Translating Best Evidence into Best Care

EDITORS NOTE: Journals reviewed for this issue: Archives of Disease in Childhood, Archives of Pediatrics and Adolescent
Medicine, British Medical Journal, Journal of the American Medical Association, The Journal of Pediatrics, The Lancet, New
England Journal of Medicine, Pediatric Infectious Diseases Journal, and Pediatrics. Heidi Marleau, MLS, Ebling Library for the
Health Sciences, University of Wisconsin, contributed to the review and selection of this months abstracts.
John G. Frohna, MD, MPH

Clinical prediction rule adequately predicts

nonbacterial conjunctivitis
Meltzer JA, Kunkov S, Crain EF. Identifying children at low
risk for bacterial conjunctivitis. Arch Pediatr Adolesc Med
2010;164:263-7.
Question Among children with conjunctivitis, what clinical
characteristics predict negative conjunctival culture for typical infectious bacteria?
Design Prospective cohort (clinical prediction rule).
Setting Pediatric emergency department in New York City.
Participants Three hundred sixty-eight sequential children,
ages 6 months to 17 years, presenting to the emergency
department with conjunctivitis.
Intervention Clinical characteristics on history and physical
exam, as well as a standardized bacterial culture of the lower
lid conjunctiva, were gathered on each child.
Outcomes The primary outcome was a positive culture for
a bacterium not considered to be normal conjunctival flora.
Predictor variables showing an association to culture outcome on bivariate analysis were tested in a multivariate logistic regression model.
Main Results Sixty-five percent of the conjunctival cultures
were positive. Four variables were found to be strongly associated with negative culture: age >5 years, presentation in
April through November, no or watery eye discharge, and
no glued eye in the morning. Having all four of these predictors present had a probability of a negative conjunctival
culture of 92% (95% confidence interval, 66.1% to 98.2%).
Conclusions Four easily gathered variables on children
presenting with conjunctivitis can adequately predict which
children will have negative bacterial cultures of their
conjunctiva.
Commentary Meltzer et al performed a valid cohort study of
sequential children presenting to the emergency department,
in an effort to sort out which children would most reliably
have negative cultures and therefore could be treated expectantly without topical antibiotics. The strengths of this study
were the sequential gathering of subjects (even on nights and
weekends), the checklist of signs and symptoms, and the
objective, prospectively defined outcome of bacterial culture.
What we do not know from the study is how good the interrater reliability was on gathering the predictive variables,
because the variables were gathered by all providers in the
emergency department: attendants, residents, and nurse
512

practitioners. Overall this is a valid clinical prediction rule

by the Users Guides criteria1 but can only be considered
a level 4 prediction rule. To become more widely useful
and validated, this rule must be restudied in other settings
and ultimately studied to ensure that it changes physician
behavior. Until it is validated by further studies, clinicians
can use this rule with some caution when approaching
children with conjunctivitis. Even with caution, however,
the clinician can be reassured that bacterial conjunctivitis
resolves spontaneously and topical antibiotic treatments
only speed this natural healing process.2
Brett Robbins, MD
University of Rochester
Rochester, New York

References
1. McGinn TG, Guyatt GH, Wyer PC, Naylor CD, Stiell IG, Richardson WS.
Users guides to the medical literature: XXII: how to use articles about
clinical decision rules. JAMA 2000;284:79-84.
2. Sheikh A, Hurwitz B. Antibiotics versus placebo for acute bacterial
conjunctivitis. Cochrane Database Syst Rev 2006;(2):CD001211.

Long-acting bagonists best option for stepup therapy for children with uncontrolled
asthma
Lemanske RJ, Mauger D, Sorkness C, Jackson D, Boehmer S,
Martinez F, et al. Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. N Engl J
Med 2010;362:975-85.
Question Among children who have uncontrolled asthma
despite the use of low-dose inhaled corticosteroids (ICS),
what is the best option for step-up therapy?
Design Randomized, blinded, multicenter study.
Setting Childhood Asthma Research and Education (CARE)
Network sites.
Participants One hundred eighty-two children (6 to 17 years
of age) who had uncontrolled asthma while receiving 100 mg
of fluticasone twice daily.
Intervention Each participant received three blinded stepup therapies in random order for 16 weeks: 250 mg of fluticasone twice daily (ICS step-up), 100 mg of fluticasone plus 50
mg of a long-acting b-agonist twice daily (LABA step-up), or

Vol. 157, No. 3  September 2010

100 mg of fluticasone twice daily plus 5 or 10 mg of a leukotriene-receptor antagonist daily (LTRA step-up).

References

Outcomes A differential response for a composite of three

outcomes (exacerbations, asthma-control days, and the
forced expiratory volume in 1 second).

1. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005;

353:487-97.
2. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther 2001;23:
1296-310.

