Low-dose inhaled nitric oxide in patients with acute lung injury: a randomized controlled trial

Context  Inhaled nitric oxide has been shown to improve oxygenation in acute lung injury. Objective  To evaluate the clinical efficacy of low-dose (5-ppm) inhaled nitric oxide in patients with acute lung injury. Design and Setting  Multicenter, randomized, placebo-controlled study, with blinding of patients, caregivers, data collectors, assessors of outcomes, and data analysts (triple blind), conducted in the intensive care units of 46 hospitals in the United States. Patients were enrolled between March 1996 and September 1999. Patients  Patients (n = 385) with moderately severe acute lung injury, a modification of the American-European Consensus Conference definition of acute respiratory distress syndrome (ARDS) using a ratio of PaO₂ to FiO₂ of 250, were enrolled if the onset was within 72 hours of randomization, sepsis was not the cause of the lung injury, and the patient had no significant nonpulmonary organ system dysfunction at randomization. Interventions  Patients were randomly assigned to placebo (nitrogen gas) or inhaled nitric oxide at 5 ppm until 28 days, discontinuation of assisted breathing, or death. Main Outcome Measures  The primary end point was days alive and off assisted breathing. Secondary outcomes included mortality, days alive and meeting oxygenation criteria for extubation, and days patients were alive following a successful unassisted ventilation test. Results  An intent-to-treat analysis revealed that inhaled nitric oxide at 5 ppm did not increase the number of days patients were alive and off assisted breathing (mean [SD], 10.6 [9.8] days in the placebo group and 10.7 [9.7] days in the inhaled nitric oxide group; P = .97; difference, –0.1 day [95% confidence interval, –2.0 to 1.9 days]). This lack of effect on clinical outcomes was seen despite a statistically significant increase in PaO₂ that resolved by 48 hours. Mortality was similar between groups (20% placebo vs 23% nitric oxide; P = .54). Days patients were alive following a successful 2-hour unassisted ventilation trial were a mean (SD) of 11.9 (9.9) for placebo and 11.4 (9.8) for nitric oxide patients (P = .54). Days alive and meeting criteria for extubation were also similar: 17.0 placebo vs 16.7 nitric oxide (P = .89). Conclusion  Inhaled nitric oxide at a dose of 5 ppm in patients with acute lung injury not due to sepsis and without evidence of nonpulmonary organ system dysfunction results in short-term oxygenation improvements but has no substantial impact on the duration of ventilatory support or mortality.      

A randomized trial of sodium intake and blood pressure in newborn infants

We studied the effect of dietary sodium on BP in a double-blind randomized trial with 245 newborn infants assigned to a normal-sodium diet and 231 to a low-sodium diet during the first six months of life. The sodium intake of the normal-sodium group was almost three times that of the low-sodium group. Systolic BP was measured every month from the first week until the 25th week. At 25 weeks, systolic pressure was 2.1 mm Hg lower in the low-sodium group than in the normal-sodium group. The difference between the groups increased significantly during the first six months of life. These observations are in agreement with the view that sodium intake is causally related to BP level.     

松龄血脉康胶囊对原发性高血压患者动态血压相关指标的影响：随机单盲对照试验

目的：在联合使用钙离子拮抗剂及血管紧张素受体拮抗剂的基础上加用中成药,观察其对24h动态血压监测相关指标的影响,评价降压效应及降压稳定性。方法：将70例初诊为原发性高血压或有原发性高血压病史但服药无规律或未正规服药,就诊时血压分级为2～3级的患者随机分为常规降压组（常规组）和常规降压加松龄血脉康组（松龄血脉康组）,每组各35例。常规组口服左旋氨氯地平片2．5mg,联合替米沙坦片40mg,1次／d。松龄血脉康组在常规组治疗的基础上加服松龄血脉康胶囊1．5g,3次／d。疗程均为2周。治疗前后分别进行24h动态血压监测,并进行谷峰比值、平滑指数等指标的计算和血压晨峰的判定。结果：两组治疗后24h、白昼及夜间平均收缩压和收缩压负荷值均低于治疗前（P〈0．05）,常规降压加松龄血脉康的降压效果优于常规降压（P〈0．05）。常规降压加松龄血脉康能降低舒张压,而常规降压对舒张压的影响不明显。常规降压加松龄血脉康降压的同时能减慢心率,常规降压则对心率影响不明显。松龄血脉康组谷峰比值高于常规降压组（P〈0．05）,两组平滑指数比较,差异无统计学意义。两组治疗后血压晨峰现象均得到改善（P〈0．05）,常规降压加松龄血脉康对血压晨峰现象的改善程度优于常规降压（P〈0．05）。结论：在联合使用左旋氨氯地平片和替米沙坦片的基础上加用中成药松龄血脉康胶囊,能更有效地降低心率和血压,特别是收缩压和收缩压负荷值,降压效应的平稳性更高,维持时间更长,还能有效控制血压晨峰现象。     

