We thank Dr Cliona M Ni Bhrolchain for her interest in our paper and her comments. With the exceptions of newborn hearing and blood spot screening, there is unacceptably wide variation at local level and a lack of commitment at national level in implementation and monitoring of preventive child health programmes. We suggest that this is just one manifestation of a wider problem - the serious inadequacy of NHS investment in leadership, education and training, both in general practice and in the specialties. Morale is low and there are chronic shortages of staff with the relevant skills, when medicine is changing and public expectations rising faster than ever before.
David Hall and David Sowden (affiliations as on our original paper)
I refer to the paper published by Palmer et al in Archives Diseases Childhood March 20181 that states the recommendation to avoid tramadol when breastfeeding and the contraindication to its use in children (including neonates) is inappropriate in their view. 1
I disagree with the authors that tramadol is a safe for babies of breastfeeding mothers. Their conclusion, in my opinion, is premature and not adequately evidence-based. While they acknowledge, the US Food and Drug Administration (FDA) reported cases, they ignore the serious warnings by both Manufacturer and FDA about administering tramadol to children and breast-feeding mothers. There is increasing concern that narcotics used for treating pain in breastfeeding mothers may increase the risk of adverse effects in newborns, including excessive sedation and respiratory depression. The American Academy of Pediatrics (AAP), the FDA and the American College of Obstetricians and Gynecologists (ACOG) advocate against the use of codeine and tramadol in women who are breastfeeding because their babies may suffer adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems. 2-5 Patient safety should be foremost in our minds in making any recommendations that are contrary to Manufacturer, FDA, and AAP recommendations. It would be difficult to justify use of tramadol in a breastfeeding mother in the event of litigation arising from adverse effects of tramadol in the baby...
I refer to the paper published by Palmer et al in Archives Diseases Childhood March 20181 that states the recommendation to avoid tramadol when breastfeeding and the contraindication to its use in children (including neonates) is inappropriate in their view. 1
I disagree with the authors that tramadol is a safe for babies of breastfeeding mothers. Their conclusion, in my opinion, is premature and not adequately evidence-based. While they acknowledge, the US Food and Drug Administration (FDA) reported cases, they ignore the serious warnings by both Manufacturer and FDA about administering tramadol to children and breast-feeding mothers. There is increasing concern that narcotics used for treating pain in breastfeeding mothers may increase the risk of adverse effects in newborns, including excessive sedation and respiratory depression. The American Academy of Pediatrics (AAP), the FDA and the American College of Obstetricians and Gynecologists (ACOG) advocate against the use of codeine and tramadol in women who are breastfeeding because their babies may suffer adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems. 2-5 Patient safety should be foremost in our minds in making any recommendations that are contrary to Manufacturer, FDA, and AAP recommendations. It would be difficult to justify use of tramadol in a breastfeeding mother in the event of litigation arising from adverse effects of tramadol in the baby, when safer alternatives are available.
MANUFACTURER WARNING
In March 2008, Janssen Ortho, the manufacturer of tramadol (ULTRAM®) stated that the effects of tramadol on growth and functional maturation of child, and safety in infants and newborn has not been studied and it is not recommended for use in the pediatric population. It issued the following information concerning tramadol:
• LABOR AND DELIVERY
1. ULTRAM® should not be used in pregnant women prior to or during labor unless the potential benefits outweigh the risks. Safe use in pregnancy has not been established. Chronic use during pregnancy may lead to physical dependence and post-partum withdrawal symptoms in the newborn.
2. Tramadol crosses the placenta. The effect of ULTRAM®, if any, on the later growth, development, and functional maturation of the child is unknown.
• NURSING MOTHERS
ULTRAM® is not recommended for obstetrical preoperative medication or for post-delivery analgesia in nursing mothers because its safety in infants and newborns has not been studied. Following a single IV 100 mg dose of tramadol, the cumulative excretion in breast milk within 16 hours, post-dose was 100μg of tramadol (0.1% of the maternal dose) and 27 μg of M1.
• PEDIATRIC USE
The safety and efficacy of ULTRAM® in patients under 16 years of age have not been established. The use of ULTRAM® in the pediatric population is not recommended. 6
FDA WARNINGS
1. In 2013, FDA placed restrictions on its use in children younger than 18 years to treat pain after surgery to remove the tonsils and/or adenoids.7
2. FDA reviewed adverse event reports submitted to it from January 1969 to May 2015, and identified 64 cases of serious breathing problems, including 24 deaths, with codeine-containing medicines in children younger than 18 years. As this included only reports submitted to FDA, there may be additional cases about which FDA is unaware. FDA also identified nine cases of serious breathing problems, including three deaths, with the use of tramadol in children younger than 18 years from January 1969 to March 2016. Most of the serious side-effects with both codeine and tramadol occurred in children younger than 12 years, and some cases occurred after a single dose of the medicine.8
3. On July1, 2015, FDA issued warning about the potential risks of using codeine cough-and-cold medicines in children on July 1, 2015,4 and in September 21, 2015, FDA issued warning on the risks of using the pain medicine tramadol in children aged 17 and younger issued on September 21, 2015. 9
4. On 1-11-2018, the FDA restricted the use of codeine and tramadol medicines in children as these medicines carry serious risks, including slowed or difficult breathing and death, which appear to be a greater risk in children younger than 12 years, and should not be used in these children. FDA warned against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants. 10
5. Use of tramadol during pregnancy could make the baby dependent on the drug and cause Life-threatening withdrawal effects that may necessitate medical treatment for several weeks. 11
Additional concerns relating to the use of tramadol are suicidal thoughts and suicide attempts have emerged. In the article: Tramadol and Suicide attempt - from FDA reports, dated November 8, 2018, suicide attempt is found among people who take Tramadol, especially female, 40-49 old, who have been taking the drug for < 1 month. In the study based on reports of 102,114 people who have side effects when taking Tramadol from FDA, and is updated regularly. 102,114 people reported side effects when taking Tramadol. Among them, 765 people (0.75%) have attempted suicide. Suicide attempts are reported in children from the age of 10 years.12
In the light of the above data, there does not appear to be adequate evidence to support Palmer et al.’s contention that both Manufacturer and FDA recommendation to avoid use of tramadol when breastfeeding and contraindication to its use in children (including neonates) should be ignored.1 The AAP, the FDA, and the ACOG recommend against the use of codeine and tramadol in women who are breastfeeding because their newborns may have adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems. 2-5
Practice of medicine should be evidence-based. Patient safety comes foremost. Safer alternatives to tramadol are available. Acetaminophen and/or ibuprofen is recommended for pain management in women who are breastfeeding. If narcotic treatment is considered necessary, the lowest effective dose of morphine for the shortest time possible could be prescribed. 2
REFERENCE
1. Greta M Palmer, Brian J Anderson, David K Linscott, Michael J Paech, Karel Allegaert. Tramadol, breast feeding and safety in the newborn. (http://dx.doi.org/10.1136/archdischild-2017-313786).
