138 e-Letters

published between 2015 and 2018

  • Cardiac Screening: Pulsatility Index, Population Studies and False-Positive Rates

    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...

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  • Perfusion index and undiagnosed critical left-sided obstructive heart defects.

    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...

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  • Socioeconomic status and risk of cardiovascular disease in childhood

    Seo et al. conducted a prospective study to identify factors for cardiovascular disease risk factor clustering (CVD-RFC) in adolescents (1). A total of 1309 children aged 6-15 years were enrolled, and higher household income was a significant predictor of lower CVD-RFC incidence with dose-response relationship. In contrast, the presence of parental CVD history, overweight or obesity, and shorter sleep duration were significant predictors of higher CVD-RFC incidence. I have some comments with special reference to socioeconomic status (SES) and metabolic components.

    First, Iguacel et al. investigated the association between socioeconomic disadvantages and metabolic syndrome (MetS) in children (2). By adjusting diet, physical activity, sedentary behaviours and well-being, standardized multiple regression coefficients (99% confidence intervals [CI]) of children from low-income families, non-traditional families, with parents of unemployment, and accumulation of >3 socioeconomic disadvantages for a higher MetS score were 0.20 (0.03-0.37), 0.14 (0.02-0.26), 0.31 (0.05-0.57), 0.21 (0.04-0.37), respectively. These data present that low SES was closely associated with MetS in children, which was in concordance with data by Seo et al (1).

    Second, Patel et al. examined the association between parental socioeconomic position (SEP) and early-life offspring body mass index (BMI) in children (3). Adjusted difference of BMI z-score (95% CI) was 0.08 (0-0.16) among girls...

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  • Big boys do cry....

    Dear Sir,

    It is with great interest that we read ‘Why do babies cry?” in which Dr. Robert Scott-Jupp have provided a concise evaluation of the research pertaining to non-pathologic crying in infants.

    Crying is a normal variant in the day 2 newborn examination however it can pose a significant source of stress and anxiety for parents. To add to the body of evidence detailed in this article we posed the question; What proportion of babies cry during the day 2 newborn examination?

    A convenience sample of data was collected on well babies during the standard day 2 physical examination on the postnatal ward in a tertiary maternity hospital. All babies on the postnatal ward were eligible for inclusion. Gestation, birth weight, gender, mode of delivery and duration of examination were recorded. The presence or absence of crying during examination was documented. The data was analysed using SPSS .

    One hundred and fifty three babies (n=153) were included in the study. There were 82 male infants (53%) and 71 female infants (47%). Mean birth weight was 3589g (range 2590g -5160g) with a mean gestation of 39+4 (Range 36+3 - 42+1). Mean duration of examination was 7 minutes. Eighty-one babies (52.9%) delivered by spontaneous vaginal delivery, 22 (14.4%) by ventouse, 26 (16.9%) by elective caesarean section, 20 (13.1%) by emergency caesarean section and 4(2.6%) by forceps. Overall, 118 (77.1%) babies were observed to cry during the physical examination (78%...

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  • The educational value of Saccades

    Dear Sir,

    As a final year medical student, I read with great interest this article highlighting the pedagogical value of gaze study. Whilst the article raises many poignant features of this new medium of data collection, I believe the definition of saccade in your article may be slightly incomplete.

    The article states that “Saccades...are movements of the eyes between fixations in which information is not meaningfully acquired or absorbed.” However, I would suggest that whilst the primary purpose of saccades may be to move between fixation points, there is subconscious information acquisition completed by these movements-- the subconscious identification of a lack of pathology.

    If one does not take certain regions of an image as fixation points, it suggests that they are not looking for pathology in those regions. This is reinforced by one study analysing gaze study in mammogram analysis which reported that “long saccades often missed the target but were followed by corrective saccades”. (1-Kundel H, Nodine C, Conant E et al. Holistic component of image perception in mammogram interpretation: gaze-tracking study. Radiology 2007;242(2):396-402.) This highlights that within a saccade is also inert analysis of a lack of pathology rather than just transformational eye movement.
    Another study analysing a gaze study of virtual histopathology slides between trained pathologists, residents and medical students reported that “fully trained pathologists h...

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  • Response to comments of Professor Marchetti

    Dear Sir

    We thank Professor Marchetti for his comments on our article in ADC (1). He raises two important questions we wish to comment on.

    Regarding which dose of aspirin to use, we are also interested in the suggestion that anti-aggregant doses of aspirin might be a preferred option for the acute inflammatory phase of Kawasaki disease (KD). It is indeed possible that future guidance may recommend low dose aspirin (3-5 mg/kg/day) at all stages of KD, as suggested by the retrospective data referred to by Professor Marchetti (2). Whilst we acknowledge the potential merits of such an approach, particularly in relation to avoidance of toxicity, there has never been a prospective controlled clinical trial to support this and therefore no high-level evidence on which to base firm guidance. Two other practical considerations are worthy of highlighting in relation to aspirin. Firstly, nonsteroidal anti-inflammatory drugs such as ibuprofen, which antagonize platelet inhibition induced by aspirin (3), should be avoided in patients with KD receiving anti-aggregant doses of aspirin. Secondly, although the risk of low dose aspirin (3-5 mg/kg) in being associated with Reye syndrome is unknown, usual advice is to discontinue in the event of inter-current infection.

