Please, please, not ABBA!

Posted on 18 March 2014 by Keith Barrington

I think whoever designed this study should be subjected to prolonged and unrelenting auditory torture. the only thing worse than ABBA that I can think of would have been Rolf Harris’s 2 little boys; so that is the sentence I pronounce on Dr Roehr and his colleagues, being subjected to that tune for a few hours every day might make them rethink this intervention.

The authors took experienced neonatal resuscitators and played different songs during resuscitation simulations. They found that the rates of chest compressions and respiratory inflations were higher when they played ABBA’s song SOS over an iphone at maximum volume.

They interpret this as meaning that the ‘music’ (and I use the term loosely) improved the compliance with recommended rates of chest compressions and ventilation, and maybe this should be more widely investigated.

I interpret as meaning that the participants, on hearing the ABBA song, wanted to get out of there as fast as possible, and did everything more quickly to try and get it to go away.

Seriously, if this becomes standard I will have to reconsider my career.

Posted in Neonatal Research | Tagged | 5 Comments

Sticking needles into babies doesn’t reduce colic. Who’d have thought…

Posted on 17 March 2014 by Keith Barrington

More nonsense, this time acupuncture for babies!

Ninety babies were randomized in a multicenter trial of sticking needles into non-existent meridians to channel imaginary Qi energy. Unfortunately the condition they were investigating, infantile colic, causes a lot of real distress to parents.

Reasonably blinded study, found nothing.

Go figure.

Posted in Neonatal Research | Tagged | 6 Comments

Waving your hands around is not analgesic! Who’d have thought…

Posted on 17 March 2014 by Keith Barrington

Really, who’d have thought it was worth testing.

I have a lot of respect for several of the authors of this trial, but I can’t for the life of me understand why they did this study. Celeste Johnston, Marsha Campbell-Yeo, Francoise Filion and I have been co-authors on a couple of studies together, and they have all done good things improving pain control in the NICU.

But this study should never have been done, and should never have received a penny of grant money. They were testing the idea that ‘therapeutic touch’  (which they start to describe as follows:

Therapeutic Touch does not involve direct tactile stimulation, but is based on a trained therapist working with energy fields)

might be analgesic in preterm babies. At that point, they should have been laughed out of town, and the grant application thrown in the waste basket. In order to be ethically valid there has to be a valid scientific rationale for doing a study. There has to be some prior plausibility to the intervention. Manipulating non-existent ‘energy fields’ is not plausibly effective at anything, no matter what kind of training the therapist has!

The intervention is described in more detail as follows:

For the Therapeutic Touch intervention, the therapist used her hands to assess and rebalance the energy field of the patient using the following steps: (1) centering her state of awareness; (2) assessing the energy field of the patient; and (3) modulating the energy field. The average time for this was 5 minutes. Both therapists were nurses and had several years of experience in Therapeutic Touch.

How on earth could the authors write that paragraph without laughing themselves silly, like I did when I read it!

Why on earth would a good journal publish such drivel? How on earth could you convince an ethics committee to allow this nonsense, and why would anyone give grant money to a team who proposed wasting it on this inanity?

The only reason I can think of for doing this, (as I said I know several of the authors, and I know they have the best interests of their patients, and of promoting good research and good patient care at heart: I hope they will still consider me a friend and colleague after my critical remarks) is that some misguided individuals are already doing such stuff, and they wanted to prove that it was ineffective, and that you should use real pain control when doing painful things to babies.

My response to that would be that anyone who is prepared to modulate a babies energy field is unlikely to be convinced with an actual scientific study. They should just be told to stop it, or go work in another environment, perhaps in a homeopathic Emergency Room.

(BTW not surprisingly, modulating the energy field, even after centering the state of awareness, didn’t do squat).

Posted in Neonatal Research | Tagged , , , | 6 Comments

Article now listed on PubMed

Posted on 17 March 2014 by Keith Barrington

The commentary that a large group of us wrote in reply to the CPS statement on extreme prematurity is now listed on PubMed.

(Janvier A, Barrington KJ,  et al: CPS position statement for prenatal counselling before a premature birth: Simple rules for complicated decisions. Paediatrics & child health 2014, 19(1):22-24.)

I am not sure, but I think it may be freely available, you can go to the link if you wish and try. If you want a pdf and it doesn’t work, a judicious inquiry might be able to get you a copy.

Posted in The CPS antenatal counselling statement | Leave a comment

Premature babies, should the school know?

Posted on 17 March 2014 by Keith Barrington

I saw a link to this article, a paediatrician from Glasgow thinks that because premature babies have more problems as they grow up than children who are born at term, the schools should have the gestational age on their entry forms.

I disagree.

