Submammary placement of implantable cardioverter defibrillators: a Singapore plastic surgeon experience

The use of implantable cardioverter defibrillators (ICDs) in young women has been increasing in recent years owing to greater awareness about inherited cardiac conditions that increase the risk of sudden death. Traditional placement of ICDs in the infraclavicular region among young women often leads to visible scars, a constant prominence that causes irritation from purse or bra straps and can result in body image concerns and device-related emotional distress. In this case series, two women with long QT syndrome required placement of ICDs for prevention of sudden cardiac death. Submammary placement of ICDs was performed in collaboration with electrophysiologists. We describe our local experience and technique in submammary placement of ICDs as well as the challenges faced.     

Continuous vs episodic prophylactic treatment with amiodarone for the prevention of atrial fibrillation: a randomized trial

Sheba Ahmed, MD; Michiel Rienstra, MD, PhD; Harry J. G. M. Crijns, MD, PhD; Thera P. Links, MD, PhD; Ans C. P. Wiesfeld, MD, PhD; Hans L. Hillege, MD, PhD; Hans A. Bosker, MD, PhD; Dirk J. A. Lok, MD; Dirk J. Van Veldhuisen, MD, PhD; Isabelle C. Van Gelder, MD, PhD; for the CONVERT Investigators

JAMA. 2008;300(15):1784-1792.

Context  Amiodarone effectively suppresses atrial fibrillation but causes many adverse events.

Objective  To compare major events in patients randomized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment while still aiming to prevent atrial fibrillation.

Design, Setting, and Participants  A randomized trial of 209 ambulatory patients with recurrent symptomatic persistent atrial fibrillation, conducted from December 2002 through March 2007 at 7 Dutch medical centers.

Intervention  Patients were randomly assigned to receive either episodic or continuous amiodarone treatment after electrical cardioversion following amiodarone loading. Episodic amiodarone treatment was discontinued after a month of sinus rhythm and reinitiated if atrial fibrillation relapsed (1 month peri–electrical cardioversion). In the continuous treatment group amiodarone was maintained throughout.

Main Outcome Measures  The primary end point was a composite of amiodarone and underlying heart disease–related major events. The secondary end points were all-cause mortality and cardiovascular hospitalizations.

Results  After a median follow-up of 2.1 years (range, 0.4-2.5 years), 51 (48%) of those receiving episodic treatment vs 64 (62%) receiving continuous treatment had sinus rhythm (P = .05). There were 85 atrial fibrillation recurrences (80%) among the episodic treatment group vs 56 (54%) in the continuous treatment group (P < .001). No significant difference existed in the incidence of the primary composite end point between each group (37 [35%] episodic vs 34 [33%] continuous; incidence rate difference, 0.2; 95% confidence interval [CI], –10.2 to 10.6). However, there were nonstatistically significant differences in the incidence of amiodarone-related major events (20 [19%] episodic vs 25 [24%] continuous; incidence rate difference, –2.0; 95% CI, –8.7 to 4.6) and underlying heart disease–related major events (17 [16%] episodic vs 9 [9%] continuous; incidence rate difference, 3.6; 95% CI, –1.6 to 8.7). All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment (56 [53%] vs 35 [34%], P = .02).

Conclusions  In this study population, there was no difference in the composite of amiodarone and cardiac major adverse events between groups. However, patients receiving episodic treatment had a significantly increased rate of atrial fibrillation recurrence and a significantly higher rate of all-cause mortality and cardiovascular hospitalizations.

Trial Registration  clinicaltrials.gov Identifier: NCT00392431

     

Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial

Context  Very-long-chain n-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish are thought to reduce risk of sudden death, possibly by reducing susceptibility to cardiac arrhythmia. Objective  To study the effect of supplemental fish oil vs placebo on ventricular tachyarrhythmia or death. Design, Setting, and Patients  The Study on Omega-3 Fatty acids and ventricular Arrhythmia (SOFA) was a randomized, parallel, placebo-controlled, double-blind trial conducted at 26 cardiology clinics across Europe. A total of 546 patients with implantable cardioverter-defibrillators (ICDs) and prior documented malignant ventricular tachycardia (VT) or ventricular fibrillation (VF) were enrolled between October 2001 and August 2004. Patients were randomly assigned to receive 2 g/d of fish oil (n = 273) or placebo (n = 273) for a median period of 356 days (range, 14-379 days). Main Outcome Measure  Appropriate ICD intervention for VT or VF, or all-cause death. Results  The primary end point occurred in 81 (30%) patients taking fish oil vs 90 (33%) patients taking placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.64-1.16; P = .33). In prespecified subgroup analyses, the HR was 0.91 (95% CI, 0.66-1.26) for fish oil vs placebo in the 411 patients who had experienced VT in the year before the study, and 0.76 (95% CI, 0.52-1.11) for 332 patients with prior myocardial infarctions. Conclusion  Our findings do not indicate evidence of a strong protective effect of intake of omega-3 PUFAs from fish oil against ventricular arrhythmia in patients with ICDs. Trial Registration  clinicaltrials.gov Identifier: NCT00110838      

Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial

Context  Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects. Objective  To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Design and Setting  Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003. Patients  Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF. Intervention  Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days). Main Outcome Measures  Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses. Results  Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001). Conclusion  Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.      

Topiramate for migraine prevention: a randomized controlled trial

Context  Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention. Objective  To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial. Design, Setting, and Patients  A 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase. Interventions  After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks. Main Outcome Measures  The primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with =" BORDER="0">50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed. Results  Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (-2.1, P = .008) and topiramate at 200 mg/d (-2.4, P<.001) vs placebo (-1.1). Statistically significant reductions (P<.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P = .01), 100 mg/d (49%, P<.001), and 200 mg/d (47%, P<.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P = .003) and 200-mg/d (P<.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P = .01) and 200-mg/d (P = .005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea. Conclusion  Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the double-blind phase.      

吡柔比星或表柔比星联合紫杉醇新辅助化疗治疗局部晚期乳腺癌的随机对照研究

目的观察吡柔比星或表柔比星联合紫杉醇新辅助化疗治疗局部晚期乳腺癌(LABC)的近期临床疗效和毒副反应。方法采用随机对照研究,40例LABC行吡柔比星联合紫杉醇方案(PT组)或表柔比星联合紫杉醇方案(PE组)行新辅助化疗。记录患者每周期肿块大小、术后病理以及毒副反应分度。结果两组患者均接受共6个疗程的化疗。其中39例新辅助化疗2～4个周期后行手术治疗,手术后完成剩余疗程;1例新辅助化疗6周期后行手术治疗。PT组20例病理完全缓解率(pCR)、临床完全缓解率(cCR)以及临床部分缓解率(cPR)分别为10.0%、20.0%和75.0%,PE组为5.0%、30.0%、70.0%,两组总有效率(RR)无统计学差异。化疗过程中两组心脏毒性和造血系统毒性均为Ⅰ～Ⅱ度,且无统计学差异;PT组Ⅲ度胃肠道反应(恶心、呕吐)发生率45.0%,低于PE组的90.0%(P<0.05)。结论吡柔比星或表柔比星联合紫杉类新辅助化疗治疗LABC近期疗效较好,化疗后手术切除率高,心脏毒性及骨髓抑制较轻,但PT较PE方案胃肠道毒副反应有显著改善。     

Cognitive therapy for the prevention of suicide attempts: a randomized controlled trial

Context  Suicide attempts constitute a major risk factor for completed suicide, yet few interventions specifically designed to prevent suicide attempts have been evaluated. Objective  To determine the effectiveness of a 10-session cognitive therapy intervention designed to prevent repeat suicide attempts in adults who recently attempted suicide. Design, Setting, and Participants  Randomized controlled trial of adults (N = 120) who attempted suicide and were evaluated at a hospital emergency department within 48 hours of the attempt. Potential participants (N = 350) were consecutively recruited from October 1999 to September 2002; 66 refused to participate and 164 were ineligible. Participants were followed up for 18 months. Intervention  Cognitive therapy or enhanced usual care with tracking and referral services. Main Outcome Measures  Incidence of repeat suicide attempts and number of days until a repeat suicide attempt. Suicide ideation (dichotomized), hopelessness, and depression severity at 1, 3, 6, 12, and 18 months. Results  From baseline to the 18-month assessment, 13 participants (24.1%) in the cognitive therapy group and 23 participants (41.6%) in the usual care group made at least 1 subsequent suicide attempt (asymptotic z score, 1.97; P = .049). Using the Kaplan-Meier method, the estimated 18-month reattempt-free probability in the cognitive therapy group was 0.76 (95% confidence interval [CI], 0.62-0.85) and in the usual care group was 0.58 (95% CI, 0.44-0.70). Participants in the cognitive therapy group had a significantly lower reattempt rate (Wald ²₁ = 3.9; P = .049) and were 50% less likely to reattempt suicide than participants in the usual care group (hazard ratio, 0.51; 95% CI, 0.26-0.997). The severity of self-reported depression was significantly lower for the cognitive therapy group than for the usual care group at 6 months (P= .02), 12 months (P = .009), and 18 months (P = .046). The cognitive therapy group reported significantly less hopelessness than the usual care group at 6 months (P = .045). There were no significant differences between groups based on rates of suicide ideation at any assessment point. Conclusion  Cognitive therapy was effective in preventing suicide attempts for adults who recently attempted suicide.      

