A multicenter, open-label, prospective, randomized, dose-ranging pharmacokinetic study of the anti-TNF-alpha antibody afelimomab in patients with sepsis syndrome

OBJECTIVE: To investigate the pharmacokinetics and safety of afelimomab, a murine antibody fragment against human tumor necrosis factor (TNF)-alpha in patients with sepsis. DESIGN: Multicenter, randomized, open-label, placebo-controlled phase I/II clinical trial. SETTING: Intensive care units of six academic medical centers in the United States. PATIENTS: Forty-eight patients with a clinical diagnosis of sepsis who received standard supportive care and antimicrobial therapy. Interventions: Patients received 0.3, 1.0, or 3.0 mg/kg afelimomab or placebo intravenously over 20 min. Three patients in each dose group received single doses; the remaining nine patients in each group received multiple (nine) doses at 8-h intervals over 72 h. MEASUREMENTS AND MAIN RESULTS: Afelimomab appeared safe and well tolerated. Single- and multiple-dose kinetics were predictable and dose related. The elimination half-life was 44.7 h. Afelimomab treatment resulted in increased serum concentrations of TNF (includes TNF-antibody complexes) and decreased serum interleukin-6 concentrations, whereas no discernible trends were observed in placebo-treated patients. There was no significant treatment effect on 28-day mortality as was expected given the small number of patients. However, overall mortality was significantly (p = 0.001) associated with baseline interleukin-6 concentration. All patients experienced adverse events, but the vast majority were considered unrelated to the study drug and demonstrated no apparent relationship to afelimomab dose. Although 41% of patients developed human anti-murine antibodies, there were no clinical sequelae. CONCLUSIONS: Multidose therapy with afelimomab was safe, well tolerated, and had predictable linear kinetics. A large randomized trial comparing afelimomab to placebo in patients with well defined sepsis has recently been completed.     

Anti-albuminuric effect of losartan versus amlodipine in hypertensive Japanese patients with type 2 diabetes mellitus: A prospective, open-label, randomized, comparative study

Abstract

Background

The antiproteinuric effect of the angiotensin II receptor-antagonist losartan has been observed in patients with type 2 diabetes mellitus (T2DM). Proteinuria is considered to be a predictor of the progression of kidney disease.

Objective

The aims of the present study were to compare and examine the ability of losartan and amlodipine to ameliorate albuminuria in hypertensive Japanese patients (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) with T2DM and whether the change in albuminuria was associated with a change in glomerular filtration rate (GFR).

Methods

This prospective, open-label, randomized, comparative study was conducted over 3 months at the Kinki University School of Medicine, Osaka-Sayama, Japan. Hypertensive patients with T2DM were enrolled and randomly assigned to 1 of 2 study groups receiving either losartan (25–100 mg/d) or the calcium channel-blocker amlodipine (2.5–5 mg/d). Urinary albumin excretion (UAE), creatinine clearance, and GFR were recorded at study initiation (baseline) and study end (month 3). The GFR was measured from the fractional renal accumulation of ^99mTc-diethylenetriaminepentaacetic acid. Adverse events (AEs) were monitored by a clinical research nurse during the examination.

Results

Fifty patients were asked to enroll and 38 returned the informed written consent. Thirty-five Japanese patients were included in the final study analysis. Seventeen patients were assigned to the losartan group (male sex, 10 [58.8%]; mean [SD] age, 58.1 [8.2] years) and 18 were assigned to the amlodipine group (male sex, 10 [55.6%]; mean [SD] age, 57.4 [8.9] years); no significant between-group difference in demographics was observed. A significant decrease from baseline to month 3 of mean (SD) UAE was observed in the losartan group (352.5 [556.6] mg/d vs 275.7 [466.1] mg/d; P = 0.048). No significant difference in mean (SD) UAE was observed in the amlodipine group for the same time period (298.2 [416.6] mg/d vs 322.7 [415.4] mg/d). There was a statistically significant difference found in the mean (SD) percent change of UAE from baseline to month 3 in the losartan group compared with the amlodipine group (−23.52 [28.42] vs +27.90 [63.51]; P = 0.004). Neither group was associated with a significant change in GFR during the course of the study. No patient discontinued the study due to AEs that were considered, by the investigator, to be possibly or probably associated with study treatment.

