左乙拉西坦治疗成人癫(疒间)临床疗效和安全性的随机对照试验

目的 评价左乙拉西坦治疗成人癫(痌)的临床疗效和安全性.方法 采用随机、双盲、双模拟、阳性药物平行对照试验设计方案,将纳入研究的120例癫(痌)受试者随机分为试验组和对照组,每组各60例.试验组给予左乙拉西坦片+丙戊酸钠缓释模拟片治疗;对照组给予丙戊酸钠缓释片+左乙拉西坦模拟片治疗.两组疗程均为26周,治疗结束后随访3个月.评定两组受试者在治疗后(治疗结束后1～3 d)及随访3个月时的总有效率、癫(痌)每周发作频率、癫(痌)发作持续时间、生活质量(QOLIE-31评分量表)及药物相关的不良反应.结果 治疗前,两组受试者的癫(痌)每周发作频率、癫(痌)发作持续时间和QOLIE-31评分比较差异均无统计学意义.治疗后及随访3个月时,试验组受试者的总有效率为95.0％(57/60)和91.7％(55/60),均分别高于对照组[71.7％(43/60),63.3％(38/60);P＜0.01].治疗后及随访3个月时,两组受试者的癫(痌)每周发作频率、癫(痌)发作持续时间和QOLIE-31评分与同组治疗前相比差异均有统计学意义(P＜0.01),两组间差异也有统计学意义(P＜0.01).治疗后两组受试者的不良反应差异无统计学意义.结论 左乙拉西坦治疗成人癫(痌)的临床疗效优于丙戊酸钠缓释片,不良反应轻微,可作为临床治疗成人癫(痌)的首选药物.     

Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial

Context  Anemia is common in critically ill patients and results in a large number of red blood cell (RBC) transfusions. Recent data have raised the concern that RBC transfusions may be associated with worse clinical outcomes in some patients. Objective  To assess the efficacy in critically ill patients of a weekly dosing schedule of recombinant human erythropoietin (rHuEPO) to decrease the occurrence of RBC transfusion. Design  A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted between December 1998 and June 2001. Setting  A medical, surgical, or a medical/surgical intensive care unit (ICU) in each of 65 participating institutions in the United States. Patients  A total of 1302 patients who had been in the ICU for 2 days and were expected to be in the ICU at least 2 more days and who met eligibility criteria were enrolled in the study; 650 patients were randomized to rHuEPO and 652 to placebo. Intervention  Study drug (40 000 units of rHuEPO) or placebo was administered by subcutaneous injection on ICU day 3 and continued weekly for patients who remained in the hospital, for a total of 3 doses. Patients in the ICU on study day 21 received a fourth dose. Main Outcome Measures  The primary efficacy end point was transfusion independence, assessed by comparing the percentage of patients in each treatment group who received any RBC transfusion between study days 1 and 28. Secondary efficacy end points identified prospectively included cumulative RBC units transfused per patient through study day 28; cumulative mortality through study day 28; change in hemoglobin from baseline; and time to first transfusion or death. Results  Patients receiving rHuEPO were less likely to undergo transfusion (60.4% placebo vs 50.5% rHuEPO; P<.001; odds ratio, 0.67; 95% confidence interval [CI], 0.54-0.83). There was a 19% reduction in the total units of RBCs transfused in the rHuEPO group (1963 units for placebo vs 1590 units for rHuEPO) and reduction in RBC units transfused per day alive (ratio of transfusion rates, 0.81; 95% CI, 0.79-0.83; P = .04). Increase in hemoglobin from baseline to study end was greater in the rHuEPO group (mean [SD], 1.32 [2] g/dL vs 0.94 [1.9] g/dL; P<.001). Mortality (14% for rHuEPO and 15% for placebo) and adverse clinical events were not significantly different. Conclusions  In critically ill patients, weekly administration of 40 000 units of rHuEPO reduces allogeneic RBC transfusion and increases hemoglobin. Further study is needed to determine whether this reduction in RBC transfusion results in improved clinical outcomes.      

Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial

CONTEXT: Adefovir dipivoxil is a nucleotide analog that has demonstrated effective antiretroviral activity against human immunodeficiency virus (HIV) with once-daily administration. OBJECTIVE: To determine if adefovir confers antiretroviral or immunologic benefit when added to stable antiretroviral therapy. DESIGN: Multicenter, 24-week, randomized, double-blind, placebo-controlled study. Enrollment was conducted from June 3, 1996, through May 6, 1997. SETTING: Thirty-three US HIV treatment centers. PARTICIPANTS: Of 1171 patients screened, 442 patients infected with HIV receiving stable antiretroviral therapy for at least 8 weeks with plasma HIV RNA greater than 2500 copies/mL and CD4+ cell count above 0.20 x 10(9)/L were randomized. INTERVENTION: Patients were randomized to receive either a single 120-mg/d dose of adefovir dipivoxil (n = 219) or an indistinguishable placebo (n = 223). All patients received L-carnitine, 500 mg/d. Open-label adefovir was offered after 24 weeks and was continued until the end of the study. MAIN OUTCOME MEASURES: Changes in HIV RNA from baseline, based on area under the curve and CD4+ cell levels, adverse events, and effect of baseline genotypic resistance on response to adefovir. RESULTS: Patients assigned to adefovir demonstrated a 0.4-log10 decline from baseline in HIV RNA compared with no change in the placebo group (P<.001), which continued through 48 weeks. CD4+ cell counts did not change. During the initial 24 weeks, elevated hepatic enzyme levels (P<.001), gastrointestinal tract complaints (P<.001), and weight loss (P<.001) were associated with use of adefovir. Between 24 weeks and 48 weeks elevations in serum creatinine occurred in 60% of patients, usually returning to baseline after discontinuation of adefovir. Patients with lamivudine or lamivudine and zidovudine resistance mutations demonstrated anti-HIV effects with adefovir (P< or =.01 vs placebo group). CONCLUSIONS: This study suggests that once-daily adefovir therapy reduces HIV RNA and is active against isolates resistant to lamivudine or lamivudine and zidovudine. Nephrotoxicity occurred when treatment extended beyond 24 weeks but was reversible.     

Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. rhNGF Clinical Investigator Group

CONTEXT: Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials. OBJECTIVE: To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial conducted from July 1997 through May 1999. SETTING: Eighty-four outpatient centers throughout the United States. PATIENTS: A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes. INTERVENTIONS: Patients were randomly assigned to receive either rhNGF, 0.1 microg/kg (n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was a change in neuropathy between baseline and week 48, demonstrated by the Neuropathy Impairment Score for the Lower Limbs, compared between the 2 groups. Secondary outcome measures included quantitative sensory tests using the CASE IV System, the Neuropathy Symptom and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global symptom assessment, as well as nerve conduction studies and occurrence of new plantar foot ulcers. Patients also were evaluated for presence of adverse events. RESULTS: Among patients who received rhNGF, 418 (83%) completed the regimen compared with 461 (90%) who received placebo. Administration of rhNGF was safe, with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes. However, neither the primary end point (P =.25) nor most of the secondary end points demonstrated a significant benefit of rhNGF. Exceptions were the global symptom assessment (P =.03) and 2 of 32 comparisons within the PBQ, which showed a modest but significant benefit of rhNGF (P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs). CONCLUSION: Unlike previous phase 2 trials, this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy. JAMA. 2000;284:2215-2221.     

Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial

Context  Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder. Objective  To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity. Design  Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997. Setting  Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers. Patients  A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault). Intervention  Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93). Main Outcome Measures  Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression–Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results  Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P=.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01). Conclusions  Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.      

Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial

Context  Children with familial hypercholesterolemia have endothelial dysfunction and increased carotid intima-media thickness (IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention therapy in the causal pathway of this disorder has been available for more than a decade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. Objective  To determine the 2-year efficacy and safety of pravastatin therapy in children with familial hypercholesterolemia. Design  Randomized, double-blind, placebo-controlled trial that recruited children between December 7, 1997, and October 4, 1999, and followed them up for 2 years. Setting and Participants  Two hundred fourteen children with familial hypercholesterolemia, aged 8 to 18 years and recruited from an academic medical referral center in the Netherlands. Intervention  After initiation of a fat-restricted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n = 106), or a placebo tablet (n = 108). Main Outcome Measures  The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 years; the principal safety outcomes were growth, maturation, and hormone level measurements over 2 years as well as changes in muscle and liver enzyme levels. Results  Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean [SD], –0.010 [0.048] mm; P = .049), whereas a trend toward progression was observed in the placebo group (mean [SD], +0.005 [0.044] mm; P = .28). The mean (SD) change in IMT compared between the 2 groups (0.014 [0.046] mm) was significant (P = .02). Also, pravastatin significantly reduced mean low-density lipoprotein cholesterol levels compared with placebo (–24.1% vs +0.3%, respectively; P<.001). No differences were observed for growth, muscle or liver enzymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Conclusion  Two years of pravastatin therapy induced a significant regression of carotid atherosclerosis in children with familial hypercholesterolemia, with no adverse effects on growth, sexual maturation, hormone levels, or liver or muscle tissue.      

