Month: January 2019

Antibiotics & Hospitalization for Asthma

Reactive airway disease and asthma exacerbations. The mainstays of treatment are beta-agonist bronchodilators, systemic corticosteroids, and other adjunctive therapies as indicated. Conspicuously absent from treatment guidelines is any role for antibiotics – but that’s not stopping folks from using them.

In this retrospective data on inpatient hospitalizations comprised of 19,811 patients with acute asthma, 8,788 (44%) received antibiotics within the first two days of hospitalization. Patients receiving early antibiotics were mildly more ill than those who did not, and in their unadjusted analysis “treatment failure” was more common and length-of-stay was longer, as were antibiotic-associated adverse effects. The authors then performed a more evenly-matched propensity score analysis, featuring comparing 6,833 patients in each cohort – and find roughly the same associations, again favoring those who were not treated with antibiotics.

As usual, the limitations are the retrospective nature of a data-dredging exercise such as this, and potential for unmeasured confounders. I wouldn’t make much of the association between no-antibiotics and decreased length-of-stay, as it’s reasonable to expect confounding from selection bias at play for those receiving antibiotics and those who do not. Regardless, antibiotics were frequently used – and rather than wait for proof they are unhelpful, it seems more prudent to wait for proof they are.

There’s also been a fair bit of talk about the so-called anti-inflammatory effect of macrolides, specifically azithromycin. These represented about half the antibiotics used in these patients, and, obviously, there weren’t any further hypothesis-generating signals of benefit along that line of physiologic plausibility.

“Association of Antibiotic Treatment With Outcomes in Patients Hospitalized for an Asthma Exacerbation Treated With Systemic Corticosteroids”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2721036

Again With The Value of CT-Diagnosed Rib Fractures

The elderly are more likely to fall. The elderly who fall are more likely to suffer rib fractures. The elderly who fall and suffer rib fractures are more likely to contract pneumonia and die. The chest x-ray is insensitive for rib fractures. So, we should always perform a CT in the elderly who fall and of whom we have suspicion for rib fractures?

This is a single-center retrospective study of 330 elderly patients, mean age 84, who presented after a fall. Each patient included in the study received a chest XR, followed by a CT of their chest. Overall, 96 patients had a rib fracture – 40 of which were seen on XR, the remainder only on CT. And, there are a number of interesting tidbits they describe in their population:

  • Neither hospital length-of-stay, ICU length-of-stay, or hospital mortality (10.3% vs. 7.3%) were (statistically) increased in those with occult rib fractures compared to those without any rib fractures.
  • These findings held true for the 63 patients with ≥2 occult rib fractures (both XR+ and XR-).
  • In patients with rib fractures seen on XR, the median number of additional rib fractures seen on CT was 2 (range 0-11).

Rates of in-hospital complications were similar between those hospitalized with rib fractures visualized on XR and those visualized only on CT. Then, in their case review, most adverse events occurring in those with occult rib fractures occurred due to associated injuries, events, or iatrogenic causes – not primarily due to the thoracic trauma itself.

This is only a small case series, and it is biased towards higher acuity – considering clinician judgement obtained CT imaging in all cases, and admission rates were nearly 90%. However, it does generally further demonstrate the low value in obtaining CT imaging to ensure no occult rib fractures are missed. An XR has low sensitivity, but these data do not support a premise of increased harm due to missed occult fractures.

“Chest CT imaging utility for radiographically occult rib fractures in elderly fall-injured patients”

https://journals.lww.com/jtrauma/Abstract/publishahead/Chest_CT_imaging_utility_for_radiographically.98414.aspx

Just Use the Slit Lamp

One is an unwieldy, medieval torture device. The other is a magnifying glass attached to a purple flashlight. In a busy Emergency Department, adapting to space requirements and patient flow needs, which one are you going to reach for?

Unfortunately – and rather obviously – the easy option is not equally effective. This small study pulled a convenience sample of anterior chamber-type eye complaints presenting to an eye urgent clinic, and evaluated them first with the Wood’s lamp, and then the slit lamp. Of the 73 patients included in the study, the overall sensitivity of the Wood’s lamp was 52% – missing, as the sensitivity might imply, about half of corneal abrasions, half of corneal ulcers, half of corneal foreign bodies, and most all of the keratitis or rust rings. Most of the provisional diagnoses given with the Wood’s lamp examination were different enough from the final diagnoses that the misses were clinically important.

