Monday, December 19, 2011

Under/Overtesting in Fever Without a Source

A curious study that observes, from the NHAMCS dataset, the testing performed by Emergency Physicians on children who have fever without a source between the ages of 3 and 36 months.

The general point of the authors, while acknowledging the limitations of this sort of data-dredging, is that testing strategies by Emergency Physicians appear to be generally non-conforming with the American Academy of Pediatrics recommendations for testing in otherwise well-appearing children.  They are hesitant to critique the patients who received laboratory testing - because they have no data on how well-appearing the child may have been or other comorbidities that might indicate testing - but they do take issue with the fact that only 43% of females under age 2 with a fever received a urinalysis and culture.  The 2008 Pediatrics guidelines - not endorsed by ACEP - would recommend that all of them receive UA and culture.  Considering the prevalence of UTI in febrile females under 2 years of age ranges from 8-17%, their criticism is probably valid.

Other trivia: 20% of children with no testing performed received antibiotics.  This could be due to missing ICD-9 data about another clinical diagnosis - but more likely due to simply treating fever unnecessarily.  

And, finally, children from zip codes with higher median incomes were more likely to receive CBC and UA.  More UAs, probably good.  More CBCs, probably bad.

Just an interesting summation of observational data.

Sunday, December 18, 2011

Early Heparin Does Not Save Lives in Pulmonary Embolism

Or, if it does, this is not the article that shows it.  It tries to show it - and Rick Bukata, who I love, includes it as part of his PE review in this month's Emergency Physician's Monthly.  It's a year and a half old, but I had to pull it because I've presented other articles showing the diagnosis and treatment of pulmonary embolism isn't changing mortality.

This is from the Mayo clinic, and it's observational, retrospective cohort data, which is red flag #1 for drawing practice-changing conclusions.  They reviewed charts on 400 symptomatic pulmonary embolism identified on CTPA that were subsequently admitted to the hospital and anticoagulated with systemic heparin.  In their introduction, they set out to show that outcomes are improved in pulmonary embolism if you initiate heparin in the Emergency Department.  In the end, their conclusion is essentially summarized by this graphic:


Seems pretty convincing, eh?

And, it's true, there was a significant association between heparin in the ED and 30-day survival.  There was also, however, a significant association between 30-day survival and: tachycardia, Wells score, leukocytosis, elevated troponin, malignancy, recent surgery, ICU admission, and hemorrhagic events.  So, did patients die because they didn't get heparin, or did they die because they were more acutely ill - and/or had a hemorrhagic event after initiating heparin?  The big one for me is the difference between positive (>0.01 ng/mL) troponins - 26.4% in their survivors and 47.8% in the non-survivors.  Considering the criteria for diagnosis of submassive pulmonary embolism - patients who occupy a different level of risk for poor outcomes - includes elevated troponins indicative of right heart strain, I think this study doesn't properly support anything it tries to imply regarding the time to heparin and survival.

"Early Anticoagulation Is Associated With Reduced Mortality for Acute Pulmonary Embolism"
www.ncbi.nlm.nih.gov/pubmed/20081101

Friday, December 16, 2011

Your Residents Would Love a Wiki

It's not a terribly profound paper - along the lines of "we did this and we liked it" sort of thing - but it is a relevant educational application of wikis in medicine.

The BIDMC Internal Medicine department undertook an initiative to essentially convert all their little handbooks and service guides to an online reference.  They chose the wiki interface so anyone could update information or add pages while allowing updates to be tracked and rolled back as necessary.  They promoted it during their intern orientation and made a significant effort both to get people to update it and use it.  And, for the most part, they were successful.  Most residents (92%) thought it was useful, it was mostly used to find phone numbers and rotation specific clinical information, and, overall, about half of the PGY-2 and -3s updated the site during the 2009-10 year.

It probably takes a lot of effort and requires just the right collaborative environment, but there are a lot of residencies, departments, or other clinical organizations that could also probably benefit from something similar - particularly if there are a lot of rotating students/residence between difference services or sites.