Main Results A differential response occurred in 161 of 165

patients who were evaluated (P < .001). The response to
LABA step-up therapy was most likely to be the best response, as compared with responses to LTRA step-up (relative probability, 1.6; 95% confidence interval [CI], 1.1 to
2.3; P = .004) and ICS step-up (relative probability, 1.7;
95% CI, 1.2 to 2.4; P = .002). Higher scores on the Asthma
Control Test before randomization (indicating better control
at baseline) predicted a better response to LABA step-up
(P = .009). White race predicted a better response to LABA
step-up, whereas black patients were least likely to have
a best response to LTRA step-up (P = .005).
Conclusions Nearly all the children in this study had a differential response to each step-up therapy. LABA step-up was
significantly more likely to provide the best response than
either ICS or LTRA step-up. However, many children had
a best response to ICS or LTRA step-up therapy, highlighting
the need to regularly monitor and appropriately adjust each
childs asthma therapy.
Commentary Using current asthma clinical practice guidelines, clinicians have several choices for step-up therapy for
children with uncontrolled asthma who are already on ICS.
This study compares the effectiveness of several strategies:
step-up ICS therapy, adding an LABA, or adding an LTRA.
In this study, although there were groups of children that responded to all three step-up strategies (ICS, LABA or LTRA),
LABA step-up therapy was significantly more likely to provide the best response compared with LTRA (relative probability, 1.6; 95% CI, 1.1 to 2.3) and ICS step-up (relative
probability, 1.7; 95% CI, 1.2 to 2.4). Post hoc analyses suggest
that patient characteristics may also be helpful in guiding
therapy. African-Americans were equally likely to respond
best to ICS step-up or LABA, and Hispanic and nonHispanic white patients were likely to respond best to
LABA. This study fills in key gaps for initial step-up therapy
in current guidelines but also reminds clinicians that therapy
eventually must be individualized. In this study, the adherence rate for study medications was well over 80%. This
adherence rate probably is higher than what most clinicians
experience in daily practice.1 In many clinical scenarios,
current therapy may be appropriate, but patient adherence
may be poor. In addition, the more complicated the medical
regimen, the lower the likelihood of patient adherence.2 As
a result, it is important to consider, investigate, and address
poor patient adherence to existing therapy before considering step-up therapy.
Michael D. Cabana, MD, MPH
University of California-San Francisco
San Francisco, California

Gastric banding results in significant weight loss

for obese adolescents
OBrien P, Sawyer S, Laurie C, Brown W, Skinner S, Veit F, et
al. Laparoscopic adjustable gastric banding in severely obese
adolescents: a randomized trial. JAMA 2010;303:519-26.
Question Among obese adolescents, is gastric banding more
effective at reducing weight compared with an optimal lifestyle program?
Design Prospective, randomized, controlled trial.
Setting Melbourne, Australia, community.
Participants Fifty adolescents, between 14 and 18 years, with
a body mass index (BMI) higher than 35.
Intervention Supervised lifestyle intervention or gastric
banding. Subjects were followed up for 2 years.
Outcomes The primary outcome was weight loss. Secondary
outcomes included change in metabolic syndrome, insulin
resistance, quality of life, and adverse outcomes.
Main Results Twenty-four of 25 patients in the gastric banding group and 18 of 25 in lifestyle group completed the study.
Twenty-one (84%) in the gastric banding and 3 (12%) in the
lifestyle groups lost more than 50% of excess weight, corrected for age (number needed to treat = 2). Overall, the
mean changes in the gastric banding group were a weight
loss of 34.6 kg (95% CI, 30.2 to 39.0), representing an excess
weight loss of 78.8% (95% CI, 66.6% to 91.0%), 12.7 BMI
units (95% CI, 11.3 to 14.2), and a BMI z score change
from 2.39 (95% CI, 2.05 to 2.73) to 1.32 (95% CI, 0.98 to
1.66). The mean losses in the lifestyle group were 3.0 kg
(95% CI, 2.1 to 8.1), representing excess weight loss of
13.2% (95% CI, 2.6% to 21.0%), 1.3 BMI units (95% CI,
0.4 to 2.9), and a BMI z score change from 2.41 (95% CI,
2.21 to 2.66) to 2.26 (95% CI, 1.91 to 2.43). At entry, 9
participants (36%) in the gastric banding group and 10
(40%) in the lifestyle group had the metabolic syndrome.
At 24 months, none of the gastric banding group had the
metabolic syndrome (P = .008; McNemar c2) compared
with 4 of the 18 completers (22%) in the lifestyle group
(P = .13). The gastric banding group had improved quality
of life with no perioperative adverse events. However, eight
operations (33%) were required in seven patients for revisional procedures either for proximal pouch dilatation or tubing
injury during follow-up.
Conclusions Among obese adolescent participants, use of
gastric banding compared with lifestyle intervention resulted
in a greater percentage achieving a loss of 50% of excess
513