2. Robert L. Barbieri. Editorial. Stop using codeine, oxycodone, hydrocodone, tramadol, and aspirin in women who are breast-feeding. OBG Manag. 2017 October;29(10):8-10,12. https://www.mdedge.com/obgyn/article/148018/obstetrics/stop-using-codein....
3. Sachs HC; Committee on Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796–e809.
4. US Food and Drug Administration. FDA Drug Safety Communication. FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. Silver Spring, MD: US Food and Drug Administration. https://www.fda.gov/Drugs/DrugSafety/ucm118113.htm. Published April 2017.
5. Practice advisory on codeine and tramadol for breast feeding women. American College of Obstetricians and Gynecologists website. https://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-A.... Published April 27, 2017.
6. ULTRAM® (tramadol hydrochloride) Tablets. Full Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020281s032s033...
7. FDA Drug Safety Communication: Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. (2-20-2013). https://www.fda.gov/downloads/Drugs/DrugSafety/UCM339116.pdf - accessed February 16, 2019.
8. FDA Drug Safety Communication: FDA evaluating the potential risks of using codeine cough-and-cold medicines in children. https://www.fda.gov/Drugs/DrugSafety/ucm453125.htm
9. FDA Drug Safety Communication: FDA evaluating the risks of using the pain medicine tramadol in children aged 17 and younger. https://www.fda.gov/Drugs/DrugSafety/ucm462991.htm (9-21-2015).
10. FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm (1-11-2018)
11. Kaci Durbin. (Updated 29-12-2018) Tramadol. https://www.drugs.com/tramadol.html
12. Tramadol and Suicide attempt - from FDA reports. http://www.ehealthme.com/ds/tramadol/suicide-attempt/
Conflict of Interest
None declared
Professor Dr. Davendralingam Sinniah
We welcome the paper by Verfurden et al1 on avoidable mortality from RTI and SUDIC with chronic conditions. We do not doubt the conclusion that chronic conditions are strongly associated with deaths from RTI, but disagree with the conclusion that chronic conditions are also associated with SUDIC or the need for changes to death certification.
The study excludes deaths of infants less than 2 months old; however the peak age for unexplained infant deaths (classified as SIDS or unascertained) is 6 weeks. Data from England for the years 2004-10 show that 45% of unexpected infant deaths occurred prior to 2 months of age2, with the exception of those infants with congenital anomalies it is unlikely that these infants will have been diagnosed with a chronic condition by the time of death. Due to these issues, the study is likely to have significantly over-estimated the association of chronic conditions with SUDIC and we would invite the authors to revise their conclusion.
The authors suggest that death registrations and hospital databases should categorise deaths as expected or unexpected to help identify potentially preventable deaths. Child Death Overview Panels in England review all deaths, determining modifiable factors; and these reviews are to be collated nationally by the new established National Child Mortality Database. A similar system of Child Death Reviews has already been recommended by the Scottish Government. It would seem more sensible to fully embrace...
We welcome the paper by Verfurden et al1 on avoidable mortality from RTI and SUDIC with chronic conditions. We do not doubt the conclusion that chronic conditions are strongly associated with deaths from RTI, but disagree with the conclusion that chronic conditions are also associated with SUDIC or the need for changes to death certification.
The study excludes deaths of infants less than 2 months old; however the peak age for unexplained infant deaths (classified as SIDS or unascertained) is 6 weeks. Data from England for the years 2004-10 show that 45% of unexpected infant deaths occurred prior to 2 months of age2, with the exception of those infants with congenital anomalies it is unlikely that these infants will have been diagnosed with a chronic condition by the time of death. Due to these issues, the study is likely to have significantly over-estimated the association of chronic conditions with SUDIC and we would invite the authors to revise their conclusion.
The authors suggest that death registrations and hospital databases should categorise deaths as expected or unexpected to help identify potentially preventable deaths. Child Death Overview Panels in England review all deaths, determining modifiable factors; and these reviews are to be collated nationally by the new established National Child Mortality Database. A similar system of Child Death Reviews has already been recommended by the Scottish Government. It would seem more sensible to fully embrace the proposed Child Death Review process than suggest small changes to child death registrations.
Yours sincerely
J Garstang and G Debelle
1. Verurden ML, Gilbert R, Sibere N, Hardelid P. Avoidable mortality from respiratory tract infection and sudden unexplained death in children with chronic conditions: a data likage study. Arch Dis Child 2018; 103: 1125 – 1131.
2. Office for National Statistics. Unexplained Death in Infancy - England and Wales, 2010. 2012; Available from: www.statistics.gov.uk.
In their editorial Paes and Mitra suggest that all patients with down syndrome (DS) <2 years should be considered to give palivizumab (Synagis®) to prevent respiratory syncytial virus (RSV) infection. We agree with the authors that DS children are at increased risk to develop RSV infections. However, we do not agree with their recommendation for palivizumab prevention in all DS children <2 years. In our opinion there is insufficient evidence on the efficiency and cost effectiveness and the recommendation is therefore premature.
For the evaluation of preventive interventions the incidence and the absolute risk of acquiring the disease, and the effectiveness of the proposed intervention are important factors. The reported incidence of clinical relevant RSV infections in the general population in western countries is about 18/1,000 in newborns <2 months, 17/1,000 in children <6 months and 3/1,000 in children <5 years ( 2,3). Considering a relative extra risk of 5.5 in DS children (1) the calculated RSV incidence is 99/1,000 <2 months ( one out of 10) , 94/1,000 <6 months and 17/1,000 <5 years, respectively. The effectiveness of prevention of clinical treatment in premature children with palivizumab is about 50% (4). The extrapolated number needed to treat (NNT) for newborns with DS is 20 to prevent one hospitalization due to RSV infection. But what is the harm of this treatment as 19 out of 20 DS newborns will be given 114 injections per year...
In their editorial Paes and Mitra suggest that all patients with down syndrome (DS) <2 years should be considered to give palivizumab (Synagis®) to prevent respiratory syncytial virus (RSV) infection. We agree with the authors that DS children are at increased risk to develop RSV infections. However, we do not agree with their recommendation for palivizumab prevention in all DS children <2 years. In our opinion there is insufficient evidence on the efficiency and cost effectiveness and the recommendation is therefore premature.
For the evaluation of preventive interventions the incidence and the absolute risk of acquiring the disease, and the effectiveness of the proposed intervention are important factors. The reported incidence of clinical relevant RSV infections in the general population in western countries is about 18/1,000 in newborns <2 months, 17/1,000 in children <6 months and 3/1,000 in children <5 years ( 2,3). Considering a relative extra risk of 5.5 in DS children (1) the calculated RSV incidence is 99/1,000 <2 months ( one out of 10) , 94/1,000 <6 months and 17/1,000 <5 years, respectively. The effectiveness of prevention of clinical treatment in premature children with palivizumab is about 50% (4). The extrapolated number needed to treat (NNT) for newborns with DS is 20 to prevent one hospitalization due to RSV infection. But what is the harm of this treatment as 19 out of 20 DS newborns will be given 114 injections per year. For DS patients <5 years these numbers are even worse: 594 injections are given to prevent 1 clinical admission, as the NNT in this DS age group is about 100. In our opinion the potential harm of palivizumab treatment does not outweigh the harm of one prevented hospital admission.
