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Recent eLetters

Displaying 1-10 letters out of 1419 published

  1. Re: Non-specific abdominal pain and appendicitis, an unespected correlation

    Dear Editor,

    We thank Dr Di Mascio and his colleagues for their interest in our study. In response we would like to point out that only a very small proportion (5.8%) of the children admitted with NSAP were subsequently hospitalised with bowel pathology (1). The increased relative risk of being diagnosed with appendicitis in the first year following a diagnosis of NSAP is clearly notable.

    Further analysis of the data shows that, considering "acute and unspecified appendicitis" (ICD10 K35 & K37) and "other appendicitis" (K36) together, of the 268 623 NSAP cohort 6274 (2%) children were admitted with appendicitis within the first year after their NSAP admission. We excluded cases where appendicitis occurred on the same admission record as the code for NSAP because this was a follow-up study based on person-days at risk. Of the 6274 children who were admitted with appendicitis within the first year following an admission with NSAP, 1926 (31% of the 6274) experienced the appendicitis admission within 1-3 days and 2505 (40%) experienced the appendicitis admission within 1-7 days of the admission with NSAP. This leaves an excess number of children who do get admitted with appendicitis some considerable time after the initial admission with NSAP, as the rate ratio remained significantly high even after 10 years (1). The small single centre study, described by Dr Di Mascio and colleagues, with just a short period of time studied between NSAP and appendicitis, is not comparable with our huge cohort constructed from linked English national hospital episode statistics with substantial follow-up.

    It is not known what pre-disposes individuals and protects others from developing acute appendicitis. One can perhaps hypothesise that a number of these children who were unwell enough to be admitted with NSAP have appendicular colic as the cause of their pain and may have some predisposition such as the luminal size or anatomical site of of their appendicular orifice which may subsequently lead to clinical appendicitis.

    Kind regards

    1- Diagnostic outcomes following childhood non-specific abdominal pain: a record-linkage study G C D Thornton, M J Goldacre, R Goldacre, L J Howarth Arch. Dis. Child. 2016 101:305-309

    Conflict of Interest:

    None declared

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  2. Do exicpients have an impact on paracetamol clearance: the jury is still out

    We support any idea or initiative to try to better understand the covariates of paracetamol PK in neonates, including the potential impact of excipients (propylene glycol, mannitol or none) on paracetamol clearance.

    We have carefully read the e-letter of Pisapia et al., and support the potential impact of mannitol co-administration on paracetamol clearance, however, we do have some relevant additional comments.

    First, in the initial versions of the paper, we have explored the potential impact of the different study as an indicator for potential differences, including excipients, but this turned out to be negative. This is a common practice for pooled datasets. This does not mean that there is no impact, but it did not reach sufficient impact to be quantified in this cohort of 150 neonates or has been superimposed by other variables;

    Second, if mannitol stimulates diuresis, it is not very likely to affect paracetamol clearance since urinary elimination of paracetamol is a very minor route of elimination in neonates, while sulphation and glucuronidation are the most important contributors (1,2). For drugs eliminated by renal route, the impact may be more relevant.

    Finally, and in order to correct the suggestions made, the estimates should correct for the 'real doses' administered, commonly below 60 mg/kg/24h while the impact of paracetamol administration on hemodynamics in both neonates and healthy adult volunteers have been quantified (3,4).

    References

    1) Allegaert K, de Hoon J, Verbesselt R, Vanhole C, Devlieger H, Tibboel D. Intra- and interindividual variability of glucuronidation of paracetamol during repeated administration of propacetamol in neonates. Acta Paediatr 2005;94:1273-9. 2) Krekels EH, van Ham S, Allegaert K, et al. Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants. Eur J Clin Pharmacol 2015;71:1075-82. 3) Allegaert K, Naulaers G. Haemodynamics of intravenous paracetamol in neonates. Eur J Clin Pharmacol 2010;66:855-8. 4) Chiam E, Weinberg L, Bailey M, McNicol L, Bellomo R. The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial. Br J Clin Pharmacol 2016;81:605-12.