早期胃肠康复治疗机械通气的脓毒症伴急性胃肠损伤患者的有效性和安全性:34例前瞻性、随机对照、先导试验

目的 探讨早期胃肠康复治疗机械通气的脓毒症伴急性胃肠损伤（AGI）患者的疗效和安全性。方法 采用前瞻性、随机、平行对照的研究方法,开放设计,对康复评定人设盲。筛选2017年5月~2018年3月在广州市一家三级甲等教学医院重症监护病房（ICU）住院的脓毒症患者,符合纳入标准则招募入组。以急性生理和慢性健康状况评分Ⅱ（APACHE Ⅱ）等为平衡因素,区组随机化分为干预组和对照组。两组均按脓毒症标准方案治疗,干预组增加早期胃肠康复。主要研究终点为AGI治愈;次要研究终点包括ICU住院病死率、机械通气预后、ICU住院天数等。数据采集时间点定为入组、呼吸机脱机、转出ICU共3个。结果 共招募 60例患者,34例完成研究。干预组 16例,对照组 18例。结果显示,康复治疗后,干预组和对照组 AGI治愈例数的差异无统计学意义（P>0.05）。比较康复治疗前后两组AGI评分的下降值,分别为（-1.9±2.1）分和（0.9±1.6）分,差异有统计学意义（P<0.05）。早期胃肠康复的不良事件发生率为3.33%,无器官损伤或意外死亡等严重不良事件。两组在ICU住院病死率、机械通气预后、ICU住院天数等指标方面,差异均无统计学意义（P>0.05）。结论 早期胃肠康复不能降低AGI患病率,但降低AGI评分,改善胃肠道症状,安全性好,但需在设计更为合理的大样本多中心临床研究中证实。     

Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial

Context  Echinacea is a widely used herbal remedy for treatment of upper respiratory tract infections (URIs). However, there are few data on the efficacy and safety of echinacea in treating URIs in children. Objectives  To determine if Echinacea purpurea is effective in reducing the duration and/or severity of URI symptoms in children and to assess its safety in this population. Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial of healthy children 2 to 11 years old recruited from a regional practice-based network and an alternative medical center in 4-month periods from 2000 through 2002. Interventions  Study patients were randomized to receive either echinacea or placebo for up to 3 URIs over a 4-month period. Study medication was begun at the onset of symptoms and continued throughout the URI, for a maximum of 10 days. Main Outcome Measures  Primary outcomes were duration and severity of symptoms and adverse events recorded by parents; secondary outcomes included peak severity of symptoms, number of days of peak severity, number of days of fever, and a global assessment of severity of symptoms by parents of study children. Results  Data were analyzed on 707 URIs that occurred in 407 children, including 337 URIs treated with echinacea and 370 with placebo. There were 79 children who completed their study period without having a URI. The median duration of URIs was 9 days (95% confidence interval, 8-10 days); there was no difference in duration between URIs treated with echinacea or placebo (P = .89). There was also no difference in the overall estimate of severity of URI symptoms between the 2 treatment groups (median, 33 in both groups; P = .69). In addition, there were no statistically significant differences between the 2 groups for peak severity of symptoms (P = .68), number of days of peak symptoms (1.60 in the echinacea group and 1.64 in the placebo group; P = .97), number of days of fever (0.81 in the echinacea group vs 0.64 in the placebo group; P = .09), or parental global assessment of severity of the URI (P = .67). Overall, there was no difference in the rate of adverse events reported in the 2 treatment groups; however, rash occurred during 7.1% of the URIs treated with echinacea and 2.7% of those treated with placebo (P = .008). Conclusions  Echinacea purpurea, as dosed in this study, was not effective in treating URI symptoms in patients 2 to 11 years old, and its use was associated with an increased risk of rash.      

Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group

CONTEXT: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. DESIGN: Randomized, placebo-controlled, double-blind study conducted January through March 1998. SETTING: Sixty primary care and university health centers throughout the United States. PARTICIPANTS: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. INTERVENTIONS: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). MAIN OUTCOME MEASURES: Duration and severity of illness in individuals infected with influenza. RESULTS: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). CONCLUSIONS: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.     

Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial

CONTEXT: Activation of the coagulation system and depletion of endogenous anticoagulants are frequently found in patients with severe sepsis and septic shock. Diffuse microthrombus formation may induce organ dysfunction and lead to excess mortality in septic shock. Antithrombin III may provide protection from multiorgan failure and improve survival in severely ill patients. OBJECTIVE: To determine if high-dose antithrombin III (administered within 6 hours of onset) would provide a survival advantage in patients with severe sepsis and septic shock. DESIGN AND SETTING: Double-blind, placebo-controlled, multicenter phase 3 clinical trial in patients with severe sepsis (the KyberSept Trial) was conducted from March 1997 through January 2000. PATIENTS: A total of 2314 adult patients were randomized into 2 equal groups of 1157 to receive either intravenous antithrombin III (30 000 IU in total over 4 days) or a placebo (1% human albumin). MAIN OUTCOME MEASURE: All-cause mortality 28 days after initiation of study medication. RESULTS: Overall mortality at 28 days in the antithrombin III treatment group was 38.9% vs 38.7% in the placebo group (P =.94). Secondary end points, including mortality at 56 and 90 days and survival time in the intensive care unit, did not differ between the antithrombin III and placebo groups. In the subgroup of patients who did not receive concomitant heparin during the 4-day treatment phase (n = 698), the 28-day mortality was nonsignificantly lower in the antithrombin III group (37.8%) than in the placebo group (43.6%) (P =.08). This trend became significant after 90 days (n = 686; 44.9% for antithrombin III group vs 52.5% for placebo group; P =.03). In patients receiving antithrombin III and concomitant heparin, a significantly increased bleeding incidence was observed (23.8% for antithrombin III group vs 13.5% for placebo group; P<.001). CONCLUSIONS: High-dose antithrombin III therapy had no effect on 28-day all-cause mortality in adult patients with severe sepsis and septic shock when administered within 6 hours after the onset. High-dose antithrombin III was associated with an increased risk of hemorrhage when administered with heparin. There was some evidence to suggest a treatment benefit of antithrombin III in the subgroup of patients not receiving concomitant heparin.     

严重脓毒症免疫炎症反应紊乱及双向免疫调节的前瞻性随机对照研究

目的 分析严重脓毒症患者的免疫炎症反应紊乱状态,探讨连续血液净化、α1胸腺肽以及两者联用对免疫炎症反应紊乱及预后的影响.方法 年龄18岁、Marshall评分>5分的严重脓毒症患者91例,监测血清白细胞介素(IL)-6、IL-10、TNFα水平和单核细胞人白细胞DR抗原(HLA-DR)、T淋巴细胞计数的动态变化;并随机分为血液净化组、胸腺肽组、联合组和对照组.血液净化组连续3 d应用连续性肾脏替代治疗(cRRT)或分子吸附再循环系统(MARS)治疗,同时给予经典SSC治疗;胸腺肽组皮下注射α1胸腺肽1.6 mg/d,连续7 d,同时给予经典SSC治疗;联合组:联合应用血液净化组和胸腺肽组治疗方案;对照组给予经典SSC治疗.观察患者治疗前及治疗后3、7 d以上免疫炎症指标及临床预后.结果 与健康对照组比较,严重脓毒症患者血清IL-6、IL-10、IL-6/IL-10和TNFα明显升高,HLA-DR、CD+3、CD+4;和CD+8T淋巴细胞明显降低(P<0.05或P<0.01),与存活者比较,死亡患者血清IL-6、IL-6/IL-10、TNFα、HLA-DR、CD+4、CD+4和CD+8;变化更明显(P<0.05或P<0.01).与对照组同期比较,胸腺肽组治疗后7d CD+3;明显升高(P<0.05),血液净化组和联合组治疗后7 d IL-6、IL-6/IL-10和TNFα均明显下降,HLA-DR、CD+3、CD+4和CD+8均明显增高,且联合组治疗后3 d TNFα已有明显下降,CD+3和CD+4就已明显升高(P<0.05或P<0.01);与胸腺肽组同期比较,血液净化组和联合组所有指标均有改善,但仅联合组治疗后3 d CD+3;明显升高,治疗后7 dIL-6/IL-10明显下降(P<0.05);3个治疗组28 d内机械通气时间、ICU停留时间均有缩短,28 d病死率和90 d病死率均有下降,其中血液净化组ICU停留时间、联合组28 d内机械通气时间和ICU停留时间明显缩短(P<0.05).结论 严重脓毒症患者全身炎症反应和免疫抑制同时存在;α1胸腺肽具有免疫增强的作用,连续血液净化具有抗炎和免疫增强双向调节作用;两者均可改善患者临床预后,且联用后效果更好.     