What about the financial burden? For the DS newborns <2 years in The Netherlands the costs to prevent one hospitalization will be about Euro 76.200 (20 * 6 * Euro 635); for DS children < 5 years these costs to prevent one admission rise to Euro 630.000 (100 * 6 * Euro 1,050). Recent studies from various countries, including The Netherlands, have evaluated the cost effectiveness of palivizumab prophylaxis for RSV infections in risk groups (5,6). These studies concluded that palivizumab prophylaxis is not cost effective with a probable exception for patients with a strongly increased risk (not DS).
Conclusion. We do not agree with the authors to treat all DS children with palivizumab. Palivizumab should only be given in well proven risk populations. We do agree with the authors that a randomized controlled trial (RCT) to prove the efficacy, safety and (cost)effectiveness of palivizumab prevention is needed in DS children.
In their editorial Paes and Mitra suggest that all patients with down syndrome (DS) <2 years should be considered to give palivizumab (Synagis®) to prevent respiratory syncytial virus (RSV) infection. We agree with the authors that DS children are at increased risk to develop RSV infections. However, we do not agree with their recommendation for palivizumab prevention in all DS children <2 years. In our opinion there is insufficient evidence on the efficiency and cost effectiveness and the recommendation is therefore premature.
For the evaluation of preventive interventions the incidence and the absolute risk of acquiring the disease, and the effectiveness of the proposed intervention are important factors. The reported incidence of clinical relevant RSV infections in the general population in western countries is about 18/1,000 in newborns <2 months, 17/1,000 in children <6 months and 3/1,000 in children <5 years ( 2,3). Considering a relative extra risk of 5.5 in DS children (1) the calculated RSV incidence is 99/1,000 <2 months ( one out of 10) , 94/1,000 <6 months and 17/1,000 <5 years, respectively. The effectiveness of prevention of clinical treatment in premature children with palivizumab is about 50% (4). The extrapolated number needed to treat (NNT) for newborns with DS is 20 to prevent one hospitalization due to RSV infection. But what is the harm of this treatment as 19 out of 20 DS newborns will be given 114 injections per year. For DS patients <5 years these numbers are even worse: 594 injections are given to prevent 1 clinical admission, as the NNT in this DS age group is about 100. In our opinion the potential harm of palivizumab treatment does not outweigh the harm of one prevented hospital admission.
What about the financial burden? For the DS newborns <2 years in The Netherlands the costs to prevent one hospitalization will be about Euro 76.200 (20 * 6 * Euro 635); for DS children < 5 years these costs to prevent one admission rise to Euro 630.000 (100 * 6 * Euro 1,050). Recent studies from various countries, including The Netherlands, have evaluated the cost effectiveness of palivizumab prophylaxis for RSV infections in risk groups (5,6). These studies concluded that palivizumab prophylaxis is not cost effective with a probable exception for patients with a strongly increased risk (not DS).
Conclusion. We do not agree with the authors to treat all DS children with palivizumab. Palivizumab should only be given in well proven risk populations. We do agree with the authors that a randomized controlled trial (RCT) to prove the efficacy, safety and (cost)effectiveness of palivizumab prevention is needed in DS children.
References.
1. Paes B, Mitra S. Palivizumab for Children with Down syndrome: is the time right for a universal recommendation? Arch Dis Child doi:10.1136/archdischild-2018-316408
2. Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009; 360: 588-98.
3. Hall CB, Weinberg GA, Blumkin AK, et al. Respiratoy syncytial virus-associated hospitalizations among children less than 24 months of age. Pediatrics 2013; 132: e341-8.
4. The Impact-RSV Study Group. Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 1998; 102: 531-7.
5. Olchanski N, Hansen RN, et al. Palivizumab prophylaxis for respiratory syncytial virus: examining the evidence around value. Open Forum Infectious Diseases OFID 2018. Doi: 10.1093/ofid/ofy031.
6. Blanken MO, Frederix GW, et al. Cost-effectiveness of rule-based immunoprophylaxis against respiratory syncytial virus infections in preterm infants. Eur J Pediatr 2018; 177: 133-44 Doi.org/10.1007/s00431-017-3046-1.
We read with interest the recent article published by Binder E et al. [1], describing the HLA-DQ analysis performed in 1624 asymptomatic children affected with type I Diabetes Mellitus (DMT1), in order to assess their predisposition to develop Celiac Disease (CD). They reported that 1344 (82.8%) patients resulted to be "HLA-DQ2 and/or -DQ8 positive", whereas 280 (17.2%) were negative: among the former group, a biopsy-proven CD diagnosis was documented in 3.6% of cases and, interestingly, even 7 patients in the second group (corresponding to 2.5%) resulted to be celiac. [1]
Thus, these two percentages are not so different and one might conclude that the HLA-DQ asset is not a necessary - even if not sufficient - genetic background, contrary to what is well known. [2] Indeed, the absence of alleles coding MHC-DQ2 and/or MHC-DQ8 heterodimers, is associated with an almost absolute negative predictive value with respect to CD. Therefore, in order to solve this apparent mismatch, it would be useful if the authors can show the complete and high-resolution HLA-DQA1 and, in particular, HLA-DQB1 typing: indeed, these 7 “HLA-DQ2 and/or -DQ8 negative” CD children may not carry all alleles coding any complete MHC-DQ2 and/or MHC-DQ8 molecule, but they may have one or two allelic variants conferring CD risk anyway, such as HLA-DQB1*02, which codes the beta chain of MHC-DQ2 heterodimer. Indeed, according to several studies, the isolate presence of one or two copies of this...
We read with interest the recent article published by Binder E et al. [1], describing the HLA-DQ analysis performed in 1624 asymptomatic children affected with type I Diabetes Mellitus (DMT1), in order to assess their predisposition to develop Celiac Disease (CD). They reported that 1344 (82.8%) patients resulted to be "HLA-DQ2 and/or -DQ8 positive", whereas 280 (17.2%) were negative: among the former group, a biopsy-proven CD diagnosis was documented in 3.6% of cases and, interestingly, even 7 patients in the second group (corresponding to 2.5%) resulted to be celiac. [1]
Thus, these two percentages are not so different and one might conclude that the HLA-DQ asset is not a necessary - even if not sufficient - genetic background, contrary to what is well known. [2] Indeed, the absence of alleles coding MHC-DQ2 and/or MHC-DQ8 heterodimers, is associated with an almost absolute negative predictive value with respect to CD. Therefore, in order to solve this apparent mismatch, it would be useful if the authors can show the complete and high-resolution HLA-DQA1 and, in particular, HLA-DQB1 typing: indeed, these 7 “HLA-DQ2 and/or -DQ8 negative” CD children may not carry all alleles coding any complete MHC-DQ2 and/or MHC-DQ8 molecule, but they may have one or two allelic variants conferring CD risk anyway, such as HLA-DQB1*02, which codes the beta chain of MHC-DQ2 heterodimer. Indeed, according to several studies, the isolate presence of one or two copies of this allelic variant resulted to be associated with significant CD risk, regardless of the concomitant presence of the appropriate HLA-DQA1 allele (*05) necessary to produce a complete MHC-DQ2 molecule. [3-4]
References
1- Binder E, Rohrer T, Denzer C, et al. Screening for coeliac disease in 1624 mainly asymptomatic children with type 1 diabetes: is genotyping for coeliac-specific human leucocyte antigen the right approach? Arch Dis Child. 2018; [Epub ahead of print].
2- Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet. 2018; 391(10115):70-81.
3- De Silvestri A, Capittini C, Poddighe D, et al. HLA-DQ genetics in children with celiac disease: a meta-analysis suggesting a two-step genetic screening procedure starting with HLA-DQ β chains. Pediatr Res. 2018; 83(3):564-572.
4- Megiorni F, Pizzuti A. HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular typing. J Biomed Sci 2012;19:88.
Many thanks for your response to the editorial ‘What are you looking at?’, which highlights some important principles for this extensively studied research area (despite being a relatively new field in healthcare) [1]
Despite the emergence of new methods to analyse gaze behaviour terminology has not been revised to reflect scientific advances. A recent article by Hessels et al. outlined significant inconsistencies in the definitions of fixations and saccades held by eye movement researchers and highlighted the conceptual confusion surrounding these terms.[2]
The term saccade is derived from the French for ‘jerk’. The phrase appears to have been coined by Emile Javal, a French ophthalmologist, in the 1800’s.[3] By 1916 it had been accepted into the English literature.[4]
Saccades are frequently defined in the literature as rapid, ballistic movements of the eyes that abruptly change the point of fixation.5 Definitions have included;
‘Rapid eye movements used to voluntarily move gaze from one target of interest to another.’[6]
‘Ballistic movements, 20-150ms long, reaching a velocity up to 800°/s. They direct the eye so that external visual objects are projected onto the fovea.’[7]
‘Rapid eye movements used in repositioning the fovea to a new location in the visual environment.’[8]
The term ballistic refers to the fact that the saccade-generating system cannot respond to subsequent changes in the position of a target during th...
Many thanks for your response to the editorial ‘What are you looking at?’, which highlights some important principles for this extensively studied research area (despite being a relatively new field in healthcare) [1]
Despite the emergence of new methods to analyse gaze behaviour terminology has not been revised to reflect scientific advances. A recent article by Hessels et al. outlined significant inconsistencies in the definitions of fixations and saccades held by eye movement researchers and highlighted the conceptual confusion surrounding these terms.[2]
The term saccade is derived from the French for ‘jerk’. The phrase appears to have been coined by Emile Javal, a French ophthalmologist, in the 1800’s.[3] By 1916 it had been accepted into the English literature.[4]
Saccades are frequently defined in the literature as rapid, ballistic movements of the eyes that abruptly change the point of fixation.5 Definitions have included;
‘Rapid eye movements used to voluntarily move gaze from one target of interest to another.’[6]
‘Ballistic movements, 20-150ms long, reaching a velocity up to 800°/s. They direct the eye so that external visual objects are projected onto the fovea.’[7]
‘Rapid eye movements used in repositioning the fovea to a new location in the visual environment.’[8]
The term ballistic refers to the fact that the saccade-generating system cannot respond to subsequent changes in the position of a target during the course of an eye movement. If the target was to move a second saccade would be required to correct the error. Acceptance of such definitions suggests that the primary function of saccades is to bring objects of interest onto or near the fovea. The fovea operates at high resolution and, although it only provides 1-2 degrees of vision, it plays a central role in resolving objects. Whilst saccades assist vision by moving the eyes rapidly to various objects of interest so that parts of a scene can be seen in greater resolution, there is probably little or no meaningful information absorbed during the saccadic movements.
However, other papers have been more liberal in their definitions defining a saccade as the inter-fixation interval.[9,10] These definitions imply that a saccade is any movement outside of periods of fixation. This definition will therefore also capture smooth pursuit movements (slower tracking movements), vestibulo-ocular movements (stabilise eyes relative to external world) and visual scanning movements. Consequentially during saccades defined in this manner visual information may be absorbed both consciously and/or subconsciously including, for example, the presence or absence of pathology, as outlined in your letter.
As the field of eye tracking research in healthcare expands it is imperative that authors explicitly define their key measurements, including fixations, dwell time and saccades, to allow accurate interpretation and comparison of results and to minimise ambiguity. Without this it will be difficult to examine the links between visual scanning patterns and decision making. For example it may be hypothesised that subconscious visual scanning behaviours may be a clue to understanding the concept of gut feeling, whereby a particular clinician sees things perhaps others do not.
We certainly agree greater understanding of saccade pathways should undoubtedly be an area for future research in eye tracking studies in healthcare.
References:
1. Roland D. What are you looking at? Arch Dis Child 2018; 103: 1098-1099.
2. Hessels RS, Niehorster DC, Nyström M, Andersson R, Hooge IT. Is the eye-movement field confused about fixations and saccades? A survey among 124 researchers. Royal Society open science. 2018 Aug 29;5(8):180502.
3. Javal E. Essai sur la physiologie de la lecture. Annales d'Ocilistique. 1878;80:61-73.
4. Wade NJ. Scanning the seen: Vision and the origins of eye-movement research. In Eye Movements 2007 (pp. 31-63).
5. Purves D, Augustine GJ, Fitzpatrick D, Katz LC, LaMantia AS, McNamara JO, Williams SM. Neuroscience 2nd Edition. Sunderland (MA) Sinauer Associates.
6. Ramat S, Leigh RJ, Zee DS, Optican LM. What clinical disorders tell us about the neural control of saccadic eye movements. Brain. 2006 Nov 21;130(1):10-35.
7. Falkmer T, Dahlman J, Dukic T, Bjällmark A, Larsson M. Fixation identification in centroid versus start-point modes using eye-tracking data. Perceptual and motor skills. 2008 Jun;106(3):710-24.
8. Duchowski AT. Eye tracking methodology. Theory and practice. 2007;328.
9. Holmqvist K, Nyström M, Andersson R, Dewhurst R, Jarodzka H, Van de Weijer J. Eye tracking: A comprehensive guide to methods and measures. OUP Oxford; 2011 Sep 22.
10. Larsson L, Nyström M, Andersson R, Stridh M. Detection of fixations and smooth pursuit movements in high-speed eye-tracking data. Biomedical Signal Processing and Control. 2015 Apr 1;18:145-52.
Hall and Sowdon regret that the Newborn Infant Physical Examination (NIPE)/child health surveillance (CHS) programme fails to deliver improved outcomes for developmental dysplasia of the hip (DDH), contrasting with the success of other screening programmes. I would like to make some proposals for improvement.
Current NIPE standards are focused on timeliness of the screening pathway and explicitly exclude treatment outcomes as ‘outside the screening pathway’1. Yet potential outcome measures are routinely available for three of the four NIPE screening programmes and shown to be measurable for two of these. McAllister et have demonstrated that records of surgical intervention for DDH can be used to show variation in outcomes2. Similarly, the NHS Atlas of Variation has demonstrated that age at orchidopexy can be used for undescended testis (UDT)3. Surgery for congenital cataract could be used in the same way. While I accept that definitions and actual measures might need some discussion to reach a national consensus, measuring these outcomes is possible from routine data.
