鼻炎具有较好的临床疗效,改善患者临床症状和生活质量,提高机体免疫力,具有一定的临床推广应用价值。     

DNase in stable cystic fibrosis infants: a pilot study

OBJECTIVE: To assess the feasibility of measuring short-term effects of inhaled recombinant human deoxyribonuclease (rhDNase, Pulmozyme on lung function, pulse oximetry and symptom scores in infants and toddlers with stable cystic fibrosis. DESIGN: open-label randomized placebo controlled cross-over pilot study. PATIENTS AND METHODS: We treated nine CF patients (0.7-1.9 years) with nebulised rhDNase (2.5 mg) and NaCl 0.9% (10 ml) via jet nebulizer cross-over once daily during 2-week treatment blocks. Measurements were performed at baseline and after treatment blocks and consisted of lung function tests (plethysmography and tidal rapid thoraco-abdominal compression technique), overnight pulse oximetry, and daily symptom scores. RESULTS: DNase treatment and the different assessments were well tolerated by all children and their parents. Lung function showed increased airway patency after treatment with rhDNase (P < 0.001), but not after NaCl 0.9%. Overnight pulse oximetry and daily symptom scores did not change during the study period. CONCLUSIONS: This pilot study indicates that objective assessment of the effects of rhDNase is feasible in infants with CF who have little or no respiratory symptoms. Our results warrant a larger randomized placebo-controlled trial.     

红花黄色素注射液治疗缺血性脑梗死临床疗效研究

目的:探讨红花黄色素注射液治疗缺血性脑梗死的临床疗效。方法:将91例缺血性脑梗死患者随机分为红花黄色素注射液治疗组46例,复方丹参注射液对照组45例,观察治疗前后神经功能缺损评分,判定其临床疗效,并化验得出其治疗前后血液流变学指标,观察其不良反应。结果:治疗组与对照组总有效率分别为82.61%和62.21%,治疗组显著高于对照组﹙P0.05﹚。治疗后两组全血粘度和血浆比粘度均有不同程度降低,红细胞压积有所升高(P均0.05或0.01),但治疗组更为显著﹙P0.01﹚。结论:红花黄色素能有效改善患者的神经功能缺损程度,促进缺血性脑梗死患者的康复,是治疗缺血性脑梗死的有效方法。     

宣降平喘汤治疗支气管哮喘随机平行对照研究

[目的]观察宣降平喘汤治疗支气管哮喘疗效。[方法]使用随机平行对照方法,将70例门诊患者按就诊顺序号法简单随机分为两组。对照组35例甲氧那明,2粒/次,3次/d。治疗组35例宣降平喘汤(半夏、苏子、麻黄炙、款冬花各12g,桂枝、地龙、五味子各10g,茯苓、杏仁、白芍、五味子、蝉蜕、白术炒各15g,干姜9g,甘草炙6g;喘息严重加白果;舌苔暗沉加红花、桃仁;痰量较多加莱菔子、葶苈子、白芥子;阳虚加肉桂),1剂/d,水煎200m L,早晚口服。连续治疗7d为1疗程。观测临床症状、用力呼气一秒容积(FEV1)、最大呼气流量(PEF)、中医证候积分(喘息、咳嗽、咳痰)、不良反应。连续治疗3疗程,判定疗效。[结果]治疗组显效22例,有效11例,无效1例,总有效率97.12%。对照组显效13例,有效15例,无效7例,总有效率80.00%。治疗组疗效优于对照组(P0.05)。中医证候评分两组均有改善(P0.05),治疗组改善优于对照组(P0.05)。[结论]宣降平喘汤治疗支气管哮喘,疗效满意,无副作用,值得推广。     