    Conflict of Interest:

    corresponding author of the initial paper

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  3. Non-specific abdominal pain and appendicitis, an unespected correlation

    Dear editor, In their study G C D Thornton and al (1) found a diagnosis of appendicitis in 6065 children out of 268623, previously diagnosed as non specific abdominal pain (NSAP) at the first access, who returned within one year. According to their data, the RR to develop appendicitis in the first year after discharge with a diagnosis of NSAP is 15.04 times higher than the risk in the control cohort. Appendicitis is an acute disease with a rapid development (2) and, as expected for an acute condition, the RR gets down considerably after the first year (RR 3.26 at 1-4 years; 2.13 at 5-9 years). We recently evaluated patients readmitted to our emergency department, from March 2015 to September 2015, with a previous diagnosis of abdominal pain without a defined cause: we had 37 patients hospitalized for appendicitis, 23 of them were diagnosed at the first access, 6 returned within 72 hours, other 7 cases were readmitted within 7 days, and only one returned in more than a week. It could be interesting to know how many patients with appendicitis in the Thornton's series were readmitted in an acute setting (defined as readmission within 72 hours) or in the first week after discharge. A high number of early readmissions would strongly clarify this otherwise very puzzling connection.

    Bibliography

    1- Diagnostic outcomes following childhood non-specific abdominal pain: a record-linkage study G C D Thornton, M J Goldacre, R Goldacre, L J Howarth Arch. Dis. Child. 2016 101:305-309

    2- Appendicitis. Lewis SR, Mahony PJ, Simpson J. BMJ. 2011 Oct 6;343:d5976

    Conflict of Interest:

    None declared

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  4. Title : Congenital hypothyroidism screening- incidence in semi-urban hospital.

    Thyroid hormone is critical for normal growth and brain development, and hypothyroidism in infancy is the leading cause of intellectual impairment worldwide. Congenital hypothyroidism (CH), defined as deficiency of thyroid hormones at birth. Congenital hypothyroidism is very important clinically since severe cases will lead to irreversible mental handicap without prompt treatment.

    The essential role of thyroid hormones in brain development during the first 24-36 months of age is well established; thus prompt normalization of thyroid hormone levels is essential . The incidence of CH diagnosed by neonatal screening varies per population, ranging from 1 in 2000 to 1 in 3000 births and is comparatively higher than the reported incidence prior to the era of screening.

    Following clinical assessment, a good venous blood sample for measurement of free thyroxine (fT4) and TSH is mandatory, since the result reflects the presence and severity of congenital hypothyroidism.

    Compared to venous serum, the concentrations in skin puncture serum were higher for thyroid stimulating hormone (TSH) (86.7%). Capillary TSH dried blood spot testing on the 3rd-5th day is the most sensitive method.

    In our setup we could use only venous blood TSH levels rather than capillary blood samples reason may be having expert nursing care to collect the blood samples but not having sufficient infrastructure and personnel to implement the same.

    In our experience 4 babies out of 1500 had transient elevated TSH levels which on follow up normalized within 3 weeks after birth without treatment. There was no proved case of congenital hypothyroidism was seen probable reasons may be use of common salt fortified with iodine for cooking and staple diet being mainly fish.

    In countries that can afford newborn screening, treatment within the first 28 days of life - so-called 'early treatment' - has transformed the outlook for children with CH so that severe growth retardation with mental handicap(congenital hypothyroidism) is no longer seen.

    It is described as primary when the gland itself is affected and central when the defect lies in the hypothalamo-pituitary axis; compensated when the hypothalamo-pituitary-thyroid axis is jeopardised but still manages to maintain normal thyroxine (T4) levels and decompensated when normal thyroid hormone levels cannot be maintained.

