Monday, January 7, 2013

The Future of Heart Failure Admissions

At least, this is how Cardiologists think the Emergency Department should be handling heart failure in The Future.

Specifically, Cardiologists would like us to stop admitting patients with acute exacerbations of established heart failure – and, interestingly, they're a bit apprehensive about discharging them.  Their earth-shaking, practice-modifying innovation is this:  observation unit management.

This strategy is founded partly out of interest of the patient's well-being, but mostly out of interest for the hospital's financial well-being.  In general, heart failure remains one of the most difficult hospital readmissions to prevent.  This is important because, suddenly, readmissions within 30 days are no longer reimbursed by CMS.  Now, rather than, re-admit patients for free, they've decided the New Fabulous Idea is to place them in outpatient observation status – which is a lower level of reimbursement, but still better than nothing.  In addition to the other obviously indicated admissions, they also feel some of the gray area discharges would probably benefit from observation, appropriately noting heart failure patients discharged from the ED are at high risk of having subsequent worsening due to a variety of contributing factors.

Overall, as far as actual patient care, there's probably little difference – somewhat cynically, the entire strategy seems mostly to be an advisory on how to minimize the impact of reimbursement losses from readmissions.

"Is Hospital Admission for Heart Failure Really Necessary?  The Role of the Emergency Department and Observation Unit in Preventing Hospitalization and Rehospitalization"

And, just as a rather inspirational aside, this is one of the longest disclosures list I have ever seen for an author:
"Dr. Gheorgiade has received support from Abbott Laboratories, Astellas, AstraZeneca, Bayer Schering Pharma AG, Cardiorentis Ltd., CorThera, Cytokinetics, CytoPherx, Inc., DebioPharm S.A., Errekappa Terapeutici, GlaxoSmithKline, Ikaria, Intersection Medical, Inc, John- son & Johnson, Medtronic, Merck & Co., Inc., Novartis Pharma AG, Ono Pharmaceuticals USA, Otsuka Pharmaceuticals, Palatin Technologies, Pericor Therapeutics, Protein Design Laboratories, sanofi-aventis, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, Takeda Pharmaceuticals North America, Inc., and Trevena Therapeutics; and has received significant (>$10,000) support from Bayer Schering Pharma AG, DebioPharm S.A., Medtronic, Novartis Pharma AG, Otsuka Pharmaceuticals, Sigma Tau, Solvay Pharmaceuticals, Sticares InterACT, and Takeda Pharmaceuticals North America, Inc."

Friday, January 4, 2013

Angiography After Cardiac Arrest

This is the worst sort of paper – nuggets of truth mired in systematic flaws.  There's certainly no ill intent by the authors to mislead, it's simply the nature of this sort of retrospective review.

The PROCAT consortium has been publishing studies of their post-arrest protocols for several years.  They're huge proponents of early coronary angiography following resuscitation for out-of-hospital arrest – and this is another in a string of articles demonstrating that patients going to coronary angiography after out-of-hospital arrest have improved outcomes.  Of the 1274 patients in their cohort, 745 received early coronary angiography, 447 identified a culprit lesion, and 347 underwent PCI.  The survival rate was 46% in patients undergoing PCI.

However, this number is conflated by other confounding variables known to be associated with good outcomes following cardiac arrest – coronary lesions are likely to be associated with VT/VF, which were also associated with good outcomes.  Additionally, significantly more survivors received therapeutic hypothermia than non-survivors, illustrating the massive problem with viewing this sort of report with anything other than reasoned curiosity: rampant selection bias.  Patients survived because they were selected for interventions based on individualized prognostic features, treatments were not applied evenly across the population.

There is absolutely a subset of OHCA that benefits from early coronary angiography – but this benefit should not be generalized to the inappropriate allocation of resources associated with taking all OHCA to the cath lab after resuscitation.

"Benefit of an early and systematic imaging procedure after cardiac arrest: Insights
from the PROCAT (Parisian Region Out of Hospital Cardiac Arrest) registry"

Wednesday, January 2, 2013

The Latest Prognostication for Stroke

We have a fairly robust vascular neurology program at my institution, and – unsurprisingly – they're rather pro-thrombolysis.  While our disagreements over the efficacy of thrombolysis for acute strokes are generally set aside in a truce stemming from academic and research interests, the main philosophical difference between our services remains this: the difference between eligible and indicated.