"Adoption of a wiki within a large internal medicine residency program: a 3-year experience"
http://www.ncbi.nlm.nih.gov/pubmed/22140210

Thursday, December 15, 2011

Why Aren't You Using Nitrous Yet?

Another massive study reviewing adverse events encountered during procedural sedation - this time with nitrous oxide given in concentrations up to 70%.  It is odd that resistance is encountered regarding high concentrations of nitrous oxide - considering 30% O2 is still greater than the fraction of inspired oxygen on room air - but this, and other studies like it, should help allay any concerns.

Out of their 7,802 nitrous administrations, they recorded 9 "potentially serious" adverse events - eight desaturations and one potential aspiration event requiring oropharyngeal suctioning.  More importantly, a reasonable percentage of these administrations were in children with comorbid diseases or potentially serious illness that needed sedation for significant procedures - LP, CT scans, NG/G-tube placement, and "other" that included EMGs and botulinium toxin injections.  Their rates of serious events are similar to other published series where either zero or <1% potentially serious events occurred - except for the study that reported 30% adverse events, but included "euphoria" and "dreaming" as adverse events.

This is not, however, an ED-only study, and one of the limitations is that they don't specifically record whether they are able to successfully complete the intended procedure with this method - however, one would imagine, if it didn't work the first 7,000 times, they wouldn't have kept doing it...

"Safety of High-Concentration Nitrous Oxide by Nasal Mask for Pediatric Procedural Sedation"
http://www.ncbi.nlm.nih.gov/pubmed/22134227

Tuesday, December 13, 2011

High-Sensitivity Troponin Dead End

Another article trying to work the unworkable - the balance between sensitivity and specificity.

From New Zealand, an attempt to evaluate the Roche Laboratories hsTnT assay in the interests of performing accelerated rule outs in the ED - looking at any combination of initial value, 2-hour value, delta between 0-2 hour value, etc.  And, essentially, any strategy you choose is wrong.

On one hand, you can get up to 91.4% specific for their gold  standard of AMI by requiring a hsTnT  >14 ng/L and a 20% delta change at 2 hours - but your sensitivity will drop to 72%.  Conversely, you can have sensitivity of 98.8% - which is the point of these hsTnT testing strategies - but your specificity drops to 56.4%.  Unless you're doing something intelligent with all those false positives that isn't harmful, expensive, or invasive, the costs of zero-miss are, once again, too high.

"High-sensitivity troponin T for early rule-out of myocardial infarction in recent onset chest pain"

Monday, December 12, 2011

Just Do It - Lytics for STEMI

PCI is fabulous - but only if you get them to the balloon in 90 minutes or less - otherwise, we should be giving thrombolytics for STEMI.  Unlike stroke, and even though many of these studies are manufacturer-supported, we have literally hundreds of thousands of patients randomized to tenecteplase, alteplase, streptokinase, etc. in combination with every different antiplatelet agent under the sun.  I still don't know whether prasugrel and lytics go together, but I'm sure we'll have GUSTO-10,000 soon enough.

Why do I bring this up?  Because it turns out we're terrible at transferring patients to PCI-capable centers fast enough.  This is a retrospective, observational study of CMS OP-3, the door-in, door-out quality measure for STEMI patients receiving transfer.  A grand total of 9.7% patients in this review of 13,776 patient encounters met the quality standard of transfer within 30 minutes.

If you agree with the literature that says a DIDO time >30 minutes is associated with a 56% increased odds for in-hospital mortality, this could be important.

Lytics.  Just do it.

In fact, depending on the recency of symptoms, the location of the infarct, and whether we're off-hours for cath lab activation, I'll give full-dose lytics on arrival while awaiting cath lab transport.  Your mileage may vary, depending on your cardiology team.

"National Performance on Door-In to Door-Out Time Among Patients Transferred for Primary Percutaneous Coronary Intervention"
www.ncbi.nlm.nih.gov/pubmed/22123793

Saturday, December 10, 2011

ED Geriatric CPOE Intervention - Win?

