Efficacy and safety of dry powder fluticasone propionate in children with persistent asthma.

BACKGROUND: Flovent Diskus is a powder formulation of the inhaled corticosteroid fluticasone propionate (FP) delivered via a breath-actuated, multidose inhaler. OBJECTIVE: To determine the efficacy and safety of dry powder FP administered once or twice daily (200 microg per day) to children with persistent asthma. METHODS: Twelve-week, randomized, double-blind, placebo-controlled, multicenter trial with a 52-week, open-label extension. Children aged 4 to 11 were required to have pulmonary function 50% to 85% of predicted values. The population was stratified for baseline therapy (inhaled corticosteroid/cromolyn or bronchodilators only). After a 2-week placebo run-in, 242 patients received dry powder FP 200 microg each morning, dry powder FP 100 microg BID, or placebo for 12 weeks; 192 were rerandomized to the QD or BID regimen for an additional 52 weeks of open-label treatment. Primary endpoints were mean changes in FEV1 and morning PEF recorded at clinic visits. RESULTS: Both dry powder FP regimens significantly improved FEV1, evening PEF, and asthma symptoms at the double-blind phase endpoint (P < or = .017 compared with placebo). The BID regimen also significantly improved morning PEF and nighttime awakenings due to asthma (P < or = .005). Among patients previously treated with inhaled corticosteroids/cromolyn, improvements observed with the QD and BID regimens were similar. Patients switched from BID to open-label QD treatment showed additional improvements at week 52 generally comparable to patients who received the BID regimen during both phases. Fluticasone propionate was well tolerated for up to 64 weeks with few reports of drug-related adverse events or morning plasma cortisol abnormalities. CONCLUSIONS: Once daily dosing of dry powder FP 200 microg is an effective and convenient alternative for children whose asthma is controlled with a more frequent dosing regimen of inhaled corticosteroids.

Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray.

OBJECTIVE: Intranasal corticosteroids are used widely for the treatment of allergic rhinitis because they are effective and well tolerated. However, their potential to suppress growth of pediatric subjects with allergic rhinitis continues to be a concern, particularly in light of reports of growth suppression after treatment with intranasal beclomethasone dipropionate or intranasal budesonide (see the article by Skoner et al in this month's issue). A 1-year study of prepubertal patients between 3 and 9 years of age with perennial allergic rhinitis was conducted to assess the effects on growth of mometasone furoate aqueous nasal spray (MFNS), a new once-daily (QD) intranasal corticosteroid with negligible bioavailability. METHODS: This was a randomized, placebo-controlled, double-blind, multicenter study. Ninety-eight subjects were randomized to treatment with either MFNS 100 microg QD or placebo for 1 year. Each subject's height was required to be between the 5th and 95th percentile at baseline, and skeletal age at screening was required to be within 2 years of chronological age, as determined by left wrist x-rays. Washout periods for medications that affect either childhood growth or allergic rhinitis symptoms were established based on estimated period of effect, and these medications were prohibited during the study. However, short courses of either oral prednisone lasting no longer than 7 days or low-potency topical dermatologic corticosteroids lasting no longer than 10 days were permitted if necessary. Height was measured with a calibrated stadiometer at baseline and at 4, 8, 12, 26, 39, and 52 weeks, and the primary safety variable was the change in standing height. The rate of growth was also calculated for each subject as the slope (linear regression) of the change in height from baseline using data from all visits of subjects who had at least 2 visits. Hypothalamic-pituitary-adrenocortical- (HPA)-axis function was assessed via cosyntropin stimulation testing at baseline and at 26 and 52 weeks. All analyses were based on all randomized subjects (intent-to-treat principle). The change from baseline in standing height was analyzed by a 2-way analysis of variance that extracted sources of variation attributable to treatment, center, and treatment-by-center interaction. RESULTS: Demographic characteristics were similar at baseline. Eighty-two subjects completed the study (42 in the MFNS group and 40 in the placebo group), and 93% of subjects achieved at least 80% compliance with therapy. After 1 year of treatment, no suppression of growth was seen in subjects treated with MFNS, and mean standing heights were similar for both treatment groups at all time points. For the primary safety variable (change in height from baseline), both treatment groups were similar at all time points except for weeks 8 and 52. Subjects treated with MFNS had a slightly greater mean increase in height than subjects treated with placebo at these time points: the change in height was 6.95 cm versus 6.35 cm at the 1-year time point. However, the rate of growth (.018 cm/day) averaged for all time points over the course of the study was similar for both treatment groups. Additional analyses found that MFNS did not retard growth in any sex or age subgroup of subjects. The use of exogenous corticosteroids other than the study drug was also similar among the 2 treatment groups. Results from cosyntropin stimulation testing confirmed the absence of systemic effects of MFNS. The change from baseline in the difference between prestimulation and poststimulation levels was similar for both treatment groups after 1 year of treatment, with no evidence of HPA-axis suppression in MFNS-treated subjects at any time point. Incidences of treatment-related adverse events were similar for both treatment groups, with 16% of MFNS-treated subjects reporting adverse events, compared with 22% of placebo-treated subjects. CONCLUSIONS: (ABSTRACT TRUNCATED)

