支气管哮喘患者外周血单个核细胞Toll样受体2基因表达与血清白细胞介素4和白细胞介素12的相关性分析

目的：观察支气管哮喘（简称哮喘）控制期、未控制期患者及正常对照人群中外周血单个核细胞Toll样受体2（TLR2）mRNA表达及血清白细胞介素4（IL-4）、IL-12水平,并探讨上述指标间有无相关性。方法根据全球哮喘防治创议（GINA）2006哮喘控制水平分级标准,选取门诊急诊哮喘控制期及未控制期患者各20例,选取体检健康者20名作为正常对照组。采用逆转录聚合酶链反应（ RT-PCR）法检测各组对象外周血单个核细胞TLR2 mRNA表达。用酶联免疫吸附测定（ ELISA）双抗体夹心法检测各组对象血清IL-4、IL-12水平。结果哮喘患者外周血单个核细胞 TLR2 mRNA 的表达水平高于正常对照组[（0．963±0．132）比（0．632±0．172）],差异有统计学意义（P＜0．01）。哮喘控制期与未控制期患者外周血单个核细胞TLR2 mRNA的表达水平差异无统计学意义[（0．936±0．117）比（0．991±0．147）]（ P＞0．05）。哮喘患者外周血IL-4水平高于正常对照组[（34．0±8．2）ng/L比（9．8±2．7）ng/L],差异有统计学意义（t＝13．87,P＜0．01）,未控制组患者外周血IL-4水平高于哮喘控制组[（42．5±5．4）ng/L比（29．4±4．2）ng/L]（t ＝8．53,P＜0．01）。哮喘患者外周血 IL-12水平低于正常对照组[（29．4±3．9）ng/L 比（55．8±6．1）ng/L]（t＝20．54,P＜0．01）,哮喘控制组与未控制组患者外周血IL-12水平差异无统计学意义[（28．7±4．5）ng/L比（30．1±3．0）ng/L]（t＝-1．16,P＞0．05）。哮喘患者外周血单个核细胞TLR2 mRNA表达与外周血IL-4水平呈正相关（r＝0．532,P＜0．01）,与外周血IL-12无明显相关（r＝-0．05,P＞0．05）。结论哮喘患者外周血单核细胞TLR2 mRNA的表达水平高于正常对照,外周血IL-4水平高于正常对照,未控制期外周血IL-4水平高于控制期,外周血IL-12水平低于正常对照。哮喘患者外周?     

肺炎支原体感染和哮喘患儿外周血嗜酸粒细胞计数及血清总IgE测定

目的观察肺炎支原体感染和哮喘患儿外周血嗜酸粒细胞计数并分别测定血清总IgE，以探讨肺炎支原体感染和意气管哮喘发病的关系。方法对支原体肺炎伴喘息者25例、支原体肺炎不伴喘息者45例、支气管哮喘患者30例、正常健康体检儿童30例，分别行外周血嗜酸细胞计数及血清总IgE检测。结果支原体肺炎伴喘息组外周血嗜酸粒细胞增高率92．0％、血清总IGE（377．9±94．0）IU／ml，显著高于支原体肺炎不伴喘息组的8．9％和（155．2±66．5）IU／ml，亦显著高于正常对照组的6．7％和（152．1±74．6）IU／ml，接近于支气管哮喘组的93．3％和（405．7±84．0）IU／ml。结论感染肺炎支原体后容易出现喘息症状，外周血嗜酸粒细胞增高，血清总IgE水平增高，肺炎支原体感染可能诱发小儿哮喘。     

支气管哮喘患者诱导痰中白细胞介素-25、嗜酸性粒细胞水平及其意义

目的 探讨支气管哮喘患者诱导痰中白细胞介素-25(IL-25)、嗜酸性粒细胞(EOS)在支气管哮喘发病中的作用.方法选择急性发作期支气管哮喘患者30例(哮喘组)、其中经治疗后23例患者病情缓解(缓解组)、同期健康体检者20例作为对照组,均采用超声雾化吸入梯度高渗盐水法采集诱导痰标本,以ELISA法测定诱导痰中IL-25水平,计数EOS,并分析两者相关性.结果 哮喘组诱导痰中IL-25及EOS水平均显著高于对照组[(313.12±75.64)ng/L与(236.43±57.90) ng/L、(0.386±0.267)×109/L与(0.005±0.002)×109/L,t=16.77、19.28,均P＜0.05],且急性发作期显著高于缓解期[(268.63±40.19) ng/L、(0.120±0.016)×109/L](t=11.65、12.37,均P＜0.05).结论 IL-25、EOS在哮喘发生、发展中具有重要作用,为监测和治疗提供了一种新的思路.     

