Category: Pediatrics

Pediatric C-Spine Injury Risk Factors

It would seem the Pediatric Emergency Care Applied Research Network (PECARN) is gearing up to develop another decision instrument – this time for cervical spine injuries.

This is a prospective, observational study of 4,091 pediatric blunt trauma patients across four pediatric level-1 trauma centers, surveying treating providers about the presence or absence of factors suspected to be implicated with cervical spine injuries. The factors were selected based on previous studies, as well as those suspected as having potential physiologic plausibility and good interrater reliability. The stated purpose – to ultimately develop a decision instrument akin to their prior work for clinically important minor head injury.

Overall, the prevalence of a cervical spine injury – vertebral fractures, ligamentous injury, intraspinal hemorrhage, or spinal cord injury – was 1.8%. The vast majority of patients in their cohort (78.2%) underwent some sort of imaging, although only 15.8% underwent CT. The most predictive items identified are those already typically considered: diving injuries, axial loading injuries, clotheslining, loss of consciousness (including intubation), neck pain, altered mental status (frequently associated with obvious head injuries), limited range of motion, focal neurologic deficits, and substantial torso and thoracic injuries. Of the 74 patients with CSI in their cohort, effectively only one would have been missed by a decision instrument based on these factors – a fall from 10 feet whose symptoms localized to the thoracic spine, and had a C7 burst with T2-T4 compression fractures. Obviously, this was not missed clinically – again revealing the role of clinical judgment outside of any decision instrument.

The most interesting tidbit, leading into the most substantial implications for generalizability, is their note regarding “high-risk MVC”. They comment previous case-control studies determined both predisposing conditions (e.g., congenital abnormalities of the cervical spine) and high-risk MVC were identified as risk factors, whereas in this study they were not. They discuss the low prevalence in their cohort of those with predisposing conditions, and, conversely, the high prevalence of high-risk mechanisms, to justify their lack of multivariate effect on predicting CSI. Even though they did not fall out as predictive elements in this cohort, a future prediction model intended for general use may yet include such features. As such, these data ought not be fully relied upon to downgrade those potential risk factors.

“Cervical Spine Injury Risk Factors in Children With Blunt Trauma”
https://pediatrics.aappublications.org/content/early/2019/06/18/peds.2018-3221

Yet Another Febrile Infant Rule

The Holy Grail in the evaluation of infants of less than 60 days remains safe discharge without a lumbar puncture. Boston, Philadelphia, Rochester, Step-by-Step and others have tried to achieve this noble goal over the years. And now, the Febrile Young Infant Research Collaborative has tossed their hat into the ring.

In this retrospective query of their Pediatric Health Information System and other electronic medical records, these authors identified 181 non-ill appearing patients across 11 Emergency Departments with invasive bacterial infection, defined as bacteremia in either blood or cerebrospinal fluid. Using 362 matched controls as a comparison cohort, these authors used the typical logistic regression route to tease out the strongest predictors of IBI – age in days, observed temperature, absolute neutrophil count, and urinalysis result. Subsequently, they condensed the continuous variables into cut-offs maximizing area under the curve. These cut-offs were then incorporated into a scoring system based on the strength of their adjusted odds ratio, and then the final output was validated on the derivation set using k-fold cross-validation with 10 sets.

The final result using their best cumulative score cut-off: sensitivity of 98.8% (95% CI 95.7-99.9) with 31.3% specificity. The two cases missed were that of a 3-day old and a 40-day old otherwise afebrile in the ED with normal UA and an ANC <5185. The authors ultimately conclude their score, if validated, may have best value as a one-way prediction tool primarily to reduce current routine invasive testing, owing to its poor specificity. Certainly, I agree it does not have much value in those who might otherwise not undergo testing; a more specific risk score may be better, if not clinician gestalt.

The other tidbit I might mention is whether there could be value in incorporating time-of-onset of fever into their evaluation. We’ve seen in other studies a few of the fallouts with regard to sensitivity of IBI stem from recency of illness onset, and it may be falsely reassuring to find a normal ANC early in an illness course. Furthermore, these authors do not specifically mention whether the lack of fever in the ED could have been associated with prehospital antipyretic use. Finally, their data collection does not appear to incorporate respiratory swab results; readily available respiratory viral panel results may also prove useful in ruling out IBI.