Vascular neurology tends to treat these terms as synonymous regarding thrombolysis and acute stroke, while it's clear from the literature that not every patient benefits from thrombolysis.  The most recent issue of Neurology features another prognostic tool, the SPAN-100, which is the simplest by far: NIHSS + age.  If this score is >100, fewer patients will benefit from tPA than will be harmed.  There's a quality-of-life discussion to be had regarding individualized treatment decisions in SPAN-positive patients, and this is derived from a very small cohort, but it's consistent with the remaining literature.

The accompanying editorial is also pro-thrombolysis, but does recognize these scoring systems are important clinical tools in educating patients and families regarding the potential for benefits and harms. Most importantly, this table from the editorial summarizes the growing body of literature available to assist the decision-making process:

I look forward to seeing these develop such that clinicians have better tools with which to separate eligible from indicated.

"Stroke Prognostication using Age and NIH Stroke Scale: SPAN-100"

Monday, December 31, 2012

Evidence Summary for Bell's Palsy

Although the incidence of stroke in young people is rising, some of these "strokes" can still be clinically diagnosed with Bell's Palsy.

However, once the diagnosis is made, the practice variation is extensive.  In light of this, the American Academy of Neurology has published an update to their evidence-based guidelines for the treatment of Bell's Palsy.

Short answer:
 - Steroids are good, with a 12 to 15% increased chance of functional recovery.
 - Antivirals have no consistent evidence of benefit.

Long answer:
 - Only ~4% of Bell's Palsy sufferers are left with severe residual deficits, with the remainder fully recovering or with slight/mild deficits.  Some folks would pose the question whether any of these treatments are necessary, considering the minimal absolute benefits, even if relative benefits are consistent.

Another risk/benefit decision to discuss with patients.

"Evidence-based guideline update: Steroids and antivirals for Bell palsy : Report of the Guideline Development Subcommittee of the American Academy of Neurology"

Friday, December 28, 2012

Breast Cancer From Pediatric Trauma Imaging

Evaluations for significant pediatric blunt trauma tend to be rather rare.  However, one flip side to improved vehicular safety is that previously fatal accidents turn into diagnostic dilemmas with otherwise well-appearing children after horrific potential injury mechanisms.

This specific article tries to address the risk/benefit ratio for imaging the pediatric thoracic spine after trauma, with a focus on the lifetime excess attributable risk for breast cancer.  They used estimates of radiation to breast tissue from plain films and CT, and then applied the predictions from the BEIR VII report to determine EAR.  From all these various calculations, their worst-case scenario derived an excess of 79.6 cases of breast cancer per 10,000 CT scans in females aged less than 12 years.

Unfortunately, the proponents of CT imaging cite these studies and say we've done nothing but document theoretical risk (based on atomic bomb exposure) – while ignoring that the risk of missed injury is equally theoretical.  As usual, the prudent course of action is to perform additional testing only when explicitly indicated – the additional cases of breast cancer are not trivial, but neither are missed injuries.  The rate of additional breast cancer cases is certainly not so high that CTs should be skipped when clinically indicated.

"Theoretical Breast Cancer Induction Risk From Thoracic Spine CT in Female Pediatric Trauma Patients"

Wednesday, December 26, 2012

Predicting Immediate Improvement After tPA

tPA for stroke remains controversial, to say the least.  The reasons behind the Emergency Medicine/Neurology disconnect are complex and covered elsewhere.  Regardless, thrombolysis is here to stay – and probably helps some patients.  The hard part is finding those patients with the most favorable risk/benefit ratio.

This is a study that looked at diffusion-weighted imaging to try and predict which patients were most likely to rapidly improve with tPA.  These authors enrolled sixty-six patients with acute stroke eligible for tPA under the Japanese license and performed diffusion-weighted MRI on each of them.  Previous studies had suggested an ASPECTS score > 7 predicted response to tPA – and this study confirmed it.  Essentially, this translates as larger vascular territories showing greater improvement in NIHSS after tPA than smaller vascular territories.