McAllister et al conclude that dedicated leadership of the DDH screening programme is associated with improved outcomes. This has also been shown for UDT4. Unfortunately, clinical leadership of the Healthy Child Programme (HCP) has been dismantled in recent years and the RCPCH recorded a community paediatric HCP lead in only 16% of services in 2015.
Hall and Sowdon regret that the Newborn Infant Physical Examination (NIPE)/child health surveillance (CHS) programme fails to deliver improved outcomes for developmental dysplasia of the hip (DDH), contrasting with the success of other screening programmes. I would like to make some proposals for improvement.
Current NIPE standards are focused on timeliness of the screening pathway and explicitly exclude treatment outcomes as ‘outside the screening pathway’1. Yet potential outcome measures are routinely available for three of the four NIPE screening programmes and shown to be measurable for two of these. McAllister et have demonstrated that records of surgical intervention for DDH can be used to show variation in outcomes2. Similarly, the NHS Atlas of Variation has demonstrated that age at orchidopexy can be used for undescended testis (UDT)3. Surgery for congenital cataract could be used in the same way. While I accept that definitions and actual measures might need some discussion to reach a national consensus, measuring these outcomes is possible from routine data.
McAllister et al conclude that dedicated leadership of the DDH screening programme is associated with improved outcomes. This has also been shown for UDT4. Unfortunately, clinical leadership of the Healthy Child Programme (HCP) has been dismantled in recent years and the RCPCH recorded a community paediatric HCP lead in only 16% of services in 2015.
Lastly poor outcomes may indicate a lack of training. The DDH and UDT examples describe multifaceted interventions including training and support of practitioners. Health visitor training now concentrates on health promotion and safeguarding with a reduced emphasis on child development and clinical skills. There are no longer any specific training requirements for general practitioners (GPs) who perform CHS. This is concerning as we know that only a proportion of GPs have any dedicated training in paediatrics before entering general practice.
There are, therefore, a series of proven measures that, if implemented, could improve the programmes’ performance.
References
1. Public Health England. Our approach to newborn and infant physical examination screening standards. 2018 https://www.gov.uk/government/publications/newborn-and-infant-physical-e... (accessed 11.01.19)
2. McAllister D A, Morling JR, Fischbacher C M et al. Enhanced detection services for developmental dysplasia of the hip in Scottish children 1997 – 2013. Arch Dis Child 2018; 103: 1021 – 1026.
3. Child and Maternal Health Observatory. NHS Atlas of Variation in Healthcare of Children and Young People. 2012. Ch Map 25 Proportion (%) of all elective orchidopexy procedures performed before the age of 2 years by PCT 2007/08–2009/10 p.68-69. Available at https://fingertips.phe.org.uk/profile/atlas-of-variation
4. Brown JJ, Wacogne I, Fleckney S, et al. Achieving early surgery for undescended testes: quality improvement through a multi-faceted approach to guideline implementation. Child: care, health and development 2004; 30: 97–102.
5. Royal College of Paediatrics and Child Health. RCPCH Medical Workforce Census 2015. London 2017. Available at https://www.rcpch.ac.uk/resources/workforce-census-2015 .
We thank Nitzan et al for their comments in relation to our article on use of pulsatility index (PI) in screening for critical congenital heart disease (Searle 2018). In particular, we are grateful that they draw further attention to the potential for current screening to miss critical lesions, such as coarctation of the aorta. Given the progressive nature of these pathologies, it is an extremely difficult challenge to design an acceptable screening tool, which highlights all affected babies in appropriate time. Despite strong biological plausibility, current evidence is unclear whether pulsatility index can translate into such a tool.
We fully agree that the local quality of both antenatal and postnatal screening significantly affects the measured benefit of pulsatility index. Several articles draw the distinction here between ‘tertiary’ and ‘non-tertiary’ units, though it may be more accurate to distinguish ‘better resourced’ from ‘less resourced’ settings, particularly in relation to antenatal scanning. As described in our original article, the apparent potential of PI screening in ‘less resourced’ settings seems strong, especially since many pulse oximetry sensors already measure it. Both Schena et al (2017) and Granelli & Ostman-Smith (2007) highlight a small but important population of babies not detected by standard screening, but with abnormal pre-morbid pulsatility indices. It seems incongruous, however, to extrapolate a single extra case detected by th...
We thank Nitzan et al for their comments in relation to our article on use of pulsatility index (PI) in screening for critical congenital heart disease (Searle 2018). In particular, we are grateful that they draw further attention to the potential for current screening to miss critical lesions, such as coarctation of the aorta. Given the progressive nature of these pathologies, it is an extremely difficult challenge to design an acceptable screening tool, which highlights all affected babies in appropriate time. Despite strong biological plausibility, current evidence is unclear whether pulsatility index can translate into such a tool.
We fully agree that the local quality of both antenatal and postnatal screening significantly affects the measured benefit of pulsatility index. Several articles draw the distinction here between ‘tertiary’ and ‘non-tertiary’ units, though it may be more accurate to distinguish ‘better resourced’ from ‘less resourced’ settings, particularly in relation to antenatal scanning. As described in our original article, the apparent potential of PI screening in ‘less resourced’ settings seems strong, especially since many pulse oximetry sensors already measure it. Both Schena et al (2017) and Granelli & Ostman-Smith (2007) highlight a small but important population of babies not detected by standard screening, but with abnormal pre-morbid pulsatility indices. It seems incongruous, however, to extrapolate a single extra case detected by the Schena et al (2017) study into a real 50% improvement in detection rates, over pulse oximetry screening alone. With such small numbers, the difference between an important finding and statistical or technical anomaly is impossible to determine. We hope this clarifies our original statement that ‘current evidence does not support inclusion of PI into newborn screening’.
Moving forward, the inclusion of pulsatility index within current screening practice would require further large population studies, particularly looking at babies within ‘less resourced’ settings. To make such a study acceptable, the methodology must either i) reduce the high false-positive rate (typically 5%) associated with previous approaches or ii) have robust and pragmatic mechanisms to safely minimise the impact of a false-positive screen on a newborn and their family. Use of different technologies may address the former requirement. Pre-to-post ductal pulse delay, for example, is an innovative approach, though it is untested within a screening context (Palmeri 2017). Within this study, all ‘case’ group babies already demonstrated significant clinical signs at time of testing. Similarly, Nitzan et al’s suggestion to repeat PI measurement after a few days has merit. Establishing the optimal timing of measurements however would be a challenge, to maximise detection without missing early cases. Granelli & Ostman-Smith (2007) could not answer this point, despite study of 10,000 babies up to day 5 of life.
It seems unacceptable to remain in the status quo, where a significant portion of babies are only detected following life-threatening collapse. PI could be an important addition to the screening armoury in ‘low resourced’ settings, but true population-specific evidence would be needed. We very much welcome an open discussion of how to overcome the challenges this would pose.
