Month: September 2018

The Appendix Strikes Back

The classic, time-honored treatments for appendicitis are various forms of shamanism – swallowing lead balls, drinking pounds of quicksilver in hot water, or the application of slain young animals to the abdomen. The disease course of the classic patient, then, was obviously poor. In modern times, appendectomy. Ultra-modern, you might say, is antibiotics. Unfortunately, while the recurrence rate after appendectomy is quite low, short-term recurrence after antibiotics is disquietingly high – leading to additional questions regarding the durability of cure.

So, here are the 5-year outcomes of those patients initially entered into the APPAC randomized clinical trial. There were 530 patients randomized between 2009 and 2012 to either appendectomy or antibiotic therapy. Of the initial 257 randomized to antibiotics, 256 completed 1 year follow-up, 70 (27.3%) with recurrent appendicitis. Now, at 5 years, 246 were contacted for follow-up, with an additional 30 having undergone appendectomy. All told, this brings the total to a failure rate of 39.1% of antibiotic therapy in the original cohort. These authors also report quality-of-life and complication outcomes, but, as with the original trial, these are skewed because the initial cohort routinely underwent open appendectomy rather than laproscopic.

So, it seems as though the appendix, once identified as misbehaving, is prone to do it again. This does not disqualify antibiotics-first as a viable strategy for the treatment of uncomplicated acute appendicitis, but it would seem the long-term durability is more a coin flip rather than a roll of the dice.  That said, as long-term data grows more robust, it continues to push us in the direction of at least offering the option to our patients.

“Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial”

https://jamanetwork.com/journals/jama/fullarticle/2703354

Clearing the Cervical Spine with Distracting Injuries

Ah, the “distracting” injury. An utterly subjective and modifiable component of cervical spine clearance in the NEXUS criteria. Is it an isolated finger dislocation? Is it a femur fracture? We’ve all seen patients writhing or stoic in the face of either. And, then, factor in any prehospital analgesia ….

This is a prospective, observational study coming out of the American Association for the Surgery of Trauma evaluating the effects of distracting injury on cervical spine clearance. For their purposes, the following injuries were considered “distracting”:

Skull fracture, >2 facial bone fractures, mandible fracture, intracranial hemorrhage (including subdural hematoma, epidural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, intraparenchymal hematoma), >2 rib fractures, clavicle fracture, sternal fracture, pelvic fracture, thoracolumbar spine fracture, intra-abdominal injury (including solid organ injury, hollow viscus injury, or diaphragmatic injury), femur fracture, tibia/fibula fracture, humerus fracture, radius/ulna fracture, and hip or shoulder dislocation.

The physical exam consisted of midline neck palpation and, absent any contraindication, active range of motion of the neck in flexion, extension and rotation. The cervical collar could be removed at the discretion of the treating team, but – in classic traumatology fashion – all patients underwent CT of the cervical spine, regardless of exam.

There were 2,929 blunt trauma patients with GCS ≥14, and 222 had cervical spine injuries identified on CT. Of these injuries, 25 were “missed” by the clinical exam. The “good news”: the rate of miss was “the same”, regardless of distracting injury – 0.7% vs. 1.3%. The bad news, of course, is that a normal physical examination missed 11% of cervical spine injuries. One patient whose injury would have otherwise been missed by a negative physical examination underwent operative intervention.

While there is some obvious spectrum bias associated with any observational cohort enrolled at trauma centers, it is still a reasonable estimate of the sensitivity and specificity of the physical examination. Clearly, it’s not bulletproof in the context of multi-system trauma – but, depending on the pretest likelihood of a cervical spine injury based on other presenting features, a distracting injury need not disqualify a patient from clinical clearance.

“Clearing the Cervical Spine in Patients with Distracting Injuries: An AAST Multi-Institutional Trial”

https://journals.lww.com/jtrauma/Abstract/publishahead/Clearing_the_Cervical_Spine_in_Patients_with.98558.aspx

Tenecteplase vs. Alteplase For … Stroke Mimics?

Bless their little hearts.