A dose-ranging study of mometasone furoate aqueous nasal spray in children with seasonal allergic rhinitis.

BACKGROUND: The efficacy and safety of mometasone furoate aqueous nasal spray (MFNS; Nasonex) 200 microg once daily for the treatment and prophylaxis of seasonal allergic rhinitis (SAR) and treatment of perennial rhinitis have been demonstrated in adults. However, the dose response of MFNS in pediatric patients has not yet been characterized. OBJECTIVE: This study was conducted to determine the dose-response relationship of 3 different doses of MFNS in a pediatric population. METHODS: This was a multicenter, double-blind, active- and placebo-controlled study of 679 children 6 to 11 years of age with histories of SAR and documented positive skin test responses. Patients were randomized to one of the following treatment groups for 4 weeks: MFNS 25 microgram once daily, MFNS 100 microgram once daily, MFNS 200 microgram once daily, beclomethasone dipropionate 84 microgram twice daily (168 microgram/day), or placebo. Physician evaluations were performed at days 4, 8, 15, and 29, and patient evaluations were analyzed for days 1 to 15 and 16 to 29. RESULTS: The mean reduction from baseline in physician-evaluated total nasal symptom scores at day 8 (the primary efficacy variable) was significantly greater in the MFNS and beclomethasone dipropionate groups than in the placebo group (P

Escherichia coli septicemia in nonperforated appendicitis.

OBJECTIVE: To determine the association between nonperforated appendicitis and Escherichia coli septicemia, and the frequency with which blood cultures are obtained in the clinical setting of appendicitis. DESIGN: Three case reports of E coli septicemia and nonperforated appendicitis and a retrospective survey. SETTING: Children's Medical Center, Dallas, Tex, a primary care and tertiary referral center. PATIENTS: All children admitted in a 2-year period with a diagnosis of appendicitis. INTERVENTIONS: None. RESULTS: Preoperative blood cultures were obtained in 20 (21%) of 96 patients with histologic evidence of appendicitis. Fifty percent of the patients had gross or microscopic evidence of appendiceal perforation. Twelve (25%) of the 48 patients with perforated appendicitis had blood cultures obtained before the initiation of antimicrobial therapy, and in two of these patients (17%) the results were positive. Blood cultures were drawn before antibiotic therapy in four (8%) of the 48 patients with nonperforated appendicitis, and in two of these the results were positive. The blood culture isolates (coagulase-negative Staphylococcus and E coli) were the same in both groups. CONCLUSIONS: Nonperforated appendicitis and septicemia may be more common than formerly appreciated. Only a prospective study can determine the true incidence of septicemia in children with perforated or nonperforated appendicitis.

Quantification of error in measurement of radial inclination angle and radial-carpal distance.