REFERENCES
Granelli A, Ostman-Smith I. Noninvasive peripheral perfusion index as a possible tool for screening for critical left heart obstruction. Acta Paediatr. 2007;96:1455–9
Palmeri L, Gradwohl G, Nitzan M, et al. Photoplethysmographic waveform characteristics of newborns with coarctation of the aorta. J Perinatol. 2017;37:77–80
Schena F, Picciolli I, Agosti M, et al. Perfusion index and pulse oximetry screening for congenital heart defects. J Pediatr. 2017;183:74–9
M Nadeem
1. Department of Paediatrics, Tallaght University Hospital, Dublin 24, Ireland
2. Trinity College Dublin
Corresponding author: M Nadeem, Department of Paediatrics, Tallaght University Hospital, Dublin 24, Ireland
So et al1 reported a case of meningococcal group W meningitis in an infant who presented within 24 hours of receiving group B meningococcal vaccine (4CMenB). Fever and focal seizure, which required two doses of intravenous lorazepam, have been reported at the time of presentation. Intravenous ceftriaxone was commenced for suspected sepsis. CSF PCR was positive for capsular group W meningococcus. With respect to the focal seizure in a febrile infant, whether viral encephalitis was excluded and whether antiviral was commenced pending the exclusion of herpes simplex encephalitis (HSE) are questions that were not addressed in the present case.
At the time of presentation, it may not be possible to clinically differentiate encephalitis from meningitis, as either syndrome may have common features including fever, headache and meningism.2 Children with encephalitis may present with fever, seizures and focal neurological signs.2 3 Moreover those with HSE may experience a progressively deteriorating level of consciousness with fever, focal seizures or focal neurological abnormalities in the absence of any other cause.2 4 However the absence of fever2 5 or the lack of altered states of consciousness5 at presentation does not exclude...
M Nadeem
1. Department of Paediatrics, Tallaght University Hospital, Dublin 24, Ireland
2. Trinity College Dublin
Corresponding author: M Nadeem, Department of Paediatrics, Tallaght University Hospital, Dublin 24, Ireland
So et al1 reported a case of meningococcal group W meningitis in an infant who presented within 24 hours of receiving group B meningococcal vaccine (4CMenB). Fever and focal seizure, which required two doses of intravenous lorazepam, have been reported at the time of presentation. Intravenous ceftriaxone was commenced for suspected sepsis. CSF PCR was positive for capsular group W meningococcus. With respect to the focal seizure in a febrile infant, whether viral encephalitis was excluded and whether antiviral was commenced pending the exclusion of herpes simplex encephalitis (HSE) are questions that were not addressed in the present case.
At the time of presentation, it may not be possible to clinically differentiate encephalitis from meningitis, as either syndrome may have common features including fever, headache and meningism.2 Children with encephalitis may present with fever, seizures and focal neurological signs.2 3 Moreover those with HSE may experience a progressively deteriorating level of consciousness with fever, focal seizures or focal neurological abnormalities in the absence of any other cause.2 4 However the absence of fever2 5 or the lack of altered states of consciousness5 at presentation does not exclude encephalitis. Neuroimaging is a key part of the investigation of a child presenting with encephalitis2, albeit cerebral CT2 or MRI scans6 can be unremarkable in the first days of the disease.
HSE is rare and the long-term consequences can be devastating in cases where therapy is commenced late.7 In those with suspected encephalitis, it was recommended that broad-spectrum antimicrobials and antiviral treatment should be initiated pending the results of diagnostic studies.7
Therefore considering the fever and the focal seizure that require two doses of intravenous lorazepam in the present case, it would be beneficial if the authors address the questions that whether viral encephalitis was excluded and whether antiviral was commenced pending the exclusion of encephalitis.
References:
1. So N, Pal R, Snape MD. Meningococcal meningitis presenting postinfant group B meningococcal immunisation. Archives of Disease in Childhood Published Online First: 05 December 2018. doi: 10.1136/archdischild-2018-316341
2. Thompson C, Kneen R, Riordan A, et al. Encephalitis in children. Archives of Disease in Childhood 2012;97:150-161.
3. Kolski H1, Ford-Jones EL, Richardson S, et al. Etiology of acute childhood encephalitis at The Hospital for Sick Children, Toronto, 1994-1995.
Clin Infect Dis. 1998 Feb;26(2):398-409.
4. Le Doare K, Menson E, Patel D, et al. Fifteen minute consultation: Managing neonatal and childhood herpes encephalitis. Archives of Disease in Childhood - Education and Practice 2015;100:58-63.
5. De Tiège X1, Rozenberg F, Burlot K, et al. Herpes simplex encephalitis: diagnostic problems and late relapse. Dev Med Child Neurol. 2006;48(1):60-3.
6. Hariri OR, Prakash L, Amin J, et al. Atypical presentation of herpes simplex encephalitis in an infant. J Am Osteopath Assoc. 2010;110(10):615-7.
The review by Searle et al “Does pulsatility index add value to newborn pulse oximetry screening for critical congenital heart disease?" (Searle 2018), provides a comprehensive overview of the current evidence regarding the addition of perfusion index to the CCHD screening algorithm.
The authors’ main concern is that adding pulsatility index (perfusion index, PI) will not significantly improve the current detection rate which is already quite high. As a proof, they cite the work of the large trial by Schena et al, (Schena 2017) that found one additional case of CCHD in 42,169 babies examined. The authors conclude that incorporating PI into current screening algorithms provides little additional benefit in detecting CCHD and confers a high false positive rate.
We would like to voice several comments regarding this article:
First, in the study of Schena et al, CCHD was suspected before screening in 36/38 cases in tertiary centers. This is the main reason that PI (and pulse oximetry screening) did not have any additional value in tertiary centers. In this study, only 23.6% of the neonates were born in non-tertiary center. We suggest that an alternative way to describe the results is that in non-tertiary centers, pulse oximetry detected 2 cases and PI detected an additional 1 case per approximately 10,000 screened neonates. Therefore, adding PI to the screening algorithm improved the detection rate by 50%. Moreover, the 2 cases detected by pulse oximetry...
The review by Searle et al “Does pulsatility index add value to newborn pulse oximetry screening for critical congenital heart disease?" (Searle 2018), provides a comprehensive overview of the current evidence regarding the addition of perfusion index to the CCHD screening algorithm.
The authors’ main concern is that adding pulsatility index (perfusion index, PI) will not significantly improve the current detection rate which is already quite high. As a proof, they cite the work of the large trial by Schena et al, (Schena 2017) that found one additional case of CCHD in 42,169 babies examined. The authors conclude that incorporating PI into current screening algorithms provides little additional benefit in detecting CCHD and confers a high false positive rate.
