Subhi et al have asked when oxygen should be given to children at high altitude observing that hypoxaemia is the most common fatal complication in deaths occurring from pneumonia in children in developing countries (1). Might the answer be never?

Supplementary oxygen appears to be harmful in climbers on Everest possibly because it eliminates the up-regulation of oxidative phosphorylation by mass action by hypocarbia (2) but the benefical effects of this up-regulation could be concealed by the adverse effects of hypothermia at this altitude. A more relevant question might be should supplementary oxygen be given to children with pneumonia or even asthma at low altitude for in these circumstances hypothermia is unlikely to be a confounding factor.

Supplementary oxygen was not a significant factor in the non- traumatic deaths that occurred in descent from the summit of Everest. Nevertheless the putative beneficial effects of hypocarbia on oxidative phosphorylation can be expected to be far greater at sea level, than on Everest, for they will not be concealed by the adverse effects of hypothermia. Asthmatics, for example, might be better off not receiving oxygen. The same applies to patients with sepsis. In the latter progressive adjustments to the ventilator settings designed to achieve as low PaCO2 as safely possible might not only up-regulate oxidative phosphorylation but also limit the severity of the metabolic acidosis that can develop in these patients. In so doing the associated development of cellular apoptosis and necrosis, the local inflammatory response induced by cellular necrosis, and organ dysfunctions and deaths might also be prevented.

Two variables would seem to be particular important in the regulation of oxidative phosphorylation: the PaCO2 and the pH, the protonmotive force increasing as the extracellular, or more specifically the extramitochondrial, pH falls. The effects appear to be independent of one another. In the first place "the mammalian central chemoreceptor for respiratory control is responsive independently to H+ and CO2 and that H+ and CO2 exert differential effects on the respiratory centre in terms of frequency and magnitude" (3). Secondly lactate is a linear function of tissue PCO2 in rats (4). Thirdly in patients with sepsis those with a high lactate paradoxically appear to have a higher tissue pH than those with a low lactate (5) presumably because up-regulation of oxidative phosphorylation decreases the likelihood of developing a "lactic acidosis".

Hypoxia exerts its effects upon respiration through peripheral chemoreceptors. In our study of ventilated dogs progressive decreases in FiO2 failed to induce oxygen supply-dependency before death from cardiac arrest (6). In retrospect this demonstrated the remarkable capacity to deliver adequate amounts of oxygen to tissues in the face of hypoxic stress, a finding confirmed by the studies on Everest. There was another study, conducted by Canadian investigators, that followed DO2 and VO2 in dying patients and found that oxygen supply-dependency failed to develop until the DO2 was so abnormally low that the findings were difficult to believe at the time. Regretably I have been unable to locate the reference. If, however, my recollection is accurate these studies add to the weight of evidence demonstrating that DO2 may not be the limiting factor in the acutely ill. More importantly, perhaps, is the hypothetical risk of ischaemia/ reperfusion or hyopoxia/reoxygenation injury if acute hypoxia is reversed with oxygen.

To prevent reprfusion/reoxygenation injury, which must be a primary objective during resuscitation, it would seem desirable to withold supplementary oxygen in all circumstances and possibly even to reduce FiO2 to abnormally low levels or give supplementary carbon monoxide during the initial phases of resuscitation. To optimize ATP resynthesis in a child who is critically ill it might be best to reduce the PaCO2 as low as possible, and that might be as low as 10 mmHg, and/or to reduce the arterial bicarbonate concentration so that the pH is clamped at normal or slightly lower (7,8). Clamping of the pH at the derisred level could in theory be achieved using the pH-stat technique using two auto-burettes, one filled with a suitable acid and the other a suitable alkali (9).

Giving supplementary oxygen to children with acute respiratory infections and even asthma might never be advisable. If oxygen is to be given it might be better to give it intraperitoneally for giving it into the lumen of the gut appears to be cardioprotective in hypoxaemia. There are good grounds for doing so (10, 11,12). The risk/benefit of such an approach has, however, not been established except in the case of ECMO.

1. Rami Subhi, Katherine Smith, Trevor Duke When should oxygen be given to children at high altitude? A systematic review to define altitude -specific hypoxaemia. Archives of Disease in Childhood 2009;94:6-10

2. Dexamethasone and hepatic energetics in climbers attempting Everest. Richard G Fiddian-Green (17 January 2009). eLetter re: Matiram Pun. Important points in analysing deaths on Mount Everest BMJ 2009; 338: b41.