支气管哮喘患者气道中白细胞介素-17表达与气道重塑关系的研究

目的初步探讨白细胞介素(IL)-17在支气管哮喘患者气道重塑中的作用。方法选取2007年9月至2008年9月门诊行气管镜检查的非急性发作期支气管哮喘患者40例,按肺功能测定结果分为2组。采用免疫组织化学方法分别检测其支气管肺泡灌洗液中肺泡巨噬细胞及气道上皮细胞的IL-17及转化生长因子(TGF)-β1的表达。采用方差分析和SNK-q检验进行统计学分析。结果支气管肺泡灌洗液肺泡巨噬细胞和气道上皮细胞中IL-17表达试验组分别为(0.361±0.190)和(0.306±0.014),较对照组[分别为(0.206±0.020)和(0.196±0.031)]明显升高,差异均有统计学意义(P<0.01);而TGF-β1表达试验组分别为(0.280±0.018)和(0.274±0.004),较对照组[分别为(0.206±0.006)和(0.193±0.015)]明显升高,差异均有统计学意义(P<0.01)。结论 IL-17可能在支气管哮喘气道重塑的发生发展中发挥作用。     

支气管哮喘患者诱导痰中白细胞介素-9水平及其与气道炎症的关系

目的探讨支气管哮喘患者诱导痰中白细胞介素-9（IL-9）的水平及其与炎症细胞和肺功能的关系。方法分别选择28例支气管哮喘急性发作患者（哮喘急性发作组）和28例健康对照（健康对照组）,分别检测哮喘急性发作期和治疗后缓解期及健康对照组的肺功能;并用酶联免疫吸附实验（ELISA）测定诱导痰上清液中IL-9的水平。结果哮喘发作组患者诱导痰中IL-9水平明显高于哮喘缓解期,比较差异有统计学意义（P〈0.05）,哮喘发作组和缓解期组痰中IL-9水平高于健康对照组,比较差异有统计学意义（P〈0.05）。哮喘发作组患者诱导痰中IL-9水平与中性粒细胞数及嗜酸性粒细胞数均呈正相关（r值分别为0.68、0.81,P〈0.05）,与第一秒用力呼气容积占预计值的百分比（FEV%）呈负相关（r=-0.65,P〈0.05）。结论支气管哮喘患者诱导痰中增高的IL-9水平与其气道炎症和气流受限有关。     

Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma

BACKGROUND AND PURPOSE

IL-13 is a pleiotropic Th2 cytokine considered likely to play a pivotal role in asthma. Here we describe the preclinical in vitro and in vivo characterization of CAT-354, an IL-13-neutralizing IgG4 monoclonal antibody (mAb), currently in clinical development.

EXPERIMENTAL APPROACH

In vitro the potency, specificity and species selectivity of CAT-354 was assayed in TF-1 cells, human umbilical vein endothelial cells and HDLM-2 cells. The ability of CAT-354 to modulate disease-relevant mechanisms was tested in human cells measuring bronchial smooth muscle calcium flux induced by histamine, eotaxin generation by normal lung fibroblasts, CD23 upregulation in peripheral blood mononuclear cells and IgE production by B cells. In vivo CAT-354 was tested on human IL-13-induced air pouch inflammation in mice, ovalbumin-sensitization and challenge in IL-13 humanized mice and antigen challenge in cynomolgus monkeys.

KEY RESULTS

CAT-354 has a 165 pM affinity for human IL-13 and functionally neutralized human, human variant associated with asthma and atopy (R130Q) and cynomolgus monkey, but not mouse, IL-13. CAT-354 did not neutralize human IL-4. In vitro CAT-354 functionally inhibited IL-13-induced eotaxin production, an analogue of smooth muscle airways hyperresponsiveness, CD23 upregulation and IgE production. In vivo in humanized mouse and cynomolgus monkey antigen challenge models CAT-354 inhibited airways hyperresponsiveness and bronchoalveolar lavage eosinophilia.