Posteroanterior wrist radiographs of eight patients were evaluated by eight orthopedists. Radial inclination angle and radial-carpal distance were measured by use of a standardized technique. The standard deviation for radial inclination angle was 2 degrees. The standard deviation for radial-carpal distance was 1 mm. The measured rotational variation of radial inclination and radial-carpal distance is 1 degree and 1 mm, respectively, through a 10-degree arc of supination and pronation.

Antimicrobial drug suspensions: a blind comparison of taste of fourteen common pediatric drugs.

Children of preschool age most often receive medications in liquid form, and smell and taste are major determinants in achieving compliance. We compared smell, taste and other characteristics of 14 commonly prescribed antimicrobial suspensions in a blind test in 30 adult volunteers to determine whether there was a difference in their acceptability. A significant difference was observed with cephalosporins ranking highest and penicillins ranking lowest. Our findings support anecdotal observations and claims often made by parents that cephalosporin antimicrobial suspensions taste good and are readily accepted by children and that penicillin suspensions have an unpleasant taste and aftertaste and are poorly accepted. Other drugs had intermediate scores. Of the two erythromycin suspensions evaluated, Ilosone tested superior to Erythromycin ES.

Impetigo. Current etiology and comparison of penicillin, erythromycin, and cephalexin therapies.

We attempted to determine the causative bacterial pathogens of impetigo in children in our area, to compare the effectiveness of three frequently used oral antimicrobial treatment regimens, and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment. Seventy-three children with impetigo were randomly assigned to receive penicillin V potassium or cephalexin monohydrate, both administered in dosages of 40 to 50 mg/kg per day, or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day. All drugs were given in three divided doses for 10 days. Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies. Forty-five (62%) cultures showed Staphylococcus aureus only, 14 (19%) showed S aureus and group A beta-hemolytic streptococci, six (8%) showed group A beta-hemolytic streptococci only, and eight (11%) showed no growth or other organisms. Treatment failure occurred in six (24%) of 25 patients treated with penicillin V, one (4%) of 25 patients treated with erythromycin estolate, and no patients treated with cephalexin. We conclude that S aureus is the most common cause of impetigo in children in our study population, that cephalexin is the most effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection.

Doppler mapping in hypothenar syndrome: an alternative to angiography.

Four patients with hypothenar hammer syndrome were evaluated preoperatively with Doppler mapping and angiography. Both tests documented ulnar artery occlusion. In one patient, the proximal extent of thrombosis could not be identified by angiography. In all cases Doppler mapping accurately documented the extent of occlusion as confirmed by surgical exploration. Doppler mapping is a noninvasive alternative to angiography in the evaluation of hypothenar hammer syndrome.

Suppression of the late cutaneous response by immunotherapy.

In a prospective, double-blind, placebo-controlled study, we examined the effect of mountain cedar (MC) immunotherapy on the MC-induced late cutaneous response (LCR). Fourteen MC-sensitive patients were intradermally skin tested before and after immunotherapy with MC extract. We measured the size of the wheal at 15 minutes and the area of tissue swelling at 6 hours. Patients were matched by the size of the LCR and started receiving either MC immunotherapy or placebo immunotherapy. MC-specific immunoglobulins (MC sIgG, MC sIgG1, MC sIgG4, and MC sIgE) were measured by ELISA. Symptom-medication scores (SMSs) were recorded on a daily basis during the MC season and tabulated at the end of the study. Comparison of the 14 paired patients revealed no significant differences between MC-treated and placebo-treated groups in preimmunotherapy MC sIgG1 and SIgG4. However, when MC immunotherapy was compared to placebo immunotherapy, patients receiving MC immunotherapy developed significantly higher MC sIgG1 (p less than 0.04) and MC sIgG4 (p less than 0.01) after immunotherapy. Patients receiving MC immunotherapy also demonstrated significantly greater suppression of the LCR after immunotherapy (p less than 0.005) with the postimmunotherapy LCR correlating significantly with both MC sIgG4 (rs = 0.715; p = 0.008) and cumulative dose of MC received (rs = 0.808; p = 0.004). MC sIgE was similar in both groups after immunotherapy. The reduction in SMSs in the MC-treated group did not reach significance, nor was there a correlation of SMSs with MC sIgE, sIgG, sIgG1, or sIgG4.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenytoin-induced IgA depression.

