Making Urine Cultures Great Again

As this blog covered earlier this month, the diagnosis of urinary tract infection – as common and pervasive as it might be – is still fraught with diagnostic uncertainty and inconclusive likelihood ratios. In practice, clinicians combine pretest likelihood, subjective symptoms, and the urinalysis to make a decision regarding treatment – and invariably err on the side of over-treatment.

This is an interesting study taking place in the Nationwide Children’s Hospital network regarding their use of urine cultures. In retrospect, these authors noted only half of patients initially diagnosed with UTI had the diagnosis ultimately confirmed by contemporaneous urine culture. Their intervention, then, in order to reduce harm from adverse effects of antibiotics, was to contact patients following a negative urine culture result and request antibiotics be stopped.

This tied into an entire quality-improvement procedure simply to use the electronic health record to accurately follow-up the urine cultures, but over the course of the intervention, 910 patients met inclusion criteria. These patients were prescribed a total of 8,648 days of antibiotics, and the intervention obviated 3,429 (40%) of those days. Owing to increasing uptake of the study intervention by clinicians, the rate of antibiotic obviation had reached 61% by the end of the study period.

There are some obvious flaws in this sort of retrospective reporting on a QI intervention, as there was no reliable follow-up of patients included. The authors report no patients were subsequently diagnosed with a UTI within 14 days of being contacted, but this is based on only 46 patients who subsequently sought care within their healthcare system within 14 days, and not any comprehensive follow-up contact. There is no verification or antibiotics actually being discontinued following contact. Then, finally, antibiotic-free days are only a surrogate for a reduction the suspected adverse events associated with their administration.

All that said, this probably represents reasonable practice. Considering the immense frequency with which urine cultures are sent and antibiotics prescribed for dysuria, the magnitude of effect witnessed here suggests a potentially huge decrease in exposure to unnecessary antibiotics.

“Urine Culture Follow-up and Antimicrobial Stewardship in a Pediatric Urgent Care Network”
http://pediatrics.aappublications.org/content/early/2017/03/14/peds.2016-2103

The Solution to Dilution is ….

Do we order a lot of urinalyses? Does the sun rise in the east? Does a bear ….

For a test we order with great frequency, there is actually quite a bit of complexity in its interpretation. The combination of symptoms, clinical context, the balance between sample contamination and presence of white blood cells, of nitrites and/or leukocyte esterase, and so on, can make it a relatively tricky test to interpret. The gold standard remains a urine culture.

Now – if you haven’t been already – you probably ought to be taking into account the urine specific gravity, as well.

This retrospective analysis of 14,971 children for whom paired urinalyses and urine cultures were available describes the test characteristics of WBCs/hpf, LE, and nitrites as stratified by urine specific gravity. There are a lot of numbers in this article – a “zillion” to be precise – across eighteen dense tables of +LR/-LR, sensitivity/specificity, and PPV/NPV, but the basic gist of the matter is: variations in urine concentration diminish the value of the test in different ways. As urine specific gravity increases, it becomes more likely a patient will not have a positive urine culture despite having typically diagnostic amounts of WBCs/hpf, +LE, and/or +nitrites. Likewise, with dilute urine, a lower threshold for WBCs/hpf may be needed to have adequate sensitivity.

Just one more layer to consider in this frequently used test of under-appreciated complexity.

“The Importance of Urine Concentration on the Diagnostic Performance of the Urinalysis for Pediatric Urinary Tract Infection”
https://www.ncbi.nlm.nih.gov/pubmed/28169050

Let’s Hyperpronate!

There are two ways to treat a Nursemaid’s elbow (radial head subluxation) – supination/flexion or hyperpronation. I’ve done both. I’m a fan of hyperpronation, so, therefore, I’m highlighting a study that agrees with my practice pattern.

