More Coverage of Inappropriate Antibiotic Prescribing

If this feels like déjà vu, it might be because it is.

This short research letter in JAMA Internal Medicine describes patterns of antibiotic prescribing for three common conditions: otitis media, sinusitis, and pharyngitis. In all of these cases – in the infrequent occasion antibiotics are necessary – the appropriate first-line antibiotic is amoxicillin/penicillin. These authors estimate, based on treatment failures, allergies, and complicated disease, approximately 80% of antibiotic prescriptions for these conditions should be the first-line agents.

How did we do? Well, better in pediatrics than adults, but first-line prescribing ranged from a low of 37% to a high of 67%. The most commonly used inappropriate antibiotics were macrolides (invariably azithromycin) and fluoroquinolones. Macrolides are usually inappropriate due to high levels of resistance among common pathogens, and fluroquinolones are simply too broad-spectrum to be appropriate.

The catch, unfortunately, is the data source: the National Ambulatory Medical Care Survey, warts and all, from 2010 to 2011. The authors state they expect practice patterns have not changed much in the last five years, but it’s still a little challenging to generalize this to current practice.

Finally, as a nice corollary, this Medical Letter article was featured in JAMA regarding fluoroquinolones and their increasingly detected serious adverse effects. When antibiotics are truly necessary, physicians should try and choose one of the many alternatives presented in the article.

“Frequency of First-line Antibiotic Selection Among US Ambulatory Care Visits for Otitis Media, Sinusitis, and Pharyngitis”

Taking First-Time Seizures Seriously

Last week, I covered a disastrous prevalence study that almost certainly over-estimates the frequency of pulmonary embolism in syncope. Today, something similar – the frequency of epilepsy in patients presenting to the Emergency Department with first-time seizure.

The most recent American College of Emergency Physicians position statement regarding first-time seizures is fairly clear: first-time seizures need not be started on anti-epileptic therapy. The thinking goes, of course, that few patients would be ultimately diagnosed with epilepsy, and most of those initiated on anti-epileptics would be exposed only to their adverse effects without any potential for benefit.

This small study tries to better clarify the frequency of an epilepsy diagnosis. At a single center, during convenience business hours Monday through Friday, consecutive patients with first-time seizure of uncertain etiology were screened for enrollment. During their enrollment period, they were able to capture 71 patients for whom they were able to complete an EEG in the Emergency Department. Of these, 15 (21%) patients were diagnosed with epilepsy based on their ED EEG. All of these patients were then initiated on an anti-epileptic, most commonly levetiracetam. Anti-epileptic therapy was additionally started on two patients with abnormal EEGs and structural brain disease on imaging, one of whom was able to be contacted in follow-up with a repeat EEG showing epilepsy. These authors use these data to suggest potential benefit for EEG performed in the ED.

This is a fairly reasonable conclusion, although the level of evidence from this single study is weak. This is probably another example of the ED filling a gap in outpatient follow-up; it would almost certainly be perfectly safe to discharge these patients without investigation or initiation of therapy if an ambulatory EEG could be arranged within a few days. Further, larger-scale evaluation of the value of an ED EEG would be needed to modify our current approach.

“The First-Time Seizure Emergency Department Electroencephalogram Study.”

The Impending Pulmonary Embolism Apocalypse

After many years of intense effort, our work in recognizing overdiagnosis and over-treatment of pulmonary embolism has been paying off. With the PERC, with adherence to evidence-based guidelines, and with a responsible approach to resource utilization, it is reasonable to suggest we’re making headway into over-investigating this diagnosis.

Prepare for all that hard work to be obliterated.

This is a prospective study of patients admitted to the hospital for syncope, evaluating each in a systematic fashion for the diagnosis of PE. Consecutive admissions with first-time syncope, who were not currently anticoagulated, underwent risk-stratification using Wells score, D-dimer testing if indicated, and ultimately either CT pulmonary angiograms or V/Q scanning. The top-line result, the big scary number you’re likely seeing circulating the medical and lay news: “among 560 patients hospitalized for a first-time fainting episode, one in six had a pulmonary embolism.”

Prepare for perpetual arguments with the admitting hospitalist for the next several eternities: “Could you go ahead an get a CTPA? You know, 17% of patients with syncope have PE.”

I’d like to tell you they’re wrong, and this study is somehow flawed, and you’ll be able to easily refute their assertions. Unfortunately, yes, they are wrong, and this study is flawed – but it won’t make it any easier to prevent the inevitable downstream overuse of CT.

The primary issue here is the almost certain inappropriate generalization of these results to dissimilar clinical settings. During the study period, there were 2,584 patients presenting to the Emergency Department with a final diagnosis of syncope. Of these, 1,867 were deemed to have an obvious or non-serious alternative cause of syncope and were discharged home. Thus, less than a third of ED visits for syncope were admitted, and the admission cohort is quite old – with a median age for admitted patients of 80 (IQR 72-85). There is incomplete descriptive data given regarding their comorbidities, but the authors state admission criteria included “severe coexisting conditions” and “a high probability of cardiac syncope on the basis of the Evaluation of Guidelines in Syncope Study score.” In short, their admission cohort is almost certainly older and more chronically ill than many practice settings.