It does seem as though this intervention had a measure of success - based on their primary outcome - but there's more shades of grey throughout the article.

This is a prospective, controlled trial of a contextual computer decision-support (CDS) incorporated into the computerized provider order entry (CPOE) system of their electronic health record (EHR).  They do a four-phase On/Off intervention where the CPOE either suggests alternative medications or dose reductions in patients >65 years of age.  They look at whether the intervention changed the rate at which medication ordering was compliant with medication safety in the elderly, and then, secondarily, at the rate of 10-fold errors, medication cancellations, and adverse drug event reports.

The oddest part of this study is their choice of primary outcome measure.  Ideally, the most relevant outcome is the patient-oriented outcome - which, in this case, ought to be a specific decrease in adverse drug events in the elderly.  However, and I can understand where they're coming from, they chose to specifically evaluate the usability/acceptability of the CDS intervention to verify the mechanism of intervention.  There are lots of studies out there documenting "alert fatigue", resulting in either no change or even increasing error rates.

As far as the main outcome measure goes, they had grossly positive findings - 31% of orders were compliant during the intervention periods vs. 23% of orders during the control periods.  But, 92.5% of recommendations for alternative medications were ignored during the intervention periods - most commonly triggered by diazepam, clonazepam, and indomethacin.  The intervention was successful in reducing doses for NSAIDs and for opiates, but had no significant effect on benzodiazepine or sedative-hypnotic dosing.

However, bizarrely, even though there was just a small difference in guideline-concordant ordering, there was a 4-fold reduction in adverse drug events - most of which occurred during the initial "off" period.  As a secondary outcome, there's much to say about it other than "huh".  None of their other secondary outcomes demonstrated any differences.

So, it's an interesting study.  It is consistent with a lot of previous studies - most alerts are ignored, but occasionally small positive effect sizes are seen.  Their primary outcome measure is one of mostly academic interest - it would be better if they had chosen more clinically relevant outcomes.  But, no doubt, if you're not already seeing a deluge of CDS alerts, just wait a few more years....

"Guided medication dosing for elderly emergency patients using real-time, computerized decision support"
http://www.ncbi.nlm.nih.gov/pubmed/22052899

Friday, December 9, 2011

Dog Bites and Antibiotics

Nicholas Genes of...well, multiple sites of fame, including recurring columns in several EM publications, SAEM leadership, and the long-standing medical blog "blogborygmi" beat me to this ACEP News item from today:

MedPage Today (12/9, Walsh) reports that a study presented in a poster session at the midyear clinical meeting of the American Society of Health-System Pharmacists (ASHP) found that only 64% of the patients presenting to the emergency department with animal bites "were discharged on the appropriate antibiotic."


I won't attempt to replicate his scathing criticism of ACEP News for publicizing a poster from an interim pharmacy conference, just read it for yourself:
http://blogborygmi.tumblr.com/post/13967004314/among-98-patients-seen-with-bites-over-the-course

TEG and Dabigatran

An interesting mini-letter from my institution regarding dabigatran, thromboelastography, and poor outcomes.

It simply notes and reinforces the fact that conventional coagulation studies in patients on dabigatran will be normal - and therefore conventional reversal options are unlikely to be of value.  The only abnormality detected was prolongation of the activated clotting time, corresponding to inhibition of enzymatic clotting.

Multiple patients have presented after traumatic injury to our institution, and they have universally had poor outcomes.

"Acutely Injured Patients on Dabigatran"
http://www.nejm.org/doi/full/10.1056/NEJMc1111095

Thursday, December 8, 2011

Journal Watch: Stroke

Mentioned in Journal Watch: Stroke -


...regarding my recently published article regarding pharmaceutical ties to thrombolysis literature.

No idea what the review says - since I don't subscribe to the service!

