Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials

Context  Nesiritide improves symptoms in patients with acutely decompensated heart failure compared with placebo and appears to be safer than dobutamine. Its short-term safety relative to standard diuretic and vasodilator therapies is less clear. Objective  To investigate the safety of nesiritide relative to noninotrope-based control therapies, primarily consisting of diuretics or vasodilators. Data Sources  Primary reports of completed clinical trials as of December 2004 were obtained from the US Food and Drug Administration (FDA), the study sponsor (Scios Inc), a PubMed literature search using the terms nesiritide, clinical trials, and humans, and a manual search of annual meetings of 3 heart associations. Study Selection  Of 12 randomized controlled trials evaluating nesiritide, 3 met all inclusion criteria: randomized double-blind study of patients with acutely decompensated heart failure, therapy administered as single infusion (6 hours), inotrope not mandated as control, and reported 30-day mortality. Data Extraction  Data were extracted from FDA and sponsor documents and corroborated with published articles when available. Thirty-day survival was assessed by meta-analysis using a fixed-effects model and time-dependent risk by Kaplan-Meier analysis with Cox proportional hazards regression modeling. Where deaths were described within a range of days after treatment, an extreme assumption was made favoring nesiritide over control therapy, an approach relevant to the time-dependent analyses. Data Synthesis  In the 3 trials, 485 patients were randomized to nesiritide and 377 to control therapy. Death within 30 days tended to occur more often among patients randomized to nesiritide therapy (35 [7.2%] of 485 vs 15 [4.0%] of 377 patients; risk ratio from meta-analysis, 1.74; 95% confidence interval [CI], 0.97-3.12; P = .059; and hazard ratio after adjusting for study, 1.80; 95% CI, 0.98-3.31; P = .057). Conclusions  Compared with noninotrope-based control therapy, nesiritide may be associated with an increased risk of death after treatment for acutely decompensated heart failure. The possibility of an increased risk of death should be investigated in a large-scale, adequately powered, controlled trial before routine use of nesiritide for acutely decompensated heart failure.      

静脉注射基因重组人脑利钠肽治疗失代偿性心力衰竭疗效观察

目的 研究该药物在失代偿性心力衰竭患者中的临床应用,观察其血流动力学效应及安全性.方法 将住院的60例失代偿性心力衰竭患者随机分为静脉滴注重组人脑利钠肽(rhBNP)组和对照组,每组30例,比较两组有创血流动力学参数和治疗2周内的左室射血分数和主要不良心脏事件(MACE)的发生情况.结果 rhBNP组和对照组治疗前后中心静脉压(CVP)和收缩压(SBP)无明显变化,但停药6 h 后rhBNP组肺毛细血管楔嵌压(PCWP)较对照组明显降低[分别为(16±5)mm Hg、(24±6)mm Hg(1 mm Hg=0.133 kPa), P<0.05].全身临床症状缓解率为62%(对照组21%,P<0.05),呼吸困难缓解率为57%(对照组19%,P<0.01),虚弱症状缓解率为32%(对照组5%,P<0.01).2周后查心脏彩超左室射血分数,rhBNP组[(44±6)%]较对照组[(37±4)%]显著改善(P<0.05).本研究发现1例与rhBNP相关的症状性低血压,无其他严重不良反应.两组治疗2周内的MACE发生情况相似.结论 对失代偿性心力衰竭患者静脉注射rhBNP能够迅速改善血流动力学指标和全身症状,治疗失代偿性心力衰竭安全有效. Abstract： Objective To investigate the clinical use of nesiritide in such patients to observe the effects and safety.Methods Patients hospitalized because of symptomatic congestive heart failure(60 cases) were randomized into rhBNP group [n = 30, 1.5 μg/kg intravenous injection followed by 0.0075 μg/(kg·min) for following 48 hours] and control group (n=30). The hemodynamic parameters were monitored by Swan-Ganz catheter at baseline, during drug infusion and 6 hours post infusion withdraw. The major adverse cardiac events (MACE) and left ventricular ejection fraction were observed up to 2 weeks after drug infusions. Results Central venous pressure and systolic blood pressure remained unchanged after rhBNP infusion or control group. Compared to baseline level, PCWP was significantly reduced, this effect remained to 6 hours before infusion withdraw. In the efficacy trial, at six hours, resulted in improvements in global clinical status in 62 percent of the patients (as compared with 21 percent, P<0.05), reduced dyspnea in 57 percent (as compared with 19 percent, P<0.01), and reduced fatigue in 32 percent (as compared with 5 percent, P<0.01). After two weeks, rhBNP group left ventricular ejection fraction significantly improved compared with control group. There was 1 case of rhBNP associated symptomatic hypotension, no other adverse event during drug infusion in both groups. MACE up to 2 weeks post drug infusion was also similar between the two groups.Conclusions In patients hospitalized with decompensated congestive heart failure, nesiritide improves hemodynamic function and clinical status. Nesiritide is useful and safe for the treatment of decompensated congestive heart failure.     

