JOURNAL CLUB

JOURNAL CLUB

The top ten of 1998

COMMENTARIES BY MICHAEL G. BURKE, MD

Editor's Note:This month we present Dr. Burke's choice of the top tenpediatric articles of 1998--in order of significance. If we've left outyour favorite, let us know.

Prolonged QT interval associated with SIDS

A new study supports the hypothesis that prolongation of the QT intervalon the electrocardiogram may be associated with sudden infant death syndrome(SIDS). According to this theory, the prolongation may result from a developmentalabnormality in cardiac sympathetic innervation, increasing the risk of life-threateningventricular arrhythmias and contributing to SIDS.

Between 1976 and 1994, investigators recorded electrocardiograms on thethird or fourth days of life in more than 33,000 Italian newborns and followedthe infants for one year. Of the 33,034 newborns for whom follow-up datawere available, 24 of the 34 who died succumbed to SIDS. Newborn periodEKGs were analyzed on these 34 babies and on a control group of 9,725 survivingbabies. The SIDS victims had a longer QT interval, corrected for heart rate(QTc), than both the survivors and the infants who died from causes otherthan SIDS. In addition, half the SIDS victims and none of the other infantswho died had a prolonged QTc, defined as greater than 440 milliseconds.Among the infants who died of SIDS, the duration of the QT interval wasnot significantly different in premature and full-term babies.

The odds ratio for SIDS among infants with a QTc greater than 440 millisecondswas approximately 41, and in boys about 47. Investigators noted that oddsratios are markedly lower for other traditional SIDS risk factors, suchas sleeping in a prone position, maternal smoking, and bed sharing (SchwartzPJ et al: N Engl J Med 1998;338:1709).

Commentary: I'm convinced. Unless measurement of the QT intervalshad some unseen bias, this huge, 19-year study holds up. The authors speculatethat up to 35% of children who later die of SIDS have a prolonged QT intervalin the first week of life. To detect the anomaly would require a screeningEKG on all infants. Approximately 250 in 10,000 would have a prolonged QT.And of those 250, five could be expected to go on to SIDS. There might beeffective medical treatment. Are we willing to screen all newborns and totreat some to protect these few?

Pediatricians prescribe unnecessary antibiotics

In light of the spread of antimicrobial resistance, investigators evaluatedantibiotic-prescribingpractices for children younger than 18 years with a diagnosis of cold, upperrespiratory tract infection (URI), or bronchitis. There is little evidencethat antibiotics improve outcomes in these conditions. The authors analyzeddata from the 1992 National Ambulatory Medical Care Survey of office-basedphysicians. Of 531 visits with a principal diagnosis of cold, URI, or bronchitis,62% were to pediatricians and 11% to family practitioners. The rest wereto general practitioners, internists, and specialists.

Antibiotics were prescribed to 44% of patients with colds, 46% with URIs,and 75% with bronchitis. Physicians prescribed antibiotics for these conditionsmore often for children from 5 to 11 years of age than for younger children.Pediatricians were about half as likely as other physicians to prescribeantibiotics for the three diagnoses. Still, because they treat most children,pediatricians prescribed the bulk of unnecessary courses of antibiotics(Nyquist A-C et al: JAMA 1998;279:875).

Commentary: If children's physicians in the United States couldagree to stop prescribing antibiotics for colds, URIs, and bronchitis, 11.2million fewer antibiotic prescriptions would be written each year. I figurethat to be about 1.68 million liters of amoxicillin.

CT recommended for suspected appendicitis

A new study shows that routine use of computed tomography (CT) to diagnoseclinically suspected appendicitis improves patient care and reduces useof hospital resources. CT is 93% to 98% accurate in confirming or rulingout appendicitis, and the savings it achieves by eliminating unnecessaryoperations and hospitalizations for observation outweighs its cost.