3. Y Harada, M Kuno, and Y Z Wang. Differential effects of carbon dioxide and pH on central chemoreceptors in the rat in vitro. J Physiol. 1985 November; 368: 679–693

4. Nakagawa Y, Weil MH, Tang W, Sun S, Yamaguchi H, Jin X, Bisera J. Sublingual capnometry for diagnosis and quantitation of circulatory shock. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1838-43.

5. Effect of dobutamine on oxygen consumption and gastric mucosal pH in septic patients. Gutierrez G, Clark C, Brown SD, Price K, Ortiz L, Nelson C. Am J Respir Crit Care Med. 1994 Aug;150(2):324-9.

6. Grum CM, Fiddian-Green RG, Pittenger GL, Grant BJ, Rothman ED, Dantzker DR. Adequacy of tissue oxygenation in intact dog intestine. J Appl Physiol. 1984 Apr;56(4):1065-9.

7. Gastric intramucosal pH, tissue oxygenation and acid-base balance. Fiddian-Green RG. Br J Anaesth. 1995 May;74(5):591-606.

8. Monitoring of tissue pH: the critical measurement. Fiddian-Green RG. Chest. 1999 Dec;116(6):1839-41.

9. Mechanisms of disposal of acid and alkali in rabbit duodenum. Fiddian-Green RG, Silen W. Am J Physiol. 1975 Dec;229(6):1641-8.

10. The intestinal factor in irreversible hemorrhagic shock. LILLEHEI RC. Surgery. 1957 Dec;42(6):1043-54.

11. The intestinal factor in irreversible endotoxin shock. LILLEHEI RC, MACLEAN LD. Ann Surg. 1958 Oct;148(4):513-24

12. Supplemental systemic oxygen support using an intestinal intraluminal membrane oxygenator. Gross BD, Sacristán E, Peura RA, Shahnarian A, Devereaux D, Wang HL, Fiddian-Green R. Artif Organs. 2000 Nov;24(11):864-9.

Dear Sir I absolutely agree with your conclusions about demand feeding being something “we might all be able to live with”, but we should really respect the children’s “demand”. I also agree that there is no strong evidence to support exclusive breast feeding for six months, but there is neither strong evidence about the optimal complementary diet and there is not any certainty that the child introduced to solid foods will accept them assuming the pediatrician's "scientifically" prescribed doses. On the contrary this is the least likely event, in the sense that children will - - in general -- eat more or less of that which was prescribed. Moreover offering solid foods to a child who is not interested at all to them, one is just looking for feeding problems. Man proposes, Child disposes. It is about eight years since a considerable group of family paediatricians, throughout Italy, started practicing what we today define “Demand Complementary Feeding”, i.e. “Baby led introduction of complementary foods in the context of family meals whenever and wherever they take place.” The proposal was first published in 2002 (1), and then reaffirmed in 2006 (2). The point is that the change in WHO recommendations about the most appropriate age of introducing solid foods, gradually sliding towards more mature stages of child development, allowed us to catch those cues you talked about, without the confusing confounding factors arising from the practice of an imposed weaning. So, today, we can not say any more that babies on an exclusive milk-diet show interest in table-food because they are hungry or antsy for something different. They do not know yet that such thing is food. They are, as every baby between five to six month old, interested in table-food as well as in every other thing parents, or other trusty caregivers, are doing all day long. Only after parents yield to their irresistible staring, flustering and reaching, babies taste, often recognize, appreciate and finally accept happily “that thing”,-- which they did not know what it was -- as food. In a cohort study (personal data) in which mothers were followed during pregnancy, they were instructed through specific courses and interviewed in the second half of the first year. Nearly all of them had recognised timely their children's "interest cues" and most of them had carried on meeting their increasing requests of any food on the table, at the children’s pace. Obviously, they did not show problems of refusal or of selected diet, and their mother never worried about insufficient intake or fights for the last crumb. And, on the other hand, there is a decrease in useless work for the paediatrician. Sooner or later all children, gradually, within the end of the first year substituted their midday and evening milk-meals with solid food. At last, but not least, all that, obviously and inevitably, entails an elementary and simple parent’s education about the optimal diet (from now on) for the whole family, that does not necessarily means a tasteless diet. Weaning, as well breast feeding, is primarily a family task.

1) Lucio Piermarini. Autosvezzamento. Medico e Bambino 2002;21:468- 471 2) Lucio Piermarini. Complementary feeding at request. Medico e Bambino 2006;25:439-442

I read this article with interest and was pleased by the emphasis given to Medical Education in this journal(1, 2). There is necessity for more literature on Medical Education in frontline journals like this.

