Oral risedronate sodium improves bone mineral density in non-ambulatory patients: a randomized, double-blind, placebo controlled trial.

AIMS: Investigate the efficacy of risedronate sodium (Procter and Gamble, Cincinnati, USA) for treating reduced lumbar spine (LS) bone mineral density (BMD) in non-ambulatory patients. METHODS: Nine (10-39 years, mean age 23.0 years, 7 males) in the risedronate arm and 10 (10-35 years, mean age 21.4 years, 8 males) in the placebo arm completed 24 months of therapy at baseline, 6, 12, 18, and 24 months. The primary outcome was change in LS BMD assessed by dual energy x-ray absorptiometry (DXA). Secondary outcomes included changes in serum bone markers, bone specific alkaline phosphatase, osteocalcin, and N-telopeptides. Mixed models examined group, time, and the group by time interaction for the 4 post-baseline time points. RESULTS: The change in LS BMD score from baseline to 24 months was 0.069 (95% CI 0.014 to 0.124) in risedronate participants compared to -0.015 (95% CI -0.073 to 0.042) (t Value = -2.40, P > t=0.03) in the controls. When controlling for baseline scores, the difference was consistent across four post-baseline time points tested (F=5.67, Pr > F=0.03). No differences in serum bone markers were observed. CONCLUSIONS: Risedronate increases LS BMD in non-ambulatory patients with minimal side effects.

Nutritional immunomodulation in critically ill children with acute lung injury: feasibility and impact on circulating biomarkers.

OBJECTIVE: Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations. DESIGN: Prospective, blinded, randomized, controlled, multicenter trial. SETTING: PICU. PATIENTS: Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers. CONCLUSIONS: Providing enteral nutrition with eicosapentaenoic acid + γ-linolenic acid to critically ill children with lung injury was feasible and caloric goals were met within 30 hrs. This feeding protocol effectively modulated plasma phospholipid fatty acid concentrations to reflect an anti-inflammatory profile. This study provides data to inform future outcome studies using enteral eicosapentaenoic acid + γ-linolenic acid in children with lung injury.

Stool pattern changes in toddlers consuming a follow-on formula supplemented with polydextrose and galactooligosaccharides.

Healthy 9- to 48-month-old children (n = 133) were randomized to receive a cow's-milk-based follow-on formula (control) or the same formula with polydextrose and galactooligosaccharides (PDX/GOS) for 108 days. Pediatricians assessed diarrheal disease, stool pattern, acute respiratory infection, systemic antibiotic use, and growth. The 2 groups had similar weight-for-length/height z score and similar odds of having diarrheal disease, acute respiratory infection, and systemic antibiotic use; however, PDX/GOS had greater odds of increased defecation than control (P ≤ 0.01). Addition of PDX and GOS to a follow-on formula was well tolerated and induced a pattern of more frequent and softer stools in toddlers.

Cognitive behavioral therapy for the treatment of juvenile fibromyalgia: a multisite, single-blind, randomized, controlled clinical trial.

OBJECTIVE: Juvenile fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder in children and adolescents for which there are no evidence-based treatments. The objective of this multisite, single-blind, randomized clinical trial was to test whether cognitive-behavioral therapy (CBT) was superior to fibromyalgia (FM) education in reducing functional disability, pain, and symptoms of depression in juvenile FMS. METHODS: Participants were 114 adolescents (ages 11-18 years) with juvenile FMS. After receiving stable medications for 8 weeks, patients were randomized to either CBT or FM education and received 8 weekly individual sessions with a therapist and 2 booster sessions. Assessments were conducted at baseline, immediately following the 8-week treatment phase, and at 6-month followup. RESULTS: The majority of patients (87.7%) completed the trial per protocol. Intent-to-treat analyses showed that patients in both groups had significant reductions in functional disability, pain, and symptoms of depression at the end of the study, and CBT was significantly superior to FM education in reducing the primary outcome of functional disability (mean baseline to end-of-treatment difference between groups 5.39 [95% confidence interval 1.57, 9.22]). Reduction in symptoms of depression was clinically significant for both groups, with mean scores in the range of normal/nondepressed by the end of the study. Reduction in pain was not clinically significant for either group (<30% decrease in pain). There were no study-related adverse events. CONCLUSION: In this controlled trial, CBT was found to be a safe and effective treatment for reducing functional disability and symptoms of depression in adolescents with juvenile FMS.

Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics.

Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 hour exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 hour of environmental exposure to Florida red tide aerosols for upto 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period.

Aerosolized Red Tide Toxins (Brevetoxins) and Asthma: Continued health effects after 1 hour beach exposure.

Blooms of the toxic dinoflagellate, Karenia brevis, produce potent neurotoxins in marine aerosols. Recent studies have demonstrated acute changes in both symptoms and pulmonary function in asthmatics after only 1 hour of beach exposure to these aerosols. This study investigated if there were latent and/or sustained effects in asthmatics in the days following the initial beach exposure during periods with and without an active Florida red tide.Symptom data and spirometry data were collected before and after 1 hour of beach exposure. Subjects kept daily symptom diaries and measured their peak flow each morning for 5 days following beach exposure. During non-exposure periods, there were no significant changes in symptoms or pulmonary function either acutely or over 5 days of follow-up. After the beach exposure during an active Florida red tide, subjects had elevated mean symptoms which did not return to the pre-exposure baseline for at least 4 days. The peak flow measurements decreased after the initial beach exposure, decreased further within 24 hours, and continued to be suppressed even after 5 days. Asthmatics may continue to have increased symptoms and delayed respiratory function suppression for several days after 1 hour of exposure to the Florida red tide toxin aerosols.

Bone loss in adolescents after bariatric surgery.

OBJECTIVE: To evaluate bone loss in adolescents after Roux-en-Y gastric bypass surgery and to determine the extent to which bone loss was related to weight loss. We hypothesized that adolescents would lose bone mass after surgery and that it would be associated with weight loss. PATIENTS AND METHODS: We conducted a retrospective case review of 61 adolescents after bariatric surgery. Whole-body bone mineral content (BMC) and density (BMD) were measured by dual-energy radiograph absorptiometry, and age- and gender-specific BMD z scores were calculated. Measurements were obtained when possible before surgery and then every 3 to months after surgery for up to 2 years. Data were analyzed by using a mixed-models approach, and regression models were adjusted for age, gender, and height. RESULTS: Whole-body BMC, BMD z score, and weight decreased significantly over time after surgery (P < .0001 for all). In the first 2 years after surgery, predicted values on the basis of regression modeling for BMC decreased by 7.4%, and BMD z score decreased from 1.5 to 0.1. During the first 12 months after surgery, change in weight was correlated with change in BMC (r = 0.31; P = .02). Weight loss accounted for 14% of the decrease in BMC in the first year after surgery. CONCLUSION: Bariatric surgery is associated with significant bone loss in adolescents. Although the predicted bone density was appropriate for age 2 years after surgery, longer follow-up is warranted to determine whether bone mass continues to change or stabilizes.

Review of Florida Red Tide and Human Health Effects.

This paper reviews the literature describing research performed over the past decade on the known and possible exposures and human health effects associated with Florida red tides. These harmful algal blooms are caused by the dinoflagellate, Karenia brevis, and similar organisms, all of which produce a suite of natural toxins known as brevetoxins. Florida red tide research has benefited from a consistently funded, long term research program, that has allowed an interdisciplinary team of researchers to focus their attention on this specific environmental issue-one that is critically important to Gulf of Mexico and other coastal communities. This long-term interdisciplinary approach has allowed the team to engage the local community, identify measures to protect public health, take emerging technologies into the field, forge advances in natural products chemistry, and develop a valuable pharmaceutical product. The Review includes a brief discussion of the Florida red tide organisms and their toxins, and then focuses on the effects of these toxins on animals and humans, including how these effects predict what we might expect to see in exposed people.

The effects of an intensive behavior and nutrition intervention compared to standard of care on weight outcomes in CF.

