Author: Ryan Radecki

A Shared Decision-Making Trial … But Fatally Flawed?

Shared decision-making is developing as the proposed solution to many of the problems with resource utilization today.  Rather than embrace “zero miss” practice without properly involving patients as the decision-makers, we are now encouraged to offer the patient choices regarding their diagnostic and treatment decisions.  By sharing the decision – and the risk – I find patients quite amenable to forgoing much low-yield testing.

To that end, a multi-center trial has begun, evaluating the use of shared decision-making in low-risk chest pain.  The trial is based on an information graphic created by the Mayo Clinic, and individualized risk assessment is supported by Jeff Kline’s attribute-matching algorithms.  This is fabulous, from a conceptual standpoint – as shared decision-making is not nearly as feasible without the proper communication tools or best available evidence available at the point of care.

However, there’s an important missing element from the proposed information graphic:

Link to high-resolution version.

The decision tool explains the 45-day risk of myocardial infarction if testing is deferred.  However, the patient-oriented decision is between stress test (or CT coronary angiogram, at the University of Pennsylvania), cardiology follow-up, and primary care follow-up – and the decision aid doesn’t actually address those choices.  It does not describe the relative risks of MI between each option, and, more importantly, it does not describe the risks or benefits of the additional testing offered.  Without information regarding the rates of true positive and false positive test results, the incremental prognostic value of such tests, or the costs associated with additional testing, the patient doesn’t have the appropriate foundational information for their choice.

Conceptually, this is a fantastic trial.  However, I’m not sure the decision-aid has been correctly designed and implemented, with regard to the choices offered.  Indeed, if the poor test characteristics of stress and CTCA in this population were shared with patients, it would probably even show more powerful reductions in resource utilization.

“Effectiveness of the Chest Pain Choice decision aid in emergency department patients with low-risk chest pain: study protocol for a multicenter randomized trial”
http://www.trialsjournal.com/content/15/1/166

Abscess Management in the Era of MRSA

Every so often, it’s good to circle back from the esoteric to the basics, and remind ourselves how to provide the best, evidence-based treatment for some of the most common diseases – in this case, abscesses.

This review in the New England Journal is a reasonable, concise overview of the evidence behind management of cutaneous abscesses, updated for the increasing prevalence of methicillin-resistant Staphylococcus aureus.  And, quite simply, there’s no evidence for any reason yet to panic.  The authors of this article summarize the literature thusly:

  • Incision & drainage is definitive treatment.  Non-complicated disease does not require additional antibiotic treatment, and the incremental benefit – if any – would be single-digit differences in clinical failure.
  • Packing of abscesses is a matter of tradition, and evidence is neither sufficient to conclusively confirm nor refute this practice.
  • Primary closure of abscesses after I&D is reasonable, particularly for larger, exposed, and cosmetically important areas.
  • Antibiotic coverage for primarily cellulitic soft-tissue infections ideally includes both MRSA and streptococcal coverage, but recent evidence showed no advantage to double-coverage.  Clinical trials regarding antibiotic use are ongoing:  NCT00729937 NCT00730028  NCT00729937
  • Wound cultures are not necessary.

One could argue covering such basics in infection and wound management is a sundry affair for a blog frequently covering the cutting edge.  However, current management of such a common condition is so highly variable and frequently low-value, ACEP even made a point to include abscess management in their Choosing Wisely campaign list.

Now, go and do as little harm as possible.

“Management of Skin Abscesses in the Era of Methicillin-Resistant Staphylococcus aureus”
http://www.ncbi.nlm.nih.gov/pubmed/24620867

SIRS is Rarely Sepsis

You already knew this – but that hasn’t stopped your hospital from purchasing the “Sepsis Alert” tool for your electronic health record.  Now, you and your nurses get blasted with computerized interruptions every time a patient is tachycardic and has an elevated WBC count.  And, you ignore it – because it’s 1) wrong, or 2) you placed a central line and admitted the patient to the ICU half an hour ago.