Reading the RCPCH document for Level 2 competency for Core Highest Specialist Training in Paediatrics(3), I was disappointed that Best Evidence Medical Education (BEME)was not included.

It is necessary to move from opinion-based education to evidence- based education. Since its introduction, the implementation of BEME has been slow due to lack of awareness. We hardly read literature on education, or more appropriately, are not even aware that such literature exists(4).

Whereas it was once assumed that a competent basic or clinical scientist would naturally be an effective teacher, it is now acknowledged that preparation for teaching is essential. In a review of this topic, authors conclude that the very nature of being professional in today's social and fiscal context demands that medical educators provide evidence of effectiveness and efficiency of their programs(5).

Fortunately we live in a time where ubiquitous acceptance of Evidence Based Medicine (EBM) has made the concept of Evidence- based practise irrefutable. All that is needed now is to lead Trainees into applying the equivalent principles of seeking evidence and implementing appropriate change based on the best available evidence to engender the thought process of Evidence –based education.

Specialist Trainee curriculum should therefore encompass guidance on how BEME can be applied. This may include:

1.encouraging reflection on teaching methods allowing the trainees to identify the gaps in their teaching practice

2.encouragement to seek feedback from students and the opportunity to discuss the feedback with experienced teachers to decide on the required strategy for improvement

3.facilitating the process by providing information about database such as the Campbell Collaboration (www.campbell.gse.upenn.edu) and Best Evidence Medical Education collaboration (www.bemecollaboration.org)

These are suggestions for creating a paradigm shift to encourage young doctors to look at teaching activities in the light of exsisting best evidence. Emphasis given to Medical Education in high impact journals will aid in achieving this goal.

Reference: 1.McGraw ME. Delivery of the paediatric curriculum of the Royal College of Paediatrics and Child Health (RCPCH). Arch Dis Child2009;94(4):254-7. 2.Bindal T, Wall D, Goodyear HM. Specialist registrars’ views on their teaching role. Arch Dis Child2009;94(4):311-3. 3.A Framework for Competences for Level 2 Training in Paediatrics, 2005 Royal College of Paediatrics and Child Health 4.BEME Guide No. 1: Best Evidence Medical Education. Medical Teacher, 1999 ;21 (6): 553 – 562 5.Dauphinee WD, Wood-Dauphinee S.The need for evidence in medical education: the development of best evidence medical education as an opportunity to inform, guide, and sustain medical education research. Acad Med. 2004;79(10):925-30.

Dear Editor.

Packman et al. responded to Howell et al.’s article (doi 10.1136/adc.2007.134114) on bilingualism and stuttering. We showed that speaking two languages in the preschool years increased the chances of children starting to stutter and decreased the likelihood of recovery from stuttering relative to speakers who learned English when they started school.

We do not consider, as Packman et al. suggest, that studying the general population of bilinguals would benefit the study of how speaking a second language affects stuttering. First, statistically speaking, demonstrating that bilingualism has no effect on stuttering, as the authors wish to do, is impossible. Also, investigating the general population of bilinguals is a flawed approach as bilingualism is massively heterogeneous within and between societies (including the US, Australia and Canada, where the authors work). Consequently, stringent controls (not biased sampling) have to be imposed in studies on bilingualism and stuttering. The controls we imposed excluded children who were brought up bilingual for social, educational or financial advantage. This reduced the heterogeneity in the bilingual sample. We compared bilinguals who had to use an additional language in the home with a matched sample who only spoke a language other than English in the home. The two groups of children selected for our study were directly comparable with respect to socio-economic status etc., and provided an appropriate sample on which to test the hypothesis of whether deferring learning English as a second language affected onset of stuttering and whether stuttering recovered. The same controls are appropriate for selecting similar groups for study across countries (unlike a sample from the general population of bilinguals at large).

They go on to state that our cohort is biased, and refer to a clinical study that followed up children from about age 3 to 8. 1 They say that the generally accepted age of stuttering onset is 3 years. However, the authoritative handbook in the area notes that the onset of developmental stuttering can occur at any age up to 13 years. 2 Consequently, studies that cease examination at age 8 bias estimates of age of onset to lower ages by excluding cases where onset occurs after age 8. They also incorrectly state that the gender ratio is 1:1 (there was a higher ratio of males/females in our study). All studies we are aware of (including the one they cited 1) show more males stutter than females. For example, the classic study by Andrews and Harris 3 from 2 to teenage reported a ratio of 2.4:1. A gender ratio of 1:1 suggests they are including children who do not stutter as stutterers (they have many false positives) and there is about an equal chance of misdiagnosis for each gender. The reasons for such misdiagnoses could be because they 4 use parental nominations for identifying cases and employ symptoms for diagnosing stuttering (whole word repetitions) that are excluded by several authorities. 5 6 7 The inclusion of these would lead to fluent children being classed as stutterers.