    Regarding the use of corticosteroids for primary treatment of KD, we have been strong advocates of this for several years, as reflected in previously published guidance (4, 5). This is now brought into...

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  • Response to comments of Dr Andrea Dotta and Dr Renato Cutrera

    Dear Editor,

    We thank you for the opportunity to discuss our data with the two correspondents who raised some concerns regarding the selected population of our analysis on neonatal outcomes following new reimbursement criteria on palivizumab use. They also reported data collected during the same time period and apparently different from our main results.

    In response to the first correspondent, our analysis is based on children < 2 years of age because the candidate for palivizumab treatments are included within this subpopulation. In fact, the therapeutic indication (1) of palivizumab includes not only the preterm infants up to 1 year of age but also children up to 2 years of age and treated for bronchopulmonary dysplasia or born with a serious heart disease. Furthermore, our selected population is consistent with previous analysis (2) that measured the association between updated guidelines-based palivizumab administration and hospitalization for Respiratory Syncytial Virus (RSV).   Table 1 of our study reports children up to 6 months of age, both at risk of RSV and including hospitalization data. We agree that this is probably the subpopulation with the major impact of the palivizumab treatment and regulatory decision. However, also in this case no differences in hospitalization rate have been detected before-after the AIFA’ limitation for palivizumab: 1031/47.608 (21.7 ‰) and 436/22715 (19.2 ‰) hospitalizations, respectiv...

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  • Response to Dr Smith - balanced fluids

    Dear Sir/ Editor,

    Dr Smith makes relevant and interesting points regarding the terminology used for fluids, which can be used for both “resuscitation” purposes and “maintenance” therapy, and we thank him for his interest and response.

    The purpose of this clinical question was to review the current evidence for paediatric patients in relation to “ balanced fluids”, a term emerging in the medical literature. NICE recommends using any isotonic crystalloid, which covers a wide range of sodium concentration from 130 to 154mmol/L (reference 1 in the article).

    The loss of electrolytes, either from the gut or as a result of renal impairment, needs regular clinical review. We observe that repeated bicarbonate measurements are not regularly undertaken after initial assessment or following admission and it is important to remind trainees to consider these losses, hence our recommendation of daily monitoring of electrolytes. By following this approach, appropriate individualised adjustments can be made to the fluid prescription of patients as necessary.

    Our conclusion from this question highlighted that research needs to be undertaken in the paediatric population of bicarbonate/ lactate containing fluids to determine whether this may affect acute kidney injury and other specific clinical outcomes. We agree attention to detail is always necessary when caring for infants and children receiving intrav...

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  • Kawasaki disease: is it time to consider the antiplatelet dose of aspirin even in the acute phase of the disease?

    The results of the British Paediatric Surveillance Unit survey show that aspirin in Kawasaki disease (KD) is used in the UK and Ireland at a medium dose of 30-50 mg/kg/day in the acute phase of the disease (1). The guidelines of the American Heart Association (AHA) of 2017 do not give a clear indication on what dose of aspirin should be used in the acute phase of KD, stating that "there are no data to suggest that one dose of aspirin is superior to the other" (3).
    However, a recent review of the evidence of literature on the use of aspirin in KD (3), clearly shows that, in conjunction with intravenous immunoglobulin, low-dose ASA (3-5 mg/kg/day) in acute KD is not inferior to high-dose ASA (80-100 mg/kg/day) for reducing the risk of coronary artery (CA) abnormalities, duration of fever, responsiveness to IVIG and time of hospitalization (3). These results supports using low-dose (3-5 mg/kg/day) aspirin in the acute phase of KD (3,4). These studies did not consider the concomitant use of steroid therapy, of which the guidelines of AHA do not define a standardized use (2).
    The question of which dose of ASA is used in the acute phase is relevant considering that aspirin treatment exposes a risk of gastrointestinal bleeding, hepatotoxicity and neurosensory hearing impairment and Reye syndrome, and that this effect is strictly dose dependent and related to duration of therapy (3).
    We believe that the time has come to reconsider and update the guideli...

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  • Correct target population for Palivizumab cost-utility analysis

    Dear authors,

    We are kindly observing that the study on hospitalizations for infection due to respiratory syncytial virus should be conducted on infants aged <1 year old [1], and not on infants aged <2 years old. Such a choice is motivated by medical literature and since the prescription of palivizumab on the general population of preterm infants is up to 1 year of age. Moreover, the study does not tightly classify the hospitalization depending on the gestational age, a lack of information that exclude the possibility of a punctual statistical analysis on the infants whose gestational age is between 29-35 weeks, population matter of the analysis, impacted by the AIFA reimbursement limitations.
    In the study infants aged <2 years old have been considered, the same subjects are statistically contributing to two consecutive seasons with different ages. The algebraic sum of the season 2014-2015 / 2015-2016 perpetuate the complexity of analysis of hospitalization for a specific season, if the infant is hospitalized in the season of his/her birth or next year.
    As reported by Medici et al. [2], respiratory syncytial virus infection has a 2-years evolution, with a less critical year following a year with more abundant virus diffusion. By algebraically summing the data from two consecutive years the seasonality, so the stochasticity, is lost. Eventually the season 2016-2017 appear to be the less critical season. Environmental and patient conditions such...

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