Month: March 2016

The Biomarker for Burnout

I’m tired.  You’re tired.  We’re all tired.  Importantly – performance suffers with exhaustion, unhealthy behaviors at work increase, and cognitive errors at work rise.  Burnout.

And now there might be a test for it.

This is a small study of resident trainees in Turkey, correlating the levels of neurotrophic factor S100 calcium binding protein B with symptoms of Burnout Syndrome – emotional exhaustion, depersonalization, and personal accomplishment.  S100B is a marker of glial activation and brain injury, and seems to fluctuate with stress and depression, although the associations have not been shown to be reliable.

Each resident trainee was asked to complete a questionnaire regarding burnout prior to, and following, a night shift, along with concomitant blood draw.  Unfortunately, the results are primarily grim, and not on account of the primary outcome: 37 of 48 participating residents scored in the severe depression category on the burnout questionnaire.  The remaining 11 scored in the moderate range.

Looking at the actual purpose of the study, however, they did find S100B levels were significantly different between severe and moderate depression, even accounting for the small sample.  The pre- and post-night shift levels were not appreciably different.  Overall, S100B seemed to correlate best with the overall burnout score, in particular the subscore for emotional exhaustion.

It’s a little hard to interpret these data, or envision how they might be applied in a real-world situation.  It does seem a reasonable biomarker to pursue as an objective measure of the stresses of training, and, frankly, it may be the on-shift changes were not detected as a result of most residents already exhibiting features of high stress and burnout even before starting their night.  Then, even assuming S100B were proven valid, the “gold standard” in this case – the burnout inventory – is probably less expensive and certainly less invasive to deploy.

I am not certain the way forward for this line of burnout biomarker research, but it is rather interesting.

“Serum S100B as a surrogate biomarker in the diagnoses of burnout and depression in emergency medicine residents.”
https://www.ncbi.nlm.nih.gov/pubmed/27018399

Hospitalization or Home After TIA

In the pursuit of “value-based care”, innovators are consistently looking for ways to deliver similar outcomes without the risks and resource utilization of inpatient hospitalization.  One of these realms is the evaluation of transient ischemic attack.  Most of the recommended follow-up tests are only relatively urgent in nature, and with medical management the typical mainstay of therapy.  As serious considerations go, it seems ripe a candidate for outpatient management.

This retrospective look at outcomes from Canada, however, suggests there may be pitfalls to such a strategy.  These authors reviewed the outcomes of 8,540 patients presenting with TIA or minor stroke, and compared those either admitted to the hospital at the index visit with those discharged, and among those discharged, referral to a specialized follow-up clinic or not.

Patients admitted to the hospital, by all measures, had more severe cerebrovascular disease – as evidenced by duration of symptoms, ABCD2 scores, diagnosis of minor stroke, and other comorbidities.  However, despite this, following hospitalization, these patients had the lowest risk or recurrent stroke or TIA within one year.  The benefit, presumably, comes from increased likelihood of undergoing risk stratification and treatment – carotid imaging, echocardiography, appropriate anticoagulation, appropriate antithrombotic therapy, and the like.  Then, among the discharged, various adjusted and propensity matched analysis demonstrated a protective effect of referral to specialty outpatient follow-up against death, but not for stroke or TIA.  These data do not have the granularity to fully describe whether the excess deaths were in some fashion related to cerebrovascular disease.

Most of the absolute differences in outcomes between groups are small – a few percentage points each, and smaller after adjustment.  That said, it’s probably clearly superior care, as configured in Ontario during this time frame, to have been admitted to the hospital.  As TIA evaluation, and other similar conditions, move to outpatient pathways rather than traditional hospitalization, this represents an important reminder of potential risks of degradation in thoroughness and quality.

“Association between hospitalization and care after transient ischemic attack or minor stroke”
https://www.ncbi.nlm.nih.gov/pubmed/27016521

Get On Up

Patients who linger in the Emergency Department may seem harmless – but, in reality, even a few minutes of added occupancy reduces availability for services by that much, to the point where excessive boarding may greatly diminish the ability to care for additional patients.  In many settings, such as County facilities or other space-limited departments, throughput is critical to maximizing the effectiveness of the resource.