This systematic review covers 7 studies enrolling 701 patients, comparing the success rate and perceived pain of each technique. Trials were, generally and for some obvious reasons, limited in terms of blinding and outcome assessment. Pooled failure rate with hyperpronation 9.1% was while failure with supination /flexion was 27.3%. In studies reporting pain scores, subjective external rating of child pain during procedure also favored the hyperpronation group.

Use it!

This video demonstrates both techniques, although I’ve seen variations on hyperpronation both using extension and flexion.

“Effectiveness of reduction maneuvers in the treatment of nursemaid’s elbow: A systematic review and meta-analysis”
https://www.ncbi.nlm.nih.gov/pubmed/27836316

Imprecise Dosing of Liquid Medications

Many parents are overdosing their kids, study says”. Is this true? Are parents poisoning their own children, as the headline implies?

Of course not; this is not in fact a study regarding overdose incidence at all. It is, quite simply, a measurement precision study.

This study involves 2,110 parents randomly assigned to measure doses of liquid medication in various quantities using either a cup, a 0.2mL syringe, or a 0.5mL syringe. Approximately a quarter of parents were >20% off with their measurement, and 2.9% doubled the instructed dose. Taking these results as a surrogate for overdose depends on the therapeutic range for a medication – so, while the headline is not technically incorrect, the implication is an exaggeration.

With regard to measurement and dosing errors, there were a few important trends to note. Health literacy had a large influence on dosing errors – regardless of whether teaspoons or mL were used in the instructions. Then, the cup: avoid the cup when possible. Almost three-quarters of parents committed measurement or dosing errors when asked to provide a 2.5mL dose in the cup. Stick to the syringe and target round numbers (5mL) to minimize errors.

With regard to the premise of overdose – for medications with a wide therapeutic range, these data are not quite as clinically relevant. However, for high-risk medications, more time and effort should be taken to demonstrate proper dosing with parents.

“Liquid Medication Errors and Dosing Tools: A Randomized Controlled Experiment”
http://pediatrics.aappublications.org/content/early/2016/09/08/peds.2016-0357

The Febrile Infant Step-by-Step

You’ve heard of the Philadelphia Criteria. You’ve heard of the Rochester Criteria. But – Step-by-Step?

This is an algorithm developed by European emergency physicians to identify low-risk infants who could be safely managed without lumbar puncture nor empiric antibiotic treatment. After retrospectively validating their algorithm on 1,123 patients, this is their prospective validation in 2,185 – looking for IBI or “Invasive Bacterial Infection” as their primary outcome.

The easiest way to summarize their algorithm and results is by this figure:

Step by Step

Sensitivity and specificity, respectively, were as follows:

  • Rochester – 81.6% and 44.5%
  • Lab-score – 59.8% and 84.0%
  • Step-by-Step – 92.0% and 46.9%

The authors attribute 6 of the 7 missed by Step-by-Step to evaluation early in the disease process – presentation within 2 hours of onset of fever.

Their algorithm is reasonable at face validity, and could be incorporated into a protocol with close follow-up to re-evaluate those early in their disease process. We still have, however, a long way to go regarding specificity.

“Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants”
http://www.ncbi.nlm.nih.gov/pubmed/27382134

Putting Children to the Flame

Many readers here are students, trainees, or otherwise academic-affiliated, and have limited exposure to the world of community practice.  In these settings, frequently, our pediatric exposure is supervised by clinician-educator sub-specialists in Pediatric Emergency Medicine.  We see the very best evidence translated into acute care of children in the Emergency Department.

The real world is a little different.

These two articles describe the shortcomings of advanced imaging practice in community pediatric settings – in the diagnosis of appendicitis, and in the evaluation of closed head injury.

