And The Stoning Continues

A couple months ago, the world of ureterolithiasis was upended by The Lancet and its publication of a trial examining medical expulsive therapy.  In direct contrast to the prior (worthless) Cochrane Review, this large, reasonably-designed trial, does away with the notion of universal benefit of alpha- and calcium channel-blockers for MET.

Following on its heels comes the publication of another trial of moderate size, but with even more rigorous follow-up.  Rather than previously mentioned trial’s “urologic intervention” as the patient-oriented outcome, this trial used a disease-oriented outcome.  This trial, enrolling patients with distal ureteral stones, required patients to under go CT at 28 days to definitively assess for stone passage.

The trial randomized 403 patients to either tamsulosin 0.4mg daily for 28 days or identical placebo, but, unfortunately, 87 did not ultimately undergo second CT.  Of the patients that did undergo CT, there was no statistically significant difference in stone passage: 87.0% tamsulosin vs. 81.9% placebo, an absolute difference of 5.0% (95% CI -3.0 to 13.0).  Of the 87, 77 were available for follow-up regarding urologic intervention.  If a combined endpoint of CT passage and lack of urologic intervention is used, the results remain unchanged.

However, the trial was designed specifically to enroll adequate numbers of patients with stones of 5-10mm in size – targeting adequate sample size with which to include at least 49 patients to detect a difference in stone passage of 5 to 25%.  They ultimately randomized 103 large stones and completed imaging or clinical follow-up on 77.  The difference in stone passage rate in the large stones was 83.3% in the tamsulosin group, compared with 61.0% with placebo, for an absolute difference of 22.4% (95% CI 3.1 to 41.6).

So, what’s the takeaway – from decades of poor-quality studies, the recent Lancet publication, and now this?  There’s probably some signal in the noise – and that signal, all along, has probably been these large, distal stones.  Unless there’s a truly diminished risk of stone passage, there’s never been any reasonableness to the use of MET – but if passage rates are ~60%, the likelihood of a clinically meaningful benefit is finally possible.

If I’ve obtained a CT in a patient and diagnosed a large, distal stone – I am offering tamsulosin.  Otherwise, no.

Rory Spiegel also shares his typically excellent similar evaluation of the evidence: EM Nerd

“Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial”

Doctor Internet Will Misdiagnose You Now

Technology has insidiously infiltrated all manner of industry.  Many tasks, originally accomplished by humans, have been replaced by computers and robots.  All manner of industrialization is now automated, Deep Blue wins at chess, and Watson wins at Jeopardy!

But, don’t rely on Internet symptom checkers to replace your regular physician.

These authors evaluated 23 different online symptom checkers, ranging from the British National Health Service Symptom Checker to privately owned reference sites such as WebMD, with a variety of underlying methodologies.  The authors fed each symptom checker 45 different standardized patient vignettes, ranging in illness severity from pulmonary embolism to otitis media.  The study evaluated twin goals: are the diagnoses generated accurate?  And, do the tools triage patients to the correct venue for medical care?

Eh.

For symptom checkers providing a diagnosis, the correct diagnosis was provided 34% of the time.  This seems pretty decent – until you go further into the data and note these tools left the correct diagnosis completely off the list another 42% of the time.  Most tools providing triage information performed well at referring emergent cases to high levels of care, with 80% sensitivity.  However, this performance was earned by simply referring the bulk of all cases for emergency evaluation, with 45% of non-emergent and 67% of self-care cases being referred to inappropriate levels of medical care.

Of course, this does not evaluate the performance of these online checkers versus telephone advice lines, or even against primary care physicians given the same limited information.  Before being too quick to tout these results as particularly damning, they should be evaluated in the context of their intended purpose.  Unfortunately, due to their general accessibility and typical over-triage, they are likely driving patients to seek higher levels of care than necessary.

“Evaluation of symptom checkers for self diagnosis and triage: audit study”
http://www.ncbi.nlm.nih.gov/pubmed/26157077

Let’s Poison Our Kids With E-Cigarettes

The hazards of the natural world are not an issue for those of us born into “civilization”.  Without lions, tigers, bears, and dingoes to endanger our babies, we’ve had to become more creative.  Firearms in the home, detergent packets, and, now:  highly concentrated nicotine from e-cigarettes.  This short review provides a brief look at an increasingly prevalent health hazard.

The lethal dose of nicotine is approximately 1 mg/kg.  Concentrations of liquid nicotine cartridges may be as high as 35 mg/mL.  A typical 10 mL refill bottle, then, has easily a lethal dose for children, while a 50 mL bottle could have more than enough to bring down a horse.  For comparison, a conventional cigarette contains 10 to 1 5mg of nicotine – certainly a danger, but on a different scale entirely.