We actually lied about Violette’s birth history when she was enrolled in school. Our reasoning was that a) we did not want her to be labelled, as many other premature babies are, we did not want teachers and the school to have lower expectations for her because she was extremely preterm. b) premature babies have more difficulties it is true, but many children born at term have difficulties at school also, they should all be able to get the assistance they need. The school should be able (and appears to be able) to identify any problems she has, and develop interventions if needed to address them. How does knowing she was born at 24 weeks help the school to help her?

On the other hand if she had a specific learning problem identified, that the school needed to know about in order to intervene, then yes, they need to be informed and we would have told them. Premature babies have a range of abilities and difficulties when they grow up, just like babies born at term, being born prematurely is not an impairment!

If she now had difficulties organizing her work, and staying on task (the kind of executive functions that many ex-preterms have) then they are not such unusual problems! Lots of children who were born at term also have those problems, and they all need strategies to help them out. Preterm babies problems in such fields tend to improve over time, so when would you stop telling people that she was an ex-premie?

If she had cerebral palsy, and needed help to climb the stairs in the school, then the school needs to know about that specific issue. They still wouldn’t need to know that she was born too early.

I am very proud of my little girl, and not at all shy about telling people that she was born extremely prematurely, but, on balance, I think the school are better to teach her, and evaluate her, without any preconceptions based on her birth history.

Posted in Neonatal Research | 10 Comments

Neonatal Intensive Care Units work!

Posted on 17 March 2014 by Keith Barrington

The first Epicure study had relatively poor survival rates, especially for the more immature babies. Of course the data were regional data, including all babies born in the UK and Ireland, so they included babies born in places with very low levels of care, many of whom were never transferred to intensive care units. Although I think EpiCure1 was an amazing effort, the results were often used as a way of suggesting that neonatology was very ineffective. Every position statement of learned societies referred to the data, often with no description of the context . In the UK though the data were used to try and improve their regionalization, with what are called managed clinical networks. There were at the time of Epicure1 many very small units treating tiny numbers of extremely preterm babies per year, the data were never presented by level of care of the birth hospital.

The new Epicure study has rectified that (Marlow N, Bennett C, Draper ES, Hennessy EM, Morgan AS, Costeloe KL. Perinatal outcomes for extremely preterm babies in relation to place of birth in England: the EPICure 2 study. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2014.. Open Access)

The data show quite convincingly that being born in a hospital with level 2 services, and then transferred later leads to much poorer survival.

They show that being born in a level 3 hospital leads to better survival, and without more morbidities, so survival free of morbidity is much better (morbidity being defined as one or more of retinopathy of prematurity requiring retinal surgery, moderate or severe bronchopulmonary dysplasia, a severe brain injury (haemorrhagic parenchymal infarct, cystic changes or hydrocephalus on cerebral ultrasound) or surgical necrotising enterocolitis. They also showed that among level 3 hospitals, those which have higher patient volume have substantially better survival.

They also show, depressingly, that

Despite national policy, only 56% of births between 22 and 26 weeks of gestation occurred in maternity services with a level 3 neonatal facility

The proportion can never be 100% of course, but adequate regionalization can make that figure much more than 56%. The exact proportion will depend upon many factors of health care organization, and geography, but aiming for 90% is reasonable, and would save many lives.

Posted in Neonatal Research | Tagged , | 1 Comment

Letter in Early Human Development

Posted on 17 March 2014 by Keith Barrington

Some of you might recall a report in Early Human Development that I strongly criticized on this blog. The title was ‘The effect of in-hospital developmental care on neonatal morbidity, growth and development of preterm Taiwanese infants: A randomized controlled trial.’

When I wrote the blog post I also sent a letter to the editor suggesting in quite strong terms that the article was fatally flawed and should be retracted. I never received any reply from the editor, but the publishers sent me an automated message asking me to submit the letter on their website. There was actually no way to submit a letter on the website, it had to be submitted as a regular article submission. Which I did, almost a year ago. I recently received an automated email congratulating me that my article had been accepted!

Anyhow, the letter has now been published, as I originally wrote it, along with a reply from the authors.

My letter is actually very rude, and I would not have written it quite like that if I had thought it would just go to publication, I intended it to be read by the editors, the tone is much more the kind of thing I write in this blog, but I will have to live with that.

The authors’ reply is, I think, entirely inadequate. you can read it yourselves, but the authors now state that some of the exclusion criteria were actually ‘early dropout’ criteria. In other words they planned the trial from the start to not be an ‘intention to treat’ analysis but to exclude certain babies after they had been enrolled. These early dropout criteria include, for example, severe intraventricular hemorrhage, and they state that there were 7 babies with intracranial hemorrhage or calcification who were enrolled and then dropped out because of those findings. Again, this makes no sense, IVH occurs in the first couple of days of life, there would be no reason for enrolling such babies and the dropping them out again.

