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

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

Zinc Gluconate Lozenges for Treating the Common Cold in Children: A Randomized Controlled Trial

Context.— The common cold is one of the most frequently occurring illnesses and is responsible for substantial morbidity and economic loss. Biochemical evidence suggests that zinc may be an effective treatment, and zinc gluconate glycine (ZGG) lozenges have been shown to reduce the duration of cold symptoms in adults. Objective.— To determine the efficacy of ZGG treatment of colds in children and adolescents. Design.— A randomized, double-masked, placebo-controlled study. Setting.— Two suburban school districts in Cleveland, Ohio. Patients.— A total of 249 students in grades 1 through 12 were enrolled within the first 24 hours of experiencing at least 2 of 9 symptoms of the common cold. Intervention.— Zinc lozenges, 10 mg, orally dissolved, 5 times a day (in grades 1-6) or 6 times a day (in grades 7-12). Main Outcome Measures.— Time to resolution of cold symptoms based on subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal congestion, nasal drainage, scratchy throat, sore throat, and sneezing. Results.— Time to resolution of all cold symptoms did not differ significantly between students receiving zinc (n=124) and those receiving placebo (n=125) (median, 9 days; 95% confidence interval [CI], 8-9 days; median, 9 days, 95% CI, 7-10 days, respectively; P=.71). There were no significant differences in the time to resolution of any of the 9 symptoms studied. Compared with controls, more students in the zinc group reported adverse effects (88.6% vs 79.8%; P=.06); bad taste (60.2% vs 37.9%; P=.001); nausea (29.3% vs 16.1%; P=.01); mouth, tongue, or throat discomfort (36.6% vs 24.2%; P=.03); and diarrhea (10.6% vs 4.0%; P=.05). Conclusions.— In this community-based, randomized controlled trial, ZGG lozenges were not effective in treating cold symptoms in children and adolescents. Further studies with virologic testing are needed to clarify what role, if any, zinc may play in treating cold symptoms.      

Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places

Context  Scotland prohibited smoking in confined public places on March 26, 2006. Objective  To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers. Design, Setting, and Participants  This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol. Main Outcome Measures  Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma quality-of-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban. Results  For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, –26%; 95% confidence interval [CI], –13.8% to –38.1%; P<.001) and 46.8% (n = 38) (–32.5%; 95% CI, –19.8% to –45.2%; P<.001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, –1.93 ng/mL; 95% CI, –2.83 to –1.03 ng/mL; P<.001) and then 2.93 ng/mL (–2.22 ng/mL; 95% CI, –3.10 to –1.34 ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/µL at 2 months (–630 cells/µL; 95% CI, –1010 to –260 cells/µL; P = .002) and from 4440 to 4030 cells/µL (–410 cells/µL; 95% CI, –740 to –90 cells/µL; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049). Conclusions  Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.      

Obesity and estrogen as risk factors for gastroesophageal reflux symptoms

Context  Gastroesophageal reflux and obesity are both increasing in prevalence. The scientific evidence for an association between these conditions is sparse and contradictory. A difference between sexes concerning this relation has been proposed. Objective  To evaluate the relation between body mass and gastroesophageal reflux symptoms and determine how this relation is influenced by female sex hormones. Design  Population-based, cross-sectional, case-control study. Setting  Two consecutive public health surveys within the county of Nord-Trondelag, Norway, conducted in 1984-1986 and 1995-1997. Participants  Among 65 363 adult participants in the second survey, 3113 individuals who reported severe heartburn or regurgitation during the last 12 months were defined as cases, whereas 39 872 persons without reflux symptoms were defined as controls. Main Outcome Measure  Risk of reflux, estimated using multivariate logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs) as measures of association. Results  There was a dose-response association between increasing body mass index (BMI) and reflux symptoms in both sexes (P for trend <.001), with a significantly stronger association in women (P<.001). Compared with those with a BMI less than 25, the risk of reflux was increased significantly among severely obese (BMI >35) men(OR, 3.3; 95% CI, 2.4-4.7) and women (OR, 6.3; 95% CI, 4.9-8.0). The association between BMI and reflux symptoms was stronger among premenopausal women compared with postmenopausal women (P<.001), although use of postmenopausal hormone therapy increased the strength of the association (P<.001). Reduction in BMI was associated with decreased risk of reflux symptoms. Conclusions  There is a significant association between body mass and symptoms of gastroesophageal reflux. The association is stronger among women, especially premenopausally, and use of hormone therapy strengthens the association, suggesting that estrogens may play an important role in the etiology of reflux disease.      