CONCLUSIONS AND IMPLICATIONS

CAT-354 is a potent and selective IL-13-neutralizing IgG4 mAb. The preclinical data presented here support the trialling of this mAb in patients with moderate to severe uncontrolled asthma.     

急性危重型哮喘抢救的经验及教训(附39例报告)

目的：本文旨在探索急性危重型哮喘抢救的经验及教训。方法：观察并分析了３９例住院患者。结果：抢救成功３５例，成功率８９７％（３５／３９）；死亡４例，占同期住院哮喘患者的５１３％（４／８４）。结论：及时正确地评估病情，合理应用糖皮质激素等药物，适时建立人工通气等均是抢救成败的关键。而血糖浓度的监测对于指导糖皮质激素量的应用有一定的意义。     

舒血宁注射液对重症哮喘患者肺功能及氧化应激状态的影响

目的观察舒血宁注射液对重症哮喘患者肺功能及氧化应激状态的影响。方法 71例重症哮喘患者随机分成治疗组(36例)及对照组(35例)。对照组给予氧疗、常规疗法;治疗组在常规治疗的基础上给予舒血宁注射液20 mL稀释后静滴,1次/d,疗程为14 d。观察治疗前后两组患者的疗效、肺功能、血气指标及血清SOD、GSH-Px浓度变化。结果治疗组的有效率高于对照组(82.86%vs.57.57%,P<0.01)。治疗前,两组患者FEV1占预计值%、FEV1/FVC%、血气指标及血清SOD、GSH-Px浓度比较差异无统计学意义。治疗后,治疗组FEV1占预计值%、FEV1/FVC%、PO2及血清SOD、GSH-Px浓度较对照组升高(P<0.05或P<0.01),PCO2下降(P<0.05或P<0.01)。血清SOD与FEV1占预计值%、FEV1/FVC%及PO2呈明显正相关(r=0.632、0.756、0.706,P<0.01),与PCO2呈明显负相关(r=-0.878,P<0.01);血清GSH-Px浓度与FEV1占预计值%、FEV1/FVC%及PO2呈明显正相关(r=0.721、0.747、0.699,P<0.01),与PCO2呈明显负相关(r=-0.733,P<0.01)。结论舒血宁注射液联合常规疗法可在一定程度上改善重症哮喘患者的肺功能,其可能通过抗氧化、改善氧化应激状态发挥作用。     

The economic value of anti-IgE in severe persistent,IgE-mediated (allergic) asthma patients:adaptation of INNOVATE to Sweden

ABSTRACT

Background: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma.

Methods: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an ‘optimized asthma control’ state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time.

Results: Total lifetime discounted costs and QALYs on ST were €52?702 and 11.60. Omalizumab add-on therapy cost an additional €42?754 for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of €56?091. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [€31?328; €120?552]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates.

Conclusions: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.     

Pharmacokinetics,pharmacodynamics and clinical efficacy of omalizumab for the treatment of asthma

Introduction: Omalizumab is a subcutaneously administrated monoclonal anti-IgE antibody indicated in adults, adolescents and children 6 years of age and older with moderate to severe allergic asthma uncontrolled by conventional pharmacological treatments and sensitization to at least one perennial allergen.

Area covered: This drug evaluation summarizes published data on pharmacokinetic and pharmacodynamic properties of omalizumab, on clinical efficacy and safety, including real-world evidence, and provides a medico-economic evaluation of the drug.

Expert opinion: Omalizumab represents an efficient therapeutic option for the management of patients with uncontrolled moderate/severe allergic asthma. It provides a significant reduction in the asthma exacerbation rate with a steroid-sparing effect, an improvement in quality of life in adults and adolescents, despite a lack of evidence about its efficacy specifically in severe allergic asthma. Clinical trials have demonstrated its efficacy in the pediatric population but further real-life evidence is expected to better characterize long-term effects in this population. There is still some debate about the optimal treatment duration but, to date, it is recommended not to stop the treatment as cessation has resulted in symptom recurrence. Omalizumab is an expensive treatment, but a key therapeutic option when used for uncontrolled severe allergic asthma.     

