Doctors are cheap

I’m sure most of us don’t think that the little trinkets (pens and notepads and such) or a few slices of pizza that we might receive from a drug company affects what we prescribe for our patients.

We would be wrong. Drug companies buy lunches for doctors because they know they have an impact. New rules have reduced the number of expensive free vacations and similar high priced gifts that were, sadly, never offered to me, but lunches and other small gifts are still allowed in some jurisdictions. The authors of this study (DeJong C, et al. Pharmaceutical Industry-Sponsored Meals and Physician Prescribing Patterns for Medicare Beneficiaries. JAMA internal medicine. 2016;176(8):1114-10) were able to get data from a registry of gifts to doctors and medicaid prescribing patterns. They focused on 4 drugs that I never prescribe and I don’t know anything about, which were the most prescribed drugs in their class of medication.

Most of the gifts were meals under $20, doctors who received a single meal promoting the drug of interest had higher rates of prescribing rosuvastatin over other statins , nebivolol over other β-blockers, olmesartan over other ACE inhibitors and ARBs  and desvenlafaxine over other SSRIs and SNRIs. Receipt of additional meals and receipt of meals costing more than $20 were associated with higher relative prescribing rates.

I am sure that most of this is unconscious, its hard to think of a shared pizza as an effective bribe, but getting a lunch free a few times in a year makes you feel more kindly disposed to the makers of rosuvastatin than the makers of the other statin whose name you can’t remember and whose rep never bothered to even get you a coffee.

You can see this graphically here:

physician-prescribing

Someone told the authors to finish the abstract with the following sentence, “The findings represent an association, not a cause-and-effect relationship” which is of course an incorrect statement. An association is not necessarily a cause and effect relationship. But it may be. Sometimes an association is found because there really is a cause and effect relationship.

Doctors can afford to buy their own lunches. Our prescribing practices should not be influenced by anything other than the good of our patients.

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Antenatal Consultations before very preterm birth; what do parents want?

Gaucher N, et al. Personalized Antenatal Consultations for Preterm Labor: Responding to Mothers’ Expectations. The Journal of pediatrics. 2016.

Call me biased, but I think is a game-changer. (One of the authors is my wife and colleague, another is a friend and colleague in the NICU at Sainte-Justine, and the others are my friends and colleagues also… just so you know). (Also, just so you know, I was not involved in this study in any way, apart from knowing about the study going on; I did review the final manuscript for language issues and suggest a few changes in wording (all the authors are francophone but speak and write excellent English) but that is my only involvement in this).

What they did was to approach mothers (who might have had their partner with them) within 72 hours after an antenatal consultation from the neonatal team for threatened preterm delivery before 32 weeks. They asked them to fill in a questionnaire, which was intended to find out what the mothers’ expectations and satisfaction with the antenatal consultation were.

The questionnaire is presented in an appendix (in an English translation).

Why did they do the study? There are many guidelines which describe what information should be transferred to parents anticipating a preterm delivery. Most of them concentrate on what information should be transferred to the parents, sometimes with a list of all the horrible things that can happen to an extremely preterm baby that parents should be informed about. Is that what parents want from their antenatal consultation? Few studies have asked that question.

Unlike many studies in this domain, the sample size was substantial, 229 mothers completed the survey instrument, they were hospitalised in one of 3 participating university teaching hospitals in Québec.

A few highlights from the results:

The women surveyed wanted information about prematurity, but also information about their role in the NICU, about feeding strategies, visiting schedules, and so on.

The majority were satisfied with the consultation, but only 57% reported getting the right amount of information, 39% felt that they received too much information about prematurity. Most (89%) were reassured, although 23% were worried by the consultation which is more than 100%, so some were both. More than half felt better prepared for their role as mothers in the NICU (58%), and many (56%) wanted a follow up meeting with the neonatologist.

In open-ended questions,women explained why they wanted a follow-up consultation: (1) they felt too stressed during the initial consultation; (2) they felt unprepared to ask questions; or (3) they did not remember all the information provided.

You will see in the methods that we do not have a decision aid or printed information sheet that we routinely give out. Although some studies have reported that decision aids are useful, the main effect that has been shown in publications is that information transfer may be increased, for example, one decision aid was considered potentially useful because “women recalled more disabilities”.  In that study the long-term complications are grossly exaggerated (for a 23 week infant the sheet states “if the baby survives, 2 out of 3 may never be able to walk, talk, see, hear”); recalling more complications certainly does not mean that the parents are more likely to find the consultation useful, that it helps in decision-making, or that better decisions are taken for the babies, especially if the complications are exaggerated.

