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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 Professor Davendralingam Sinniah Paediatrician
In response to your letter. We agree with you patient safety comes first in all age groups.
1. Tramadol is not a full agonist opioid. The issue that we have highlighted with tramadol (and codeine) is when the patient is a CYP2D6 ultrametaboliser there is potential for serious adverse events. The CYP2D6 issue is not at play for the alternative pure opioid agonists oxycodone and morphine (the latter as you suggested). However all these agents have potentially serious adverse effects, including sedation, respiratory depression (in therapeutic doses) and fatality (usually in excessive dosing or at risk patients).
2. We agree with you that the simple non-opioid analgesics (paracetamol and NSAIDs when not contraindicated) are preferred. We are advocating for tramadol when stronger analgesia is required as a 3rd line alternative to the pure opioid agonists. We each work in tertiary centres where tramadol is used: one a women’s hospital where it is used perioperatively post caesarean and vaginal delivery; and the others where is is used off label in children of all ages (including infants).
3. There are few data concerning respiratory depression and tramadol in neonates. However concentrations in breast fed neonates are low and not expected to cause respiratory depression after usual doses.
4. Please point to evidence in the literature that tramadol administered to women who are breastfeeding cause...
Dear Professor Davendralingam Sinniah Paediatrician
In response to your letter. We agree with you patient safety comes first in all age groups.
1. Tramadol is not a full agonist opioid. The issue that we have highlighted with tramadol (and codeine) is when the patient is a CYP2D6 ultrametaboliser there is potential for serious adverse events. The CYP2D6 issue is not at play for the alternative pure opioid agonists oxycodone and morphine (the latter as you suggested). However all these agents have potentially serious adverse effects, including sedation, respiratory depression (in therapeutic doses) and fatality (usually in excessive dosing or at risk patients).
2. We agree with you that the simple non-opioid analgesics (paracetamol and NSAIDs when not contraindicated) are preferred. We are advocating for tramadol when stronger analgesia is required as a 3rd line alternative to the pure opioid agonists. We each work in tertiary centres where tramadol is used: one a women’s hospital where it is used perioperatively post caesarean and vaginal delivery; and the others where is is used off label in children of all ages (including infants).
3. There are few data concerning respiratory depression and tramadol in neonates. However concentrations in breast fed neonates are low and not expected to cause respiratory depression after usual doses.
4. Please point to evidence in the literature that tramadol administered to women who are breastfeeding causes adverse neonatal effects such as excessive sleepiness, difficulty breathing, and fatal breathing problems. Patient safety is always foremost in our minds but we could find little evidence of these adverse effects. Further we present pharmacokinetic evidence as to why that is unlikely
5. You present warnings, not evidence, concerning these complications, like the FDA, AAP and ACOGs conservative and reactive stance. We acknowledge your concerns. Please note that our editorial was a consequence of these warnings that we felt were unjustified. That was the point of the review.
We wish to advocate for pain relief in postpartum mothers who have moderate to severe pain and require analgesic escalation beyond the acetaminophen and nsNSAID. The emphasis from a safety perspective, as you have suggested, is that opioid agonists and tramadol should be prescribed at the lowest effective dose and for the shortest time possible. Sensible advice should be provided to all patients receiving opioid and tramadol scripts at discharge including breastfeeding mothers.
Greta M Palmer1, Brian J Anderson2, David K Linscott3, Michael J Paech4,5, Karel Allegaert6,7
affiliations as per primary article
I was deeply surprised that this leading paper in citing the 2018 ‘Turning the tide 5 years on’ does not mention ‘virtual Biomedical Research Units and Centres’ (1,2). The establishment of such centres had been specifically recommended in the seminal 2012 RCPCH Report ‘Turning the Tide: Harnessing the power of child health research’ (3).
We in Northampton established a Virtual Academic Unit (VAU) in 2004, and published our experience of its first 10 years experience in Archives in 2015 (4).