Efficacy of cariprazine across symptom domains in patients with acute exacerbation of schizophrenia: Pooled analyses from 3 phase II/III studies

Schizophrenia affects various symptom domains, including positive and negative symptoms, mood, and cognition. Cariprazine, a dopamine D₃/D₂ receptor partial agonist and serotonin 5-HT_1A receptor partial agonist, with preferential binding to D₃ receptors, is approved for the treatment of adult patients with schizophrenia (US, Europe) and mania associated with bipolar I disorder (US). For these investigations, data were pooled from 3 positive, 6-week, double-blind, placebo-controlled, phase II/III trials of cariprazine in patients with acute exacerbation of schizophrenia (NCT00694707, NCT01104766, NCT01104779); 2 trials were fixed-dose and 1 trial was flexible-dose. Post hoc analyses evaluated mean change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) -derived symptom factors (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, anxiety/depression) and PANSS single items for cariprazine (1.5–9.0?mg/d) versus placebo. P values were not adjusted for multiple comparisons. At week 6, statistically significant differences versus placebo were seen for cariprazine on all 5 PANSS factors (P?<?0.01 all). Effects sizes ranged from 0.21 (anxiety/depression) to 0.47 (disorganized thought). Dose-response analysis from the fixed-dose studies found significant differences for all cariprazine doses (1.5, 3.0, 4.5, and 6.0?mg/d) versus placebo in PANSS total score, and in negative symptom and disorganized thought factor scores (P?<?0.001). Differences between cariprazine and placebo were also statistically significant on 26 of 30 PANSS single items (P?<?0.05). In these post hoc analyses, cariprazine was effective versus placebo in improving all 5 PANSS factor domains, suggesting that it may have broad-spectrum efficacy in patients with acute schizophrenia.     

非小细胞肺癌患者外周血中EGFR基因突变与埃克替尼治疗效果的相关性

目的 探讨非小细胞肺癌（NSCLC）患者外周血液中表皮生长因子受体（EGFR）基因突变与埃克替尼治疗效果的相关性。方法 选取洛阳市第三人民医院自2014年2月-2018年2月收治的101例NSCLC患者作为实验对象,采用RT-PCR技术检测外周血液中EGFR基因突变情况,依据测定结果分为基因突变组和野生型组,均采用埃克替尼治疗分析其治疗效果;选取同期做健康体检的患者50例作为对照组,比较NSCLC患者与健康人外周血液中EGFR突变差异。结果 50例健康人外周血液检测EGFR基因突变率为0,NSCLC患者中EGFR基因突变率为41.58%（42例）,EGFR野生型组患者31.68%（32例）,EGFR基因未突变者27例。基因突变组患者疾病控制率为85.71%,治疗有效率为64.29%;野生型组疾病控制率为59.38%,总有效率仅为12.5%,数据差异有统计学意义（P<0.05）。随访6个月内两组患者生存率差异无统计学意义,随访1、2年间EGFR基因突变组的生存率均远高于野生型组,数据差异有统计学意义（P<0.05）。结论 NSCLC患者外周血中EGFR基因突变患者行埃克替尼治疗效果更高,因此在晚期的NSCLC患者治疗中可以通过测定是否EGFR基因突变来指导靶向药物治疗。     

老年重症肺炎患者血清中炎症细胞因子及髓样分化因子88水平与预后的关系

目的 探讨老年重症肺炎患者血清中炎症细胞因子、髓样分化因子88(myeloid differentiation factor 88,MyD88)水平与预后的关系。方法选择2018年5月～2021年4月在某院ICU诊治的老年重症肺炎患者68例作为肺炎组,选择同期老年健康体检者68例为健康组,检测两组血清白细胞介素（Interleukin,IL）-1β、IL-8、MyD88水平,调查患者的急性生理学和慢性健康状况Ⅱ（acute physiology and chronic health evaluation Ⅱ,APACHEⅡ）评分、预后并进行相关性分析。结果 肺炎组的血清IL-1β、IL-8、MyD88水平都高于健康组（P <0.05）。在肺炎组中,APACHE Ⅱ评分为（24.51±1.58）分,Pearson相关分析显示APACHEⅡ评分与IL-1β、IL-8、MyD88相关（P <0.05）。Logistic回归分析显示IL-1β、IL-8、MyD88为导致患者预后不良的危险因素（P <0.05）。ROC曲线分析显示IL-1β、IL-8、MyD88水平预测患者预后...     

