External validation of the Canadian CT Head Rule and the New Orleans Criteria for CT scanning in patients with minor head injury

Context  Two decision rules for indications of computed tomography (CT) in patients with minor head injury, the Canadian CT Head Rule (CCHR) and the New Orleans Criteria (NOC), suggest that CT scanning may be restricted to patients with certain risk factors, which would lead to important reductions in the use of CT scans. Objective  To validate and compare these 2 published decision rules in Dutch patients with head injuries. Design, Setting, and Patients  A prospective multicenter study conducted between February 11, 2002, and August 31, 2004, in 4 university hospitals in the Netherlands of 3181 consecutive adult patients with minor head injury who presented with a Glasgow Coma Scale (GCS) score of 13 to 14 or with a GCS score of 15 and at least 1 risk factor. Main Outcome Measures  Primary outcome was any neurocranial traumatic finding on CT scan. Secondary outcomes were neurosurgical intervention and clinically important CT findings. Sensitivity and specificity were estimated for each outcome for the CCHR and the NOC, using both rules as originally derived and also as adapted to apply to an expanded patient population. Results  Of 3181 patients with a GCS score of 13 to 15, neurosurgical intervention was performed in 17 patients (0.5%); neurocranial traumatic CT findings were present in 312 patients (9.8%). Sensitivity for neurosurgical intervention was 100% for both the CCHR and the NOC. The NOC had a higher sensitivity for neurocranial traumatic findings and for clinically important findings (97.7%-99.4%) than did the CCHR (83.4%-87.2%). Specificities were very low for the NOC (3.0%-5.6%) and higher for the CCHR (37.2%-39.7%). The estimated potential reduction in CT scans for patients with minor head injury would be 3.0% for the adapted NOC and 37.3% for the adapted CCHR. Conclusions  For patients with minor head injury and a GCS score of 13 to 15, the CCHR has a lower sensitivity than the NOC for neurocranial traumatic or clinically important CT findings, but would identify all cases requiring neurosurgical intervention, and has greater potential for reducing the use of CT scans.      

6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial

Context  Survival benefit in the management of high-grade clinically localized prostate cancer has been shown for 70 Gy radiation therapy combined with 3 years of androgen suppression therapy (AST), but long-term AST is associated with many adverse events. Objective  To assess the survival benefit of 3-dimensional conformal radiation therapy (3D-CRT) alone or in combination with 6 months of AST in patients with clinically localized prostate cancer. Design, Setting, and Patients  A prospective randomized controlled trial of 206 patients with clinically localized prostate cancer who were randomized to receive 70 Gy 3D-CRT alone (n = 104) or in combination with 6 months of AST (n = 102) from December 1, 1995, to April 15, 2001. Eligible patients included those with a prostate-specific antigen (PSA) of at least 10 ng/mL, a Gleason score of at least 7, or radiographic evidence of extraprostatic disease. Main Outcome Measures  Time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits) and overall survival. Results  After a median follow-up of 4.52 years, patients randomized to receive 3D-CRT plus AST had a significantly higher survival (P = .04), lower prostate cancer–specific mortality (P = .02), and higher survival free of salvage AST (P = .002). Kaplan-Meier estimates of 5-year survival rates were 88% (95% confidence interval [CI], 80%-95%) in the 3D-CRT plus AST group vs 78% (95% CI, 68%-88%) in the 3D-CRT group. Rates of survival free of salvage AST at 5 years were 82% (95% CI, 73%-90%) in the 3D-CRT plus AST group vs 57% (95% CI, 46%-69%) in the 3D-CRT group. Conclusion  The addition of 6 months of AST to 70 Gy 3D-CRT confers an overall survival benefit for patients with clinically localized prostate cancer.      

Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review

Context  Neuroendocrine dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage may occur with a much higher prevalence than previously suspected. This sequela is a potentially serious but treatable complication of brain injury. Objective  To review research on hypothalamopituitary dysfunction as an underdiagnosed consequence of traumatic brain injury and subarachnoid hemorrhage, the natural history of this complication, and the potential clinical and public health implications of posttraumatic hypopituitarism. Evidence Acquisition  The MEDLINE database was searched for articles published between 2000 and 2007 using any combination of the terms traumatic brain injury or subarachnoid hemorrhage with pituitary, hypopituitarism, growth hormone deficiency, hypogonadism, hypocortisolism, hypothyroidism, or diabetes insipidus. The reference lists of articles identified by this search strategy were also searched. All articles reporting original data on endocrine outcomes after traumatic brain injury or aneurysmal subarachnoid hemorrhage in peer-reviewed journals with regard to prevalence, pathogenesis, risk factors, outcomes, and clinical course were selected. We pooled data and calculated prevalence rates and 95% confidence intervals (CIs). Results  We identified 19 studies including 1137 patients. The pooled prevalences of hypopituitarism in the chronic phase after traumatic brain injury and aneurysmal subarachnoid hemorrhage were 27.5% (95% confidence interval [CI], 22.8%-28.9%) and 47% (95% CI, 37.4%-56.8%), respectively. The pooled prevalence of hypopituitarism was greater in patients with severe compared with those with mild or moderate traumatic brain injury. Early neuroendocrine abnormalities were transient in some patients while, less commonly, hypopituitarism evolved over time in others. Patients with posttraumatic hypopituitarism showed an impaired quality of life and an adverse metabolic profile. Conclusion  Hypopituitarism is a common complication of both traumatic brain injury and aneurysmal subarachnoid hemorrhage and might contribute to morbidity and poor recovery after brain injury.      

Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress

Context  Tandem mass spectrometry now allows newborn screening for more than 20 biochemical genetic disorders. Questions about the effectiveness and risks of expanded newborn screening for biochemical genetic disorders need to be answered prior to its widespread acceptance as a state-mandated program. Objectives  To compare newborn identification by expanded screening with clinical identification of biochemical genetic disorders and to assess the impact on families of a false-positive screening result compared with a normal result in the expanded newborn screening program. Design  Prospective study involving an inception cohort of newly diagnosed children. Setting  Massachusetts, Maine, and a private laboratory in Pennsylvania with expanded newborn screening; other New England states with limited screening. Participants  Families of 50 affected children identified through expanded newborn screening (82% of eligible cases); 33 affected children identified clinically (97% of eligible cases); 94 screened children with false-positive results (75% of eligible cases); and 81 screened children with normal results (63% of eligible cases). Main Outcome Measures  Child's health and development and the Parental Stress Index. Results  Within the first 6 months of life, 28% of children identified by newborn screening compared with 55% of clinically identified children required hospitalization (P = .02). One child identified by newborn screening compared with 8 (42%) identified clinically performed in the range of mental retardation (P<.001). Mothers in the screened group reported lower overall stress on the Parental Stress Index than mothers in the clinically identified group (z = 3.38, P<.001). Children with false-positive results compared with children with normal results were twice as likely to experience hospitalization (21% [n = 20] vs 10% [n = 8], respectively; P = .06). Mothers of children in the false-positive group compared with mothers of children with normal screening results attained higher scores on the Parental Stress Index (z = 4.25, P<.001) and the Parent-Child Dysfunction subscale (z = 5.30, P<.001). Conclusions  Expanded newborn screening may lead to improved health outcomes for affected children and lower stress for their parents. However, false-positive screening results may place families at risk for increased stress and parent-child dysfunction.      

Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990-1992 to 2001-2003

Context  Little is known about trends in suicidal ideation, plans, gestures, or attempts or about their treatment. Such data are needed to guide and evaluate policies to reduce suicide-related behaviors. Objective  To analyze nationally representative trend data on suicidal ideation, plans, gestures, attempts, and their treatment. Design, Setting, and Participants  Data came from the 1990-1992 National Comorbidity Survey and the 2001-2003 National Comorbidity Survey Replication. These surveys asked identical questions to 9708 people aged 18 to 54 years about the past year’s occurrence of suicidal ideation, plans, gestures, attempts, and treatment. Trends were evaluated by using pooled logistic regression analysis. Face-to-face interviews were administered in the homes of respondents, who were nationally representative samples of US English-speaking residents. Main Outcome Measure  Self-reports about suicide-related behaviors and treatment in the year before interview. Results  No significant changes occurred between 1990-1992 and 2001-2003 in suicidal ideation (2.8% vs 3.3%; P = .43), plans (0.7% vs 1.0%; P = .15), gestures (0.3% vs 0.2%; P = .24), or attempts (0.4%-0.6%; P = .45), whereas conditional prevalence of plans among ideators increased significantly (from 19.6% to 28.6%; P = .04), and conditional prevalence of gestures among planners decreased significantly (from 21.4% to 6.4%; P = .003). Treatment increased dramatically among ideators who made a gesture (40.3% vs 92.8%) and among ideators who made an attempt (49.6% vs 79.0%). Conclusions  Despite a dramatic increase in treatment, no significant decrease occurred in suicidal thoughts, plans, gestures, or attempts in the United States during the 1990s. Continued efforts are needed to increase outreach to untreated individuals with suicidal ideation before the occurrence of attempts and to improve treatment effectiveness for such cases.      

Invasive meningococcal disease in adolescents and young adults

Context  Incidence of invasive meningococcal disease has increased recently in persons aged 15 through 24 years. Objective  To characterize meningococcal infection in adolescents and young adults in Maryland during the 1990s. Design and Setting  Population-based surveillance study for meningococcal disease from January 1, 1990, through December 31, 1999, in Maryland. Patients  Maryland residents diagnosed as having invasive meningococcal disease. Main Outcome Measure  Invasive meningococcal infection. Results  Of 295 total cases, 71 (24.1%) occurred among persons aged 15 through 24 years. Sixteen (22.5%) of these cases were fatal. The annual incidence rate increased from 0.9 to 2.1 cases per 100 000 among 15 through 24 year olds (P = .01). The proportion of all disease increased from 16.0% to 28.9% (P = .03). The incidence and proportion of cases subsequently decreased to 1.0 and 16.4% in 1998 through 1999, respectively. Infection in 15 through 24 year olds was more likely to be fatal than infection in those younger than age 15 years (22.5% vs 4.6%; P = .001). Infection in 15 through 24 year olds, compared with those aged 25 years or older, was more likely to be associated with male sex (66.2% vs 34.8%; P<.001) and serogroup C infection (46.9% vs 20.2%; P<.001), respectively. Infections were potentially preventable with the licensed meningococcal vaccine in 82.8% of 15 through 24 year olds, 68.1% of those younger than 15 years, and 76.8% of adults aged 25 years or older. Conclusions  Incidence of meningococcal infection in 15 through 24 year olds in Maryland increased and then declined during the 1990s. Infection in this age group was associated with an unusually high case-fatality ratio, and the vast majority of cases were potentially vaccine preventable.      

Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial

Context  Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder. Objective  To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity. Design  Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997. Setting  Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers. Patients  A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault). Intervention  Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93). Main Outcome Measures  Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression–Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results  Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P=.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01). Conclusions  Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.      

Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial

Context  Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed. Objective  To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial. Interventions  Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n = 203) or placebo (n = 201) for 24 weeks. Main Outcome Measures  Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study–Activities of Daily Living Inventory (ADCS-ADL₁₉). Secondary outcomes included a Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale). Results  The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs –2.5 (0.69), respectively (P<.001); ADCS-ADL₁₉ (possible score range, 0-54), –2.0 (0.50) vs –3.4 (0.51), respectively (P = .03); and the CIBIC-Plus (possible score range, 1-7), 4.41 (0.074) vs 4.66 (0.075), respectively (P = .03). All other secondary measures showed significant benefits of memantine treatment. Treatment discontinuations because of adverse events for memantine vs placebo were 15 (7.4%) vs 25 (12.4%), respectively. Conclusions  In patients with moderate to severe AD receiving stable doses of donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, global outcome, and behavior and was well tolerated. These results, together with previous studies, suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD.      

