Month: December 2018

Don’t Bother With the Parachute!

Most folks erroneously believe a parachute is necessary when jumping from an aircraft. There’s never been evidence to support such a belief in the form of a true randomized-controlled trial. That said, it would be hard to achieve the ethics board approval to perform such a study – and this concept of treatments and medical devices as “parachutes” persists, supposedly obviated from prospective evaluation. The lesson here is a cautionary one, actually, that too many medical practices are inappropriately characterized as parachutes, not so much that parachutes require an RCT.

However, this is precisely what we’ve received for Christmas – an RCT of parachute use for preventing death and major trauma. In this trial, 92 aircraft passengers were screened, and ultimately 23 were randomized to jump from an aircraft wearing either a parachute or an empty backpack. This was an unblinded trial, as well, in which all participants knew whether they were wearing a parachute or an empty backpack at the time of jump. With regard to their primary outcome of death from impact with the ground, there was 0% mortality in the parachute cohort and – wait for it – 0% mortality in the empty backpack cohort.

There were some important differences noted – not between those randomized, but between those screened and those randomized. The altitude of those screened but not randomized was 9,146m, at a velocity of 800 km/h. The altitude of those randomized is best described by the following representative photo:

It should probably be noted zero parachutes were actually deployed by jumpers randomized to that arm.

The lesson here is another fabulous one. The results from clinical trials cannot necessarily be applied to all those included in the eligibility criteria, but can rather be best generalized from those actually receiving the intervention. Insidiously controlling the population undergoing an intervention, among many others, is one of the various tricks those who design clinical trials can use to bias their results, and ultimately mislead.

“Parachute use to prevent death and major trauma when jumping from aircraft: randomized controlled trial”
https://www.bmj.com/content/363/bmj.k5094

Rochester v. Philadelphia, Pediatric Edition

It’s a little tough for Rochester to go head-to-head against Philadelphia – with apologies to the Americans, Red Wings, Rhinos, Knighthawks, and Razorsharks. The playing field of … the playing field … is just on another level in Philadelphia. The playing field of febrile infants, however, is another matter.

This small study re-analyzed prospective data from 135 febrile children ≤60 days of age with documented invasive bacterial illness, and applied the Rochester and modified Philadelphia criteria for risk-stratification. IBI was defined as having a positive blood or CSF culture, if obtained. In this small sample, both Rochester and Philadelphia were 100% sensitive for all cases of meningitis in infants greater than 28 days of age, but each missed similar numbers of those with bacteremia. A comparison for those below 28 days is frankly irrelevant, as the modified Philadelphia criteria specifically applies only to those >28 days of life – so, yes, it is comically 100% sensitive and 0% specific in neonates. The Rochester criteria, which does not mandate CSF, if applied to those ≤28 days, would have missed two cases of meningitis, and is therefore not suitable for use.

The takeaway here is not so much which criteria is superior to the other – the elements of each are virtually identical. Moreso, it is the recognition that each is about 83% sensitive, and all children in this age range evaluated in the ED and discharged will require close follow-up for re-evaluation of clinical status.

“Risk Stratification of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture”
https://www.ncbi.nlm.nih.gov/pubmed/30425130

Did You Miss … CATCH2?

We’ve talked about the PECARN vs. CATCH vs. CHALICE cage-match before. PECARN has been the subject of multiple sub-investigations, but CHALICE has been neglected and gone to seed. CATCH, on the other hand, has a sequel.

What’s new in CATCH2? Vomiting!

Adding to the original 4 + 3 item list, these authors conducted a new multi-center study comprised of 4,060 children with minor head injury. The stated purpose was to prospectively evaluate CATCH, with a secondary plan to improve performance if found to be deficient – and, although it is not explicitly stated, it appears these authors anticipated the missing link to be inclusion of vomiting.

Only 23 children in their cohort required neurosurgical intervention, while 197 had any brain injury on CT. The original CATCH had sensitivity of 97.5% and specificity of 59.6% for any brain injury, while adding “≥4 episodes of vomiting” increased sensitivity to 99.5% and decreased specificity to 47.8%. Sensitivity of CATCH2 was 100% for any cases requiring neurosurgical intervention, although confidence intervals are obviously wide, given the paucity of events.

So, another entrant arrives to the pediatric head injury decision-instrument sweepstakes. Interestingly enough, these instruments were created because of concerns of CT overuse – up to 53% in 2005! – as cited by these authors. With CATCH2, the CT ordering rate would be 55%. This is both greater than the 34% rate witnessed in this study, and vastly greater than the 8% seen in Australian and New Zealand, although with different entry criteria. It would seem to me these instruments are rather making the problem worse, rather than better ….