I think this study is a game-changer as I said, because we should surely be adjusting our approaches to the individual mother (and father) to fulfill their wishes for the consultation, and not just to have a decision about intensive care versus comfort care, which has been the focus of the position statements I mentioned. We should be trying to personalize the encounter in order to give them the amount of information they want (either to make the best decision, or to be adequately informed if there is no real decision to make). From the results of this study we should also be giving information about the local NICU practices, about the mother’s participation in feeding, and discuss how to be a parent of an NICU baby, and we should be providing an easy way for the family to get a follow up visit; improvements which could help us to better address the needs of our families. Whether the same results would be found elsewhere is unclear, but having worked in other parts of North America, I don’t think our parents are much different to parents in southern California or Alberta.

The article ends with this statement :

Current investigations mainly concentrate on optimizing and standardizing information transfer regarding prematurity outcomes, and women want personalized and individualized information. Future studies should investigate how parents want to receive this information. The actual format of the antenatal consultation might not be ideal for these information needs. It is possible that some parents may prefer an interactive Web site, a group meeting with other parents, or to meet ex-NICU parents.

Interesting ideas, but I don’t think those alternatives should be alternatives, rather additional resources for parents, an in-person meeting with the neonatal team would still, I think be essential, but perhaps not, it is something that could be studied prospectively.

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Theatrical Placebos in Neonatology

Acupuncture is nonsense. There I have said it. I’ll probably get at least a few comments for this post, but I’m not backing down. Acupuncture is based on pre-scientific ideas about how the body works, believing that some sort of vital energy flows along meridians in the body, and that sticking a needle into the skin at certain specific points can have distant effects, by letting out the Xi.

Xi is non-existent, meridians are non-existent and there are no acupuncture points, they just don’t exist.

This is all ridiculous, and people with a medical education should know better. Trials of acupuncture in adults have shown that it doesn’t matter where you put the needles, or even if you puncture the skin or not. The better controlled the trials are the less effect there is, and trials with really good sham procedures don’t show a difference between the sham procedure controls and the actually needled groups.

Any effect is simply a placebo effect, and the whole procedure with its  insertion of needles and fake explanations has been characterized as a “theatrical placebo”. For a sampling of deconstructions of acupuncture studies just search acupuncture on the blog “respectful insolence” which you can do by following this link .

Unfortunately there are many who have been taken in by the pseudoscience of this quackery, even in neonatology. A few trials have even been published, including those using electrical stimulators of non-existent acupuncture points, and a few where lights have been shone onto those same points.

The two most recent studies I glimpsed are examples of those 2 methods, Abbasoglu A, et al. Laser acupuncture before heel lancing for pain management in healthy term newborns: a randomised controlled trial. Acupuncture in medicine. 2015;33(6):445-50. 42 term babies having a heelstick were randomized to laser acupuncture or sucrose. The study found that sucrose was better than shining a light on the Yintang point (the non-existent acupuncture points, scattered along the non-existent meridians, all have names, this one is between the eyebrows and is also called EX2).

Mitchell AJ, et al. Does Noninvasive Electrical Stimulation of Acupuncture Points (NESAP) reduce heelstick pain in neonates? Acta Paediatrica. 2016. This study used different fake acupuncture points (ZuSanLi (ST36), SanYinJiao (SP6), KunLun(Bl60), and TaiXi (KI3) which are on the legs) and randomized babies undergoing heelstick to 4 groups, sucrose with “Sham NESAP”, NESAP plus water, NESAP with sucrose, and sham NESAP with water. They randomized 142 term infants who were undergoing a heelstick procedure and analyzed the videos of their faces for PIPP scoring. In the Sham NESAP groups the electrodes were placed adjacent to these fantasy acupuncture points but the stimulator was not turned on, All babies at least had facilitated tucking and a soother, which are both effective at reducing pain from heelstick, which was shown by the relatively small mean increases in PIPP scores in all the groups. Sucrose limited the increases in PIPP compared to the groups which didn’t get sucrose, and electrical stimulation of ZuSanLi etc didn’t do anything. This study did at least have the potential for a measurable effect, because, unlike shining a light on the skin, there is at least a potential that the transcutaneous electrical stimulation could have an analgesic effect. As it appears to for, in particular, chronic pain.

Although the NESAP groups without sucrose didn’t have a large mean increase in PIPP scores, the mean peak scores were up to 4.9 and 5 (compared to 4 or less for the sucrose groups), but the standard deviations of those scores were much larger than the sucrose groups, (4 compared to less than 2) which means that there were probably substantially larger numbers of babies who had pain scores of over 6, and had appreciable pain. Which means that yet again I can say that we shouldn’t be performing heelsticks without using all the proven evidence-based methods for reducing pain prior to such procedures, of which sucrose is top of the list.