Then, there are some befuddling features presented that would serve to inflate their overall prevalence estimate. A full 40.2% of those diagnosed with pulmonary embolism had “Clinical signs of deep-vein thrombosis” in their lower extremities, while 45.4% were tachypneic and 33.0% were tachycardic. These clinical features raise important questions regarding the adequacy of the Emergency Department evaluation; if many of these patients with syncope had symptoms suggestive of PE, why wasn’t the diagnosis made in ED? If even only the patients with clinical signs of DVT were evaluated prior to admission, those imaging studies would have had a yield for PE of 65%, and the prevalence number seen in this study would drop from 17.3% to 10.3%. Further evaluation of either patients with tachypnea or tachycardia might have been similarly high-yield, and further reduced the prevalence of PE in admitted patients.

Lastly, any discussion regarding a prevalence study requires mention of the gold-standard for diagnosis. CTPA confirmed the diagnosis of PE in 72 patients in this study. Of these, 24 involved a segmental or sub-segmental pulmonary artery – vessels in which false-positive results typically represent between one-quarter to one-half. Then, V/Q scanning was used to confirm the diagnosis of PE in 24 patients. Of these, the perfusion defect represented between 1% and 25% of the area of both lungs in 12 patients. I am not familiar with the rate of false-positives in the context of small perfusion defects on V/Q, but, undoubtedly a handful of these would be as well.  Add this to the inadequate ED evaluation of these patients, and suddenly we’re looking at only a handful of true-positive occult PE in this elderly, chronically ill cohort with syncope.

My view of this study is that its purported take-home point regarding the prevalence of PE in syncope is grossly misleading, yet this “one in six” statistic is almost guaranteed to go viral among those on the other side of the admission fence.  This study should not change practice – but I fear it almost certainly will.

“Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope”

When Cured Meat Kills

We’ve seen cured meat as a lifesaver – a last-resort hemostatic agent for refractory epistaxis. But, cured meat has a dark side, as well.

In this case report, a father and daughter arrive to the Emergency Departent short of breath, cyanotic, and hypoxic after ingesting “beef jerky”. Poisoned! But how?

This family had prepared their own, homemade beef jerky – and inadvertently oversalted the meat. In this case, the salt – sodium nitrate – resulted in methemoglobinemia. Rather than use 0.05 ounces of sodium nitrate to 5lbs. of food consistent with food preparation guidelines, these folks unwittingly added a full 1 ounce. This twenty-fold overdose resulted in methemoglobin levels >30% in each. Both recovered after treatment with methylene blue.

Other foods previously implicated in inadvertent sodium nitrate poisoning: blood sausage, kosher sausage, and bamboo shoot soup.

“The Beef Jerky Blues: Methemoglobinemia From Home Cured Meat”

@emlitofnote at #ACEP16

Off to Las Vegas!

Come say “Hello” anywhere you see me, or at:

FOAMBar, Monday October 17th, 1-2:30pm at the Annals of Emergency Medicine Kiosk

#ACEP16 Social Media Meet-Up, Monday October 17th, 6pm at the Border Grill at Mandalay Bay

Annals of Emergency Medicine Podcast, with Rory Spiegel, Tuesday October 18th, 12-1:00pm at the recording booth in the ACEP16 Exhibit Hall

See you soon!

The Mechanical Doctor Turk

Automated diagnostic machines consisting of symptom checklists have been evaluated in medicine before. The results were bleak:  symptom-checkers put the correct diagnosis first only 34% of the time, and had the correct diagnosis in the top three only 51% of the time.

However, when these authors published their prior study, they presented these findings in a vaccuum – despite their poor performance, how did this compare against human operators? In this short research letter, then, these authors, compare the symptom-checker performance against clinicians contributing to a sort of crowdsourced medical diagnosis system.

And, at least for awhile longer, the human-machine is superior than the machine-machine. Humans reading the same vignettes placed the correct diagnosis first 72.1% of the time, and in the top three 84.3% of the time.

With time and further natural language processing and machine learning methods, I expect automated diagnosis engines to catch up with humans – but we’re not there yet!

“Comparison of Physician and Computer Diagnostic Accuracy.”

Antibiotics for Diverticulitis, the End Must Be Near

I’ve talked about the inflammatory vs. infectious theory for diverticulitis in a couple of my national and international presentations, and I’ve talked about the evidence supporting an observation-only strategy. Until now, that evidence was mostly a single-center randomized trial from Finland, followed by an observational report from the same.

Now, this non-treatment paradigm has migrated across the little river between Scandanavia and Europe, and has been taken up by the Dutch in this latest randomized trial. In this trial, 22 clinical sites randomized 570 patients with uncomplicated diverticulitis to either admission for antibiotic treatment, or observation and disposition per clinical stability. The antibiotic chosen was amoxicillin-clavulanic acid, with ciprofloxacin/metronidazole in the case of allergy. The primary outcome was time to recovery, with secondary outcomes relating to complications and recurrence.