But, just how often do these sepsis alerts, based on systemic inflammatory response criteria, fire erroneously?  That is the question asked by this group from Harbor-UCLA and UC Davis.  Using the National Hospital Ambulatory Medical Care Survey from 2007 to 2010, these authors attempted to estimate the frequency of true infection in the setting of SIRS.  Unfortunately, while the NHAMCS set now includes vital signs obtained at triage, it does not include results of tests, such as the WBC.  Therefore, these authors – and this is where the study breaks down a bit – were required to mathematically conjure up a range of estimates for the frequency with which patients would meet the WBC criterion for SIRS.  Based on minimum and maximum estimates, the percentage of Emergency Department visits estimated to have SIRS ranged from 9.7% to 26.0%, and the authors ultimately split the difference at 17.8% for their analysis.

Based on their estimate, there were approximately 66 million visits to Emergency Departments meeting SIRS criteria, and the largest cohort of eventual diagnoses for these patients was indeed infection – but this constituted a mere 26% of all SIRS.  The remaining diagnoses were scattered among trauma, mental disorders, respiratory diseases, and other non-specific, organ-system dysfunction, catch-all ICD-9 codes.  While the interruptions and low specificity of SIRS alert tools are the obvious problem addressed by this study, the other implication is the troubling scope of the problem:  after trauma and infection are excluded, there are approximately 42 million other ED visits that may erroneously trip institutional protocols, costly unnecessary testing, and additional resource utilization targeting sepsis.

This is the sort of decision-support that simply doesn’t add any proven value, and another venue of encroachment into efficient and effective care.

“Epidemiology of the Systemic Inflammatory Response Syndrome (SIRS) in the Emergency Department”
http://www.ncbi.nlm.nih.gov/pubmed/24868313

Conclusively Settling Azithromycin’s Cardiac Toxicity Forever

We’ve been obsessed with azithromycin’s cardiovascular effects for quite some time – with some studies showing an increase in events, and other studies using azithromycin as the active agent to decrease coronary events.  Why is it such an issue?  Mostly because azithromycin has become the nonsensical cure-all of eager-to-please primary care physicians for self-limited or viral conditions, let alone the mainstay of treatment for pneumonia.

This latest study comes from a retrospective cohort of Veterans Affairs patients admitted and receiving IDSA guideline-compliant treatment for community-acquired pneumonia.  These authors compared a cohort of patients receiving ß-lactam + azithromycin with any other guideline-compliant therapy, typically fluoroquinolone monotherapy.  They created two propensity-matched cohorts based on known confounders, resulting in comparison groups of 31,863 patients each, with a treatment period spanning 2001 to 2012.

Of these, 1,948 patients exposed to azithromycin had a myocardial infarction recorded within 90 days, compared with 1,523 in the non-azithromycin cohort, for an OR of 1.11 (95% CI 1.03-1.20).  No other cardiovascular disease was increased, and no specific subgroup conferred a higher or lower risk of MI after azithromycin use.  Most of the difference in MI occurred within 30 days of exposure.

However, interestingly, the overall 90-day mortality was 6,582 in the azithromycin cohort, compared with 8,152 in the non-azithromycin cohort, for an OR of 0.73 (95% CI 0.70-0.76).  And, the authors happily run with this mortality advantage – concluding “azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality (number needed to treat of 21)”.  But, how does a short course of a macrolide antibiotic generate such a profound survival curve that progressively widens months after exposure?  The authors do not provide data on causes of death, nor do they provide much explanation for the observed survival advantage.  Either short-course azithromycin provides a powerful, anti-inflammatory effect with long-term advantage – as implied by the authors – or there’s a problem with the data and the matching.

My vote is for problems with the data.  Propensity matching is only as good as the prognostic importance of variables included in the algorithm, and suffers tremendously when performed on retrospective data not gathered specifically to support such analyses.  Sadly, this study is probably best served to be assigned to the scrap heap of unreliable retrospective observations.