We would like to voice several comments regarding this article:
First, in the study of Schena et al, CCHD was suspected before screening in 36/38 cases in tertiary centers. This is the main reason that PI (and pulse oximetry screening) did not have any additional value in tertiary centers. In this study, only 23.6% of the neonates were born in non-tertiary center. We suggest that an alternative way to describe the results is that in non-tertiary centers, pulse oximetry detected 2 cases and PI detected an additional 1 case per approximately 10,000 screened neonates. Therefore, adding PI to the screening algorithm improved the detection rate by 50%. Moreover, the 2 cases detected by pulse oximetry did not have ductal dependent systemic circulation. Therefore, the most important detection in this study was by PI. We agree with the authors that pulse oximetry CCHD screening, with or without PI, has a low detection rate in tertiary units. However, we believe that this study demonstrates the potential utility of PI as a supplementary screening method in non-tertiary units. This information may be of value in regions with limited access to fetal diagnosis which is expensive and requires advanced technical skills while PI is inexpensive and may be performed by nurses and midwives.
Second, we would like to draw attention to the three missed cases of critical left-sided obstruction described in this study. Two of the neonates presented with signs of shock and cardiac failure. We believe that the current screening algorithms may be improved by measuring the pulse wave delay between extremities (Palmeri 2017) as was mentioned in the review. Detection rates may also increase by improving the method of derivation of PI and by comparing pre and post-ductal PI values (Palmeri 2017, Nitzan 2018). Another option that may be relevant in some regions, is a repeated screening test performed in the community clinic or during a home visit after hospital discharge in the hope of detecting critical left-sided obstruction during the process of duct closure before the onset of cardiac failure.
We thank the authors for raising awareness of this important question, and we hope that future studies will address this issue.
Searle J, Thakkar DD, Banerjee J.Does pulsatility index add value to newborn pulse oximetry screening for critical congenital heart disease? Arch Dis Child. 2018 Nov 9. pii: archdischild-2018-315891. doi: 10.1136/archdischild-2018-315891. [Epub ahead of print]
Schena F, Picciolli I, Agosti M, et al. Perfusion index and pulse oximetry screening for
congenital heart defects. J Pediatr 2017;183:74–9.
Palmeri L, Gradwohl G, Nitzan M, et al. Photoplethysmographic waveform
characteristics of newborns with coarctation of the aorta. J Perinatol 2017;37:77–80.
Nitzan I, Hammerman C, Fink D, Nitzan M, Koppel R, Bromiker R. The effect of patent ductus arteriosus on pre-ductal and post-ductal perfusion index in preterm neonates. Physiol Meas. 2018 Jul 20;39(7):075006. doi: 10.1088/1361-6579/aacf25.
We thank Dr Cliona M Ni Bhrolchain for her interest in our paper and her comments. With the exceptions of newborn hearing and blood spot screening, there is unacceptably wide variation at local level and a lack of commitment at national level in implementation and monitoring of preventive child health programmes. We suggest that this is just one manifestation of a wider problem - the serious inadequacy of NHS investment in leadership, education and training, both in general practice and in the specialties. Morale is low and there are chronic shortages of staff with the relevant skills, when medicine is changing and public expectations rising faster than ever before.
David Hall and David Sowden (affiliations as on our original paper)
I refer to the paper published by Palmer et al in Archives Diseases Childhood March 20181 that states the recommendation to avoid tramadol when breastfeeding and the contraindication to its use in children (including neonates) is inappropriate in their view. 1
Show MoreI disagree with the authors that tramadol is a safe for babies of breastfeeding mothers. Their conclusion, in my opinion, is premature and not adequately evidence-based. While they acknowledge, the US Food and Drug Administration (FDA) reported cases, they ignore the serious warnings by both Manufacturer and FDA about administering tramadol to children and breast-feeding mothers. There is increasing concern that narcotics used for treating pain in breastfeeding mothers may increase the risk of adverse effects in newborns, including excessive sedation and respiratory depression. The American Academy of Pediatrics (AAP), the FDA and the American College of Obstetricians and Gynecologists (ACOG) advocate against the use of codeine and tramadol in women who are breastfeeding because their babies may suffer adverse reactions, including excessive sleepiness, difficulty breathing, and potentially fatal breathing problems. 2-5 Patient safety should be foremost in our minds in making any recommendations that are contrary to Manufacturer, FDA, and AAP recommendations. It would be difficult to justify use of tramadol in a breastfeeding mother in the event of litigation arising from adverse effects of tramadol in the baby...
We welcome the paper by Verfurden et al1 on avoidable mortality from RTI and SUDIC with chronic conditions. We do not doubt the conclusion that chronic conditions are strongly associated with deaths from RTI, but disagree with the conclusion that chronic conditions are also associated with SUDIC or the need for changes to death certification.
Show MoreThe study excludes deaths of infants less than 2 months old; however the peak age for unexplained infant deaths (classified as SIDS or unascertained) is 6 weeks. Data from England for the years 2004-10 show that 45% of unexpected infant deaths occurred prior to 2 months of age2, with the exception of those infants with congenital anomalies it is unlikely that these infants will have been diagnosed with a chronic condition by the time of death. Due to these issues, the study is likely to have significantly over-estimated the association of chronic conditions with SUDIC and we would invite the authors to revise their conclusion.
The authors suggest that death registrations and hospital databases should categorise deaths as expected or unexpected to help identify potentially preventable deaths. Child Death Overview Panels in England review all deaths, determining modifiable factors; and these reviews are to be collated nationally by the new established National Child Mortality Database. A similar system of Child Death Reviews has already been recommended by the Scottish Government. It would seem more sensible to fully embrace...
In their editorial Paes and Mitra suggest that all patients with down syndrome (DS) <2 years should be considered to give palivizumab (Synagis®) to prevent respiratory syncytial virus (RSV) infection. We agree with the authors that DS children are at increased risk to develop RSV infections. However, we do not agree with their recommendation for palivizumab prevention in all DS children <2 years. In our opinion there is insufficient evidence on the efficiency and cost effectiveness and the recommendation is therefore premature.
Show MoreFor the evaluation of preventive interventions the incidence and the absolute risk of acquiring the disease, and the effectiveness of the proposed intervention are important factors. The reported incidence of clinical relevant RSV infections in the general population in western countries is about 18/1,000 in newborns <2 months, 17/1,000 in children <6 months and 3/1,000 in children <5 years ( 2,3). Considering a relative extra risk of 5.5 in DS children (1) the calculated RSV incidence is 99/1,000 <2 months ( one out of 10) , 94/1,000 <6 months and 17/1,000 <5 years, respectively. The effectiveness of prevention of clinical treatment in premature children with palivizumab is about 50% (4). The extrapolated number needed to treat (NNT) for newborns with DS is 20 to prevent one hospitalization due to RSV infection. But what is the harm of this treatment as 19 out of 20 DS newborns will be given 114 injections per year...