While these data are certainly alluring, considering the desire to avoid invasive procedures in young infants, substantial prospective work is still likely required.

As a sad aside, the authors state:

However, these criteria were developed >25 years ago, and the epidemiology of serious bacterial infections has changed considerably since that time.

Unfortunately, as vaccination frequency continues to decline, even since patients were enrolled for this study, our “modern” cohort may better begin to resemble that of 25 years ago.

“A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of
Invasive Bacterial Infection”

https://www.ncbi.nlm.nih.gov/pubmed/31167938

Levetiracetam vs. Phenytoin

The epic, classic showdown from time immemorial: new vs. old.

But, more specifically, these are two trials set to determine relative utility of each in pediatric seizures, vying for the coveted “second-line” therapy recommendation once benzodiazepines have failed. The thought and hope is, of course, the newer agent – levetiracetam – is at least as efficatious, if not moreso, as it can be infused more quickly. The authors then propose levetiracetam is associated with fewer long-term adverse effects and medication interactions during oral maintenance, and, as such, allows for convenient continuation after intravenous initiation.

Generally speaking, these two trials are very similar – both open-label trials randomizing pediatric patients with ongoing seizures, both analyzing about 250 patients … and both demonstrating effectively similar results by different routes. EcLiPSE, interestingly, was designed as a superiority trial, with a primary outcome of time from randomization to seizure cessation. Median time to seizure cessation not statistically different at 35 minutes for fosphenytoin and 45 minutes for levetiracetam, with similar numbers of treatment failures for additional anticonvulsants or intubation. In ConSEPT, the primary outcome was cessation of seizure activity within 5 minutes of the end of the infusion, and here results favored phenytoin at 60% versus 50% for levetiracetam.

Effectively, however, the sample sizes are small enough, the types of patients heterogenous enough, and the differences small enough, the Bayesian interpretation is probably a wash. These are both fine second-line options, but these trials do not provide any data supporting levetiracetam as a superior option.

“Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial”
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30724-X/fulltext

“Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial”
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30722-6/fulltext

A Brief BRUE Follow-Up

The “apparent life-threatening event” has long since been replaced by the “brief resolved unexplained event – an event occurring in an infant <1 year of age with:

  • Cyanosis or pallor
  • Absent, decreased or irregular breathing
  • Marked changes in tone
  • Altered level of responsiveness.

This is just a brief, single-center, retrospective chart review identifying children hospitalized for BRUE and their outcomes up to 5 years. These authors identified 120 hospitalized infants under one year of age meeting criteria for BRUE, and performed telephone follow-up at least 6 months after the event. Most children hospitalized were less than 1 month of age, and about half were hospitalized for apnea or breathing issues. Of the 87 they were able to contact, none had died or developed chronic medical illness, 71 had developed normally, and the remainder developed either a global or verbal developmental delay.

This is a small sample, to be sure, but these data suggest children hospitalized for BRUE are not specifically at risk for long-term poor neurologic or cardiac outcomes above the baseline population level.

“Long-Term Follow-Up of Infants After a Brief Resolved Unexplained Event–Related Hospitalization”

https://www.ncbi.nlm.nih.gov/pubmed/30951030

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

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

That Lego is Gone

Lego, a portmanteau of Danish words meaning “play well”, are ubiquitous toys around the world. This means the bite-sized bits are equally prevalent in the hands of infants and toddlers around the world – and in their mouths. What goes in a toddler’s mouth goes into their stomach.

This brief study evaluates six toddlers – ahem, pediatricians – who each swallowed a Lego head:

These adult children subsequently searched stools for signs of the swallowed item, as well as performed an assessment of stool consistency. Most importantly, they were able to derive infantile acronyms for their assessments – the SHAT and FART scores.

One of the six participants was never able to locate the ingested Lego part, despite two weeks of stool searching. The other five found them in their second or third bowel movement, which, on average, was 1.71 days later.  Stool consistency was unrelated to passage of the head.

