Tuesday, February 14, 2012

Automagical Problem Lists

This is a nice informatics paper that deals mostly with problem lists.  These are meticulously maintained (in theory) by inpatient and ambulatory physicians to accurately reflect a patient's current medical issues.  Then, when they arrive in the ED, you do your quick chart biopsy from the EMR, and you can rapidly learn about your patient.  However, these lists are invariably inaccurate - studies show they'll appropriately be updated with breast cancer 78% of the time, but as low as 4% of the time for renal insufficiency.  This is bad because, supposedly, accurate problem lists lead to higher-quality care - more CHF patients receiving ACE or ARBs if it was on their diagnosis list, etc.

These authors created a natural language processing engine, as well as a set of inference rules based on medications, lab results, and billing codes for 17 diagnoses, and implemented an alert prompt to encourage clinicians to update the problem list as necessary.  Overall, 17,043 alerts were fired during the study period, and clinicians accepted the recommendations of 41% - which could be better, but it's really quite good for an alert.  As you might expect, the study group with the alerts generated 3 times greater additions to the patient problem lists.  These authors think this is a good thing - although, I have seen some incredible problem list bloat.

What's interesting is that a follow-up audit of alerts to evaluate their accuracy based on clinical reading of the patient's chart estimated the alerts were 91% accurate - which means all those ignored alerts were actually mostly correct.  So, there's clearly still a lot of important work that needs to go into finding better ways to integrate this sort of clinical feedback into the workflow.

So, in theory, better problem lists, better outcomes.  However, updating your wife's problem list can probably wait until after Valentine's Day.

"Improving completeness of electronic problem lists through clinical decision support: a randomized, controlled trial."

Sunday, February 12, 2012

Eat Your Vegetables!

This may be a candidate for an IgNobel Prize, published as a research letter in JAMA: how to get schoolchildren to eat their vegetables!

Control group: normal lunch trays.  Intervention group: lunch trays with compartments specifically labeled with photographs of green beans and carrots.  Results: success!  Green bean choice went from 6.3% of children to 14.8% of children, and carrot choice went from 11.6% to 36.8%.  Amount of green bean and carrot consumption was stable on an individual basis, resulting in an overal net consumption of both green beans and carrots by their cohort.

Of course, this was only a single day intervention - my guess is the effect would fatigue - but, at least, for one day, children ate more vegetables.

This has far-reaching implications for Emergency Medicine.

"Photographs in Lunch Tray Compartments and Vegetable Consumption Among Children in Elementary School Cafeterias"

Friday, February 10, 2012

Ketamine For Acute Pain Control

So, there's effective.  And then there's effective, but insane.  I am aware that low-dose continuous infusions of ketamine are excellent adjunctive therapies to decrease narcotic use in trauma and orthopedic patients, but I have never seen ketamine used in bolus form to treat acute pain in the out-of-hospital setting.

But, that's what we have.  After an initial 5mg IV bolus of morphine, patients were randomized to receive either additional morphine or ketamine boluses - 1 to 5mg of morphine every five minutes, or 10 to 20mg of ketamine every three minutes.  Pain medication was given per protocol until relief or adverse events.  And, the ketamine group was superior - pain scores dropped 5.6 points on the numerical verbal scale with ketamine and 3.2 with morphine.

However, the ketamine group also had a 39% incidence of adverse effects, compared with 14% of the morphine group.  The morphine group had mostly nausea, with one patient exhibiting a change in level of consciousness.  However, the ketamine group had multiple patients with decreased consciousness, disorientation, and emergence phenomena.  So, while the editor capsule summary states "Supplementing out-of-hospital opiods with low-dose ketamine is an effective strategy to mitigate trauma pain" he is technically correct, but the insanity of this strategy is trying to make an evidence-based decision about intracranial imaging after iatrogenically altering your patients prehospital.

What I appreciate best about this paper is how aggressive the paramedics were with treating pain - the patients receiving morphine averaged 14.4mg, with a standard deviation of 9.4mg!  I see my residents ordering 2mg at a time and it drives me nuts.

"Morphine and Ketamine Is Superior to Morphine Alone for Out-of-Hospital Trauma Analgesia: A Randomized Controlled Trial"

Wednesday, February 8, 2012

Finally, A Useful TPA Concept

Frequent readers of this site will be familiar with my distaste for TPA in stroke - not because I think it's a therapeutically invalid option, but mostly because its use is being promoted beyond its original scope, too many stroke mimics are receiving TPA, and the published literature supporting new "innovations" in TPA have a skewed interpretation of "safe".