Conclusions

Treatment with losartan, but not amlodipine, was associated with a reduction in albuminuria in these hypertensive Japanese patients with T2DM within a period as short as 3 months. Neither drug was associated with a significant change in GFR. Therefore, the reduction of UAE was independent of a change in the GFR.Key Words: albuminuria, hypertension, glomerular filtration rate, losartan, amlodipine     

D型人格对冠状动脉支架置入术病人生命质量影响的研究

[目的]比较冠心病病人中D型人格与非D型人格病人冠状动脉支架置入术后生命质量的差异;探索D型人格对冠状动脉支架病人生命质量的影响。[方法]采用目的抽样法,选取冠心病行支架置入术病人,运用简明36项健康问卷（SF-36）、D型人格量表（DS14）及一般人口统计学问卷,分别于冠状动脉支架手术前、术后3个月进行调查。[结果]在所调查的104例病人中,D型人格病人占37.5%,支架置入术后D型人格病人生命质量评分为69.8分±10.5分,非D型人格病人为74.5分±9.2分,二者比较有统计学意义。在术后生命质量的＂生理机能＂＂情感职能＂＂精神健康＂方面D型人格比非D型人格病人得分低,D型人格进入到生命质量的多元逐步回归方程中。[结论]D型人格是影响冠状动脉支架置入术病人生命质量的危险因素,这类人格的病人在行冠状动脉支架置入术后较非D型人格病人恢复差,表现在生命质量的多个方面,在临床中应重视这类病人的护理。     

Levofloxacin compared with imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia: a multicenter,prospective, randomized,open-label study

BACKGROUND: Therapy of nosocomial pneumonia is usually empiric and includes > or = 1 broad-spectrum antimicrobial agent. When considering the use of fluoroquinolones in these difficult-to-treat infections--in which drug delivery to the site of infection may be impaired or organisms with higher minimum inhibitory concentrations may be present--an agent should be chosen whose pharmacodynamics ensure maximal drug exposure. Use of the 750-mg dose of levofloxacin should enhance therapeutic benefit in patients with nosocomial pneumonia. OBJECTIVE: The goal of this study was to compare the efficacy and safety of levofloxacin 750 mg and imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia. METHODS: This was a multicenter, prospective, randomized, open-label trial conducted in North America. Patients were randomly assigned to 1 of 2 treatment arms: levofloxacin 750 mg QD given i.v. and then orally for 7 to 15 days or imipenem/cilastatin 500 mg to 1 g i.v. every 6 to 8 hours, followed by oral ciprofloxacin 750 mg every 12 hours for 7 to 15 days. Adjunctive antibacterial therapy was mandatory in patients with documented or suspected Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus infection. The primary predefined outcome measure was the clinical response (cure, improvement, failure, or unable to evaluate) in microbiologically evaluable patients 3 to 15 days after the end of therapy. RESULTS: The study enrolled 438 adult patients (315 men, 123 women; mean [SD] age, 55.7 [20.04] years). Two hundred twenty patients received levofloxacin, and 218 received the comparator regimen. Demographic and baseline clinical characteristics were similar in the intent-to-treat and clinically evaluable populations. In patients evaluable for microbiologic efficacy, clinical success (cure or improvement) was achieved in 58.1% (54/93) of patients who received levofloxacin, compared with 60.6% (57/94) of patients who received the comparator regimen (95% CI, -12.0 to 17.2). Similar clinical results were seen in patients evaluable for clinical efficacy and in the intent-to-treat population. In the 187 patients evaluable for microbiologic efficacy, eradication was achieved in 66.7% (62/93) of patients receiving levofloxacin and 60.6% (57/94) of patients receiving the comparator regimen (95% CI, -20.3 to 8.3). CONCLUSION: In this study, levofloxacin was at least as effective and was as well tolerated as imipenem/cilastatin followed by ciprofloxacin in adult patients with nosocomial pneumonia, as demonstrated by comparable clinical and microbiologic success rates.     