Effect of prone positioning on clinical outcomes in children with acute lung injury: a randomized controlled trial

Context  In uncontrolled clinical studies, prone positioning appeared to be safe and to improve oxygenation in pediatric patients with acute lung injury. However, the effect of prone positioning on clinical outcomes in children is not known. Objective  To test the hypothesis that at the end of 28 days infants and children with acute lung injury treated with prone positioning would have more ventilator-free days than those treated with supine positioning. Design, Setting, and Patients  Multicenter, randomized, controlled clinical trial conducted from August 28, 2001, to April 23, 2004, of 102 pediatric patients from 7 US pediatric intensive care units aged 2 weeks to 18 years who were treated with supine vs prone positioning. Randomization was concealed and group assignment was not blinded. Intervention  Patients were randomized to either supine or prone positioning within 48 hours of meeting acute lung injury criteria, with those patients in the prone group being positioned within 4 hours of randomization and remaining prone for 20 hours each day during the acute phase of their illness for a maximum of 7 days, after which they were positioned supine. Both groups were treated using lung protective ventilator and sedation protocols, extubation readiness testing, and hemodynamic, nutrition, and skin care guidelines. Main Outcome Measure  Ventilator-free days to day 28. Results  The trial was stopped at the planned interim analysis on the basis of the prespecified futility stopping rule. There were no differences in the number of ventilator-free days between the 2 groups (mean [SD], 15.8 [8.5] supine vs 15.6 [8.6] prone; mean difference, –0.2 days; 95% CI, –3.6 to 3.2; P = .91). After controlling for age, Pediatric Risk of Mortality III score, direct vs indirect acute lung injury, and mode of mechanical ventilation at enrollment, the adjusted difference in ventilator-free days was 0.3 days (95% CI, –3.0 to 3.5; P = .87). There were no differences in the secondary end points, including proportion alive and ventilator-free on day 28 (P = .45), mortality from all causes (P>.99), the time to recovery of lung injury (P = .78), organ-failure–free days (P = .88), and cognitive impairment (P = .16) or overall functional health (P = .12) at hospital discharge or on day 28. Conclusion  Prone positioning does not significantly reduce ventilator-free days or improve other clinical outcomes in pediatric patients with acute lung injury.      

Maternal and infant characteristics associated with perinatal arterial stroke in the infant

Janet Lee, MS; Lisa A. Croen, PhD; Kendall H. Backstrand, BA; Cathleen K. Yoshida, MS; Louis H. Henning, BA; Camilla Lindan, MD; Donna M. Ferriero, MD; Heather J. Fullerton, MD; A. J. Barkovich, MD; Yvonne W. Wu, MD, MPH

JAMA. 2005;293:723-729.

Context  Perinatal arterial ischemic stroke (PAS) is a common cause of hemiplegic cerebral palsy. Risk factors for this condition have not been clearly defined.

Objective  To determine maternal and infant characteristics associated with PAS.

Design, Setting, and Patients  Case-control study nested within the cohort of all 199 176 infants born from 1997 through 2002 in the Kaiser Permanente Medical Care Program, a managed care organization providing care for more than 3 million residents of northern California. Case patients were confirmed by review of brain imaging and medical records (n = 40). Three controls per case were randomly selected from the study population.

Main Outcome Measure  Association of maternal and infant complications with risk of PAS.