Inadequate intake and suboptimal growth are common problems for patients with CF and a critical target for intervention. The purpose of this study was to compare the growth outcomes of children with CF who participated in a randomized clinical trial to improve energy intake and weight to children with CF receiving standard of care during the same time period. Our primary outcome was change in body mass index z-score (BMI z-score) over 2 years. An exploratory outcome was forced expiratory volume at 1-sec (FEV(1) ) over 2 years. Participants were children ages 4-12 with CF, who participated in a randomized clinical trial of behavior plus nutrition intervention versus nutrition education alone, and a matched Comparison Sample receiving standard of care drawn from the Cystic Fibrosis Foundation (CFF) Registry. Children in the Clinical Trial Group (N=67) participated in a 9-week, nutrition intervention and were followed at regular intervals (3, 6, 12, 18, and 24 months) for 2 years post-treatment to obtain anthropometric and pulmonary function data. For each child in the Comparison Sample (N=346), these measures were obtained from the CFF Registry at matching intervals for the 27-month period corresponding to the clinical trial. Over 27 months, children in the Clinical Trial Group (the combined sample of the behavior plus nutrition and the nutrition alone) demonstrated significantly less decline in BMI z-score, -0.05 (SD=0.68, CI= -0.23 to 0.13), as compared to children in the Comparison Sample, -0.21 (SD=0.67, CI= -0.31 to -0.11). No statistically significant differences were found for decline in FEV(1) between children in the Clinical Trial Group and the Comparison Sample. The key implication of these findings is that intensive behavioral and nutritional intervention is effective and needs to be adapted so that it can be broadly disseminated into clinical practice.

The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children.

OBJECTIVE: To investigate the incidence of allergic and respiratory diseases through age 3 years in children fed docosahexaenoic acid (DHA)- and arachidonic acid (ARA)-supplemented formula during infancy. STUDY DESIGN: Children who completed randomized, double-blind studies of DHA/ARA-supplemented (0.32%-0.36%/0.64%-0.72% of total fatty acids, respectively) versus nonsupplemented (control) formulas, fed during the first year of life, were eligible. Blinded study nurses reviewed medical charts for upper respiratory infection (URI), wheezing, asthma, bronchiolitis, bronchitis, allergic rhinitis, allergic conjunctivitis, otitis media, sinusitis, atopic dermatitis (AD), and urticaria. RESULTS: From the 2 original cohorts, 89/179 children participated; 38/89 were fed DHA/ARA formula. The DHA/ARA group had significantly lower odds for developing URI (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.08-0.58), wheezing/asthma (OR, 0.32; 95% CI, 0.11-0.97), wheezing/asthma/AD (OR, 0.25; 95% CI, 0.09-0.67), or any allergy (OR, 0.28; 95% CI, 0.10-0.72). The control group had significantly shorter time to first diagnosis of URI (P = .006), wheezing/asthma (P = .03), or any allergy (P = .006). CONCLUSIONS: DHA/ARA supplementation was associated with delayed onset and reduced incidence of URIs and common allergic diseases up to 3 years of age.

Pharmacokinetics of amantadine in children with impaired consciousness due to acquired brain injury: preliminary findings using a sparse-sampling technique.

OBJECTIVE: To evaluate the pharmacokinetics of amantadine in children with impaired consciousness from acquired brain injury. DESIGN: Randomized, double-blind, placebo-controlled, crossover study with sparse sampling for pharmacokinetics. SETTING: Tertiary care pediatric hospital. PARTICIPANTS: Children, ages 6-18 years, with impaired consciousness 5-10 weeks after acquired brain injury. METHODS: Subjects received amantadine for 3 weeks. Subjects were randomized to placebo or amantadine 4 mg/kg/day for 7 days followed by 6 mg/kg/day for 14 days. Crossover was after a 7-day washout period. MAIN OUTCOME MEASURES: The Coma/Near-Coma Scale and Coma Recovery Scale-Revised were done 3 times per week to evaluate arousal and consciousness. Plasma concentrations of amantadine were determined for pharmacokinetic parameter estimation and evaluation of the exposure-response relationship. Adverse events were monitored. RESULTS: Nine subjects met the final inclusion and exclusion criteria, 7 of whom agreed to participate. Five subjects completed both arms of the study. Amantadine total body clearance was 0.17 L/h/kg with a half-life of 13.9 hours. Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness. CONCLUSIONS: Amantadine was well-tolerated in children with acquired brain injury and demonstrates pharmacokinetics similar to those reported for healthy young adults. Based on the preliminary data, higher dosing may be considered in the setting of brain injury.