    Van der Sluijs Veer et al. studied 95 toddlers with CH in whom L- thyroxine treatment had been started at a median age of 9 days, with normalization of the serum free T4 concentration within 2.1 days and of the serum TSH level within 18.6 days.

    Cord FT4 identifies only infants with severe CH. Cord TSH is more sensitive than cord FT4 screening. Capillary TSH dried blood spot testing on the 3rd-5th day is the most sensitive method. In our experience it was found that serum thyrotropin values at 2nd and 3rd day were useful in screening and early treatment of congenital hypothyroidism.

    References :

    Nikolina Zdraveska, Violeta Anastasovska and Mirjana Kocova. Frequency of thyroid status monitoring in the first year of life and predictors for more frequent monitoring in infants with congenital hypothyroidism. J Pediatr Endocrinol Metab 2016; aop

    Ari J. Wassner and Rosalind S. Brown. Hypothyroidism in the Newborn Period. Curr Opin Endocrinol Diabetes Obes. 2013 Oct; 20(5): 449-454. doi: 10.1097/01.med.0000433063.78799.c2

    Deladoey J, Ruel J, Gigu?re Y, et al. Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Quebec. J Clin Endocrinol Metab 2011;96:2422-9.

    Grosse SD, Van Vliet G. Prevention of intellectual disability through screening for congenital hypothyroidism: how much and at what level? Arch Dis Child 2011;96:374-9.

    Corbetta C, Weber G, Cortinovis F, Calebiro D, Passoni A, Vigone MC et al. A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol (Oxf). 2009 Nov;71(5):739-45. doi: 10.1111/j.1365- 2265.2009.03568.x. Epub 2009 Mar 28.

    Hardy JD, Zayed R, Doss I, Dhatt GS. Cord blood thyroxine and thyroid stimulating hormone screening for congenital hypothyroidism: how useful are they? J Pediatr Endocrinol Metab. 2008 Mar;21(3):245-9.

    Hardy JD1, Zayed R, Doss I, Dhatt GS. Cord blood thyroxine and thyroid stimulating hormone screening for congenital hypothyroidism: how useful are they? J Pediatr Endocrinol Metab. 2008 Mar;21(3):245-9.

    Heyerdahl S. Long-term outcome in children with congenital hypothyroidism. Acta Paediatr 2001;90:1220-2.

    Falch DK. Clinical chemical analyses of serum obtained from capillary versus venous blood, using Microtainers and Vacutainers. Scand J Clin Lab Invest. 1981 Feb;41(1):59-62.

    Conflict of Interest:

    None declared

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  5. MANNITOL CONTRIBUTION TO IV PARACETAMOL CLEARANCE VARIANCE IN NEONATES

    To the editor:

    We have found very interesting the paper by Dr Allegaert et al. about iv paracetamol pharmacokinetics (1) in which they referred that between- subject variability (BSV) is explained by covariates such as size, weight, disease characteristics or co-administration of drugs. They mentioned that they found an unexplained variance in paracetamol clearance, and that it remained high (39,1 per cent) even after taking size, age and bilirubin into account.

    Regarding the co-administration of drugs as a covariate, an issue that was not addressed in the paper, we would like to note that the neonates included in the pooled analysis (n: 158) were from different studies and had been administered three different iv paracetamol formulations; one of them (Perfalgan) with a considerable amount of mannitol (3,85g/100ml) as excipient. Thus, the neonates in study 3 (n: 50) were administered every 6 hours a concomitant mannitol dose of 58 mg/Kg with each paracetamol dose of 15 mg/Kg; they received 232 mg/Kg/day of mannitol during 2 to 7 days.

    The amount of mannitol included as excipient in pharmaceutical products licensed for adults and children is considered a non-active ingredient because it is far below the pharmacologically significant dose for them. However, it could be enough to show an osmotic diuretic effect in neonates, especially in low weight preterm infants. This enhanced osmotic effect would be greater in the most immature neonates and would decline logarithmically during the first few weeks of life(2). The osmotic diuretic effect of the same dose of mannitol could be considerably different in accordance with the maturation of the renal function.