Lets stop investigating this nonsense in neonatology, we should be using our time and efforts and resources to examine therapies that have some basis in reality and science. Whatever next, ear candling, or craniosacral therapy for newborns? OH NO!

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Reducing apnea

When a baby has an apneic spell, we often respond by physically stimulating them. Usually they will start breathing again; but how does that work? If it is more than a coincidence (and I think it is, even though there are no randomized trials to prove that apneas are shorter when you shake them, compared to just waiting for them to start breathing again), then what is the mechanism that leads to babies restarting to breathe?

You might think that the mechanism is that they wake up, and breathe again because they are awake, but preterm babies have apneas regardless of their sleep state, in quiet or active sleep, or when they are awake. There is one study I am aware of (Thoppil CK, et al. Behavioural arousal in newborn infants and its association with termination of apnea. J Appl Physiol. 1991;70:2479.) which looked at this carefully analyzing videos of the babies, signs of arousal were only present a minority of the time when a baby terminated an apnea, and started breathing again: so arousal is not essential to restart breathing.

What else might be going on? Well the movement detectors in our muscles (proprioceptors) are known to be linked to the respiratory centers. Which is why sprinters start to increase their ventilation even before there is any detectable increase in oxygen consumption; just moving one’s limbs stimulates breathing!

Now a group has tested this by examining the effects of transcutaneous proprioception stimulation on respiratory pauses. (Kesavan K, Frank P, Cordero DM, Benharash P, Harper RM. Neuromodulation of Limb Proprioceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia. PLoS One. 2016;11(6):e0157349.)

The stimulation consisted of a battery driven vibrating pair of disks placed on a hand, and another on a foot. This was a short-term crossover study looking at the incidence of breathing pauses, and of longer apneas associated with hypoxia or bradycardia, using continuous recording of the signals from the bedside monitor, analyzed by an individual who was unaware of the (randomized) sequence of whether the device was switched on for 6 hours, or left off.

There were fewer pauses, fewer hypoxic spells and fewer bradycardias during the periods with the device vibrating.

Which suggests to me that when we stimulate a baby and they start breathing, they might be responding to a similar sort of pathway.

It’s also of course a potential active treatment for apnea of prematurity. Apnea is associated with worse outcomes in preterm babies, perhaps because of frequent hypoxia, and re-oxygenation (often including hyperoxia, which may be fairly prolonged).

My biggest question is whether the effect will be maintained, I can easily imagine that babies will habituate to the stimulation, and it may not have a persistent effect, but this very nicely done study could now easily be repeated with a much longer intervention period, to see if the reduction of apneas is maintained over a few days. If that does work, then wide introduction of this device could have significant benefits to our babies, and an RCT, probably as an add-on to babies already receiving caffeine, given the proven benefits of caffeine, would be important.

The device vibrates at 128 Hertz, which is about 1 octave below middle C (I think), in the future, ward rounds may be accompanied by a gentle buzzing from little discs stimulating our babies to breathe. I wonder if we tune them to different frequencies, and have a little symphony going on…

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A new publication

Janvier A, Farlow B, Barrington KJ. Parental hopes, interventions, and survival of neonates with trisomy 13 and trisomy 18. Am J Med Genet C Semin Med Genet. 2016: This new article draws on the results of the on-line survey that Annie and Barb performed with Ben Wilfond. It is an exploration of parental hopes, medical interventions, and factors associated with survival among a cohort of families who had a live-born child with trisomy 13 or trisomy 18.

We found that the hopes of parents in this group fitted a number of very frequent themes, they hoped to meet their child alive, to take them home, to be a family, and to give their child a good life.

We also found that about 100% of parents recall receiving a recommendation soon after the diagnosis to pursue comfort care, and most of those with antenatal diagnosis had a recommendation to terminate the pregnancy. Some of those recommendations were quite directive, and a few of the remarks made by medical professional that the parents quoted are shockingly inappropriate.

One of the comparisons that we made, that was quite a powerful predictor of outcomes, in fact the most powerful predictor of outcomes, was when the diagnosis was made. Babies with an antenatal diagnosis had fewer interventions, were much more likely to die on the first postnatal day (compared to almost none of the postnatal diagnoses), were much less likely to go home with their family, and had a very restricted approach to comfort care, often without oxygen or tube feeding. Those diagnosed after birth were very likely to be able to go home (87%) and had more interventions, even when the decision was made for comfort care.