天麻素注射液对老年难治性高血压患者血压和血管活性物质影响的随机对照研究

目的：检测并比较老年难治性高血压患者血浆内皮素（endothelin，ET）和一氧化氮（nitric oxide，NO）含量变化．观察天麻素注射液对老年难治性高血压患者血压及血浆ET和NO含量的影响。 方法：选取老年难治性高血压患者63例，普通高血压患者30例，健康人群30例，检测并比较其血浆ET和NO含量变化；将难治性高血压患者随机分为2组：天麻素治疗组和常规治疗组。天麻素治疗组在常规治疗的基础上加用天麻素注射液1000mg静脉滴注2个疗程，共4周，常规治疗组继续常规降压药物治疗，观察治疗前和每个疗程后血压的变化，并比较血浆ET和NO含量的变化。 结果：难治性高血压患者血浆ET含量明显高于普通高血压者（t=3．27，P=0．008），NO含量明显低于普通高血压者（t=-3．81．P=0．002）。天麻素治疗组患者在治疗1个疗程后收缩压和脉压差均明显下降（t=1．85，P=0．03；t=1．74．P=0．04）。天麻素治疗组随着治疗疗程的增加，ET含量逐渐下降，但2个疗程结束后与治疗前相比，差异仍无统计学意义；而NO含量在2个疗程结束后明显升高，与治疗前相比．差异有统计学意义（t=-2．70，P=0．04）。 结论：与普通高血压患者比较，难治性高血压患者血浆ET明显升高，NO含量显著降低。天麻素注射液可以降低老年难治性高血压患者的血压，且其降低收缩压的作用相对较强。可能通过调节患者血管活性物质来实现降压，但具体机制尚需进一步研究。     

Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial

Context  Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. Objective  To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. Design, Setting, and Participants  Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. Interventions  A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. Main Outcome Measures  Systolic blood pressure and low-density lipoprotein cholesterol. Results  Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P = .002) and by 3.5 mm Hg (P = .006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P = .01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P = .02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P = .005) and by 2.9 mm Hg among those with hypertension (P = .02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P = .03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P = .02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. Conclusion  In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk. Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00051350.      

Effects of inhaled nitric oxide in neonatal hypoxemic respiratory failure from a multicenter controlled trial

Background  Hypoxemic respiratory failure (HRF) is one of the most common causes for neonatal infants requiring aggressive respiratory support. Inhaled nitric oxide (iNO) has been established routinely as an adjunct to conventional respiratory support in developed countries. The aim of this study was to investigate effects of iNO in neonates with HRF in resource limited condition with no or limited use of surfactant, high frequency oscillatory ventilation (HFOV) and extracorporeal membrane oxygenation.

Methods  A non-randomized, open, controlled study of efficacy of iNO was conducted over 18 months. Eligible term and near-term neonates from 28 hospitals with HRF (oxygenation index >15) were enrolled prospectively into two groups as either iNO or control. Oxygenation improvement and mortality as primary endpoint were determined in relation with dosing and timing of iNO, severity of underlying diseases, complications and burden. Intention-to-treat principle was adopted for outcome assessment. Response to iNO at 10 or 20 parts per million (ppm) was determined by oxygenation in reference to the control (between-group) and the baseline (within-group).

