November 2014 – Page 2 – Emergency Medicine Literature of Note

The Remarkable Power of Placebo

Have you ever felt pressured to provide a patient with something at the time of discharge? Something, anything to ease their suffering for an illness of unalterable benign progression? Never? You cold-hearted bastard.

This tiny trial, despite its small size, provides yet another beautiful look at the magical healing power of placebo. Or, more accurately, rather than healing power, at least the satisfying power. After all – most families in the ED at two in the morning are not there because their child is awake from coughing, but because the parents are.

This trial, in the same vein of several honey trials before it, compared no treatment, a placebo treatment (grape-flavored water), and agave nectar for the treatment of pediatric cough-related illness. Agave nectar was chosen for its similarity to honey, while not carrying the hypothetical botulism risk. With ~40 patients in each group, all patients improved during the duration of the study. However, despite the small sample, both agave nectar and placebo provided durable advantage over no treatment across all surveyed measures of patient and parent comfort. There was, however, no difference between placebo and agave nectar – or, if there was, it was too small to be detected in this study.

What is most remarkable about this study is the authors discussion – that placebo treatments could be considered ethical, even when no benefit to such treatment is found in controlled studies. Providing patients – or parents – with, at least, an inexpensive, harmless treatment option takes advantage of the power of belief, to the extent that real patient/parent-oriented benefits may be observed.

Unfortunately, the lead author of this study was a paid consultant to Zarbee’s Inc (a maker of “natural” over-the-counter remedies) at the time the study was initiated, and Zarbee’s provided funding for the study. But, thanks to their contribution to science, we now know they only work as well as you expect ….

“Placebo Effect in the Treatment of Acute Cough in Infants and Toddlers”
http://www.ncbi.nlm.nih.gov/pubmed/25347696

Homeopathic Accident & Emergency

No Good Ever Comes of Dabigatran

Is anyone actually still using this drug? If so, why? There has been nothing but an endless progression of bad news associated with this medication – from Boehringer Ingelheim settling a massive lawsuit, the authors from RE-LY admitting they “missed” additional adverse events for a second time, and, now, further evidence describing flawed real-world effectiveness contrary to its supposed demonstrated efficacy.

The RE-LY trial showed non-inferiority for dabigatran at stroke prevention in non-valvular atrial fibrillation, but appeared to place patients at significantly lower risk of bleeding compared with warfarin. One of the critiques of RE-LY, however, is the patients were not appropriately representative of the general population at-risk for atrial fibrillation. By omitting chronic kidney disease and enrolling a generally white population in Europe, the generalizability of their findings is ultimately impaired.

And, thus, we see the fruits of such critiques. This is a retrospective cohort of Medicare beneficiaries prescribed either dabigatran or warfarin for atrial fibrillation. Based on propensity matched samples of 1,302 dabigatran users and 8,102 warfarin users, major bleeding of the dabigatran cohort exceeded that of the warfarin cohort – 9.0% (95% CI 7.8 – 10.2) versus 5.9% (95% CI 5.1 – 6.6). Risks were increased in the elderly, blacks, those with chronic kidney disease, and those on concomitant anti-platelet therapy.

So, we have a lesson – one of effectiveness versus efficacy, or one that’s an indictment of the original RE-LY study protocol. Medications should not be expected to perform the same in general use as they do in clinical trials – even those with tens of thousands of patients, such as RE-LY. Independent, confirmatory study ought be mandatory to ensure the safety of the public.

“Risk of Bleeding With Dabigatran in Atrial Fibrillation”

http://archinte.jamanetwork.com/article.aspx?articleid=1921753

Addendum:
Walid Gellad on Twitter points out this study in Circulation, published last week to much lesser fanfare, which uses a larger Medicare sample to come to the opposite conclusion – that dabigatran is better than, and safer than, warfarin. Which is correct? A subject for continued debate, to be certain. The correct answer is probably somewhere in between – dabigatran is safer for some, but more dangerous for others. However, given the lack of reversal – wouldn’t a Factor Xa inhibitor be a better choice, regardless?

Scientific Writing is a Tragicomedy! Destroy!

Modern scientific writing – both in the exercises of writing and reading – is obtuse and uninviting. Rather than clearly communicate an unbiased reflection of the conduct and findings of a particular study, the medical literature most commonly succeeds in doing the opposite. After all, how else would I find enough to complain about on this blog?

This editorial elucidates so many joyfully preposterous notions it cannot help yet be loved. It is best described as a no holds-barred cagematch versus all the inane pageantry of scientific writing. Just a few of the gems, paraphrased:

Don’t let the authors write the abstract; they’ll just misrepresent the study!
Delete the introduction; uninsightful filler.
No one cares the brand and manufacturer of the statistical package used.
Unequal composite end-points and subgroup analyses should be banished.
The discussion section only serves authors’ purposes of dubious claims through selective reporting and biased interpretation of their results.

Some elements of this brief report are, indeed, novel. Others are simply accepted best practices long since forgotten. Regardless, it is a refreshing reminder of how brutally poorly the current medical literature serves effective knowledge translation.

“Ill communication: What’s wrong with the medical literature and how to fix it.”
http://www.ncbi.nlm.nih.gov/pubmed/25145940

What Do People Remember From Cardiac Arrest?

The anecdotal experiences and reports from survivors of cardiac arrest are diverse, yet frequently describe common themes. Detailed memories, “near death experiences” of entering another world, and sights and sounds from the arrest context are frequently reported. And, what better place to collect cardiac arrest events than in a hospital?

As one might imagine, the population available for such interviews is rather limited – so it requires a massive undertaking, in this case, a four-year prospective evaluation across 15 hospitals in the U.S., UK, and Austria. Essentially, the local investigator at each institution received notification of every adult, in-hospital cardiac arrest. Survivors were identified and interviews conducted as soon as feasible, given continued comorbid illness.

Out of 2,060 cardia arrests, only 330 were eligible for study inclusion. Investigators conducted 140 interviews – and only 55 had any memories. Of these, 53 had detailed memories, whether unrelated or classic “crossing-over” phenomena – but nothing relating to the circumstances of their arrest event. Only two patients had detailed memories of the circumstances of their event – one set of memories was not able to be verified, but the authors were able to fully verify the other set of memories by interview of the resuscitation staff.

So, essentially, very rarely do patients have any recollection of their arrest event.

Interestingly, one part of this study attempted to verify the veracity of the “floating above and watching” aspect of some individual’s arrest recollections. The authors constructed shelves in areas thought most likely to have cardiac arrest, and then placed objects on the shelf that would only be visible from a perspective near the room ceiling. Unfortunately, 70% of the cardiac arrests in this study occurred in locations where there were no shelves, including both arrests with detailed recollection.

“AWARE—AWAreness during REsuscitation—A prospective study”
http://www.ncbi.nlm.nih.gov/pubmed/25301715