替罗非班应用在药物涂层支架植入术后老年患者实行非心脏手术的可行性和安全性

目的:明确替罗非班是否可以在药物涂层支架植入老年患者实行非心脏手术围手术期替代口服双联抗血小板药物而发挥预防支架内血栓的作用,同时不增加外科手术的出血。方法:入选入院前1年内曾因冠心病植入药物涂层支架服用双联抗血小板药物而后无缺血性胸痛症状,因外科疾病保守治疗无效需手术治疗的12例患者配对分组,手术前5d停用口服双联抗血小板药物,治疗组6例患者应用替罗非班0.1μg/(kg·min)持续静脉微量泵泵入,对照组6例患者应用低分子肝素依诺肝素1mg/kg皮下注射(每天2次),手术结束后在重症监护室中继续术前应用方法,根据外科情况允许,停用替罗非班及低分子肝素,尽早恢复口服双联抗血小板药物使用,分析围手术期两组新发心血管事件以及严重出血事件。结果:两组患者围手术期均未发生缺血性室性恶性心律失常、心绞痛、心肌梗死、心源性猝死,未发生大量出血而导致输血或需二次手术止血等出血事件。结论:替罗非班应用在药物涂层支架植入术后患者实行非心脏手术替代口服双联抗血小板药物预防围手术期支架内血栓的治疗作用不亚于低分子肝素,没有严重的出血并发症,而且有半衰期短的特点,其优势需要大样本随机对照试验以进一步证实。     

Sex-based influence on clinical outcomes after drug-eluting stent implantation in real-world patients: insight from the FOCUS registry

Objectives: To investigate the impact of sex on clinical outcomes after drug-eluting stent (DES) implantation in real-world patients.

Methods and results: A total number of 4720 patients (3365 males and 1355 females) undergoing the second-generation cobalt-chromium sirolimus-eluting stent (CoCr-SES) implantation from the FOCUS registry were included in this analysis. The cumulative incidences of major adverse cardiovascular event (MACE) (1.5% vs. 2.4%; p?=?.03), cardiovascular death (0.5% vs. 1.0%; p?=?.02) and target vessel revascularization (TVR) (0.3% vs. 0.8%; p?=?.01) within six months were significantly higher in females and the risks of MACE (adjusted hazard ratio [HR] 0.5 (0.3–0.9); p?=?.01) and TVR (adjusted HR 0.1(0.0–0.5); p?=?.001) remained significant in multivariate analysis. Reversely, the cumulative incidences of MACE (5.4% vs. 4.8%; p?=?.04) and any revascularization (5.1% vs. 3.3%; p?=?.01) were significantly higher in males beyond six months and the risks of all-cause death (adjusted HR 1.6 (1.1–2.5); p?=?.03) and cardiovascular death (adjusted HR 1.9 (1.1–3.6); p?=?.03) turned out to be significant in multivariate analysis. Notes: All cumulative incidences were presented as male vs. female; all HRs were calculated as male relative to female.

Conclusions: Females were associated with higher risk of early adverse events, while, males were associated with higher risk of late adverse events.

• Key messages

• Females undergoing PCI are typically older, have more cardiovascular risk factors, while, males in need of PCI are more frequently associated with complex lesions.

• The overall three-year cumulative incidences of adverse events are not significantly different between males and females but numerically higher in males.

• Females are associated with significantly higher risks of MACE and TVR within six months, while, males are associated with significantly higher risk of all-cause mortality and cardiac mortality beyond 6 months.

     

Metoclopramide or domperidone improves post-pyloric placement of spiral nasojejunal tubes in critically ill patients: a prospective,multicenter, open-label,randomized, controlled clinical trial