Wednesday, December 7, 2011

No More Excuses For Not Giving TPA

Rather than restrict TPA for acute ischemic stroke to the small cohort of patients identified by strict exclusion criteria in the few completed randomized trials, the current crusade is to continue to try and give it to more patients on the fringes of eligibility.

This article promotes giving TPA to patients with "minor or rapidly improving" strokes, because the lead author (sponsored by Genentech) sees this classification of patients is responsible for 50% of the documented reasons why patients were excluded from receiving TPA.  In fact, if patients with mild and improving strokes received TPA, it would immediately double the rate of TPA use - and provide potentially excellent outcomes at 90 days for the manufacturers.

They base their assertions on a retrospective, uncontrolled evaluation of the discharge disposition of patients in this "minor or rapidly improving" cohort - and observe that only 72% of patients in this group were discharged home.  In their mind, patients could do much better (as measured by disposition location) if they had received TPA - and their final conclusion is that this exclusion criteria should be further studied so that it may be revoked.

But, their conclusions are a preposterous farce conjured out of fictionalization of the data.  Considering the median age of their cohort was 72, 30% of whom had prior stroke/TIAs, 26% were diabetic, 76% were hypertensive, etc. - the sheer fact that only 28% went to rehab/SNF/died is probably rather good performance.  The authors also admit they had no information regarding the initial residence of this mostly elderly cohort and have no idea if the patients discharged to nursing facilities originally resided there.  Finally, the article additionally states "outcomes for patients with mild/rapidly improving stroke were better than for rtPA-treated patients with mild stroke (NIHSS score of 0 to 5) but worse for patients with a final diagnosis of TIA."

Yes, they compared this mild stroke cohort data to the mild stroke cohort data that received TPA, and all outcomes - adjusted and unadjusted for NIHSS - significantly favored the non-TPA cohort.

....so the obvious conclusion is to find a way to give more of them TPA.

Lunacy.  Another example of bad literature undermining trust in a probably efficacious treatment.

"Outcomes in Mild or Rapidly Improving Stroke Not Treated With Intravenous Recombinant Tissue-Type Plasminogen Activator"
www.ncbi.nlm.nih.gov/pubmed/21903949

Tuesday, December 6, 2011

It's Another Chest Pain Prediction Rule!

Yet again, the insanity of the race to a zero-miss culture funds another chest pain discharge prediction rule.  In fact, the most telling part of this paper is in the very end when they compare the chest pain admission rates of the Canadian hospitals in this article to the U.S. hospital - 18% and 20% in Canada compared to 96% in the U.S. (combined ED observation status and inpatient).  The difference in those numbers is insane - and I'm sure people could easily debate which is the preferred side of those numbers to be on.

In any event, the study is a prospective, observational data-gathering study of 64 variables related to the presentation of chest pain - some of which are objective and some of which are historical.  It's an interesting read - in part because the inter-observer kappa for a lot of the historical variables is so terrible they weren't even usable.  After collecting all their data, they did 30-day telephone follow-up or vital records review to evaluate the combined endpoint of death, myocardial infarction, or revascularization.

Via the magic of recursive partitioning, a patient without new EKG changes, a negative initial troponin, no history of CAD, atypical pain, and age less than 40 years separated out 7.1% of their study population that had zero 30-day outcomes.  Adding a second negative troponin six hours later for the 41-50 year group gives another 11.2% of patients that had zero outcomes.  So, a facility that admits 96% of their patients could potentially reduce admissions - but it might have less utility in Canada.

I'd rather see a two-hour second troponin than a six-hour one; it might reduce sensitivity, but it's wholly impractical to tie up a bed in the ED for 6 hours for a patient you want to send home.  And, like most of these articles, the combined endpoint of death, MI, and revascularization is irritating.  Considering there were twice as many revascularizations as myocardial infarctions, there really ought to be more granularity in these sorts of studies with regard to the actual coronary lesions identified rather than simply lumping them into a combined endpoint.

