Thank you for the opportunity to reply, here is our response.
We would like to thank the authors for their valuable comments, we believe that these comments add to and complement our article. Our article aimed to cover a wide breadth of common gynaecological conditions that can affect children and unfortunately we were therefore not able to go in to great detail for each condition covered. We would certainly agree on the importance of an early diagnosis for lichen sclerosus and collaboration with a dermatologist for treatment if available. The British Association of Dermatologists guidelines for the management of lichen sclerosus was not published when we wrote our article, we can see that this is a very valuable resource.
Dr Smith makes relevant and interesting points regarding the terminology used for fluids, which can be used for both “resuscitation” purposes and “maintenance” therapy, and we thank him for his interest and response.
The purpose of this clinical question was to review the current evidence for paediatric patients in relation to “ balanced fluids”, a term emerging in the medical literature. NICE recommends using any isotonic crystalloid, which covers a wide range of sodium concentration from 130 to 154mmol/L (reference 1 in the article).
The loss of electrolytes, either from the gut or as a result of renal impairment, needs regular clinical review. We observe that repeated bicarbonate measurements are not regularly undertaken after initial assessment or following admission and it is important to remind trainees to consider these losses, hence our recommendation of daily monitoring of electrolytes. By following this approach, appropriate individualised adjustments can be made to the fluid prescription of patients as necessary.
Our conclusion from this question highlighted that research needs to be undertaken in the paediatric population of bicarbonate/ lactate containing fluids to determine whether this may affect acute kidney injury and other specific clinical outcomes. We agree attention to detail is always necessary when caring for infants and children receiving intrav...
Dr Smith makes relevant and interesting points regarding the terminology used for fluids, which can be used for both “resuscitation” purposes and “maintenance” therapy, and we thank him for his interest and response.
The purpose of this clinical question was to review the current evidence for paediatric patients in relation to “ balanced fluids”, a term emerging in the medical literature. NICE recommends using any isotonic crystalloid, which covers a wide range of sodium concentration from 130 to 154mmol/L (reference 1 in the article).
The loss of electrolytes, either from the gut or as a result of renal impairment, needs regular clinical review. We observe that repeated bicarbonate measurements are not regularly undertaken after initial assessment or following admission and it is important to remind trainees to consider these losses, hence our recommendation of daily monitoring of electrolytes. By following this approach, appropriate individualised adjustments can be made to the fluid prescription of patients as necessary.
Our conclusion from this question highlighted that research needs to be undertaken in the paediatric population of bicarbonate/ lactate containing fluids to determine whether this may affect acute kidney injury and other specific clinical outcomes. We agree attention to detail is always necessary when caring for infants and children receiving intravenous fluids of any type.
We thank you for the opportunity to discuss our data with the two correspondents who raised some concerns regarding the selected population of our analysis on neonatal outcomes following new reimbursement criteria on palivizumab use. They also reported data collected during the same time period and apparently different from our main results.
In response to the first correspondent, our analysis is based on children < 2 years of age because the candidate for palivizumab treatments are included within this subpopulation. In fact, the therapeutic indication (1) of palivizumab includes not only the preterm infants up to 1 year of age but also children up to 2 years of age and treated for bronchopulmonary dysplasia or born with a serious heart disease. Furthermore, our selected population is consistent with previous analysis (2) that measured the association between updated guidelines-based palivizumab administration and hospitalization for Respiratory Syncytial Virus (RSV). Table 1 of our study reports children up to 6 months of age, both at risk of RSV and including hospitalization data. We agree that this is probably the subpopulation with the major impact of the palivizumab treatment and regulatory decision. However, also in this case no differences in hospitalization rate have been detected before-after the AIFA’ limitation for palivizumab: 1031/47.608 (21.7 ‰) and 436/22715 (19.2 ‰) hospitalizations, respectiv...
We thank you for the opportunity to discuss our data with the two correspondents who raised some concerns regarding the selected population of our analysis on neonatal outcomes following new reimbursement criteria on palivizumab use. They also reported data collected during the same time period and apparently different from our main results.