Carvedilol for children and adolescents with heart failure: a randomized controlled trial

Context  Although -blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. Objective  To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. Design, Setting, and Participants  A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). Interventions  Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight 62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight 62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. Main Outcome Measures  The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. Results  There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). Conclusions  These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. Trial Registration  clinicaltrials.gov Identifier: NCT00052026      

Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture

The diuretic effect of the supine position was evaluated in six patients with cirrhosis and ascites and six with congestive cardiac failure. After fasting overnight in bed the patients received bumetanide 1 mg intravenously and were then immediately randomly assigned to either bed rest in the supine position or normal daily activity in the upright position for the next six hours. Two days later the procedure was repeated, the patients being assigned to the other posture. The diuretic response was similar in patients with heart failure and cirrhosis, and was significantly greater in the supine than in the upright position: mean 1133 v 626 ml/6 h (p less than 0.01). The natriuresis was similarly larger during recumbency: mean sodium 96 v 45 mmol(mEq)/6h (p less than 0.01), and the excreted potassium in six hours was similar in both postures. The glomerular filtration rate was 100 and 66 ml/min (p less than 0.01) and heart rate 76 and 83 beats/min (p less than 0.01) in the supine and upright positions respectively. Plasma concentrations of noradrenaline, renin, and aldosterone were all raised even when the patient adopted the supine position, and a further significant rise was observed during the upright position. The results suggest that the attenuated response to intravenous bumetanide in the upright position and during normal daily activity may be due to the activation of several homeostatic mechanisms that may reduce the excretion of water and salt.     

Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial

CONTEXT: Little randomized evidence is available to guide the in-hospital management of patients with an acute exacerbation of chronic heart failure. Although intravenous inotropic therapy usually produces beneficial hemodynamic effects and is labeled for use in the care of such patients, the effect of such therapy on intermediate-term clinical outcomes is uncertain. OBJECTIVE: To prospectively test whether a strategy that includes short-term use of milrinone in addition to standard therapy can improve clinical outcomes of patients hospitalized with an exacerbation of chronic heart failure. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial conducted from July 1997 through November 1999. SETTING: Seventy-eight community and tertiary care hospitals in the United States. PARTICIPANTS: A total of 951 patients admitted with an exacerbation of systolic heart failure not requiring intravenous inotropic support (mean age, 65 years; 92% with baseline New York Heart Association class III or IV; mean left ventricular ejection fraction, 23%). INTERVENTION: Patients were randomly assigned to receive a 48-hour infusion of either milrinone, 0.5 microg/kg per minute initially (n = 477), or saline placebo (n = 472). MAIN OUTCOME MEASURE: Cumulative days of hospitalization for cardiovascular cause within 60 days following randomization. RESULTS: The median number of days hospitalized for cardiovascular causes within 60 days after randomization did not differ significantly between patients given milrinone (6 days) compared with placebo (7 days; P =.71). Sustained hypotension requiring intervention (10.7% vs 3.2%; P<.001) and new atrial arrhythmias (4.6% vs 1.5%; P =.004) occurred more frequently in patients who received milrinone. The milrinone and placebo groups did not differ significantly in in-hospital mortality (3.8% vs 2.3%; P =.19), 60-day mortality (10.3% vs 8.9%; P =.41), or the composite incidence of death or readmission (35.0% vs 35.3%; P =.92) CONCLUSION: These results do not support the routine use of intravenous milrinone as an adjunct to standard therapy in the treatment of patients hospitalized for an exacerbation of chronic heart failure.     