支气管哮喘患儿血清SIL-2R和T淋巴细胞亚群的相关性探讨

目的 探讨血清可溶性白细胞介素-2受体(SIL-2R)和T淋巴细胞亚群在支气管哮喘患儿中的作用.方法 应用双抗体夹心ELISA法和单克隆抗体法对32例支气管哮喘患儿进行了血清SIL-2R和T淋巴细胞亚群的测定,并以35名正常人作对照.结果 支气管哮喘患儿在治疗前血清SIL-2R水平非常显著地高于正常人组(P＜0.01),至恢复期虽然SIL-2R水平有所下降,但与正常人组比较差异仍有显著性(P＜0.01).SIL-2R水平与T淋巴细胞亚群中CD8细胞比值密切相关.结论 检测支气管哮喘患儿血清SIL-2R和T淋巴细胞亚群水平可以作为患者病情变化、预后判断的重要检测指标.     

Safety and efficacy of teneligliptin in Japanese patients with type 2 diabetes mellitus: a pooled analysis of two Phase III clinical studies

Objective: To assess the safety and efficacy of long-term administration of teneligliptin alone and in combination with oral antidiabetic drugs in Japanese type 2 diabetes mellitus (T2DM) patients with insufficient glycemic control.

Methods: This post-hoc pooled analysis used data from two Phase III clinical studies involving 702 Japanese patients. We evaluated teneligliptin as monotherapy and combined with a sulfonylurea, glinide, biguanide, or α-glucosidase inhibitor. Safety measures included adverse events (AEs), adverse reactions and hypoglycemia. The main efficacy measure was the change in glycated hemoglobin (HbA_1c) from baseline.

Results: Incidences of AEs and adverse reactions were similar among the teneligliptin monotherapy group and all combination therapy groups except the combination with sulfonylurea. Hypoglycemia was more frequent in the sulfonylurea combination therapy group than in other groups. Teneligliptin administered once daily as monotherapy or combination therapy resulted in a decrease in HbA_1c, which was maintained for 52 weeks. Bodyweight showed no change or a slight increase at the end of 52 weeks in all groups.

Conclusions: This pooled analysis provides evidence for the safety and efficacy of long-term use of teneligliptin as monotherapy or combination therapy in Japanese T2DM patients.     

无创通气对支气管哮喘急性发作的疗效及对血清CRP、IL-6的影响

目的 探讨无创机械通气对支气管哮喘急性发作的临床疗效及其可能机制.方法 选择2013年6月至2015年12月间在本院确诊并治疗的中重度支气管哮喘急性发作的患者作为研究对象,随机分为试验组及对照组.两组患者均接受常规治疗,试验组在此基础上进行无创机械通气,共3d.比较两组患者治疗前后,第一秒用力呼气容积(FEVl)、FEVl/用力呼气肺活量(FVC)、呼气峰流量(PEF)、血清C-反应蛋白(C-reactive protein,CRP)、白细胞介素-6(IL-6)及临床症状改善情况.结果 治疗后,试验组平均喘息缓解时间、平均哮鸣音消失时间及平均住院时间均显著短于对照组,两组比较差异有统计学意义(P＜0.05).两组患者治疗后,FEV1、FEVl/FVC％及PEF均较治疗前显著改善,但试验组改善程度更大,两组比较差异均有统计学意义(P＜0.05).两组患者血清中CRP及IL-6均显著下降,但试验组下降程度更大,两组比较差异均有统计学意义(P＜0.05).结论 无创通气可有效改善支气管哮喘急性发作期的临床症状及肺功能,值得临床推广.     

The rationale,efficacy and safety evidence for tegaserod in the treatment of irritable bowel syndrome

A growing body of evidence implicates abnormal serotonergic regulation of gastrointestinal function in the pathogenesis of the irritable bowel syndrome (IBS). Drugs targeting this system are therefore attractive concepts. The partial 5-HT₄ receptor agonist tegaserod might be predicted to have positive therapeutic effects on a constipated and uncomfortable gut. However, IBS runs a chronic, benign course and carries no associated mortality, so it is imperative that the safety profile of new pharmacological agents made available to physicians is exemplary. The authors review the evidence for 5-HT in the aetiology of IBS and its symptoms, and the data available concerning the partial 5-HT₄ receptor agonist tegaserod, in terms of rationale, efficacy and safety.     