Preparation and characterization of monoclonal antibody against recombinant human tissue factor pathway inhibitor

OBJECTIVE: To prepare and identify monoclonal antibody (McAb) against recombinant human tissue factor pathway inhibitor (rhTFPI) and to use it for measurement of TFPI by ELISA, and to evaluate the effects of the McAb on dilute prothrombin time (PT) and activated partial thromboplastin time (APTT). METHODS: After intrasplenic immunization of Balb/c mouse with TFPI, hybridoma technique was used to raise monoclonal antibody against rhTFPI. The McAb was well-characterized and labelled with horseradish peroxidase (HRP) by using assay of TFPI in ELISA. Furthermore, the McAb was added to normal and factor IX deficient plasma for observation of dilute PT and APTT. RESULTS: Two hybridomas (4F4, 4F8) secreting McAb against TFPI were established. The Ig class and subclass of the McAb purified from 4F8 was IgG1. Immunoblotting results indicated that the McAb4F8 only recognized a single band of TFPI with molecular weight of 34.8 KD. The results of Sandwich enzyme-linked immunosorbent assay (ELISA) by using the HRP labelled McAb4F8 showed that the mean of TFPI in normal human plasma is 103.2 +/- 11.5 micrograms/L. The McAb 4F8 was also proved to shorten markedly dilute prothrombin time of factor IX deficient plasma and normal plasma. CONCLUSIONS: We established two hybridomas cell lines (4F4, 4F8) and obtained the McAb4F8 against TFPI and reported the levels of TFPI in healthy adult human plasma by Sandwich ELISA with HRP labelled McAb4F8 in Chinese.     

胰腺癌患者血浆组织因子和组织因子途径抑制物水平的变化及其意义

目的 观察胰腺癌患者血浆组织因子(TF)和组织因子途径抑制物(TFPI)的水平变化,并分析它们之间的相关性,探讨凝血因子在胰腺癌病程中的临床意义.方法 应用ELISA法分别检测46例胰腺癌患者和30例正常对照者血浆TF和TFPI的水平,并结合临床病理资料进行分析.结果 胰腺癌转移组患者血浆TF和TFPI水平显著高于非转移组和对照组(P<0.05),非转移组血浆TFPI水平亦显著高于对照组(P<0.05);胰腺癌患者手术前血浆TF和TFPI水平均明显高于对照组,术后2周水平回落并基本恢复正常;术后复发患者血浆TF和TFPI水平又明显升高.结论 胰腺癌患者血浆TF和TFPI水平的变化与疾病的发生、发展及侵袭转移密切相关.     

Efficacy,safety, and cost-effectiveness of triple therapy in preventing relapse in rheumatoid arthritis: A randomized controlled trial (ESCoRT study)

Background:Biological agents, such as tumor necrosis factor inhibitors (TNFi), have been widely used in rheumatoid arthritis (RA) patients and greatly improved goal achievement. The aim of this study was to investigate whether conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combination was better in reducing relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi plus MTX in RA patients who achieved low disease activity (LDA) with TNFi and MTX therapy.Methods:RA patients who failed to csDMARDs received an induction therapy of MTX plus TNFi for maximally 12 weeks. Those achieving LDA in 12 weeks were randomly assigned at a 1:1:1 ratio into three groups: (A) adding hydroxychloroquine and sulfasalazine for the first 12 weeks and then discontinuing TNFi for the following 48 weeks; (B) maintaining TNFi and MTX for 60 weeks; and (C) maintaining TNFi and MTX for the first 12 weeks and then discontinuing TNFi for the following 48 weeks. The primary outcome was relapse.Results:A total of 117 patients were enrolled for induction therapy and 67 patients who achieved LDA within 12 weeks were randomized, with 24, 21, and 22 patients in groups A, B, and C, respectively. The relapse rates of groups A and B during the entire 60 weeks were comparable [10/22 (45.5%) vs. 7/20 (35.0%), χ² = 0.475, P = 0.491], however, significantly lower than that of group C [10/22 (45.5%) vs. 17/20 (85.0%), χ² = 5.517, P = 0.019; 7/20 (35.0%) vs. 17/20 (85.0%), χ² = 11.035, P = 0.004, respectively]. Taking RMB 100,000 Yuan as the threshold of willingness to pay, compared to MTX monotherapy (group C), both TNFi maintenance and triple csDMARDs therapies were cost-effective, but triple csDMARDs therapy was better.Conclusion:For RA patients who have achieved LDA with TNFi and MTX, csDMARDs triple therapy was a cost-effective option in favor of reducing relapse.Trial registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT02320630","term_id":"NCT02320630"}}NCT02320630.     