This is a single-center descriptive study of a process improvement effort regarding the use of ED holding orders.  Rather than wait for the admitting team to fully evaluate a patient and place admission orders, the ED providers were given the authority to admit patients using a set of basic bridging orders prior to full assessment.  Their story is a success story – which is not at all surprising because their baseline state was that of nearly 7-hour ED length-of-stay for admitted patients.  Of that 7 hour baseline, over 3 hours was time elapsed between the ED physician making a decision to admit and the patient departing the ED.  After implementation of these holding orders, the ~200 minute ED loitering period was reduced to ~90 minutes – which, frankly, is still quite excessive.

It probably ought surprise no one giving the power to move patients to those most motivated to move them dramatically improves the alacrity of their departure.  These authors, however, appropriately note very little of the downstream effects were measured.  Their determination of attributable harms is reported as “purely anecdotal”, and only one instance of potential harm – a patient without the proper glucose monitoring orders on the floor – was observed.  This is probably not an entirely adequate assessment of this process change intervention, although I tend to agree true harms are likely to be vanishingly rare.

Simply put – there’s not much downside, and, in our increasingly space-strapped EDs, there’s a great deal of upside.  Clearly, unless your institution is as inefficient at baseline as the one featured in this article, the improvements will not be as profound.  But, for many hospital systems, these sorts of orders have been routine for quite some time – and it’s one more reasonable venue to intervene to improve ED LOS.

“Sustainable Mechanism to Reduce ED Length of Stay: The Use of Emergency Department Holding (ED Transition) Orders to Reduce ED Length of Stay.”
https://www.ncbi.nlm.nih.gov/pubmed/26999707

NSAIDs Probably Best for Renal Colic

It has long held that non-steroidal anti-inflammatory treatment is specifically ideal for symptomatic ureterolithiasis – leading to the popularity of such treatments as intravenous and intramuscular ketorolac, diclofenac, and the like.

However, I hadn’t quite seen as large and well-designed comparative efficacy trial as this, as recently published in The Lancet.  This trial, a placebo-control, double-blind, randomized trial compared 75mg intramuscular diclofenac, 1g intravenous paracetamol, and 0.1mg/kg intravenous morphine for patients with acute renal colic.  This means, most impressively, every patient received three injections – one active and two placebo.  The primary outcome was 50% reduction in initial pain score by 30 minutes, with relevant secondary outcomes of persistent pain and need for secondary analgesia.

Based on an analysis only of those who ultimately had confirmed diagnosis of stone on imaging (CT or ultrasound), both diclofenac and paracetamol were similar or superior to morphine, with fewer adverse effects.  Pain scores were halved in 68% of diclofenac, 66% of paracetamol, and 61% of morphine.  Most importantly, need for rescue medication in this trial was only 12% with the intramuscular diclofenac, an important consideration when potentially forgoing an IV start.  The authors actually probably understate the advantage of diclofenac here, as time zero is the time of study medication administration, not time of ED arrival, as an intramuscular injection can be provided much more rapidly than one requiring an IV.

Generalizability may be limited, as it is a single-center study from Qatar in which 80+% of patients were male.  At least however, the nationality of patients were quite diverse, representing Indian, Egyptian, Nepalese, Pakistani, Bangladeshi, Sri Lankan, and many others.

“Delivering safe and effective analgesia for management of renal colic in the emergency department: a double-blind, multigroup, randomised controlled trial”
https://www.ncbi.nlm.nih.gov/pubmed/26993881

Emergency Physicians are Mostly Just Hungry

Starving – but not for money – is probably the best way to sum up these descriptive statistics from CMS Open Payments.

This is simply a summary and breakdown of the 2014 calendar years’ worth of physician payments from industry, as reported to Open Payments.  This includes a range of details, from as mundane items as free snacks to large institutional grants for research.  All told, there were 46,405 payments to 12,883 emergency physicians, or approximately 1/3rd of all practicing EM physicians.  39,774 of these payments were related to “Food and Beverage”, and typically between $10 and $50.

So, most EM physicians are just hungry.

However, such food-related expenses were just 12.2% of the total pharmaceutical spend on EM physicians.  The two highest-grossing categories were 1,257 physicians with lecture fees and 833 with consulting fees, averaging over $1000 each.  The products associated with the greatest number and/or largest payments were antibiotics and anti-thrombotics, mostly: rivaroxaban, apixaban, dabigatran, ticagrelor, alteplase, ceftaroline, and linezolid.  Rather unexpectedly to me, at least, a few of the other top spots were taken up by agents for glycemic control: insulin detemir, canagliflozin, and liraglutide.

Finally, EM physicians were actually fairly low on the payout list, compared with other specialties, ranking 25th of 28th evaluated by this study.  The “winners”, if it weren’t already obvious from your hospital parking garage: orthopedic surgery, cardiology, endocrinology, allergy & immunology, gastroenterology, and urology.

