Journal Club

JOURNAL CLUB

COMMENTARIES BY MICHAEL G. BURKE, MD

Acellular pertussis vaccine as a booster?

Investigators evaluated the immunogenicity and reactogenicity of an acellular pertussis vaccine for possible use as a booster in adolescents. Bordetella pertussis infection in previously immunized adolescents and adults increasingly has been recognized as a reservoir for spread of infection to susceptible infants. Investigators hope that availability of less reactogenic acellular pertussis vaccines may allow for the eventual elimination of this reservoir of disease.

The study assigned 510 healthy Finnish children from 10 to 13 years of age to receive an acellular pertussis vaccine (pa). One group received the vaccine formulated with diphtheria and tetanus toxoids (dTpa); the other group received a licensed tetanus and diphtheria vaccine (Td) and, one month later, the pa vaccine alone. The quantities of three pertussis antigens in the dTpa and the pa vaccines were one third of those in the pertussis vaccine licensed for use in infants. Investigators obtained blood samples before immunization and one month later to measure pertussis antibody response. Parents recorded local and systemic reactions on diary cards for 15 days after immunization.

Youngsters in both groups had significant and comparable rises of antibodies to each of the pertussis antigens. Immunization with dTpa or Td produced significant rises in diphtheria and tetanus antibodies as well. Incidence of severe local reactions was low in both groups, and the largely mild and transient adverse reactions (most often pain) resolved spontaneously. Investigators concluded that vigorous booster responses can be elicited by reduced quantities of pertussis vaccine antigens in previously primed subjects, without an increase in adverse reactions. This indicates that the use of acellular pertussis vaccines as a booster for adolescents is feasible (Minh NNT et al: Pediatrics 1999; 104 [6]:e70).

Commentary: It is clear that to eradicate pertussis in infants we will need to change our current approach to immunization. Perhaps boosters for adolescents and adults will be the solution.

Secretin no magic bullet for autism

In response to publicity about a child with autism whose condition markedly improved after a single dose of secretin, investigators evaluated the effects of one dose of synthetic human secretin in 56 children with autism or pervasive developmental disorder. Half the children, who ranged in age from 3 to 14 years, received secretin and the other half a placebo. Study clinicians, parents, and teachers made detailed assessments of each child's behavioral symptoms before the study began, on the first and second day after infusion, and at the end of the first, second, and fourth weeks. They measured the severity of autistic symptoms with the Autism Behavior Checklist.

Compared with placebo, secretin treatment was not associated with significantly greater improvements in any of the 16 outcome measures. Significant decreases from baseline in the severity of symptoms on six of these measures were reported for both the placebo and secretin groups over the course of the assessment period, but the magnitude of these decreases was similar in both groups. Investigators concluded that a single dose of synthetic human secretin is not an effective treatment for autism or pervasive developmental disorder (Sandler AD et al: N Engl J Med 1999;341:1801).

Commentary: If you follow children with autism in your practice, spend some time searching the Internet to see what your patients' parents are reading about secretin. I believe that it will take more than one study to stop widespread use of secretin for autism.

Clean-catch urine and UTI diagnosis

Investigators in Scotland compared the accuracy of diagnosing urinary tract infection in infancy with urine cultures obtained by clean-catch urine (CCU) collection and cultures obtained by suprapubic aspiration (SPA). They obtained 58 paired urine specimens, by CCU collection and SPA, from 49 infants younger than 24 months with suspected urinary tract infection (some patients were used in more than one pair). Cultures were considered positive if they grew more than 105 colony-forming units/mL of a single organism from CCU or any organism from SPA. Cultures of CCU­collected specimens had a false-positive rate of 5% (95% specificity) and a false-negative rate of 12% (88.9% sensitivity), compared with specimens collected by the gold-standard SPA. Investigators noted that these rates of false positives and false negatives are much lower than those in other investigations, which they attributed to good CCU collection techniques resulting from adequate instruction of parents of infants in the study. They conclude that CCU collection is a reliable technique for obtaining urine specimens from infants, though invasive specimen collection remains the technique of choice for urine collection in sick febrile infants who merit rapid initiation of therapy (Ramage IJ et al: J Pediatr 1999;135:765).

Commentary: This study evaluates clean-catch urine collection, not sterile bag urine collection. To collect the urine, parents or staff undressed the precontinent children and waited with sterile cup in hand!

The authors endorse this method of urine collection except in the child in whom you want to start antibiotics. Here is why. The positive predictive value (PPV) of a positive CCU culture was 89% in this study, meaning that nearly 90% of positive cultures were true positives. But that was in a population with lots of UTIs (31% prevalence). When the test is applied to a population with UTI prevalence of 5% (a reasonable guess for young children with fever and no source), the PPV would be expected to drop to 48%. That means that more than half of positive cultures would be false positives. If you are starting antibiotics and can't go back for a confirmatory, repeat culture, you may want to stick with a gold standard SPA or at least a catheterized urine specimen. And that way you won't have to duck.