Take a few minutes to re-familiarize yourself with the dials and widgets on your slit lamp – and use it. These data are hardly conclusive the slit lamp is, in fact, a “gold standard”, or that the Wood’s lamp is non-inferior in a general ED setting when used by emergency physicians. However, I’d rather put the onus on the evidence to demonstrate the effectiveness of the less-intensive diagnostic method, rather than base my practice on the assumption.

“Prospective study of the sensitivity of the Wood’s lamp for common eye abnormalities”
https://www.ncbi.nlm.nih.gov/pubmed/30630841

Bonus link: “What Really Glows” with the Wood’s lamp.

How Do Trauma Patients Die?

Comprised of 1,536 patients in an 18-center, prospective, observational study coordinated though the Western Trauma Association:

  • Traumatic brain injury – 45.0%
  • Exsanguination – 23.0%
  • “Late physiologic collapse” – 15.6%
  • “Early physiologic collapse.” – 9.7%
  • Pre-trauma medical event. – 3.8%
  • Airway issue. – 1.5%
  • Sudden unexpected event. – 1.0%

Unpacking the details, there are a handful of anticipated associations. Exanguination patients made up a much larger proportion of penetrating trauma patients. TBI proportion was actually only slightly higher in blunt trauma patients, but penetrating TBI was more likely to be deemed non-survivable on initial presentation. Almost half the deaths in penetrating trauma patients were in the Emergency Department – which also reflects a high proportion of pre-hospital arrest – followed by another quarter in the OR. Blunt trauma patients typically survived admission to the hospital. All patients for whom a pre-trauma medical event was determined to the causative factor were in the blunt trauma cohort, rather than penetrating.

There isn’t anything specifically prescriptive in this descriptive study, but it’s a building block for designing interventions in attempts to address the causes and timeframes of preventable death from trauma.

“The Why & How Our Trauma Patients Die: A Prospective Multi-center Western Trauma Association Study”
https://www.ncbi.nlm.nih.gov/pubmed/30633095

IDSA Influenza – Class A, Level III

The last time the IDSA updated their influenza practice guidelines, it was the time of the 2009 H1N1 influenza pandemic. Fittingly, we are entering another season of H1N1 – and we have new guidelines, incorporating all the new evidence gathered in the meantime.

And, unfortunately, that is to say: we don’t really have any new, high-quality evidence.

The grading system for their recommendations includes two categories. Strength of recommendation:

  • A: Good evidence to support a recommendation for or against use
  • B: Moderate evidence to support a recommendation for or against use
  • C: Poor evidence to support a recommendation

Quality of evidence:

  • I: Evidence from 1 or more properly randomized controlled trials
  • II: Evidence from 1 or more well-designed clinical trials, without randomization; from cohort or case-controlled analytic studies (preferably from >1 center); from multiple time-series; or from dramatic results from uncontrolled experiments
  • III: Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

It would follow, then, for an “A” strength recommendation, this ought to reflect I or II quality of evidence – but a bizarrely staggering number of their recommendations are A-III, effectively self-contradicting. Most of their “Which Patients Should Be Tested for Influenza?” recommendations are A-III. The critical “Which Patients With Suspected or Confirmed Influenza Should Be Treated With Antivirals?” section features another batch of A-III recommendations, followed by several C-I and C-IIIs.

A long story short, this is simply paradoxical, making level A recommendations from class III evidence in the form of manufacturer sponsored trials, indirectly-sponsored meta-analyses, and observational data. Many authors of this piece are neck deep in reported financial and professional conflicts of interest with industry, which almost certainly eases any pain felt by distributing such internally invalid recommendations. After decades of controversy and hundreds of millions of dollars in profit for Genetech/Roche, we’re still bumbling along with our original momentum lacking a full understanding of the effectiveness and value of these medications.

“Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza”
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy866/5251935

To COPD, or Not to COPD

This is yet another typically Canadian study, which is to say it’s Ian G. Stiell, et al, producing yet another high-quality risk-stratification profile for Emergency Department patients.

In this week’s episode, we find our heroes prospectively validating the Ottawa COPD Risk Scale (OCRS), a set of 10 criteria identifying COPD patients in the ED at highest-risk for short-term serious outcomes. Short-term serious outcomes, by their definition, was the occurrence of death, admission to a monitored unit, intubation, non-invasive ventilation, myocardial infarction, or hospital re-admission. Their target population was effectively patients with COPD who weren’t otherwise obviously ill, with a set of exclusion criteria for those who clearly necessitated admission on the index visit.