Effects of a low-glycemic load diet on resting energy expenditure and heart disease risk factors during weight loss

Context  Weight loss elicits physiological adaptations relating to energy intake and expenditure that antagonize ongoing weight loss. Objective  To test whether dietary composition affects the physiological adaptations to weight loss, as assessed by resting energy expenditure. Design, Study, and Participants  A randomized parallel-design study of 39 overweight or obese young adults aged 18 to 40 years who received an energy-restricted diet, either low–glycemic load or low-fat. Participants were studied in the General Clinical Research Centers of the Brigham and Women’s Hospital and the Children’s Hospital, Boston, Mass, before and after 10% weight loss. The study was conducted from January 4, 2001, to May 6, 2003. Main Outcome Measures  Resting energy expenditure measured in the fasting state by indirect calorimetry, body composition by dual-energy x-ray absorptiometry, cardiovascular disease risk factors, and self-reported hunger. Results  Resting energy expenditure decreased less with the low–glycemic load diet than with the low-fat diet, expressed in absolute terms (mean [SE], 96 [24] vs 176 [27] kcal/d; P = .04) or as a proportion (5.9% [1.5%] vs 10.6% [1.7%]; P = .05). Participants receiving the low–glycemic load diet reported less hunger than those receiving the low-fat diet (P = .04). Insulin resistance (P = .01), serum triglycerides (P = .01), C-reactive protein (P = .03), and blood pressure (P = .07 for both systolic and diastolic) improved more with the low–glycemic load diet. Changes in body composition (fat and lean mass) in both groups were very similar (P = .85 and P = .45, respectively). Conclusions  Changes in dietary composition within prevailing norms can affect physiological adaptations that defend body weight. Reduction in glycemic load may aid in the prevention or treatment of obesity, cardiovascular disease, and diabetes mellitus.      

Evaluating iatrogenic risk of youth suicide screening programs: a randomized controlled trial

Context  Universal screening for mental health problems and suicide risk is at the forefront of the national agenda for youth suicide prevention, yet no study has directly addressed the potential harm of suicide screening. Objective  To examine whether asking about suicidal ideation or behavior during a screening program creates distress or increases suicidal ideation among high school students generally or among high-risk students reporting depressive symptoms, substance use problems, or suicide attempts. Design, Setting, and Participants  A randomized controlled study conducted within the context of a 2-day screening strategy. Participants were 2342 students in 6 high schools in New York State in 2002-2004. Classes were randomized to an experimental group (n = 1172), which received the first survey with suicide questions, or to a control group (n = 1170), which did not receive suicide questions. Main Outcome Measures  Distress measured at the end of the first survey and at the beginning of the second survey 2 days after the first measured on the Profile of Mood States adolescent version (POMS-A) instrument. Suicidal ideation assessed in the second survey. Results  Experimental and control groups did not differ on distress levels immediately after the first survey (mean [SD] POMS-A score, 5.5 [9.7] in the experimental group and 5.1 [10.0] in the control group; P = .66) or 2 days later (mean [SD] POMS-A score, 4.3 [9.0] in the experimental group and 3.9 [9.4] in the control group; P = .41), nor did rates of depressive feelings differ (13.3% and 11.0%, respectively; P = .19). Students exposed to suicide questions were no more likely to report suicidal ideation after the survey than unexposed students (4.7% and 3.9%, respectively; P = .49). High-risk students (defined as those with depression symptoms, substance use problems, or any previous suicide attempt) in the experimental group were neither more suicidal nor distressed than high-risk youth in the control group; on the contrary, depressed students and previous suicide attempters in the experimental group appeared less distressed (P = .01) and suicidal (P = .02), respectively, than high-risk control students. Conclusions  No evidence of iatrogenic effects of suicide screening emerged. Screening in high schools is a safe component of youth suicide prevention efforts.      