It’s almost as though this is a submission fo the IgNobel Prize, rather than a serious scientific manuscript. “How well does a medicine work when the patient doesn’t have the disease?” is basically a joke, right?

Not in the magical world of stroke neurology, replete with its array of meretricious interventions.

This is a secondary analysis of NOR-TEST, a phase III trial comparing alteplase with tenecteplase. A few folks believe tenecteplase has superior fibrinolysis to alteplase, and therefore ought to be potentially favored in acute ischemic stroke. NOR-TEST, for what it’s worth, could not detect any statistically significant difference between the two.

What is notable in this trial, of course, is the 17% rate of stroke mimics. And, this is a Very Important publication comparing the safety of these two medications when given to patients inappropriately. And, of course, there is no difference. There were three cases of intracerebral hemorrhage and three cases of extracranial bleeding, none of whom – you know – died, but were clearly all unnecessary iatrogenic injury.

Some more interesting notes, at least, from their analysis of stroke mimics. The average NIHSS in this entire study was 4, with the IQR for mimics 2-6 and for acute ischemia 2-8. There’s no useful evidence to suggest thrombolysis is superior to placebo in this sort of mild stroke cohort, but, here we are. Absent this evidence, some neurologists make an argument based on the Get With the Guidelines-Stroke registry, observing many patients with mild stroke are ultimately unable to be discharged to home due to persistent disability. In the NOR-TEST cohort of mimics, however, only 79% were assessed to have mRS 0-1 at 3 months, while their treated stroke cohort achieved mRS 0-1 only 60% of the time.  It would seem the base rate of mimic- or mild-stroke disability is effectively as observed in the GWTG-Stroke registry, regardless of treatment.

In sum, these authors have basically provided us with an unwitting glimpse into how acute stroke treatment has gone utterly off the rails in Norway.  Now, I wonder if they’re related to the group trying to push tPA in less than 20 minutes ….

“Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST)”

https://www.ncbi.nlm.nih.gov/pubmed/30019629

The Fluoroquinolone/Aortic Dissection Association

We’ve been hearing about elevated incidence of connective-tissue disorders in patients having been prescribed fluoroquinolones for quite some time, primarily in the context of tendonopathies. Now, with aortic dissection.

The differences are quite small, but probably real. This retrospective case-crossover from Taiwan included 1,213 patients hospitalized with aortic pathology, and compared their fluoroquinolone exposure with those who did not experience aortic dissection despite similar disease risk scores from a national database. Using their time-period referent design, patients were about twice as likely to have been exposed to a fluoroquinolone in the aortic pathology group.

This isn’t the only recent look at the association between fluoroquinolone exposure and aortic pathology. Combine this with the profound impact on gastrointestinal flora these broad-spectrum antibiotics have, and the reasons are just piling up to avoid fluoroquinolones whenever clinically reasonable.

“Oral Fluoroquinolone and the Risk of Aortic Dissection”
https://www.ncbi.nlm.nih.gov/pubmed/30213330

Starting Treatment on First-Time Seizures

We see a fair bit of ostensibly “first-time” seizure in the Emergency Department. With some room for nuance and debate, general practice is typically still to defer initiation of anti-epileptic therapy.

This decision analysis in the neurology literature ultimately comes to the alternative conclusion – initiation of AEDs is reasonable even absent a clear or likely diagnosis of epilepsy. Based on their cases and parameters regarding seizure recurrence, the degradation of quality-of-life relating to seizure recurrence, and the features of modern AEDs, these authors find in favor of initiation of AEDs. Specifically, they find the previous threshold of ≥60% or greater chance of seizure recurrence after a first seizure is likely too high, and 30-40% may be more reasonable.

These conclusions are appropriate, considering the decision analysis model parameters – but, of course, by definition they also depend on the validity of these parameters. Then, whether this decision analysis can be applied clinically in the Emergency Department is another question, considering the challenges with regard to determine whether a seizure is truly unprovoked. Regardless, as AEDs evolve, have fewer adverse effects, and reach generic status, more liberal strategies of AED initiation in the Emergency Department may be in our future.