There's a bit of a bias in this study, since smaller vascular territories may have produced smaller initial NIHSS.  The population was quite old for a stroke study – median age 79.  And, truly, the more interesting data presented is the breakdown demonstrating the massively favorable impact of early (within 1 hour) recanalization after tPA administration.

But, mildly interesting paper, important as part of a slow, gradual trend of attempts to delineate which patients have the best potential to benefit from tPA.

"DWI-ASPECTS as a Predictor of Dramatic Recovery After Intravenous Recombinant Tissue Plasminogen Activator Administration in Patients With Middle Cerebral Artery Occlusion"

Monday, December 24, 2012

Saving Lives Through More Sleep

Or, at least, that's the theory.  Ever since the infamous Libby Zion case – surely exemplar of similar occurrences throughout medicine training programs – institutional focus on resident workload and wellness has been emphasized as a surrogate marker for patient safety.  Better-rested residents, working fewer hours, will have fewer misses and derive more substantial benefit from their educational opportunities.

This randomized trial from the University of Pennsylvania evaluating the performance of the new protected sleep time afforded to interns under ACGME rules.  These authors used wrist-based sleep activity monitors to measure the cumulative sleep time on-shift for interns randomized to either traditional 30-hour blocks or blocks with a nap period between 12:30am and 5:30am.  The primary outcome was sleep obtained on shift, with secondary outcomes being total hours of sleep during a call cycle, and post-call scores on the Karolinska Sleepiness Scale.

Well, protected sleep time works – 2.86 vs. 1.98 hours of sleep at the VA hospital, and 3.04 vs. 2.04 at the University hospital, with significantly fewer no-sleep nights as well.  And, the Karolinska Sleepiness Scale means also favored the nap-time group 7.10 vs. 6.65 at the VA and 6.79 vs 5.91 at the University.

But, as I said before, these are surrogate markers for patient safety.  One extra hour of sleep?  Less than a full point on the KSS?  Let's look specifically at the subjective self-reported meaning of the KSS in the range these physicians were reporting:

  • 5 = neither alert nor sleepy
  • 6 = some signs of sleepiness
  • 7 = sleepy, but no effort to keep awake
  • 8 = sleepy, some effort to keep awake

Regardless of intervention group, they're ... pretty much a little sleepy, but not generally struggling to stay awake.  I remain a little skeptical this will account for a substantial improvement in patient safety – at least, at this single-residency experience.

"Effect of a Protected Sleep Period on Hours Slept During Extended Overnight In-hospital Duty Hours Among Medical Interns"

Friday, December 21, 2012

The AAP Policy on Firearm Safety

Might not it be helpful if, coincidentally, the Council on Injury, Violence, and Poison Prevention for the American Academy of Pediatrics had just updated their policy statement regarding firearm-related injuries?  Indeed, just two months ago, the AAP published an update, featuring a mere 66 citations worth of evidence, rather than politicized talking points.

A couple interesting statistics from their summary:
 - The firearm-associated death rate among youth ages 15 to 19 has fallen from its peak of 27.8 deaths per 100 000 in 1994 to 11.4 per 100 000 in 2009.
 - However, of all injury deaths of individuals younger than 20 years, still 1 in 5 were firearm related.
 - For youth 15 to 24 years of age, firearm homicide rates were 35.7 times higher than in other high-income countries.
 - For children 5 to 14 years of age, firearm suicide rates were 8 times higher, and death rates from unintentional firearm injuries were 10 times higher in the United States than other high-income countries. 
 - The difference in rates is postulated to the ease of availability of guns in the United States compared with other high-income countries.

Their recommendations section seems quite straightforward:
 - The most effective measure to prevent suicide, homicide, and unintentional firearm-related injuries to children and adolescents is the absence of guns from homes and communities.
 - Health care professionals should counsel the parents of all adolescents to remove guns from the home or restrict access to them.
 - Trigger locks, lock boxes, gun safes, and safe storage legislation are encouraged by the AAP.
 - Other measures aimed at regulating access of guns should include legislative actions, such as mandatory waiting periods, closure of the gun show loophole, mental health restrictions for gun purchases, and background checks.
 - The AAP recommends restoration of the ban on the sale of assault weapons to the general public.

Any chance policymakers might listen to the society of physicians "Dedicated to the health and well-being of infants, children, adolescents and young adults"?