    In Argentina iv paracetamol is available only since last year, with mannitol as excipient. In 2006 we had seen that a low amount of mannitol could have some influence on the less oliguria observed with ibuprofen compared to indomethacin for PDA closure.(3) Last year, a new investigation by Chiam et al. showed that the majority of the formulations with 1g iv paracetamol also contain near 4g of mannitol (38-39mg/ml). They explained that this low amount of mannitol was a clinically relevant dose which might cause hypotension in critically ill adults due to its diuretic nature even in low doses.(4)

    The fact that only 1/3 of neonates (50/158) in Allegaert et als study were co-administered a concomitant diuretic dose of mannitol should be considered, as it could have contributed to the extensive variability and the unexplained high variance they found in iv paracetamol clearance.

    Further research is necessary to evaluate the effects of low doses of mannitol in neonates, especially in low birth weight infants, and to determine how iv paracetamol pharmacodynamics and pharmacokinetics are influenced, if so, by the mannitol content of the medication.

    Jorge Pisapia. Matias Lucero. Leonardo Giunta.

    Clinica y Maternidad Suizo Argentina. Department of Pharmacy. SWISS MEDICAL GROUP. Buenos Aires. Argentina.

    REFERENCES 1- Allegaert K, Palmer GM, Anderson BJ. The pharmacokinetics of intravenous paracetamol in neonates: size matters most. Arch Dis Child 2011; 96:575???580.

    2- Kleinman LI, Disney TA. Renal osmotic in the neonatal and adult dog. Am J Physiol Renal Physiol 1984; 247 Issue 3 F396-F402.

    3- Pisapia J, Giunta L, Alonso MR. Mannitol influence on the less renal side effects of ibuprofen vs indomethacin for PDA closure. Arch Dis Child 2003;88:1135.adc.bmj.com/content/88/12/1134.full/reply#archdischild_el_1881 Jan 2006

    4- Chiam E, Weinberg L, Bellomo R. Paracetamol: a review with specific focus on the haemodynamic effects of intravenous administration. Heart Lung Vessel 2015; 7(2):121-32.

    Conflict of Interest:

    None declared

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  6. Exploring the impact of early life factors

    The MCS research by Massion and colleagues on childhood obesity should be read in the light of other recent cohort studies exploring the impact of early life factors in the UK and the USA (1). Kimbro and Augustine found that US children living in married two biological parent households had a lower risk of obesity than those living in other family types. In the presence of other controls, poverty was not a significant risk factor for childhood obesity (2).

    The reported associations of childhood obesity with parents' educational attainment and smoking status are certainly important. Goodman and Greaves, using the MCS, found that the educational attainment of mothers was the strongest predictor of cognitive and social development in children born in two parent households. This attenuated a significant effect of parental marriage. Early parental separation had a major impact on cognitive and social development, and this was much more common among unmarried couples (3). Also, unmarried adults are more likely to smoke (4).

    Conclusions about the impact of early life factors on health inequalities for children cannot be made without controlling for family structure. Some of the reported findings of this research might be confounded by the marital status of parents and parental separation.

    1. Massion S, Wickham S, Pearce A, Barr B, Law C, Taylor-Robinson D. Exploring the impact of early life factors on inequalities in risk of overweight in UK children: findings from the UK Millenium Cohort Study. Arch Dis Child 2016

    2. Augustine J, Kimbro R. Family Structure and Obesity among US Children. Journal of Applied Research on Children 2013

    3. Goodman A, Greaves E. Cohabitation, marriage and child outcomes. IFS Commentary C114 2010

    4. Adult Smoking Habits in Great Britain: 2014. ONS 2016

    Conflict of Interest:

    None declared

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  7. Re:Holes in the net: safety netting in Emergency Departments needs to improve

    Dear editor,

    In their letter, colleagues Jacob et al. raised further evidence of the lack of standardised safety netting. We thank them for their comments emphasizing the disparity between paediatric trainees' perception of their safety netting practice and their documentation in the medical notes.