This paper from Stroke is the first I've seen that finally tries to determine whether a patient will actually benefit from TPA in acute ischemic stroke, rather than chaining together studies in a logical fallacy to extend treatment to a larger population.  These authors have developed the "iScore" (no affiliation with Apple Computer), which was developed by logistic regression to predict outcomes in patients with ischemic stroke not treated with TPA.  The components include age, stroke severity, stroke subtype, and medical comorbidities in a scoring system that defines low (>50% good outcome), moderate (10-50%), and high-risk (<10%) groups.

These authors then apply the iScore in a retrospective fashion to their stroke database, looking both at their TPA recipients as well as propensity-matched patients in their non-TPA group.  Now, it's not exactly prospective, randomized, controlled, but it's an interesting trick that provides a limited comparison.  The stroke patients in the low-risk group had ~12% absolute outcomes benefit from TPA, the, the moderate group ~10% benefit, and the high-risk group ~2.6%.  There were no statistically significant benefits (or harms) from TPA in the high-risk group, but those patients were >90% disabled or dead at 30 days, regardless of therapy.

One weakness the authors point out in their study - it is sometimes clinically difficult to determine stroke subtype in the acute setting based solely off clinical presentation, particularly when baseline functional status is not perfect.  Regardless, it's nice to see a paper that looks at better individualizing the risk/benefit equation for TPA - seems as though the 400 patients in the high-risk group did not benefit from spending $2000 on alteplase or the associated increased DRG billing associated with it.  Money isn't free, after all....

"The iScore Predicts Effectiveness of Thrombolytic Therapy for Acute Ischemic Stroke"

Monday, February 6, 2012

Would Free Medications Help?

It's too bad this study doesn't actually look at what I would have hoped it would - but it's interesting, nonetheless.  One of my hospitals is a true safety-net hospital and we see, repeatedly, repeatedly, repeatedly, the complications of neglected chronic disease.  One of our frequent laments is whether the costs of recurrent acute hospitalization wouldn't be prevented a hundred times over if we'd simply sink some costs into preventative maintenance care, free medications, etc.

This study almost looks at that.  This is from the NEJM which compared the outcomes of patients following myocardial infarction, and they follow a group which receives completely free medication and a group that does not.  Unfortunately, the group that does not receive free medications is still receiving heavily subsidized medication support, and is only responsible for a co-pay.

Despite only needing to come up with a co-pay, there's a significant difference in medication compliance, with an average absolute difference in full adherence with medications of ~5-6%.  With this minimal absolute difference in adherence, the full adherence group had significantly fewer future vascular events - mostly from stroke and myocardial infarction - approximately a 1% absolute decrease.  There was a non-significant decrease in total costs associated with the patients who were on the full-coverage medication plan.

Now, they don't follow-up any medication-related adverse events, so this is the most optimistic interpretation of benefits of full-coverage, but it would seem that it is overall cheaper and more beneficial to supply medications for free.  And, it makes me wonder what the results of a similar cost/health-benefit study would show in our safety-net population.

"Full Coverage for Preventive Medications after Myocardial Infarction"

Saturday, February 4, 2012

Safety-Nets & ED Length of Stay

This is a relatively intriguing public policy article in JAMA following up in a timely fashion regarding the new CMS Emergency Department quality measures.  These new measures include various time-to-X measures, including length of stay, length of time to admission from bed request, etc.  There is some concern that these quality measures may be tied to federal funding, unfairly targeting "safety-net" hospitals that are not at baseline provided with the resources to address patient flow issues.

This article is a review of the NHAMCS database, a national probability sample survey of patient visits, looking at independent predictors of increased length of stay in patients admitted and discharged from the Emergency Department.  Based on the review of this sample, they do not see a significant difference in ED length of stay - and conclude that these quality measures should not be of concern to "safety net" EDs.  However, these general time-based measures mask most of the problems encountered in "safety net" institutions.

There are some baseline differences in patient characteristics between the safety-net and non-safety-net hospitals in their sample, and they tend to work in favor of safety-net hospitals.  The safety net hospitals in this sample tended to have younger patients with lower triage acuities, which should work in favor of reduced ED overall average length of stay.  My anecdotal experience suggests that, once the quality measures track more detailed ED transit times, I believe we will see more significant deficiencies drop out in the safety-net group.