In the appendicitis article, the authors compare two settings both staffed by PEM physicians – an academic medical center with in-house pediatric surgical coverage, and a community center with consultation available only by phone.  Each site had similar rates of appendicitis diagnoses – 4.7% vs. 4.0% at the academic and community site, respectively.  The academic site, however, evaluated fewer patients with abdominal pain with blood work, and then fewer still of those went on to advanced imaging.  Then, of those receiving advanced imaging, the rates were 10.8% CT at the academic center vs. 28.1% CT at the community center.  Ultrasound however, was employed in 16.6% of cases at the academic center versus 6.5% at the community practice.  Nearly all this difference, however, seemed to be made up of patients admitted to the hospital without any operative intervention.  The obvious reality, then:  radiation in lieu of observation.

The second article here describes the neuroimaging (CT or MRI) of patients evaluated following trauma, along with their ultimate disposition.  Of 2,679 patients reviewed, there were 94 patients with important non-surgical, trauma-related diagnoses, and an additional 16 patients who required neurosurgical intervention.  These authors, however, based on GCS estimates recorded and the distribution of outcomes in the PECARN study, estimate the prevalence of entry criteria into appropriate scanning would have obviated >2000 of these scans.  While I believe they are probably mis-applying the evidence and overstating the inappropriateness of CT, the rarity of serious diagnoses suggests at least a majority of these CTs probably could have been avoided.

In short, we’re still doing too many CTs on children.  Some of the contributing issues are systems based, and some are related to practice re-education.  More ultrasound and more observation, please – and less nuking of children.

“Imaging for Suspected Appendicitis: Variation Between Academic and Private Practice Models”
https://www.ncbi.nlm.nih.gov/pubmed/27050738

“Neuroimaging Rates for Closed Head Trauma in a Community Hospital”

Where Acute Otitis Media is Born

Is it 3 AM in your Emergency Department?  Is there a febrile infant with their still-awake parents straggling in the door?  Do you hear the first few bars of the “it’s just a virus” song start playing over Spotify?

This little study prospectively enrolled healthy infants at birth and followed them to their first episode of acute otitis media or 12 months of age.  They were followed specifically to determine predictive clinical and epidemiological factors influencing the first diagnosis of AOM.  Additionally, as they aged and during illness, nasopharyngeal swabs were taken to evaluate viral and bacterial flora.

Based on a sample of 367 infants followed for a total of 286 child-years, there were 887 presentations for viral URIs and 180 presentations for AOM –and all but two of AOMs were preceded by a URI.  The median time from URI presentation to AOM diagnosis was 3 days.  These authors also present a fair bit of microbiologic data regarding specific risks for URI and AOM, although these are not specifically modifiable and of lesser clinical relevance.  From a modifiable environmental outlook, however, there are a few interesting tidbits tying into what we already suspected to be true:  breastfeeding is good, the new PC13 vaccine is good, and daycare is a cesspool.

Overall, this would tend to support our typical advice to parents to have their children present for a recheck 48-72 hours following Emergency Department visit, particularly if there has not been clinical improvement or in the context of apparent clinical re-worsening.

“Acute Otitis Media and Other Complications of Viral Respiratory Infection”
https://www.ncbi.nlm.nih.gov/pubmed/27020793

You Can Make Unnecessary Care Go Away

Low-value care is such a pervasive problem, ABIM developed the Choosing Wisely initiative.  However, Choosing Wisely is, unfortunately, a disengaged and toothless activity.  And it hasn’t worked.

But, as this study shows, you can eliminate unnecessary care with a more proactive and involved approach.

This is a quality improvement collaborative across 21 hospitals aimed at reducing the use of unnecessary or ineffective care relating to bronchiolitis.  As we’ve seen time and time again, if anything works at all for bronchiolitis, the ambiguity over its effectiveness probably means the effect size is clinically meaningless.  To this end, these hospitals banded together to deploy a QI program targeting reductions in bronchodilator use, steroid use, chest radiography, and other process measures.  Across all measures, the pre- and post-intervention measures demonstrated pooled meaningful and statistically significant improvement.  Bronchodilator use dropped from 46.2% to 32.7%, steroids from 10.9% to 2.2%, and CXRs from 12% to 6.7%.  A secondary effect of these interventions was a reduction in length of stay by 5 hours, from 49.6 to 44.6.