Which suggests a number of things, first of all, many children with these diagnoses survive to discharge if they have some medical interventions immediately after birth; there appears to be decreased respiratory drive after birth that tends to resolve quickly if they get a little support, so CPAP, non-invasive ventilation, or invasive ventilation may be an approach that gets the babies through the first couple of days; caffeine might also help to shorten or avoid mechanical respiratory support.

Secondly, palliative care means a lot of different things, so much that maybe it has become a term that means nothing, some children in palliative care mode had cardiac surgery, presumably with the idea that they would be more comfortable afterward, which I think may well be the right thing for those babies, but is it really palliative care? Or is it just good medicine?

Many children who received comfort care survived to discharge, mostly those who had a postnatal diagnosis, but also some of those also who had a prenatal diagnosis. Part of our planning with these families, even when comfort care is decided, should be to consider how to facilitate a discharge home.

This study adds the decision-making part of the picture that you can’t get from registry or population based studies. Although this is a self-selected group the results overall for survival don’t look that much different from the population based study I posted about recently, with much longer survival among those who opt for some active medical intervention than we are used to seeing in the older literature. Most children who have surgery will be able to be discharged home.

 

Posted in Advocating for impaired children, Neonatal Research | Tagged | 3 Comments

Preterm babies have fixed dilated pupils

There is a reason we don’t perform pupillary reactions to light in preterm babies, and that is that they don’t react. They also tend to be large. This post is in response to my trying to find out what had been published about this phenomenon, when a case in our NICU raised a teaching point. I decided to go back through the literature to find out what was actually documented in peer-reviewed publications, and found, for a change, some good quality data.

The first of these, chronologically, is from 1989 Isenberg SJ, et al. The pupils of term and preterm infants. Am J Ophthalmol. 1989;108(1):75-9. This group from UCLA studied prospectively pupils of 100 babies from 26 weeks through to 46 weeks, with a standardized methodology; pupils were larger in mm for more immature infants, even though their eyes are a bit smaller. Pupillary light responses were usually absent before 30 weeks PMA, and only reliable after 32 weeks.

Robinson J, Fielder AR. Pupillary diameter and reaction to light in preterm neonates. Arch Dis Child. 1990;65(1 Spec No):35-8. A similar study from Birmingham, England followed 50 babies, and found similar things, the few babies who responded before 31 weeks all had a slow reaction.

Isenberg SJ, et al. The fixed and dilated pupils of premature neonates. Am J Ophthalmol. 1990;110(2):168-71. The UCLA group again, this time with a cohort of 30 babies who were examined every week, they were all less than 31 weeks at the first examination and none of them reacted at that time. The proportion having a detectable response to light increased, and most were reacting by 32 weeks.

Isenberg SJ, Vazquez M. Are the pupils of premature infants affected by intraventricular hemorrhage? J Child Neurol. 1994;9(4):440-2. The answer to the question in the title is no. The pupils of babies with any grade of hemorrhage (1 to 4) are not larger and do not have different reactions to light than those without hemorrhage.

There are a couple of more recent publications, but they don’t really add anything. Until the baby has passed 32 weeks post-menstrual age, there is no point looking for pupillary light reflexes, and the pupils will look fixed and dilated.

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Hey, doctor, leave those guts alone!

Intestinal function is often sluggish after preterm delivery. Establishing early enteral nutrition, the goal of all of us, is interrupted often by repeated regurgitation, or large residuals (if you measure them) or abdominal distension. There are also reported correlations between delayed meconium passage and the later development of NEC.

This has led many clinicians and investigators to look at the use of various methods to stimulate gut function, hopefully with the goal of reducing time on intravenous nutrition, and maybe even reducing NEC.

If we look at the downstream result of those methods, that is, methods to improve evacuation, do they actually promote earlier stooling, or feeding tolerance?

No.

At least that is the conclusion of a systematic review of 5 RCTs and a couple or observational studies. Kamphorst K, et al. Enemas, suppositories and rectal stimulation are not effective in accelerating enteral feeding or meconium evacuation in low birth weight infants: A systematic review. Acta Paediatrica. 2016. To prove no effect, of course, is just about impossible, but we can have reasonable confidence that there is not a clinically important effect on accelerating enteral feeding, and does not speed up the evacuation of meconium.

And there is no evidence that these interventions achieve any of the laudable goals of reducing TPN duration or reducing NEC incidence. A systematic review published last year suggested the opposite, a risk of increased NEC.

I think the best we can do improve feeding tolerance at present is the early introduction of breast milk, as periods of being npo slow down gut recovery (Maybe I should say ‘probably’, there as the evidence is limited).

And the use of probiotics. When reported as an outcome variable, probiotics have almost always improved feeding tolerance, and decreased time on TPN, which was certainly the case in our study, and is confirmed in the latest version of the Cochrane review.

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