Packman et al. suggest that the Lidcombe program of therapy may be appropriate to treat bilingual children who stutter. However, the study they cited excluded children who did not have “proficiency in English” and there is no translation of the procedure into several of the languages spoken by our participants. In addition to the fact that they may be treating children who do not stutter, the statistical treatment in the study they cite has been faulted and long-term follow-up indicates that some “children [treated by Lidcombe] may start to stutter again”. 8

They state that an epidemiological study is appropriate to determine whether there is a relationship between stuttering and bilingualism. We have warned about the problems of grouping together heterogeneous bilinguals for study, as is necessary in epidemiological work. They overlook the fact that our work reported on the risk of starting to stutter and chance of recovery, using longitudinal data through to teenage. They suggest the onset age is about three years and that most recovery occurs in the first three years after onset. Conceivably, an epidemiological study at ages less than 8 could provide information about risk factors for onset of stuttering. However, it would not be informative about recovery since 50% of cases still stuttering at age 8 will recover 9 10, and recovery is not resolved until teenage. 3 9 10 Although epidemiological work does not require a longitudinal dimension, this is necessary when studying recovery, where results on the same speakers are needed in order to avoid biases. As in our study, they will need to use standardized instruments to establish persistence and recovery at teenage. If they intend to asses the impact bilingualism has on school performance, they will again need to extend examination to teenage.

In their last paragraph, they state that 4% stutter-like dysfluencies suggests our children would still be stuttering. Frequencies around this value have been used to differentiate young children who stutter from normally fluent speaking peers for English 1 and Dutch. 11 As discussed earlier, relatively high rates of supposed stuttering events may be due to inclusion of monosyllabic whole word repetitions, which are a common feature in fluent children’s and adults’ speech. 12

In summary, we consider our conclusions to be valid. Our experimental groups were matched appropriately and thoroughly documented with respect to language background and assessment for stuttering. The authors of the letter make statements that are contradicted in the literature. There are major faults in the way the authors of the letter propose to study the relationship between bilingualism and stuttering.

Acknowledgement This work was supported by grant 072639 from the Wellcome Trust to Peter Howell. Address Correspondence to: Peter Howell, Division of Psychology and Language Sciences, University College London, Gower Street, London WC1E 6BT, England. Email: p.howell@ucl.ac.uk

References

1Yairi E., Ambrose NG. Early childhood stuttering. Austin, TX: Pro- Ed, 2005.

2Bloodstein O., Bernstein Ratner N. A handbook on stuttering, 6th ed. Clifton Park, NY: Thomson, 2007.

3Andrews G., Harris M. The syndrome of stuttering. Clinics in Developmental medicine (No 17). London: Heinemann, 1964.

4Reilly S., et al. Predicting stuttering onset by the age of 3 years. Pediatrics, 2009;123:270-277.

5Conture EG. Stuttering. 2nd ed. Englewood-Cliffs: Prentice Hall; 1990.

6Ryan B. A longitudinal study of articulation, language, rate, and fluency of 22 preschool children who stutter. Journal of Fluency Disorders, 2001;26:107-127.

7Wingate ME. Foundations of stuttering. San Diego: Academic; 2002.

8Packman A., Kuhn L. Looking at stuttering through the lens of complexity. International Journal of Speech-Language Pathology, 2009;11:77– 82.

9Fritzell B. The prognosis of stuttering in schoolchildren: A 10-year longitudinal study. In Proceedings of the XVI Congress of the International Society of Logopedics and Phoniatrics, 186-187. Basel: Karger, 1976.

10Howell P, Davis S, Williams R. Late childhood stuttering. Journal of Speech Language and Hearing Research, 2008;51:669-687.

11 Boey et al., Characteristics of stuttering-like disfluencies in Dutch speaking older children, adolescents and adults. Journal of Fluency Disorders, 2007;32:310-329..

12 Levelt W. Speaking: From intention to articulation. Cambridge, MA: Bradford Books, 1989.

Peter Howell,

Stephen Davis,

Division of Psychology and Language Sciences, University College London, United Kingdom

Roberta Williams,

Department of Language and Communication Science, City University London, United Kingdom