"Association of Emergency Department Length of Stay With Safety-Net Status"

Thursday, February 2, 2012

Half of Fractures Received No Analgesia

One of the new CMS quality measures involves measuring time to receipt of pain medication for patients diagnosed with long bone fractures.  While this isn't the most exciting quality measure in terms of outcomes, it is probably a reasonable expectation that fractures receive pain control, and it might be a plausible surrogate marker for overall Emergency Department operations - at least, until the powers that be focus solely on these few measures at the expense of other clinical operations.

This article is a retrospective review of all pediatric long bone fractures evaluated at their facility.  They used the electronic medical record to track the timing of any "adequate" pain medication.  They have a specific weight-based definition of "adequate" for IV narcotics, PO narcotics, and non-narcotic analgesics, and they specifically break down pain medication received within 1 hour of arrival.

They identified 773 cases in their records, and by their definitions, 75 patients received an "adequate" dose of pain medication within 1 hour.  One can quibble with their definition of "adequate" because there is a range of pain needs that don't necessarily require maximal dosing.  But, you cannot quibble with the fact that 353 children received no pain medication at all within an hour of ED arrival (or prior to ED arrival).  Certainly, some individual factors at play would result in reasonable delays to pain medication, but definitely not nearly half.

"Analgesic Administration in the Emergency Department for Children Requiring Hospitalization for Long-Bone Fracture"

Tuesday, January 31, 2012

Congratulations Michelle Lin!

One of the prominent medical education bloggers - who is really much more than just a great blogger - has been awarded an endowed chair by the University of San Francisco School of Medicine to support her medical education efforts.  This is notable to me because, in the press release, they specifically mention part of the mission of the award specifically notes "keep up her active 'Academic Life in Emergency Medicine' blog".  

It's fascinating to see how alternative publication sources and online media are influencing the perception of "academic achievement".  For instance, my JAMA commentary - a journal with Impact Factor of 30 - has been viewed as full text or downloaded as PDF ~2000 times in the last six months.  This blog, on the other hand, exceeds 400 views per day.  There's no question which has been more rewarding to my brief career so far.

Again, congratulations to Michelle!  Now she has to do, not just great things, but insanely great things!  (also, go Stanford!)

"Inaugural Academy Chair in Emergency Medicine"

Dosing Errors With IV Acetaminophen

As a follow-up to the recent posting regarding IV acetaminophen, this recent article in Pediatrics highlights a few case reports regarding overdose.

According to the authors, the most frequent error in administration when the order is written in milligrams, but the medication order is administered in milliliters - a 10-fold overdose.  All of the patients in this series received n-acetylcysteine infusion, and none appeared to suffer significant liver injury specifically attributed to the overdose.

Another lovely demonstration of the potential for iatrogenic injury in healthcare.  Even the most apparently benign orders can have unanticipated harmful consequences, and a demonstration how intravenous administration is at higher risk.

"Intravenous Acetaminophen in the United States: Iatrogenic Dosing Errors"

Monday, January 30, 2012

Scattering Tacks In The Road

I might be the only one who finds the irony in this, but, at long last, we have a rapid assay to estimate the activity of the new oral direct thrombin inhibitor, dabigatran.

Just to recap, with coumadin, we can measure PT/INR; for heparin, PTT; and for enoxaparin and its brood, (less rapidly) Factor Xa levels.

Now, we have the HEMOCLOT test.

Created and marketed by Boehringer Ingelheim, the manufacturers of dabigatran. (Edit: sorry!  This is not manufactured by Boehringer - they only published this study.  Boehringer is, however, working on a FAB antibody to dabigitran to use as an antidote, however.)

It's a beautiful piece of business to put a dangerous medication on the market, and then sell the only practical means of monitoring levels.

"Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran."

Sunday, January 29, 2012

Further Harms of IV Contrast

Radiation: cancer.  Iodinated contrast: renal injury.  Now, iodinated contrast: thyroid dysfunction.

This is a retrospective, matched, case-control study performed in Boston to evaluate any association between CT administration of IV contrast and hyper- and hypothyroidism.  They gathered 178 new-onset hyperthyroid and 213 new-onset hypothyroid cases and statistically matched them in their patient database to euthyroid "controls".  There were no significant differences between the groups at baseline - although, they don't match between terribly many clinical variables.