Among the articles published through the VAU there is ‘Ethical Research Involving Children.’ (2013) UNICEF, which predates the College own Children’s and Young People’s Child Health Research Charter. (5)
The Virtual Academic Unit is continuing to collaborate on and publish in clinical child health research to this day. (6) However, it has remained totally unfunded with no allocated research time in spite of every possible endeavour to address this.
We have to be pragmatic and recognise that with present and future increasing pressures within the NHS having any research time within a job plan is seen by most NHS managers as an unproductive luxury given the immediate pressing necessities of delivering a clinical service.
As my 2015 article relates
‘A VAU has its place and in a present and future environment where resources are continuing to be constrained, a method of working that allows something meaningful to be produced, from where previousl...
I was deeply surprised that this leading paper in citing the 2018 ‘Turning the tide 5 years on’ does not mention ‘virtual Biomedical Research Units and Centres’ (1,2). The establishment of such centres had been specifically recommended in the seminal 2012 RCPCH Report ‘Turning the Tide: Harnessing the power of child health research’ (3).
We in Northampton established a Virtual Academic Unit (VAU) in 2004, and published our experience of its first 10 years experience in Archives in 2015 (4).
Among the articles published through the VAU there is ‘Ethical Research Involving Children.’ (2013) UNICEF, which predates the College own Children’s and Young People’s Child Health Research Charter. (5)
The Virtual Academic Unit is continuing to collaborate on and publish in clinical child health research to this day. (6) However, it has remained totally unfunded with no allocated research time in spite of every possible endeavour to address this.
We have to be pragmatic and recognise that with present and future increasing pressures within the NHS having any research time within a job plan is seen by most NHS managers as an unproductive luxury given the immediate pressing necessities of delivering a clinical service.
As my 2015 article relates
‘A VAU has its place and in a present and future environment where resources are continuing to be constrained, a method of working that allows something meaningful to be produced, from where previously nothing could be expected at all. …Some realistic mechanism translating into sustained funding for VAUs would be very helpful.’ (4)
2 Hunter L, Greenough A, Modi N . Turning the tide 5 years on. London: Royal College of Paediatrics and Child Health, 2018.
3 Royal College of Paediatrics and Child Health. Turning the Tide: Harnessing the power of child health research. RCPCH, 2012. http://www.rcpch.ac.uk/system/files/protected/page/
Turning%20the%20Tide%20Full%20Report.pdf
4 Williams A.N. A Virtual Academic Unit – the first 10 years. Arch Dis Child Educ Pract 2015; 100(3):164-5
5 Williams AN. Facilitating future benefit when a participant has a degenerative illness and cannot give consent. In: Graham A, Powell M, Taylor N, et al., eds. Ethical research involving
children. Florence: UNICEF Office of Research—Innocenti, 2013:118–9. http://childethics.com/wp-content/uploads/2013/11/ERIC_Compendium_Case-S...
6 Developmental disabilities among children younger than 5 years in 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Global Research on Developmental Disabilities Collaborators* Lancet Global Health 2018 http://dx.doi.org/10.1016/S2214-109X(18)30309-7
We commend the DEPICT group for gathering evidence to support or refute the current set of performance standards for specialist paediatric intensive care retrieval teams (PICRTs), for which there is currently limited evidence base.
A key tenet of ‘the paper’ was geographical distance as the sole reason for a breach in the 180 minute to bedside standard.[1] In our experience, the commonest reason to breach was ‘team availability’. In 2018 South Thames Retrieval Service (STRS) performed 824 emergency retrievals. In 4% of these, the team did not reach the bedside within 180 minutes. On 33/36 occasions, the reason for delay was lack of availability of retrieval team due to concurrent deployment.
STRS is commissioned to staff two teams on every shift. In 2018 32% of retrievals were performed concurrently. STRS is the second busiest PICRT in the UK, however on 29 % of shifts, no retrieval team was launched. STRS is a fully integrated retrieval service –all staff are based in the intensive care unit, and when not on retrieval work clinically in the PICU. This allows flexible staffing and in times of high demand, helps support increased PICU bed capacity. In 2018, 98.8% of patients were kept within region.