Investigators performed focused, helical, appendiceal CT after Gastrografinenema on 100 consecutive patients in the emergency department who were tobe hospitalized for observation for suspected appendicitis or for urgentappendectomy. They compared pre­CT surgical management plans to plansdeveloped after CT results were available. Results of CT led to 63 changesin pre­CT treatment plans for 59 patients, including prevention of thefollowing procedures: unnecessary appendectomy in 13 patients, hospitalizationfor observation before needed appendectomy in 21 patients, delay in findinganother diagnosis in 11 patients, and admission for observation in 18 patients.Elimination of unnecessary appendectomy saved $47,281; prevention of unnecessaryhospital admission for 50 patient days of observation saved $20,250. Theappendiceal CT studies cost $22,800, bringing the net savings for the 100examinations to $44,731 or $447 per patient (Rao PM et al: N Engl J Med1998; 338:141).

Commentary: We all know that diagnosing appendicitis is no easytask. A test that would truly help in making this diagnosis would certainlybe welcome--and this may be it. In this study, appendiceal CT was 98% sensitive,98% specific, and had 98% overall accuracy for diagnosing or ruling outappendicitis. CTs were not performed on every person with abdominal pain,which would diminish the accuracy of the test. Instead, the test was performedonly on those in whom clinical suspicion for appendicitis was high.

This is not a conventional CT. Your local radiologist will need to becomfortable with the procedure before you can match the results seen here.

Are blood cultures necessary in cellulitis?

Blood cultures are performed in children hospitalized for cellulitisbecause these children have had a high rate of bacteremia with Haemophilusinfluenzae. Now researchers show thatdue to the vaccine-associated decreaseof this pathogen, blood cultures are not cost-effective and are more likelyto be contaminated than positive in patients with uncomplicated cellulitis.

In this retrospective study, blood cultures were taken in 243 childrenwith a mean age of 6.2 years admitted with cellulitis--mostly uncomplicated.Blood cultures were positive in five patients and contaminated in 13. Thepositive blood cultures grew streptococcus and staphylococcus organisms;all patients with group A
b-hemolytic streptococcus had active infection with varicella. Comparedwith other children, those with positive blood cultures had a lower meanage (26 months compared with 75 months) and a higher mean band-to-neutrophilratio. Management in patients with positive cultures and uncomplicated cellulitiswas the same as for patients with negative cultures and uncomplicated cellulitis,except that repeat cultures were obtained in those who tested positive.

Investigators noted that if they had used a band-to-neutrophil ratioof 0.20 as a threshold for sending blood cultures, they would have missedonly one positive blood culture, avoided cultures in 213 patients, and savedan estimated $42,850. They recommend that clinicians limit cultures in childrenwith cellulitis to those who are either very young or appear toxic, or whohave varicella or another focus of infection, such as a septic joint (SadowKB et al: Pediatrics 1998;101[3]:e4).

Commentary: I find it very hard to bypass blood cultures in childrensick enough to be admitted for cellulitis, partly because once the antibioticsare started, the opportunity is gone. The authors argue that the cultureresults no longer change patient management. They may be right.

Xylitol prevents otitis media: How sweet it is

Xylitol, a common sweetener that inhibits the in vitro growth of pneumococci,may prevent acute otitis media (AOM), a new study of xylitol-sweetened syrup,gum, and lozenges shows. Finnish investigators assigned 857 children recruitedfrom day-care centers to one of five groups. Children too young to chewgum received either xylitol syrup or a control syrup--5 mL five times aday after a meal. The children who were able to chew gum received eithera xylitol chewing gum, a control chewing gum, or xylitol-sweetened lozenges.Twopieces of gum or three lozenges were given five times a day after eating.The daily dose of xylitol ranged from 8.4 grams in the chewing gum to 10grams in the syrup.

After three months, 41% of the children who took control syrup had AOMat least once, compared with 29% of the children who took xylitol syrup--a30% decrease in incidence. Similarly, occurrence of otitis was 40% lowerin the children who used xylitol chewing gum than in control subjects. Thegroup who took xylitol lozenges did not have significantly less AOM thanchewing gum controls (Uhari M et al: Pediatrics 1998;102:879).

