pediatric

Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial.

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Background

Little evidence is available for the effect of nebulised magnesium sulphate (MgSO4) in acute asthma in children. We assessed the effect of MgSO4 treatment in children with severe acute asthma.

Methods

In this randomised placebo-controlled, multi-centre, parallel trial, we enrolled children (aged 2—16 years) with severe acute asthma who did not respond to standard inhaled treatment from 30 hospitals in the UK. Children were randomly allocated (1:1) to receive nebulised salbutamol and ipratropium bromide with either 2·5 mL of isotonic MgSO4 (250 mmol/L; 151 mg per dose; MgSO4 group) or 2·5 mL of isotonic saline (placebo group) on three occasions at 20-min intervals. Randomisation was done with a computer-generated randomisation sequence, with random block sizes of two to four. Both patients and researchers were masked to treatment allocation. The primary outcome measure was the Yung Asthma Severity Score (ASS) at 60 min post-randomisation. We used a statistical significance level of p<0·05 for a between-group difference, but regarded a between-group difference in ASS of 0·5 as the minimal clinically significant treatment effect. Analysis was done by intention to treat. This trial is registered with controlled-trials.com, number ISRCTN81456894.

Findings

Between Jan 3, 2009, and March 20, 2011, we recruited and randomly assigned 508 children to treatment: 252 to MgSO4and 256 to placebo. Mean ASS at 60 min was lower in the MgSO4 group (4·72 [SD 1·37]) than it was in the placebo group (4·95 [SD 1·40]; adjusted difference −0·25, 95% CI −0·48 to −0·02; p=0·03). This difference, however, was not clinically significant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). We detected no difference in the occurrence of adverse events between groups.

Interpretation

Overall, nebulised isotonic MgSO4, given as an adjuvant to standard treatment, did not show a clinically significant improvement in mean ASS in children with acute severe asthma. However, the greatest clinical response was seen in children with more severe attacks (SaO2<92%) at presentation and those with preceding symptoms lasting less than 6 h.

Source: lancet

 

Metreleptin improved metabolic parameters in children with lipodystrophy .

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Positive results from an NIH-supported analysis indicate an investigational recombinant analogue of human leptin has potential as a therapy for pediatric lipodystrophy, according to data presented at the 2013 Pediatric Academic Societies Annual Meeting.

The literature has established that lipodystrophy is known to cause metabolic abnormalities (ie, hypertriglyceridemia, insulin resistance, diabetes andsteatohepatitis), which tend to become severe through childhood and adolescence, and may be resistant to current treatment options.

Rebecca Brown, MD, assistant clinical investigator of the diabetes, endocrinology and obesity branch at the National Institute of Diabetes and Digestive and Kidney Diseases, and colleagues included pediatric patients in an ongoing, open-label study at the NIH (2000 to present).

According to abstract data, patients included in the study (n=39; nine male and 30 female; mean age, 11.9 years) had four subtypes of the disease: congenital generalized lipodystrophy (n=26, 67%), acquired generalized lipodystrophy (n=9, 23%), familial partial lipodystrophy (n=2, 5%), and acquired partial lipodystrophy (n=2, 5%).

On average, the researchers administered metreleptin 4.4 mg (Bristol-Myers Squibb and AstraZeneca) subcutaneously once or twice daily for a mean duration of 3.9 years.

Data indicate that baseline HbA1c (9.8%) decreased significantly to 7.7% after 12 months (–2.3; 95% CI, –3.2 to –1.4) in adolescent patients aged 12 to 18 years.

Triglycerides were notably high in the same group at baseline (1,378 mg/dL), but improved significantly to 385 mg/dL after 12 months (–44; 95% CI, –73 to –15), according to data.

Both age groups displayed significantly elevated mean alanine aminotransferase (ALT; ≤12 years: 193 U/L; adolescents: 105 U/L) and aspartate aminotransferase (AST; ≤12 years: 119 U/L; adolescents: 87 U/L) at baseline. However, ALT (≤12 years: 155 U/L; adolescents: 59 U/L) and AST (≤12 years: 90 U/L; adolescents: 57 U/L) decreased after metreleptin therapy, according to data.

“Metabolic disorders resulting from lipodystrophy can develop in childhood and adolescence and are exacerbated over time,” Brown said in a press release. “This new analysis supports the continued study of investigational metreleptin as a potential treatment option for pediatric patients with lipodystrophy.”

Overall, metreleptin was well tolerated, and the most common adverse events reported were decreased weight (n=3, 7.7%) and hypoglycemia (n=3, 7.7%), followed by fatigue (n=2, 5.1%) and nausea (n=2, 5.1%), the researchers wrote.

According to the press release, metreleptin has acquired orphan designation from the FDA, and the European Medicines Agency is evaluating the agent.

  • o    Source: Endocrine Today