The authors highlight the importance of mobilisation time. Despite the integration of our service within a busy PICU, STRS recorded the highest national compliance with the mobilisation standard for 2017.[2]
We commend the DEPICT group for gathering evidence to support or refute the current set of performance standards for specialist paediatric intensive care retrieval teams (PICRTs), for which there is currently limited evidence base.
A key tenet of ‘the paper’ was geographical distance as the sole reason for a breach in the 180 minute to bedside standard.[1] In our experience, the commonest reason to breach was ‘team availability’. In 2018 South Thames Retrieval Service (STRS) performed 824 emergency retrievals. In 4% of these, the team did not reach the bedside within 180 minutes. On 33/36 occasions, the reason for delay was lack of availability of retrieval team due to concurrent deployment.
STRS is commissioned to staff two teams on every shift. In 2018 32% of retrievals were performed concurrently. STRS is the second busiest PICRT in the UK, however on 29 % of shifts, no retrieval team was launched. STRS is a fully integrated retrieval service –all staff are based in the intensive care unit, and when not on retrieval work clinically in the PICU. This allows flexible staffing and in times of high demand, helps support increased PICU bed capacity. In 2018, 98.8% of patients were kept within region.
The authors highlight the importance of mobilisation time. Despite the integration of our service within a busy PICU, STRS recorded the highest national compliance with the mobilisation standard for 2017.[2]
In our region 90% of intubations are performed by the referring team. The integrated PICU- PICRT model allows all staff to remain proficient in practical skills required for retrieval but infrequently performed during transfer.
An additional benefit of co-location of services is the reduction in re-deployment time when a patient returns to the base PICU. Co-location in the busiest receiving units would allow maximum benefit from this time saving and should be considered in future analyses.
We agree with the authors and acknowledge PICRT as an expensive resource. We suggest therefore that the most flexible, practical, financially viable team utilisation models need to be considered in any service redesign. As well as co-location with a PICU, we argue for greater integration of the teams within the PICUs themselves.
1. King M, Ramnarayan P, Seaton SE et al Modelling the allocation of paediatric intensive care retrieval teams in England and Wales. Archives of disease in Childhood Published online First: 11 February 2019.
2. Paediatric Intensive Care Audit Network Annual Report 2017 (published November 2017): Universities of Leeds and Leicester.
Professors Bush and Parvord usefully highlight key recommendations from their Lancet commission on asthma and acknowledge they are deliberately controversial. They accept the benefits of inhaled corticosteroids, but cite current shortcomings in meeting the needs of asthma sufferers as a reason to shift from a reductionist to a more detailed phenotyic approach to drive the development and use of new biological ‘precision medicines’.
We do have a problem with our current approach and especially in the UK, which like the US, Australia and New Zealand, has an asthma death rate amongst adolescents at least three times higher than other European countries for which there is reliable data.1 However, emphasizing a need for basic science to focus on developing new drugs for specific patient groups, risks underestimating and misunderstanding the importance of psycho-social factors in determining all asthma phenotypes and especially those at risk of fatal asthma.
Social and environmental factors are more than co-morbidities causing dysfunctional breathing and poor adherence to prescribed therapies. Systematic reviews and meta-analyses consistently show that pre-natal stress and stress in early childhood significantly increase the risk of subsequent wheeze and asthma.2 In prospective studies, depression in adults is associated with developing asthma and there are many studies demonstrating that anxiety can cause bronchoconstriction and lung inflammation.3,4 Mechanistic st...
Professors Bush and Parvord usefully highlight key recommendations from their Lancet commission on asthma and acknowledge they are deliberately controversial. They accept the benefits of inhaled corticosteroids, but cite current shortcomings in meeting the needs of asthma sufferers as a reason to shift from a reductionist to a more detailed phenotyic approach to drive the development and use of new biological ‘precision medicines’.
We do have a problem with our current approach and especially in the UK, which like the US, Australia and New Zealand, has an asthma death rate amongst adolescents at least three times higher than other European countries for which there is reliable data.1 However, emphasizing a need for basic science to focus on developing new drugs for specific patient groups, risks underestimating and misunderstanding the importance of psycho-social factors in determining all asthma phenotypes and especially those at risk of fatal asthma.