IntroductionThe use of prokinetic agents on post-pyloric placement of spiral nasojejunal tubes is controversial. The aim of the present study was to examine if metoclopramide or domperidone can increase the success rate of post-pyloric placement of spiral nasojejunal tubes.MethodsA multicenter, open-label, randomized, controlled trial was conducted in seven hospitals in China between April 2012 and February 2014. Patients admitted to the intensive care unit and requiring enteral nutrition for more than three days were randomly assigned to the metoclopramide, domperidone or control groups (1:1:1 ratio). The primary outcome was defined as the success rate of post-pyloric placement of spiral nasojejunal tubes, assessed 24 hours after initial placement. Secondary outcomes included success rate of post-D1, post-D2, post-D3 and proximal jejunum placement and tube migration distance. Safety of the study drugs and the tubes during the entire study period were recorded.ResultsIn total, 307 patients were allocated to the metoclopramide (n = 103), domperidone (n = 100) or control group (n = 104). The success rate of post-pyloric placement after 24 hours in the metoclopramide, domperidone and control groups was 55.0%, 51.5% and 27.3%, respectively (P = 0.0001). Logistic regression analysis identified the use of prokinetic agents, Acute Physiology and Chronic Health Evaluation (APACHE) II score <20, Sequential Organ Failure Assessment (SOFA) score <12 and without vasopressor as independent factors influencing the success rate of post-pyloric placement. No serious drug-related adverse reaction was observed.ConclusionsProkinetic agents, such as metoclopramide or domperidone, are effective at improving the success rate of post-pyloric placement of spiral nasojejunal tubes in critically ill patients.

Trial registration

Chinese Clinical Trial Registry ChiCTR-TRC-12001956. Registered 21 February 2012.     

Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study

BACKGROUND: Patients undergoing major abdominal surgery carry a high risk of venous thromboembolism (VTE), but the optimal duration of postoperative thromboprophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and safety of thromboprophylaxis with the low molecular weight heparin (dalteparin), administered for 28 days after major abdominal surgery compared to 7 days' treatment. PATIENTS/METHODS: A multicenter, prospective, assessor-blinded, open-label, randomized trial was performed in order to evaluate prolonged thromboprophylaxis after major abdominal surgery. In total, 590 patients were recruited, of whom 427 were randomized and received at least 1 day of study medication, and 343 reached an evaluable endpoint. The primary efficacy endpoint was objectively verified VTE occurring between 7 and 28 days after surgery. All patients underwent bilateral venography at day 28. RESULTS: The cumulative incidence of VTE was reduced from 16.3% with short-term thromboprophylaxis (29/178 patients) to 7.3% after prolonged thromboprophylaxis (12/165) (relative risk reduction 55%; 95% confidence interval 15-76; P=0.012). The number that needed to be treated to prevent one case of VTE was 12 (95% confidence interval 7-44). Bleeding events were not increased with prolonged compared with short-term thromboprophylaxis. CONCLUSIONS: Four-week administration of dalteparin, 5000 IU once daily, after major abdominal surgery significantly reduces the rate of VTE, without increasing the risk of bleeding, compared with 1 week of thromboprophylaxis.     

A randomized, open-label pilot study comparing desirudin and argatroban in patients with suspected heparin-induced thrombocytopenia with or without thrombosis: PREVENT-HIT Study

Because of an extreme risk for thromboemboli, patients with suspected heparin-induced thrombocytopenia (HIT) require immediate initiation of an alternative anticoagulant. The only therapies approved by the Food and Drug Administration require intravenous infusion of expensive direct thrombin inhibitors. This prospective, randomized, open-label, exploratory study compared the clinical and economic utility of subcutaneous desirudin vs argatroban, the most frequently used agent for suspected or immunologically confirmed HIT, with or without thrombosis. Sixteen patients were randomized to treatment with fixed-dose desirudin (15 or 30 mg) every 12 hours or activated partial thromboplastin time-adjusted argatroban by intravenous infusion. Arm A included 8 patients naive to direct thrombin inhibitor therapy, whereas Arm B included 8 patients on argatroban for at least 24 hours before randomization. The primary efficacy measure was the composite of new or worsening thrombosis (objectively documented), amputation, or death. Other end points included major and minor bleeding while on drug therapy, time to platelet count recovery, and pharmacoeconomics. No amputations or deaths occurred. One patient randomized to argatroban had worsening of an existing thrombosis. Major bleeding occurred in 2 patients on argatroban and in none during desirudin treatment. There was 1 minor bleed in each treatment group. The average medication cost per course of treatment was $1688 for desirudin and $8250 for argatroban. Desirudin warrants further study as a potentially cost-effective alternative to argatroban in patients with suspected HIT.     