Health of previously uninsured adults after acquiring Medicare coverage

J. Michael McWilliams, MD; Ellen Meara, PhD; Alan M. Zaslavsky, PhD; John Z. Ayanian, MD, MPP

JAMA. 2007;298(24):2886-2894.

Context  Uninsured near-elderly adults, particularly those with cardiovascular disease or diabetes, experience worse health outcomes than insured adults. However, the health benefits of providing insurance coverage for uninsured adults have not been clearly demonstrated.

Objective  To assess the effect of acquiring Medicare coverage on the health of previously uninsured adults.

Design and Setting  We conducted quasi-experimental analyses of longitudinal survey data from 1992 through 2004 from the nationally representative Health and Retirement Study. We compared changes in health trends reported by previously uninsured and insured adults after they acquired Medicare coverage at age 65 years.

Participants  Five thousand six adults who were continuously insured and 2227 adults who were persistently or intermittently uninsured from ages 55 to 64 years.

Main Outcome Measures  Differential changes in self-reported trends after age 65 years in general health, change in general health, mobility, agility, pain, depressive symptoms, and a summary measure of these 6 domains; and adverse cardiovascular outcomes (all trend changes reported in health scores per year).

Results  Compared with previously insured adults, previously uninsured adults reported significantly improved health trends after age 65 years for the summary measure (differential change in annual trend, +0.20; P = .002) and several component measures. Relative to previously insured adults with cardiovascular disease or diabetes, previously uninsured adults with these conditions reported significantly improved trends in summary health (differential change in annual trend, +0.26; P = .006), change in general health (+0.02; P = .03), mobility (+0.04; P = .05), agility (+0.08; P = .003), and adverse cardiovascular outcomes (–0.015; P = .02) but not in depressive symptoms (+0.04; P = .32). Previously uninsured adults without these conditions reported differential improvement in depressive symptoms (+0.08; P = .002) but not in summary health (+0.10; P = .17) or any other measure. By age 70 years, the expected difference in summary health between previously uninsured and insured adults with cardiovascular disease or diabetes was reduced by 50%.

Conclusion  In this study, acquisition of Medicare coverage was associated with improved trends in self-reported health for previously uninsured adults, particularly those with cardiovascular disease or diabetes.

     

Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials

Context  The benefits of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) are still a matter of debate. Objective  To combine data from all randomized trials conducted with abciximab in STEMI. Data Sources  Formal searches of electronic databases (MEDLINE, PubMed) from from January 1990 to December 2004. Study Selection  We examined all completed, published, randomized trials of abciximab in STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, facilitated angioplasty, stenting, fibrinolysis, IIb-IIIa inhibitors, and abciximab. Data Extraction  Information on study design, type and dosage of drugs, inclusion and exclusion criteria, number of patients, and clinical outcome was extracted by 2 investigators. Disagreements were resolved by consensus. Data Synthesis  Eleven trials were analyzed, involving 27115 patients (12 602 [46.5%] in the abciximab group, 14 513 [53.5%] in the control group). When compared with the control group, abciximab was associated with a significant reduction in short-term (30 days) mortality (2.4% vs 3.4%, P = .047) and long-term (6-12 months) mortality (4.4% vs 6.2%, P = .01) in patients undergoing primary angioplasty but not in those treated with fibrinolysis or in all trials combined. Abciximab was associated with a significant reduction in 30-day reinfarction, both in all trials combined (2.1% vs 3.3%, P<.001), in primary angioplasty (1.0% vs 1.9%, P = .03), and in fibrinolysis trials (2.3% vs 3.6%, P<.001). Abciximab did not result in an increased risk of intracranial bleeding (0.61% vs 0.62%, P = .62) but was associated with an increased risk of major bleeding complications when combined with fibrinolysis (5.2% vs 3.1%, P<.001) but not with primary angioplasty (4.7% vs 4.1%, P = .36). Conclusions  This meta-analysis shows that, when compared with the control group, adjunctive abciximab for STEMI is associated with a significant reduction in 30-day and long-term mortality in patients treated with primary angioplasty but not in those receiving fibrinolysis. The 30-day reinfarction rate is significantly reduced in patients treated with either fibrinolysis or primary angioplasty. A higher risk of major bleeding complications is observed with abciximab in association with fibrinolysis.      