Social and environmental factors are more than co-morbidities causing dysfunctional breathing and poor adherence to prescribed therapies. Systematic reviews and meta-analyses consistently show that pre-natal stress and stress in early childhood significantly increase the risk of subsequent wheeze and asthma.2 In prospective studies, depression in adults is associated with developing asthma and there are many studies demonstrating that anxiety can cause bronchoconstriction and lung inflammation.3,4 Mechanistic studies to improve our understanding about how stress induced physiological changes cause asthma might lead to a more effective approach to treating patients irrespective of their endotype. Such an approach might prove to be more cost-effective than the pursuit of biologicals.
Professor Bush’s 'canary in the mine', as used in his analogy to low spirometry in young adults being a marker for cardio-pulmonary mortality, might once have been a very stressed chick.
References.
1. International comparisons of health and wellbeing in adolescence and early adulthood. https://www.nuffieldtrust.org.uk/files/2019-02/1550657729_nt-ayph-adoles... accessed 29th March 2019
2. Rosa MJ, Lee AG, Wright RJ. Evidence establishing a link between prenatal and early-life stress and asthma development. Curr Opin Allergy Clin Immunol. 2018;18(2):148-158. doi: 10.1097/ACI.0000000000000421.
3. Gao YH, Zhao HS, Zhang FR et al. The Relationship between Depression and Asthma: A Meta-Analysis of Prospective Studies. PLoS One. 2015;10(7):e0132424. doi: 10.1371/journal.pone.0132424.
4. Miyasaka T, Dobashi-Okuyama K, Takahashi T. The interplay between neuroendocrine activity and psychological stress-induced exacerbation of allergic asthma. Allergol Int. 2018;67(1):32-42. doi: 10.1016/j.alit.2017.04.013.
The response to our article was received with interest. Grosse and Lanzieri raise important points in connection with our recent paper [1], noting concerns that the paper overestimates the financial cost burden associated with congenital cytomegalovirus (cCMV). These points are contingent on our estimate that at least 50% total costs associated with cCMV stemmed from the cost of autism spectrum disorder (ASD) among individuals with cCMV.
First, Grosse and Lanzieri point out that an association between cCMV and ASD has not been conclusively established, citing a systematic review and meta-analysis by Maeyama et al. (2017) [2]. We agree that there is uncertainty over this association and the prevalence estimates used (along with many of the other estimates), and have emphasised throughout our article that (i) the model is limited by the validity of the inputs, and (ii) more research is required to fully understand the epidemiology, aetiology and prognosis of cCMV. Indeed, Maeyama et al. (2017) [2] report a significant association between cCMV and ASD, but caution that these calculations are seriously limited by the infrequent number of events in the included studies. As we do, they stress the need for further research to clarify this issue.
Second, Grosse and Lanzieri suggest that the prevalence calculation of ASD attributable to cCMV should have been calculated as the proportion of cCMV individuals with ASD minus the proportion of non-cCMV individuals with AS...
The response to our article was received with interest. Grosse and Lanzieri raise important points in connection with our recent paper [1], noting concerns that the paper overestimates the financial cost burden associated with congenital cytomegalovirus (cCMV). These points are contingent on our estimate that at least 50% total costs associated with cCMV stemmed from the cost of autism spectrum disorder (ASD) among individuals with cCMV.
First, Grosse and Lanzieri point out that an association between cCMV and ASD has not been conclusively established, citing a systematic review and meta-analysis by Maeyama et al. (2017) [2]. We agree that there is uncertainty over this association and the prevalence estimates used (along with many of the other estimates), and have emphasised throughout our article that (i) the model is limited by the validity of the inputs, and (ii) more research is required to fully understand the epidemiology, aetiology and prognosis of cCMV. Indeed, Maeyama et al. (2017) [2] report a significant association between cCMV and ASD, but caution that these calculations are seriously limited by the infrequent number of events in the included studies. As we do, they stress the need for further research to clarify this issue.