    To overcome the lack of information on the difference of given safety netting advice and its documentation in the medical notes, the authors propose the introduction of a checklist. However, at this moment the effective components or the best way to perform this safety netting management still remains unknown.

    A systematic review of Neill et al. states that incomplete information on the illness of their child leaves parents still in need for help.(1) Moreover, irrelevant information reduces parents' trust in the intervention.(1) We know that parental knowledge and satisfaction improved more after video discharge instructions than after written discharge instructions alone.(2) So to proceed we think the next step is to focus on the parental role in the decision making process. One could think of parental monitoring of alarming signs and symptoms of their febrile child. A study on self-referred children with fever emphasized that many parents properly judged and acted on their febrile child's severity of illness.(3) In England every parent is trained to recognise petechial rash,(4) we might enlarge this knowledge to other alarming or reassuring signs and symptoms. This could be initiated for example for respiratory rate, a useful marker of pneumonia, one of the most frequent serious illness at the ED.(5) We are aware of current projects on this topic. A next step is evaluating the impact of such strategies providing improved information on patient (re)consultation.

    In addition to the recognition of deterioration, an important gap in safety netting literature is its time frame strategy. The development of optimal safety netting management should include clinical signs and symptoms, but also a disease specific time frame to inform parents when they should seek help again. This combination of safety netting determinants may establish new starting points for improvement of care.

    References: 1. Neill S, Roland D, Jones CH, Thompson M, Lakhanpaul M, group ASs. Information resources to aid parental decision-making on when to seek medical care for their acutely sick child: a narrative systematic review. BMJ Open. 2015;5:e008280 doi: 10.1136/bmjopen-2015-008280 [published Online. 2. Bloch SA, Bloch AJ. Using video discharge instructions as an adjunct to standard written instructions improved caregivers' understanding of their child's emergency department visit, plan, and follow-up: a randomized controlled trial. Pediatr Emerg Care. 2013;29:699-704 doi: 10.1097/PEC.0b013e3182955480 [published Online. 3. van Ierland Y, Seiger N, van Veen M, et al. Self-referral and serious illness in children with fever. Pediatrics. 2012;129:e643-51 doi: 10.1542/peds.2011-1952 [published Online. 4. Acutely sick kid safety netting interventions for families. http://asksniff.org.uk/ 5. Taylor JA, Del Beccaro M, Done S, Winters W. Establishing clinically relevant standards for tachypnea in febrile children younger than 2 years. Arch Pediatr Adolesc Med. 1995;149:283-7 Online.

    Conflict of Interest:

    None declared

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  8. Treatment of Bronchiolitis in a Poor- Resourced Settings

    Bronchiolitis is on rise, both in prevalence and severity in our country due to many social and life style factors. in our hospital we adopted a protocol named: SuProNO INCLUDE:- - PROVIDE VITAL SIGN ASSESSMENT and close monitoring - PROVIDE O2 AS NEEDED - Provide IV fluid/ NGT Feeds as appropriate -provide Hypertonic (3%) saline nebulization -provide nasal decongestant drops/ spray and suctioning as needed - provide antipyretics if needed -NO NO NO antibiotics NO NO NO steroids.

    with this protocol, the out come is excellent even for severe cases, with short hospitalization, and no need for high facility respiratory support like CPAP or ventilator.

    Conflict of Interest:

    None declared

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  9. Holes in the net: safety netting in Emergency Departments needs to improve

    Safety netting in the Emergency Department (ED) is key to the practice of safe medicine. Following the article by de Vos-Kerkhof (1), we present further evidence to suggest that there is a lack of standardised safety netting. In addition, we found a disparity between paediatric trainees' perception of their safety netting practice and what they actually documented in the medical notes.