The authors state that the publication did indeed follow the CONSORT statement, but there are many ways in which that statement is not accurate. One major example is the following, item 6a from the CONSORT statement of things which must be included in the report:

Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed

As I mentioned before there is no primary outcome mentioned in their report, the authors state in their reply to my letter :

the primary purpose of our study was to investigate the effect of early intervention (consisting of in-hospital and after-discharge developmental care) on child, parent and mother–child interaction outcomes in VLBW  infants

Which is so vague as to be meaningless. they go on to state

Previous in-hospital intervention studies and have commonly used child medical, growth and developmental variables as the short-term outcome measures. Our paper has therefore considered all these variables as the primary outcomes.

Which just shows that they don’t understand what a primary outcome variable is. Rather than continue to beat down on these authors, I really want to ask the question, how on earth did all this get through peer review? Someone clearly did not do their job.

Posted in Neonatal Research | Leave a comment

Screening for Hyperbilirubinemia

Posted on 14 March 2014 by Keith Barrington

When I was chair of the CPS Fetus and Newborn committee, we produced several position statements, one of which I was quite proud was written by myself and by Dr Sankaran from Saskatoon, it was a guideline for the screening and treatment of hyperbilirubinemia in full term babies. The guideline recommended among other things, universal pre-discharge bilirubin screening.

When you write these things you are never sure what sort of effect it will have, we hoped that it would reduce the numbers of babies receiving phototherapy, and reduce the frequency of kernicterus, while having little effect on hospital costs or the total number of bilirubin tests prescribed. Of course, there will only be an effect if people actually follow the guidelines.

So I was pleased to see that in Ontario at least most hospitals that deliver babies do now screen routinely for high bilirubin at discharge, and most of them started doing so after the guidelines were published.

That is not to say there aren’t problems, the new study shows that the biggest problem is how to organize follow up testing. To clarify, infants at significant risk who have levels at discharge that are high, but not high enough to need immediate phototherapy, have to get follow up testing. In some communities this can be a problem, especially at weekends. In many places the mothers (or fathers) bring the baby back to the hospital, either to the lab or to the newborn nursery in order to be re-tested. This is certainly not optimal, requiring often longer journeys, and disrupting the post-partum period. Community based testing available 7 days a week is needed. Testing at home with optical bilirubinometers during a home visit from a health professional who can also check on breast feeding and progress of weight would be optimal.

Finally did it work? Is there a reduction in kernicterus? well, we don’t yet know, is I think the right answer, the guidelines were published in 2007, this new article from Ontario shows that it took until 2011 for 75% of the hospitals to be screening. In 2007, 2008 kernicterus was still a problem (albeit rare) in Canada; and not as rare as we might think, with a calculated incidence of at least 1 in 44,000 live births. It would be great to repeat the Canadian Paediatric Surveillance Program study on kernicterus to see if the guideline had an effect. I think I will drop them a line and see if that is possible…

Posted in Neonatal Research | Tagged , | Leave a comment

On the radio

Posted on 14 March 2014 by Keith Barrington

I was interviewed for the excellent Radio-Canada program on science, known as ‘les années lumières’ recently. The subject was about whether breast feeding is really best for babies. The reason for them doing the story was a recent publication by a sociologist who analyzed a database which included some siblings. Among the siblings, by parental report there were some pairs where one had been breastfed and the other had not. The authors of that study did some analyses to ‘correct’ for other influences on outcome and concluded that breast feeding had no effect. The outcomes they tested included asthma, obesity, child behaviour and some indices of intelligence.

Apart from serious deficiencies in data quality, research design and analysis, the study is only one of a very large number examining the benefits of breast feeding, some others have also examined discordant sibling pairs. There is an excellent systematic review by the US Agency for health care research and quality with the first author being Stanley Ip. A summary of which you can find here. There is also a nice take down of the article in The Huffington Post.

Anyway the interview went fairly well I think, if you want to listen it is here (it is in French) my part starts at about 18 minutes, the link should take you to the start of that specific segment, which is about 15 minutes into the show.

Posted in Neonatal Research | Tagged , | Leave a comment

Public citizen are becoming a public danger

Posted on 13 March 2014 by Keith Barrington

Public citizen are at it again, they have written another letter to the director of the DHHSS to try and follow up on their previous nonsense. I didn’t write about this when I first heard about it, as 1. it is dumb and 2. I didn’t think anyone will take any notice of more misguided criticism of SUPPORT. But with a very interesting and thoughtful viewpoint article in JAMA just published, about comparative effectiveness research, I thought I would come back to the issues briefly. 

In this new missive to Kathleen Sebelius they introduce more ridiculous arguments, criticizing the SUPPORT trial for study design lapses, inadequate oversight and failure to stop the study early.

