126 e-Letters

published between 2016 and 2019

  • Comment on “Economic cost of congenital CMV in the UK” by Retzler et al.

    Retzler et al. report estimates of the economic cost of congenital cytomegalovirus (cCMV) in the United Kingdom.1 The projected costs of autism spectrum disorder (ASD) among persons with cCMV accounted for at least 50% of the total costs attributed to cCMV. However, an association between cCMV and ASD has not been conclusively established,2 and, in their analysis, Retzler et al. did not take into account the cost of ASD among children without cCMV.

    Retzler et al. used published ASD prevalence estimates from a Dutch study of >30,000 children screened for cCMV at 6 years of age using stored dried blood specimens, of whom 133 were CMV-positive. Of 26 children classified with symptomatic cCMV, 2 (7.7%) had ASD, as did 2/107 (1.9%) with asymptomatic cCMV.3 Retzler et al. assumed 11% of children with cCMV are symptomatic, which implies a weighted average ASD prevalence of 2.5% among children with cCMV. Five of 274 (1.8%) matched children without cCMV in the Dutch study also had ASD. If ASD were causally associated with cCMV, which has not been shown, the cost of ASD attributable to cCMV would be the cost difference of ASD among children with and without cCMV. Therefore, the projected cost of cCMV has been overestimated. Moreover, if the reported association of cCMV with ASD turns out to be non-causal, the total cost of cCMV could be half that estimated by Retzler et al.

    1. Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV...

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  • Recent insights into the role and dose of aspirin in acute Kawasaki disease

    I would like to add to the article ‘What dose of aspirin should be used in the initial treatment of Kawasaki disease?’ by Luke Guo Yang Ho and Nigel Curtis (Archives, 2017, 102, 1180-1182). Fifteen months have passed since this article concluded that low-dose aspirin is not inferior to higher doses in reducing the risk of coronary artery abnormalities in acute Kawasaki disease. Since then, it is worth considering what and if anything has changed in the field. A recent study not included in the review is a retrospective cohort study by Huang et al1 (2018), where 910 patients followed up for 2 years, which showed that there was no significant difference between 3 groups in terms of anti-inflammation or prevention of coronary artery abnormalities. This paper concluded that the role of aspirin in the treatment of the acute phase of Kawasaki disease should be questioned, as a definite benefit has not been shown. Therefore, in concordance with the conclusion of the review, this rapid response poses that current data remains unchanged with regards to the role and effects of administration of higher doses of aspirin on coronary outcome in acute Kawasaki disease. In the absence of evidence to support higher doses in prevention of coronary artery abnormalities, low-dose aspirin (3–5 mg/kg) may be the safest, most rational approach until better evidence becomes available.

    There are currently three prospective randomised control trials in process to continue this inv...

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  • Milk and respiratory problems. Why is the myth persisting over the facts? The power of information

    Authors (full names and academics degrees)
    • Laura Moreno-Galarraga1 MD PhD
    • Miguel Ángel Martínez-González2 MD PhD MPH
    • Diego Mauricio Peñafiel Freire3 MD
    • Elsie M Taveras4 MD MPH

    1) Department of Pediatrics, Complejo Hospitalario de Navarra. IdisNa; Instituto de Investigación Sanitaria de Navarra, Health Research Institute of Navarra, Pamplona, Spain.
    2) Department of Preventive Medicine and Public Health, University of Navarra Pamplona, Spain. Dpt. Nutrition, Harvard TH Chan School of Public Health, Boston, MA. CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain.
    3) Department of Pediatrics, Complejo Hospitalario de Navarra, Pamplona, Spain
    4) Division of General Academic Pediatrics, Massachusetts General Hospital for Children, Boston, MA; Department of Pediatrics, Harvard Medical School, Boston, MA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.

    Dear Editor;

    We have read the article about myths, milk and mucus, and we couldn’t agree more.1 We have observed the prevalence of the same myth and the same concern that many parents are limiting their child’s consumption of dairy products or replacing milk with vegetable drinks, despite the current recommendations.2

    We conducted a study in 169 school-age children in Spain and we did not find any association between dairy products consumption (milk, cheese or yo...

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  • Palivizumab for children with Down syndrome: is the time right for a universal recommendation?