“Financial Ties Between Emergency Physicians and Industry: Insights From Open Payments Data”

Ureterolithiasis: There’s a Better Way

Much as been made of a debate over the efficacy of tamsulosin.  Once in favor, espoused by urologists the world ‘round – but now the subject of multiple neutral, high-quality, trials.

But, what if I told you there might be a better way?

This prospective, randomized trial enrolled male patients with distal ureterolithiasis into three arms: symptomatic care-only control, daily tamsulosin, or a prescription for sexual intercourse at least three times a week.  Furthermore, patients in the symptomatic care arm and tamsulosin arms were forbidden from real or simulated sexual relations for the duration of the study.  Stone presence was confirmed by plain x-ray, and passage confirmed by correlating patient report of stone passage with absence of stone on follow-up x-ray.

As you’ve probably already gleaned from the build-up, the sexual intercourse group was the clear winner.  Mean stone size was 4.7 to 5mm across groups, so these were fairly large stones.   83% of the intercourse group had stone passage within 2 weeks, compared with 48% of tamsulosin and 35% of control.  By the end of follow-up, the other two groups had improved – but still hadn’t entirely caught up.

Unfortunately, there were only 90 total patients in this trial – and 15 were lost to follow-up.  There was no mechanism in place to confirm compliance with the treatment protocol.  Finally, of course, patients could not be blinded to treatment allocation, and no placebo for tamsulosin was provided to other groups.

Presumably, this is a low-cost, low-harm treatment intervention – and there’s some reasonable physiologic basis for the observed effect.  It may be a bit of brilliance – or, at the minimum, it might be worth an IgNobel prize?

“Can Sexual Intercourse Be an Alternative Therapy for Distal Ureteral Stones? A Prospective, Randomized, Controlled Study”
https://www.ncbi.nlm.nih.gov/pubmed/26142575

Predicting the Demise of the Elderly at Discharge

The Emergency Department is a high-risk setting.  The elderly are a high-risk population – if only by actuarial measures alone.  Despite the inherit natural risks – might there be a clue on top of physician gestalt predicting poor outcomes of the elderly discharged from the Emergency Department?

This is a retrospective, chart review, case-control study looking at discharges matched from the Kaiser Permanente Southern California cohort.  Non-hospice patients aged greater than 65 were eligible for inclusion if they were discharged from the Emergency Department, and were subsequently dead or hospitalized in the intensive care unit within 7 days.

There’s good news and bad news here.  The good news is there were a few items that seemed to leap out on their structured chart review as clues to poor outcomes.  These items could, potentially, stick in your mind as portending ill.  The bad news is, despite the presence of these features, the reasonable clinician judgement for these patients in the acute setting still felt as though they were safer discharged than in the hospital.  This implies it is challenging to incorporate these few high-risk items into clinical decision-making, and potentially the incompleteness of their retrospective abstraction.  And, more bad news – even though there were some significant odds ratios between groups, the absolute differences between groups were minor.  Therefore, overall, these groups were really quite similar.

Without much further ado, the items with the most relevant adjusted odds ratios for their combined outcome:

  • Systolic blood pressure <120 bpm.
  • Pulse greater than 90 mmHg.
  • Mental status change.
  • Initial documentation of intention to admit, subsequently changed to discharge.

Interestingly, the Methods section extolls the virtues of data-mining the electronic health record of a large health system for rare outcomes.  Just how rare was death or ICU admission within 7 days of ED discharge for patients over 65?  Approximately 0.58% met this combined outcome.  Although, it is difficult to fully generalize the Kaiser membership base to the rest of ED patients, this is a reasonable baseline to reflect upon.

“Poor Outcomes After Emergency Department Discharge of the Elderly: A Case-Control Study”
http://www.annemergmed.com/article/S0196-0644(16)00008-1/abstract

Acetaminophen is Good, But Morphine is Better

Much has been made recently of the risks and harms of opiates.  The main problem – sometimes they really do work.  Thanks to this study, we again confirm our prior conception of just how well they do work – at least for sciatica.

This trial randomized 300 patients with sciatica to intravenous morphine, paracetamol (acetaminophen), or placebo.  For obvious ethical concerns, all patients received fentanyl rescue at 30 minutes, as needed.  All groups started out around 80 on the pain VAS.  Placebo dropped patients to a mean of 66.  Paracetamol dropped patients to 41.  And morphine dropped patients to 24.  More interestingly, 80% of placebo needed rescue therapy – which implies 20% did not.  Then, 18% of acetaminophen received rescue therapy, followed by 6% of morphine.