In this new letter they state for example that oxygen saturation targets should normally be adjusted according to capillary filling time, hepatic function, intravascular volume and impending NEC (among other indications). As far as I can see they have just made these things up.

Let me make this clear in case anyone from Public Citizen is reading this blog.

THIS IS CRAP.

We do not do this. We do NOT adjust saturation targets according to capillary filling, hepatic function or intravascular volume it doesn’t make any sort of physiologic sense, and if anyone in my NICU did this we would have a very serious discussion. We do NOT adjust saturation targets in the case of non-existent diagnoses either, such as ‘impending NEC’ even if we knew when NEC was impending we have no evidence from any sort of trial (and certainly not from high quality large RCTs such as SUPPORT) that changing saturation limits is appropriate.

So here is my advice for people who want to criticize clinical research in a particular field, if you have no idea what you are talking about, either shut up, or go and ask someone who does know. Otherwise you just make yourself look stupid.

The authors of the letter then make certain points about early termination of the study which show still more clearly that they don’t understand clinical research, or how this sort of study is run.

Most trials, and all large multicenter trials, now have an independent data safety monitoring committee (DSMC). They are set up by the study steering group, but are completely independent of them, they have access to study data as the study is being run. At pre-specified points in the study the are supplied with data from currently enrolled subjects, which is usually supplied as 2 groups of data, 1 from each arm of the study, but without necessarily revealing which arm is which. They then look at the data to see if there are safety concerns, the idea being that if one group is clearly having worse outcomes on an important outcome variable than the other group, then the study can be stopped. This is an important principle to avoid exposing further patients to risks when the answer is already crystal clear.

There are risks to doing this, every time you look at the data there is a chance that you will find a difference just because of random variation, and the more times you look at the data these risks accumulate. You protect against such risks by having a limited number of looks at the data, and by requiring highly significant differences in clinically important outcomes in order to stop a trial.

What the Public Citizen authors claim is that there was no plan to examine retinopathy and death separately, and that if that had been done then the study could have been stopped after 25% enrollment. Which would have spared the remaining infants from the risks of death or severe retinopathy.

Firstly it is highly likely that the DSMC (data safety monitoring committee) did look at components of the primary outcome separately. The DSMC is independent, and is tasked with protecting future enrollees, they are not in any way restricted in what they can examine, and often ask for extra details and clarifications. I can give the example of the CAP trial, where the DSMC noted a difference in PDA ligation rates between the groups, even though that was not at all in their list of outcomes to examine according to the approved protocol.

Secondly the letter writers guess what the retinopathy rates were after 25% of the enrollment, assuming that retinopathy was uniformly distributed amongst patients. In fact that is highly unlikely. If 10% of the patients have an adverse even, it is highly unlikely that every tenth patient will be the one affected, it is equally (un)likely that the first 10 all have the adverse event and the next 90 are fine. That is one reason why much higher levels of statistical significance are required for early stopping of a trial. So according to their calculations there would have been a statistically significant difference in retinopathy between the groups after 25% enrollment. All that statement does is to show their profound ignorance. A p<0.05 level of significance is not used for early stopping of trials; more commonly a 3SD difference is required in an important outcome, equivalent to about p<0.001, for the reasons outlined above.

If that had indeed happened, however, and the study had been stopped as they suggest it should have been, this would, of course, have prevented the investigators from noting the increased mortality in the low saturation group, and the result of the trial would have encouraged everyone to start using lower saturations and causing the death of many preterm babies.

According to the Public Danger (my new pet name for the group) authors, this would not have happened because there was no ‘usual care’ group, and therefore everyone would have ignored the results and carried on as before!!!

Public Danger’s lack of understanding of what constitutes ‘usual care’ in a modern NICU is not just profound, it is persistent. It resembles schizophrenic delusions that persist despite all the evidence to the contrary.

Le me try and explain this again in case any of them are listening, which I doubt. Both arms of the SUPPORT trial were ‘usual care’. It is ‘usual care’ for an NICU to have pre-specified limits of saturations for all the preterm babies in the unit, which are not changed based on clinical factors, but stay unchanged in the face of, for example liver disease or ‘impending NEC’.

Since SUPPORT and the other oxygen trials have been published we, and many other centers, have changed our oxygen saturation limits, we now aim for over 90% for all of our preterm babies (and try to stay below 95%). We may have more retinopathy as a result, but will try to compensate by optimizing nutrition, and investigating other interventions such as perhaps omega3 fatty acids.

It would have been an enormous disaster for preterm babies, in the USA, Canada, and around the world, if the viewpoint of Public Danger had prevailed and we had all set our saturations to less than 90% because the study had terminated early. Thousands of dead babies would not have thanked us for that.

Posted in Neonatal Research | Tagged , , , , | Leave a comment