Donald L. Uden

Clinical efficacy of antimicrobial drugs for acute otitis media: Metaanalysis of 5400 children from thirty-three randomized trials

OBJECTIVE To reconcile conflicting published reports concerning the absolute and comparative clinical efficacy of antimicrobial drugs for acute otitis media in children. STUDY SELECTION Articles were identified by MEDLINE search, Current Contents, and references from review articles, textbook chapters, and retrieved reports. Randomized, controlled trials of therapeutic antimicrobial drugs used in the initial empiric therapy for simple acute otitis media were selected by independent, blinded observers, and scored on 11 measures of study validity. Thirty English and three foreign-language articles met all inclusion criteria. DATA EXTRACTION Data were abstracted for an end point of complete clinical resolution (primary control), exclusive of middle ear effusion, within 7 to 14 days after therapy started. DATA SYNTHESIS The spontaneous rate of primary control--without antibiotics or tympanocentesis--was 81% (95% confidence interval, 69% to 94%). Compared with placebo or no drug, antimicrobial therapy increased primary control by 13.7% (95% confidence interval, 8.2% to 19.2%). No significant differences were found in the comparative efficacy of various antimicrobial agents. Extending antimicrobial coverage to include beta-lactamase-producing organisms did not significantly increase the rates of primary control or resolution of middle ear effusion. Pretreatment tympanocentesis was positively associated with individual group primary control rates, negatively associated with the ability to detect differences in clinical efficacy and unassociated with resolution of MEE. CONCLUSIONS Antimicrobial drugs have a modest but significant impact on the primary control of acute otitis media. Treatment with beta-lactamase-stable agents does not increase resolution of acute symptoms or middle ear effusion; initial therapy should be guided by considerations of safety, tolerability, and affordability, and not by the theoretical advantage of an extended antibacterial spectrum.

Tetracaine, Epinephrine (Adrenalin), and Cocaine (TAC) Versus Lidocaine, Epinephrine, and Tetracaine (LET) for Anesthesia of Lacerations in Children

STUDY OBJECTIVE To compare the duration of anesthesia experienced with lidocaine, epinephrine, and tetracaine (LET) solution and that with tetracaine, epinephrine (Adrenalin), and cocaine (TAC) solution during suturing of uncomplicated lacerations on the face or scalp. DESIGN Double-blind, randomized, controlled trial. SETTING The emergency department of a university-affiliated private childrens hospital. PARTICIPANTS One hundred seventy-one children with lacerations on the face and scalp requiring suturing. INTERVENTIONS After standard application of the anesthetic solution, patients were assessed for signs of discomfort before and during laceration repair. Duration of anesthesia during laceration repair was determined on the basis of the length of time after removal of the anesthetic solution to the first sign(s) of discomfort that required additional anesthesia. RESULTS There was no statistical difference between TAC and LET in adequacy of anesthesia before suturing or in duration of anesthesia during suturing. CONCLUSION LET is an effective alternative to TAC for topical anesthesia during suturing of uncomplicated lacerations on the face and scalp in children.

Pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic disease

Study Objective. To describe the pharmacokinetics of fluconazole in immune‐compromised children with leukemia or other hematologic disease.

Topical Anesthesia for Pediatric Lacerations: A Randomized Trial of Lidocaine-Epinephrine-Tetracaine Solution Versus Gel

STUDY OBJECTIVE To compare the adequacy and efficacy of anesthesia experienced with lidocaine-epinephrine-tetracaine (LET) solution versus LET gel during suturing of uncomplicated lacerations on the face or scalp in children. METHODS Two hundred children with lacerations of the face and scalp requiring suturing were enrolled in this blinded, randomized controlled trial, in the emergency department of a university-affiliated childrens hospital. After the application of anesthetic solution or gel, adequacy of anesthesia was determined before suturing. Efficacy of anesthesia during laceration repair was determined by the length of time after removal of the topical anesthetic to the first sign of discomfort that required additional anesthesia or until suture completion. RESULTS Adequacy of initial anesthesia was equivalent between LET solution and LET gel. There was a significant difference in efficacy of anesthesia between the LET formulations. There were more patients with complete anesthesia (85% versus 76%), fewer persons with partial anesthesia (5% versus 21%), and more persons with incomplete anesthesia (9% versus 3%) in the gel group. CONCLUSION LET gel is at least as effective as LET solution and possesses theoretical advantages for topical anesthesia during suturing of uncomplicated lacerations on the face and scalp in children.

Inactivation of heparin during extracorporeal circulation in infants

Heparin anticoagulation is necessary to prevent clotting during procedures involving the extracorporeal circulation of blood. Our preliminary observations suggested that heparin was inactivated in the extracorporeal circuit during extracorporeal membrane oxygenation. We tested this hypothesis by comparing heparin pharmacokinetics in five infants during extracorporeal circulation with kinetics, respectively determined in each patient and in the isolated circuit immediately after discontinuation of the procedure. Heparin clearance was 1.6 ± 0.5 ml/kg/min in the patient and 2.1 ± 0.8 ml/kg/min in the separated circuit. In each patient, the total of heparin clearances in the patient and circuit, 3.7 ± 1.0 ml/kg/min, was virtually identical with the heparin clearance during the procedure, 3.8 ± 1.9 ml/kg/min (r = 0.94, p < 0.01). We conclude that more than one half of the heparin administered to infants during extracorporeal membrane oxygenation is eliminated by the extracorporeal circuit itself or by blood components in the circuit. These data explain the relatively large heparin doses needed to maintain anticoagulation in infants during extracorporeal circulation. In light of these findings, a reexamination of the normal mechanisms of elimination of heparin activity appears to be warranted.