Gastrointestinal Emergency Room Admissions and Florida Red Tide Blooms.

Human exposure to brevetoxins during Florida red tide blooms formed by Karenia brevis has been documented to cause acute gastrointestinal, neurologic, and respiratory health effects.. Traditionally, the routes of brevetoxin exposure have been through the consumption of contaminated bivalve shellfish and the inhalation of contaminated aerosols. However, recent studies using more sensitive methods have demonstrated the presence of brevetoxins in many components of the aquatic food web which may indicate potential alternative routes for human exposure.This study examined whether the presence of a Florida red tide bloom affected the rates of admission for a gastrointestinal diagnosis to a hospital emergency room in Sarasota, FL. The rates of gastrointestinal diagnoses admissions were compared for a 3-month time period in 2001 when Florida red tide bloom was present onshore to the same 3-month period in 2002 when no Florida red tide bloom occurred. A significant 40% increase in the total number of gastrointestinal emergency room admissions for the Florida red tide bloom period was found compared to the non red tide period.These results suggest that the healthcare community may experience a significant and unrecognized impact from patients needing emergency medical care for gastrointestinal illnesses during Florida red tide blooms. Thus, additional studies characterizing the potential sources of exposure to the toxins, as well as the dose/effect relationship of brevetoxin exposure, should be undertaken.

Baseline BMI is a strong predictor of nadir BMI after adolescent gastric bypass.

OBJECTIVE: Surgical treatment of extreme obesity may be appropriate for some adolescents. We hypothesized that surgical weight loss outcomes may differ by preoperative level of extreme obesity (body mass index [BMI] > or=99th percentile). STUDY DESIGN: A longitudinal assessment of clinical characteristics from 61 adolescents who underwent laparoscopic Roux-en-Y gastric bypass at a single pediatric center from 2002 until 2007 was performed. Patients were categorized into 1 of 3 preoperative BMI groups: group 1, BMI = 40.0 to 54.9 (n = 23); group 2, BMI = 55.0 to 64.9 (n = 21); group 3, BMI = 65.0 to 95.0 (n = 17). Changes in BMI and cardiovascular risk factors between baseline and year 1 were evaluated using repeated-measures mixed linear modeling. RESULTS: BMI in the overall cohort at baseline (60.2 +/- 11 kg/m(2)) decreased by 37.4% at 1 year after surgery (P < .001). Percent BMI change varied little by preoperative BMI groups (-37.2%, -36.8%, and -37.7% for groups 1, 2, and 3 respectively; P = .8762). The rate of change in absolute BMI units significantly varied by preoperative BMI class (group x time interaction, P < .0001), with 1-year nadir BMI values for groups 1, 2, and 3 falling to 31 +/- 4 kg/m(2), 38 +/- 5 kg/m(2), and 47 +/- 9 kg/m(2), respectively. One year after surgery, only 17% of patients achieved a nonobese BMI (<30 kg/m(2)). Significant improvements in systolic and diastolic blood pressure (P < .0001), fasting insulin (P < .0001), total cholesterol (P = .0007), and triglyceride levels (P < .0001) were seen after surgery irrespective of baseline BMI class. Mean albumin levels remained normal despite significant caloric restriction and weight loss. CONCLUSIONS: Laparoscopic gastric bypass resulted in improvement or reversal of cardiovascular risk factors and resulted in a decrease in BMI of approximately 37% in all patients, regardless of starting BMI, 1 year after surgery. The timing of surgery for adolescent extreme obesity is an important consideration, because "late" referral for bariatric surgery at the highest of BMI values may preclude reversal of obesity.