In response to the first correspondent, our analysis is based on children < 2 years of age because the candidate for palivizumab treatments are included within this subpopulation. In fact, the therapeutic indication (1) of palivizumab includes not only the preterm infants up to 1 year of age but also children up to 2 years of age and treated for bronchopulmonary dysplasia or born with a serious heart disease. Furthermore, our selected population is consistent with previous analysis (2) that measured the association between updated guidelines-based palivizumab administration and hospitalization for Respiratory Syncytial Virus (RSV). Table 1 of our study reports children up to 6 months of age, both at risk of RSV and including hospitalization data. We agree that this is probably the subpopulation with the major impact of the palivizumab treatment and regulatory decision. However, also in this case no differences in hospitalization rate have been detected before-after the AIFA’ limitation for palivizumab: 1031/47.608 (21.7 ‰) and 436/22715 (19.2 ‰) hospitalizations, respectively. As in our main analysis, we were not able to see an increase of hospitalization related to the new reimbursement decision but a significant reduction (p=0.033) that we assume could be related to a more accurate coding by hospital or with an increase for palivizumab compliance in babies with higher risk of RSV infections.
In the second letter the authors presented data from three different hospitals supporting hypothetical opposite trend in hospitalization compared with our results. However, data from two of the three hospitals are related to general cases of bronchiolitis not specifically associated with RSV. None of the three separate groups of patients have statistically significant differences between the considered periods. Furthermore, these data do not take into account the potential mobility of all patients from one hospital to another. The subjects included in our analysis come for 70% of cases by the same three hospitals located in Rome quoted by the correspondents; all others patients are from regional hospitals where patients may receive assistance under the regional health coverage. From our point of view this give a better and comprehensive prospective compared to single hospital analysis.
We recognise in the limitations of the study that our ecological analysis was not able to measure the impact on specific subpopulations and administrative data can lose some clinically relevant information.
However, we cannot understand how the data presented in these correspondences can be considered more real than those collected in our study and to disprove our conclusions.
Antonio Addis, Valeria Belleudi
Department of Epidemiology, Lazio Regional Health Service, Roma, Italy
1. European Medicine Agency - Synagis : EPAR - Product Information https://www.ema.europa.eu/documents/product-information/synagis-epar-product-information_en.pdf
2. Grindeland CJ, Mauriello CT, Leedahl DD, et al. Association Between Updated Guideline-Based Palivizumab Administration and Hospitalizations for Respiratory Syncytial Virus Infections. Pediatr Infect Dis J 2016;35:728–32.doi:10.1097/INF.0000000000001150Google Scholar
We thank Professor Marchetti for his comments on our article in ADC (1). He raises two important questions we wish to comment on.
Regarding which dose of aspirin to use, we are also interested in the suggestion that anti-aggregant doses of aspirin might be a preferred option for the acute inflammatory phase of Kawasaki disease (KD). It is indeed possible that future guidance may recommend low dose aspirin (3-5 mg/kg/day) at all stages of KD, as suggested by the retrospective data referred to by Professor Marchetti (2). Whilst we acknowledge the potential merits of such an approach, particularly in relation to avoidance of toxicity, there has never been a prospective controlled clinical trial to support this and therefore no high-level evidence on which to base firm guidance. Two other practical considerations are worthy of highlighting in relation to aspirin. Firstly, nonsteroidal anti-inflammatory drugs such as ibuprofen, which antagonize platelet inhibition induced by aspirin (3), should be avoided in patients with KD receiving anti-aggregant doses of aspirin. Secondly, although the risk of low dose aspirin (3-5 mg/kg) in being associated with Reye syndrome is unknown, usual advice is to discontinue in the event of inter-current infection.
Regarding the use of corticosteroids for primary treatment of KD, we have been strong advocates of this for several years, as reflected in previously published guidance (4, 5). This is now brought into...