We read with interest the recent article published by Binder E et al. [1], describing the HLA-DQ analysis performed in 1624 asymptomatic children affected with type I Diabetes Mellitus (DMT1), in order to assess their predisposition to develop Celiac Disease (CD). They reported that 1344 (82.8%) patients resulted to be "HLA-DQ2 and/or -DQ8 positive", whereas 280 (17.2%) were negative: among the former group, a biopsy-proven CD diagnosis was documented in 3.6% of cases and, interestingly, even 7 patients in the second group (corresponding to 2.5%) resulted to be celiac. [1]
Show MoreThus, these two percentages are not so different and one might conclude that the HLA-DQ asset is not a necessary - even if not sufficient - genetic background, contrary to what is well known. [2] Indeed, the absence of alleles coding MHC-DQ2 and/or MHC-DQ8 heterodimers, is associated with an almost absolute negative predictive value with respect to CD. Therefore, in order to solve this apparent mismatch, it would be useful if the authors can show the complete and high-resolution HLA-DQA1 and, in particular, HLA-DQB1 typing: indeed, these 7 “HLA-DQ2 and/or -DQ8 negative” CD children may not carry all alleles coding any complete MHC-DQ2 and/or MHC-DQ8 molecule, but they may have one or two allelic variants conferring CD risk anyway, such as HLA-DQB1*02, which codes the beta chain of MHC-DQ2 heterodimer. Indeed, according to several studies, the isolate presence of one or two copies of this...
Many thanks for your response to the editorial ‘What are you looking at?’, which highlights some important principles for this extensively studied research area (despite being a relatively new field in healthcare) [1]
Despite the emergence of new methods to analyse gaze behaviour terminology has not been revised to reflect scientific advances. A recent article by Hessels et al. outlined significant inconsistencies in the definitions of fixations and saccades held by eye movement researchers and highlighted the conceptual confusion surrounding these terms.[2]
The term saccade is derived from the French for ‘jerk’. The phrase appears to have been coined by Emile Javal, a French ophthalmologist, in the 1800’s.[3] By 1916 it had been accepted into the English literature.[4]
Saccades are frequently defined in the literature as rapid, ballistic movements of the eyes that abruptly change the point of fixation.5 Definitions have included;
‘Rapid eye movements used to voluntarily move gaze from one target of interest to another.’[6]
‘Ballistic movements, 20-150ms long, reaching a velocity up to 800°/s. They direct the eye so that external visual objects are projected onto the fovea.’[7]
‘Rapid eye movements used in repositioning the fovea to a new location in the visual environment.’[8]
The term ballistic refers to the fact that the saccade-generating system cannot respond to subsequent changes in the position of a target during th...
Show MoreHall and Sowdon regret that the Newborn Infant Physical Examination (NIPE)/child health surveillance (CHS) programme fails to deliver improved outcomes for developmental dysplasia of the hip (DDH), contrasting with the success of other screening programmes. I would like to make some proposals for improvement.
Current NIPE standards are focused on timeliness of the screening pathway and explicitly exclude treatment outcomes as ‘outside the screening pathway’1. Yet potential outcome measures are routinely available for three of the four NIPE screening programmes and shown to be measurable for two of these. McAllister et have demonstrated that records of surgical intervention for DDH can be used to show variation in outcomes2. Similarly, the NHS Atlas of Variation has demonstrated that age at orchidopexy can be used for undescended testis (UDT)3. Surgery for congenital cataract could be used in the same way. While I accept that definitions and actual measures might need some discussion to reach a national consensus, measuring these outcomes is possible from routine data.
McAllister et al conclude that dedicated leadership of the DDH screening programme is associated with improved outcomes. This has also been shown for UDT4. Unfortunately, clinical leadership of the Healthy Child Programme (HCP) has been dismantled in recent years and the RCPCH recorded a community paediatric HCP lead in only 16% of services in 2015.
Lastly poor outcomes may indicate...
Show MoreWe thank Nitzan et al for their comments in relation to our article on use of pulsatility index (PI) in screening for critical congenital heart disease (Searle 2018). In particular, we are grateful that they draw further attention to the potential for current screening to miss critical lesions, such as coarctation of the aorta. Given the progressive nature of these pathologies, it is an extremely difficult challenge to design an acceptable screening tool, which highlights all affected babies in appropriate time. Despite strong biological plausibility, current evidence is unclear whether pulsatility index can translate into such a tool.
We fully agree that the local quality of both antenatal and postnatal screening significantly affects the measured benefit of pulsatility index. Several articles draw the distinction here between ‘tertiary’ and ‘non-tertiary’ units, though it may be more accurate to distinguish ‘better resourced’ from ‘less resourced’ settings, particularly in relation to antenatal scanning. As described in our original article, the apparent potential of PI screening in ‘less resourced’ settings seems strong, especially since many pulse oximetry sensors already measure it. Both Schena et al (2017) and Granelli & Ostman-Smith (2007) highlight a small but important population of babies not detected by standard screening, but with abnormal pre-morbid pulsatility indices. It seems incongruous, however, to extrapolate a single extra case detected by th...
Show MoreM Nadeem
1. Department of Paediatrics, Tallaght University Hospital, Dublin 24, Ireland
2. Trinity College Dublin
Corresponding author: M Nadeem, Department of Paediatrics, Tallaght University Hospital, Dublin 24, Ireland
So et al1 reported a case of meningococcal group W meningitis in an infant who presented within 24 hours of receiving group B meningococcal vaccine (4CMenB). Fever and focal seizure, which required two doses of intravenous lorazepam, have been reported at the time of presentation. Intravenous ceftriaxone was commenced for suspected sepsis. CSF PCR was positive for capsular group W meningococcus. With respect to the focal seizure in a febrile infant, whether viral encephalitis was excluded and whether antiviral was commenced pending the exclusion of herpes simplex encephalitis (HSE) are questions that were not addressed in the present case.
At the time of presentation, it may not be possible to clinically differentiate encephalitis from meningitis, as either syndrome may have common features including fever, headache and meningism.2 Children with encephalitis may present with fever, seizures and focal neurological signs.2 3 Moreover those with HSE may experience a progressively deteriorating level of consciousness with fever, focal seizures or focal neurological abnormalities in the absence of any other cause.2 4 However the absence of fever2 5 or the lack of altered states of consciousness5 at presentation does not exclude...
Show MoreThe review by Searle et al “Does pulsatility index add value to newborn pulse oximetry screening for critical congenital heart disease?" (Searle 2018), provides a comprehensive overview of the current evidence regarding the addition of perfusion index to the CCHD screening algorithm.
Show MoreThe authors’ main concern is that adding pulsatility index (perfusion index, PI) will not significantly improve the current detection rate which is already quite high. As a proof, they cite the work of the large trial by Schena et al, (Schena 2017) that found one additional case of CCHD in 42,169 babies examined. The authors conclude that incorporating PI into current screening algorithms provides little additional benefit in detecting CCHD and confers a high false positive rate.
We would like to voice several comments regarding this article:
First, in the study of Schena et al, CCHD was suspected before screening in 36/38 cases in tertiary centers. This is the main reason that PI (and pulse oximetry screening) did not have any additional value in tertiary centers. In this study, only 23.6% of the neonates were born in non-tertiary center. We suggest that an alternative way to describe the results is that in non-tertiary centers, pulse oximetry detected 2 cases and PI detected an additional 1 case per approximately 10,000 screened neonates. Therefore, adding PI to the screening algorithm improved the detection rate by 50%. Moreover, the 2 cases detected by pulse oximetry...
Pages