Results  The population prevalence of PAS was 20 per 100 000 live births. The majority (85%) of infants with PAS were delivered at term. The following prepartum and intrapartum factors were more common among case than control infants: primiparity (73% vs 44%, P = .002), fetal heart rate abnormality (46% vs 14%, P<.001), emergency cesarean delivery (35% vs 13%, P = .002), chorioamnionitis (27% vs 11%, P = .03), prolonged rupture of membranes (26% vs 7%, P = .002), prolonged second stage of labor (25% vs 4%, P<.001), vacuum extraction (24% vs 11%, P = .04), cord abnormality (22% vs 6%, P = .01), preeclampsia (19% vs 5%, P = .01), and oligohydramnios (14% vs 3%, P = .01). Risk factors independently associated with PAS on multivariate analysis were history of infertility (odds ratio [OR], 7.5; 95% confidence interval [CI], 1.3-45.0), preeclampsia (OR, 5.3; 95% CI, 1.3-22.0), prolonged rupture of membranes (OR, 3.8; 95% CI, 1.1-12.8), and chorioamnionitis (OR, 3.4; 95% CI, 1.1-10.5). The rate of PAS increased dramatically when multiple risk factors were present.

Conclusions  Perinatal arterial ischemic stroke in infants is associated with several independent maternal risk factors. How these complications, along with their potential effects on the placenta and fetus, may play a role in causing perinatal stroke deserves further study.

     

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.      

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.      

Chronic conditions, functional limitations, and special health care needs of school-aged children born with extremely low-birth-weight in the 1990s

Context  Information on the school-age functioning and special health care needs of extremely low-birth-weight (ELBW, <1000 g) children is necessary to plan for medical and educational services. Objective  To examine neurosensory, developmental, and medical conditions together with the associated functional limitations and special health care needs of ELBW children compared with normal-birth-weight (NBW) term-born children (controls). Design, Setting, and Participants  A follow-up study at age 8 years of a cohort of 219 ELBW children born 1992 to 1995 (92% of survivors) and 176 NBW controls of similar sociodemographic status conducted in Cleveland, Ohio. Main Outcome Measures  Parent Questionnaire for Identifying Children with Chronic Conditions of 12 months or more and categorization of specific medical diagnoses and developmental disabilities based on examination of the children. Results  In logistic regression analyses adjusting for sociodemographic status and sex, ELBW children had significantly more chronic conditions than NBW controls, including functional limitations (64% vs 20%, respectively; odds ratio [OR], 8.1; 95% confidence interval [CI], 5.0-13.1; P<.001), compensatory dependency needs (48% vs 23%, respectively; OR, 3.0; 95% CI, 1.9-4.7; P<.001), and services above those routinely required by children (65% vs 27%, respectively; OR, 5.4; 95% CI, 3.4-8.5; P<.001). These differences remained significant when the 36 ELBW children with neurosensory impairments were excluded. Specific diagnoses and disabilities for ELBW vs NBW children included cerebral palsy (14% vs 0%, respectively; P<.001), asthma (21% vs 9%; OR, 3.0; 95% CI, 1.6-5.6; P = .001), vision of less than 20/200 (10% vs 3%; OR, 3.1; 95% CI, 1.2-7.8; P = .02), low IQ of less than 85 (38% vs 14%; OR, 4.5; 95% CI, 2.7-7.7; P<.001), limited academic skills (37% vs 15%; OR, 4.2; 95% CI, 2.5-7.3; P<.001), poor motor skills (47% vs 10%; OR, 7.8; 95% CI, 4.5-13.6; P<.001), and poor adaptive functioning (69% vs 34%; OR, 6.5; 95% CI, 4.0-10.6; P<.001). Conclusion  The ELBW survivors in school at age 8 years who were born in the 1990s have considerable long-term health and educational needs.      