Comparison of nebulized terbutaline and subcutaneous epinephrine in the treatment of acute asthma

Nineteen children who presented for treatment of acute asthma symptoms were studied. They were randomized to receive either subcutaneous epinephrine 0.01 mg/kg (0.3 mg maximum) or nebulized terbutaline 1 mg in 2 mL normal saline. The drugs were administered using the double-blind method. Each patient received either subcutaneous epinephrine with concurrent nebulized normal saline or nebulized terbutaline with a concurrent subcutaneous injection of normal saline. Depending on the patients clinical status, up to three doses of the same drug and placebo were administered. Pulmonary functions (FEV1, FVC, FEF25-75), heart rate, respiratory rate, and pulmonary index were obtained before treatment, at 20 minutes, and at one hour after the final treatment. Except for the baseline respiratory rate, the mean number of treatments, pulmonary index, heart rate, and respiratory rate (at 20 minutes and one hour) were not statistically different. Pulmonary functions were not significantly different at any time. The one-hour post-treatment pulmonary functions (percentage of predicted normal) for terbutaline and epinephrine were FEV1, 49.2 +/- 18.4% and 49.4 +/- 16.9%; FVC, 72.7 +/- 23.4% and 62.7 +/- 21.6%; and FEF25-75, 31.8 +/- 18.6% and 39.0 +/- 12.2%, respectively. The data presented support our hypothesis that terbutaline by nebulization is at least as effective as epinephrine in the management of children with similar degrees of pulmonary obstruction.

Intravenous glycerol and mannitol therapy in children with intracranial hypertension

Acute intracranial hypertension may respond to intravenous mannitol, but frequent administration can cause cerebral edema or renal problems. We evaluated the use of 20% glycerol administered intravenously as an alternative to mannitol. Intravenous glycerol and mannitol were equally effective in lowering acute elevations of intracranial pressure. The duration of effect was similar for both agents. Side effects of intravenous glycerol were related to concentration, rate, and frequency of administration. In severe encephalopathies, such as Reye syndrome, we recommend infusions of 20% glycerol or 20% mannitol at a dose of 0.5-1.0 gm per kilogram. Glycerol should be administered in 0.45% or 0.9% saline, no faster than 1.5 ml (3.3 mOsm) per minute.

Cefpodoxime proxetil vs. penicillin V in pediatric streptococcal pharyngitis/tonsillitis

This multicenter, randomized, parallel treatment, observer-blinded study was designed to evaluate the safety and efficacy of cefpodoxime proxetil (5 mg/kg twice daily for 10 days) compared with penicillin V (13.4 mg/kg three times daily for 10 days) for treatment of Group A streptococcal pharyngitis and tonsillitis in pediatric patients. Clinical and microbiologic results were evaluated before therapy, during therapy (Study Days 3 to 5), at the end of therapy (Study Days 14 to 18) and at long term follow-up (Study Days 30 to 32). Both drugs were well-tolerated in 578 patients evaluable for safety. Mild gastrointestinal complaints were noted in 6.7% of 386 cefpodoxime-treated patients and in 5.2% of 192 penicillin-treated patients. In 413 patients evaluable for efficacy, both treatment regimens resulted in comparably favorable clinical outcome; cure rates were 83.8% for 275 cefpodoxime-treated patients and 77.5% for 138 penicillin-treated patients. However, eradication of S. pyogenes at end of therapy was significantly higher with cefpodoxime (93.1%) than with penicillin (81.2%) (P < 0.01). Cefpodoxime proxetil provides an effective alternative to penicillin V for the treatment of streptococcal pharyngitis and tonsillitis.

Prematurity prevention programs: An analysis of successes and failures

OBJECTIVE Our purpose was to assess the long-term results of established prematurity prevention programs. STUDY DESIGN A population cohort of pregnant women from two major urban health care organizations were examined. Rates and cost-benefit analysis of prematurity and patient, system, or physician failures were analyzed. During 1990 1143 pregnant women were prospectively reviewed. RESULTS A total of 11.8% of the mothers were high risk and responsible for 108 (50.2%) of the preterm deliveries. The preterm birth rate of all enrollees was 4.6%. One percent of the preterm neonates required level III care for complications. The average charge for a 35 week infant was 18 times, and a 36 week infant was five times more costly than a term infant. Patient, physician, and health care system failures occurred at different rates. CONCLUSIONS This preterm prevention program resulted in low preterm birth rates. Potentially preventable preterm births most often occurred as a result of patient and physician failures.

Rural interprofessional service-learning: the Minnesota experience.

The Minnesota Rural Health School (MRHS), which operated from 1996 to 2003, was the University of Minnesotas first initiative that provided rural, community-based, interdisciplinary health professions education. The newly funded Minnesota Area Health Education Center (AHEC) is now coordinating interprofessional rural clinical education at the Academic Health Center level for the university. The service-learning curricular component is one of the most lasting legacies of the MRHS. This article provides a descriptive summary of the initial 61 service-learning projects completed by students from various health professions who participated in the MRHS and indicates the type of projects that have continuing effects. The seven community site coordinators affiliated with the MRHS completed a survey analyzing service-learning projects performed in their communities. Student interest was predominant in selecting 28% of the 61 projects, community interest was paramount in selecting 10%, and a mixture of both student and community interest contributed to 62% of project selection. Thirty of the projects were designed as single interventions, and the remaining 31 projects have ongoing impact. Students demonstrated interprofessional group synergy and significant creativity in addressing multiple community health care issues and needs, within time constraints of only ten to 12 days in which to develop and implement a service-learning project. Two project examples are described in detail to illustrate the challenges and successes of this type of civic engagement.