Month: June 2014

A Prehospital Transfusion Confusion

Which is to say – endorsing conclusions founded on sparse data is worse than simply admitting the limitations of our knowledge.

Clearly, if a patient requires blood, the more, the sooner, the better with severe injury.  However, starting that transfusion outside a setting fully capable of assessing injury severity and physiology can mean wasted or inappropriate product use.

These authors attempt to show patients receiving blood in the pre-trauma center setting have markedly decreased mortality and traumatic coagulopathy.  However, they do so using a retrospective database of patients from 2003 to 2010, of which only 50 patients received pre-trauma center transfusion, compared with 1,365 who did not.  Additionally, there were diverse differences in ISS, base deficit, and total crystalloid and product transfusion.  They subsequently attempt to control for this using logistic regression and by deriving a propensity-matched cohort – which then compares 35 patients with pre-hospital transfusion with 78 patients without, but still has diverse significant differences in initial physiology and total product transfusion.

So, because of all these intrinsic differences, all their reported odds ratios are adjusted after “controlling for confounders”.  After all the statistical wrangling, “covariate-adjusted” 30 day survival was ~95% in the cohort with pre-trauma center transfusion, and ~88% in others.  The propensity-matched results showed similar odds ratios.  Unadjusted mortality in the cohorts is not presented.

Who knows what this really shows?  The data used is retrospective, heterogenous and collected over the course of 8 years, their sample of pre-trauma center transfusions is tiny, and all their reported odds ratios required huge statistical adjustments.  Pre-trauma center transfusions are probably helpful, if used judiciously, but this is not the study that shows it.

“Pretrauma Center Red Blood Cell Transfusion Is Associated With Reduced Mortality and Coagulopathy in Severely Injured Patients With Blunt Trauma”

Let’s Make MRSA Stronger

Yesterday, the NEJM published two new trials regarding new lipoglycopeptide antibiotics targeting MRSA.  And, it remains to be seen whether their use represents the beginning of the end.

Oritavancin and dalbavancin differ from vancomycin – and this is their primary advertised advantage – in terms of substantially lengthened terminal half-life.  This means oritavancin may be used as a one-time dose, and dalbavancin as a two-dose regimen a week apart.  Both trials involved severe soft-tissue infection, and were non-inferiority trials comparing each against either intravenous vancomycin alone or intravenous vancomycin transitioning to oral linezolid.  Exclusion criteria were extensive for each, but the ultimate non-inferiority results for treatment failure are reasonably generalizable.  Adverse events, as well, were similar between study populations.  At face validity – if you trust trials that are designed, conducted, and analyzed by pharmaceutical companies – these treatments are safe and effective.

The accompanying editorial enthusiastically supports these new options, saving patients unnecessary costs and risks associated with hospitalization or indwelling intravenous catheters.  This is likely true, although it remains to be see whether single-dose infusion pricing will ultimately prove less expensive than a transition to oral linezolid.  Then, single-dose antibiotic strategies may have a horrible downside: induced resistance.  With terminal half-lives up to two weeks in the case of oritavancin, the active metabolite will be present in the body for a prolonged period of time below the minimum inhibitory concentration.  As we’ve seen with azithromycin, another antibiotic with a long half-life, increased use was associated with a rapid rise in macrolide resistant streptococcus.  It’s hardly a stretch to project similar effects here.

Widespread use of these “convenient” antibiotics may eventually result in significant unintended harms, and possibly the loss of an entire class of effective treatment for MRSA.

“Once-Weekly Dalbavancin versus Daily Conventional Therapy for Skin Infection”
http://www.nejm.org/doi/full/10.1056/NEJMoa1310480

“Single-Dose Oritavancin in the Treatment of Acute Bacterial Skin Infections”
http://www.nejm.org/doi/full/10.1056/NEJMoa1310422

Time is Brain, Perhaps – in Trauma

Or, at least, that’s what the adjusted analysis here wants to suggest – and, by implication, validate using aeromedical transport for patients with traumatic brain injury.

This is a retrospective evaluation of 209,529 TBI patients in the National Trauma Data Bank between 2009 and 2011, comparing ground-based transport to Level I and Level II centers with aeromedical transport to these same centers.  Patients flown to Level I and II trauma centers were far more likely to die – in the unadjusted analysis, owing to much higher injury severity scores.  Using two methods of adjustment, however, and incorporating propensity score matching, patients with TBI had odds ratios between 1.73 and 1.95 for survival (95% CI 1.55 to 2.10).  The adjusted absolute risk reductions for death ranged from 4.69% to 6.37% (95% CI 4.08% to 6.85%).

These are fairly substantial improvements in a reasonably important patient-oriented outcome (mortality).  There are, of course, serious limitations in doing this sort of retrospective analysis, making these statistical adjustments, and extrapolating this association out to the presumed benefit of the intervention – that a reduction in trauma response and transport time confers the survival advantage.

This study provides a very low level of evidence moving the needle in favor of aeromedical transport.  It’s reasonably clear there are patients that benefit from aeromedical transport – but at $10,000+ per transport, and field over-triage already a problem, this study alone should not inform any change in practice.

“Prehospital Helicopter Transport and Survival of Patients With Traumatic Brain Injury”
http://www.ncbi.nlm.nih.gov/pubmed/24743624

Dr. Wikipedia is In

… and Dr. Wikipedia is wrong.  Or, at least, that’s what most of the popular media coverage of this study perpetuated.

Given estimates of Wikipedia utilization for medical advice range from 40-70% of physicians, this group thought it important to undertake a comparison of Wikipedia articles with peer-reviewed references for accuracy.  Looking at ten Wikipedia articles representative of the top ten most costly healthcare conditions, two reviewers compared declarative statements from the Wikipedia article to those cited by a reference source – limited, unfortunately, to only those articles cited by UpToDate.  In the end, the reviewers generally found a good deal that was similar between Wikipedia and UpToDate – but also a great deal that was not fully supported by peer-reviewed references.

Reviewers were generally in agreement over which facts from Wikipedia were unsupported, but not entirely.  And, of course, UpToDate and its references are hardly the definitive source of medical fact.  However, it’s probably fair to say – physicians ought to exercise a substantial level of caution when considering basing patient care off Wikipedia.

“Wikipedia vs Peer-Reviewed Medical Literature for Information About the 10 Most Costly Medical Conditions”
http://www.ncbi.nlm.nih.gov/pubmed/24778001