Transition of extremely low-birth-weight infants from adolescence to young adulthood: comparison with normal birth-weight controls

Context  Traditionally, educational attainment, getting a job, living independently, getting married, and parenthood have been considered as markers of successful transition to adulthood. Objective  To describe and compare the achievement and the age at attainment of the above markers between extremely low-birth-weight (ELBW) and normal birth-weight (NBW) young adults. Design, Setting, and Participants  A prospective, longitudinal, population-based study in central-west Ontario, Canada, of 166 ELBW participants who weighed 501 to 1000 g at birth (1977-1982) and 145 sociodemographically comparable NBW participants assessed at young adulthood (22-25 years). Interviewers masked to participant status administered validated questionnaires via face-to-face interviews between January 1, 2002, and April 30, 2004. Main Outcome Measures  Markers of successful transition to adulthood, including educational attainment, student and/or worker role, independent living, getting married, and parenthood. Results  At young adulthood, 149 (90%) of 166 ELBW participants and 133 (92%) of 145 NBW participants completed the assessments at mean (SD) age of 23.3 (1.2) years and 23.6 (1.1) years, respectively. We included participants with neurosensory impairments (ELBW vs NBW: 40 [27%] vs 3 [2%]) and 7 proxy respondents. The proportion who graduated from high school was similar (82% vs 87%, P = .21). Overall, no statistically significant differences were observed in the education achieved to date. A substantial proportion of both groups were still pursuing postsecondary education (47 [32%] vs 44 [33%]). No significant differences were observed in employment/school status; 71 (48%) ELBW vs 76 (57%) NBW young adults were permanently employed (P = .09). In a subanalysis, a higher proportion of ELBW young adults were neither employed nor in school (39 [26%] vs 20 [15%], P = .02 by Holm's correction); these differences did not persist when participants with disabilities were excluded. No significant differences were found in the proportion living independently (63 [42%] vs 70 [53%], P = .19), married/cohabitating (34 [23%] vs 33 [25%], P = .69), or who were parents (16 [11%] vs 19 [14%], P = .36). The age at attainment of the above markers was similar for both cohorts. Conclusion  Our study results indicate that a significant majority of former ELBW infants have overcome their earlier difficulties to become functional young adults.      

Efficacy and safety of pyridoxal 5'-phosphate (MC-1) in high-risk patients undergoing coronary artery bypass graft surgery: the MEND-CABG II randomized clinical trial

Context  Coronary artery bypass graft (CABG) surgery is frequently performed and effective; however, perioperative complications related to ischemia-reperfusion injury, including myocardial infarction (MI), remain common and result in significant morbidity and mortality. MC-1, a naturally occurring pyridoxine metabolite and purinergic receptor antagonist, prevents cellular calcium overload and may reduce ischemia-reperfusion injury. Phase 2 trial data suggest that MC-1 may reduce death or MI in high-risk patients undergoing CABG surgery. Objective  To assess the efficacy and safety of MC-1 administered immediately before and for 30 days after surgery in patients undergoing CABG surgery. Design, Setting, and Participants  The MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II Trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, with 3023 intermediate- to high-risk patients undergoing CABG surgery with cardiopulmonary bypass enrolled between October 2006 and September 2007 at 130 sites in Canada, the United States, and Germany. Interventions  Patients received either MC-1, 250 mg/d (n = 1519), or matching placebo (n = 1504) immediately before and for 30 days after CABG surgery. Main Outcome Measures  The primary efficacy outcome was cardiovascular death or nonfatal MI, defined as a creatine kinase (CK) MB fraction of at least 100 ng/mL or new Q waves through postoperative day 30. Results  The primary efficacy outcome occurred in 140 of 1510 patients (9.3%) in the MC-1 group and 133 of 1486 patients (9.0%) in the placebo group (risk ratio, 1.04; 95% confidence interval, 0.83-1.30; P = .76). All-cause mortality was higher among patients assigned to MC-1 than placebo at 4 days (1.0% vs 0.3%; P = .03) but was similar at 30 days (1.9% vs 1.5%; P = .44). There was no difference in the 8- to 24-hour CK-MB area under the curve between the MC-1 and placebo groups (median, 270 [interquartile range, 175-492] vs 268 [interquartile range, 170-456] hours x ng/mL; P = .11). Conclusion  In this population of intermediate- to high-risk patients undergoing CABG surgery, MC-1 did not reduce the composite of cardiovascular death or nonfatal MI. Trial Registration  clinicaltrials.gov Identifier: NCT00402506      

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.      

Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury: a randomized controlled trial

Context  Prehospital hypertonic saline (HTS) resuscitation of patients with traumatic brain injury (TBI) may increase survival but whether HTS improves neurological outcomes is unknown. Objective  To determine whether prehospital resuscitation with intravenous HTS improves long-term neurological outcome in patients with severe TBI compared with resuscitation with conventional fluids. Design, Setting, and Patients  Double-blind, randomized controlled trial of 229 patients with TBI who were comatose (Glasgow Coma Scale score, <9) and hypotensive (systolic blood pressure, <100 mm Hg). The patients were enrolled between December 14, 1998, and April 9, 2002, in Melbourne, Australia. Interventions  Patients were randomly assigned to receive a rapid intravenous infusion of either 250 mL of 7.5% saline (n = 114) or 250 mL of Ringer's lactate solution (n = 115; controls) in addition to conventional intravenous fluid and resuscitation protocols administered by paramedics. Treatment allocation was concealed. Main Outcome Measure  Neurological function at 6 months, measured by the extended Glasgow Outcome Score (GOSE). Results  Primary outcomes were obtained in 226 (99%) of 229 patients enrolled. Baseline characteristics of the groups were equivalent. At hospital admission, the mean serum sodium level was 149 mEq/L for HTS patients vs 141 mEq/L for controls (P<.001). The proportion of patients surviving to hospital discharge was similar in both groups (n = 63 [55%] for HTS group and n = 57 [50%] for controls; P = .32); at 6 months, survival rates were n = 62 (55%) in the HTS group and n = 53 (47%) in the control group (P = .23). At 6 months, the median (interquartile range) GOSE was 5 (3-6) in the HTS group vs 5 (5-6) in the control group (P = .45). There was no significant difference between the groups in favorable outcomes (moderate disability and good outcome survivors [GOSE of 5-8]) (risk ratio, 0.99; 95% confidence interval, 0.76-1.30; P = .96) or in any other measure of postinjury neurological function. Conclusion  In this study, patients with hypotension and severe TBI who received prehospital resuscitation with HTS had almost identical neurological function 6 months after injury as patients who received conventional fluid.      

Myocardial injury and long-term mortality following moderate to severe carbon monoxide poisoning

Context  Carbon monoxide (CO) poisoning is a common cause of toxicological morbidity and mortality. Myocardial injury is a frequent consequence of moderate to severe CO poisoning. While the in-hospital mortality for these patients is low, the long-term outcome of myocardial injury in this setting is unknown. Objective  To determine the association between myocardial injury and long-term mortality in patients following moderate to severe CO poisoning. Design, Setting, and Participants  Prospective cohort study of 230 consecutive adult patients treated for moderate to severe CO poisoning with hyperbaric oxygen and admitted to the Hennepin County Medical Center, a regional center for treatment of CO poisoning, between January 1, 1994, and January 1, 2002. Follow-up was through November 11, 2005. Main Outcome Measure  All-cause mortality. Results  Myocardial injury (cardiac troponin I level 0.7 ng/mL or creatine kinase-MB level 5.0 ng/mL and/or diagnostic electrocardiogram changes) occurred in 85 (37%) of 230 patients. At a median follow-up of 7.6 years (range: in-hospital only to 11.8 years), there were 54 deaths (24%). Twelve of those deaths (5%) occurred in the hospital as a result of a combination of burn injury and anoxic brain injury (n = 8) or cardiac arrest and anoxic brain injury (n = 4). Among the 85 patients who sustained myocardial injury from CO poisoning, 32 (38%) eventually died compared with 22 (15%) of 145 patients who did not sustain myocardial injury (adjusted hazard ratio, 2.1; 95% confidence interval, 1.2-3.7; P = .009). Conclusion  Myocardial injury occurs frequently in patients hospitalized for moderate to severe CO poisoning and is a significant predictor of mortality.      