    We thank Drs Bok et al. for their comments on our recent editorial about the use of palivizumab in children with Down syndrome (DS).[1] However, most of their arguments are not pertinent to DS. First, they describe the general incidence of respiratory syncytial virus (RSV) in children aged <5years. Second, they discuss the efficacy of palivizumab based on the IMpact trial [2] that did not include children with DS. We provided concrete evidence from [3] metanalyses conducted in 1.1 million children with DS, that the risk of RSV-related hospitalisation (RSVH) is 6.1–8.7- fold higher than children without DS.1 Drs Bok et al. also fail to appreciate that the overall relative risk of RSVH without palivizumab, is 5.5-fold (95% CI 3.97 to 7.7) higher based on robust, high quality evidence.[3] In our previous study we also reported that for every 1000 children with DS with RSV there will be 200 more (95% CI,131-297) hospitalisations compared with 1000 children without DS with RSV (RR, 5.53; 95% CI,3.97-7.73; high GRADE).[4] Moreover, Drs Bok et al. have extrapolated the number needed to treat (NNT) with prophylaxis to prevent one RSVH in children with DS using sub-optimal data. In a prospective case-control, cohort study conducted in the Netherlands and Canada, the estimated NNT in children with DS, adjusted for confounding variables, is 12 and not 20.[5] This number also aligns with the report from the CARESS registry [6] and compares favourably with the NNT of 16 for preter...

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  • Comment to Response by M Nadeem to Letter ‘Meningococcal Meningitis Post-Infant Group B Meningococcal Immunisation’

    Dear Sir,

    We thank Dr Nadeem, for highlighting that the clinical features of drowsiness and infant focal seizures in our case report indicates that early treatment for viral/herpes encephalitis was an imperative.

    We would like to reassure Dr Nadeem that our infant did indeed receive a combination of early intravenous antiviral treatment (acyclovir) and antibiotics (cefotaxime and amoxicillin) and this was continued until final viral/bacterial PCR and CSF culture results were obtained. The use of acyclovir and amoxicillin was omitted from the original report due to word count limitations.

    Viral PCR tested was negative for a range of viruses including herpes simplex (HSV). Although PCR assay is an important diagnostic modality for viral encephalitis HSV, we would add that due to focal seizures, our infant case received investigations and treatment as per national (1) and local guidelines: immediate brain CT imaging was performed to exclude neurosurgical conditions, and a later cranial MRI scan did not show selective damage to the mesial temporal lobe structures or the hippocampus. In addition, an early electroencephalogram (EEG) was normal. The EEG severity and the presence of epileptic seizures at the initial presentation would be significant indicators for predicting the 6-month clinical outcome in patients with HSE.

    The seriousness of HSV CNS infections suggests that clinicians maintain a high index of suspicion to initiate evaluation under s...

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  • Response to letter re: ‘Improving newborn and infant screening’

    We thank Dr Cliona M Ni Bhrolchain  for her interest in our paper and her comments.  With the exceptions of newborn hearing and blood spot screening,  there is unacceptably wide variation at local level and a lack of commitment at national level in implementation and monitoring of preventive child health programmes.   We suggest that this is just one manifestation of a wider problem - the serious inadequacy of NHS investment  in leadership, education and training, both in general practice and in the specialties.  Morale is low and there are chronic shortages of staff with the relevant skills, when medicine is changing and public expectations rising faster than ever before. 

    David Hall and David Sowden (affiliations as on our original paper)


    I refer to the paper published by Palmer et al in Archives Diseases Childhood March 20181 that states the recommendation to avoid tramadol when breastfeeding and the contraindication to its use in children (including neonates) is inappropriate in their view. 1
    I disagree with the authors that tramadol is a safe for babies of breastfeeding mothers. Their conclusion, in my opinion, is premature and not adequately evidence-based. While they acknowledge, the US Food and Drug Administration (FDA) reported cases, they ignore the serious warnings by both Manufacturer and FDA about administering tramadol to children and breast-feeding mothers. There is increasing concern that narcotics used for treating pain in breastfeeding mothers may increase the risk of adverse effects in newborns, including excessive sedation and respiratory depression. The American Academy of Pediatrics (AAP), the FDA and the American College of Obstetricians and Gynecologists (ACOG) advocate against the use of codeine and tramadol in women who are breastfeeding because their babies may suffer adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems. 2-5 Patient safety should be foremost in our minds in making any recommendations that are contrary to Manufacturer, FDA, and AAP recommendations. It would be difficult to justify use of tramadol in a breastfeeding mother in the event of litigation arising from adverse effects of tramadol in the baby...