"Firearm-Related Injuries Affecting the Pediatric Population"

Wednesday, December 19, 2012

Pain Control on the Wrong Track

Codeine, the oral narcotic analgesia that is long past its prime.  Approximately 8% of the caucasian population cannot metabolize codeine into morphine – and then a small handful are rapid metabolizers that will overdose on an otherwise therapeutic dose.  But, this didn't stop these folks in Montreal from evaluating its efficacy for pediatric musculoskeletal limb pain.

Pediatric pain is a little odd.  Overall, the Emergency Department does a poor job of treating pain.  Studies in pediatric EDs show significant percentages of injured patients don't receive any pain control. But, then, we all have the anecdotal experience in which a child is sitting on a stretcher watching TV with a fractured arm denying he's in any pain at all – why are you bothering me again?  Spongebob is on.

Long story short, this study randomized children to receive either ibuprofen alone or ibuprofen plus codeine.  At each time point, the difference in pain scales was no different between groups.  Pain scores weren't that high to begin with, and had moderate improvement after either treatment.

For minor pain, acetaminophen and ibuprofen are adequate options.  For more severe pain, intravenous narcotics, intranasal narcotics, or even intramuscular ketamine are probably better options.

"Efficacy of an Ibuprofen/Codeine Combination for Pain Management in Children Presenting to the Emergency Department With a Limb Injury: A Pilot Study"

Monday, December 17, 2012

Pouring Money Into Prehospital Stroke Thrombolysis

Staying consistent with the "brain attack!" slogan folks developed for stroke, the innovations in treatment continue to progress in their attempts to mimic myocardial infarction.  In myocardial infarction, a great deal of focus has been placed on rapid diagnosis and either thrombolysis or interventional catheterization.  This extends to the prehospital arena, with experimentation with ECG transmission, pre-hospital lytics, and pre-hospital cath lab activations.

For stroke, they're still trying to replicate this pre-hospital diagnosis and treatment – made slightly more complex because the diagnostics involved requires CT scanning.  However, with enough funding from telehealth and imaging industry, "mobile stroke units" have been created for feasibility evaluations. 

And, these authors have certainly demonstrated that it is feasible, diagnosing 48 acute strokes in the prehospital setting and giving half of them thrombolysis.  One patient given rt-PA had sepsis rather than an acute stroke, which is of uncertain significance in an underpowered feasibility case series such as this.

However, there's a difference between can and should.  I'm uncertain whether we should even be exploring the can portion in this pilot, considering should means a grossly excessive allocation of resources for a therapy of uncertain benefit.  Given the small absolute benefits seen in the handful of trials that even showed a benefit, I can't possibly see how trials of pre-hospital lytics could favor anything but surrogate endpoints, rather than patient-oriented endpoints.  30 minutes faster to TPA?  At what cost, and did outcomes change?

I won't fault the authors for their interesting experiment – as long as they don't seriously propose it as The Future based on our current evidence.

"Prehospital thrombolysis in acute stroke : Results of the PHANTOM-S pilot study"

Friday, December 14, 2012

More C-Spine "Doom and Gloom"

If you haven't been paying attention to the literature, then you're practicing completely unawares of an epidemic of missed spinal cord injuries.  From the literature that suggests CT isn't adequately sensitive and the final common pathway for c-spine clearance should be MRI, to this new article that says all of those studies in summary aren't enough – and patients might also need "erect cervical spine radiographs".

This is a case series – the authors bill it as a retrospective review, but the methods are laughably absent, at best – of four patients the authors identified as having cervical spine instability missed through traditional diagnostic methods.  These patients, aged 61 through 87, received Emergency Department evaluation for cervical spine injury, were treated conservatively initially, and eventually needed operative intervention.  The ED work-up of these patients can probably best be described as "interesting" – e.g., a 61 year-old female thrown from horse whose initial work-up involved only three-view radiographs of the cervical spine.  Or, a seventy-five year old man with a cervical fracture on CT who was managed initially in a semi-rigid collar without other assessment for ligamentous injury.

Regardless, each of these patients had some combination of eventual CT or MRI that failed to adequately describe the extent of cervical spine instability, but a simple erect radiograph demonstrated subluxation.  Interestingly, this is a little bit of full circle back to the days of flexion/extension films.  While other studies have demonstrated MRI picks up signal abnormalities not detected on CT imaging, the clinical significance of this is debatable.  Conversely, these dynamic/load-bearing plain radiographs offer a true functional test without precisely describing the injury – akin to the difference between cardiac stress testing and coronary angiograms.