Commentary: The mechanism of action for xylitol is unclear thoughthis natural sugar is known to inhibit Streptococcus pneumoniae and mayinhibitadhesion of bacteria in the nasopharynx. Xylitol, in these large doses,is not currently available in the United States. Large-scale follow-up studiesare planned here to further investigate this sweet idea.

Community policy slows adolescent smoking

A randomized community trial indicates that policies designed to reduceyouth access to tobacco can have a significant effect on adolescent smokingrates. Fourteen communities in Minnesota were randomly assigned to interventionor control conditions. The communities in the intervention group participatedin a 32-month community effort to change ordinances, merchant policies andpractices, and law enforcement practices to reduce youth access to tobacco.The communities used various ways to raise public awareness about the issue,including letter and petition drives and media campaigns. Each interventioncommunity passed a comprehensive youth access ordinance.

After the campaign, investigators surveyed more than 6,000 students toassess perceived availability and sources of cigarettes and smoking prevalence.Whereas the prevalence of smoking climbed sharply in the control communitiesduring the course of the study, the increase in the intervention communitieswas less pronounced. In addition, youths in the intervention communitiesreported that it had become more difficult to purchase cigarettes in thecommunity, though not harder to get cigarettes from friends and family (ForsterJL et al: Am J Public Health 1998;88:1193).

Commentary: This information comes on the heels of another reportfrom the Centers for Disease Control and Prevention that increased cigaretteprices would decrease cigarette use, especially among minorities, low-incomepopulations, and young people (MMWR 1998;47:506). We know what needs tobe done to decrease adolescent smoking. I think that our legislators knowwhat needs to be done, too. So what's holding things up?

Obstructive sleep apnea affects schoolwork

Sleep-associated gas exchange abnormalities are highly prevalent in academicallyinsecure first graders and adversely affect learning performance, a newstudy shows. Investigators screened first-grade children whose school performancewas in the lowest 10% of their class for obstructive sleep apnea syndrome.Using a detailed parental questionnaire, they determined the nature of thechild's breathing during sleep, occurrence and type of snoring, and daytimesleepiness. They also assessed incidence of sleep-associatedgas exchangeabnormalities with an overnight recording of pulse oximetry, pulse, andtranscutaneous carbon dioxide tension. Of 194 children screened, 54 appearedto have sleep-associated gas exchange abnormalities. Investigators alertedparents of these children, encouraging them to contact their pediatriciansfor further evaluation and possible surgical treatment.

More than a year later, investigators asked these parents whether thechild had received any surgical therapy for the sleep condition and readministeredthe questionnaire. Twenty-four of the children had undergone tonsillectomyand adenoidectomy; the remaining 30 children had no therapeutic intervention.In the children undergoing surgery, mean grades during the second gradeimproved; grades of the children with no therapy did not alter significantly.Academic improvements also were not seen in children without obstructivesleep apnea syndrome (Gozal D: Pediatrics 1998;102[3]:616).

Commentary: I was surprised that 18% of the first-grade childrenin the lowest 10% academically had evidence of "sleep associated gasexchange abnormalities." School performance in the children who wereidentified and treated improved significantly. Should this evaluation becomeroutine for children with school problems?

Antibodies to CD4 cells in asthma therapy

Investigators assessed the hypothesis that since CD4 lymphocytes mayhave a role in the pathogenesis of chronic asthma, antibody to CD4 mightbe a useful management tool. They assigned 22 asthma patients who were dependenton daily doses of oral corticosteroids to receive a single intravenous infusionof keliximab, a chimeric monoclonal antibody to CD4, in one of three dosesor a placebo. In the patients receiving the highest dose of keliximab, 3.0mg/kg, changes from baseline in morning and evening peak expiratory flow(PEF) were significantly greater than in the placebo recipients. Symptomscore changes from baseline, derived from a daily symptom diary, in thekeliximab and placebo recipients varied only slightly, and changes in forcedexpiratory volume in one second (FEV₁) were the same in bothgroups of patients. In the lower- dose keliximab treatment groups, changesfrom baseline in PEF, FEV₁, and symptom scores did not differbetween treatment and placebo recipients. No patients had serious adverseeffects from treatment. Investigators concluded that T-cell-directed treatmentmay be an alternative approach to the treatment of severe asthma (Kon OMet al: Lancet1998;352:1109).