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  • Over-estimation of association between SUDIC and chronic conditions

    We welcome the paper by Verfurden et al1 on avoidable mortality from RTI and SUDIC with chronic conditions. We do not doubt the conclusion that chronic conditions are strongly associated with deaths from RTI, but disagree with the conclusion that chronic conditions are also associated with SUDIC or the need for changes to death certification.
    The study excludes deaths of infants less than 2 months old; however the peak age for unexplained infant deaths (classified as SIDS or unascertained) is 6 weeks. Data from England for the years 2004-10 show that 45% of unexpected infant deaths occurred prior to 2 months of age2, with the exception of those infants with congenital anomalies it is unlikely that these infants will have been diagnosed with a chronic condition by the time of death. Due to these issues, the study is likely to have significantly over-estimated the association of chronic conditions with SUDIC and we would invite the authors to revise their conclusion.
    The authors suggest that death registrations and hospital databases should categorise deaths as expected or unexpected to help identify potentially preventable deaths. Child Death Overview Panels in England review all deaths, determining modifiable factors; and these reviews are to be collated nationally by the new established National Child Mortality Database. A similar system of Child Death Reviews has already been recommended by the Scottish Government. It would seem more sensible to fully embrace...

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  • Palivizumab for children with Down syndrome: is the time right for a universal recommendation?

    In their editorial Paes and Mitra suggest that all patients with down syndrome (DS) <2 years should be considered to give palivizumab (Synagis®) to prevent respiratory syncytial virus (RSV) infection. We agree with the authors that DS children are at increased risk to develop RSV infections. However, we do not agree with their recommendation for palivizumab prevention in all DS children <2 years. In our opinion there is insufficient evidence on the efficiency and cost effectiveness and the recommendation is therefore premature.
    For the evaluation of preventive interventions the incidence and the absolute risk of acquiring the disease, and the effectiveness of the proposed intervention are important factors. The reported incidence of clinical relevant RSV infections in the general population in western countries is about 18/1,000 in newborns <2 months, 17/1,000 in children <6 months and 3/1,000 in children <5 years ( 2,3). Considering a relative extra risk of 5.5 in DS children (1) the calculated RSV incidence is 99/1,000 <2 months ( one out of 10) , 94/1,000 <6 months and 17/1,000 <5 years, respectively. The effectiveness of prevention of clinical treatment in premature children with palivizumab is about 50% (4). The extrapolated number needed to treat (NNT) for newborns with DS is 20 to prevent one hospitalization due to RSV infection. But what is the harm of this treatment as 19 out of 20 DS newborns will be given 114 injections per year...

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  • Relevance of specific HLA-DQ allelic components in the screening strategies for pediatric Celiac Disease

    We read with interest the recent article published by Binder E et al. [1], describing the HLA-DQ analysis performed in 1624 asymptomatic children affected with type I Diabetes Mellitus (DMT1), in order to assess their predisposition to develop Celiac Disease (CD). They reported that 1344 (82.8%) patients resulted to be "HLA-DQ2 and/or -DQ8 positive", whereas 280 (17.2%) were negative: among the former group, a biopsy-proven CD diagnosis was documented in 3.6% of cases and, interestingly, even 7 patients in the second group (corresponding to 2.5%) resulted to be celiac. [1]
    Thus, these two percentages are not so different and one might conclude that the HLA-DQ asset is not a necessary - even if not sufficient - genetic background, contrary to what is well known. [2] Indeed, the absence of alleles coding MHC-DQ2 and/or MHC-DQ8 heterodimers, is associated with an almost absolute negative predictive value with respect to CD. Therefore, in order to solve this apparent mismatch, it would be useful if the authors can show the complete and high-resolution HLA-DQA1 and, in particular, HLA-DQB1 typing: indeed, these 7 “HLA-DQ2 and/or -DQ8 negative” CD children may not carry all alleles coding any complete MHC-DQ2 and/or MHC-DQ8 molecule, but they may have one or two allelic variants conferring CD risk anyway, such as HLA-DQB1*02, which codes the beta chain of MHC-DQ2 heterodimer. Indeed, according to several studies, the isolate presence of one or two copies of this...

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