We thank Professor Marchetti for his comments on our article in ADC (1). He raises two important questions we wish to comment on.
Regarding which dose of aspirin to use, we are also interested in the suggestion that anti-aggregant doses of aspirin might be a preferred option for the acute inflammatory phase of Kawasaki disease (KD). It is indeed possible that future guidance may recommend low dose aspirin (3-5 mg/kg/day) at all stages of KD, as suggested by the retrospective data referred to by Professor Marchetti (2). Whilst we acknowledge the potential merits of such an approach, particularly in relation to avoidance of toxicity, there has never been a prospective controlled clinical trial to support this and therefore no high-level evidence on which to base firm guidance. Two other practical considerations are worthy of highlighting in relation to aspirin. Firstly, nonsteroidal anti-inflammatory drugs such as ibuprofen, which antagonize platelet inhibition induced by aspirin (3), should be avoided in patients with KD receiving anti-aggregant doses of aspirin. Secondly, although the risk of low dose aspirin (3-5 mg/kg) in being associated with Reye syndrome is unknown, usual advice is to discontinue in the event of inter-current infection.
Regarding the use of corticosteroids for primary treatment of KD, we have been strong advocates of this for several years, as reflected in previously published guidance (4, 5). This is now brought into sharp focus in the light of emerging data from several countries regarding poor coronary artery outcomes despite Intravenous immunoglobulin (IVIG) (1, 6-9). Indeed, the use of corticosteroids as primary adjunctive treatment of patients with severe KD has an increasingly compelling evidence-base. Despite that and UK guidance that was published halfway during the BPSU survey (5), our study demonstrates that UK paediatricians are not yet widely using corticosteroids for the treatment of KD (1). The soon-to-be published European SHARE (single hub access for rheumatology in Europe) guidance hopefully will improve that situation for high risk cases, but there clearly remains significant equipoise over the use of corticosteroids as adjunctive therapy for unselected cases of KD. Thus, at the time of writing we are currently setting up a major international clinical trial of corticosteroids as adjunctive treatment for unselected KD cases in the UK and Europe, KDCAAP (the Kawasaki Disease Coronary Artery Aneurysm Prevention trial). It is possible that the added potent anti-inflammatory effect of adjunctive corticosteroids for the primary treatment of KD will obviate the need for any further discussion about anti-inflammatory doses of aspirin. We hope that the UK and European paediatric community will recruit patients to this important clinical trial to resolve this issue once and for all.
Professor Robert Tulloh, Bristol Royal Hospital for Children, Bristol, UK
Professor Paul Brogan, Great Ormond Street Hospital, London, UK
1. Tulloh RMR, Mayon-White R, Harnden A, Ramanan AV, Tizard EJ, Shingadia D, Michie CA, Lynn RM, Levin M, Franklin OD, Craggs P, Davidson S, Stirzaker R, Danson M, Brogan PA. Kawasaki disease: a prospective population survey in the UK and Ireland from 2013 to 2015. Archives of Disease in Childhood. 2018.
2. Ho LGY, Curtis N. What dose of aspirin should be used in the initial treatment of Kawasaki disease? Archives of Disease in Childhood. 2017;102(12):1180-2.
3. Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, Vyas SN, FitzGerald GA. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345(25):1809-17.
4. Brogan PA, Bose A, Burgner D, Shingadia D, Tulloh R, Michie C, Klein N, Booy R, Levin M, Dillon MJ. Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research. Arch Dis Child. 2002;86(4):286-90.
5. Eleftheriou D, Levin M, Shingadia D, Tulloh R, Klein NJ, Brogan PA. Management of Kawasaki disease. Arch Dis Child. 2014;99(1):74-83.
6. Mossberg M, Segelmark M, Kahn R, Englund M, Mohammad AJ. Epidemiology of primary systemic vasculitis in children: a population-based study from southern Sweden. Scand J Rheumatol. 2018;47(4):295-302.