Efficacy and safety of tauroursodeoxycholic acid in the treatment of liver cirrhosis: A double-blind randomized controlled trial

No direct comparison of tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA) has yet been carried out in the treatment of liver cirrhosis in China. We designed a double-blind randomized trial to evaluate the potential therapeutic efficacy of TUDCA in liver cirrhosis, using UDCA as parallel control. The enrolled 23 patients with liver cirrhosis were randomly divided into TUDCA group (n=12) and UDCA group (n=11), and given TUDCA and UDCA respectively at the daily dose of 750 mg, in a randomly assigned sequence for a 6-month period. Clinical, biochemical and histological features, and liver ultrasonographic findings were evaluated before and after the study. According to the inclusion criteria, 18 patients were included in the final analysis, including 9 cases in both two groups. Serum ALT, AST and ALP levels in TUDCA group and AST levels in UDCA group were significantly reduced as compared with baseline (P<0.05). Serum albumin levels were significantly increased in both TUDCA and UDCA groups (P<0.05). Serum markers for liver fibrosis were slightly decreased with the difference being not significant in either group. Only one patient in TUDCA group had significantly histological relief. Both treatments were well tolerated and no patient complained of side effects. It is suggested that TUDCA therapy is safe and appears to be more effective than UDCA in the treatment of liver cirrhosis, particularly in the improvement of the biochemical expression. However, both drugs exert no effect on the serum markers for liver fibrosis during 6-month treatment.     

Immunogenicity and safety of a combination pneumococcal-meningococcal vaccine in infants: a randomized controlled trial

Context  The success of conjugate vaccines in decreasing invasive disease due to Streptococcus pneumoniae and group C Neisseria meningitidis has placed pressure on crowded infant immunization schedules, making development of combination vaccines a priority. Objective  To determine the safety and immunogenicity of a combination 9-valent pneumococcal–group C meningococcal conjugate candidate vaccine (Pnc9-MenC) administered as part of the routine UK infant immunization schedule at ages 2, 3, and 4 months. Design, Setting, and Participants  Phase 2 randomized controlled trial conducted from August 2000 to January 2002 and enrolling 240 healthy infants aged 7 to 11 weeks from 2 UK centers, with home follow-up visits at ages 2, 3, 4, and 5 months. Intervention  Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b [Hib] polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine). Main Outcome Measures  Group C meningococcal immunogenicity measured by serum bactericidal titer (SBT) 1 month following the third dose; rates of postimmunization reactions. Results  MenC component immunogenicity was reduced in the Pnc9-MenC vs the MenC group (geometric mean SBT, 179 [95% confidence interval {CI}, 133-243] vs 808 [95% CI, 630-1037], respectively; P<.001). The proportion with group C meningococcal SBT greater than 1:8 was lower in the Pnc9-MenC vs the MenC group (95% vs 100%, P = .05). The geometric mean concentration of antibodies to concomitantly administered Hib vaccine was reduced in the Pnc9-MenC vs the MenC group (2.11 [95% CI, 1.57-2.84] µg/mL vs 3.36 [95% CI, 2.57-4.39] µg/mL; P = .02), as were antibodies against diphtheria (0.74 [95% CI, 0.63-0.87] µg/mL vs 1.47 [95% CI, 1.28-1.69] µg/mL; P<.001). Pnc9-MenC was immunogenic for each of 9 contained pneumococcal serotypes, with responses greater than 0.35 µg/mL observed in more than 88% of infants. Increased irritability and decreased activity were observed after the third dose in the Pnc9-MenC group. Conclusions  Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes. The reduced MenC immunogenicity may limit the development of the Pnc9-MenC vaccine.      