"Development of a Clinical Prediction Rule for 30-Day Cardiac Events in Emergency Department Patients With Chest Pain and Possible Acute Coronary Syndrome"
www.ncbi.nlm.nih.gov/pubmed/21885156

Sunday, December 4, 2011

Mistakes In Cardiac Arrest Cause Bad Outcomes

Not surprising, of course, but an interesting analysis of a large data set.

The authors pulled 108,636 in-hospital cardiac arrest cases out of the National Registry of Cardiopulmonary Resuscitation and evaluated them for "errors" - such as multiple intubation attempts, incorrect medication administration, delays in code team activation, etc.  After attempting to control for all the differences (of which there were many) in level of care and type of patient suffering cardiac arrest, they finally find that any documented error in resuscitation led to a 9.9% increase in adjusted hazard ratio for death in non-VF/pVT, and a 34.2% increase in VF/pVT patients.

Specifically, when they break out the different types of errors, essentially all the effect size was related to delays in medication administration for non-VF/pVT, and delays in medication and failure to defibrillate in VF/pVT.

"Impact of resuscitation system errors on survival from in-hospital cardiac arrest"
www.ncbi.nlm.nih.gov/pubmed/21963583

Saturday, December 3, 2011

Physician Profiteering From Self-Referral

Unfortunately, another distasteful – and likely more common than the authors estimate – assessment of the unethical behavior of physicians.

This is from JAMA.  It's a health-insurance carrier records review regarding differences in rate of ordering nuclear stress testing and stress echocardiography depending on the cardiologist financial conflict-of-interest.  Basically, they were asking the question – if the ordering cardiologist had a financial interest in the imaging performance and interpretation, would they order more tests?

Sadly, as you might imagine, the answer is yet.  If the physician billed technical and professional fees for the nuclear stress, the adjusted OR for ordering a nuclear stress was 2.3 compared to physicians who had no financial interests in the nuclear stress.  For stress echocardiography, the adjusted OR was 12.6.

I have no doubt the same sort of thing happens with neurologists who own their own MRI facilities, etc.  Money corrupts physicians just the same as any other human being.

"Association Between Physician Billing and Cardiac Stress Testing Patterns Following Coronary Revascularization"
jama.ama-assn.org/content/306/18/1993

Thursday, December 1, 2011

C1-Esterase Inhibitor Might Improve Some Sepsis Outcomes

...or it might not.  This is a tiny study using a very expensive medication that probably works only on a few patients, but it's interesting nonetheless.

As part of the inflammatory cascade, C1-esterase inhibitor (C1INH) modulates the coagulation cascade, impacts leukocyte activation, enhances bactericidal activity, and prevents endotoxin shock in sepsis models.  So, sounds like a good thing - let's give it to patients and see what happens!

This was an open-label, randomized, controlled study in Moscow and St. Petersburg with 62 ICU patients - 20 controls and 42 treatment patients - that met inclusion criteria.  There were, unfortunately, a lot of differences between the control group and the treatment group.  These differences included a lot more post-operative patients, much more pneumonia, and more on the ventilator, and probably favored the treatment group.  The mortality is way better for the treatment group - 12% dead versus 45% - but it's simply impossible to attribute all the effects to C1INH with all the other confounding differences.

That being said, this study is consistent the effects from other small studies.  Therefore, we will likely hear more about C1INH after larger, manufacturer-sponsored trials also undoubtedly find a way to spin positive results.

"C1-esterase inhibitor infusion increases survival rates for patients with sepsis"
www.ncbi.nlm.nih.gov/pubmed/22080632

Wednesday, November 30, 2011

ED Blood Pressure Management In Acute Stroke Is Terrible

This is a non-TPA article regarding the medical management of hypertension in acute ischemic stroke in the Emergency Department.

The authors remind us that for every 10 mmHg drop in SBP <150 mmHg, there is a 17.9% increase in risk for death at 14 days.  They additionally remind us that antihypertensive therapy is only recommended for BP >220/120 mmHg, with a 15-25% goal decrease in the first 24 hours.