Randomized clinical trial of behavioral intervention and nutrition education to improve caloric intake and weight in children with cystic fibrosis.

OBJECTIVE: To evaluate the efficacy of a behavioral plus nutrition education intervention, Be In CHARGE!, compared with that of a nutrition education intervention alone on caloric intake and weight gain in children with cystic fibrosis and pancreatic insufficiency. DESIGN: Randomized controlled trial. SETTING: Cystic fibrosis centers in the eastern, midwestern, and southern United States. PARTICIPANTS: Seventy-nine children aged 4 to 12 years below the 40th percentile for weight for age were recruited. Sixty-seven completed the intervention and 59 completed a 24-month follow-up assessment. INTERVENTION: Comparison of a behavioral plus nutrition education intervention with a nutrition education intervention alone. MAIN OUTCOME MEASURES: Primary outcomes were changes from pretreatment to posttreatment in caloric intake and weight gain. Secondary outcomes were changes from pretreatment to posttreatment in percentage of the estimated energy requirement and body mass index z score. These outcomes were also examined 24 months posttreatment. RESULTS: After treatment, the behavioral plus nutrition education intervention as compared with the nutrition education intervention alone had a statistically greater average increase on the primary and secondary outcomes of caloric intake (mean, 872 vs 489 cal/d, respectively), percentage of the estimated energy requirement (mean, 148% vs 127%, respectively), weight gain (mean, 1.47 vs 0.92 kg, respectively), and body mass index z score (0.38 vs 0.18, respectively). At the 24-month follow-up, children in both conditions maintained an estimated energy requirement of around 120% and did not significantly differ on any outcomes. CONCLUSIONS: A behavioral plus nutrition education intervention was more effective than a nutrition education intervention alone at increasing dietary intake and weight over a 9-week period. However, across the 24-month follow-up, both treatments achieved similar outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00006169.

Exposure and effect assessment of aerosolized red tide toxins (brevetoxins) and asthma.

BACKGROUND: In previous studies we demonstrated statistically significant changes in reported symptoms for lifeguards, general beach goers, and persons with asthma, as well as statistically significant changes in pulmonary function tests (PFTs) in asthmatics, after exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols. OBJECTIVES: In this study we explored the use of different methods of intensive ambient and personal air monitoring to characterize these exposures to predict self-reported health effects in our asthmatic study population. METHODS: We evaluated health effects in 87 subjects with asthma before and after 1 hr of exposure to Florida red tide aerosols and assessed for aerosolized brevetoxin exposure using personal and ambient samplers. RESULTS: After only 1 hr of exposure to Florida red tide aerosols containing brevetoxin concentrations > 57 ng/m(3), asthmatics had statistically significant increases in self-reported respiratory symptoms and total symptom scores. However, we did not see the expected corresponding changes in PFT results. Significant increases in self-reported symptoms were also observed for those not using asthma medication and those living >/= 1 mile from the coast. CONCLUSIONS: These results provide additional evidence of health effects in asthmatics from ambient exposure to aerosols containing very low concentrations of brevetoxins, possibly at the lower threshold for inducing a biologic response (i.e., toxicity). Consistent with the literature describing self-reported symptoms as an accurate measure of asthmatic distress, our results suggest that self-reported symptoms are a valuable measure of the extent of health effects from exposure to aerosolized brevetoxins in asthmatic populations.

Dental development in children with growth hormone insensitivity syndrome: Demirjian analysis of serial panoramic radiographs.