“Antiepileptic drug treatment after an unprovoked first seizure: A decision analysis”
http://n.neurology.org/content/early/2018/09/12/WNL.0000000000006319

Adult Head CT Decision Instrument Showdown

Every country seems to have their own pediatric imaging rule for minor head trauma, featuring PECARN, CHALICE, and CATCH. Recently, a head-to-head-to-head comparison (no pun intended) found the clear winner was: clinical judgement in Australia and New Zealand. Adoption of any of the rules would not have reliably increased sensitivity, but all would dramatically increase imaging.

Now, what about adult head trauma? The same story of every-country-has-a-flavor seems to be the case, with the CT in Head Injury Patients rule, the New Orleans criteria, the Canadian CT Head rule, and the National Institute for Health and Care Excellence guideline. This time, we have the Dutch performing the comparison.

In this multicenter, observational study conducted in 2015 and 2016, the authors enrolled neurologically-intact patients aged greater than 16 years and presenting with blunt head trauma within 24 hours of injury. Clinical data with the elements necessary for each decision instrument were completed by treating clinicians and collected by study staff. Decisions to perform imaging were based on individual clinician discretion, but primarily based on the CHIP rule. Outcomes were ascertained by electronic record review.

There were 5,839 patients entered in their study database, 5,517 meeting eligibility criteria. At three centers, only patients undergoing CT were entered in the database, while the remaining six centers included a handful of patients who did not undergo CT. Obviously, this grossly limits the descriptive capacity of the study, as clearly a massive number of patients with minor head injury who did not undergo CT were not followed for outcomes.

Overall, 384 of the 3,742 patients undergoing CT had positive traumatic findings. Most were small skull fractures, but about half had intracranial bleeding of some variety or another, with a further 74 being judged potential neurosurgical lesions. The most sensitive of the decision instruments in this study was the New Orleans criteria, while NICE guidelines were the least. Of course, the New Orleans criteria also would have recommended CT in all but 189 patients, for a specificity of 4.2%.

Ultimately, there’s no clear “winner” in this study, and, unfortunately, there’s also no obvious superior “clinician judgement” comparison lurking. The underlying rate of imaging was effectively the same as CHIP, as this was the national guideline in the Netherlands at the time of the study. Whether this is the “best” depends on tolerance for risk and the reliability of their estimate of “potential neurosurgical lesion”. Then, regardless of the decision instrument chosen, each still recommends imaging in thousands of patients in order to pick up the few with positive findings. Considering data from children, it seems we ought to be able to do much better – but current practice does not appear to be moving in that direction.

“External validation of computed tomography decision rules for minor head injury: prospective, multicentre cohort study in the Netherlands”
https://www.bmj.com/content/362/bmj.k3527

Homeopathy and Cardiac Arrest

Following up on the most recently published prehospital trials, we’re going back to an article published a few months ago. We’ve seen the data regarding epinephrine versus placebo – some does something, nothing does nothing, but the benefit of either strategy is debatable. Is there a better way?

This little retrospective report looks at the middle ground – a “well, let’s try and give a little less” protocol implemented in the King County prehospital system. Moving from their original protocol based on 1mg dosing with intervals indicated by rhythm, they halved it to 0.5mg. This resulted in patients generally getting a mean dose of epinephrine of about 2.5-3mg per arrest, rather than the 3.5-4mg total prior to implementation.

Did any outcome – survival, or, more importantly, neurologically-intact
survival – change? Not reliably, no.

These data provide only the lowest level of evidence as applied to determining the most advantageous use of epinephrine in the prehospital setting. This neither confirms nor refutes the premise of their practice change, and provides little specific insight into where the serial dilution of epinephrine loses its potency. There may yet be a sweet spot where return of spontaneous circulation occurs with minimal collateral damage, but we’ll need to wait for future research to provide additional data.

“Lower-dose epinephrine administration and out-of-hospital cardiac arrest outcomes”
https://www.ncbi.nlm.nih.gov/pubmed/29305926