硝酸甘油和重组人脑利钠肽对急性失代偿性心力衰竭的疗效比较

目的 比较重组人脑利钠肽(rhBNP)和硝酸甘油对失代偿性心力衰竭的临床疗效.方法 我院50例失代偿性心力衰竭住院患者随机分为硝酸甘油组和rhBNP组,分别记录两组患者给药前及给药后30 min、6 h及24 h的呼吸困难程度以及整体临床情况.以及用药24 h后液体的出入量和血流动力学参数.其中硝酸甘油组使用硝酸甘油开始剂量为5?g/min.每3～5分钟增加5?g/min,根据个体的血流动力学参数来调整用量;rhBNP组使用rhBNP,首先以1.5 ?g/kg弹丸式静脉冲击,随后以0.0075 ?g穔g-1穖in-1连续静脉滴注72 h.结果 rhBNP组患者静脉给药后30 min和6h的呼吸困难好转程度(P值分别为0.042和0.019)和整体临床状况好转程度(P值分别是0.018和0.044)均显著优于硝酸甘油组,24h后两组未有明显差异(P值分别是0.192和0.179);用药24 h后的尿量rhBNP组(1513.8±242.9)ml明显多于硝酸甘油组(1341.2±239.7)ml(P=0.015);用药24h时rhBNP组患者射血分数的增加以及肺动脉压和收缩压的降低均明显多于硝酸甘油组(P值分别是0.001、0.000及0.002),用药72 h后rhBNP组室性期前收缩、成对期前收缩和阵发性室性心动过速等室性心律失常发作的次数明显减少(P值分别是0.000、0.001和0.002).结论 rhBNP通过促进尿量的排泄、降低肺动脉压及增加左室射血分数等途径明显改善失代偿性心力衰竭患者呼吸困难和整体临床状况,以及明显减少室性心律失常的发作.     

Surgery vs orthosis vs watchful waiting for hallux valgus: a randomized controlled trial

CONTEXT: Hallux valgus is a common foot deformation in adults, but evidence for effectiveness of surgical and conservative treatments for this condition is limited. OBJECTIVE: To compare the effectiveness of surgical and orthotic treatment with no treatment in patients with hallux valgus. DESIGN AND SETTING: Randomized controlled trial conducted in 4 general community hospitals in Finland in 1997-1998, with a follow-up period of 12 months. PARTICIPANTS: Two hundred nine consecutive patients (mean age, 48 years; 93% women) with a painful bunion and a hallux valgus angle 35 degrees or less. INTERVENTIONS: Patients were randomly assigned to surgery (distal chevron osteotomy; n = 71), orthosis (n = 69), or a 1-year waiting list (control group, n = 69). MAIN OUTCOME MEASURES: Pain intensity during walking on a visual analog scale (0-100), patient assessment of global improvement, number of painful days, cosmetic disturbance, footwear problems, functional status, and treatment satisfaction, compared among treatment groups. RESULTS: Follow-up rates at 6 and 12 months were 99% and 98%, respectively. At 6 months, pain intensity decreased more in the surgical group than in the control group (adjusted mean differences, -20 [95% confidence interval (CI), -28 to -12]) and more in orthosis than in the control groups (adjusted mean difference, -14 [95% CI, -22 to -6. At 1 year, pain intensity decreased more in the surgical than in the control groups (adjusted mean difference, -19 [95% CI, -28 to -10]) and more than in the surgical and orthosis groups (adjusted mean difference, -14 [95% CI, -22 to -5]). At 1 year, 83%, 46%, and 24% in the surgery, orthosis, and control groups, respectively, thought they had improved compared with baseline (number needed to treat), 1.7 between surgical and control groups). Number of painful days, cosmetic disturbance, and footwear problems were least and functional status and satisfaction with treatment were best in the surgical group. CONCLUSIONS: Surgical osteotomy is an effective treatment for painful hallux valgus. Orthoses provide short-term symptomatic relief.     