7. Lyskina G, Bockeria O, Shirinsky O, Torbyak A, Leontieva A, Gagarina N, Satyukova A, Kostina J, Vinogradova O. Cardiovascular outcomes following Kawasaki disease in Moscow, Russia: A single center experience. Global cardiology science & practice. 2017;2017(3):e201723.
8. Jakob A, Whelan J, Kordecki M, Berner R, Stiller B, Arnold R, von KR, Neumann E, Roubinis N, Robert M, Grohmann J, Hohn R, Hufnagel M. Kawasaki Disease in Germany: A Prospective, Population-based Study Adjusted for Underreporting. Pediatr Infect Dis J. 2016;35(2):129-34.
9. Friedman KG, Gauvreau K, Hamaoka-Okamoto A, Tang A, Berry E, Tremoulet AH, Mahavadi VS, Baker A, deFerranti SD, Fulton DR, Burns JC, Newburger JW. Coronary Artery Aneurysms in Kawasaki Disease: Risk Factors for Progressive Disease and Adverse Cardiac Events in the US Population. Journal of the American Heart Association. 2016;5(9).
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)
We thank Dr. Garstang and Dr. Debelle for their comments on our article in ADC (1).
We are pleased that the correspondents support our finding of a strong association between chronic conditions and respiratory tract Infection mortality in children which, though well-recognised by clinicians, has not previously been quantified.
The correspondents rightly highlight that our analyses concentrate only on unexpected deaths after age 2 months. We chose this definition because these early deaths are more prone to linkage error and more importantly, tend to be related to maternal health during pregnancy and delivery, preterm birth, intrapartum events and congenital anomalies, and therefore may not be avoidable through improved care after postnatal discharge.
As our paper highlights, an indication of whether a death was expected or not on a death certificate or in hospital records is necessary in order to assess whether a death was avoidable or amenable to healthcare intervention. A classification of whether a death was expected or unexpected could also be notified to Child Death Overview Panels and other agencies by those completing the death certificates. This would be helpful to Child Death Overview Panels in their deliberations as well as feeding into the collation of mortality statistics.
References:
1. 1. Verfürden ML, Gilbert R, Sebire N, Hardelid P. Arch Dis Child 2018;103:1125–1131.
Re: Professor Andrew N Williams’ letter to ADC “Failing to consider Virtual Academic Units within UK infrastructure for research that benefits infants, children and young people”
We were pleased to hear the success of the Virtual Academic Unit and invited Professor Andrew Williams to contribute to the RCPCH research bulletin of March 2019.
At the RCPCH, we know from our research and from speaking to our membership, that paediatricians around the country have little or no allocated funding or designated research time. We, therefore, applaud all those paediatricians who continue to go above and beyond to undertake research to achieve better health outcomes for children and young people.
The RCPCH is fully committed to strengthening basic science and clinical research and the development of devices, medicines and technologies that address the needs of children. Furthermore, our committment includes supporting our members and growing and promoting opportunities for research within paediatrician’s careers.
We will continue to work with our partners across the UK to influence, promote and grow child health research.
Lindsey Hunter, Research Development Manager, RCPCH
Professor Anne Greenough, immediate past Vice President Science and Research, RCPCH and Professor of Neonatology and Clinical Respiratory Physiology, King's College London
We thank Professor Wright for her comments, and we welcome the opportunity to provide some clarification and further analysis.
We reported Z-scores rather than percentiles, although some comments on approximate percentiles can be made. Assuming that Z scores of -1.96 and -3 represent approximately the 2.5th and 0.2nd centiles respectively, 36/101 children were below the 2.5th centile, and 17/101 were below the 0.2nd centile for weight. Additionally, our mixed effects model (accounting for multiple measurements) modelling the group trend over time estimated the mean weight Z score at 11 years to be -1.63 (approximately 5th centile).
