Month: July 2013

Copeptin & Publication Bias

There is a phenomenon in the medical literature called publication bias.  It results from two phenomena – authors are more likely to submit the results of trials with positive results, and editors tend to publish articles with positive results.  This results in all sorts of flaws with regard to the composition of the scientific literature, and exerts a particularly troubling hidden effect in meta-analyses and systematic reviews.

I comment upon this in the context of yet another cardiovascular assay article that has – essentially – negative results that are spun to be positive.  Copeptin, as I’ve discussed before, is another acute phase indicator of myocardial demise – but sacrificing specificity for sensitivity.  These authors combine copeptin with hs-TnT for evaluation of chest pain in the Emergency Department, and report several favorable findings in their abstract and the text of their discussion.

In reality only one of the findings they focus on is truly positive – an increase in sensitivity from 76% to 96%.  The NPV increases from 95% (90.4-98.3) to 98.9% (94.2-100) and is not truly a positive result.  More importantly, the authors report copeptin “adds incremental value” – when the area under the receiver operating curve is statistically identical at 0.886 (0.85-0.922) vs. 0.928 (0.89-0.967).

Perhaps copeptin will someday be proven to add true clinical value in an algorithm for the rapid assessment of chest pain in the Emergency Department.  This paper, however, seems to have exaggerated the positivity of its results.  Considering the spate of other recent “positive” copeptin articles – I foresee systematic reviews and meta-analyses of the test characteristics further perpetuating any unremarkable reported advantage in test characteristics.

“Early rule out of acute myocardial infarction in ED patients: value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission”
http://www.ncbi.nlm.nih.gov/pubmed/23816196

Subsegmental Pulmonary Emboli Are Just As Deadly?

A couple weeks back, I posted my algorithm regarding (not) evaluating patients with chest pain for pulmonary embolism.  As has been written multiple times – most recently in this BMJ article – the evidence for overdiagnosis is rather overwhelming, and I’m trying to come up with strategies to do my small part to reduce it.

These Dutch authors, however, perform a retrospective analysis of prospectively-collected data and conclude “patients with symptomatic [subsegmental pulmonary embolism] appear to mimic those with segmental or more proximal PE as regards their risk profile and short term clinical course.”  If correct, it would imply there are no “clinically insignificant” PE – which flies in the face of our evidence of overdiagnosis.

These authors found 116 SSPE, 632 proximal PE, and 2980 patients without PE.  They found the folks with proximal and SSPE, by almost every measure, had significantly more thromboembolic risk factors – particularly malignancy – than the folks without PE.  Unsurprisingly, given the identical VTE risk profile between proximal and SSPE, there was essentially no difference in rate of recurrent VTE in the proximal and SSPE groups during 3 month follow-up – 4 patients (3.6%) with SSPE and 14 patients (2.5%) for proximal PE.  Given an absence of risk factors, the patients without PE at baseline had only 1.1% incidence of VTE during the follow-up period.  For all-cause mortality, the risk was 10.3% for SSPE, 6.3% for proximal PE, and 5.4% for patients without PE at baseline.  1.6% of both the SSPE and proximal PE group suffered major bleeding complications from anticoagulation.

So, there is some truth to the authors’ conclusion that SSPE has a clinical course similar to proximal PE.  However, the clinical significance of SSPE is almost certainly confounded by co-occurrence of comorbid conditions.  It is reasonable to suggest true PE and SSPE are poor prognostic indicators of background disease burden, and not the salient pathologic diagnosis.  Anticoagulation may not be the most important course of action; rather, identifying and treating the underlying cause, if present.

This article ought not support any argument regarding the necessity of diagnosis and treatment of sub-segmental PE, except in the context of a broader approach to a patient.

“Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism”
www.ncbi.nlm.nih.gov/pubmed/23736701

Happy Independence Day!

I ought to have posted this piece regarding firework injuries on Wednesday to get folks in the mood – but, better late than never!

This is an entertaining little experiment published in JAMA investigating the mechanism of ocular trauma from fireworks.  These authors created a setup in which a cadaveric eye was suspended in a network of sensors – and then concussive charges and fireworks were exploded at various distances.

Based on their experiments, these authors conclude most of the ocular injury potential is superficial and results from flying debris, rather from any explosive pressure wave.  Fascinating little study!

“Mechanisms of Eye Injuries From Fireworks”
www.ncbi.nlm.nih.gov/pubmed/22760285

BMJ Rapid Responses

The BMJ article highlighting conflict-of-interest in medical guidelines has a thriving Rapid Response section – including responses from Michael Bracken, Peter Sandercock, Fred Geisler, and David Newman.  A fascinating microcosm of sorts of some of the recent controversies in Emergency Medicine!

“Why we can’t trust clinical guidelines – Rapid Responses”
http://www.bmj.com/content/346/bmj.f3830?tab=responses

Does Funding Source Influence Guidelines?

There’s been a little hullabaloo recently regarding the influence of financial conflicts-of-interest on guidelines – the result of a recent BMJ investigative report.  But, what effect do these conflicts truly have?  Is there any way to compare, side-by-side, a conflicted guideline with a non-conflicted guideline?

Why – yes!

In the very popular American Journal of Medical Quality comes this tiny gem, a comparison between two guidelines written just over a year apart.  Both guidelines describe treatment options for Primary Immune Thrombocytopenia, and were both published in the same journal.  One guideline was written by a financially untarnished societal group, while the other guideline was written by sponsored experts.  In addition, the sponsored guideline had supplemental assistance by a professional scientific writing group funded by pharma.

Table 4 is a lovely, side by side comparison of the major treatment recommendations.  Unsurprisingly, various thrombopoietin-receptor agonists and anti-D immunoglobulin received top billing in the sponsored guideline, while more conventional therapies were recommended in the non-sponsored guideline.

This article was, however, written by members of the non-conflicted guideline group – so, perhaps there’s some ulterior motive at work.  Regardless, at least, it’s a fascinating look at the tangible effects of financial conflicts-of-interest.

“Conflicts of Interest and Clinical Recommendations: Comparison of Two Concurrent Clinical Practice Guidelines for Primary Immune Thrombocytopenia Developed by Different Methods”
www.ncbi.nlm.nih.gov/pubmed/23550214

The Return of Lidocaine?

Lidocaine as adjunctive treatment following cardiac arrest in the context of ventricular fibrillation/ventricular tachycardia has generally fallen out of favor and been replaced with amiodarone, a result of historical data and more recent trials.  However, the quality of the evidence is generally poor, and confounders are frequent.

So, here’s some more chaotic, retrospective evidence gathered over the course of 16 years.  This is the King County registry of OHCA, of which 1,721 patients with VF/VT and ROSC were identified.  Of these, 1296 patients received prophylactic lidocaine after ROSC, in theory, to prevent re-occurrence of VF/VT.  And, in both their unadjusted, adjusted, and propensity matched cohorts, there was a reduction in recurrence of VT/VF.  However, in their propensity-matched cohort – which may or may not be a better tool for comparing two groups than their multivariate adjustment – there was no difference in admission rate or survivors to hospital discharge.

At the least, as these authors suggest, this data provides the clinical equipoise needed to justify prospective OHCA trials exempt from informed consent.

“Prophylactic lidocaine for post resuscitation care of patients with out-of-hospital ventricular fibrillation cardiac arrest”
www.ncbi.nlm.nih.gov/pubmed/23743237‎