This is a retrospective review of cases from 16 Cincinnati region hospitals looking at the blood pressure observed in the ED along with any treatment.  They found 1739 cases, 1520 of whom did not receive treatment and 219 who did.  It turned out that 2.6% of the non-treated patients should have had some blood pressure lowering - oops.  But, amazingly even worse, only 31.5% of patients who did receive treatment actually required lowering.

Of the 217 patients that were treated, 52 of them had greater than a 20% drop in blood pressure in the Emergency Department.  So, we treat a lot of blood pressure that shouldn't be treated - and when we treat it, it is not uncommon to treat it too aggressively.

Stop it!

"Emergency Department Adherence to American Heart Association Guidelines for Blood Pressure Management in Acute Ischemic Stroke"
http://www.ncbi.nlm.nih.gov/pubmed/22033993

Monday, November 28, 2011

Computer Reminders For Pain Scoring Improve Treatment

This is a paper on an important topic - considering the CMS quality measures coming up that will track time to pain medication for long bone fractures - that demonstrates a mandatory computer reminder improved pain treatment more than an educational campaign did.

This is a prospective study of 35,628 patients visiting an Australian emergency department in which they went through several phases of intervention, the most salient in their minds was requiring assessment of a pain score at triage.  They started by simply observing their performance, then they altered their electronic medical record with a mandated input of the pain score at triage.  After the mandated scoring, time to analgesia went from median of 123 minutes to 95 minutes.  After the mandate phase, the ED staff underwent an education program regarding pain management in the ED - and the time to analgesia didn't improve any further.

So, it is reasonable to infer that mandating the pain score at triage had the desired effect on decreasing time to analgesia.  However, 95 minutes until analgesia is still terrible.  It would be far more interesting of an article if it truly broke down all the times - such as time to triage, time to room, time to physician, time to analgesia order, etc., because there are a lot more data points to gather.

Additionally, it seems it might simply be higher yield if - in addition to asking pain in triage - they had a triage protocol to treat the pain immediately at that point, rather than later downstream.

"Mandatory Pain Scoring at Triage Reduces Time to Analgesia"
www.ncbi.nlm.nih.gov/pubmed/21908072

Sunday, November 27, 2011

False-Negative Abdominal CTs

This is an article from the radiology literature that essentially tries to say that CT is not the imaging modality of choice for upper abdominal pain.

It's a retrospective review of 235 patients over a four-year period who had CTs of the abdomen reported as "normal" or "non-diagnostic" in the setting of upper abdominal pain.  They determine false-negative studies if another diagnostic modality eventually provided a definitive diagnosis for the patient's symptoms.  Out of the 235, 81 were lost to follow-up and 27 were excluded for other reasons.  Of the remaining 127, 46 were classified as false-negative and 81 were classified as true-negative.

The misses?  23 cases of pancreaticobiliary disease (biliary colic, cholecystitis, choledocholithiasis), 12 cases of gastritis/gastric ulcer disease, and 6 miscellaneous cases that included Mediterranean fever and prosthetic valve endocarditis.

So, yes, there is some inkling that CT of the upper abdomen is going to miss a segment of pathology.  On the other hand, this paper presents incomplete data regarding the true positives and false positives - making evaluation of this specific imaging indication incomplete other than to remind clinicians that the evaluation may need to continue in the setting of a negative CT.

"Negative predictive value of intravenous contrast-enhanced CT of the abdomen for patients presenting to the emergency department with undifferentiated upper abdominal pain"
www.ncbi.nlm.nih.gov/pubmed/22072086

Friday, November 25, 2011

TPA Is "Safe" In Prior Stroke and Diabetics

Another recent Journal Watch article about TPA - relaying the manufacturer-sponsored message that TPA can, in fact, be given to the patients who were excluded from ECASS III because of diabetes or prior stroke.

Papers like this are fabulous.  I am 100% in agreement with the physiologic premise that timely reperfusion of the ischemic penumbra is beneficial in acute stroke.  I am less enthusiastic about using systemic thrombolysis, because it's akin to smashing a teacup with a sledgehammer.  But, until PCI-like therapy is available/safe for the brain, it's all we have.