“Validation and refinement of a clinical decision rule for the use of computed tomography in children with minor head injury in the emergency department”
http://www.cmaj.ca/content/190/27/E816

Dentist, Dealer?

In the Emergency Department, we appreciate all the various sources of opiates in our healthcare system. We are, after all, effectively the last-resort after-hours refill destination – and patients with dental complaints are not uncommon.

These authors performed a retrospective, claims-based analysis of adolescents and young adults with exposures to opiates via a dental provider. In this database, there were 754,002 patients with continuous enrollment during the study period, 97,462 of whom received at least one prescription for an opiate. Of these, 29,791 (30.6%) received a prescription from a dental clinician. As compared with a randomly-selected opiate non-exposed cohort, the difference between subsequent healthcare encounters with an opioid abuse-related diagnosis was profound: 5.6% of the exposed cohort, compared with 0.4% of those unexposed.

It’s the same sort of high-level analysis with vast gulfs of inference as the “Emergency Physicians Are The Problem” article in the NEJM a few months back. It has obvious face validity, however, that an exposure to a potentially dependence-forming medication can result in downstream harms. Dental providers are not obviously any greater problem than other surgical specialties, but, yes, we are all similarly responsible for appropriate prescribing practices.

I also incidentally applaud these authors for their use of absolute risk differences – it would have been all too easy to breathlessly report relative risks, considering the low prevalence of opioid-abuse among “controls”.

“Association of Opioid Prescriptions From Dental Clinicians for US Adolescents and Young Adults With Subsequent Opioid Use and Abuse”
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2717503

Precog for Medical Errors

Medical errors are grossly under-reported, with only an estimated 10% safety events ever identified via voluntary reporting systems. There’s an entire line of academic inquiry simply targeted at increasing the proportion of safety events detected, with the overall goal of informing subsequent practice change. This study – mentioned in the daily ACEP News briefing – takes it one step further, attempting to predict future safety events in real-time.

These authors used a continuous stream of data from the electronic health record to create a “patient safety active management” system. They created an initial model based on four years worth of data from 2009-13, and subsequently validated it by pilot implementation at two hospitals between 2014-17. During these pilot phases, each nursing unit was provided with a dashboard for every patient indicating whether a trigger event had occurred, along with a twice-daily updated score of their overall risk for an event. A nurse reviewer followed all the automated positive triggers and evaluated their downstream harms, as well as the harm severity.

We’re a long way from prime time. There were 775,415 trigger events in 147,503 inpatient admissions, resulting in 3,896 clinically validated safety events. The vast majority of events were “temporary harm” or “increased length-of-stay”, although there were a few serious safety events as well. Worse still, these authors don’t specifically delve into “preventable” harms, as their list of most common adverse events do not clearly offer clues as to whether the harms could specifically be mitigated or avoided. For example, many of their harms were medication-related bleeding or medication-related Clostridium difficile infection – unintended harms, to be sure, but frankly known risks of the likely medically-appropriate treatment pathways.

Every project has to start somewhere, of course, and these early steps will hopefully further inform more specific tools. Hopefully – though I’m unfortunately skeptical – I primarily expect more low-value, alert fatigue-inducing hiccups along the way.

“An Electronic Health Record–Based Real-Time Analytics Program For Patient Safety Surveillance And Improvement”
https://www.healthaffairs.org/doi/abs/10.1377/hlthaff.2018.0728

The Probiotic Hoax?

The concept of probiotic therapy is a compelling one: under duress from illness or adverse effects from medications, the gastrointestinal biome becomes altered. Orally repleting this biome to restore “normal balance” ought to improve morbidity. Sounds good, right?  Unfortunately, plausibility is not the same as practical efficacy.

Other indications or specific contexts notwithstanding, this multi-center trial shows probiotics confer no advantage for progression of gastroenteritis in children. These authors conducted a randomized, double-blinded trial in six pediatric Emergency Departments in Canada, including 886 children presenting with fewer than 72 hours of infectious diarrheal symptoms. They each received a 5-day course of either Lactobacillus rhamnosus R0011 and L. helveticus R0052 or placebo. Short answer: about 25% of each cohort progressed to moderate-to-severe gastroenteritis, and the duration of diarrhea was a little over two days, regardless.

The authors note “5 out of 12 leading guidelines endorse the use of probiotics”, although it does not appear they have a citation regarding how many dentists would recommend.  While these data do not generalize to all indications, nor potentially all possible probiotic formulations, these data certainly tilt the board away from “potentially useful” towards “probably not useful”.  Adverse events were common and similar between groups, so probiotics are unlikely to be harmful in a population with normal baseline health status – but you might as well just visualize your money concurrently swirling along down the toilet.

“Multicenter Trial of a Combination Probiotic for Children with Gastroenteritis”

https://www.nejm.org/doi/full/10.1056/NEJMoa1802597