OBJECTIVE: This study evaluates the effects of 8 years of insulinlike growth factor-I therapy on tooth development in patients with growth hormone insensitivity syndrome. METHODS: Forty-nine panoramic radiographs were evaluated from eight patients (six boys, two girls). Seven teeth in the mandibular left region were graded according to the Demirjian system. Radiographs were taken at the start of insulinlike growth factor-I therapy and were continued at approximately yearly intervals for 8 years. RESULTS: Three of six boys and one of two girls who began treatment with insulinlike growth factor-I at earlier ages experienced an increase in the rate of tooth development. One of six boys who began treatment with insulinlike growth factor-I at a later age had a slower rate of dental development. The patients had more rapid tooth maturation during the beginning of treatment. By the end of treatment, all patients had normal dental maturity for their age. CONCLUSIONS: Treatment of growth hormone insensitivity syndrome with insulinlike growth factor-I appears to lead to an increase in dental maturation, particularly in younger patients. After 8 years all patients had achieved normal dental development.

Effects of amantadine in children with impaired consciousness caused by acquired brain injury: a pilot study.

OBJECTIVE: To conduct a pilot study of amantadine in children with impaired consciousness caused by acquired brain injury, to establish design feasibility, and to assess the effect on level of arousal and consciousness. DESIGN: Randomized, double-blind, placebo-controlled crossover trial. Seven subjects (mean age, 12.7 yrs) with an acquired brain injury (mean duration, 6 wks) were randomized to receive either 3 wks of placebo or amantadine, followed by a 1-wk washout period and then 3 wks of the other agent. Main outcome measures were the Coma/Near-Coma Scale and Coma Recovery Scale-Revised, each done three times per week. Subjective evaluations of change in arousal and consciousness by the parent and physician were done weekly. RESULTS: Five subjects completed the study. There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). CONCLUSIONS: This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies.

Reversal of type 2 diabetes mellitus and improvements in cardiovascular risk factors after surgical weight loss in adolescents.

OBJECTIVES: Type 2 diabetes mellitus is associated with obesity, dyslipidemia, and hypertension, all well-known risk factors for cardiovascular disease. Surgical weight loss has resulted in a marked reduction of these risk factors in adults. We hypothesized that gastric bypass would improve parameters of metabolic dysfunction and cardiovascular risk in adolescents with type 2 diabetes mellitus. PATIENTS AND METHODS: Eleven adolescents who underwent Roux-en-Y gastric bypass at 5 centers were included. Anthropometric, hemodynamic, and biochemical measures and surgical complications were analyzed. Similar measures from 67 adolescents with type 2 diabetes mellitus who were treated medically for 1 year were also analyzed. RESULTS: Adolescents who underwent Roux-en-Y gastric bypass were extremely obese (mean BMI of 50 +/- 5.9 kg/m(2)) with numerous cardiovascular risk factors. After surgery there was evidence of remission of type 2 diabetes mellitus in all but 1 patient. Significant improvements in BMI (-34%), fasting blood glucose (-41%), fasting insulin concentrations (-81%), hemoglobin A1c levels (7.3%-5.6%), and insulin sensitivity were also seen. There were significant improvements in serum lipid levels and blood pressure. In comparison, adolescents with type 2 diabetes mellitus who were followed during 1 year of medical treatment demonstrated stable body weight (baseline BMI: 35 +/- 7.3 kg/m(2); 1-year BMI: 34.9 +/- 7.2 kg/m(2)) and no significant change in blood pressure or in diabetic medication use. Medically managed patients had significantly improved hemoglobin A1c levels over 1 year (baseline: 7.85% +/- 2.3%; 1 year: 7.1% +/- 2%). CONCLUSIONS: Extremely obese diabetic adolescents experience significant weight loss and remission of type 2 diabetes mellitus after Roux-en-Y gastric bypass. Improvements in insulin resistance, beta-cell function, and cardiovascular risk factors support Roux-en-Y gastric bypass as an intervention that improves the health of these adolescents. Although the long-term efficacy of Roux-en-Y gastric bypass is not known, these findings suggest that Roux-en-Y gastric bypass is an effective option for the treatment of extremely obese adolescents with type 2 diabetes mellitus.

The combined approach to lysis utilizing eptifibatide and rt-PA in acute ischemic stroke: the CLEAR stroke trial.