“Association of Azithromycin With Mortality and Cardiovascular Events Among Older Patients Hospitalized With Pneumonia”

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

Predicting Past Massive Transfusion Practices

Traumatic resuscitation is evolving – and reasonably so – to an aggressive, early-intervention strategy.  The current evidence seems to suggest patients benefit from early, whole blood volume replacement in the setting of hemorrhage.

But, in order to aggressively intervene early, it’s necessary to predict such need equally early in the initial trauma assessment process.  Therefore, a variety of prediction decision-instruments have been derived, such as this one from Japan.  These authors looked retrospectively at 119 severely injured trauma patients, developed odds ratios for massive transfusion via logistic regression, and then created a scoring system with a cut-off predicting massive transfusion.  They then subsequently validated this score on another retrospective cohort of 113 patients from the same institution.  Their score contains, essentially, the expected elements – age, lactic acid level, systolic blood pressure, FAST exam findings, and pelvic fracture type – and a score of 15 or higher was 97.4% sensitive and 96.2% specific for massive transfusion.

However, what this rule predicts is not the population that needs massive transfusion – but, because both steps were performed retrospectively, it simply describes the consistency in the authors’ general practice at this single institution.  At the authors’ institution, the patients that looked like the ones described by the rule – elderly, hypotensive, positive FAST, etc. – are the ones that received massive transfusion.  Therefore, when they look back to derive a decision instrument – they’ll find it simply reflects their general practice.  Subsequently, to validate the instrument – again, if their practices haven’t changed, the decision rule will simply accurately reflect the continued practice pattern from which it was derived.  The authors do not mention whether they had a formal early massive transfusion protocol or practice in place, but, if so, this would further skew the decision instrument to reflect the guidelines guiding practice, rather than actual patient need.  Finally, for one last hit to external generalizability, a “massive transfusion” was defined as 10 units of PRBCs – which, in Japan, are about 1/3rd the volume of those in the United States.

Despite its reportedly excellent performance, this rule cannot be relied upon until prospective, external study validates its use.

“Predicting the need for massive transfusion in trauma patients: The Traumatic Bleeding Severity Score”
http://www.ncbi.nlm.nih.gov/pubmed/24747455

Infections & Transfusions

We love our transfusions down in the Emergency Department.  We especially love them in our trauma patients – and, if anything, the move is to provide earlier, more aggressive volume replacement, and to use more FFP, cryoprecipitate, and platelet product to maintain optimal coagulation parameters.

The downside?  Besides cost, over-utilization of a limited resource, and the various adverse reactions that may occur – there’s a bit of an infection risk.

This JAMA meta-analysis pools together the results of 18 trials comparing “restrictive” vs. “liberal” transfusion strategies for PRBCs.  These trials ranged across medicine from cardiovascular settings, the critically ill, sickle cell disease, and other surgical settings.  In most trials, the restrictive transfusion setting ranged from a Hgb of 7 to 9 g/dL, while the liberal strategies were typically goals above 10 g/dL.  These authors simply looked at the pooled incidence of “serious infection”, which was typically reported as wound infection, bacteremia, pneumonia, or a broad definition of sepsis.

In the “restrictive” transfusion group, there was an overall pooled risk of infectious complication of 11.8% (95% CI, 7.0%-16.7%), compared with an infectious complication rate of 16.9% (95% CI, 8.9%-25.4%) in the “liberal” transfusion group.  The authors estimated a “number needed to harm” between 20 and 38, depending on the restrictive transfusion threshold.

This study does not, by itself, indicate transfusions ought to be withheld when indicated.  Rather, these authors primarily suggest, in order to fully describe the risks and benefits of any transfusion strategy, that infectious complications be included in data collection during trials.  This ought to be of even greater importance in the new surveillance of massive transfusion protocols – as PRBC products aren’t typically even the highest-risk for subsequent infectious complications.

“Health Care–Associated Infection After Red Blood Cell Transfusion”
http://www.ncbi.nlm.nih.gov/pubmed/24691607