A Little Proof of Harms from CTs

It is popular to worry about the harms of CT scans in small children.  A retrospective Swedish study suggests decreased intelligence.  And, our models based on nuclear weapon exposure data combined with dummy CT exposure suggest these scans are likely to result in an increased risk of malignancy.

This is another retrospective study in the National Health Service of Britain comparing malignancy outcomes with their exposure to CT in childhood.  The scary headline: CT scan radiation triples the risk of leukemia and primary brain malignancy.  Of course, triple the risk is essentially 1 additional case of leukemia and 1 additional case of primary brain malignancy in the first 10 years after exposure.  So, this is potentially another study you can use to discuss the Number Needed to Harm with families when discussing the need for CT radiation in pediatric cases.

Now, whether articles like this trigger a wave of legal trolling for malignancies preceded by CT remains to be seen….

“Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours:  a retrospective cohort study”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60815-0/abstract

News Flash: Diagnostic Tests Take Time

It’s a little more insightful than my cynical title indicates, but it is, essentially an article that tries to quantify what we already know – blood tests, MRI, and CT all add to ED length-of-stay.

While the article isn’t specifically earthshaking, it interests me in the context of patient flow through the Emergency Department and the utilization of finite ED resources.  Every ED has a waiting room – and, if you’re like me, sometimes you look at the board and there are 34 waiting – on a good day.  In that sense, one becomes acutely aware of the value of space in the ED with which to evaluate new patients.  If blood tests and imaging tests are adding over an hour to ED LOS for each of your bed, then it would seem prudent to minimize those tests whenever possible.  It might also, perhaps, even be feasible to consider “standard of care” to be a malleable concept based on a need to ration testing specifically to increase patient flow, balancing the risks of diagnostic uncertainty against the risks of prolonged waiting room times.

Just brought to mind some interesting issues.

“Effect of Testing and Treatment on Emergency Department Length of Stay Using a National Database”
www.ncbi.nlm.nih.gov/pubmed/22594356

Daily Aspirin Harms More Than It Helps

Patients with cardiovascular disease are routinely placed on daily, low-dose aspirin for primary prevention of cardiac events.

Unfortunately, antiplatelet effects promote other types of bleeding, while the cyclooxygenase pathway has a deleterious effect on the gastric mucosal.  This 4.1 million patient propensity matched retrospective database study from Italy demonstrated approximately 2 excess cases of major bleeding events – whether intracranial or gastrointestinal – per 1000 patients treated per year.

Which is approximately the number of major cardiovascular events prevented by the daily aspirin use during the same time period.

Not specifically relevant to Emergency Medicine, but yet another example of how it’s naive to think many treatments in medicine – even those (or particularly those!) that have been part of routine practice for eons – are benefiting patients without a significant risk of harms.

“Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes”
jama.jamanetwork.com/article.aspx?articleid=1172042

The Ehrlanger HEARTS3 Score

I hate using the TIMI score to risk-stratify patients in the Emergency Department.  It wasn’t derived from a question asked in the Emergency Department, but has been co-opted by hundreds of studies as it has some value as part of our common language with inpatient medicine and cardiology teams.  We’re familiar enough with it’s shoehorning into our environment that we can use it to assist in some rough decisions about prognosis, but, clearly a better tool must exist.

A couple years back, the HEART score came out of the Netherlands.  In a small derivation and validation cohort, it did a reasonable job of predicting outcomes, using language and variables more relevant to the Emergency Department.  However, these authors from Ehrlanger in Chattanooga recognized one of the limitations of the HEART score was the somewhat arbitrary “expert” weighting of the various elements.  They therefore undertook a study with the goal of using logistic regression and likelihood ratios of the various included elements to expand the score and modify the weighting.

The good news: they improved the AUC of the scoring system from 0.827 and 0.816 for acute MI and 30-day ACS, respectively, to 0.959 and 0.902.  At the reasonable cut-off, the HEARTS3 score gets up close to ~98% sensitivity with ~60% specificity for 30-day ACS.

The bad news: a complex clinical situation requires a complex clinical decision instrument.  No one will be able to hold this in their head like the NEXUS criteria, the TIMI score, or Wells criteria – if we were even bothering to hold all these hundreds of decision instruments in our heads to start.  Luckily, smartphones, the Internet, and decision-support built-in to electronic health records is making progress towards readily available peripheral brains with which to quickly reference risk-stratification instruments such as this.

