Safety and efficacy of omadacycline for treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in patients with mild-to-moderate renal impairment

BackgroundMany antibiotics require dosage adjustments in patients with renal impairment. In Phase III studies, omadacycline was non-inferior to moxifloxacin and linezolid in adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), respectively. This analysis evaluated efficacy and safety measures from three omadacycline studies by patient renal function.MethodsPatients were stratified as having normal renal function (creatinine clearance >89 mL/min), mild renal impairment (creatinine clearance 60–89 mL/min) or moderate renal impairment (creatinine clearance <60 mL/min); creatine clearance ≤30 mL/min (severe renal impairment) was an exclusion criterion. Efficacy endpoints were clinical success at the early clinical response (ECR) and post-treatment evaluation (PTE) time-points. Safety was evaluated as treatment-emergent adverse events (TEAEs) and laboratory measures.ResultsThis subgroup analysis included 773 patients with CABP and 1339 patients with ABSSSI in intent-to-treat (ITT) and modified ITT populations, respectively. Clinical success rates were high at ECR and PTE across the studies (CABP 75–90%; ABSSSI 74–95%), and broadly similar between treatments, irrespective of renal function. Rates of TEAEs in patients with ABSSSI ranged from 33% to 52%, and were similar across renal function groups. In patients with CABP, higher rates were observed in patients with moderate renal impairment (56–61%) compared with patients with normal renal function or mild renal impairment (35–49%). The most common TEAEs were nausea and vomiting.ConclusionsClinical success was similar across renal function groups, indicating no notable difference in the efficacy of omadacycline in patients with mild or moderate renal impairment. Omadacycline and comparators displayed similar safety profiles.ClinicalTrials.gov registryOPTIC (NCT02531438); OASIS-1 (NCT02378480); OASIS-2 (NCT02877927).     

我国人群细胞因子水平与抑郁症的相关性研究的系统评价

目的:系统评价我国人群细胞因子水平与抑郁症的相关性。方法:计算机检索PubMed、中国生物医学文献数据库、维普中文数据库、中国期刊全文数据库和万方数据库,收集研究国内细胞因子与抑郁症相关性的病例对照研究,由两名研究者按照纳入与排除标准筛选文献、提取资料和评价质量后,采用Rev Man 5.1.5统计软件进行Meta分析。结果:共纳入7项研究,合计577例患者,其中试验组331例,健康对照组246例。Meta分析结果显示,试验组患者白细胞介素(IL)-6浓度[WMD=13.71,95%CI(6.91,20.51),P<0.000]和IL-1β浓度[SMD=2.15,95%CI(1.04,3.26),P<0.000]均高于健康对照组,两组比较差异有统计学意义;而抑郁组患者IL-2浓度亦高于健康对照组,但两组比较差异无统计学意义。结论:我国人群患抑郁症与IL-6、IL-1β水平升高存在一定的相关性。由于本研究的局限性,IL-6、IL-1β浓度与抑郁症的发作性质、严重程度的定量关系等内容尚需开展更多高质量、大样本的研究。     

