Never give up

In 1992, the paediatric network for treatment of AIDS (PENTA) began to recruit children for an RCT of zidovudine (ZDV). As it became clear in adults that combination therapy was superior to ZDV, the paediatric trial was terminated in October 1995.

Vital information has nonetheless become available and appears in this month's ADC (page 230). When the trial was unblinded, parents of children receiving ZDV were offered a second drug and those who had received placebo started on combination therapy. One result is that the trialists are now able to compare the results of children starting “late” or “early” on mono, dual, or triple therapy.

The authors found no evidence of benefit in favour of early ZDV monotherapy. At three years from trial entry, 14% of children had progressed to AIDS or had died. However, progression was significantly lower in 1997–8, probably because more children received dual therapy in later years. This study does not answer the question of when to start antiretroviral therapy but the authors claim that slow disease progression in untreated infants and potential drug toxicity means that a case can be made for delaying therapy in asymptomatic children. US guidelines advise treating all HIV infected children diagnosed in their first year. We look forward to transatlantic rapid responses to the findings of the PENTA-1 trial.

Save the NHS, use fewer venflons®

A Swiss group have compared 3 days of intravenous cephalosporins followed by 12 days of oral cephalosporins with 10 days of intravenous cephalosporins and 5 days of oral cephalosporins as treatment for pyelonephritis (page 241). Their aim was to see whether there was any difference in subsequent renal scarring, as evidenced by DMSA scanning. A secondary outcome was recurrence within 3 months despite trimethoprim prophylaxis. Even with all sorts of sub-group analysis, the authors were unable to show any benefit from prolonged IV therapy. Whatever you do, scars probably develop in about 1 in 3.

The authors deal with the obvious question by pointing out that 36% of their patients with pyelonephritis vomited, and outpatient treatment may not always be complied with so that they are not keen on oral medication alone.

And cardiorespiratory monitors

Talking of compliance, what do parents do if you give them a sophisticated cardiorespiratory monitor to assuage their fears over SIDS (or better still stop it happening to their babies) (page 270)? The study group were 39 preterm babies for whom apnoea had been a problem, 13 sibs of children who had succumbed to SIDS, and 16 who had experienced acute life-threatening events (ALTE) were evaluated, educated, trained, supported and followed up. You might wonder how any would presume to be non-compliant but 13% of parents of prems, 7% of those with ALTEs, and a stunning 46% of those who had already lost a child to SIDS failed to monitor their baby daily.

Could it be that doctors are more anxious than parents?

New insights in cerebral malaria

We are particularly pleased to publish a meticulous study from Kenya, looking at what happens to the electroencephalogram of children with cerebral malaria (page 247). Two thirds of the 65 patients had seized before admission and in more than half this heralded coma, 75% being deeply unconscious on arrival at hospital—only a minority because of a post-ictal state.

The authors report, as a striking feature, consistent ictal localisation over the posterior temporo-paretal areas, a recognised “watershed” site.

Fifteen children had electrographic changes only. In others, seizure activity persisted for up to 140 minutes (median 45 minutes) after successful clinical resolution with diazepam.

The authors conclude that seizures are important in the pathogenesis of coma as well as traditionally recognised events such as raised intracranial pressure, anaemia, hypoglycaemia, and cytokine release. The most likely cause is cerebral hypoxia; certain EEG features seem to carry a poor prognosis and the authors hope that the information they provide may help gain insight into other paediatric encephalopathies.

Closer to home

Encephalopathies in Europe are more likely associated with non-traumatic coma, which has an incidence of about three per 10 000 children annually. The paediatric neuroscience group at Newcastle upon Tyne (UK) has recruited 278 such children (page 193). About a third presented with CNS related symptoms, nearly half with systemic findings such as fever, lethargy, poor feeding and shortness of breath and the remainder with signs suggesting other organ system involvement, such as a rash or sore throat.

Infection was the commonest cause, followed by “unknown”, intoxication, epilepsy, and metabolic disease. Those anxious about missing rare metabolic disorders will be relieved to learn that just three children previously undiagnosed (all with MCAD deficiency) first presented in coma.

In a companion paper (page 200) Forsyth and colleagues describe their follow up of survivors at 6 weeks and 12 months. Their particular interest was how much age at insult affected outcome. At least 7% of apparently previously normal children suffered significant post-event disability; early age at first insult was associated with poor outcome.