It still needs external validation, but this is one of the tools seeming to have the greatest potential I’ve recently seen

“Improving risk stratification in patients with chest pain: the Erlanger HEARTS3 score”
http://www.ncbi.nlm.nih.gov/pubmed/22626816

How Many Emergency Physicians Are On Twitter?

672.

Or, at least, that’s how many self-identified in their Twitter profiles as professional physicians in Emergency Medicine at the time this descriptive study was undertaken.  According to the author estimates, this accounts for ~1.6% of the ~20,000 U.S. board-certified Emergency Physicians.  The true number may be higher, owing to profiles that do not identify themselves professionally.

About half were “active” with a tweet within the last 15 days, and the other half were “inactive”.  Active accounts followed more users and were followed by more users.  They also have a visualization figure showing the interconnectedness of the active Twitter accounts, and, unsurprisingly, everyone tweets to the same group of twits, and vice versa.

So, it’s a small social media extension of the greater online presence of Emergency Physicians.  I’d probably say that the primary flaw with the service, regarding promoting wider interaction between online EPs, is that it is a closed, self-contained system separate from the other online resources visited by EPs.  The value is probably most to those who communicate and interact professionally in an active manner, whereas it doesn’t have as much to offer the passive observer.

“Analysis of emergency physicians’ Twitter accounts”
http://www.ncbi.nlm.nih.gov/pubmed/22634832

Cephalosporins Can Be Used in Penicillin Allergy

Did you know the literature describing the cross-reactivity between cephalosporins and penicillins is 30-40 years old?  It sort of takes the “modern” out of “modern medicine.”

At any rate, this is a literature review that aims to update the classical teaching that cross-reactivity between cephalosporins and PCN is ~10%.  They identified 406 articles on the topic and distilled it down to 27 respectable articles for inclusion in summary.  They rate the quality of the articles, and, unfortunately, find only a few good or outstanding articles and a preponderance of adequate evidence.
But, essentially, what they find is the cross-reactivity boils down to the presence of a shared R1 side chain present on first-generation and some second-generation cephalosporins.  Specific first-generation cephalosporins, such as cefadroxil (Duracef), were seen to have up to 28% cross-reactivity in some series, though the typical rate was lower, down to 0.11% with cefazolin (Ancef).  The largest meta-analyses estimated the true cross-reactivity at ~1% rather than 10%, with most of these occurring with first-generation cephalosporins.
In summary – 3rd-generation and greater cephalosporins with disimilar R1 side chains can probably be used in appropriate clinical situations despite a PCN allergy without incidence of allergy greater than in those patients who do not have a documented PCN allergy.
“The use of cephalosporins in penicillin-allergic patients: A literature review.”

Everyone Is On the Cardiac CT Bandwagon

The NEJM is on the wagon with their recent publication.  Annals of EM has been publishing all the ROMICAT trials.  And, not to be outdone, the American College of Cardiology is publishing the CT-STAT trial – a head to head comparison between coronary CT angiogram in the Emergency Department and stress perfusion imaging.

The endpoint of interest, however, is length of stay – and by association total index visit costs – rather than accuracy or safety.  And, in this sense, it was successful.  The primary difference in LOS was the length of time it took to perform the CT or stress test, which was approximately 4 hours quicker in the CT group.  ED costs were also lower, somehow, presumably billing for an observation code while awaiting the stress test and results.

However, what the authors don’t include are the total downstream costs and time of additional testing after the Emergency Department visit.  The stress test group had 34 abnormal or non-diagnostic scans, while the CT group had 64.  27 patients in the stress group underwent additional testing vs. 51 in the CT group – mostly stress tests that were subsequently normal – and none of these costs or times are included in their analysis.  I imagine if these extra tests are included in their analysis, the cost difference shrinks or disappears.

It seems to be a trend to advertise more than CT angiography actually delivers.

Several authors are sponsored by Siemens.

“The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) Trial”
www.ncbi.nlm.nih.gov/pubmed/21939822

Dabigatran – In Annals of Internal Medicine

My short review article warning the internists of the dangers associated with rushing into overuse of dabigatran was published today in Annals of Internal Medicine.


It was actually originally entitled “Dabigatran – Sinking Into Uncharted Waters,” but the editor changed it after the Italian cruise ship disaster.