I am really tired of endless papers from the TPA literature with authors falling all over themselves to present fundamentally flawed data as definitive evidence.  In this paper, the authors take the non-randomized TPA population from the SITS-ISTR - and compare it to the non-randomized, non-thrombolyzed population from the VISTA registry.  Why is this a problem?  Because even though the relative differences are large, the absolute differences are small - and we've already see that what makes the largest absolute difference is stroke after-care, and that all stroke centers are not created equal.  The authors acknowledge this, but then justify their results by stating that their numbers are similar to prior, retrospective, non-randomized comparisons performed on subsets of registry data.  It's a self-fulfilling prophecy.

They conclude with "Hence, we find no justification to exclude patients from receiving alteplase for acute ischemic stroke if they have a [prior stroke] and also have [diabetes mellitus]" - which is true, unless it bothers you that the mRS 6 (dead) group nearly doubles when TPA is given to the stroke/diabetes groups.  Imagine what the reaction to ECASS III would be if TPA wasn't 52% good outcome vs 6.7% death - and was one of these 29% good outcome vs. 23% death, or 25% good outcome vs. 28% death comparisons from the registry data (totally different baseline severity vs. ECASS III, just throwing the numbers out there for hyperbole).

...and, the obligatory:

"Dr. Mishra reports no disclosures. Dr. Ahmed is an employee of SITS International, which received a grant from Boehringer Ingelheim for the SITS-MOST/SITS-ISTR study with alteplase. Dr. Davalos has received speaker or consultancy honoraria from AstraZeneca, Boehringer Ingelheim, Lundbeck Inc., ev3, Ferrer, and Talecris Biotherapeutics. Dr. Iversen has served on scientific advisory boards for Boehringer Ingelheim and Allergan, Inc.; and has received research support from the Danish National Advanced Science Foundation. Dr. Melo reports no disclosures. Dr. Soinne serves on speakers’ bureaus for and has received speaker honoraria from Boehringer Ingelheim, Pfizer Inc, and Siemens; and has served as a consultant for Boehringer Ingelheim. Dr. Wahlgren serves as Chairman of the SITS Scientific Committee; has served on scientific advisory boards for Boehringer Ingelheim and ThromboGenics NV; has received funding for travel and speaker honoraria from Boehringer Ingelheim, Lundbeck Inc., and Ferrer; and serves on the editorial boards of Stroke and Cerebrovascular Diseases. Dr. Lees serves on scientific advisory boards for Boehringer Ingelheim, Talecris Biotherapeutics, Lundbeck Inc., Ferrer, and PhotoThera; and has received speaker honoraria from Boehringer Ingelheim, Lundbeck Inc., ThromboGenics NV, and Talecris Biotherapeutics."

I want to use TPA to treat stroke without reservations, but the literature is broken.  Still hoping IST-3 will help define a low-risk population that benefits.

"Thrombolysis outcomes in acute ischemic stroke patients with prior stroke and diabetes mellitus"

Thursday, November 24, 2011

We Overestimate CAD Pretest Probability

The ACC/AHA clinical practice guidelines have a set of reference values for the pretest probability of >50% stenotic coronary artery disease based on the type of pain and age.  These values range from 2% in a 30 year old woman with non-anginal pain to 94% in a 60 year old man with typical angina.

And, turns out, this is way off.

This is a CTCA registry study of patients undergoing coronary angiography, 14,048 consecutive patients with suspected CAD, looking at both the incidence of 50% luminal narrowing (clinically interesting) and the incidence of 70% luminal narrowing (potentially flow-limiting), and correlating it to asymptomatic, non-anginal, atypical angina, typical angina, or "dyspnea only".

The meaningful tables of results somewhat defy summarization, but, they have plenty of hypertensives with dyslipidemia - but not very many diabetics or smokers - in their cohort.  In the end, however, none of the observed CAD was anywhere close to the predicted pretest probabilities.  The cohort with the highest prevalence of CAD was the typical angina in age 70+ males - but even that led to only 53% having a 50% lesion.  More than anything, age and gender the most significant predictors of CAD - with no population of women having greater than 29% incidence.