In the end, they find the patients who developed thyroid dysfunction had higher rates of iodinated contrast exposure - primarily from cardiac catheterization, but also from CT scans.  For hyperthyroidism, 6.1% of controls had contrast exposure, whereas 10.7% of their hyperthyroid patients had received contrast.  For hypothyroidism, the numbers are 8.5% controls vs. 12.2% hypothyroid.

It's a bit of a backwards way to approach it - ideally they'd compare a group receiving iodinated contrast against a group that did not, and observe the incidence of thyroid dysfunction - but it seems that's not the format of data to which they have access.  In any event, the physiologic basis is reasonable for the association - more data needed to confirm these findings.

Just in case you needed another reason to not order a contrasted CT.

"Association Between Iodinated Contrast Media Exposure and Incident Hyperthyroidism and Hypothyroidism"

Friday, January 27, 2012

The Harmful Rush To Hypothermia

Mild hypothermia seems to be a clinically useful therapeutic modality for improving neurologic outcomes following return of spontaneous circulation in cardiac arrest.

However, like any emerging therapy, the precise details regarding which patients are most likely to benefit and how to best apply it are still in flux.  This is an Italian registry study that gathered prospective data on all individuals at 17 hospitals who underwent therapeutic hypothermia following cardiac arrest.  The specific question asked by these authors is regarding the optimal time for initiation of hypothermia - using 2 hours after ROSC as their cut-off.

Turns out, they found an association between "early" (< 2 hours to initiation) therapeutic hypothermia and worsened mortality - 47% mortality vs. 23% mortality in the ICU.  This ~20% absolute difference in outcomes holds up over the 6 month follow-up period.  No difference in cerebral performance category is observed between the two groups, although there is a nonsignificant trend towards better CPC in the "early" group.

Hard to know what to actually do with data.  Is early hypothermia truly harmful?  Because of the observational design, it's hard to say whether there aren't confounding baseline differences in the "late" population that produces selection bias for higher survival rates.  Or, are the mortality rates higher in the early group because patients are incompletely resuscitated before initiating hypothermia?

More questions, no answers.

"Early- versus late-initiation of therapeutic hypothermia after cardiac arrest: Preliminary observations from the experience of 17 Italian intensive care units"

Wednesday, January 25, 2012

Helping TPA Help Patients Bleed

TPA for stroke, the miracle therapy that has your Emergency Department shoving people out of the way to drag someone to the CT scanner within 10 minutes of ED arrival, isn't good enough.  After all, TPA, a "clot-busting" drug that saves dying brain cells by restoring flow, only completely opens up the occluded target vessel within 2 hours in 20 to 30% of the cases, with partial recanalization occurring in up to 60%.  So, the "Texas Biotechnology Corporation" and their equity stakeholders at The University of Texas Health Science Center at Houston have undertaken a project to add additional anticoagulation - argatroban - to TPA in the interests of actually delivering on the "clot-busting" part of the promise.

This is an open-label, pilot safety study enrolling 65 patients.  It was stopped after the first 15 patients for safety review after two experienced intracranial hemorrhage.  After review, it was restarted with additional restrictions on only giving it to milder stroke patients with NIHSS score < 15 (right hemisphere) and < 20 (left hemisphere).  All patients subsequently underwent vascular imaging to assess for recanalization, and the authors reported safety outcomes for events within seven days.

The good news: sorry, no good news.  14 had sustained complete recanalization at 2 hours - 30%.  An additional 12 patients had sustained partial recanalization at 2 hours - 25%.  Of course, this isn't a controlled trial, so comparison to the recanalization rates demonstrated in existing literature is flawed - but it's certainly not an order of magnitude better.

But, this wasn't an efficacy trial, this was a safety trial.  And seven patients met the ultimate safety endpoint of death - 10%.  For intracranial hemorrhage, 19 (29%) patients had ICH, 3 of which were symptomatic. Because NIHSS score predicts bleeding, we can compare to the NINDS trial TPA group, whose median NIHSS score of 14 compared with this trial's median of 13.  The NINDS trial showed a 10.8% rate of ICH and about 4% mortality at 7 days.