CFS associated with Ehlers-Danlos syndrome

A new study shows that chronic fatigue syndrome (CFS), which is known to be associated with orthostatic intolerance, also is related to Ehlers-Danlos syndrome (EDS), a heterogeneous group of inherited abnormalities of connective tissue characterized by skin hyperextensibility, joint hypermobility, and fragility of connective tissue.

Of about 100 adolescents and young adults examined in a CFS clinic during a one-year period, 12 (11 girls and one boy) were identified with EDS as well as CFS. In addition to meeting diagnostic criteria for these two disorders, these 12 patients, who had a median age of 15, also had either orthostatic tachycardia or neurally mediated hypotension in response to orthostatic stress.

Investigators concluded that some patients with CFS and orthostatic intolerance also have EDS and that their number is larger than could be attributed to chance. This suggests, they say, that in patients with CFS clinicians should pay particular attention to the family history and examine the patient for joint hypermobility and cutaneous features of EDS. Establishing a diagnosis of EDS in patients with CFS could avoid unnecessary diagnostic evaluations and promote preventive measures for known EDS complications, such as easy bruising, joint hypermobility, hernias, scoliosis, and subcutaneous nodules (Rowe PC et al: J Pediatr 1999;135:494).

Commentary: This group of investigators continues to expand our understanding of chronic fatigue syndrome as a complicated, multifactorial disease. I admire their patience and flexibility in dealing with this diverse group of patients.

Homosexuality and mental health problems

A 21-year longitudinal study of more than 1,000 children born in New Zealand shows that gay, lesbian, and bisexual young people are at increased risk of mental health problems. When the young people were 21 years old, investigators questioned them about their sexual orientation, and 20 (2%) identified themselves as gay, lesbian, or bisexual. To examine the association between sexual orientation and psychopathology, investigators used interviews and tests at various times when the study subjects were between the ages of 14 and 21 to uncover major depression, generalized anxiety disorder, conduct disorder, nicotine dependence, alcohol and other illicit substance abuse or dependence, and suicidal behaviors. Youths who were gay, lesbian, and bisexual were from 1.9 to 6.2 times more likely than other youths to have a psychiatric disorder. They were at especially high risk of having several of these disorders and of suicidal behavior. These results appeared to apply to both men and women.

Investigators also compared social, family, and childhood characteristics for gay, lesbian, and bisexual youths with the control group. This comparison revealed just two distinguishing factors: Gay, lesbian, and bisexual youths tended to have experienced more parental change (such as divorce, death, or remarriage) during childhood and were more likely to have parents with a history of criminal offenses than the control group (Fergusson DM et al: Arch Gen Psychiatry 1999; 56:876).

Commentary: This article and others that have come to the same conclusion have generated ongoing discussion in the psychiatric literature about the causes of this association. As pediatricians we need to keep the link in mind as we care for and counsel homosexual adolescents.

Enterovirus 71 implicated in fatal epidemic

In 1998, an epidemic of enterovirus 71 caused about 90,000 cases of hand, foot, and mouth disease in Taiwanese children. The epidemic resulted in 400 hospitalizations and 78 deaths. Investigators recently described the clinical course of 154 children with culture-proven EV71 infection during this epidemic. The children were divided into three groups: 11 patients with pulmonary edema, 38 patients with central nervous system (CNS) involvement and no pulmonary edema, and 105 children with no complications. Investigators compared the clinical features, laboratory findings, risk factors, and outcomes in these three groups.

Of the 11 children with pulmonary edema, nine had hand, foot, and mouth disease, one had herpangina, and one had febrile illness; eight of these children had limb weakness and one had limb hypesthesia. In all these children, tachycardia, tachypnea, and cyanosis began suddenly one to three days after onset of disease. All 11 children died—nine within 12 hours of intubation and the other two within three months. In the 38 children with CNS complications and no pulmonary edema, one child died of pneumonia after four months of ventilator support and four children had sequelae. All 105 children without complications recovered completely.

Investigators concluded, based on clinical manfestations, cerebrospinal fluid studies, image results, and necropsy findings, that neurogenic pulmonary edema was the cause of death in this epidemic. Hyperglycemia was the most significant risk factor, and prognostic factor, for development of pulmonary edema. Leukocytosis and limb weakness also were risk factors (Chang L-Y et al: Lancet 1999;354:1682).

Commentary: Here's a sobering quote from the authors: "In the absence of a readily available vaccine and effective therapy, EV71 could replace poliomyelitis as a cause of paralytic disease and death with bulbar encephalitis in young children."

Medication works best for core ADHD symptoms

The first long-term comparison of pharmacotherapy and behavior therapy for attention deficit hyperactivity disorder (ADHD) shows that over a 14-month period, medication management with methylphenidate (Ritalin) is superior to behavioral treatment for the core ADHD symptoms, inattention and hyperactivity-impulsivity.