So, while morphine is obviously statistically superior to paracetamol, the clinically important difference is less apparent.  The vast majority of patients will have enough relief from paracetamol that additional therapy is unneeded – and, in general, intravenous paracetamol is not likely to have quite the risk of adverse effects.

However, some of the generalizability of this study is limited, as many contexts attempt to manage this pain with oral medications, rather than intravenous.  And, this study may also only be generalizable to your patients based on how similar they are to the typical Emergency Department visitor in Turkey.

“Comparison of Intravenous Morphine vs Paracetamol in Sciatica: A Randomized Placebo Controlled Trial”

No Single Reliable Criterion for Diagnosing Acute Heart Failure

Some disease processes have been discretely boiled down to a single affirmative or exclusive test.  The positive or negative likelihood ratios associated with these tests can be applied to specific diagnoses almost absent any clinical context.

Acute heart failure is not one of these diagnoses.

This systematic review of clinical and laboratory features associated with a diagnosis of acute heart failure in the Emergency Department reveals the cupboard is mostly barren.  Most folks suggest a +LR >10 or a -LR <0.1 is a reasonable threshold for judging the informational value of a test.  These authors – in order to generate anything like a positive reflection of the evidence – were charitable enough to include anything with a +LR >4 or -LR of <0.25 as meaningful.

And, even that didn’t generate much:

  • An S3 on cardiac auscultation (+LR ~4.0).
  • Chest x-ray sigs of fluid overload (+LR ~4.8-6.5)
  • BNPs <100 or NT-proBNP <300 (-LR ~0.1)
  • BNPs >500 ranged in +LR from ~4-9, while NT-proBNP never exceeded a +LR of ~3.3.
  • Lung ultrasound probably had the best combination of LRs, with B-line scan having +LR ~7.4 and -LR ~0.16.
  • Specific findings on bedside echocardiography seem potentially valuable, but very few patients were included in these studies.

The short answer: acute heart failure remains a multifactorial evaluation, and it would be erroneous to routinely rely on any single test.

“Diagnosing Acute Heart Failure in the Emergency Department: A Systematic Review and Meta-analysis”
http://onlinelibrary.wiley.com/doi/10.1111/acem.12878/full

Are Antibiotics Back in Favor for Abscesses?

A couple years ago, the IDSA came out with antibiotic treatment guidelines covering uncomplicated cutaneous abscesses.  The simple, straightforward treatment many of us have been advocating: incision and drainage without antibiotics.

Sadly, such days may be finished.

A few years back, a small trial found no statistically difference in clinical cure for patients randomized to trimethoprim-sulfamethoxazole or placebo – but there were concerns regarding whether the study was appropriately powered.  This, larger, multi-center, double-blind, randomized, placebo-controlled trial aims to rectify that flaw.

With the usual exclusions for patients with serious comorbid disease, these authors enrolled 1,265 to ultimately analyze 1,247.  Acute abscesses of greater than 2.0cm, but still appropriate for outpatient management, were randomized either to 7 days of TMP-SMX or identical-appearing placebo.  There were several different follow-up time frames: for initial clinical improvement, “test of cure”, and for secondary outcomes of abscess recurrence.

There’s not much debate on the outcome – with the TMP-SMX arm generating a fairly consistent ~7% absolute cure rate improvement over placebo.  In the per-protocol population, which excluded patients lost to follow-up, cure rate was 92.9% in the TMP-SMX group versus 85.7% in the placebo cohort.  Furthermore, throughout every meaningful secondary outcome – particularly new skin infection at another site or an infection occurring in a household member – TMP-SMX was favored in proportions of similar absolute magnitude.  Adverse events were similar between each group, without a preponderance of apparent harms from TMP-SMX.

An NNT of ~14 is nothing at which to scoff.  The costs of the intervention are fairly low.  We are definitely missing some of the granular detail in this first publication, and it is difficult to say whether it’s generalizable to smaller abscess or how to manage abscesses with minimal surrounding cellulitis.  I look forward to these follow-up analyses to potentially improve the precision of treatment – but, in the meantime, it may be time to roll back some of our antibiotic stewardship movements in MRSA-endemic regions.

“Trimethoprim–Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess”
http://www.nejm.org/doi/full/10.1056/NEJMoa1507476