纳武利尤单抗联合安罗替尼治疗晚期非小细胞肺癌的临床研究

目的 探究纳武利尤单抗注射液联合盐酸安罗替尼胶囊治疗晚期非小细胞肺癌的临床疗效。方法 选取2019年1月—2020年1月临汾市中心医院收治的60例晚期非小细胞肺癌患者为研究对象,根据患者治疗方法不同分为对照组（29例）和治疗组（31例）。对照组患者早餐前口服盐酸安罗替尼胶囊,12 mg/次,1次/d,连续服药2周,停药1周。治疗组患者在对照组治疗的基础上静脉输注纳武利尤单抗注射液,3 mg/kg,1次/2周,评估患者耐受性和疗效。两组患者均持续治疗9周。观察两组近期临床疗效,比较治疗前后两组生活质量、T淋巴细胞亚群、血管内皮细胞生长因子（VEGF）水平变化和生存情况。结果 治疗后,治疗组客观缓解率（ORR）、疾病控制率（DCR）均较高于对照组,组间比较差异具有显著差异（P<0.05）。治疗后,两组患者CD3⁺、CD4⁺、CD4⁺/CD8⁺均明显升高,CD8⁺、VEGF均明显降低（P<0.05）;治疗组CD3⁺、CD4⁺、CD4⁺/CD8⁺均明显高于对照组,CD8⁺、VEGF均明显低于对照组（P<0.05）。治疗后2、4、6个月,两组EORTC QLQ-C30总评分均明显降低（P<0.05）,且治疗组EORTC QLQ-C30总评分明显低于同期对照组（P<0.05）。治疗后,治疗组中位无进展生存期（PFS）、总生存期（OS）较对照组明显增长（P<0.05）。结论 纳武利尤单抗注射液联合盐酸安罗替尼胶囊治疗晚期非小细胞肺癌具有较好的临床疗效,可改善患者的生活质量,调节患者免疫功能,降低VEGF水平,且不增加不良反应。     

Hallux Valgus Correction Comparing Percutaneous Oblique Osteotomy and Open Chevron Osteotomy at a 2‐year Follow‐up

ObjectiveThis study aimed to compare the percutaneous oblique osteotomy (POO) and the open chevron osteotomy technique for correction of hallux valgus deformity at a 2‐year follow‐up.MethodsThis is a retrospective study of consecutive patients undergoing operative correction of hallux valgus using one of two techniques (POO vs open chevron osteotomy) from 2014 to 2018. Forty eight feet (41 patients) that underwent the POO was compared with 64 feet (58 patients) that underwent open chevron osteotomy. The hallux valgus angle (HVA), intermetatarsal angle (IMA) and American Orthopedic Foot & Ankle Society Hallux Metatarsophalangeal‐Interphalangeal scores (AOFAS‐HMI) were assessed preoperatively and postoperatively at the 1, 2‐year follow‐up. The Manchester–Oxford Foot Questionnaire (MOXFQ) were assessed preoperatively and postoperatively at the 2‐year follow‐up. The VAS score was collected preoperatively and on 2 weeks,1 year and 2‐year follow‐up.ResultsBoth groups achieved significant correction of the hallux deformity. The HVA in the POO group during the follow‐up period were 12.5 ± 2.22 and 17.9 ± 9.31, respectively, and in the open chevron group were 14.1 ± 6.78 and 14.8 ± 7.83, respectively. The IMA in the POO group during the follow‐up period were 7.61 ± 1.63 and 6.94 ± 1.53, respectively, and in the open chevron group were 6.89 ± 3.06 and 6.97 ± 2.95, respectively. Postoperative MOXFQ scores in all domains were significantly improved in both groups, however there was no significant difference in the improvement of any domain between POO and open groups at a 2‐year follow‐up. The AOFAS HMI scores in the POO group during the follow‐up period were 86.5 ± 10.7 and 85.2 ± 13.8, respectively, and in the open chevron group were 88.2 ± 10.8 and 79.5 ± 23.7, respectively. The VAS scores in the POO group during the follow‐up period were 2.00 ± 0.98, 2.00 ± 0.99 and 1.55 ± 1.11, respectively, and in the open chevron group were 5.51 ± 1.45, 2.56 ± 2.88 and 2.56 ± 2.88 respectively. The 1‐year and 2‐year follow‐up outcomes between POO and open groups showed no significant difference regarding AOFAS HMI scores and VAS scores, however the POO group showed statistically significant improvement of VAS scores in the postoperative 2 weeks (P < 0.001). There was no statistical significance between the POO and open group in terms of complications rates (8.3% vs 12.5%, P = 0.480).ConclusionThe POO technique is reliable and shows a comparable outcome to the open chevron osteotomy. However, the POO technique shows significantly less pain in the first 2 weeks after surgery.