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Recent eLetters

Displaying 1-10 letters out of 96 published

  1. How to interpret malaria tests

    Dyer et al. wrote an instructive review on how to interpret malaria tests (1). However there are two important caveats in the interpretation of these tests which they did not mention. First, a positive test does not necessarily confirm a diagnosis of malaria. Second, a positive test does not necessarily mean that malaria is the only diagnosis.

    Strictly speaking, the tests described by Dyer et al. are parasite detection tests rather than malaria tests, since the diagnosis of malaria requires that there is symptomatic infection with a Plasmodium species. This is not just a semantic point. Children who live in a malaria endemic country may develop naturally acquired immunity with repeated infections (2, 3). This immunity decreases the likelihood of developing symptoms during infection and permits the asymptomatic carriage of blood stage parasites. Children from high transmission countries who are visiting or migrating to the UK and develop a febrile illness may be found to have a positive parasitological test, but their illness may have a totally different cause. In these cases it is always sensible to treat for malaria, but a high index of suspicion of another cause should be maintained, particularly if the child is seriously ill.

    Related to this, there is a well-recognised association between malaria and risk of invasive bacterial infection (4). Children with malaria are more likely to develop Gram-negative bacteraemia, particularly infection with non-Typhoidal Salmonella. For this reason, it should not be assumed that a positive parasite detection test in an unwell febrile child makes a diagnosis of malaria and excludes another infection. Recent guidelines recommend the prudent approach that any child with features of severe malaria should be treated with broad spectrum antibiotics until it is clear that there is no co-infection (5).

    1. Dyer E, Waterfield T, Eisenhut M. How to interpret malaria tests. Arch Dis Child Educ Pract Ed 2016;101(2):96-101. 2. Crompton PD, Moebius J, Portugal S, et al. Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease. Annual review of immunology 2014;32:157-87. 3. White NJ, Pukrittayakamee S, Hien TT, et al. Malaria. Lancet 2014;383(9918):723-35. 4. Takem EN, Roca A, Cunnington A. The association between malaria and non -typhoid Salmonella bacteraemia in children in sub-Saharan Africa: a literature review. Malar J 2014;13:400. 5. Lalloo DG, Shingadia D, Bell DJ, et al. UK malaria treatment guidelines 2016. J Infect 2016.

    Conflict of Interest:

    None declared

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  2. Re:A different view of studies with deferred consent

    The author makes an interesting point about the current legislation and automatic inclusion of data in trials where prior informed consent is not possible.

    EU legislation focuses on when research without prior consent (RWPC) can occur and the need to obtain consent for continued participation, but does not cover the options for use of data collected prior to consent. The exception to this is where consent is not provided: ???he or she should be informed of their right to object to the use of data obtained from the clinical trial???. Therefore, this situation is open to interpretation.

    We acknowledge the concerns of the letter author regarding not automatically including data. If data are not automatically included there is the potential for bias in the study results if the decision to provide consent for use the data is associated with patient outcome. This could potentially lead to erroneous conclusions with far reaching implications. However, the research community needs to consider the timeframes around stabilisation of the patient with respect to the potential need for continued delivery of the intervention, additional tests and timing of data to be collected after this point. It would be difficult to argue against the current legislation that consent should not be requested here.

    CONNECT and studies conducted in neonatal intensive care indicate that children and parents not only want to be informed, but also want to make the decision about the inclusion of their information in research. One question to reflect on is who ???owns??? the data? If it???s the patient, then they (and their parents) surely have the right to be asked for it to be used.

    We believe that the automatic inclusion of data with an ???opt out??? approach should be limited to circumstances where a face to face discussion with the family has not been possible before they leave hospital, or is not deemed appropriate at that point in time (e.g. when a child had died) and there has been no response to attempts to contact the family. This approach is currently used in a NIHR HTA funded EcLiPSE Study: Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus: http://www.nets.nihr.ac.uk/projects/hta/12127134

    In developing the CONNECT guidance we had to work within UK and EU legislation ??? otherwise our guidance would have been of no practical use. Article 35 of the 2014 EU legislation stipulates that research in emergency situations should only pose ???a minimal risk to, and impose a minimal burden on the subject in comparison with the standard treatment of the subject???s condition???. Our interpretation is that if a trial intervention posed more than a minimal risk, then a REC should not approve the trial. The CONNECT study findings were in keeping with this, showing that parents supported doing RWPC in trials of interventions already used in clinical care, although they were concerned about doing RWPC in trials involving new interventions, or significant changes in clinical practice.