D型人格对冠状动脉支架置入术病人生命质量影响的研究

[目的]比较冠心病病人中D型人格与非D型人格病人冠状动脉支架置入术后生命质量的差异;探索D型人格对冠状动脉支架病人生命质量的影响。[方法]采用目的抽样法,选取冠心病行支架置入术病人,运用简明36项健康问卷(SF-36)、D型人格量表(DS14)及一般人口统计学问卷,分别于冠状动脉支架手术前、术后3个月进行调查。[结果]在所调查的104例病人中,D型人格病人占37.5%,支架置入术后D型人格病人生命质量评分为69.8分±10.5分,非D型人格病人为74.5分±9.2分,二者比较有统计学意义。在术后生命质量的"生理机能""情感职能""精神健康"方面D型人格比非D型人格病人得分低,D型人格进入到生命质量的多元逐步回归方程中。[结论]D型人格是影响冠状动脉支架置入术病人生命质量的危险因素,这类人格的病人在行冠状动脉支架置入术后较非D型人格病人恢复差,表现在生命质量的多个方面,在临床中应重视这类病人的护理。     

A prospective,randomized, double-blind,multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients

Purpose  

To compare the quality of analgesia provided by a remifentanil-based analgesia regime with that provided by a fentanyl-based regime in critically ill patients.     

Comparison of levalbuterol and racemic albuterol in hospitalized patients with acute asthma or COPD: A 2-week, multicenter, randomized, open-label study.

Background: The National Heart, Lung, and Blood Institute guideline recommends that dosing racemic albuterol be administered every 1 to 4 hours for treating patients with asthma or chronic obstructive pulmonary disease (COPD) in the hospital. Previously published preliminary and retrospective studies suggested that levalbuterol can be administered every 8 hours for the treatment of bronchoconstriction in hospitalized patients. However, it is unclear how the different dosing regimens affect the total number of nebulizations (scheduled plus as-needed treatments) and the costs of treatment of bronchoconstriction in a hospital setting. Moreover, it is not clear how the different dosing regimens affect symptom outcomes and health status in hospitalized patients with asthma or COPD. Objective: The aim of this study was to evaluate these issues in hospitalized patients with acute asthma or COPD. Methods: In this prospective, multicenter, randomized, open-label study, hospitalized patients aged >/=18 years were randomly assigned to receive 14-day treatment with levalbuterol 1.25 mg q6-8h or racemic albuterol 2.5 mg q1-4h, administered per routine hospital practice at each institution. The primary efficacy end point was total number of nebulizations during hospitalization. Pulmonary function, symptom evaluation (subject general well-being score [SGWB], disease symptom assessment [DSA], and beta-mediated adverse effect scores), hospital costs (excluding medication costs) and hospital length of stay (LOS) were also evaluated. Results: In the intent-to-ttreat population (n = 479; levalbuterol, 241;racemic albuterol, 238), the mean (SE) age was 55.3 (16.9) years, the majority of patients were white (57.8%), and the mean (SE) weight was 80.9 (24.5) kg. Demographic characteristics were similar between the 2 treatment groups, except that there were more females with COPD in the levalbuterol treatment group (63.88%) compared with the racemic albuterol treatment group (45.5%) (P = 0.005). Patients treated with levalbuterol required significantly fewer median total nebulizations (10 vs 12; P = 0.031) and scheduled nebulizations (9 vs 11; P = 0.009) compared with those in the racemic albuterol group. The 2 treatment groups required 0 rescue nebulizations. Mean (SD) forced expiratory volume in 1 second improved from baseline with both levalbuterol and racemic albuterol (0.06 [0.43] and 0.10 [0.37] L, respectively); these improvements were maintained throughout the hospital stay (0.11 [0.48] and 0.16 [0.52] L). DSA and SGWB scores improved significantly from baseline in both treatment groups, and beta-mediated adverse effects mean scores were significantly greater with levalbuterol versus racemic albuterol (P < 0.001). In the levalbuterol and racemic albuterol treatment groups, hospital LOS (70.6 and 65.7 hours, respectively), time to discharge (66.0 and 62.8 hours), and total hospital costs (least squares mean [SE], US $4869.30 [$343.58] and $4899.41 [$343.20]) were similar. Conclusions: In these hospitalized patients with acute asthma or COPD treated with levalbuterol every 6 to 8 hours or racemic albuterol every 1 to 4 hours, significantly fewer total nebulizations were required with levalbuterol, without an increased need for rescue nebulizations during 14 days of hospitalization. Both treatments were associated with improvements from baseline in symptoms and health status. The costs of treating bronchoconstriction in hospitalized patients were similar between the levalbuterol and racemic albuterol groups.     