Depressive symptoms and health-related quality of life: the Heart and Soul Study

Context  Little is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease. Objective  To compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease. Design, Setting, and Participants  Cross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002. Main Measures  Measurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor. Results  Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score =" BORDER="0">10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), mildly diminished quality of life (67% vs 31%; P<.001), and fair or poor overall health (66% vs 30%; P<.001). In multivariate analyses adjusting for measures of cardiac function and other patient characteristics, depressive symptoms were strongly associated with greater symptom burden (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P = .002), greater physical limitation (OR, 3.1; 95% CI, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% CI, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% CI, 1.3-2.9; P<.001). Although decreased exercise capacity was associated with worse health status, left ventricular ejection fraction and ischemia were not. Conclusions  Among patients with coronary disease, depressive symptoms are strongly associated with patient-reported health status, including symptom burden, physical limitation, quality of life, and overall health. Conversely, 2 traditional measures of cardiac function—ejection fraction and ischemia—are not. Efforts to improve health status should include assessment and treatment of depressive symptoms.      

Cognitive-behavior therapy, sertraline, and their combination for children and adolescents with obsessive-compulsive disorder: the Pediatric OCD Treatment Study (POTS) randomized controlled trial

Context  The empirical literature on treatment of obsessive-compulsive disorder (OCD) in children and adolescents supports the efficacy of short-term OCD-specific cognitive-behavior therapy (CBT) or medical management with selective serotonin reuptake inhibitors. However, little is known about their relative and combined efficacy. Objective  To evaluate the efficacy of CBT alone and medical management with the selective serotonin reuptake inhibitor sertraline alone, or CBT and sertraline combined, as initial treatment for children and adolescents with OCD. Design, Setting, and Participants  The Pediatric OCD Treatment Study, a balanced, masked randomized controlled trial conducted in 3 academic centers in the United States and enrolling a volunteer outpatient sample of 112 patients aged 7 through 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD and a Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score of 16 or higher. Patients were recruited between September 1997 and December 2002. Interventions  Participants were randomly assigned to receive CBT alone, sertraline alone, combined CBT and sertraline, or pill placebo for 12 weeks. Main Outcome Measures  Change in CY-BOCS score over 12 weeks as rated by an independent evaluator masked to treatment status; rate of clinical remission defined as a CY-BOCS score less than or equal to 10. Results  Ninety-seven of 112 patients (87%) completed the full 12 weeks of treatment. Intent-to-treat random regression analyses indicated a statistically significant advantage for CBT alone (P = .003), sertraline alone (P = .007), and combined treatment (P = .001) compared with placebo. Combined treatment also proved superior to CBT alone (P = .008) and to sertraline alone (P = .006), which did not differ from each other. Site differences emerged for CBT and sertraline but not for combined treatment, suggesting that combined treatment is less susceptible to setting-specific variations. The rate of clinical remission for combined treatment was 53.6% (95% confidence interval [CI], 36%-70%); for CBT alone, 39.3% (95% CI, 24%-58%); for sertraline alone, 21.4% (95% CI, 10%-40%); and for placebo, 3.6% (95% CI, 0%-19%). The remission rate for combined treatment did not differ from that for CBT alone (P = .42) but did differ from sertraline alone (P = .03) and from placebo (P<.001). CBT alone did not differ from sertraline alone (P = .24) but did differ from placebo (P = .002), whereas sertraline alone did not (P = .10). The 3 active treatments proved acceptable and well tolerated, with no evidence of treatment-emergent harm to self or to others. Conclusion  Children and adolescents with OCD should begin treatment with the combination of CBT plus a selective serotonin reuptake inhibitor or CBT alone.      