Investigators working at six sites across the country assigned 579 7- to 10-year-old children with ADHD to one of four different treatment groups for 14 months:

• Medication management (titration followed by monthly visits)

• Intensive behavioral treatment (parent training, a school-based intervention, a therapeutic summer camp, and interaction with a therapist that decreased over time)

• A combination of medication management and behavioral treatment

• Standard community treatment (generally including medication).

Symptoms in all four groups decreased significantly over time—but the degree of change varied substantially. Like medication management, combined treatment was superior to behavioral treatment for ADHD symptoms, according to parents' and teachers' ratings of inattention and hyperactivity-impulsivity. Combined treatment also provided significant benefit for non­ADHD symptoms and functioning, such as oppositional/ aggressive symptoms, depression and anxiety, social skills, parent-child relations, and reading achievement. In these areas, combined treatment was superior to intensive behavioral treatment, community care, and, to a lesser extent, medication treatment (The MTA Cooperative Group: Arch Gen Psychiatry 1999; 56:1073).

Commentary: This is an endorsement for careful, well-monitored use of medication therapy for ADHD. We need to be aware of concerns about overuse of these medications, while recognizing that many children benefit tremendously from them. The medication group in this study was not simply started on medication and ignored. The choice of medication, dosage schedule, and dosage were carefully adjusted. The children were seen monthly not only to detect side effects, but to offer support and encouragement. Monthly evaluations also included systematic, regular feedback from teachers. Investigators speculate that this intensive management may explain the medication group's success compared with the group treated in the community, whose therapy often included medication.

Also of note

Zinc prevents disease in developing countries. In response to strong evidence that zinc deficiency is related to childhood infections, investigators conducted a pooled analysis of original data from 10 trials of zinc supplementation in nine developing countries. In all the trials, children younger than 5 years took oral supplements containing at least one half the United States Recommended Daily Allowance of zinc and were evaluated for the effects of the supplement in preventing serious infectious illness. Reductions in incidence and prevalence of diarrhea in the zinc-supplemented children were about 18% and 25%, respectively, compared with a control group. Pneumonia incidence was reduced by 41%. (Bhutta ZA et al: J Pediatr 1999;135:689).

Many but not all parents are responding to airbag dangers. Some drivers are responding to the much-publicized hazard of passenger airbags by seating children in the rear of their cars, a new study finds. At least one in six New England drivers still seats children younger than 13 in front of airbags, however. Children traveling with unbelted drivers or alone with one parent and children who are older than 6 years are most likely to be seated in the right front seat of the car (Wittenberg E et al: Pediatrics 1999; 104:1247).

Lighten up those backpacks! To determine if heavy backpacks may be contributing to increasing rates of low back pain in children, investigators studied 237 children in Milan, Italy, during a three-week period. It has been proposed that children carry a maximum load of 10% to 15% of body weight. Yet children in the study, whose mean age was 11.6 years, carried more than 30% of their body weight at least once during each six-day school week, investigators determined. The average load carried was 9.3 kg or 22% of body weight. Findings in this study, along with others showing that backpack load contributes to low back pain in children, suggest that measures should be taken to ensure that children do not carry heavy backpacks (Negrini S et al: Lancet 1999;354:1974).

CLINICAL TIP

Cutting a bandage problem down to size

Large adhesive bandages, which are necessary for some wounds, are difficult to apply to little fingers because the adhesive tails are longer than the diameter of the finger. I snip off half of one tail of the bandage and apply the short tail first. This makes it easier to remove the bandage as well as put it on.

Jerome T. Combs, MD

New Haven, CT

Do you have a Clinical Tip to share with colleagues? Let us know; we'll pay $50 for each item accepted for publication. Tips sent by mail should be addressed to Molly Frederick, Clinical Tips Editor, Contemporary Pediatrics, 5 Paragon Drive, Montvale, NJ 07645-1742. If you submit by E-mail (Molly.Frederick@medec.com), please include your mailing address.

CLINICAL TIP

A reassuring loss of face

When I examine a child between 9 months and 2 or 3 years of age, I hide my face to get the child to relax. I sit in front of the parent, who holds the child on her lap or shoulder. Then I put my free hand on my forehead as though I were shading my eyes. Removing the threat of a stranger's face so close helps most children relax. I'm then free to examine the lungs, heart, and abdomen.

Ron Dionne

Bremerton, WA

Do you have a Clinical Tip to share with colleagues? Let us know; we'll pay $50 for each item accepted for publication. Tips sent by mail should be addressed to Molly Frederick, Clinical Tips Editor, Contemporary Pediatrics, 5 Paragon Drive, Montvale, NJ 07645-1742. If you submit by E-mail (Molly.Frederick@medec.com), please include your mailing address.

Marian Freedman. Journal Club.

Contemporary Pediatrics

2000;2:147.