Folic acid for the prevention of colorectal adenomas: a randomized clinical trial

Context  Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine. Objective  To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas. Design, Setting, and Participants  A double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma. Intervention  Participants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later). Main Outcome Measures  The primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (25% villous features, high-grade dysplasia, size 1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or 3 adenomas). Results  During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation. Conclusions  Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia. Trial Registration  clinicaltrials.gov Identifier: NCT00272324      

Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial

Context  The development of contrast-induced nephropathy in patients undergoing invasive cardiac procedures is associated with a marked increase in cardiovascular morbidity and mortality. Fenoldopam mesylate, a specific agonist of the dopamine-1 receptor, preserves renal blood flow after iodinated contrast administration and has shown promise in ameliorating contrast nephropathy in previous observational and small randomized trials. Objective  To examine the efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive cardiovascular procedures. Design  Prospective, placebo-controlled, double-blind, multicenter randomized trial with serial serum creatinine levels measured at a central biochemistry laboratory (at baseline and 1, 24, 48, and 72 to 96 hours after study drug administration) and 30-day clinical follow-up. Patients and Setting  Between March 2001 and July 2002, 315 patients with creatinine clearance less than 60 mL/min (1.00 mL/s) at 28 centers in the United States were randomized to receive fenoldopam mesylate (n = 157) or placebo (n = 158). Interventions  Patients were hydrated and randomized to receive intravenous fenoldopam (0.05 µg/kg/min titrated to 0.10 µg/kg/min) vs matching placebo, starting 1 hour prior to angiography and continuing for 12 hours. Main Outcome Measure  Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine level within 96 hours postprocedure. Results  Mean (SD) patient age was 70 (11) years, and 49% had diabetes mellitus. Mean (SD) baseline creatinine clearance was 29.0 (10.0) mL/min (0.48 [0.16] mL/s) (range, 7.5-56.8 mL/min [0.12-0.94 mL/s]), and 157 (108) mL of contrast was administered during the procedures. The primary end point of contrast-induced nephropathy occurred in 33.6% of patients assigned to receive fenoldopam vs 30.1% assigned to receive placebo (relative risk, 1.11; 95% confidence interval, 0.79-1.57; P = .61). There were no significant differences in the 30-day rates of death (2.0% vs 3.8%, P = .50), dialysis (2.6% vs 1.9%, P = .72), or rehospitalization (17.6% vs 19.9%, P = .66) in fenoldopam vs placebo randomized patients, respectively. Conclusion  The selective dopamine-1 agonist fenoldopam mesylate does not prevent further renal function deterioration after contrast administration in patients with chronic renal insufficiency.      

Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials

Context  Implantable cardioverter defibrillator (ICD) therapy is effective in primary and secondary prevention of sudden cardiac death among patients with prior myocardial infarction and depressed ejection fraction. However, conclusive evidence of survival benefit in patients with nonischemic cardiomyopathy (NICM) is still lacking. Objective  To determine whether ICD therapy reduces all-cause mortality in patients with NICM. Data Sources  MEDLINE (1966-2004), EMBASE (1991-2004), the Cochrane Central Register of Controlled Trials (through first quarter, 2004), reports presented at scientific meetings (2003-2004), and bibliographic review of secondary sources. Search terms included defibrillator, randomized controlled trials, clinical trials, andsudden death. Study Selection  Eligible studies were prospective randomized controlled trials of ICD or combined cardiac resynchronization therapy and defibrillator (CRT-D) vs medical therapy enrolling at least some individuals with NICM and reporting all-cause mortality as an outcome. Of 675 potentially relevant articles screened initially, 8 reports of randomized trials enrolling a total of 2146 patients with NICM were included. Data Extraction  Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, primary end point, mortality of ICD cohort, and mortality of control cohort. Data Synthesis  Five primary prevention trials enrolling 1854 patients with NICM were identified; pooled analysis suggested a significant reduction in total mortality among patients randomized to ICD or CRT-D vs medical therapy (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.55-0.87; P = .002). Mortality reduction remained significant even after elimination of CRT-D trials. Two of the 3 secondary prevention trials presented subgroup estimates for ICD efficacy in NICM. Pooled analysis of these secondary prevention trials (n = 256 patients with NICM) indicated an equivalent but nonsignificant mortality reduction with ICD therapy (RR, 0.69; 95% CI, 0.39-1.24; P = .22). Analysis of all 7 trials combined demonstrated a statistically significant 31% overall reduction in mortality with ICD therapy (RR, 0.69; 95% CI, 0.56-0.86; P = .002). Conclusion  ICD therapy appears to significantly reduce mortality in selected patients with NICM.      

Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial

Context  Basic research and observational evidence as well as results from trials of colon polyp recurrence suggest a role for aspirin in the chemoprevention of cancer. Objective  To examine the effect of aspirin on the risk of cancer among healthy women. Design, Setting, and Participants  In the Women’s Health Study, a randomized 2 x 2 factorial trial of aspirin and vitamin E conducted between September 1992 and March 2004, 39 876 US women aged at least 45 years and initially without previous history of cancer, cardiovascular disease, or other major chronic illness were randomly assigned to receive either aspirin or aspirin placebo and followed up for an average of 10.1 years. Intervention  A dose of 100 mg of aspirin (n=19 934) or aspirin placebo (n=19 942) administered every other day. Main Outcome Measures  Confirmed newly diagnosed invasive cancer at any site, except for nonmelanoma skin cancer. Incidence of breast, colorectal, and lung cancer were secondary end points. Results  No effect of aspirin was observed on total cancer (n = 2865; relative risk [RR], 1.01; 95% confidence interval [CI], 0.94-1.08; P = .87), breast cancer (n = 1230; RR, 0.98; 95% CI, 0.87-1.09; P = .68), colorectal cancer (n = 269; RR, 0.97; 95% CI, 0.77-1.24; P = .83), or cancer of any other site, with the exception of lung cancer for which there was a trend toward reduction in risk (n = 205; RR, 0.78; 95% CI, 0.59-1.03; P = .08). There was also no reduction in cancer mortality either overall (n = 583; RR, 0.95; 95% CI, 0.81-1.11; P = .51) or by site, except for lung cancer mortality (n = 140; RR, 0.70; 95% CI, 0.50-0.99; P = .04). No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was found. Conclusions  Results from this large-scale, long-term trial suggest that alternate day use of low-dose aspirin (100 mg) for an average 10 years of treatment does not lower risk of total, breast, colorectal, or other site-specific cancers. A protective effect on lung cancer or a benefit of higher doses of aspirin cannot be ruled out.      

Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial

Context  Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery. An exaggerated inflammatory response has been proposed to be one etiological factor. Objective  To test whether intravenous corticosteroid administration after cardiac surgery prevents AF after cardiac surgery. Design, Setting, and Patients  A double-blind, randomized multicenter trial (study enrollment August 2005–June 2006) in 3 university hospitals in Finland of 241 consecutive patients without prior AF or flutter and scheduled to undergo first on-pump coronary artery bypass graft (CABG) surgery, aortic valve replacement, or combined CABG surgery and aortic valve replacement. Intervention  Patients were randomized to receive either 100-mg hydrocortisone or matching placebo as follows: the first dose in the evening of the operative day, then 1 dose every 8 hours during the next 3 days. In addition, all patients received oral metoprolol (50-150 mg/d) titrated to heart rate. Main Outcome Measure  Occurrence of AF during the first 84 hours after cardiac surgery. Results  The incidence of postoperative AF was significantly lower in the hydrocortisone group (36/120 [30%]) than in the placebo group (58/121 [48%]; adjusted hazard ratio, 0.54; 95% confidence interval, 0.35-0.83; P = .004; number needed to treat, 5.6). Compared with placebo, patients receiving hydrocortisone did not have higher rates of superficial or deep wound infections, or other major complications. Conclusion  Intravenous hydrocortisone reduced the incidence of AF after cardiac surgery. Trial Registration  clinicaltrials.gov Identifier: NCT00442494      