Within their 10 items, there are 16 points available to assign, and the expected risk of short-term outcomes ranged from 2.2% at a score of 0, up to 91.4% at a score of 10. Their validation, however, demonstrated potentially important differing results – with nearly two-fold greater risks for short-term poor outcomes in the lowest (and most common) strata. Then, at the high-end, there simply weren’t enough patients with scores >4 to come to any reliable consensus regarding the accuracy of the risk stratification. In fact, of the 65 patients with scores >4, the overall incidence of serious outcome was only 23% – while the expected risk from their derivation scale would probably be upwards of 40 or 50%. Their explanation: these higher-risk patients were all hospitalized at the index visit, thereby decreasing their expected rate of short-term serious outcome. This may, in fact, be true, but it is rather a hypothesis rather than a well-supported conclusion.

The other question, even assuming this tool is valid, is “what now?” The authors emphasize these data and risk levels are not necessarily prescriptive, but rather give the clinician an objective tool to supplement their decision-making. Will incorporating this tool this improve care delivery and outcomes? Unfortunately, it is impossible to tell. These authors have done the “easy” research, a data collection and number-crunching exercise. Determining its effect on clinical care is another, much harder step – and fraught with limitations due to generalizability from one practice setting to another. I would be wary of incorporating this into your clinical care until better data is available regarding its effect on patient-oriented and resource utilization outcomes – unless you’re ready to prospectively study it!

“Clinical validation of a risk scale for serious outcomes among patients with chronic obstructive pulmonary disease managed in the emergency department”

http://www.cmaj.ca/content/190/48/E1406

Who Are Buying Emergency Physicians?

It’s CMS Open Payments Database time again, updated for 2017. Sadly, it turns out you or at least one of your closest colleagues is a witting or unwitting puppet of the pharmaceutical industry: a full 35.4% of practicing U.S. emergency physicians received payments from industry last year.

The details:

  • The median payment was $18 – 90% of you just got lunch (or dinner)(or less).
  • Over 75% of emergency physicians in Mississippi were the recipient of some industry payment.
  • Ethicon Endo-Surgery and Janssen Pharmaceuticals were the largest of many contributors, and Xarelto, Eliquis, Activase, and Pradaxa were the most frequently cited products.
  • There were 35 EPs receiving industry sponsored research payments, primarily from device manufacturers – Covidien, Taro, and Zoll.

That said, these data also only scratch the surface of accountability, as about half of payments could not be associated with a product, and reporting to the OPD does not include other general grants and payments to organizations, rather than individuals.

And now you know, and knowing is half.

“Analysis of current financial relationships between emergency physicians and industry”
https://www.ajemjournal.com/article/S0735-6757(18)31001-5/abstract

The Beginning of the End of Heparin for ACS?

We’ve been routinely starting anticoagulation therapy on patients diagnosed with an acute coronary syndrome for a couple decades. The evidence from the preceding era is clear – patients treated with anticoagulation plus aspirin are at much lower risk for subsequent ischemic events than those treated with aspirin alone.

However, these trials are not generalizable to most modern care for ACS. For example, the FRISC and ATACS trial discharged patients with nSTEMI or unstable angina with continued anticoagulation for weeks to months. Revascularization procedures were performed only as rescue therapy, rather than the routine early invasive strategies in use today. Dual anti-platelet and other adjunctive therapies were unavailable. So – do we actually still need the heparin?

These authors retrospectively evaluated the association between parenteral anticoagulation therapy and in-hospital death and in-hospital major bleeding. There were 6,804 patients included in their 4-year, multi-center data set, about two-thirds of whom did not receive parenteral anticoagulation prior to PCI. There were small, probably unimportant differences reported between groups, excepting one feature: time to intervention. Time to intervention was a median of 1 day in those managed without anticoagulation versus a median of 3 days in those managed with. Overall, there was no difference in in-hospital death, nor 30-day, 1-year, or 3-year death for those included in long-term follow-up. A handful of cases suffered bleeding complications, with a small absolute excess in those managed with anticoagulation.

This is neither prospective nor a randomized trial, and there could certainly be unexamined confounding baseline characteristics favoring one treatment group over the other. The authors also note bleeding complications could be ameliorated by use of fondaparinux rather than heparinoids, but this would still be moot if there is still no benefit to anticoagulation. Finally, in-hospital mortality is a fabulous patient-oriented endpoint, but it does not tell the entire story with regard to any additional morbidity potentially resulting from anticoagulation being withheld. We should not change practice based on this level of evidence, but these data should prompt further examination and potentially prospective evaluation.

“Association of Parenteral Anticoagulation Therapy With Outcomes in Chinese Patients Undergoing Percutaneous Coronary Intervention for Non–ST-Segment Elevation Acute Coronary Syndrome”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2719425