Success!

Of course, the QI intervention did not have the same effect at all participating hospitals.  Some, clearly, were on the ball, and almost entirely eliminated some unnecessary care (steroids).  Others, however, had no change from baseline, or, even, an increase – like two hospitals demonstrating 150%+ increase in bronchodilator use, and three hospitals with 100%+ increases in CXR use.  It would be interesting to see some qualitative analysis regarding the lack of improvement at certain hospitals.

But, in general, widespread improvement in unnecessary care can be realized.  In contrast to Choosing Wisely, it requires motivated agents of change and constant feedback.  The Choosing Wisely lists and their elements, unfortunately, seem adrift.

“A Multicenter Collaborative to Reduce Unnecessary Care in Inpatient Bronchiolitis”

Hypertonic Saline No Help for Bronchiolitis

There’s probably no common illness with quite so much flailing about in the evidence base than bronchiolitis.  Between bronchodilators, steroids, saline, and epinephrine, they’ve thrown the kitchen sink at it.  Some show potential benefit, while others do not.

This is another study following up the suspected benefit of nebulized hypertonic (3%) saline in reducing length of stay in hospitalized patients.  In a randomized trial, these authors enrolled 227 patients to receive either nebulized 3% saline or 0.9% saline placebo.  There were no important differences between patients randomized to each arm.  By all outcome measures – intensive care unit admission, objective deterioration of respiratory status, inpatient length-of-stay, or readmission – there was no difference between therapies.

The effect seen here – with seemingly contradictory results – is probably precisely as predicted by Ioannidis’ statistical theory regarding “Why Most Published Research Findings are False”.  Simply put, the prior probability of any of these treatments being helpful is quite low – and the extent of random bias associated most of these studies high.  The net effect, then, is the posterior probability associated with any significant finding is barely changed.

Nebulized hypertonic saline is probably harmless, but if it’s not helpful, it still doesn’t have a role.

“3% Hypertonic Saline Versus Normal Saline in Inpatient Bronchiolitis: A Randomized Controlled Trial”
http://pediatrics.aappublications.org/content/early/2015/11/04/peds.2015-1037

Not So Fast on Race-Related Oligoanalgesia

This recent study regarding pain control received a lot of press, covered by both Reuters and NBC News.  The general gist of the breathless coverage seems to indict physicians for latent biases against treating African American children with opiates.

I’m not so certain.

This is a retrospective evaluation of a national Emergency Department database of seven years of ED visits for appendicitis, looking at pain control disparity between white children and minorities.  Pain management was documented in only 57% of children, 41% of which was opiates.  Children of African American descent received opiate medication only 12% of the time, leading to the authors’ observations of an apparent reluctance to treat this population with opiates.

But, I think the foundation of their analysis may be misleading.  The authors state: “The following covariates were included in our analyses to adjust for potential confounding: ethnicity, age, sex, insurance status, triage acuity level, pain score, geographic region, ED type, and survey year.”  However, I think these data need to be addressed at a within-hospital level, not as a pooled cohort.  African Americans have been previously shown to be over-represented at low-quality, safety-net hospitals – the sort of hospitals almost assuredly do a poor job of addressing and managing pain across all their patients.  Indeed, when other researchers have looked at racial disparities in care for acute myocardial infarction, performing within-hospital analyses dramatically altered their findings, with individual hospital inadequacies accounting for a greater effect than ethnicity.

The foundational issues in race-related difference in care may yet be present, but I do not believe to the magnitude these data reflect.  Rather than suggesting “there may be a higher threshold of pain score for administering analgesia to black patients with appendicitis,” these data probably reflect the underlying under-resourced care available to this population.  A tremendous and embarrassing problem, to be sure, but with a different approach needed for a solution.

“Racial Disparities in Pain Management of Children With Appendicitis in Emergency Departments”
http://archpedi.jamanetwork.com/article.aspx?articleid=2441797