Obviously, the generalizability and reliability of such a study is quite low, being adults and only six of them. Then, although these authors report “no complications”, they have not yet located one of the six heads – perhaps a future case report: “Acute appendicitis involving an unusual appendicolith”?  At the least, a potential future IgNobel prize awardee.

“Everything is awesome: Don’t forget the Lego”
https://onlinelibrary.wiley.com/doi/full/10.1111/jpc.14309

I Choose You! Observation, I Hope.

We’re back with another patient-oriented clinical decision aid from the folks who brought you Chest Pain Choice – Pediatric Head CT Choice! In this episode, our noble heroes are out to educate parents regarding the risk of intracranial injury in children who are at “intermediate risk” for clinically-important traumatic brain injury by PECARN criteria.

In this multicenter, cluster-randomized, controlled-trial, these authors tested an information graphic and educational tool against usual care, with a primary outcome of parental knowledge. Additional measures of engagement in the decision-making processes, decisional conflict, and parental trust were measured as secondary outcomes related to the cognitive aspects, along with patient-oriented outcomes such as ciTBI and imaging utilization. They included 172 clinicians at 7 sites, and enrolled 971 patients, including 516 patients who consented for recording of their discussion regarding imaging. Follow-up by telephone was obtained in 890 (92%) of patients, with the remainder of outcomes assessment limited to electronic health record and vital records follow-up.

The results are mostly good news regarding the decision aid. Parents in the intervention arm could answer 6 of 10 questions about their choice correctly, compared with 5 of 10 receiving usual care. Secondary cognitive outcomes also favored the decision instrument, and physicians surveyed were generally in favor of the decision aid, as well. Imaging at the index visit was similar between the two groups, but downstream healthcare resource use and subsequent imaging was lower in the decision aid cohort.

There are findings here to critique, of course. There was only one ciTBI in the entire cohort, and they were imaged at the index visit. The expectation – and the tool – were constructed based on a 0.9% ciTBI rate, when the actual observed incidence was 0.1%. It is reasonable to consider the practical implementation of PECARN over-classifies patients into the “intermediate risk” cohort, placing additional children at risk for unneeded imaging – which, in turn, renders their “1 in 100” information graphic misleading. Then, clinicians spent an extra 2 minutes – 38% longer – with parents when using the decision aid. How much of the improved knowledge and trust stems from the decision aid, and how much from simply spending more time in the discussion? Finally, there are uncertain manifestations of the Hawthorne effect, particularly considering over half the encounters were recorded.

Overall, however, I have few quibbles with this decision aid. At the least, it is unlikely to exert a negative effect on parental knowledge or paradoxically increase unnecessary scanning.

“Effect of the Head Computed Tomography Choice Decision Aid in Parents of Children With Minor Head Trauma”
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2703135

More Snapshots of Awful Antibiotic Use

Is there ever any good news these days? Geopolitical disasters, unwarranted pharmaceutical price increases – and physicians can’t even manage to get the evaluation for group A strep right.

This is a “successful” quality improvement paper wrapped around depressing and embarrassing data from a typical primary care pediatrics practice. These authors, primarily pediatric infectious disease specialists, were dismayed by the rate of guideline-non-compliant group A streptococcal testing and treatment in their group.

How bad?

The base rate of unnecessary GAS testing was 64% of all rapid strep tests performed. The base rate of inappropriate antibiotic prescribing – driven primarily by treating positive results in those who should never have been tested (e.g., likely non-pathogenic colonization) – was 49%.

After their multifaceted year-long intervention, they were able to achieve the amazing results of: 40% unnecessary testing … and the same, inappropriate 49% for antibiotic prescribing. When restricted to selection of antibiotic, at least, first-line antibiotics used 87% of the time.

Is this really the best we can possibly do, even after intent focus on practice improvement? And for a disease entitiy with such limited benefit for antibiotic in most modern settings?

“Improving Guideline-Based Streptococcal Pharyngitis Testing: A Quality Improvement Initiative”
http://pediatrics.aappublications.org/content/early/2018/06/18/peds.2017-2033