Comparison of the effects of ketamine or lidocaine on fentanyl-induced cough in patients undergoing surgery: A prospective, double-blind, randomized, placebo-controlled study

Background: Fentanyl-induced cough is common but has not been viewed as a serious anesthetic problem. However, the cough may be explosive at times, may require immediate intervention, and may be associated with undesirable increases in intracranial, intraocular, and intra-abdominal pressures. Prevention of fentanylinduced cough in such situations is of paramount importance. Ketamine, at concentrations achieved with standard clinical doses, has a direct relaxant effect on airway smooth muscle.Objective: This study was designed to assess the effects of ketamine or lidocaine on fentanyl-induced cough.Methods: This double-blind, randomized, placebo-controlled study was conducted at the Erciyes University Medical School, Kayseri, Turkey. Consecutive adult patients aged 18 to 65 years and classified as American Society of Anesthesiologists physical status I or II who were undergoing elective surgery with general anesthesia were enrolled. Patients were randomly allocated equally into 3 groups to receive lidocaine 1 mg/kg, ketamine 0.5 μg/kg, or placebo intravenously 1 minute before fentanyl administration. Following intravenous fentanyl (1.5 μg/kg over 2 seconds) injection, an observer, unaware of the type of medication given to the patients, recorded the number of episodes of coughing, if any. Any episode of cough was classified as coughing and graded by investigators blinded to treatment as mild (1-2 coughs), moderate (3-4), or severe (≥5). Blood pressure, heart rate, pulse oximetry oxygen saturation (SpO₂), and adverse effects (AEs) were recorded.Results: A total of 368 patients were approached for inclusion; 300 patients met the inclusion criteria and were enrolled in the study. No patients in the ketamine group had cough. The frequency of cough was significantly lower in the lidocaine (11/100 [11%]; P = 0.024) and ketamine (0/100; P = 0.001) groups compared with the placebo group (23/100 [23%]). The intensity of cough was significantly lower in the lidocaine (mild, 7/100 [7%]; moderate, 4/100 [4%]; P = 0.037) and ketamine (0/100; P < 0.001) groups compared with the placebo group (mild, 10/100 [10%]; moderate, 12/100 [12%]; severe, 1/100 [1%]). Severe cough (≥5) was observed in 1 patient in the placebo group. Incidence and intensity of cough were significantly decreased in the ketamine group compared with the lidocaine group (incidence, P = 0.001; intensity, P = 0.003). There were no significant differences between groups with respect to systolic blood pressure, diastolic blood pressure, heart rate, SpO₂, and AEs.Conclusion: Intravenous ketamine (0.5 mg/kg) significantly reduced the reflex cough induced by fentanyl compared with lidocaine and placebo, and was well tolerated.     