    Conflict of Interest:

    None declared

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  3. A different view of studies with deferred consent

    Thank you for outlining so clearly the current basis for "deferred consent" studies and suggesting good practice in dealing with the issues it raises. Unfortunately I believe that the current practice is the worst of possible worlds: not only do we submit vulnerable subjects to interventions without the expression of their/their parents' autonomy (ie consent), but also we risk losing any data obtained because we retrospectively seek permission to use their data. In other words we would have put the subject at risk/burden with no gain. Current rules of governance for research, based ultimately on the declaration of Helsinki, are designed to protect the subject/society from harm, understanding that ends do not justify means. There is no possibility that the RECs and REC members of which I have experience would approve a study where undue harm could result. I believe that if an REC has approved such a study, this is an endorsement of its relative safety and utility, and should automatically permit inclusion of the data gathered. Retrospectively inform the subject/parents, but do not seek permission for inclusion. If they go as far as requesting withdrawal of the data, then that could be honored.

    Conflict of Interest:

    Member of Research Ethics Committee

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  4. Re: Toe walking in infancy

    We agree that baby walkers and door suspenders can be associated with transient toe walking and delayed walking, which usually would correct spontaneously relatively quickly once the children stop using the device. The use of such devices should be strongly discouraged as part of normal parenting practice. Enquiry regarding inappropriate use of either of these devices in a toddler who has tip toe gait on independent or supported walking can be helpful in evaluation.

    Conflict of Interest:

    None declared

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  5. Not all petechial rashes require admission.

    This was succinct and helpful article. However as a paediatric emergency doctor I would query the phrase "There is still a risk of meningococcal disease even when blood tests are normal; therefore, admit all children for 4-6 hours with hourly observations". It may seem pedantic, but this is not what NICE says. The pathway states "Assess clinical progress (vital signs) and carry out observations at least hourly over the next 4-6 hours." the next step in the full guideline(1) is "If doubt remains, treat with antibiotics and admit to hospital". Even a short hospital admission is several times more expensive than an ED attendance and these children should not automatically be admitted as the great majority can safely be observed then discharged.

    1) National Institute for Health and Care Excellence. Bacterial meningitis and meningococcal septicaemia: management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16?years in primary and secondary care. CG 102. London: National Institute for Health and Care Excellence, 2010

    Conflict of Interest:

    None declared

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  6. Toe walking in infancy

    I read with interest Sivaramakrishnan et al's structured approach to a child with toe walking [1]. Various levels of contexts such as parenting, maternal education, poverty and social networks interact with each other and with genetic expression to create long-lasting consequences for development [2,3]. Sometimes, single or isolated negative environmental factors may make a major contribution to developmental problems with most negative influence occurring in infancy. Here, we discussed two infants without any underlying medical condition who walk on their toes. Case 1: A 18-month-old girl comes with delay the attainment of standing and independent walking. Her perinatal and family history was unremarkable. Her antropometric measurements were all appropriate for his age. Her Denver II was normal at 9 months of age, however, gross motor development was abnormal at 18 months. While the infant was kept standing with holding her arms, she jumped continuously or she did toe walking and she couldn't stand alone. Further history revealed that she had sat on "doorway jumper" as a baby-sitter, 2-3 hours a day for 6 months. Then, parents were urged not to use jumper and put their infant on carpet to crawl and creep. The infant begin to walk alone within three months. Case 2: A 21-month-old boy, presented to our center with toe walking. Her delivery and neonatal-infant course were uneventful. There was no positive family history. He achieved gait at 13 months and walked independently at 16 months. On physical examination weight, height and head circumference were all appropriate for his age. Physical examination revealed intermittent toe walking. His Denver II Test was normal. Specific history revealed that he used a baby walker between 9 and 15 months of age and the infant begin to walk predominantly on the forefoot at 16 months of age. Parents was reassured that it was likely to resolve spontaneously. We advised parents to play "heel down, squate, pick a ball up, stand up". Toe walking was corrected at 23 months of age. The American Association of Pe?diatrics advice against the use of baby walker due to the high number of accidents and the possible delay of gait acquisition related to its use [4]. This is the first report about jumper and delay the attainment of standing. If clinician didn't ask these environmental risk factors, unnecessary analysis, misdiagnosis and inappropriate treatment could be done. We would thus like to emphasize that a child with toe walking should also be assessed for baby walker or jumper. Competing interests: None. References 1. Sivaramakrishnan S, Seal A. Fifteen-minute consultation: A child with toe walking. Arch Dis Child Educ Pract Ed. 2015 Apr 8. pii: edpract-2014-307852. 2. Lagstrom H, Rautava P, Kaljonen A, et al. Cohort profile: Steps to the healthy development and well-being of children (the STEPS Study). Int J Epidemiol 2013;42:1273-84. 3. Yalcin SS, Yurdakok K, Tezel B, et al. Family and infant characteristics in relation to age at walking in Turkey. Turk J Pediatr 2012;54:260-8. 4. American Academy of Pediatrics; Committee on Injury and Poison Prevention. Injuries associated with infant walkers. Pediatrics 2001;108:790-2.