Results  Compared to 93 controls, initial dose of iNO at 10 ppm in 107 treated infants significantly improved oxygenation from first hour (P=0.046), with more partial- and non-responders improved oxygenation with subsequent 20 ppm NO (P=0.018). This effect persisted on days 1 and 3, and resulted in relatively lower mortalities (11.2% vs. 15%) whereas fewer were treated with surfactant (10% vs. 27%), HFOV (<5%) or postnatal corticosteroids (<10%) in both groups. The overall outcomes at 28 days of postnatal life in the iNO-treated was not related to perinatal asphyxia, underlying diseases, severity of hypoxemia, or complications, but to the early use of iNO. The cost of hospital stay was not significantly different in both groups.

Conclusions  With relatively limited use of surfactant and/or HFOV in neonatal HRF, significantly more responders were found in the iNO-treated patients as reflected by improved oxygenation in the first three days over the baseline level. It warrants a randomized, controlled trial for assessment of appropriate timing and long-term outcome of iNO.

     

Antihypertensive treatment based on blood pressure measurement at home or in the physician's office: a randomized controlled trial

Context  Self-measurement of blood pressure is increasingly used in clinical practice, but how it affects the treatment of hypertension requires further study. Objective  To compare use of blood pressure (BP) measurements taken in physicians' offices and at home in the treatment of patients with hypertension. Design, Setting, and Participants  Blinded randomized controlled trial conducted from March 1997 to April 2002 at 56 primary care practices and 3 hospital-based outpatient clinics in Belgium and 1 specialized hypertension clinic in Dublin, Ireland. Four hundred participants with a diastolic BP (DBP) of 95 mm Hg or more as measured at physicians' offices were enrolled and followed up for 1 year. Interventions  Antihypertensive drug treatment was adjusted in a stepwise fashion based on either the self-measured DBP at home (average of 6 measurements per day during 1 week; n = 203) or the average of 3 sitting DBP readings at the physician's office (n = 197). If the DBP guiding treatment was above (>89 mm Hg), at (80-89 mm Hg), or below (<80 mm Hg) target, a physician blinded to randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively. Mean Outcome Measures  Office and home BP levels, 24-hour ambulatory BP, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and costs of treatment. Results  At the end of the study (median follow-up, 350 days; interquartile range, 326-409 days), more home BP than office BP patients had stopped antihypertensive drug treatment (25.6% vs 11.3%; P<.001) with no significant difference in the proportions of patients progressing to multiple-drug treatment (38.7% vs 45.1%; P = .14). The final office, home, and 24-hour ambulatory BP measurements were higher (P<.001) in the home BP group than in the office BP group. The mean baseline-adjusted systolic/diastolic differences between the home and office BP groups averaged 6.8/3.5 mm Hg, 4.9/2.9 mm Hg, and 4.9/2.9 mm Hg, respectively. Left ventricular mass and reported symptoms were similar in the 2 groups. Costs per 100 patients followed up for 1 month were only slightly lower in the home BP group (3875 vs 3522 [$4921 vs $4473]; P = .04). Conclusions  Adjustment of antihypertensive treatment based on home BP instead of office BP led to less intensive drug treatment and marginally lower costs but also to less BP control, with no differences in general well-being or left ventricular mass. Self-measurement allowed identification of patients with white-coat hypertension. Our findings support a stepwise strategy for the evaluation of BP in which self-measurement and ambulatory monitoring are complementary to conventional office measurement and highlight the need for prospective outcome studies to establish the normal range of home-measured BP.      

Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial

CONTEXT: Epidemiologic data demonstrate that moderate alcohol intake is associated with improved insulin sensitivity in nondiabetic individuals. No controlled-diet studies have addressed the effects of daily moderate alcohol consumption on fasting insulin and glucose concentrations and insulin sensitivity. OBJECTIVE: To determine whether daily consumption of low to moderate amounts of alcohol influences fasting insulin and glucose concentrations and insulin sensitivity in nondiabetic postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled crossover trial of 63 healthy postmenopausal women, conducted at a clinical research center in Maryland between 1998 and 1999. INTERVENTIONS: Participants were randomly assigned to consume 0, 15, or 30 g/d of alcohol for 8 weeks each as part of a controlled diet. All foods and beverages were provided during the intervention. An isocaloric beverage was provided in the 0-g/d arm. Energy intake was adjusted to maintain constant body weight. MAIN OUTCOME MEASURES: Fasting insulin, triglyceride, and glucose concentrations, measured at the end of each dietary period; insulin sensitivity, estimated with a published index of glucose disposal rate corrected for fat-free mass based on fasting insulin and fasting triglyceride concentrations, compared among treatments with a mixed-model analysis of variance. RESULTS: A complete set of plasma samples was collected and analyzed for 51 women who completed all diet treatments. Consumption of 30 g/d of alcohol compared with 0 g/d reduced fasting insulin concentration by 19.2% (P =.004) and triglyceride concentration by 10.3% (P =.001), and increased insulin sensitivity by 7.2% (P =.002). Normal-weight, overweight, and obese individuals responded similarly. Only fasting triglyceride concentration was significantly reduced when comparing 0 and 15 g/d of alcohol (7.8%; P =.03), and no difference was found between consumption of 15 and 30 g/d of alcohol; however, there was a significant linear trend (P =.001). Fasting glucose concentrations were not different across treatments. CONCLUSIONS: Consumption of 30 g/d of alcohol (2 drinks per day) has beneficial effects on insulin and triglyceride concentrations and insulin sensitivity in nondiabetic postmenopausal women.     

Effectiveness of home blood pressure monitoring, Web communication, and pharmacist care on hypertension control: a randomized controlled trial

Beverly B. Green, MD, MPH; Andrea J. Cook, PhD; James D. Ralston, MD, MPH; Paul A. Fishman, PhD; Sheryl L. Catz, PhD; James Carlson, PharmD; David Carrell, PhD; Lynda Tyll, RN, MS; Eric B. Larson, MD, MPH; Robert S. Thompson, MD

JAMA. 2008;299(24):2857-2867.

Context  Treating hypertension decreases mortality and disability from cardiovascular disease, but most hypertension remains inadequately controlled.

Objective  To determine if a new model of care that uses patient Web services, home blood pressure (BP) monitoring, and pharmacist-assisted care improves BP control.

Design, Setting, and Participants  A 3-group randomized controlled trial, the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model. The trial was conducted at an integrated group practice in Washington state, enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access. Care was delivered over a secure patient Web site from June 2005 to December 2007.

Interventions  Participants were randomly assigned to usual care, home BP monitoring and secure patient Web site training only, or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications.

Main Outcome Measures  Percentage of patients with controlled BP (<140/90 mm Hg) and changes in systolic and diastolic BP at 12 months.

Results  Of 778 patients, 730 (94%) completed the 1-year follow-up visit. Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP (<140/90 mm Hg) compared with usual care (36% [95% confidence interval {CI}, 30%-42%] vs 31% [95% CI, 25%-37%]; P = .21). Adding Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP (56%; 95% CI, 49%-62%) compared with usual care (P < .001) and home BP monitoring and Web training only (P < .001). Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care. Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups. Compared with usual care, the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP (–13.2 mm Hg [95% CI, –19.2 to –7.1]; P < .001) and diastolic BP (–4.6 mm Hg [95% CI, –8.0 to –1.2]; P < .001), and improved BP control (relative risk, 3.32 [95% CI, 1.86 to 5.94]; P<.001).

Conclusion  Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension.

Trial Registration  clinicaltrials.gov Identifier: NCT00158639

     

Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial

Context  Poor medication adherence diminishes the health benefits of pharmacotherapies. Elderly patients with coronary risk factors frequently require treatment with multiple medications, placing them at increased risk for nonadherence. Objective  To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C). Design, Setting, and Patients  A multiphase, prospective study with an observational phase and a randomized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications. The study was conducted from June 2004 to August 2006. Intervention  After a 2-month run-in phase (measurement of baseline adherence, BP, and LDL-C), patients entered a 6-month intervention phase (standardized medication education, regular follow-up by pharmacists, and medications dispensed in time-specific packs). Following the intervention phase, patients were randomized to continued pharmacy care vs usual care for an additional 6 months. Main Outcome Measures  Primary end point of the observation phase was change in the proportion of pills taken vs baseline; secondary end points were the associated changes in BP and LDL-C. Primary end point of the randomization phase was the between-group comparison of medication persistence. Results  A total of 200 elderly patients (77.1% men; mean [SD] age, 78 [8.3] years), taking a mean (SD) of 9 (3) chronic medications were enrolled. Coronary risk factors included drug-treated hypertension in 184 patients (91.5%) and drug-treated hyperlipidemia in 162 (80.6%). Mean (SD) baseline medication adherence was 61.2% (13.5%). After 6 months of intervention, medication adherence increased to 96.9% (5.2%; P<.001) and was associated with significant improvements in systolic BP (133.2 [14.9] to 129.9 [16.0] mm Hg; P = .02) and LDL-C (91.7 [26.1] to 86.8 [23.4] mg/dL; P = .001). Six months after randomization, the persistence of medication adherence decreased to 69.1% (16.4%) among those patients assigned to usual care, whereas it was sustained at 95.5% (7.7%) in pharmacy care (P<.001). This was associated with significant reductions in systolic BP in the pharmacy care group (–6.9 mm Hg; 95% CI, –10.7 to –3.1 mm Hg) vs the usual care group (–1.0 mm Hg; 95% CI, –5.9 to 3.9 mm Hg; P = .04), but no significant between-group differences in LDL-C levels or reductions. Conclusions  A pharmacy care program led to increases in medication adherence, medication persistence, and clinically meaningful reductions in BP, whereas discontinuation of the program was associated with decreased medication adherence and persistence. Trial Registration  clinicaltrials.gov Identifier: NCT00393419      

Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial

Context  High-density lipoprotein (HDL) cholesterol is an inverse predictor of coronary atherosclerotic disease. Preliminary data have suggested that HDL infusions can induce atherosclerosis regression. Objective  To investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound (IVUS). Design and Setting  A randomized placebo-controlled trial was conducted at 17 centers in Canada. Intravascular ultrasound was performed to assess coronary atheroma at baseline and 2 to 3 weeks after the last study infusion. Patients  Between July 2005 and October 2006, 183 patients had a baseline IVUS examination and of those, 145 had evaluable serial IVUS examinations after 6 weeks. Intervention  Sixty patients were randomly assigned to receive 4 weekly infusions of placebo (saline), 111 to receive 40 mg/kg of reconstituted HDL (CSL-111); and 12 to receive 80 mg/kg of CSL-111. Main Outcome Measures  The primary efficacy parameter was the percentage change in atheroma volume. Nominal changes in plaque volume and plaque characterization index on IVUS and coronary score on quantitative coronary angiography were also prespecified end points. Results  The higher-dosage CSL-111 treatment group was discontinued early because of liver function test abnormalities. The percentage change in atheroma volume was –3.4% with CSL-111 and –1.6% for placebo (P = .48 between groups, P<.001 vs baseline for CSL-111). The nominal change in plaque volume was –5.3 mm³ with CSL-111 and –2.3 mm³ with placebo (P = .39 between groups, P<.001 vs baseline for CSL-111). The mean changes in plaque characterization index on IVUS (–0.0097 for CSL-111 and 0.0128 with placebo) and mean changes in coronary score (–0.039 mm for CSL-111 and –0.071 mm with placebo) on quantitative coronary angiography were significantly different between groups (P = .01 and P =.03, respectively). Administration of CSL-111 40 mg/kg was associated with mild, self-limiting transaminase elevation but was clinically well tolerated. Conclusions  Short-term infusions of reconstituted HDL resulted in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography. Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions, including trials with clinical end points, appear warranted. Trial Registration  clinicaltrials.gov Identifier: NCT00225719 Published online: March 26, 2007 (doi:10.1001/jama.297.15.jpc70004).      

Continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial

Context  Hypoxemia complicates the recovery of 30% to 50% of patients after abdominal surgery; endotracheal intubation and mechanical ventilation may be required in 8% to 10% of cases, increasing morbidity and mortality and prolonging intensive care unit and hospital stay. Objective  To determine the effectiveness of continuous positive airway pressure compared with standard treatment in preventing the need for intubation and mechanical ventilation in patients who develop acute hypoxemia after elective major abdominal surgery. Design and Setting  Randomized, controlled, unblinded study with concealed allocation conducted between June 2002 and November 2003 at 15 intensive care units of the Piedmont Intensive Care Units Network in Italy. Patients  Consecutive patients who developed severe hypoxemia after major elective abdominal surgery. The trial was stopped for efficacy after 209 patients had been enrolled. Interventions  Patients were randomly assigned to receive oxygen (n = 104) or oxygen plus continuous positive airway pressure (n = 105). Main Outcome Measures  The primary end point was incidence of endotracheal intubation; secondary end points were intensive care unit and hospital lengths of stay, incidence of pneumonia, infection and sepsis, and hospital mortality. Results  Patients who received oxygen plus continuous positive airway pressure had a lower intubation rate (1% vs 10%; P = .005; relative risk [RR], 0.099; 95% confidence interval [CI], 0.01-0.76) and had a lower occurrence rate of pneumonia (2% vs 10%, RR, 0.19; 95% CI, 0.04-0.88; P = .02), infection (3% vs 10%, RR, 0.27; 95% CI, 0.07-0.94; P = .03), and sepsis (2% vs 9%; RR, 0.22; 95% CI, 0.04-0.99; P = .03) than did patients treated with oxygen alone. Patients who received oxygen plus continuous positive airway pressure also spent fewer mean (SD) days in the intensive care unit (1.4 [1.6] vs 2.6 [4.2], P = .09) than patients treated with oxygen alone. The treatments did not affect the mean (SD) days that patients spent in the hospital (15 [13] vs 17 [15], respectively; P = .10). None of those treated with oxygen plus continuous positive airway pressure died in the hospital while 3 deaths occurred among those treated with oxygen alone (P = .12). Conclusion  Continuous positive airway pressure may decrease the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery.      

Exhaled nitric oxide as a guiding tool for bronchial asthma: A randomised controlled trial

BackgroundEvidence regarding the role of non-invasive marker of airway inflammation, fractional exhaled nitric oxide (FeNO) to guide asthma treatment is equivocal. We aimed to evaluate if the use of FeNO to adjust inhaled corticosteroid treatment resulted in reduced daily corticosteroid use and lesser exacerbations.Methods100 patients of bronchial asthma in the age group of 12–70 years were randomised to receive inhaled corticosteroids based on either FeNO measurements (n = 50) or as per Global Initiative for Asthma (GINA) guidelines. Follow up was done every 2 months for period of 12 months. Results were compared in terms of mean daily inhaled corticosteroid use and number of exacerbations.ResultsAfter the follow up period of 12 months, mean daily dose of ICS (SD) required in FeNO group was 267.5 μg (126.29), as opposed to control group in which mean daily dose of steroid was 320.00 μg (138.69). However this observed difference in steroid dose was statistically insignificant (p value = 0.061). The estimated mean (SD) rate of asthma exacerbation experienced in follow up period of 12 months in FeNO group was 0.3 episodes (0.54) per patient per year (95% confidence interval, 0.145–455) and 0.4 episodes (0.61) per patient per year in control group (95% confidence interval, 0.228–572). However this difference in rate of exacerbations between the two study groups was not statistically significant (p = 0.387).ConclusionFeNO guided management strategy for asthma did not result in statistically significant reduction in dose of inhaled corticosteroids or number of asthma exacerbations.     

Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial

Context  Low levels of cardiorespiratory fitness are associated with high risk of mortality, and improvements in fitness are associated with reduced mortality risk. However, a poor understanding of the physical activity–fitness dose response relation remains. Objective  To examine the effect of 50%, 100%, and 150% of the NIH Consensus Development Panel recommended physical activity dose on fitness in women. Design, Setting, and Participants  Randomized controlled trial of 464 sedentary, postmenopausal overweight or obese women whose body mass index ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to 159.9 mm Hg. Enrollment took place between April 2001 and June 2005 in the Dallas, Tex, area. Intervention  Participants were randomly assigned to 1 of 4 groups: 102 to the nonexercise control group and 155 to the 4-kcal/kg, 104 to the 8-kcal/kg, and 103 to the 12-kcal/kg per week energy-expenditure groups for the 6-month intervention period. Target training intensity was the heart rate associated with 50% of each woman's peak O₂. Main Outcome Measure  The primary outcome was aerobic fitness assessed on a cycle ergometer and quantified as peak absolute oxygen consumption (O₂abs, L/min). Results  The mean (SD) baseline O₂abs values were 1.30 (0.25) L/min. The mean (SD) minutes of exercising per week were 72.2 (12.3) for the 4-kcal/kg, 135.8 (19.5) for the 8-kcal/kg, and 191.7 (33.7) for the 12-kcal/kg per week exercise groups. After adjustment for age, race/ethnicity, weight, and peak heart rate, the exercise groups increased their O₂abs compared with the control group by 4.2% in the 4-kcal/kg, 6.0% in the 8-kcal/kg, and 8.2% in the 12-kcal/kg per week groups (P<.001 for each vs control; P for trend <.001). There was no treatment x subgroup interaction for age, body mass index, weight, baseline O₂abs, race/ethnicity, or baseline hormone therapy use. There were no significant changes in systolic or diastolic blood pressure values from baseline to 6 months in any of the exercise groups vs the control group. Conclusion  In this study, previously sedentary, overweight or obese postmenopausal women experienced a graded dose-response change in fitness across levels of exercise training. Trial Registration  clinicaltrials.gov Identifier: NCT00011193      

