Month: April 2015

No Additive Value for Macrolides?

As we’ve been repeatedly drilled by our quality groups – and in part to pneumonia core measures – appropriate empiric treatment for hospitalized community-acquired pneumonia is: 1) a beta-lactam plus a macrolide, or 2) respiratory fluoroquinolone monotherapy.

Or is it?

This cluster-randomized trial across seven hospitals in the Netherlands questioned the additive value of the macrolide, in the name of antibiotic resistance, and appear to have come out ahead.

Participants admitted to non-ICU settings with a clinical diagnosis of CAP received either beta-lactam monotherapy, beta-lactam plus macrolide, or respiratory fluoroquinolone monotherapy.  With between ~650 and ~890 patients enrolled during the time periods assigned to each arm, the final outcome was: no difference.  In fact, across nearly all intention-to-treat, radiographically-confirmed, and strategy-adherent analyses, beta-lactam monotherapy was solidly on the “better than” side of the confidence intervals versus added macrolide therapy.  There was no detectable trend with regard to the fluoroquinolone group – excepting the notable advantage of oral administration.  Nearly 30% of the fluoroquinolone group received their entire therapy by the oral route alone – an appreciable resource savings, at the least.

The authors do note the low seasonal prevalence of atypical pathogens during the time of the trial.  And, as with nearly all topics in medicine, the ultimate conclusion is not an “always” or “never” proposition.  However, in the patients selected for this trial, it certainly did not appear harmful to withhold a macrolide when treating with a beta-lactam.

“Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults”
http://www.nejm.org/doi/full/10.1056/NEJMoa1406330

Too Many Tests! Or, So We Believe ….

Yes, Virginia, we order too many tests.  And, we know it – as evidenced by such conferences on overdiagnosis and costs of care.  And, even more relevant than such academic exercises, as this study indicates, even the general clinician seems to have a fair bit of self-awareness.

In this survey consisting of 435 respondents, 85% of emergency physicians believed excessive testing occurred in their Emergency Department.  Most frequently, such testing was motived by fear of missing even rare diagnoses, but defensive medicine and malpractice came a close second.  Patient expectations, local practice patterns, and time saving were also substantially cited as motivators for ordering.  Thankfully, administrative and personal motivations to increase reimbursement were rarely reported as reasons.

Despite the protestations of some policy-makers, the clinicians surveyed believed the most helpful change to the system would be malpractice reform.  Interestingly, the next ranked helpful interventions included educating patients and increasing shared decision-making.  While the first item may be logistically (or politically) unachievable, there are no obstacles to integrating improved communication behaviors into routine practice.  It does, however, show a need for increased availability of tools for clinicians to use at the point of care.

There are flaws in these sorts of perception-based surveys with regard to the accuracy of such anecdotal self-assessment.  Physician assessment of their own practice and that of others can certainly be questioned.  It must be admitted, however, a more intensive just-in-time surveying method would likely impact the variables measured.

There are also some highly entertaining outliers in Figure 2, of course, the perception of self vs. colleague ordering.  There is a handful of physicians who believe they, themselves, order over 80% of their CTs and MRIs unnecessarily – but that no one else in their group does.  Likewise, there is a handful with just the opposite perception – that their colleagues over-order, while they, themselves rarely do.  I wonder if they work in the same department?

Regardless, first step is admitting you have a problem.  We have many steps yet to go.

“Emergency Physician Perceptions of Medically Unnecessary Advanced Diagnostic Imaging”
http://onlinelibrary.wiley.com/doi/10.1111/acem.12625/abstract

All Hail n-tPA! [April Fools]

As much of a naysayer I’ve been over the past few years, holding out as a skeptic, waiting for a study to finally settle the issue on thrombolytics in acute ischemic stroke – that day has come.

Except, it’s not tPA.  It’s a novel isoform of tPA, dissimilar to all of the versions we’re familiar with – alteplase, desmoteplase, tenecteplase, etc.  The novel effect seems to be, according to these authors, related to cross-linking between n-tPA molecules rather than the intrinsic structure of the molecule itself, in which the n-tPA forms a sort of fibrinolytic meshwork.  The best conceptual physiologic analogy is probably phagocytosis, in which the intracerebral obstruction is more devoured than lysed.  As a result, outcomes appear to be dramatically improved – both in terms of efficacy and safety.

These authors describe the first phase of a single-center dose-finding study in which ischemic stroke patients otherwise meeting criteria for tPA were given 0.8 mg/kg, 1.2 mg/kg, or 1.6 mg/kg of n-tPA.  All patients had demonstrable arterial occlusion on CT angiography prior to administration.  Recanalization, as measured by repeat angiography, was 40%, 70%, and 70% in each cohort – with zero cases of intracranial hemorrhage or neurologic deterioration.

In the second phase, the authors expanded the protocol to randomize 200 patients either to tPA or n-tPA at the 1.6 mg/kg dose.  Unfortunately, they only report functional outcomes at hospital discharge, rather than the typical long-term follow-up of contemporary stroke studies.  That said, at discharge, 59% of n-tPA patients achieved favorable outcome, mRS 0-1, compared with 28% of the usual care group.  Rates of sICH were 1% in the n-tPA cohort compared with 4.5% in usual care.

As with all relatively preliminary data – and coming from a single-center – these results should be treated with caution.  But, has the impossible happened?  Has the day finally come where I can enthusiastically support the use of thrombolytics in stroke?

“Dose-Ranging and Outcomes Using a Novel Tissue Recombinant Activator in Acute Ischemic Stroke”
http://bit.ly/1acPEXp