    Conflict of Interest:

    None declared

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  7. The Wiggle Sign

    Dear Editor, We were interested to read the article by Parige and Power entitled, 'A chest x-ray that doesn't look right'. (Archives of Disease in Childhood - Education and Practice Edition 2014; 99: 72). This article described extravasation of TPN from a PICC line resulting in a pleural effusion. Our attention was drawn to the initial 'check x-ray' which identified what we refer to locally as the "wiggle sign". The "wiggle sign" refers to an undulating path taken by a malpositioned PICC line.

    The potential complications following insertion of a PICC line are well known including infection, thrombosis, catheter breakdown and malposition. The x-ray should show the catheter following a smooth course. The "wiggle' sign" as the name implies, is when the catheter has a tortuous appearance, suggesting that the distal end is not in the desired anatomical position. In this situation we believe that the distal end has become impacted after entering a smaller vessel or lodging against another structure.

    Given the significant morbidity and mortality that is associated with the incorrect placement of a PICC line, our policy over the past 3 years is to remove all lines if there is a positive "wiggle sign". It is our impression that this sign is not widely recognised in neonatal units and we feel a heightened awareness may help reduce the sequelae post PICC insertion. We would recommend the removal of a PICC line if a positive "wiggle sign" is demonstrated.

    Conflict of Interest:

    None declared

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  8. There is an association between herpes simplex encephalitis and anti-NMDAR antibodies

    We read with interest the review by Le Doare et al. discussing the presentation and management of neonatal and childhood herpes simplex encephalitis (HSE). The article nicely outlines the importance of timely treatment of this potentially catastrophic infection. The authors have provided practical advice that is applicable for many of the challenges that clinicians might be faced with.

    Although they mentioned the possibility of autoimmune encephalitis following HSE, it is important to emphasise this likelihood. More specifically, there is growing evidence to show an association between HSE and subsequent N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis. The NMDAR is a type of glutamate receptor found throughout the brain. Its role in autoimmune encephalitis has only been recently described by Dalmau et al in 2007 (1) as a paraneoplastic phenomenon leading to autoimmune encephalitis, although the presence of a causative tumour is less likely in younger patients (2).

    Pruss et al described the presence of NMDAR antibodies occurring in the course of 30% of individuals with HSE (3). In a paediatric sample, 7 out of 20 individuals (35%) relapsed and 3 out of those 7 patients were found to be NMDAR antibodies positive (4). This highlights the importance of considering this diagnosis in patients presenting with a possible relapse of HSE or even in patients not responding to appropriate antiviral therapy. Common symptoms may include a movement disorder, seizures and encephalopathy. Antibodies can be tested in serum and CSF specimens.

    Early recognition and referral of autoimmune encephalitis of this entity is paramount as early aggressive immunotherapy can lead to good outcomes (5).

