Household transmission of community MRSA
Community-associated methicillin-resistant Staphylococcus aureus (cMRSA) skin and soft tissue infections are common and often transmitted within families. A longitudinal US study examined risk factors for transmission of cMRSA within families.1 The study group was 236 children who presented with cMRSA infections and had no risk factors for hospital-acquired infection and 712 household contacts. Home visits conducted within 90 days of presentation (average 69 days) found MRSA nasal colonisation in 13% of previously infected children and 12% of their household contacts; both figures are lower than in other studies. Risk factors for colonisation of household contacts were that the contacts helped bath the child and that they shared skin products like lotions, balms or ointments with the child. Contacts who used antibacterial soap for washing hands, as compared to ordinary soap, had a lower incidence of MRSA colonisation. These data can provide useful advice to the families of infected children on ways to reduce household transmission.
Reviewer: David Isaacs (email@example.com), The Children's Hospital at Westmead, Westmead.
Leukotriene antagonists in asthma
A recent article on adults with asthma describes a new style of clinical trial, a pragmatic trial.1 The purpose of the pragmatic design is to take into account the vagaries of clinical practice and simulate ‘real life’. This trial highlights the difficulties in the performance, reporting and interpretation of such trials. The paper includes two parallel, multicentre pragmatic trials that compare leukotriene antagonists and inhaled corticosteroids as ‘first line’ (n= 306) and ‘add on’ (n= 352) asthma controller therapy in a primary care setting in the UK. The primary outcome measure was the Mini Asthma Quality of Life Questionnaire (AQLQ). In both trials, there was no difference between groups in the mini AQLQ score or in secondary outcome measures at 2 months or at 2 years. However, there are many factors producing potential bias favouring equivalence, including enrolment of patients without asthma (e.g. chronic obstructive pulmonary disease), poor adherence, open label design, use of concomitant therapy, lack of placebo and lack of objective outcome measures. We are concerned that because this is published in such a high-impact journal, busy clinicians may misinterpret it as ‘proof of equivalence’ between the two therapies. As pointed out in the accompanying editorial,2 although this paper provides a useful focus for discussion of pragmatic trials, the result should be viewed with caution.
Reviewers: John Widger and John Massie (firstname.lastname@example.org), Royal Children's Hospital, Melbourne
Intermittent budesonide in preschool children with recurrent wheezing
Recurrent wheeze in pre-school children, most commonly caused by viral infections, is hard to prevent. Predictive tools such as the asthma predictive index and the more recent European Respiratory Society Task force proposed ‘multiple trigger wheeze’ can identify children at highest risk of developing true allergic asthma who are more likely to respond to regular inhaled corticosteroid (ICS)-based preventer therapy.
The authors of the current study1 previously showed benefit with nebulised budesonide 0.5 mg daily compared to placebo in this ‘at-risk’ group. Here they compare this daily regimen to intermittent high dose budesonide (1 mg twice daily with respiratory illness) in pre-school children who had an average of seven episodes of wheeze per year, at least one requiring oral steroids, with some or no interval symptoms.1 No difference in outcomes was seen despite intermittent budesonide therapy reducing the total yearly dose of budesonide administered by two thirds compared to daily use.
This non-inferiority style study is of interest as we look for ways to achieve symptom benefit whilst minimising ICS side effects (although no difference in height between the groups occurred in this study). However, nebulised budesonide is now rarely used in many countries and these results must not be extrapolated to metered-dose inhaler (MDI) administered ICS which may deliver a different dose to the lung. A previous study using intermittent high-dose fluticasone was associated with a significant reduction in growth over 6–12 months (median 40 weeks) compared to placebo.2 Further studies of MDI based therapy are therefore needed to evaluate intermittent high dose ICS for this indication.
Reviewers: Paul Robinson (email@example.com) and Peter Van Asperen, Department of Respiratory Medicine, The Children's Hospital at Westmead, Westmead.
Genetic risk and cell-mediated immunity in multiple sclerosis
Epidemiological studies in multiple sclerosis have shown a substantial increase in frequency of the disease in relatives of affected individuals. Studies of multiple families have shown that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Genome-wide association studies have identified more than 20 additional risk loci, and have shown that multiple variants with modest individual effects have, when summed, a key role in disease susceptibility. The genetics of multiple sclerosis are very complex and will require very large cohorts for definitive studies. This large collaborative genome-wide association study involved 23 research groups in 15 different countries, and included data from 9772 cases and 17 376 controls.1 The study replicated previously identified associations and identified at least 29 novel susceptibility loci. The study refined the identified HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies a protective effect attributable to the class I region. The identified loci are heavily weighted towards immunologically relevant genes, supporting evidence from many other studies that T-helper-cell differentiation is very important in the pathogenesis of multiple sclerosis.
Reviewer: Monique Ryan (firstname.lastname@example.org), Royal Children's Hospital, Melbourne.