Despite the overall short stature of the group, 24/101 children had a BMI Z score of less than -1.96. So, by this approach, their weight was low even after taking into account stature. We agree that we cannot infer causality from this observational study, but we believe a proportion of the stunted growth is explained by low weight. We are exploring other measures of malnutrition, such as skin-fold thickness.
Whilst our patient numbers are small, they do give some weight to the argument that PEG feeding halts the progression of malnutrition. We investigated the rate of decline of weight after PEG insertion. In a mixed effects model with a random intercept for individual patients, the rate of wei...
We thank Professor Wright for her comments, and we welcome the opportunity to provide some clarification and further analysis.
We reported Z-scores rather than percentiles, although some comments on approximate percentiles can be made. Assuming that Z scores of -1.96 and -3 represent approximately the 2.5th and 0.2nd centiles respectively, 36/101 children were below the 2.5th centile, and 17/101 were below the 0.2nd centile for weight. Additionally, our mixed effects model (accounting for multiple measurements) modelling the group trend over time estimated the mean weight Z score at 11 years to be -1.63 (approximately 5th centile).
Despite the overall short stature of the group, 24/101 children had a BMI Z score of less than -1.96. So, by this approach, their weight was low even after taking into account stature. We agree that we cannot infer causality from this observational study, but we believe a proportion of the stunted growth is explained by low weight. We are exploring other measures of malnutrition, such as skin-fold thickness.
Whilst our patient numbers are small, they do give some weight to the argument that PEG feeding halts the progression of malnutrition. We investigated the rate of decline of weight after PEG insertion. In a mixed effects model with a random intercept for individual patients, the rate of weight Z score decline was 0.01 units per year, in contrast with 0.1 per year in the un-operated population, although low numbers prevent a meaningful statistical comparison. Given the ultra-rare nature of the disease, a randomised trial is effectively impossible and probably anyway unethical.
The multifactorial aetiology of wasting is unique in A-T. The disease compromises varying components of chronic inflammation, poor feeding ability, and increased calorie consumption due to dystonic and athetoid movements. The prognosis in A-T is truly appalling, and therefore we aim for the best possible quality of life. As well as showing that PEG feeding halts the progression of malnutrition (albeit in small numbers of children as compared to controls) and making feeding safer in the presence of possible aspiration, one consistent theme (not reported in our paper but consistently reported by parents in our clinic and previously published by other groups(1)) is significant caregiver satisfaction and reduction in very lengthy meals times. This has a very significant impact in improving the quality of life of carers and patients.
It is well recognised in other chronic paediatric diseases, such as cystic fibrosis and chronic kidney disease that nutrition is a predictor of overall quality of life. Currently, we have very little to offer patients with A-T in terms of intervention to prevent the development of malignancy or neurological progression, but we believe by extrapolating from other similar patient groups, we can reduce the risk of death from pulmonary failure. Key to this is prevention of wasting.
All long term invasive medical technologies interfere with the human condition of childhood, and we wholeheartedly agree that a PEG is life-changing and should always be carefully considered on an individual basis. However, given the poor weight gain in many A-T children, we believe it is important to discuss whether a PEG would be useful early, and consider placement prior to the respiratory deterioration of the child.
Yours sincerely
Emma Stewart1, Andrew P Prayle2, Alison Tooke1, Sara Pasalodos3, Mohnish Suri3, Andy Bush4,5,6, Jayesh M Bhatt1
Author affiliations:
1 Nottingham Children's Hospital, National Paediatric Ataxia Telangiectasia Clinic, QMC, Nottingham, UK
2 University of Nottingham, School of Clinical Science, Queens Medical Centre, Child Health, Nottingham, UK
3 Nottingham Clinical Genetics Service, National Paediatric Ataxia Telangiectasia Clinic, Clinical Genetics Service, City Hospital Campus, Nottingham, UK
4 Imperial College, London, UK
5 National Heart and Lung Institute, London, UK
6 Royal Brompton & Harefield NHS Foundation Trust, London, UK
1. Lefton-Greif MA, Crawford TO, McGrath-Morrow S, Carson KA, Lederman HM. Safety and caregiver satisfaction with gastrostomy in patients with Ataxia Telangiectasia. Orphanet J Rare Dis. 2011;6:23.