It's an interesting table worth looking at - CAD really doesn't kick in until after age 40, and, even then, only mostly in men, and, even then, only in patients with typical symptoms.  Once you hit age 50 in men, however, there's CAD everywhere, even with atypical (or no) symptoms.

There was also some variability by study site - with the 2,225 from Korea having very little CAD and the 29 from the Swiss site having markedly more, but the remainder are relatively similar.

I love studies that just present reams of data and don't try to push any particular sponsored agenda.

"Performance of the Traditional Age, Sex, and Angina Typicality–Based Approach for Estimating Pretest Probability of Angiographically Significant Coronary Artery Disease in Patients Undergoing Coronary Computed Tomographic Angiography"
http://www.ncbi.nlm.nih.gov/pubmed/22025600


Tuesday, November 22, 2011

Another Call to Retire Dopamine

The slow, gradual shift from dopamine to norepinephrine as the vasopressor of choice in septic shock has another piece of ammunition - this time a meta-analysis of the observational and randomized trials.

They perform two separate analyses - an analysis of five observational trials and an analysis of six randomized trials.  They find heterogeneity and no difference in the observational analysis - and then drop the observational trial responsible for the heterogeneity, and find an RR for mortality of 1.23 favoring norepinephrine.  Then, with the randomized trials, they find an RR for mortality of 1.10 favoring norepinephrine.  The RR for arrhythmias associated with dopamine use was 2.34 in their pooled analysis.

Of the RCTs, most of the patients came from one trial with 1044 patients and includes four trials with fewer than 50, so it's not exactly as though this analysis adds a lot of statistical power - but it's enough to reinforce the trends from each trial.

It is reasonable to suggest that norepinephrine is superior to dopamine - but I would also suggest the magnitude of that difference, given the data we have so far, has only been shown to be small.

"Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis"
http://www.ncbi.nlm.nih.gov/pubmed/22036860

Monday, November 21, 2011

Prolonged QT - Don't Believe The Hype?

Much ado is made about the risk of QT prolongation and the development of malignant arrhythmias, particularly Torsades de Pointes - but how frequently does TdP actually occur in these patients who QT prolongation?  Should we be worried about every EKG that crosses our paths with a prolonged QT?

It seems, like so many things, the answer is yes and no.  This is a prospective observational study from a single institution that installed cardiac monitoring that enabled minute-by-minute measurement and recording of QT intervals in their monitored inpatient population.  They evaluated 1,039 inpatients for 67,648 hours worth of time, and found these patients spent 24% of their monitored time with a prolonged QTc (>500ms).  One single patient had a cardiac arrest event where TdP was evident on the monitoring strip - a comorbidly ill heart failure patient whose QTc ranged as high as 691ms.

The authors then went back to attempt to determine whether the prolonged QT was associated with all-cause mortality with the 41 patients who died during their study period, and they found that 8.7% had QT prolongation versus 2.6% who did not.  However, as you can imagine, there are massive baseline differences between the QT prolonged population and the non-QT prolonged population, many of which contribute greater effects to in-hospital all-cause mortality.  The authors attempt logistic regression and finally come up with an OR of 2.99 for QT prolongation for all-cause mortality - which is lower in effects than CVA, obesity, pro-arrhythmic drug administration, and high serum BUN.

It's reasonable to say that patients with a prolonged QT are at higher risk for death - but it's also reasonable to say that sick patients at a higher risk of death are more likely to have a prolonged QT.  Torsades was rare, even with the thousands of hours of QT prolongation noted.  I would not get over-excited about QT prolongation in isolation, but, rather, only in the context of multiple risk factors for mortality in acute illness.

"High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: Results of the QT in Practice (QTIP) Study"
http://www.ncbi.nlm.nih.gov/pubmed/22001585