In a survey of 1011 pediatric patients with seizure disorders, 93 children (9.2%) were found to have depressed serum IgA concentrations when compared with age-matched controls; 27 of these values were less than 0.1 g/L (less than 10 mg/dL). Two thirds (64/93) of these patients were being treated with phenytoin, and ten had been previously treated with phenytoin. No relationship between IgA deficiency and serum phenytoin concentration nor use of other anticonvulsant medications was found. The prevalence of phenytoin-induced IgA depression was similar in patients with "primary" or "secondary" seizure disorders. Approximately 40% of the patients with low serum IgA concentrations had mild to moderate depression of serum IgG and/or IgM concentrations when compared with age-matched controls.

Sleep apnea and vocal cord paralysis secondary to type I Chiari malformation.

A previously healthy 13-year-old boy without myelodysplasia who had mild scoliosis was seen with complaints of nasal congestion, noisy nighttime breathing, and difficulty sleeping. Flattening of the inspiratory loop on the flow-volume curve was found on pulmonary function testing, suggesting a variable extrathoracic obstruction due to a laryngeal lesion. Bilateral abductor vocal cord paralysis and sleep apnea developed precipitously following general anesthesia. Further workup demonstrated a type-I Chiari malformation with syringomyelia. Brainstem abnormalities such as Chiari malformation with secondary tenth cranial nerve deficits should be considered in previously healthy children and adolescents with signs and symptoms of upper airway obstruction and apnea.

Sunflower oil is not allergenic to sunflower seed-sensitive patients.

The allergenicity of edible oils derived from sunflower seeds was investigated in two patients with anaphylactic sensitivity to sunflower seeds. Specific IgE-mediated hypersensitivity to sunflower seed was demonstrated by history, prick skin tests, positive passive transfer skin test, and RAST. Specific IgE directed toward sunflower oil, refined or cold pressed, could not be conclusively demonstrated. The Prausnitz-Küstner reaction with sunflower oils performed with one patient's serum was negative. Although the cold-pressed sunflower oil was found to contain a minute amount of protein, open challenge with the derivative oils resulted in no immediate or delayed reaction in the two patients studied. Sunflower oil ingestion in these patients who were highly sensitive to the parent material proved safe. Nonallergenicity of derivative products needs to be proven for each case.

Treatment of subtrochanteric fractures with a sliding screw-plate device.

In a series of 45 subtrochanteric fractures treated with a sliding screw-plate device, union was achieved in 43 patients (95.3%). Most were Seinsheimer Type II C (9), Type IIIA (12), and Type V (18). Fractures were stabilized in a valgus position (average, 140 degrees), with primary medial displacement of the femoral shaft (25 patients). Radiographic analysis of the degree of postoperative impaction of the fragments correlated with the fracture pattern. Fractures with medial cortical comminution such as Type IIIA and Type V were the most unstable, with an average of 10.8 and 8.0 mm axial impaction, respectively, and were at the greatest risk of complication. The sliding screw-plate device is a reliable method of achieving union in subtrochanteric fractures.

Selective hindfoot arthrodesis in rheumatoid arthritis.

Rheumatoid arthritis that involves the hindfoot is disabling because it affects the patient's ability to walk. Fifteen patients with ankle pain who demonstrated isolated hindfoot arthritis clinically and radiographically underwent 19 selective hindfoot arthrodeses. At followup averaging 3 ½ years, results were rated good in 16, fair in four, and none were rated poor. Selective hindfoot fusion is effective in relieving pain and restoring the foot to ambulatory status.