Second, Grosse and Lanzieri suggest that the prevalence calculation of ASD attributable to cCMV should have been calculated as the proportion of cCMV individuals with ASD minus the proportion of non-cCMV individuals with ASD. While we understand the criticism of the calculation of ASD prevalence in cCMV, had we calculated the prevalence in the way suggested here (i.e. making assumptions that the underlying level of ASD in the cCMV population not attributable to the virus would match that observed in the non-cCMV population, and that this should be removed from our estimates) we would be treating ASD differently to the other impairments reported. For all impairments, the estimated number of children with cCMV affected by that impairment was used, not accounting for the level of diagnosis in the general population. We appreciate that where data are robust, the suggested approach would be advisable, but given the scarcity of prevalence studies for some impairments and level of variation in prevalence estimates for others, we sought to simplify assumptions as far as possible.
While our study aimed to estimate the financial burden of cCMV to the UK, we acknowledge, and indeed state in the discussion, that there is a lack of robust evidence for use as inputs into such an analysis. On the basis of the estimates we have imputed from the available data, we believe the true cost of cCMV is likely to be substantial. Our paper emphasises the need for further and more detailed research into both the costs and impairments associated with cCMV to allow greater accuracy in the calculation of cost estimates.
[1] Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV in the UK. Arch Dis Child 2018 doi: 10.1136/archdischild-2018-316010 [published Online First: 2018/11/26]
[2] Maeyama K, Tomioka K, Nagase H, et al. Congenital cytomegalovirus infection in children with autism spectrum disorder: systematic review and meta-analysis. J Autism Dev Disord 2018;48(5):1483-91. doi: 10.1007/s10803-017-3412-x [published Online First: 2017/12/01]
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.
I was very pleased to read this letter on involving children and young people (CYP) which is so important.
RheumMates (https://www.facebook.com/groups/rheumates/) is a group which was already set up together with young people with rheumatological conditions (based on the highly successful NeoMates model, which provides parent peer support for neonatal unit parents) for this purpose.
This came about after we presented NeoMates at the Royal College of Paediatrics and Child Health annual conference at the same time that an inspirational young person presented her work on setting up Raiise (https://raiise.co.uk) to improve care and provide support for young people with "invisible illnesses".
It is a place where CYP can chat to each other safely, knowing that everyone in the group has a common link.
It is also a source of expert knowledge and information.
To complement it, we also set up RheumMatesParents where parents can also chat, gaining the peer support that the NeoMates parents have had for many years.
I wonder if these could in some way be combined to help improve peer support and patient engagement?
Thank you for your attention to this research. Firstly, this systematic review showed that LOS was decreased in the HFNC group comparing with SOT group in low-income and middle-income countries. As you mentioned in the letter that even in high-income countries, it’s not realistic to treat all bronchiolitis patients with HFNC during RSV peaks. The inconsistent result of LOS in different countries may be caused by the level of medical practice in different areas because the LOS in low-income and middle-income countries was significantly longer than in high-income countries. So the clinical heterogeneity suggested that the level of medical practice was also important for bronchiolitis. Secondly, two studies showed that patients with treatment failures in SOT group could be treated with HFNC in the wards. This meta-analysis showed that there was a significant increase in the incidence of treatment failure in HFNC group compared with nCPAP group (RR 1.61, 95% CI 1.06 to 2.42, p=0.02). Therefore, we need more research to explore which choice (HFNC or nCPAP) is better for patients with treatment failures in standard oxygen supplementation.
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.
References
1. Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV...
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.
References
1. Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV in the UK. Arch Dis Child 2018 doi: 10.1136/archdischild-2018-316010 [published Online First: 2018/11/26]
2. Maeyama K, Tomioka K, Nagase H, et al. Congenital cytomegalovirus infection in children with autism spectrum disorder: systematic review and meta-analysis. J Autism Dev Disord 2018;48(5):1483-91. doi: 10.1007/s10803-017-3412-x [published Online First: 2017/12/01]
3. Korndewal MJ, Oudesluys-Murphy AM, Kroes ACM, et al. Long-term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study. Dev Med Child Neurol 2017;59(12):1261-68. doi: 10.1111/dmcn.13556 [published Online First: 2017/10/11]
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 Professor Davendralingam Sinniah Paediatrician
Show MoreIn response to your letter. We agree with you patient safety comes first in all age groups.