BACKGROUND AND PURPOSE: Multiple approaches are being studied to enhance the rate of thrombolysis for acute ischemic stroke. Treatment of myocardial infarction with a combination of a reduced-dose fibrinolytic agent and a glycoprotein (GP) IIb/IIIa receptor antagonist has been shown to improve the rate of recanalization versus fibrinolysis alone. The combined approach to lysis utilizing eptifibatide and recombinant tissue-type plasminogen activator (rt-PA) (CLEAR) stroke trial assessed the safety of treating acute ischemic stroke patients within 3 hours of symptom onset with this combination. METHODS: The CLEAR trial was a National Institutes of Health/National Institute of Neurological Disorders and Stroke-funded multicenter, double-blind, randomized, dose-escalation and safety study. Patients were randomized 3:1 to either low-dose rt-PA (tier 1=0.3 mg/kg, tier 2=0.45 mg/kg) plus eptifibatide (75 microg/kg bolus followed by 0.75 microg/kg per min infusion for 2 hours) or standard-dose rt-PA (0.9 mg/kg). The primary safety end point was the incidence of symptomatic intracerebral hemorrhage within 36 hours. Secondary analyses were performed regarding clinical efficacy. RESULTS: Ninety-four patients (40 in tier 1 and 54 in tier 2) were enrolled. The combination group of the 2 dose tiers (n=69) had a median age of 71 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 14, and the standard-dose rt-PA group (n=25) had a median age of 61 years and a median baseline NIHSS score of 10 (P=0.01 for NIHSS score). Fifty-two (75%) of the combination treatment group and 24 (96%) of the standard treatment group had a baseline modified Rankin scale score of 0 (P=0.04). There was 1 (1.4%; 95% CI, 0% to 4.3%) symptomatic intracranial hemorrhage in the combination group and 2 (8.0%; 95% CI, 0% to 19.2%) in the rt-PA-only arm (P=0.17). During randomization in tier 2, a review by the independent data safety monitoring board demonstrated that the safety profile of combination therapy at the tier 2 doses was such that further enrollment was statistically unlikely to indicate inadequate safety for the combination treatment group, the ultimate outcome of the study. Thus, the study was halted. There was a trend toward increased clinical efficacy of standard-dose rt-PA compared with the combination treatment group. CONCLUSIONS: The safety of the combination of reduced-dose rt-PA plus eptifibatide justifies further dose-ranging trials in acute ischemic stroke.

Inhaled corticosteroid use in asthmatic children receiving Ohio Medicaid: trend analysis, 1997-2001.

BACKGROUND: In 1997, national guidelines emphasized that inhaled corticosteroids (ICSs) are key therapy for individuals with all classes of persistent asthma, including children. OBJECTIVE: To examine the effect of these guidelines via time-trend analysis of ICS dispensation among children with asthma and Ohio Medicaid insurance. METHODS: A retrospective cross-sectional analysis by yearly cohorts was performed. From January 1, 1997, to December 31, 2001, all children from birth to the age of 18 years with 6 months of Ohio Medicaid enrollment or more, 1 or more asthma diagnoses associated with a provider claim, and 1 or more prescription claims for an asthma medication in a given calendar year were identified using claims data. The daily beclomethasone equivalent (BME) dose, the daily albuterol equivalent dose, and asthma-related health care use were calculated for each child within each yearly cohort. A time-trend regression analysis of subjects enrolled in all 5 years examined factors associated with BME. RESULTS: A total of 77,557 children met the study criteria. Among the 1,475 children enrolled during all 5 years, year of enrollment was a positive independent predictor of BME after adjustment for age, race, sex, systemic steroid bursts, albuterol equivalent dose, and health care use (P < .001). CONCLUSIONS: The daily BME dose significantly increased for children with asthma insured by Ohio Medicaid from 1997 to 2001. However, the percentages of children receiving both ICS and a therapeutic BME dose were alarmingly low. The mean BME dose was particularly low among children with 1 or more emergency department visits, no hospitalizations, and 3 or fewer physician visits for asthma per year, suggesting that broader efforts to target this group are needed.