老年糖尿病冠心病患者支架植入术后抗血小板治疗的研究

目的 探讨三联抗血小板治疗对预防有出血性卒中病史老年糖尿病冠心病患者金属裸支架(BMS)植入术后支架内血栓形成和再狭窄的有效性及安全性.方法 60例患者行支架植入术后被随机分为治疗组(30例)和对照组(30例).两组均长期服用阿司匹林100 mg/d、氯吡格雷75 mg/d,连用1个月;治疗组加用西洛他唑200 mg/d,连用6个月.6～9个月后进行冠状动脉(冠脉)造影随访.结果 治疗组9个月靶病变重建率明显低于对照组[13.3%比33.3%,P<0.05].随访6个月,治疗组最小管腔直径明显大于对照组,管腔狭窄程度明显小于对照组,再狭窄率和管腔晚期丢失均明显低于对照组(P均<0.05).治疗组患者除心动过速发生率高于对照组(P<0.05)外,其余不良反应发生情况与对照组无明显差异.治疗组随访期间花生四烯酸诱导血小板抑制率明显高于对照组(P均<0.05).结论 对冠脉病变参考血管直径≥3 mm且靶血管病变长度≤20 mm、合并出血性卒中病史的老年糖尿病冠心病患者行BMS植入术后,在阿司匹林、氯吡格雷抗血小板治疗基础上加用6个月西洛他唑,有降低支架内血栓形成的趋势,可增加随访期的冠脉最小管腔直径、减少BMS植入术后再狭窄率和靶病变重建率,且不增加出血并发症.     

Comparison of methimazole/hydrocortisone ointment with oral methimazole in patients with graves disease: A prospective, randomized, open-label, parallel-group, 18-month study

Background: Thionamide antithyroid drugs (ATDs) have certain disadvantages and are associated with some adverse events (AEs). To overcome the problems associated with ATDs, a compound antithyroid ointment (CATO) containing methimazole (MMI) and hydrocortisone has been developed for use as a local thyroid treatment (LTT).Objective: The aim of this study was to assess the clinical effectiveness and tolerability of CATO LTT in patients with Graves disease (GD).Methods: This was a prospective, randomized, open-label, parallel-group clinical trial conducted at the Provincial Hospital Affiliated to Shandong University (Jinan, China). Patients with GD aged 19 to 65 years were randomized to receive either CATO LTT 0.3 g/d or oral MMI 37.5 mg/d (control group) treatment for 18 months, with a 4-year follow-up period. Hyperthyroid symptoms, thyroid function, granulocyte count, liver function, and AEs were assessed at baseline and every 2 weeks until serum thyroid hormone (TH) concentration normalized, at which point patients were assessed monthly. The primary efficacy end points were the duration of treatment required for serum TH concentration to normalize and the remission rate after completing the 18-month treatment regimen.Results: A total of 154 patients (133 women, 21 men; mean [SD] age, 39.6 [11.8] years; all Han Chinese) participated in the study; all patients completed the 18-month treatment period. Compared with the MMI group (n 76), the CATO- treated group (n 78) had a significantly shorter median (range) time to restoration of normal serum thyroid hormone concentration (43 [12-150] vs 22 [7-60] days; P < 0.001), a significantly lower rate of recurrence of hyperthyroidism (309/1520 [20.3%] vs 193/1368 [14.1%] person-time; P < 0.001), a significantly lower drug hypothyroidism rate (185/1520 [12.2%] vs 54/1368 [3.9%] person-time; P < 0.001), and a higher remission rate (year 1:46/69 [66.7%] vs 65/72 [90.3%] patients, P 0.001; year 2:40/69 [58.0%] vs 60/72 [83.3%] patients, P - 0.001; year 3:34/69 [49.3%] vs 57/72 [79.2%] patients, P < 0.001; and year 4:30/69 [43.5%] vs 55/72 [76.4%] patients, P < 0.001). Systemic AEs occurred in 6 patients (7.9%) in the MMI group (drug neutropenia, 2 patients [2.6%]; epistaxis, 1 [1.3%]; hepatopathy, 1 [1.3%]; and other systemic AEs, 2 [2.6%]), while no systemic AEs were observed/reported in the CATO group.Conclusion: This study suggests that CATO LTT was well tolerated and more effective than oral MMI treatment in controlling thyrotoxicosis and promoting remission of GD in these Han Chinese patients.     