In the section titled 'Neurodevelopmental conditions', Taylor et al. state, "One study reported data separately for 2012 and 2015 and demonstrated an increase from 1.8% to 15.1%". However, the last row in Table 2 in the paper cited, Morandini et al, seems to give the relevant figure as 13.8%, not 1.8%.[1]
Ocham's Razor would suggest this was a simple typographical error that was missed during proofreading and peer review rather than some Machiavellian attempt to mislead as I don't think that Taylor or Cass rely on this particular figure for any conclusions or recommendations.
Note that this error was reported in a paper by Grijseels.[2]
References
1 Shifts in demographics and mental health co-morbidities among gender dysphoric youth referred to a specialist gender dysphoria service - James S Morandini, Aidan Kelly, Nastasja M de Graaf, Polly Carmichael, Ilan Dar-Nimrod, 2022. https://journals.sagepub.com/doi/abs/10.1177/13591045211046813 (accessed 23 June 2024)
2 Grijseels DM. Biological and psychosocial evidence in the Cass Review: a critical commentary. International Journal of Transgender Health. 2024;0:1–11. doi: 10.1080/26895269.2024.2362304
The PROSPERO registration of the Gender Identity Service Series https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289659 specifies the use of the Mixed Methods Appraisal Tool (MMAT) as its tool for assessing study quality, however in the final review series, a number of different appraisal tools were used, primarily the Newcastle-Ottowa Scale (NOS).
The Review's modified NOS scale specifies a score cutoff of <= 50% for designating studies as low quality.
The methodology also indicates that studies in languages other than English would be excluded, but "Clinical guidelines for children and adolescents experiencing gender dysphoria or incongruence: a systematic review of guideline quality (part 1)" notes that guidelines that could be reliably translated would be included.
Could the authors please clarify:
a) When this change in methodology took place
b) The reasoning behind this change in methodology
c) Why the PROSPERO record has been updated on April 24 2024 with the completion of the study without noting the change in methodology
d) How the 50% cutoff was decided
e) Why the decision to include documents that could be reliably translated was only applied to one study in the series
Thank you for the opportunity to reply, here is our response.
We would like to thank the authors for their valuable comments, we believe that these comments add to and complement our article. Our article aimed to cover a wide breadth of common gynaecological conditions that can affect children and unfortunately we were therefore not able to go in to great detail for each condition covered. We would certainly agree on the importance of an early diagnosis for lichen sclerosus and collaboration with a dermatologist for treatment if available. The British Association of Dermatologists guidelines for the management of lichen sclerosus was not published when we wrote our article, we can see that this is a very valuable resource.
Kind Regards
Jo Ritchie
Dear Sir/ Editor,
Dr Smith makes relevant and interesting points regarding the terminology used for fluids, which can be used for both “resuscitation” purposes and “maintenance” therapy, and we thank him for his interest and response.
The purpose of this clinical question was to review the current evidence for paediatric patients in relation to “ balanced fluids”, a term emerging in the medical literature. NICE recommends using any isotonic crystalloid, which covers a wide range of sodium concentration from 130 to 154mmol/L (reference 1 in the article).
The loss of electrolytes, either from the gut or as a result of renal impairment, needs regular clinical review. We observe that repeated bicarbonate measurements are not regularly undertaken after initial assessment or following admission and it is important to remind trainees to consider these losses, hence our recommendation of daily monitoring of electrolytes. By following this approach, appropriate individualised adjustments can be made to the fluid prescription of patients as necessary.
Our conclusion from this question highlighted that research needs to be undertaken in the paediatric population of bicarbonate/ lactate containing fluids to determine whether this may affect acute kidney injury and other specific clinical outcomes. We agree attention to detail is always necessary when caring for infants and children receiving intrav...