Effects of cognitive training interventions with older adults: a randomized controlled trial

Context  Cognitive function in older adults is related to independent living and need for care. However, few studies have addressed whether improving cognitive functions might have short- or long-term effects on activities related to living independently. Objective  To evaluate whether 3 cognitive training interventions improve mental abilities and daily functioning in older, independent-living adults. Design  Randomized, controlled, single-blind trial with recruitment conducted from March 1998 to October 1999 and 2-year follow-up through December 2001. Setting and Participants  Volunteer sample of 2832 persons aged 65 to 94 years recruited from senior housing, community centers, and hospital/clinics in 6 metropolitan areas in the United States. Interventions  Participants were randomly assigned to 1 of 4 groups: 10-session group training for memory (verbal episodic memory; n = 711), or reasoning (ability to solve problems that follow a serial pattern; n = 705), or speed of processing (visual search and identification; n = 712); or a no-contact control group (n = 704). For the 3 treatment groups, 4-session booster training was offered to a 60% random sample 11 months later. Main Outcome Measures  Cognitive function and cognitively demanding everyday functioning. Results  Thirty participants were incorrectly randomized and were excluded from the analysis. Each intervention improved the targeted cognitive ability compared with baseline, durable to 2 years (P<.001 for all). Eighty-seven percent of speed-, 74% of reasoning-, and 26% of memory-trained participants demonstrated reliable cognitive improvement immediately after the intervention period. Booster training enhanced training gains in speed (P<.001) and reasoning (P<.001) interventions (speed booster, 92%; no booster, 68%; reasoning booster, 72%; no booster, 49%), which were maintained at 2-year follow-up (P<.001 for both). No training effects on everyday functioning were detected at 2 years. Conclusions  Results support the effectiveness and durability of the cognitive training interventions in improving targeted cognitive abilities. Training effects were of a magnitude equivalent to the amount of decline expected in elderly persons without dementia over 7- to 14-year intervals. Because of minimal functional decline across all groups, longer follow-up is likely required to observe training effects on everyday function.      

Effects of extended outpatient rehabilitation after hip fracture: a randomized controlled trial

Context  Hip fractures are common in the elderly, and despite standard rehabilitation, many patients fail to regain their prefracture ambulatory or functional status. Objective  To determine whether extended outpatient rehabilitation that includes progressive resistance training improves physical function and reduces disability compared with low-intensity home exercise among physically frail elderly patients with hip fracture. Design, Setting, and Patients  Randomized controlled trial conducted between August 1998 and May 2003 among 90 community-dwelling women and men aged 65 years or older who had had surgical repair of a proximal femur fracture no more than 16 weeks prior and had completed standard physical therapy. Intervention  Participants were randomly assigned to 6 months of either supervised physical therapy and exercise training (n = 46) or home exercise (control condition; n = 44). Main Outcome Measures  Primary outcome measures were total scores on a modified Physical Performance Test (PPT), the Functional Status Questionnaire physical function subscale (FSQ), and activities of daily living scales. Secondary outcome measures were standardized measures of skeletal muscle strength, gait, balance, quality of life, and body composition. Participants were evaluated at baseline, 3 months, and 6 months. Results  Changes over time in the PPT and FSQ scores favored the physical therapy group (P = .003 and P = .01, respectively). Mean change (SD) in PPT score for physical therapy was +6.5 (5.5) points (95% confidence interval [CI], 4.6-8.3), and for the control condition was +2.5 (3.7) points (95% CI, 1.4-3.6 points). Mean change (SD) in FSQ score for physical therapy was +5.2 (5.4) points (95% CI, 3.5-6.9) and for the control condition was +2.9 (3.8) points (95% CI, 1.7-4.0). Physical therapy also had significantly greater improvements than the control condition in measures of muscle strength, walking speed, balance, and perceived health but not bone mineral density or fat-free mass. Conclusion  In community-dwelling frail elderly patients with hip fracture, 6 months of extended outpatient rehabilitation that includes progressive resistance training can improve physical function and quality of life and reduce disability compared with low-intensity home exercise.      

Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial

Context  Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration. Objective  To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE–The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years. Intervention  Daily dose of natural source vitamin E (400 IU) or matching placebo. Main Outcome Measures  Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations. Results  Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure. Conclusion  In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure.      

益气散聚方治疗非酒精性脂肪性肝病随机对照临床试验

目的：观察中药益气散聚方对非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）患者的疗效。方法：将符合纳入标准的67例NAFLD患者,随机分为益气散聚方组39例和安慰剂对照组28例。分别予益气散聚方和安慰剂治疗3个月,观察治疗前后临床症状、肝脾CT比值、体质量指数（body mass index,BMI）、腰围、稳态模型胰岛素抵抗指数（homeostatic model assessment for insulin resistance,HOMA2-IR）、肝功能、肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）、高敏C反应蛋白（high sensitivity C-reactive protein,hs-CRP）和血脂等方面的变化。结果：治疗后,益气散聚方组临床症状明显缓解,肝脾CT比值明显上升,BMI、HOMA2-IR水平下降,肝功能好转,TNF-α、hs-CRP和血脂水平明显下降,与安慰剂组相比,差异有统计学意义;益气散聚方组总有效率为94.87%。结论：中药益气散聚方治疗NAFLD疗效确切。     

苦参素对维持性血液透析患者微炎症状态的影响：随机对照试验

背景：维持性血液透析（maintenance hemodialysis,MHD）患者体内普遍存在微炎症状态。它严重影响MHD患者长期生存率,改善MHD患者微炎症状态具有重要意义。 目的：观察苦参素对MHD患者微炎症状态的影响,探讨苦参素对MHD患者微炎症的治疗作用。 设计、场所、对象和干预措施：选择2008年6～9月在武汉市第一医院血液净化中心进行规律性维持血液透析治疗的60例慢性肾衰竭患者,随机分为治疗组和对照组,每组各30例。治疗组给予苦参素胶囊0．4g口服,1次／d,连续服用3个月,对照组不用药。 主要结局指标：检测治疗前及治疗3个月后血清超敏C反应蛋白（high-sensitivity C-reactive protein,hs-CRP）、白细胞介素1β（interleukin-1β,IL—1β）、肿瘤坏死因子α（tumor necrosis factor—α,TNF—α）、血清白蛋白（albumin,Alb）、血清前白蛋白（pre-albumin,PAB）、总胆固醇（total cholesterol,TC）和三酰甘油（triglyceride,TG）浓度。 结果：治疗组3例服药后当天出现胃痛,其中2例退出,1例经停药观察后症状消失,继续服药后胃痛未再次出现。治疗组2例服药第2天出现皮疹,经停药观察后症状消失,继续服药后未再次出现皮疹。其他患者均未发现不良反应,共58例完成观察。与治疗前比较,治疗组治疗后hs-CRP、IL-1β和TNF-α水平降低（P〈0.01）,Alb,PAB、TC及TG水平升高（P〈0．01）,与对照组比较,差异亦有统计学意义（P〈0．01,P〈0．05）。结论：苦参素能够改善MHD患者的微炎症状态。     

Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial

Context  The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain. Objective  To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD. Design, Setting, and Participants  Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS). Interventions  Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion. Main Outcome Measures  The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume. Results  Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P = .003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P = .16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P = .10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P = .12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P = .02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P = .08), and no progression in the amlodipine group (P = .31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P = .07. Conclusions  Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.