    In a retrospective case notes review of 100 consecutive ED attendances to our hospital seen by the paediatric team and discharged from ED, only 16% had documentation that the families had been told about the existence of uncertainty around the diagnosis and the course of the illness. This compares unfavourably with the fact that 73% of surveyed paediatric trainees reported that they routinely mentioned this to families. Furthermore, the signs and symptoms to look for had only been documented in 27% of cases, though 88% of trainees reported discussing this with the family. 39% of the notes reviewed had no specific safety netting documentation of any kind.

    It is clear that for non-consultant paediatricians, who are the clinicians seeing most referred children in ED, a gap exists between the safety netting that they report undertaking and what is documented. This may be in part because they provided verbal safety netting advice without documenting it but it also suggests that safety netting procedures are poor, despite the clinical and medico-legal imperative for adequate safety netting and documentation advocated by the National Institute for Health and Care Excellence(2).

    Clearly training for junior doctors on safety netting and its documentation needs to improve. A safety netting checklist and more high quality patient information leaflets may help clinicians to offer adequate advice and information to families at the time of discharge. (297 words)

    1. de Vos-Kerkhof E, Geurts DH, Wiggers M, Moll HA and Oostenbrink R. Tools for 'safety netting' in common paediatric illnesses: a systematic review in emergency care. Archives of Disease in Childhood. 2016; 101: 131 -9.

    2. Fields E, Chard J, Murphy MS and Richardson M. Assessment and initial management of feverish illness in children younger than 5 years: summary of updated NICE guidance. BMJ (Clinical Research Ed). 2013; 346: f2866.

    Conflict of Interest:

    None declared

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  10. Point of care lactate testing in resource-poor settings

    Khan et al. make a strong case for investment in point-of-care lactate testing in low and middle income countries (LMICs) (1). They believe that this would identify children at high risk of death, and would save lives because these children could receive earlier resuscitation. Unfortunately the optimal management of children with hyperlactataemia in LMICs is far from clear. Although Khan et al. extrapolate from findings in well-resourced settings to suggest that early fluid resuscitation would be beneficial, this is contrary to the findings of the FEAST study in which bolus fluid resuscitation in African children with signs of shock produced an increase in mortality (2). Of note, this effect was also observed in the subgroup of children with hyperlactataemia.

    Not only is hyperlactataemia a consequence of sepsis, but it is also a defining feature of severe malaria which is a common cause of death in many LMICs (3). Unlike the situation in sepsis, the pathophysiology of hyperlactataemia in malaria is thought to involve microvascular obstruction by parasitized red blood cells, microvascular dysfunction, and anaemia (4,5). Aggressive fluid resuscitation is discouraged in severe malaria, and detailed physiological studies in adults with severe malaria showed that fluid resuscitation failed to reduce microvascular obstruction and lactate concentrations (5). However, when hyperlactataemia is associated with severe malarial anaemia, blood transfusion can be lifesaving (3).

    It is likely that point of care lactate testing in LMICs would achieve the goal of identifying children at higher risk of death, but it is far from certain whether this would be accompanied by the improved outcomes that would be needed to justify the investment. Amongst children with malaria it may identify the need for parenteral artesunate or blood transfusion, but in children with sepsis further research is needed to define the optimal management strategies when intensive care is limited or unavailable.

    1. Khan M, Brown N, Mian AI. Point-of-care lactate measurement in resource-poor settings. Arch Dis Child 2016;101(4):297-8. 2. Maitland K, Kiguli S, Opoka RO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011;364(26):2483-95. 3. World Health Organization. Guidelines for the treatment of malaria. Third edition, 2015. 4. Miller LH, Ackerman HC, Su XZ, et al. Malaria biology and disease pathogenesis: insights for new treatments. Nature medicine 2013;19(2):156- 67. 5. Hanson JP, Lam SW, Mohanty S, et al. Fluid resuscitation of adults with severe falciparum malaria: effects on Acid-base status, renal function, and extravascular lung water. Crit Care Med 2013;41(4):972-81.

    Conflict of Interest:

    None declared

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