Of the 570 randomized, ultimately, only 528 were analyzed. A handful were lost to follow-up, and then 35 patients withdrew from the study after allocation – 22 in the observation cohort and 13 in the antibiotics cohort. There were minor, potentially confounding differences between the two cohorts analyzed – about 8% more of the antibiotics cohort suffered from mild or severe comorbid disease.

Most patients selected for observation were admitted – with only 13% managed as outpatients. With respect to the primary outcome, there was no difference between cohorts in time to recovery. There were also few statistically significant differences in secondary outcomes, although the numbers suggest a small magnitude of harm relating to observation. Complications – ongoing diverticulitis within 6 months, need for sigmoid resection, and hospital readmission – all favored the antibiotic cohort by small, non-significant amounts. Conversely, morbidity numbers generally favored the observation cohort – relating mostly to antibiotic-related adverse effects.

Regardless, the sum of benefits and harms – in the context of the other evidence – supports antibiotic-free strategies for uncomplicated diverticulitis.

“Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis”

Finding the Holes in CPOE

Our digital overlords are increasingly pervasive in medicine. In many respects, the advances of computerized provider order-entry are profoundly useful: some otherwise complex orders are facilitated, serious drug-interactions can be checked, along with a small cadre of other benefits. But, we’ve all encountered its limitations, as well.

This is a qualitative descriptive study of medication errors occurring despite the presence of CPOE. This prospective FDA-sponsored project identified 2,522 medication errors across six hospitals, 1,308 of which were related to CPOE. These errors fell into two main categories: CPOE failed to prevent the error (86.9%) and CPOE facilitated the error (13.1%).

CPOE-facilitated errors are most obvious. For example, these include instances in which an order set was out-of-date, and a non-formulary medication order resulted in delayed care for a patient; interface issues resulting in mis-clicks or misreads; or instances in which CPOE content was simply erroneous.

More interesting, however, are the “failed to prevent the error” issues – which are things like dose-checking and interaction-checking failures. The issue here is not specifically the CPOE, but that providers have become so dependent upon the CPOE to be a reliable safety mechanism that we’ve given up agency to the machine. We are bombarded by so many nonsensical alerts, we’ve begun to operate under an assumption that any order failing to anger our digital nannies must be accurate. These will undoubtedly prove to be the most challenging errors to stamp out, particularly as further cognitive processes are offloaded to automated systems.

“Computerized prescriber order entry– related patient safety reports: analysis of 2522 medication errors”

Which is Safer – Rivaroxaban or Dabigatran (or Neither?)

The world of anticoagulation turned upside-down with dabigatran, and continued with the Factor Xa inhibitors: rivaroxaban, apixaban, and edoxaban. While RE-LY and its ilk showed, in the settings of controlled clinical trials, that these new agents were potentially superior, or at least non-inferior, to warfarin – which is best? Do we have any idea?

Unfortunately, such comparative effectiveness work is sadly lacking, and we are forced to try and glean safety data indirectly following approval. This study pools Medicare beneficiaries using the new agents for stroke prevention in the setting of nonvalvular atrial fibrillation, and attempts to observe “real world” outcomes.

The winner on stroke prevention: rivaroxaban, by a hair. The winner on bleeding: dabigatran, by a long shot, both intra-cranial and extra-cranial. Overall mortality, then, slightly favored dabigatran.

These data are retrospective and tortured by statistical matching methods, so their reliability is hardly bulletproof. What this does raise are more questions about the appropriate usage of these new agents – and further emphasizes the importance of prospectively performed patient-centered effectiveness research.

“Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation”

Don’t CTPA With Your Gut Alone

Many institutions are starting to see roll-out of some sort of clinical decision-support for imaging utilization. Whether it be NEXUS, Canadian Head CT, or Wells for PE, there is plenty of literature documenting improved yield following implementation.

This retrospective evaluation looks at what happens when you don’t obey your new robot overlords – and perform CTPA for pulmonary embolism outside the guideline-recommended pathway. These authors looked specifically at non-compliance at the low end – patients with a Wells score ≤4 and performed with either no D-dimer ordered or a normal D-dimer.

During their 1.5 year review period, there were 2,993 examinations and 589 fell out as non-compliant. Most – 563 – of these were low-risk by Wells and omitted the D-dimer. Yield for these was 4.4% positivity, compared with 11.2% for exams ordered following the guidelines. This is probably even a high-end estimate for yield, because this includes 8 (1.4%) patients who had subsegmental or indeterminate PEs but were ultimately anticoagulated, some of whom were undoubtedly false positives. Additionally, none of the 26 patients that were low-risk with a normal D-dimer were diagnosed with PE.

Now, the Wells criteria are just one tool to help reinforce gestalt for PE, and it is a simple rule that does not incorporate all the various factors with positive and negative likelihood ratios for PE. That said, this study should reinforce that low-risk patients should mostly be given the chance to avoid imaging, and a D-dimer can be used appropriately to rule-out PE in those where PE is a real, but unlikely, consideration.

“Yield of CT Pulmonary angiography in the emergency Department When Providers Override evidence-based clinical Decision support”