Six-year follow-up of preventive interventions for children of divorce: a randomized controlled trial

Context  Compared with their peers with nondivorced parents, adolescents with divorced parents are more likely to have mental health problems, drop out of school, and become pregnant. The long-term effects of intervention programs for this population are unknown. Objective  To evaluate the long-term effectiveness of 2 programs designed to prevent mental health problems in children with divorced parents. Design and Setting  Six-year follow-up of a randomized controlled trial of 2 intervention programs (mother program: 11 group and 2 individual sessions; mother plus child program: mother program and 11 group sessions for children) and a control condition (books on postdivorce adjustment), which was conducted in a large metropolitan US city from April 1998 through March 2000. Participants  A total of 218 families (91% of the original sample) with adolescents aged between 15 and 19 years were reinterviewed. Main Outcome Measures  Externalizing and internalizing problems, diagnosed mental disorders, drug and alcohol use, and number of sexual partners. Results  Eleven percent of adolescents in the mother plus child program (95% confidence interval [CI], 3.8%-18.2%) had a 1-year prevalence of diagnosed mental disorder compared with 23.5% (95% CI, 13.8%-33.2%) of adolescents in the control program (P = .007). Adolescents in the mother plus child program had fewer sexual partners (mean [SE], 0.68 [0.16]) compared with adolescents in the control program (1.65 [0.37]; P = .01). Adolescents with higher initial mental health problems whose families were in the mother plus child program had lower externalizing problems (P = .007) and fewer symptoms of mental disorder (P = .02) compared with those in the control program. Compared with controls, adolescents whose mothers participated in the mother program and who had higher initial mental health problems had lower levels of externalizing problems (P<.001); fewer symptoms of mental disorder (P = .005); and less alcohol (P = .005), marijuana (P = .02), and other drug use (P = .01). Conclusions  In adolescents of divorced parents, the mother program and the mother plus child program reduced symptoms of mental disorder; rates of diagnoses of mental disorder; levels of externalizing problems; marijuana, alcohol, and other drug use; and number of sexual partners.      

Effectiveness of a quality improvement intervention for adolescent depression in primary care clinics: a randomized controlled trial

Context  Depression is a common condition associated with significant morbidity in adolescents. Few depressed adolescents receive effective treatment for depression in primary care settings. Objective  To evaluate the effectiveness of a quality improvement intervention aimed at increasing access to evidence-based treatments for depression (particularly cognitive-behavior therapy and antidepressant medication), relative to usual care, among adolescents in primary care practices. Design, Setting, and Participants  Randomized controlled trial conducted between 1999 and 2003 enrolling 418 primary care patients with current depressive symptoms, aged 13 through 21 years, from 5 health care organizations purposively selected to include managed care, public sector, and academic medical center clinics in the United States. Intervention  Usual care (n = 207) or 6-month quality improvement intervention (n = 211) including expert leader teams at each site, care managers who supported primary care clinicians in evaluating and managing patients’ depression, training for care managers in manualized cognitive-behavior therapy for depression, and patient and clinician choice regarding treatment modality. Participating clinicians also received education regarding depression evaluation, management, and pharmacological and psychosocial treatment. Main Outcome Measures  Depressive symptoms assessed by Center for Epidemiological Studies-Depression Scale (CES-D) score. Secondary outcomes were mental health–related quality of life assessed by Mental Health Summary Score (MCS-12) and satisfaction with mental health care assessed using a 5-point scale. Results  Six months after baseline assessments, intervention patients, compared with usual care patients, reported significantly fewer depressive symptoms (mean [SD] CES-D scores, 19.0 [11.9] vs 21.4 [13.1]; P = .02), higher mental health–related quality of life (mean [SD] MCS-12 scores, 44.6 [11.3] vs 42.8 [12.9]; P = .03), and greater satisfaction with mental health care (mean [SD] scores, 3.8 [0.9] vs 3.5 [1.0]; P = .004). Intervention patients also reported significantly higher rates of mental health care (32.1% vs 17.2%, P<.001) and psychotherapy or counseling (32.0% vs 21.2%, P = .007). Conclusions  A 6-month quality improvement intervention aimed at improving access to evidence-based depression treatments through primary care was significantly more effective than usual care for depressed adolescents from diverse primary care practices. The greater uptake of counseling vs medication under the intervention reinforces the importance of practice interventions that include resources to enable evidence-based psychotherapy for depressed adolescents.      

Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial

Context  The scarcity of data addressing the health effects of popular diets is an important public health concern, especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention. Objective  To assess adherence rates and the effectiveness of 4 popular diets (Atkins, Zone, Weight Watchers, and Ornish) for weight loss and cardiac risk factor reduction. Design, Setting, and Participants  A single-center randomized trial at an academic medical center in Boston, Mass, of overweight or obese (body mass index: mean, 35; range, 27-42) adults aged 22 to 72 years with known hypertension, dyslipidemia, or fasting hyperglycemia. Participants were enrolled starting July 18, 2000, and randomized to 4 popular diet groups until January 24, 2002. Intervention  A total of 160 participants were randomly assigned to either Atkins (carbohydrate restriction, n=40), Zone (macronutrient balance, n=40), Weight Watchers (calorie restriction, n=40), or Ornish (fat restriction, n=40) diet groups. After 2 months of maximum effort, participants selected their own levels of dietary adherence. Main Outcome Measures  One-year changes in baseline weight and cardiac risk factors, and self-selected dietary adherence rates per self-report. Results  Assuming no change from baseline for participants who discontinued the study, mean (SD) weight loss at 1 year was 2.1 (4.8) kg for Atkins (21 [53%] of 40 participants completed, P = .009), 3.2 (6.0) kg for Zone (26 [65%] of 40 completed, P = .002), 3.0 (4.9) kg for Weight Watchers (26 [65%] of 40 completed, P < .001), and 3.3 (7.3) kg for Ornish (20 [50%] of 40 completed, P = .007). Greater effects were observed in study completers. Each diet significantly reduced the low-density lipoprotein/high-density lipoprotein (HDL) cholesterol ratio by approximately 10% (all P<.05), with no significant effects on blood pressure or glucose at 1 year. Amount of weight loss was associated with self-reported dietary adherence level (r = 0.60; P<.001) but not with diet type (r = 0.07; P = .40). For each diet, decreasing levels of total/HDL cholesterol, C-reactive protein, and insulin were significantly associated with weight loss (mean r = 0.36, 0.37, and 0.39, respectively) with no significant difference between diets (P = .48, P = .57, P = .31, respectively). Conclusions  Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year. Overall dietary adherence rates were low, although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group.      

Effects of reviparin, a low-molecular-weight heparin, on mortality, reinfarction, and strokes in patients with acute myocardial infarction presenting with ST-segment elevation

Context  Although reperfusion therapy, aspirin, -blockers, and angiotensin-converting enzyme inhibitors reduce mortality when used early in patients with acute myocardial infarction (MI), mortality and morbidity remain high. No antithrombotic or newer antiplatelet drug has been shown to reduce mortality in acute MI. Objective  To evaluate the effects of reviparin, a low-molecular-weight heparin, when initiated early and given for 7 days in addition to usual therapy on the primary composite outcome of death, myocardial reinfarction, or strokes at 7 and 30 days. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled trial (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation [CREATE]) of 15 570 patients with ST-segment elevation or new left bundle-branch block, presenting within 12 hours of symptom onset at 341 hospitals in India and China from July 2001 through July 2004. Intervention  Reviparin or placebo subcutaneously twice daily for 7 days. Main Outcome Measure  Primary composite outcome of death, myocardial reinfarction, or stroke at 7 and 30 days. Results  The primary composite outcome was significantly reduced from 854 (11.0%) of 7790 patients in the placebo group to 745 (9.6%) of 7780 in the reviparin group (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96; P = .005). These benefits persisted at 30 days (1056 [13.6%] vs 921 [11.8%] patients; HR, 0.87; 95% CI, 0.79-0.95; P = .001) with significant reductions in 30-day mortality (877 [11.3%] vs 766 [9.8%]; HR, 0.87; 95% CI, 0.79-0.96; P = .005) and reinfarction (199 [2.6%] vs 154 [2.0%]; HR, 0.77; 95% CI, 0.62-0.95; P = .01), and no significant differences in strokes (64 [0.8%] vs 80 [1.0%]; P = .19). Reviparin treatment was significantly better when it was initiated very early after symptom onset at 7 days (<2 hours: HR, 0.70; 95% CI, 0.52-0.96; P = .03; 30/1000 events prevented; 2 to <4 hours: HR, 0.81; 95% CI, 0.67-0.98; P = .03; 21/1000 events prevented; 4 to <8 hours: HR, 0.85; 95% CI, 0.73-0.99; P = .05; 16/1000 events prevented; and 8 hours: HR, 1.06; 95% CI, 0.86-1.30; P = .58; P = .04 for trend). There was an increase in life-threatening bleeding at 7 days with reviparin and placebo (17 [0.2%] vs 7 [0.1%], respectively; P = .07), but the absolute excess was small (1 more per 1000) vs reductions in the primary outcome (18 fewer per 1000) or mortality (15 fewer per 1000). Conclusions  In patients with acute ST-segment elevation or new left bundle-branch block MI, reviparin reduces mortality and reinfarction, without a substantive increase in overall stroke rates. There is a small absolute excess of life-threatening bleeding but the benefits outweigh the risks.      

Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial

Context  Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. Objective  To evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. Design, Setting, and Participants  Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12 092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. Main Outcome Measures  Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months). Results  Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days. Conclusion  In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes. Trial Registration  ClinicalTrials.gov Identifier NCT00064428      

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.      

Patent foramen ovale and high-altitude pulmonary edema

Context  Individuals susceptible to high-altitude pulmonary edema (HAPE) are characterized by exaggerated pulmonary hypertension and arterial hypoxemia at high altitude, but the underlying mechanism is incompletely understood. Anecdotal evidence suggests that shunting across a patent foramen ovale (PFO) may exacerbate hypoxemia in HAPE. Objective  We hypothesized that PFO is more frequent in HAPE-susceptible individuals and may contribute to more severe arterial hypoxemia at high altitude. Design, Setting, and Participants  Case-control study of 16 HAPE-susceptible participants and 19 mountaineers resistant to this condition (repeated climbing to peaks above 4000 m and no symptoms of HAPE). Main Outcome Measures  Presence of PFO determined by transesophageal echocardiography, estimated pulmonary artery pressure by Doppler echocardiography, and arterial oxygen saturation measured by pulse oximetry in HAPE-susceptible and HAPE-resistant participants at low (550 m) and high altitude (4559 m). Results  The frequency of PFO was more than 4 times higher in HAPE-susceptible than in HAPE-resistant participants, both at low altitude (56% vs 11%, P = .004; odds ratio [OR], 10.9 [95% confidence interval {CI}, 1.9-64.0]) and high altitude (69% vs 16%, P = .001; OR, 11.7 [95% CI, 2.3-59.5]). At high altitude, mean (SD) arterial oxygen saturation prior to the onset of pulmonary edema was significantly lower in HAPE-susceptible participants than in the control group (73% [10%] vs 83% [7%], P = .001). Moreover, in the HAPE-susceptible group, participants with a large PFO had more severe arterial hypoxemia (65% [6%] vs 77% [8%], P = .02) than those with smaller or no PFO. Conclusions  Patent foramen ovale was roughly 4 times more frequent in HAPE-susceptible mountaineers than in participants resistant to this condition. At high altitude, HAPE-susceptible participants with a large PFO had more severe hypoxemia. We speculate that at high altitude, a large PFO may contribute to exaggerated arterial hypoxemia and facilitate HAPE.      