These injuries are quite rare, and not every patient needs an MRI or dynamic testing for cervical stability.  However, in the end, these tests have a role and should be utilized as necessary in the appropriate clinical situation.

"Erect Radiographs to Assess Clinical Instability in Patients with Blunt Cervical Spine Trauma"

Wednesday, December 12, 2012

Next Up – Apixaban!

The latest installment of propaganda in the NEJM comes from Pfizer and Bristol-Meyers Squibb, the joint venture behind apixaban.  Along with rivaroxaban, apixaban is an oral Factor Xa inhibitor, another option in the procession of potential warfarin replacements.  The Xa inhibitors, while they've had their problems, improve upon their main competitor – dabigatran – because they can be reversed in the emergency setting using prothrombin concentrate complexes (PCCs).  Dabigatran, as we all know, has no practical reversal strategy.

This is AMPLIFY-EXT, the extended treatment option from AMPLIFY – where apixaban is continued for an additional 12 months for prophylaxis against recurrent venous thromboembolism.  In isolation, looks great!  The placebo group had an 8.8% VTE recurrence in the study period vs. 1.7% in either of the two apixaban doses.  And, major bleeding in the placebo group exceeded the apixaban groups – 0.5% vs. 0.2% and 0.1%.  More effective and safer than a sugar pill!

So, what's the problem?  Well, this is the third apixaban trial to be published in the NEJM in the last two years.  The first one, apixaban for acute coronary syndrome, showed no benefit and increased bleeding.  The next, apixaban for stroke prevention in non-valvular atrial fibrillation (ARISTOTLE), showed non-inferiority to warfarin – but the rate of major bleeding in that study was 2.1% per year.  Then, the NEJM also has a recent article regarding aspirin for the prevention of recurrent VTE – where the placebo group only had a VTE recurrence risk of 6.5% rather than the 8.8% observed in AMPLIFY-EXT.

You can't directly compare trial populations, of course, but it doesn't make any sense that bleeding would be reduced compared to placebo.  And, it's a straw man comparison with placebo – the correct comparison is rather head-to-head against a potentially efficacious agent, such as low-dose aspirin.  After all, low-dose ASA is pennies a day, rather than the ~$10 per day for apixaban.

Can't blame the pharmaceutical companies for selling, can only blame the suckers for buying.

"Apixaban for Extended Treatment of Venous Thromboembolism"

Monday, December 10, 2012

End-Tidal to Predict Operative Intervention in Trauma

In penetrating trauma, sometimes it's very simple to predict operative intervention.  However, sometimes, the perfusion states of our patients are less easy predict – vital signs frequently obfuscate the underlying clinical picture as the body compensates.

This is a prospective study that indirectly aims to validate end-tidal CO2 as a predictor of operative intervention in penetrating trauma by correlating it to serum lactate levels.  And, as their primary outcome, these investigators observed a strong correlation between ETCO2 and lactate levels (R^2 = 0.74).  For secondary endpoints – unsurprisingly, considering it was correlated with lactate – ETCO2 was also predictive of operative intervention.  In fact, the authors report ETCO2 was more predictive of intervention than lactate, although it seems a little odd to significantly outperform lactate, given the strength of their linear correlation.

Compared with systolic blood pressure, the test performance characteristics essentially tell us what we already know: normal blood pressure isn't helpful, low blood pressure is obviously helpful (98% specificity).  Lactate and ETCO2 are more sensitive to hypoperfusion states not reflected in vital signs, although, in this small study, even elevated ETCO2 would miss 1 in 5 operative interventions (sensitivity 82%) and would incorrectly predict 1 operative intervention for every 4 correct predictions (specificity 82%).

If prospective study confirms that ETCO2 outperforms lactate levels as an indicator of hypoperfusion, perhaps it adds something to the trauma bay evaluation.  Otherwise, it seems the most useful function might be to add to prehospital triage protocols – an environment where lactate wouldn't be available.

"Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of operative intervention in penetrating trauma patients: A prospective cohort study"