    References:

    1. Dalmau J, Tuzun E and Wu H et al. Paraneoplastic anti-N-methyl-D- aspartate receptor encephalitis associated with ovarian teratoma. Ann Neurol 2007; 6(1): 25-36 2. Florance NR, Davis RL, Lam C et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009; 66(1): 11-8 3. Pruss H, Finke C, Holtje M et al. N-methyl-D-aspartate receptor antibodies in herpes simplex encephalitis. Ann Neurol 2012; 72(6): 902-911 4. Hacohen U, Deiva K, Pettingill P et al. N-methyl-D-aspartate receptor antibodies in post-herpes simplex virus encephalitis neurological relapse. Mov Disord. 2014; 29 (1): 90-96 5. Titulaer M, McCracken L, Gabilondo I et al. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013; 12(2): 157-165

    Conflict of Interest:

    None declared

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  9. Properly randomised trial of tongue tie division is needed!

    The paper cites various studies but in only one is the placebo effect studied it seems and it found that almost half the mothers said that feeding was improved. The inference is that almost 50% of the treated children did not require the procedure and so have been subjected to a surgical procedure on one of the most sensitive organs in the body un- necessarily.

    Until the placebo effect is fully investigated in the division of tongue tie, is it ethical to continue to perform a surgical procedure on an infant for the comfort of a third party, even if that is the mother? I would strongly suggest not. Perhaps a look at a psychological intervention with the mother would be more appropriate as there appears to be such a strong placebo effect?

    Conflict of Interest:

    None declared

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  10. Prenatal and neonatal paracetamol (acetaminophen) may increase the risk for ADHD and asthma.

    Dr. Catherine Williams argues against and Dr. Damian Roland for using antipyretics in feverish children (Arch Dis Child Educ Pract Ed 2014;99:158-159) but they do not mention that paracetamol may be a risk factor for ADHD and asthma.

    In the last two years, an animal study1, two cohort studies2 3, and an ecologic study4 have presented evidence for an increased risk of disturbed neuropsychiatric development after prenatal or neonatal exposure to paracetamol.

    In a very large randomized, controlled trial, asthmatic children with an acute respiratory infection who used paracetamol needed more outpatient asthma visits compared to those on ibuprofen5. McBride6 pointed out that many observations suggest a causative association between acetaminophen and asthma: (1) the strength of the association; (2) the consistency across geography, culture, and age; (3) the dose-response relationship; (4) the coincidence of increasing asthma prevalence and increasing acetaminophen use; (5) no other abrupt environmental change that could explain this increase in asthma morbidity; (6) the relationship between per-capita sales of acetaminophen and asthma morbidity across countries; and (7) the biologically plausible mechanism of glutathione depletion in airway mucosa.

    It is not true that there is "absence of evidence of harm" of antipyretics. Ibuprofen has been less studied and may or may not be safer than paracetamol after 6 months of age. Given the small benefits of antipyretics, my conclusion is that paracetamol could be used by pregnant women, infants and children for acute pain (benefit probably outweighs harm) but not for fever (benefit close to nil).

    References 1. Viberg H, Eriksson P, Gordh T, et al. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice. Toxicol Sci. 2013 Dec 21. 2. Brandlistuen RE, Ystrom E, Nulman I, et al. Prenatal paracetamol exposure and child neurodevelopment: a sibling-controlled cohort study. Int J Epidemiol. 2013 Dec;42(6):1702-13. 3. Liew Z, Ritz B, Rebordosa C, et al. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr 2014 Feb 24 [Epub ahead of print]. 4. Bauer AZ, Kriebel D. Prenatal and perinatal analgesic exposure and autism: an ecological link. Environmental Health 2013 12:41. 5. Lesko SM, Louik C, Vezina RM, et al. Asthma morbidity after the short- term use of ibuprofen in children. Pediatrics. 2002 Feb;109(2):E20. 6. McBride JT. The Association of Acetaminophen and Asthma Prevalence and Severity. Pediatrics 2011;128:1181-1185.

    Conflict of Interest:

    I have been editor, coauthor or peer reviewer for Swedish national clinical guidelines for infections in children. These guidelines recommend less use of antipyretics, especially to infants younger than 6 months.

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