Excel雷帕霉素药物洗脱支架治疗冠心病临床疗效观察

目的探讨国产Excel雷帕霉素药物洗脱支架对冠心病患者介入治疗的安全性和近期疗效。方法2006年7月至2008年12月共对162例冠心病患者进行介入治疗。术后随访6—12个月观察有无心绞痛、心肌梗死、猝死及再次血管重建事件。结果对182处血管病变,共使用216枚Excel支架,成功置入支架215枚,1例置入失败,置入支架成功率99．5％,1例合并糖尿病患者手术后5个月支架内再狭窄致心绞痛反复发作,又置入支架一枚后症状消失,术后6～12个月内主要不良反应事件发生率0．62％。结论Excel雷帕霉素药物洗脱支架治疗冠心病具有良好的安全性和满意的近期临床效果。     

艾司西酞普兰治疗冠心病支架植入术患者伴发焦虑抑郁情绪对照研究

目的：探讨放松训练联合草酸艾司西酞普兰对冠心病支架植入术后患者伴发焦虑抑郁情绪的临床疗效和安全性以及对生活质量的影响。方法将65例冠心病冠脉支架植入术后伴焦虑抑郁患者随机分为两组,均予以冠心病常规治疗及放松训练,研究组在此基础上联合草酸艾司西酞普兰治疗,观察8周。采用汉密顿焦虑量表、汉密顿抑郁量表评定焦虑抑郁情绪,生活质量量表评定生活质量,副反应量表评定不良反应。结果治疗后两组汉密顿焦虑量表、汉密顿抑郁量表评分较治疗前显著下降（P＜0．01）,研究组较对照组下降更显著（P＜0．01）;研究组生活质量量表的4个领域、对照组1个领域评分较治疗前显著升高（P＜0．01）,研究组5个领域评分显著高于对照组（P＜0．01）。治疗过程中两组不良反应均轻微,各项实验室检查均无异常改变。结论放松训练联合草酸艾司西酞普兰能显著改善冠心病冠脉支架植入术患者伴发的焦虑抑郁情绪,提高患者的生活质量,且安全性高,优于单用放松训练治疗。     

A multicenter study of the tolerability of tirofiban versus placebo in patients undergoing planned intracoronary stent placement

BACKGROUND: The use of intravenous glycoprotein IIb/IIIa-receptor antagonists has been shown to improve outcomes in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Tirofiban has shown benefit in a wide range of patients presenting with acute coronary syndromes. Although this agent has been used in patients undergoing percutaneous coronary intervention, a literature search identified no prospective data comparing tirofiban with placebo in patients undergoing planned intracoronary stent placement. OBJECTIVE: This study examined the tolerability of tirofiban in patients undergoing percutaneous intervention with planned intracoronary stent placement. METHODS: This was a multinational, multicenter, prospective, randomized, double-blind, placebo-controlled trial in patients scheduled to undergo PTCA with planned intracoronary stent placement. Patients were randomized in a 3:2 ratio to receive tirofiban as an intravenous bolus (10 microg/kg over 3 minutes) and maintenance infusion (0.10 microg/kg per minute for 36 hours) or a bolus and infusion of placebo. All patients received periprocedural aspirin and heparin and an optional postprocedural thienopyridine (ticlopidine or clopidogrel). Laboratory and safety monitoring were performed throughout the 36 hours after the procedure and at hour 40 or hospital discharge. The primary end point was the proportion of patients with bleeding, defined according to Thrombolysis in Myocardial Infarction (TIMI) trial criteria. The number of patients with cardiac events (death, myo- cardial infarction, urgent revascularization) during the first 30 days after stent placement was also assessed. RESULTS: Eight hundred ninety-four patients (536 tirofiban, 358 placebo) were enrolled, all of whom received aspirin and heparin periprocedurally and optional ticlopidine or clopidogrel after the procedure. No significant between-group differences were observed in the incidence of TIMI major bleeding (0.2% tirofiban, 0.6% placebo) or any TIMI bleeding (3.2% and 1.7%, respectively). The incidence of TIMI minor bleeding was higher with tirofiban than with placebo (2.8% vs 0.6%). The 30-day incidence of the composite end point of any cardiac event was 3.9% in both groups. CONCLUSIONS: On a background of concomitant aspirin, heparin, and a thienopyridine, tirofiban was generally well tolerated in patients undergoing PTCA with planned intracoronary stent placement. Further investigation is needed to ascertain the optimal dosing of tirofiban and heparin to achieve reductions in ischemic complications of intracoronary stenting with an acceptable incidence of bleeding complications.