Constipation and cow's milk intolerance

Italian researchers have shown that constipation can be a presentationof cow's milk intolerance. The investigators studied 65 children with chronicconstipation, ages 11 to 72 months, to measure the effect of restrictingconsumption of cow's milk. All the children had been unsuccessfully treatedwith laxatives and were being fed full-fat cow's milk, dairy products, orcommercial formulas derived from cow's milk. Each child was assigned toreceive either soy milk or cow's milk for two weeks. This was followed bya one-week period on an unrestricted diet, after which study subjects wereswitched to the other type of milk for another two weeks.

Constipation resolved in 44 of the 65 children (68%) while they consumedsoy milk. Constipation did not resolve in any of the children while theydrank cow's milk. A challenge with cow's milk after the two two-week studyperiods confirmed the association between cow's milk and constipation inall 44 children whose constipation resolved during the soy-milk diet. Childrenwith a response to soy milk were more likely than nonresponders to haveother manifestations of intolerance of cow's milk, such as bronchospasm,dermatitis, and rhinitis, and signs of hypersensitivity, such as specificIgE antibodies to cow's milk antigens. When the study began, respondersalso were more likely than nonresponders to have anal fissures and evidenceof inflammation of the rectal mucosa on biopsy (Iacono G et al: N Engl JMed 1988; 339:1100).

Commentary: The authors note that they may be seeing a very selectedpopulation--all the children were constipated despite laxatives and werereferred to a pediatric gastroenterologist. In your population fewer than68% of constipated patients may respond to elimination of cow's milk. Restrictingmilk intake may be worth a try, however, especially if rhinitis, dermatitis,bronchospasm, or anal inflammation accompanies constipation.

Complications after E coliO157:H7 infection

To help estimate the age-specific risks of hemolytic uremic syndrome(HUS) and hemolytic anemia after sporadic Escherichia coli O157:H7 infection,investigators in Canada conducted a prospective study in several centersacross the province of Alberta. Children in the study were younger than15 years and had either HUS or documented E coli O157:H7 gastroenteritis.Investigators compared rates of HUS and hemolytic anemia after E coli infectionin this group with rates in children evaluated at tertiary care centerselsewhere in Canada. The authors hypothesized that since tertiary care hospitalsare referral centers for the most severely ill patients, complication ratesafter sporadic E coli O157:H7 infection are higher at these hospitals thanat others.

Investigators obtained hemoglobin, blood smear, urinalysis, and serumcreatinine eight to 10 days after the onset of diarrhea to assess hemolysis,anemia, thrombocytopenia, and renal injury. They monitored patient symptomsfor one month for evidence of HUS or hemolysis. HUS was diagnosed in 205children from June 1991 to March 1994. Of these, 77% had evidence of E coliinfection. An additional 582 children had E coli gastroenteritis, including18 with hemolytic anemia. The risk of HUS after E coli O157:H7 infectionwas 8.1% in Alberta; this compares with 31.4% in referral centers in therest of Canada. In Alberta, children younger than 5 years old were morelikely (12.9%) than any other age group to have HUS or hemolytic anemiaafter E coli infection (Rowe PC et al: J Pediatr 1998; 132:777).

Commentary: I think the take-home message from this article andthe accompanying editorial is: If you send stool cultures, have the labcheck for E coli O157:H7. And if you find the E coli, expect to see complications,from hemolysis to full-blown HUS, in about 8% of your patients.

DR. BURKE, Section Editor for Journal Club, is Chairman of the Departmentof Pediatrics at Saint Agnes Hospital, Baltimore, and a Contributing Editorfor Contemporary Pediatrics.