1. Tramadol is not a full agonist opioid. The issue that we have highlighted with tramadol (and codeine) is when the patient is a CYP2D6 ultrametaboliser there is potential for serious adverse events. The CYP2D6 issue is not at play for the alternative pure opioid agonists oxycodone and morphine (the latter as you suggested). However all these agents have potentially serious adverse effects, including sedation, respiratory depression (in therapeutic doses) and fatality (usually in excessive dosing or at risk patients).
2. We agree with you that the simple non-opioid analgesics (paracetamol and NSAIDs when not contraindicated) are preferred. We are advocating for tramadol when stronger analgesia is required as a 3rd line alternative to the pure opioid agonists. We each work in tertiary centres where tramadol is used: one a women’s hospital where it is used perioperatively post caesarean and vaginal delivery; and the others where is is used off label in children of all ages (including infants).
3. There are few data concerning respiratory depression and tramadol in neonates. However concentrations in breast fed neonates are low and not expected to cause respiratory depression after usual doses.
4. Please point to evidence in the literature that tramadol administered to women who are breastfeeding cause...
I was deeply surprised that this leading paper in citing the 2018 ‘Turning the tide 5 years on’ does not mention ‘virtual Biomedical Research Units and Centres’ (1,2). The establishment of such centres had been specifically recommended in the seminal 2012 RCPCH Report ‘Turning the Tide: Harnessing the power of child health research’ (3).
We in Northampton established a Virtual Academic Unit (VAU) in 2004, and published our experience of its first 10 years experience in Archives in 2015 (4).
Among the articles published through the VAU there is ‘Ethical Research Involving Children.’ (2013) UNICEF, which predates the College own Children’s and Young People’s Child Health Research Charter. (5)
The Virtual Academic Unit is continuing to collaborate on and publish in clinical child health research to this day. (6) However, it has remained totally unfunded with no allocated research time in spite of every possible endeavour to address this.
We have to be pragmatic and recognise that with present and future increasing pressures within the NHS having any research time within a job plan is seen by most NHS managers as an unproductive luxury given the immediate pressing necessities of delivering a clinical service.
As my 2015 article relates
‘A VAU has its place and in a present and future environment where resources are continuing to be constrained, a method of working that allows something meaningful to be produced, from where previousl...
Show MoreWe commend the DEPICT group for gathering evidence to support or refute the current set of performance standards for specialist paediatric intensive care retrieval teams (PICRTs), for which there is currently limited evidence base.
A key tenet of ‘the paper’ was geographical distance as the sole reason for a breach in the 180 minute to bedside standard.[1] In our experience, the commonest reason to breach was ‘team availability’. In 2018 South Thames Retrieval Service (STRS) performed 824 emergency retrievals. In 4% of these, the team did not reach the bedside within 180 minutes. On 33/36 occasions, the reason for delay was lack of availability of retrieval team due to concurrent deployment.
STRS is commissioned to staff two teams on every shift. In 2018 32% of retrievals were performed concurrently. STRS is the second busiest PICRT in the UK, however on 29 % of shifts, no retrieval team was launched. STRS is a fully integrated retrieval service –all staff are based in the intensive care unit, and when not on retrieval work clinically in the PICU. This allows flexible staffing and in times of high demand, helps support increased PICU bed capacity. In 2018, 98.8% of patients were kept within region.
The authors highlight the importance of mobilisation time. Despite the integration of our service within a busy PICU, STRS recorded the highest national compliance with the mobilisation standard for 2017.[2]
In our region 90% of intubations are p...