Show MoreDear Editor,
We thank you for the opportunity to discuss our data with the two correspondents who raised some concerns regarding the selected population of our analysis on neonatal outcomes following new reimbursement criteria on palivizumab use. They also reported data collected during the same time period and apparently different from our main results.
In response to the first correspondent, our analysis is based on children < 2 years of age because the candidate for palivizumab treatments are included within this subpopulation. In fact, the therapeutic indication (1) of palivizumab includes not only the preterm infants up to 1 year of age but also children up to 2 years of age and treated for bronchopulmonary dysplasia or born with a serious heart disease. Furthermore, our selected population is consistent with previous analysis (2) that measured the association between updated guidelines-based palivizumab administration and hospitalization for Respiratory Syncytial Virus (RSV). Table 1 of our study reports children up to 6 months of age, both at risk of RSV and including hospitalization data. We agree that this is probably the subpopulation with the major impact of the palivizumab treatment and regulatory decision. However, also in this case no differences in hospitalization rate have been detected before-after the AIFA’ limitation for palivizumab: 1031/47.608 (21.7 ‰) and 436/22715 (19.2 ‰) hospitalizations, respectiv...
Show MoreDear Sir
We thank Professor Marchetti for his comments on our article in ADC (1). He raises two important questions we wish to comment on.
Regarding which dose of aspirin to use, we are also interested in the suggestion that anti-aggregant doses of aspirin might be a preferred option for the acute inflammatory phase of Kawasaki disease (KD). It is indeed possible that future guidance may recommend low dose aspirin (3-5 mg/kg/day) at all stages of KD, as suggested by the retrospective data referred to by Professor Marchetti (2). Whilst we acknowledge the potential merits of such an approach, particularly in relation to avoidance of toxicity, there has never been a prospective controlled clinical trial to support this and therefore no high-level evidence on which to base firm guidance. Two other practical considerations are worthy of highlighting in relation to aspirin. Firstly, nonsteroidal anti-inflammatory drugs such as ibuprofen, which antagonize platelet inhibition induced by aspirin (3), should be avoided in patients with KD receiving anti-aggregant doses of aspirin. Secondly, although the risk of low dose aspirin (3-5 mg/kg) in being associated with Reye syndrome is unknown, usual advice is to discontinue in the event of inter-current infection.
Regarding the use of corticosteroids for primary treatment of KD, we have been strong advocates of this for several years, as reflected in previously published guidance (4, 5). This is now brought into...
Show MoreWe 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)
We thank Dr. Garstang and Dr. Debelle for their comments on our article in ADC (1).
We are pleased that the correspondents support our finding of a strong association between chronic conditions and respiratory tract Infection mortality in children which, though well-recognised by clinicians, has not previously been quantified.
The correspondents rightly highlight that our analyses concentrate only on unexpected deaths after age 2 months. We chose this definition because these early deaths are more prone to linkage error and more importantly, tend to be related to maternal health during pregnancy and delivery, preterm birth, intrapartum events and congenital anomalies, and therefore may not be avoidable through improved care after postnatal discharge.
As our paper highlights, an indication of whether a death was expected or not on a death certificate or in hospital records is necessary in order to assess whether a death was avoidable or amenable to healthcare intervention. A classification of whether a death was expected or unexpected could also be notified to Child Death Overview Panels and other agencies by those completing the death certificates. This would be helpful to Child Death Overview Panels in their deliberations as well as feeding into the collation of mortality statistics.
References:
1. 1. Verfürden ML, Gilbert R, Sebire N, Hardelid P. Arch Dis Child 2018;103:1125–1131.
Dear Editor,
Re: Professor Andrew N Williams’ letter to ADC “Failing to consider Virtual Academic Units within UK infrastructure for research that benefits infants, children and young people”
We were pleased to hear the success of the Virtual Academic Unit and invited Professor Andrew Williams to contribute to the RCPCH research bulletin of March 2019.