人脑型利钠肽治疗慢性收缩性心力衰竭随机对照试验的Meta分析

目的了解人脑型利钠肽(BNP)治疗慢性收缩性心力衰竭患者对血流动力学方面的效应及其安全性和耐受性。方法以慢性收缩性心力衰竭为主题词,BNP和Nesiritide(重组人脑钠肽)分别为文本词,对MEDLINE数据库(1966～2007)进行检索,纳入临床随机对照试验(RCT)。结果对13个RCT的纳入对象、方法学和结果等方面进行评价。Nesifitide可平均降低肺毛细血管楔压(PCWP)4.06 mm Hg,95%可信区间(95%CI)[-4.79,-3.33,(P<0.01)];增加心脏指数(CI)0.08 L·min~(-1)·m~(-2),95%CI[0.02,0.15,(P=0.01)],不同程度地降低心率(HR),改善血流动力学指标以及心电图指标。对高危患者使用Nesiritide可降低各种原因的病死率。结论BNP有效改善心力衰竭患者的血流动力学,减少严重心力衰竭患者远期病死率,治疗量安全能耐受,推荐小剂量使用。     

氯沙坦治疗慢性充血性心衰的临床观察

目的观察比较氯沙坦与开搏通治疗慢性心衰的疗效,安全性及耐受性.方法采用随机法,将慢性心衰(CHF)病人83例,NYHA分级为Ⅱ至Ⅳ级,在常规治疗基础上,分成氯沙坦组(A组)44例,开搏通组(B组)39例,2组疗程均为48周.观察用药前后各相关指标,各组的临床疗效,安全性及耐受性.结果临床有效率,A、B组相似,无显著差异(P＞0.05),心超及心功能指标A、B组无显著差异(P＞0.05),LVMI的变化A组好于B组.不良反应A组较少,且有降低尿酸作用,停药率明显低于B组.结论氯沙坦治疗CHF疗效好,不良反应少,耐受性佳.     

Splinting vs surgery in the treatment of carpal tunnel syndrome: a randomized controlled trial

Context  Carpal tunnel syndrome (CTS) can be treated with nonsurgical or surgical options. However, there is no consensus on the most effective method of treatment. Objective  To compare the short-term and long-term efficacy of splinting and surgery for relieving the symptoms of CTS. Design, Setting, and Patients  A randomized controlled trial conducted from October 1998 to April 2000 at 13 neurological outpatient clinics in the Netherlands. A total of 176 patients with clinically and electrophysiologically confirmed idiopathic CTS were assigned to wrist splinting during the night for at least 6 weeks (89 patients) or open carpal tunnel release (87 patients); 147 patients (84%) completed the final follow-up assessment 18 months after randomization. Main Outcome Measures  General improvement, number of nights waking up due to symptoms, and severity of symptoms. Results  In the intention-to-treat analyses, surgery was more effective than splinting on all outcome measures. The success rates (based on general improvement) after 3 months were 80% for the surgery group (62/78 patients) vs 54% for the splinting group (46/86 patients), which is a difference of 26% (95% confidence interval [CI], 12%-40%; P<.001). After 18 months, the success rates increased to 90% for the surgery group (61/68 patients) vs 75% for the splinting group (59/79 patients), which is a difference of 15% (95% CI, 3%-27%; P = .02). However, by that time 41% of patients (32/79) in the splint group had also received the surgery treatment. Conclusion  Treatment with open carpal tunnel release surgery resulted in better outcomes than treatment with wrist splinting for patients with CTS.      

Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial

Context  Herbal extracts from Commiphora mukul (guggul) have been widely used in Asia as cholesterol-lowering agents, and their popularity is increasing in the United States. Recently, guggulsterones, the purported bioactive compounds of guggul, have been shown to be potent antagonists of 2 nuclear hormone receptors involved in cholesterol metabolism, establishing a plausible mechanism of action for the hypolipidemic effects of these extracts. However, there are currently no published safety or efficacy data on the use of guggul extracts in Western populations. Objective  To study the short-term safety and efficacy of 2 doses of a standardized guggul extract (guggulipid, containing 2.5% guggulsterones) in healthy adults with hyperlipidemia eating a typical Western diet. Design  Double-blind, randomized, placebo-controlled trial using a parallel design, conducted March 2000-August 2001. Participants and Setting  A total of 103 ambulatory, community-dwelling, healthy adults with hypercholesterolemia in the Philadelphia, Pa, metropolitan area. Intervention  Oral, 3 times daily doses of standard-dose guggulipid (1000 mg), high-dose guggulipid (2000 mg), or matching placebo. Main Outcome Measures  Percentage change in levels of directly measured low-density lipoprotein cholesterol (LDL-C) after 8 weeks of therapy. Secondary outcome measures included levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and directly measured very low-density lipoprotein cholesterol (VLDL-C), as well as adverse events reports and laboratory safety measures including electrolyte levels and hepatic and renal function. Results  Compared with participants randomized to placebo (n = 36), in whom levels of LDL-C decreased by 5%, both standard-dose guggulipid (n = 33) and high-dose guggulipid (n = 34) raised levels of LDL-C by 4% (P = .01 vs placebo) and 5% (P = .006 vs placebo), respectively, at 8 weeks, for a net positive change of 9% to 10%. There were no significant changes in levels of total cholesterol, HDL-C, triglycerides, or VLDL-C in response to treatment with guggulipid in the intention-to-treat analysis. While guggulipid was generally well tolerated, 6 participants treated with guggulipid developed a hypersensitivity rash compared with none in the placebo group. Conclusions  Despite plausible mechanisms of action, guggulipid did not appear to improve levels of serum cholesterol over the short term in this population of adults with hypercholesterolemia, and might in fact raise levels of LDL-C. Guggulipid also appeared to cause a dermatologic hypersensitivity reaction in some patients.      

Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: a randomized controlled trial

Context  Despite evidence that methadone maintenance treatment (MMT) is effective for opioid dependence, it remains a controversial therapy because of its indefinite provision of a dependence-producing medication. Objective  To compare outcomes of patients with opioid dependence treated with MMT vs an alternative treatment, psychosocially enriched 180-day methadone-assisted detoxification. Design  Randomized controlled trial conducted from May 1995 to April 1999. Setting  Research clinic in an established drug treatment service. Patients  Of 858 volunteers screened, 179 adults with diagnosed opioid dependence were randomized into the study; 154 completed 12 weeks of follow-up. Interventions  Patients were randomized to MMT (n = 91), which required 2 hours of psychosocial therapy per week during the first 6 months; or detoxification (n = 88), which required 3 hours of psychosocial therapy per week, 14 education sessions, and 1 hour of cocaine group therapy, if appropriate, for 6 months, and 6 months of (nonmethadone) aftercare services. Main Outcome Measures  Treatment retention, heroin and cocaine abstinence (by self-report and monthly urinalysis), human immunodeficiency virus (HIV) risk behaviors (Risk of AIDS Behavior scale score), and function in 5 problem areas: employment, family, psychiatric, legal, and alcohol use (Addiction Severity Index), compared by intervention group. Results  Methadone maintenance therapy resulted in greater treatment retention (median, 438.5 vs 174.0 days) and lower heroin use rates than did detoxification. Cocaine use was more closely related to study dropout in detoxification than in MMT. Methadone maintenance therapy resulted in a lower rate of drug-related (mean [SD] at 12 months, 2.17 [3.88] vs 3.73 [6.86]) but not sex-related HIV risk behaviors and in a lower severity score for legal status (mean [SD] at 12 months, 0.05 [0.13] vs 0.13 [0.19]). There were no differences between groups in employment or family functioning or alcohol use. In both groups, monthly heroin use rates were 50% or greater, but days of use per month dropped markedly from baseline. Conclusions  Our results confirm the usefulness of MMT in reducing heroin use and HIV risk behaviors. Illicit opioid use continued in both groups, but frequency was reduced. Results do not provide support for diverting resources from MMT into long-term detoxification.      

Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial

Context  Three-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen. Objective  To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection. Design  The AIDS Clinical Trials Group (ACTG) A5095 study, a randomized, double-blind, placebo-controlled study with enrollment and follow-up conducted from March 22, 2001, to March 1, 2005, and enrolling treatment-naive, HIV-1–infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG. Interventions  Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/lamivudine/abacavir plus efavirenz (4-drug regimen). Main Outcome Measures  Time to virologic failure (defined as time to first of 2 successive HIV-1 RNA levels 200 copies/mL at or after week 16), CD4 cell count changes, and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless of treatment changes. Results  Seven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log₁₀ (72 444) copies/mL and CD4 cell count of 240 cells/mm³ were randomized. After a median 3-year follow-up, 99 (26%) of 382 and 94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively, reached protocol-defined virologic failure; time to virologic failure was not significantly different (hazard ratio, 0.95; 97.5% confidence interval, 0.69-1.33; P = .73). In planned subgroup analyses, increased risk for virologic failure was seen in non-Hispanic black patients (adjusted hazard ratio, 1.66; 95% confidence interval, 1.18-2.34; P = .003). At 3 years, the HIV-1 RNA level was less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients receiving the 3-drug and 4-drug regimens, respectively (P = .59), and less than 50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients (P = .39). CD4 cell count increases and grade 3 or 4 adverse events were not significantly different. Conclusions  In treatment-naive patients, there were no significant differences between the 3-drug and 4-drug antiretroviral regimens; overall, at least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years. These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding abacavir as a fourth drug provided no additional benefit. Clinical Trials Registration  clinicaltrials.gov Identifier: NCT00013520      

Cognitive behavioral therapy vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial

Context  Insomnia is a common condition in older adults and is associated with a number of adverse medical, social, and psychological consequences. Previous research has suggested beneficial outcomes of both psychological and pharmacological treatments, but blinded placebo-controlled trials comparing the effects of these treatments are lacking. Objective  To examine short- and long-term clinical efficacy of cognitive behavioral therapy (CBT) and pharmacological treatment in older adults experiencing chronic primary insomnia. Design, Setting, and Participants  A randomized, double-blinded, placebo-controlled trial of 46 adults (mean age, 60.8 y; 22 women) with chronic primary insomnia conducted between January 2004 and December 2005 in a single Norwegian university-based outpatient clinic for adults and elderly patients. Intervention  CBT (sleep hygiene, sleep restriction, stimulus control, cognitive therapy, and relaxation; n = 18), sleep medication (7.5-mg zopiclone each night; n = 16), or placebo medication (n = 12). All treatment duration was 6 weeks, and the 2 active treatments were followed up at 6 months. Main Outcome Measures  Ambulant clinical polysomnographic data and sleep diaries were used to determine total wake time, total sleep time, sleep efficiency, and slow-wave sleep (only assessed using polysomnography) on all 3 assessment points. Results  CBT resulted in improved short- and long-term outcomes compared with zopiclone on 3 out of 4 outcome measures. For most outcomes, zopiclone did not differ from placebo. Participants receiving CBT improved their sleep efficiency from 81.4% at pretreatment to 90.1% at 6-month follow-up compared with a decrease from 82.3% to 81.9% in the zopiclone group. Participants in the CBT group spent much more time in slow-wave sleep (stages 3 and 4) compared with those in other groups, and spent less time awake during the night. Total sleep time was similar in all 3 groups; at 6 months, patients receiving CBT had better sleep efficiency using polysomnography than those taking zopiclone. Conclusion  These results suggest that interventions based on CBT are superior to zopiclone treatment both in short- and long-term management of insomnia in older adults. Trial Registration  clinicaltrials.gov Identifier: NCT00295386