脓毒症患者血清中炎性因子、组织因子和组织因子途径抑制物水平变化及临床意义

目的探讨脓毒症患者血清中炎性因子、组织因子(TF)及组织因子途径抑制物(TFPI)水平的变化及临床意义。方法选择2012年1月至2015年12月郑州市儿童医院收治的89例脓毒症患者为研究对象,根据患者病情分为脓毒症组(n=61)、严重脓毒症组(n=17)和脓毒性休克组(n=11)。各组患者入院后立即采集静脉血2 m L,采用酶联免疫吸附试验检测血清中C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、TF及TFPI水平,采用电化学发光法检测血清中降钙素原(PCT)水平;并分析各指标与小儿危重病例评分(PCIS)的相关性。结果严重脓毒症组和脓毒性休克组患者血清中CRP、TNF-α、PCT及TF水平高于脓毒症组,TFPI水平低于脓毒症组(P <0. 05);脓毒性休克组患者血清中CRP、TNF-α、PCT和TF水平高于严重脓毒血组,TFPI水平低于严重脓毒症组(P <0. 05)。脓毒症患者血清中CRP、TNF-α、PCT及TF水平与PCIS呈显著负相关(r=-0. 76、-0. 72、-0. 81、-0. 70,P <0. 05),TFPI水平与PCIS呈显著正相关(r=0. 73,P <0. 05)。结论血清中CRP、TNF-α、PCT、TF及TFPI水平在评估脓毒症患者的病情严重程度中具有一定的价值,CRP、TNF-α、PCT及TF水平越高,TFPI水平越低,患者病情越严重。     

乌灵胶囊联合黛力新治疗脑卒中后抑郁疗效和安全性的随机对照研究

目的：观察乌灵胶囊联合黛力新治疗脑卒中后抑郁的临床疗效和安全性。 方法：采用平行对照研究方法，将卒中后抑郁病人随机分为乌灵胶囊组（n=39），给予乌灵胶囊，每次3粒，3次/d；黛力新组（n=37），给予黛力新片，每次10．5mg．2次/d，早上、中午各服1次；联合组（n=38）．在黛力新治疗基础上，加服乌灵胶囊。6周为1个疗程，于治疗前，治疗后2、4、6周用汉密顿抑郁量表（Hamilton Depression Scale，HAMD）评估疗效一治疗副反应量表（Treatment Emergent sympton Scale．TESS）评定药物的不良反应，并检测血常规、尿常规、肝肾功能及心电图等。 结果：乌灵胶囊组、黛力新组、联合治疗组总有效率分别为64．1％、64．9％和89．5％，乌灵胶囊组和黛力新组两组疗效差异无统计学意义（P〉0．05），联合组疗效优于另两组（P〈0．05）。单纯应用乌灵胶囊组未见不良反应，应用黛力新的两组不良反应发生率均为9％。 结论：乌灵胶囊联合黛力新治疗脑卒中后抑郁疗效优于单药治疗。     

Efficacy and safety of a parylene-coated occluder for atrial septal defect: a prospective,multi-center,randomized controlled clinical trial

Background:Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD).Methods:One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran–Mantel–Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups.Results:At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [−4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P < 0.05 vs. baseline). In the trial group, there was no significant difference in the serum nickel level before vs. after device implantation (P > 0.05).Conclusions:The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.     

阿普唑仑联合降压药治疗顽固性高血压的临床疗效和安全性评价

目的观察阿普唑仑联合降压药治疗顽固性高血压的临床疗效和安全性。方法于2008年2月—2010年10月治疗顽固性高血压患者102例,随机分为试验组和对照组各51例,2组在常规治疗基础上分别加用阿普唑仑或安慰剂治疗8周,观察患者的血压情况及不良反应。在治疗结束后随访8周,再次评价临床疗效。结果试验组显效37例(72.6%),有效10例(19.6%),总有效率92.2%,而对照组显效21例(41.2%),有效15例(29.4%),总有效率70.6%;2组间显效率和总有效率比较差异均有统计学意义(P<0.05)。试验组早期不良反应率(31.4%)高于对照组(21.6%),但差异无统计学意义(P>0.05)。随访8周时和试验结束时相比,试验组临床症状改善且血压稳定;而对照组舒张压水平升高(P<0.05)。结论阿普唑仑联合降压药治疗顽固性高血压疗效肯定,且不良反应少而轻微。