MELD scores of liver transplant recipients according to size of waiting list: impact of organ allocation and patient outcomes

Context  The Model for Endstage Liver Disease (MELD) score serves as the basis for the distribution of deceased-donor (DD) livers and was developed in response to "the final rule" mandate, whose stated principle is to allocate livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area. However, in selected areas of the United States, organs are kept in organ procurement organizations (OPOs) with small waiting lists and transplanted into less-sick patients instead of being allocated to sicker patients in nearby transplant centers in OPOs with large waiting lists. Objective  To determine whether there is a difference in MELD scores for liver transplant recipients receiving transplants in small vs large OPOs. Design and Setting  Retrospective review of the US Scientific Registry of Transplant Recipients between February 28, 2002, and March 31, 2003. Transplant recipients (N = 4798) had end-stage liver disease and received DD livers. Main Outcome Measures  MELD score distribution (range, 6-40), graft survival, and patient survival for liver transplant recipients in small (<100) and large (=" BORDER="0">100 on the waiting list) OPOs. Results  The distribution of MELD scores was the same in large and small OPOs; 92% had a MELD score of 18 or less, 7% had a MELD score between 19 and 24, and only 2% of listed patients had a MELD score higher than 24 (P = .85). The proportion of patients receiving transplants in small OPOs and with a MELD score higher than 24 was significantly lower than that in large OPOs (19% vs 49%; P<.001). Patient survival rates at 1 year after transplantation for small OPOs (86.4%) and large OPOs (86.6%) were not statistically different (P = .59), and neither were graft survival rates in small OPOs (80.1%) and large OPOs (81.3%) (P = .80). Conclusions  There is a significant disparity in MELD scores in liver transplant recipients in small vs large OPOs; fewer transplant recipients in small OPOs have severe liver disease (MELD score >24). This disparity does not reflect the stated goals of the current allocation policy, which is to distribute livers according to a patient's medical need, with less emphasis on keeping organs in the local procurement area.      

Handheld cellular telephone use and risk of brain cancer

Context  A relative paucity of data exist on the possible health effects of using cellular telephones. Objective  To test the hypothesis that using handheld cellular telephones is related to the risk of primary brain cancer. Design and Setting  Case-control study conducted in 5 US academic medical centers between 1994 and 1998 using a structured questionnaire. Patients  A total of 469 men and women aged 18 to 80 years with primary brain cancer and 422 matched controls without brain cancer. Main Outcome Measure  Risk of brain cancer compared by use of handheld cellular telephones, in hours per month and years of use. Results  The median monthly hours of use were 2.5 for cases and 2.2 for controls. Compared with patients who never used handheld cellular telephones, the multivariate odds ratio (OR) associated with regular past or current use was 0.85 (95% confidence interval [CI], 0.6-1.2). The OR for infrequent users (<0.72 h/mo) was 1.0 (95% CI, 0.5-2.0) and for frequent users (>10.1 h/mo) was 0.7 (95% CI, 0.3-1.4). The mean duration of use was 2.8 years for cases and 2.7 years for controls; no association with brain cancer was observed according to duration of use (P = .54). In cases, cerebral tumors occurred more frequently on the same side of the head where cellular telephones had been used (26 vs 15 cases; P = .06), but in the cases with temporal lobe cancer a greater proportion of tumors occurred in the contralateral than ipsilateral side (9 vs 5 cases; P = .33). The OR was less than 1.0 for all histologic categories of brain cancer except for uncommon neuroepitheliomatous cancers (OR, 2.1; 95% CI, 0.9-4.7). Conclusions  Our data suggest that use of handheld cellular telephones is not associated with risk of brain cancer, but further studies are needed to account for longer induction periods, especially for slow-growing tumors with neuronal features.