Seems like a treatment with triple the ICH and double the mortality, and that isn't proven superior, shouldn't support the conclusion of "potentially safe" or that "Further study of this treatment combination appears warranted."

"The Argatroban and Tissue-Type Plasminogen Activator Stroke Study : Final Results of a Pilot Safety Study"

Monday, January 23, 2012

Progress In Combating Publication Bias

...if from abysmally terrible to embarrassingly bad represents progress.

A certain subgroup of trials registered with ClinicalTrials.gov are required to report their results within one year of conclusion of study.  These mandatory-reporting requirements include clinical trials of FDA-approved drugs, devices, or biological agents that have at least one study site in the U.S.  In the future, this will expand to include unapproved drugs.  These requirements, ideally, should help reduce publication and sponsorship bias by ensuring result availability regardless of ability to obtain publication or the desire of a pharmaceutical corporation to publish negative results.

And, so far, these authors discover that it is a tremendous success - trials subject to the mandatory reporting complied with the requirement in twice as many of identified trials as compared with registered trials that were not required to report results.

Unfortunately, twice as many was only 22% compared with 10%.  So, there's still quite a ways to go before we have full transparency in clinical trial reporting - but it's "progress."

"Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study"

Saturday, January 21, 2012

Observation For Anticoagulated Head Trauma

Coming in a future issue of Annals, the Editor's capsule summary: "Delayed intracranial hemorrhage is common after minor head injury when patients are receiving warfarin. A minimum protocol of 24-hour observation followed by repeated scanning is necessary to detect most such occurrences."

Now, this isn't a terribly management agnostic statement.  It does not specifically state this is something we need to start doing - but it rather implies that, if you don't, you'll be missing this "common" phenomenon.  It isn't an alien concept - since 2002, the European Federation of Neurological Societies has recommended admission for observation after minor head trauma - but it's certainly not the standard of care here.  So, for the Annals editors to state that observation and repeat scanning is "necessary", they must obviously have excellent evidence.

Or they have an observational case series consisting of 87 patients from Italy.

These authors present a prospective case series of all patients at their institution who were admitted for observation specifically for minor head trauma while on oral anticoagulation.  At the time of repeat CT scanning 24 hours later, the authors report five of them had new bleeding detected.  In addition, two patients who were discharged after two negative CT scans returned with symptomatic bleeding, one at two days, and one at eight days.

So, should we be observing and rescanning every anticoagulated minor head trauma patient as these authors suggest (and as they do in Europe)?  If you practice in a zero-miss litigation environment, this article and ACEP's apparent embrace of the results will hamstring your decision-making.  This data is completely inadequate to change clinical practice, and inconsistent with prior literature documenting delayed hemorrhage in only 2 of 137 patients.

Clearly, some patients will have delayed bleeding - a subset of which will be clinically significant.  However, we simply cannot expose all anticoagulated patients with minor head trauma to the harms and costs of hospitalization.  Better studies are required to prospectively determine the risk profile of patients who require further observation in a hospital setting, rather than a watchful discharge home.

"Management of Minor Head Injury in Patients Receiving Oral Anticoagulant Therapy: A Prospective Study of a 24-Hour Observation Protocol"

Friday, January 20, 2012

Correspondence in Nature Reviews Neurology

After publishing an article that alluded to the "antipathy" of emergency physicians towards TPA in acute ischemic stroke, the editors were nice enough to publish my correspondence defending the reasonableness of a cautious attitude.

"Skepticism about thrombolytics in stroke is not unreasonable."

Thursday, January 19, 2012

EMLit on ERCast

It's like podcasting with Jack Buck - always a pleasure.  Rob Orman does great work, and he's got a huge archive of invaluable wisdom accumulated through his podcasts.  I hope you enjoy our most recent episode together.

"Decision Tools: PERC, NEXUS and CURB-65"

Lies, Damned Lies, and Tamiflu (oseltamivir)

Receiving quite a bit of press yesterday, and rightfully so, the Cochrane Collaboration published their analysis of oseltamivir - the miracle influenza antiviral that (at great cost) is part of our nation's strategic stockpile for an influenza pandemic.  The story is interesting both regarding what they found, and what they didn't find.

As for the data from the review, the numbers are similar to what we've been basing our practice upon - oseltamivir significantly shortens the length of time until symptom improvement from 160 hours to 139 hours.  However, it did not demonstrate any difference in hospitalization rates.  Additionally - whether through study bias or by direct medication effects - the oseltamivir groups were significantly less likely to have a confirmed diagnosis of influenza.