At the RCPCH, we know from our research and from speaking to our membership, that paediatricians around the country have little or no allocated funding or designated research time. We, therefore, applaud all those paediatricians who continue to go above and beyond to undertake research to achieve better health outcomes for children and young people.
The RCPCH is fully committed to strengthening basic science and clinical research and the development of devices, medicines and technologies that address the needs of children. Furthermore, our committment includes supporting our members and growing and promoting opportunities for research within paediatrician’s careers.
We will continue to work with our partners across the UK to influence, promote and grow child health research.
Lindsey Hunter, Research Development Manager, RCPCH
Professor Anne Greenough, immediate past Vice President Science and Research, RCPCH and Professor of Neonatology and Clinical Respiratory Physiology, King's College London
Dear Editor,
We thank Professor Wright for her comments, and we welcome the opportunity to provide some clarification and further analysis.
We reported Z-scores rather than percentiles, although some comments on approximate percentiles can be made. Assuming that Z scores of -1.96 and -3 represent approximately the 2.5th and 0.2nd centiles respectively, 36/101 children were below the 2.5th centile, and 17/101 were below the 0.2nd centile for weight. Additionally, our mixed effects model (accounting for multiple measurements) modelling the group trend over time estimated the mean weight Z score at 11 years to be -1.63 (approximately 5th centile).
Despite the overall short stature of the group, 24/101 children had a BMI Z score of less than -1.96. So, by this approach, their weight was low even after taking into account stature. We agree that we cannot infer causality from this observational study, but we believe a proportion of the stunted growth is explained by low weight. We are exploring other measures of malnutrition, such as skin-fold thickness.
Whilst our patient numbers are small, they do give some weight to the argument that PEG feeding halts the progression of malnutrition. We investigated the rate of decline of weight after PEG insertion. In a mixed effects model with a random intercept for individual patients, the rate of wei...
Show MoreIn the section titled 'Neurodevelopmental conditions', Taylor et al. state, "One study reported data separately for 2012 and 2015 and demonstrated an increase from 1.8% to 15.1%". However, the last row in Table 2 in the paper cited, Morandini et al, seems to give the relevant figure as 13.8%, not 1.8%.[1]
Ocham's Razor would suggest this was a simple typographical error that was missed during proofreading and peer review rather than some Machiavellian attempt to mislead as I don't think that Taylor or Cass rely on this particular figure for any conclusions or recommendations.
Note that this error was reported in a paper by Grijseels.[2]
References
1 Shifts in demographics and mental health co-morbidities among gender dysphoric youth referred to a specialist gender dysphoria service - James S Morandini, Aidan Kelly, Nastasja M de Graaf, Polly Carmichael, Ilan Dar-Nimrod, 2022. https://journals.sagepub.com/doi/abs/10.1177/13591045211046813 (accessed 23 June 2024)
2 Grijseels DM. Biological and psychosocial evidence in the Cass Review: a critical commentary. International Journal of Transgender Health. 2024;0:1–11. doi: 10.1080/26895269.2024.2362304
The PROSPERO registration of the Gender Identity Service Series https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289659 specifies the use of the Mixed Methods Appraisal Tool (MMAT) as its tool for assessing study quality, however in the final review series, a number of different appraisal tools were used, primarily the Newcastle-Ottowa Scale (NOS).
The Review's modified NOS scale specifies a score cutoff of <= 50% for designating studies as low quality.
The methodology also indicates that studies in languages other than English would be excluded, but "Clinical guidelines for children and adolescents experiencing gender dysphoria or incongruence: a systematic review of guideline quality (part 1)" notes that guidelines that could be reliably translated would be included.
Could the authors please clarify:
a) When this change in methodology took place
b) The reasoning behind this change in methodology
c) Why the PROSPERO record has been updated on April 24 2024 with the completion of the study without noting the change in methodology
d) How the 50% cutoff was decided
e) Why the decision to include documents that could be reliably translated was only applied to one study in the series
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