Respiration during snow burial using an artificial air pocket

Context  Asphyxia is the most common cause of death after avalanche burial. A device that allows a person to breathe air contained in snow by diverting expired carbon dioxide (CO₂) away from a 500-cm³ artificial inspiratory air pocket may improve chances of survival in avalanche burial. Objective  To determine the duration of adequate oxygenation and ventilation during burial in dense snow while breathing with vs without the artificial air pocket device. Design  Field study of physiologic respiratory measures during snow burial with and without the device from December 1998 to March 1999. Study burials were terminated at the subject's request, when oxygen saturation as measured by pulse oximetry (SpO₂) dropped to less than 84%, or after 60 minutes elapsed. Setting  Mountainous outdoor site at 2385 m elevation, with an average barometric pressure of 573 mm Hg. Participants  Six male and 2 female volunteers (mean age, 34.6 years; range, 28-39 years). Main Outcome Measures  Burial time, SpO₂, partial pressure of end-tidal CO₂ (ETCO₂), partial pressure of inspiratory CO₂(PICO₂), respiratory rate, and heart rate at baseline (in open atmosphere) and during snow burial while breathing with the device and without the device but with a 500-cm³ air pocket in the snow. Results  Mean burial time was 58 minutes (range, 45-60 minutes) with the device and 10 minutes (range, 5-14 minutes) without it (P=.001). A mean baseline SpO₂ of 96% (range, 90%-99%) decreased to 90% (range, 77%-96%) in those buried with the device (P=.01) and to 84% (range, 79%-92%) in the control burials (P=.02). Only 1 subject buried with the device, but 6 control subjects buried without the device, decreased SpO₂ to less than 88% (P=.005). A mean baseline ETCO₂ of 32 mm Hg (range, 27-38 mm Hg) increased to 45 mm Hg (range, 32-53 mm Hg) in the burials with the device (P=.02) and to 54 mm Hg (range, 44-63 mm Hg) in the control burials (P=.02). A mean baseline PICO₂ of 2 mm Hg (range, 0-3 mm Hg) increased to 32 mm Hg (range, 20-44 mm Hg) in the burials with the device (P=.01) and to 44 mm Hg (range, 37-50 mm Hg) in the control burials (P=.02). Respiratory and heart rates did not change in burials with the device but significantly increased in control burials. Conclusions  In our study, although hypercapnia developed, breathing with the device during snow burial considerably extended duration of adequate oxygenation compared with breathing with an air pocket in the snow. Further study will be needed to determine whether the device improves survival during avalanche burial.      

Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial

Context  Few depressed older adults receive effective treatment in primary care settings. Objective  To determine the effectiveness of the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) collaborative care management program for late-life depression. Design  Randomized controlled trial with recruitment from July 1999 to August 2001. Setting  Eighteen primary care clinics from 8 health care organizations in 5 states. Participants  A total of 1801 patients aged 60 years or older with major depression (17%), dysthymic disorder (30%), or both (53%). Intervention  Patients were randomly assigned to the IMPACT intervention (n = 906) or to usual care (n = 895). Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education, care management, and support of antidepressant management by the patient's primary care physician or a brief psychotherapy for depresssion, Problem Solving Treatment in Primary Care. Main Outcome Measures  Assessments at baseline and at 3, 6, and 12 months for depression, depression treatments, satisfaction with care, functional impairment, and quality of life. Results  At 12 months, 45% of intervention patients had a 50% or greater reduction in depressive symptoms from baseline compared with 19% of usual care participants (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.71-4.38; P<.001). Intervention patients also experienced greater rates of depression treatment (OR, 2.98; 95% CI, 2.34-3.79; P<.001), more satisfaction with depression care (OR, 3.38; 95% CI, 2.66-4.30; P<.001), lower depression severity (range, 0-4; between-group difference, -0.4; 95% CI, -0.46 to -0.33; P<.001), less functional impairment (range, 0-10; between-group difference, -0.91; 95% CI, -1.19 to -0.64; P<.001), and greater quality of life (range, 0-10; between-group difference, 0.56; 95% CI, 0.32-0.79; P<.001) than participants assigned to the usual care group. Conclusion  The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practices.      

Secondary aerosolization of viable Bacillus anthracis spores in a contaminated US Senate Office

Context  Bioterrorist attacks involving letters and mail-handling systems in Washington, DC, resulted in Bacillus anthracis (anthrax) spore contamination in the Hart Senate Office Building and other facilities in the US Capitol's vicinity. Objective  To provide information about the nature and extent of indoor secondary aerosolization of B anthracis spores. Design  Stationary and personal air samples, surface dust, and swab samples were collected under semiquiescent (minimal activities) and then simulated active office conditions to estimate secondary aerosolization of B anthracis spores. Nominal size characteristics, airborne concentrations, and surface contamination of B anthracis particles (colony-forming units) were evaluated. Results  Viable B anthracis spores reaerosolized under semiquiescent conditions, with a marked increase in reaerosolization during simulated active office conditions. Increases were observed for B anthracis collected on open sheep blood agar plates (P<.001) and personal air monitors (P = .01) during active office conditions. More than 80% of the B anthracis particles collected on stationary monitors were within an alveolar respirable size range of 0.95 to 3.5 µm. Conclusions  Bacillus anthracis spores used in a recent terrorist incident reaerosolized under common office activities. These findings have important implications for appropriate respiratory protection, remediation, and reoccupancy of contaminated office environments.