So, this suggests that it's a little troubling that we've gone to all the expense to stockpile this expensive medication that does not appear to reduce hospitalizations from influenza - and it remains an individual decision whether that extra day of symptom improvement is worth exposure to the side effects of the medication.  But the reason this is national news is that Roche pharmaceuticals refused to supply the promised clinical data requested by the Cochrane Collaboration; the published analysis is based on 15 oseltamivir studies with complete information, and excludes 42 other studies with discrepancies in the data.  This sort of behavior is just another representative sample of the unethical, but completely understandable, profit-motivation of pharmaceutical corporations protecting their financial interests.

I would be greatly surprised if the clinical data Roche is holding onto supports oseltamivir efficacy.

"Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children - a review of clinical study reports"

"Flu Drugs: Search for evidence goes on"

Tuesday, January 17, 2012

100,000 Incorrect TIA Diagnoses Every Year

...if we extrapolate the results from this single-center study to the entire United States.

In Annals this month, a chart review of the "discordance" between the final neurologist "gold standard" diagnosis and the provisional Emergency Department diagnosis.  Apparently, in Cleveland, 36% of the patients receiving an initial diagnosis of transient ischemic attack in the Emergency Department are subsequently evaluated by a neurologist and given an alternative diagnosis.  As the authors note in their introduction, the diagnosis of TIA is made 300,000 yearly - and if 36% of those cases are made incorrectly, then we're theoretically admitting 100,000 patients for extensive and expensive evaluation.

So, are they right?  Well, if the three neurologists responsible for 93% of their 427 evaluations are representative of the entire country, perhaps.  Or, if their chart review methods are adequate - as the authors note, one of their chart audits changed an abstracted diagnosis of TIA to "right hip pain" - then, perhaps.  If you ignore that ED physicians have a few minutes of history, examination, and limited imaging available at their disposal - compared with the neurologists that can subsequently perform any manner of inpatient studies that might uncover an alternative diagnosis mimicking a TIA - then, perhaps.

If neurologists are walking into the ED and evaluating patients under the same constraints as we are and producing this level of discordance, then we have a problem.  But, I don't think this study tells us anything we can use to evaluate ED physicians' ability to appropriately include or exclude TIA in the differential for neurologic complaints of a transient nature.

Somewhat disappointing that a small, retrospective chart review with results that might not be internally or externally valid are in the premier, #1 Impact Factor journal of our profession.

"Variables Associated With Discordance Between Emergency Physician and Neurologist Diagnoses of Transient Ischemic Attacks in the Emergency Department"

Sunday, January 15, 2012

PERC - Still (Mostly) Useless

...except, perhaps, in a risk-management sense - but, only if we keep beating it down into its narrowest application due to its terrible specificity.

This most recent Annals publishes a systematic review of the Pulmonary Embolism Rule-Out Criteria, a decision instrument recommended in ACEP's pulmonary embolism clinical guidelines as a reasonable tool to risk-stratify a patient into a so-called "zero-risk" population that does not require any testing - not even a D-dimer.  And, I think they do a reasonable job including studies and summarizing the data, especially considering the width of the error bars on a lot of these studies.

The key points - pooled sensitivity is 97% when applied to a low-risk (Wells, Geneva, gestalt, whichever) population with a negative LR of 0.18.  This means, if you had someone who you already didn't think had a PE and they meet PERC criteria, it helps you with your medicolegal documentation, since it's in ACEP's guidelines.  The negative LR is strong enough to be helpful - but when you're already looking at single-digit percentage risk for PE, the absolute reduction in risk is quite small.

The important point to hammer home is the positive LR is only 1.23, which makes it the D-dimer of decision instruments.  Please don't justify further work-up just because they fail PERC - it barely moves the needle with its terrible specificity.  You need to have another clinical justification for further work-up in pulmonary embolism.

As an aside, in this era of over-testing and over-diagnosis of PE, the diagnosis of PE isn't necessarily the ideal endpoint - what we should be following are patient-oriented outcomes such as death/heart failure in untreated PE in PERC-negative patients to truly make it a valid tool.

"Diagnostic Accuracy of Pulmonary Embolism Rule-Out Criteria: A Systematic Review and Meta-analysis"