哮喘、慢性阻塞性肺病患者血清IL-18和总IgE水平的相关性

目的 探讨IL-18、总IgE、Th1和Th2类细胞因子在哮喘、慢性阻塞性肺病(COPD)发病时血清水平的变化及其相关性.方法 随机收集哮喘急性发作期患者50例(哮喘组),老年COPD急性加重期患者80例(COPD组),健康者50例(对照组)血清,采用双抗体夹心酶联免疫吸附试验检测血清IL-18、总IgE、IL-8、IL-4、IFN-γ水平.结果 CDPD组急性期IL-18、IL-8、IL-4、IFN-γ水平分别高于对照组1.8、25.2、116、150.8倍.哮喘组IL-18、IL-8、IL-4分别高于对照组29.9、3.4、5.2倍.哮喘组血清总IgE水平高于对照组223.2倍,而COPD组血清总IgE水平与对照组相比无显著性差异.COPD血清中IL-18与IL-8、IFN-γ,IL-8与IL-4呈正相关;哮喘组IL-18与IL-8、IL-4、总IgE,IL-4与总IgE呈正相关.结论 高血清IL-18提示细胞闪子参与哮喘及COPD的发病过程.哮喘发作时IL-18与总IgE正相关,而在COPD急性加重期无相关性,表明COPD和哮喘是两类有不同发生机制的气道炎症.     

重症感染患者病情危重程度与血清降钙素原、C-反应蛋白及血小板的相关性分析

目的 探讨重症感染患者病情危重程度与血清降钙素原、C-反应蛋白及血小板的相关性,以期降低感染率和感染程度.方法 回顾性分析2012年6月至2015年10月重症感染患者56例,作为研究组,其中13例住院期间死亡(死亡组),余均好转(好转组).以同时期上呼吸道感染52例作为对照组,抽取静脉血,观察在不同组别、不同时间点血清降钙素原、C-反应蛋白及血小板计数变化情况,并以APACHEⅡ评分作为感染程度与以上3个指标相关性.结果 研究组在降钙素素原、C-反应蛋白上显著高于对照组,而在血小板上则显著低于对照组,2组比较差异有统计学意义(P<0.05);入院第1天死亡组和好转组在C-反应蛋白、血小板上比较差异无统计学意义(P>0.05);而降钙素原则好转组显著低于死亡组(P<0.05),入院后第3天、入院后第7天在降钙素原、C-反应蛋白上死亡组显著高于好转组,在血小板上则显著低于好转组,2组比较差异有统计学意义(P<0.05);重症感染危重程度和降钙素原、C-反应蛋白正相关,和血小板负相关,即重症感染越危重,则降钙素原、C-反应蛋白越高,而血小板则越低(P<0.05).结论 重症感染病情危重程度和血清降钙素原、C-反应蛋白、血小板计数有相关性,结合APACHEⅡ评分可作为重要参考指标.     

A multicenter,randomized, double-blind,placebo-controlled trial to assess the efficacy and safety of single-entity,once-daily hydrocodone tablets in patients with uncontrolled moderate to severe chronic low back pain

Objectives: This multicenter, randomized, double-blind, placebo-controlled study with an enriched enrollment, randomized withdrawal design was conducted to evaluate the analgesic efficacy and safety of single-entity, once-daily hydrocodone 20 to 120 mg tablets (HYD) in opioid-naive and opioid-experienced patients with uncontrolled moderate to severe chronic low back pain (CLBP).

Research design and methods: The primary endpoint was week 12 pain intensity scores (11-point scale, 0 = no pain) using a mixed effect model with repeated measures incorporating a pattern mixture model framework. Responder analysis was a secondary endpoint. Safety was assessed.

Results: Out of 905 patients who were treated with HYD during the open-label titration period, 588 (65%) were randomized to continue to receive HYD (n = 296, 20 – 120 mg taken once daily, average daily dose 57 mg) or a matching placebo (n = 292). HYD demonstrated superior pain reduction (p = 0.0016); this result was supported by sensitivity analyses using different approaches to handling missing data. Proportions of patients achieving ≥ 30 and ≥ 50% improvement in pain from screening to week 12 also favored HYD (p = 0.0033 and 0.0225, respectively). HYD was generally well tolerated.

Conclusions: HYD was shown to be an efficacious treatment for CLBP in this study. There were no new or unexpected safety concerns detected.