Show MoreProfessors Bush and Parvord usefully highlight key recommendations from their Lancet commission on asthma and acknowledge they are deliberately controversial. They accept the benefits of inhaled corticosteroids, but cite current shortcomings in meeting the needs of asthma sufferers as a reason to shift from a reductionist to a more detailed phenotyic approach to drive the development and use of new biological ‘precision medicines’.
Show MoreWe do have a problem with our current approach and especially in the UK, which like the US, Australia and New Zealand, has an asthma death rate amongst adolescents at least three times higher than other European countries for which there is reliable data.1 However, emphasizing a need for basic science to focus on developing new drugs for specific patient groups, risks underestimating and misunderstanding the importance of psycho-social factors in determining all asthma phenotypes and especially those at risk of fatal asthma.
Social and environmental factors are more than co-morbidities causing dysfunctional breathing and poor adherence to prescribed therapies. Systematic reviews and meta-analyses consistently show that pre-natal stress and stress in early childhood significantly increase the risk of subsequent wheeze and asthma.2 In prospective studies, depression in adults is associated with developing asthma and there are many studies demonstrating that anxiety can cause bronchoconstriction and lung inflammation.3,4 Mechanistic st...
The response to our article was received with interest. Grosse and Lanzieri raise important points in connection with our recent paper [1], noting concerns that the paper overestimates the financial cost burden associated with congenital cytomegalovirus (cCMV). These points are contingent on our estimate that at least 50% total costs associated with cCMV stemmed from the cost of autism spectrum disorder (ASD) among individuals with cCMV.
First, Grosse and Lanzieri point out that an association between cCMV and ASD has not been conclusively established, citing a systematic review and meta-analysis by Maeyama et al. (2017) [2]. We agree that there is uncertainty over this association and the prevalence estimates used (along with many of the other estimates), and have emphasised throughout our article that (i) the model is limited by the validity of the inputs, and (ii) more research is required to fully understand the epidemiology, aetiology and prognosis of cCMV. Indeed, Maeyama et al. (2017) [2] report a significant association between cCMV and ASD, but caution that these calculations are seriously limited by the infrequent number of events in the included studies. As we do, they stress the need for further research to clarify this issue.
Second, Grosse and Lanzieri suggest that the prevalence calculation of ASD attributable to cCMV should have been calculated as the proportion of cCMV individuals with ASD minus the proportion of non-cCMV individuals with AS...
Show MoreWe 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.
I was very pleased to read this letter on involving children and young people (CYP) which is so important.
RheumMates (https://www.facebook.com/groups/rheumates/) is a group which was already set up together with young people with rheumatological conditions (based on the highly successful NeoMates model, which provides parent peer support for neonatal unit parents) for this purpose.
This came about after we presented NeoMates at the Royal College of Paediatrics and Child Health annual conference at the same time that an inspirational young person presented her work on setting up Raiise (https://raiise.co.uk) to improve care and provide support for young people with "invisible illnesses".
It is a place where CYP can chat to each other safely, knowing that everyone in the group has a common link.
It is also a source of expert knowledge and information.
To complement it, we also set up RheumMatesParents where parents can also chat, gaining the peer support that the NeoMates parents have had for many years.
I wonder if these could in some way be combined to help improve peer support and patient engagement?
Thank you for your attention to this research. Firstly, this systematic review showed that LOS was decreased in the HFNC group comparing with SOT group in low-income and middle-income countries. As you mentioned in the letter that even in high-income countries, it’s not realistic to treat all bronchiolitis patients with HFNC during RSV peaks. The inconsistent result of LOS in different countries may be caused by the level of medical practice in different areas because the LOS in low-income and middle-income countries was significantly longer than in high-income countries. So the clinical heterogeneity suggested that the level of medical practice was also important for bronchiolitis. Secondly, two studies showed that patients with treatment failures in SOT group could be treated with HFNC in the wards. This meta-analysis showed that there was a significant increase in the incidence of treatment failure in HFNC group compared with nCPAP group (RR 1.61, 95% CI 1.06 to 2.42, p=0.02). Therefore, we need more research to explore which choice (HFNC or nCPAP) is better for patients with treatment failures in standard oxygen supplementation.
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.
References
Show More1. Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV...
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