5-单硝酸异山梨醇酯和普萘洛尔预防肝硬化食管静脉曲张再出血的随机对照研究

目的 探讨5－单硝酸异山梨醇酯和普萘洛尔联合治疗预防食管曲张静脉再出血的有效性。方法 66例肝硬化食管胃底曲张静脉出血的病人被随机分成5－单硝酸慢山梨醇酯（IM）加普萘洛尔（PR）组（34例）和普萘洛尔（32例）组接受治疗。结果 5例PR＋IM组病人和9例PR组病人在接受治疗后随访1年期间发生再出血,PR＋IM组再出血的可能性低于单用PR组,但差异无显著意义。在把随访时间延长到20个月时,两组再出血的危险性下降差异有显著意义（P＝0．047）,但再出血指数和生存时间差异无显著意义,多元COX分析显示年龄（0．045）、肝病严重程度（0．03）和治疗（0．04）是再出血的预示指数,PR＋IM使再出血的危险减少了一半（相对危险度0．54）。结论 联用5－单硝酸异山梨醇酯增加了普萘洛尔预防肝硬化食管曲张静脉再出血的有效性,但未明显改善肝硬化病人的生存期。     

Oral fibrinogen-depleting agent lumbrokinase for secondary ischemic stroke prevention: results from a multicenter, randomized, parallel-group and controlled clinical trial

Background Elevated fibrinogen （Fg） level is a known risk factor for ischemic stroke. There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention. We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention.     

Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial

Context  Non–cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy. Objective  To determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs. Design, Setting, and Patients  Randomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women’s health clinics in Khayelitsha, South Africa. Interventions  All patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation. Main Outcome Measures  Biopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy. Results  The prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (P<.001 and P = .02 for the HPV DNA and VIA groups, respectively). A subset of women underwent a second colposcopy 12 months after enrollment. At 12 months the cumulative detection of CIN 2+ among women in the HPV DNA group was 1.42% (95% CI, 0.88%-1.97%), 2.91% (95% CI, 2.12%-3.69%) in the VIA group, and 5.41% (95% CI, 4.32%-6.50%) in the delayed evaluation group. Although minor complaints, such as discharge and bleeding, were common after cryotherapy, major complications were rare. Conclusion  Both screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months. Trial Registration  http://clinicaltrials.gov Identifier: NCT00233727.      

Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial

Context  Blacks are disproportionately affected by stroke, and they are about 2 times more likely than most other individuals in the United States to die of or experience stroke. Objective  To determine the efficacy and safety of aspirin and ticlopidine to prevent recurrent stroke in black patients. Design, Setting, and Patients  Randomized, double-blind, investigator-initiated, multicenter trial of 1809 black men and women who recently had a noncardioembolic ischemic stroke and who were recruited between December 1992 and October 2001 from 62 academic and community hospitals in the United States and followed up for up to 2 years. Intervention  A total of 902 patients received 500 mg/d of ticlopidine and 907 received 650 mg/d of aspirin. Main Outcome Measures  Recurrent stroke, myocardial infarction, or vascular death was the composite primary end point (according to intention-to-treat analysis). The secondary outcome was fatal or nonfatal stroke. Results  The blinded phase of the study was halted after about 6.5 years when futility analyses revealed a less than 1% probability of ticlopidine being shown superior to aspirin in the prevention of the primary outcome end point. The primary outcome of recurrent stroke, myocardial infarction, or vascular death was reached by 133 (14.7%) of 902 patients assigned to ticlopidine and 112 (12.3%) of 907 patients assigned to aspirin (hazard ratio, 1.22; 95% confidence interval, 0.94-1.57). Kaplan-Meier curves for time to event for the primary outcome did not differ significantly (P = .12 by log-rank test). Kaplan-Meier curves for time to the secondary outcome of fatal or nonfatal stroke approached a statistically significant reduction favoring aspirin over ticlopidine (P = .08 by log-rank test). The frequency of laboratory-determined serious neutropenia was 3.4% for patients receiving ticlopdine vs 2.2% for patients receiving aspirin (P = .12) and 0.3% vs 0.2% for thrombocytopenia, respectively (P = .69). One ticlopidine-treated patient developed thrombocytopenia, which was thought to be a case of possible thrombotic thrombocytopenia purpura, and recovered after therapy with plasmapheresis. Conclusions  During a 2-year follow-up, we found no statistically significant difference between ticlopidine and aspirin in the prevention of recurrent stroke, myocardial infarction, or vascular death. However, there was a nonsignificant trend for reduction of fatal or nonfatal stroke among those in the aspirin group. Based on these data and the risk of serious adverse events with ticlopidine, we regard aspirin as a better treatment for aspirin-tolerant black patients with noncardioembolic ischemic stroke.      

Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial

Context  Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis. Objective  To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure. Design, Setting, and Participants  Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001. Intervention  The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868). Main Outcome Measures  The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued. Results  After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P = .23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo. Conclusion  Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.