“Dabigatran — Uncharted Waters and Potential Harms”
http://www.annals.org/content/early/2012/05/23/0003-4819-157-1-201207030-00467

ADAPT 2-Hour Rule Out

I’ve had a couple questions recently about accelerated rule-out strategies – considering they’re in the ACEP Guidelines, but the AHA seems to endorse a viewpoint that any suspicion for cardiac chest pain needs to be taken to its bitter end with a provocative test.  Unfortunately, an all-in strategy doesn’t mesh quite as well with reality where the costs are astronomical, and the yield abysmal.

Conveniently, this is another recent study highlighting the use of two sets of biomarkers, two hours apart – using conventional troponin assays.  This is an observational cohort study in Australia and New Zealand investigating the feasibility of their stratification instrument, with the endpoints of “Major Adverse Cardiac Events” within 30 days – an endpoint that, for once, excludes revascularizations.  Specifically, the decision protocol being evaluated includes:
 – Negative troponins at 0 and 2 hours from presentation.
 – No new ischemic changes on ECG.
 – TIMI Score of zero.

Of their 1,976 enrolled patients, 392 met these criteria and were followed for 30 days.  Their single miss was reported as an nSTEMI with two initially negative troponins who subsequently had a positive 12-hour troponin.  Therefore, their sensitivity for 30-day MACE is statistically 98.1% to 99.9%.  This is one of the eight patients in the low-risk cohort who underwent a revascularization procedure in the course of their routine care.

Essentially, using a normal EKG, two negative sets of enzymes, and a risk-stratification instrument – TIMI, Geneva, etc. – the evidence out there lets you have a discussion with the patient regarding their overall risk for a poor outcome.  If you’re stuck in a zero-miss environment, then any of these 2-hour protocols will be of no use – they all have a non-negligible miss rate.  But, if you have a grey area to work with, and an otherwise relatively low-risk patient, a quick two-hour troponin helps you catch a few extra fish you otherwise would have missed.

“2-Hour Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker The ADAPT Trial”
www.ncbi.nlm.nih.gov/pubmed/22578923

The Third International Stroke Trial: IST-3

The Cochrane systematic review of the 11 complete trials of rt-PA for thrombolysis encompasses 3,977 total patients.  IST-3 enrolled 3,035, nearly doubling our cohort of randomized data.  Unfortunately, this influx of new data does very little to resolve any of the outstanding issues regarding stroke care.

Before even looking at the results, it’s particularly important to wade through the dense study design and methods – and realize this is a non-blinded study in which patients were enrolled if the treating clinician was “uncertain of the benefits or harms of TPA”.  Considering this study began back in 2003, prior to ECASS III, a large chunk of their enrolled patients fell into the 3-4.5 hour time frame, with the remaining majority falling into the up to six hour limit.  The other major area of interest this study was intended to evaluate was the efficacy and safety in patients aged >80 years of age, of which they enrolled 1,616.  And, in a shocking twist, this study actually manages to enroll TPA and control cohorts with nearly identical baseline variables.

IST-3 is negative for the primary endpoint, which is the proportion of patients functionally independent at six months (Oxford Handicap Score 0-2, a scoring system similar to the Modified Rankin Score), with a 95% CI of 0.95 to 1.35.  On ordinal secondary analysis, there are non-significant trends towards improvements in OHS favoring rt-PA, which is probably what you’ll hear when people refer to IST-3 as “positive.”

Then, regarding the patients aged >80, there is a trend towards benefit with TPA, CI 0.97-1.88.  Unfortunately, in a neutral study, that means there is actually a trend towards harm in ages <80, CI 0.67-1.26.  Likewise, between 4.5-6 hours, there is a trend towards benefit with TPA, CI 0.89-1.93.  Therefore, between 3 and 4.5 hours, there is a trend towards harm with TPA, CI 0.50-1.07.  TPA is also essentially neutral or trends towards harm up until NIHSS 14, with more pronounced benefit shown in severe strokes.

Interestingly enough, the “blinded” phase of the study trended towards favoring control, CI 0.42-1.98, while the open phase favored TPA, CI 0.89-1.45.

So, what does this all mean?  It means, there’s still plenty of shades of grey open for interpretation and discussion.  Indeed, when added into the systematic review, IST-3 brings several of the previously significant benefits back into the nonsignificant range.  To me, this reinforces what I’ve been arguing for awhile – that the focus shouldn’t be on massive expansion of TPA eligibility, but specifically targeting those who have the best benefit/harm profile.

As with any major stroke trial, many of the investigators have financial associations with Boehringer Ingelheim.

“The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial”
http://www.lancet.com/journals/lancet/article/PIIS0140-6736(12)60738-7/fulltext