基于肺水肿模型探讨葶苈子升降浮沉药性

目的 基于葶苈子药性沉降，根据“病位在里者宜沉降”的治则，建立病位在里的肺水肿模型，结合病势趋向的改变，验证葶苈子药性“沉降”的科学性，以期初步阐释中药升降浮沉药性的科学内涵。方法 选择60只雄性SD大鼠，随机分为假手术组、模型组（20 mg·kg^-1）、阳性药地塞米松组（0.075 mg·kg^-1）、葶苈子低、中、高剂量（1.167、2.334、4.668 g·kg^-1）组并通过胸膜腔注射1%角叉菜胶（2 mL·kg^-1）建立肺水肿模型，检测肺水肿评价指标（肺剖检、胸腔渗出液量、白细胞数量、肺湿重/干重比、肺含水量及肺通透性），确定葶苈子干预肺水肿的最佳剂量；检测与机体气机调节密切相关的五大系统（中枢系统、呼吸系统、循环系统、消化系统、泌尿系统）相关指标，观察葶苈子干预对肺水肿大鼠病势趋向的改变，确定其升降浮沉之性；并观察各组大鼠苏木素-伊红（HE）染色切片、炎症细胞种类和数目等，初步探究葶苈子改善肺水肿的作用机制。结果 与假手术组比较，胸腔积水量和胸腔积水中白细胞渗出量显著增加（P<0.01），肺湿重/干重比、肺含水量及肺通透性显著升高（P<0.01），并出现咳嗽、喘促、呼吸困难、弓背现象，少量大鼠鼻子湿润，鼻孔出现泡沫状液体等症状，剖检时肺出现体积增大或伴有瘀血，气管处出现大量粉红色泡沫状液体；与模型组比较，葶苈子可减少大鼠胸腔积水量和胸腔积水中白细胞渗出量，降低肺脏器系数、肺湿重/干重及肺含水量，改善肺组织水肿出血等，且以葶苈子中剂量治疗肺水肿效果最佳（P<0.01）；对于呼吸系统，与假手术组比较，模型组大鼠咳嗽潜伏时间、引喘潜伏时间明显减少（P<0.05，P<0.01），咳嗽次数和喘息次数显著增加（P<0.01），与模型组比较，葶苈子低、中、高剂量组均显著增加咳嗽潜伏期、引喘潜伏期，减少咳嗽次数、喘息次数（P<0.01）；对于泌尿系统，与假手术组比较，模型组大鼠显著减少尿量，葶苈子中、高剂量显著增加尿量（P<0.01），低剂量组明显增加尿量（P<0.05），但均对排汗无影响；对于消化系统，与假手术组比较，模型组大鼠胃残留率显著增加（P<0.01），胃排空率、小肠推动率显著下降（P<0.01），胃泌素（GT）明显增加（P<0.05），和模型组比较，葶苈子低剂量组显著增加小肠推动率（P<0.01），中、高剂量组可显著增加胃排空率、小肠推动率（P<0.01），显著减少胃残留率（P<0.01），显著或显著减少GT以促进胃肠运动及胃肠道的运输（P<0.01），增加胃动素（MTL）促进大鼠的胃排空（P<0.05，P<0.01）；对于循环系统，与假手术组比较，大鼠左室射血分数（LVEF）、左室短轴缩短率（LVFS）、心输出量（CO）显著降低（P<0.01），模型组大鼠的心率有升高趋势，收缩压（SBP）显著升高（P<0.01），舒张压（DBP）明显升高（P<0.05）；与模型组比较，葶苈子低剂量组明显增加LVEF、降低大鼠的DBP（P<0.05），葶苈子中剂量组显著增加LVEF、LVFS、CO和SBP（P<0.01），明显降低大鼠的DBP（P<0.05），葶苈子高剂量组显著增加LVFS（P<0.01），显著降低大鼠的SBP（P<0.01），明显降低大鼠的DBP（P<0.05）；对于中枢系统，与假手术组比较，模型组大鼠站立次数显著降低（P<0.01），葶苈子明显减少大鼠的运动距离、运动时间、站立次数和在旷场中心活动时间，增加静止时间和旷场边缘活动时间（P<0.05，P<0.01）；此外，与假手术组比较，模型组大鼠肺管腔周围的炎症浸润严重，气管增厚、内有水肿液聚集，肺组织破坏严重，血中白细胞计数、中性粒细胞比例显著增加（P<0.01），单核细胞比例明显增加（P<0.05），肺泡灌洗液中γ干扰素（IFN-γ）显著降低（P<0.01），白细胞介素-4（IL-4）明显提高（P<0.05）、免疫球蛋白E（IgE）水平显著升高（P<0.01），肺组织活性氧（ROS）水平显著升高（P<0.01），与模型组比较，葶苈子能减少白细胞计数和中性粒细胞积聚，减少肺小血管充血和肺间质水肿，降低肺泡灌洗液中IFN-γ和IL-4水平，升高IgE水平，降低肺组织ROS水平（P<0.05，P<0.01）。结论 葶苈子对病位在里的肺水肿模型具有显著改善作用，通过泻水逐饮、调节水液排泄，降泻肺气、调节气机、泻肺气之壅闭，促肺气肃降、调节气机下行，提示葶苈子作用趋势为沉降。其中以葶苈子中剂量作用最佳，其作用机制可能是通过调控中性粒细胞炎症反应来发挥干预作用的。     

The Thompson Test for Ruptured Achilles Tendon

Active plantar flexion at the ankle does not rule out an Achilles tendon rupture. The authors review an easy way to diagnose this injury promptly.     

Predictors of Total Calories Purchased at Fast-food Restaurants: Restaurant Characteristics,Calorie Awareness,and Use of Calorie Information

ObjectiveTo examine purchase patterns at fast-food restaurants and their relation to restaurant characteristics, customer characteristics, and use of calorie information.DesignCross-sectional survey.SettingFast-food restaurants in New York State.ParticipantsAdult fast-food restaurant customers (n = 1,094).Variables MeasuredRestaurant characteristics (fast-food chain type, presence of calorie labels, and poverty of location), participant characteristics (demographics, calorie knowledge, awareness, and use), and customer purchasing patterns (ordering low-calorie or no beverage, small or no fries, or < 3 items) were used as predictors of total calories purchased.AnalysisMultiple regression.ResultsIn a regression model including restaurant and customer characteristics, fast-food chain customer age, sex, calorie use, and calorie awareness were independently associated with total calories purchased (all P < .05; model R² = .19). When 3 purchasing patterns were added to the model, calorie use (P = .005), but not calorie awareness, remained associated with total calories purchased. The 3 purchase patterns collectively accounted for the majority of variance in calorie totals (Δ model R² = .40).Conclusions and ImplicationsPromoting use of calorie information, purchase strategies, and calorie awareness represents complementary ways to support lower-calorie choices at fast-food chains.