The expected clinical effects are consistent with the classical nicotinic and muscarinic toxodromes – vomiting, diarrhea, salivation, bronchorrhea, seizures, rhabdomyolysis, and respiratory failure.  Therapeutic management remains supportive – intravenous fluids, atropine, and mechanical ventilation as needed.  Inadvertent exposures are typical, but liquid nicotine may also be used for intentional overdose in suicide attempts.

Another proud cultural innovation for the 21st century.

“Liquid Nicotine Toxicity”
http://www.ncbi.nlm.nih.gov/pubmed/26148101

Expunging “Zero-Miss” from Chest Pain Evaluation

The admit rate for chest pain from the Emergency Department varies widely.  In some instances, the rule “chest pain = admit” is the norm – or, at the least, observation and provocative or anatomic radiology from the Emergency Department.  Indeed, such studies exhorting the advantages of CCTA in the ED included those aged as low as 30 years – patients in whom the false positives from testing far outweigh the true.

The typical motivating factor for such aggressive admission rates has been a culture of “zero miss”, motivated by huge settlements for missed MI.  Accordingly, this brief study followed Emergency Physicians and asked – what if there were no legal liability?  What if there was an acceptable miss rate of 1 or 2% in chest pain?  How many of these people would be discharged instead of admitted?

Based on 259 surveys completed regarding a convenience sample of admitted chest pain patients, the answer from this single-center study is: 30%.

With over 5 million ED visits for chest pain annually, cutting the current 35% admission rate by 30% turns into a massive reduction in resource utilization.  And, frankly, it’s not as daunting to implement such thresholds as one might imagine: ED physicians set the standard of care, not lawyers.  As Jeff Kline has alluded to the possibility, it’s time for domain experts to set reasonable practice variation and resource utilization, rather than leave it up to lawyers and their hired guns:

This definitely should be done.

“The Association Between Medicolegal and Professional Concerns and Chest Pain Admission Rates”
http://www.ncbi.nlm.nih.gov/pubmed/26118834

Narcotic Overdoses Are Just Who We Expect

Deaths from narcotic overdose have jumped tremendously in the past years – to the point where naloxone distribution has become a life-saving public health initiative.  But, far more effective than treatment of overdose is prevention – and this small retrospective evaluation of Medicaid enrollees provides an insight into those at risk.

Based on an analysis of 90,010 Medicaid beneficiaries prescribed long-term opiate therapy, these authors made the following observations:
  • Patients without overlapping narcotic prescriptions, and who did not fill prescriptions at more than 3 pharmacies: 0.63% overdose incidence
  • Patients with overlapping narcotic prescriptions, and who filled prescriptions at more than 3 pharmacies: 6.09% overdose incidence
Other strongly predictive features for overdose were:
  • Morphine equivalent opioid doses >50mg per day
  • Concurrent sedative use
  • History of alcohol abuse
  • Depression diagnosis
Considering the increasing morbidity and mortality associated with opioid use and abuse, studies such as these help proactively identify those at greatest risk for early intervention.

“Defining Risk of Prescription Opioid Overdose: Pharmacy Shopping and Overlapping Prescriptions Among Long-Term Opioid Users in Medicaid”
http://www.ncbi.nlm.nih.gov/pubmed/25681095

The Utility of Urinalysis in Young Infants

When faced with the diagnostic evaluation of the young, febrile infant fewer than three months of age, the definitive tool for sepsis from urinary tract infection has traditionally been urine culture.  This stems from uncertainty over the adequacy of urinalysis sensitivity for serious bacterial infection, i.e., those truly bacteremic from a urinary source.

This is an analysis of a multicenter database of infants with bacteremia and urinary tract infection, as measured by isolation of the same pathologic organism from both blood and urine.  The key numbers:
  • Trace or greater leukocyte esterase: 97.6% (94.5-99.2) sensitive and 93.9% (87.9-97.5) specific.
  • Pyuria, >3 WBC/HPF: 96% (92.5-98.1) sensitive and 91.3% (84.6-95.6) specific.
  • Pyuria or any LE: 99.5% (98.5-100) sensitive and 87.8% (80.4-93.2) specific.
These are pretty impressive statistics, and differ significantly from the prior supposed sensitivity of the UA in young infants.  These authors postulate the problem with prior study has been its over-reliance on urine culture, and the resulting false positives.  If this seems a reasonable interpretation of the evidence, it has substantial ramifications for the diagnostic evaluation of young infants.  Importantly, it has the potential for obviating invasive procedures and unnecessary over-treatment.

I would like to see independent confirmation of these authors' findings, but, considering this study required 15 years to produce the 276 patients analyzed in this paper, this may be the best evidence we see for awhile.

“Diagnostic Accuracy of the Urinalysis for Urinary Tract Infection in Infants, 3 Months of Age”
http://www.ncbi.nlm.nih.gov/pubmed/26009628