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"

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"

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:

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"

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. 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"

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"

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"

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"

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"

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"

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"

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"

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"

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"

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"

Saturday, November 19, 2011

Health Information Exchanges Might Save Money

Though, from this data, it's not clear through what mechanism.

This is an retrospective billing database evaluation of Memphis Emergency Department visits between 2007 and 2008.  In Memphis, 12 EDs participate in an online data repository, which may be accessed by secure web connection.  The authors compared patients presenting to the Emergency Department for whom this medical record was accessed to patients for whom this record was not.

There were no baseline differences between the demographics of the study groups, although, this retrospective evaluation cannot account for the factors contributing to why physicians chose to access the information exchange for individual patients.

The results are rather odd.  The authors cite cost savings as a result of an OR of 0.27 for inpatient hospitalization after accessing the information exchange.  However, the frequency of basically every other type of activity stayed flat or increased - in fact, the OR for Head CT was 5.0 and a chest x-ray was 4.3 if information exchange records were accessed.

More tests?  Fewer admissions?  I'm not sure it's practical to generalize the effects of an information exchange on medical decision making in a retrospective fashion such as this.

"The financial impact of health information exchange on emergency department care."

Friday, November 18, 2011

Skipping the LP in Infants 30-90 Days - Eh.

This is another one of those "practice-changing" types of articles, where the authors try to debunk some specific aggressive diagnostic or therapeutic modality that is over-utilized in a low-prevalence, high-risk population.  This article, which you may have already seen, is regarding the need for a lumbar puncture in infants between 30 and 90 days.

They perform a retrospective review of nonconsecutive infants between 30 and 90 days of age who presented to the Emergency Department and received the "septic workup" - urinalysis/culture, blood culture, and lumbar puncture/CSF culture.  They analyze a data set of 392 infants, the overwhelming majority of which are completely culture negative.  52 of them are culture positive on their urinalysis, 13 are culture positive in the blood, and 4 are CSF culture positive.  The authors note that only one patient who had a positive urinalysis also had a positive CSF fluid culture – and that infant did not qualify as a low-risk infant by the Rochester criteria – so a well-appearing infant with a positive urinalysis need not undergo LP.

So, essentially, this study tells us only that meningitis is rare and that UTIs are common.  The authors attempt to make the flawed logical argument against LP in their discussion by emphasizing the negative predictive value for meningitis in the setting of an abnormal UA is 98.2%.  However, they erroneously discount the negative likelihood ratio of 0.87 (95% CI, 0.5–1.5).  Therefore, statistically speaking, based on their results, repeating this study 100 times could lead to nearly half the study results showing a positive urinalysis favored concomitant meningitis.

Now, in a clinical sense, the authors are likely correct.  An infant who looks well, meets the Rochester criteria, has an identified source for fever, and will be receiving antibiotics is at low risk for meningitis – by prevalence alone, not by anything this study shows – and is probable to have a good clinical outcome since they're receiving antibiotics (in the event that same organism is resulting in a well-appearing, subclinical systemic and cerebrospinal bacteremia).  The argument should not be that you can generate a zero-risk population with their combination of +UA and Rochester, but that the risk of bad outcome may be similar to the risk of harms associated with the lumbar puncture, false positives, and follow-on treatment/testing.

"Is a Lumbar Puncture Necessary When Evaluating Febrile Infants (30 to 90 Days of Age) With an Abnormal Urinalysis?"

Wednesday, November 16, 2011

ED Nursing Hand-Offs & Stroke Outcomes

Yet again, in the "little things matter more" series of dull, but important, Emergency Department literature.  TPA or no, what matters more in terms of their ultimate outcome is everything that happens down the line.

This is a retrospective review of consecutively-collected prospective registry data for acute ischemic stroke patients in Louisiana, looking at patients who were present in the ED during shift change.  They simply reviewed and compared the outcomes of 366 consecutive patients, looking at good outcome, neurologic worsening, discharge status, and development of pneumonia.

There are, unfortunately, huge, irreconcilable differences between the shift-change and non-shift change groups - the group that was in the ED had milder strokes and was less likely to have TPA 9.5% vs. 4.5% - but still ended up developing more pneumonia.  After their mathematical adjustments for various baseline differences, being present during shift change ended up with a five-fold increased odds of developing pneumonia, resulting in decreased likelihood of discharge to home or rehab.  The authors attribute this primarily to non-adherence with stroke unit dysphagia precautions, which is probably reasonable.  This is just retrospective and observational, but it probably identifies an important operations issue for the Emergency Department.

So, perhaps it does matter whether you give TPA or not - if TPA gets them out of the ED faster, that will help more than anything.

"Emergency Department Shift Change Is Associated With Pneumonia in Patients With Acute Ischemic Stroke"

Tuesday, November 15, 2011

The Cure For Bleeding is More Bleeding?

Intraventricular TPA for intraventricular hemorrhage - I wouldn't call it counter-intuitive, but I would certainly call it unusual.

This is a small placebo-controlled, randomized, blinded, prospective trial enrolling 48 patients with intraventricular hemorrhage requiring placement of an intraventricular catheter for CSF drainage.  They were testing the theory that low-dose TPA would assist in clot breakdown, thus speeding recovery.  There are probably not significant differences between groups - although the placebo group was oddly mostly women.  Also fascinatingly, the predicted mortality of each group was ~74% - and ended up being 23% in the placebo group and 19% in the TPA group.  Serious adverse events including 61% in the TPA group and 36% in the TPA group.  Due to the small sample size of the cohort, none of these differences reached statistical significance.

Unfortunately, the screaming major flaw in this study is that they do not truly have a control group - a true control would be standard care without the use of placebo administration through the intraventricular catheter.  Their rate of ventriculitis (8% and 9%) is higher than the typically expected rate for intraventricular catheter placement (probably below 5%), and is consistent with prior studies that showed increased incidence of ventriculitis when the catheter is used for administration of drugs or irrigation.  So, the safety profile and minimal outcome trend in favor of the TPA group can't truly be evaluated because it isn't being compared to the current standard of care, which is leaving the catheter alone for drainage only.

The authors conclude these results support further evaluation - which is already ongoing in the CLEAR III trial - and that the treatment met their pre-defined safety profile cut-offs.  Unfortunately, yet again, propagating their skew on the data is motivated by financial interests - Johns Hopkins has applied for a use patent and Genentech is behind the rtPA licensing and funding.  

"Low-Dose Recombinant Tissue-Type Plasminogen Activator Enhances Clot Resolution in Brain Hemorrhage"

Sunday, November 13, 2011

Big Pharma Is Behind The Money Hemorrhage

This is a research letter from the Archives of Internal Medicine that received a good deal of press recently, examining exactly where in the health system we were wasting money.

They focused on the ambulatory setting, used the NAMCS/NHAMCS database, and evaluated for the activities identified in the "Good Stewardship Working Group" identified by consensus to be low-yield and unnecessary.  They considered this to include antibiotics for afebrile/non-strep pharyngitis, routine EKGs, CT and MRI for uncomplicated low back pain, DEXA scans for young women, etc.  And they found - and this is where the big story comes in - $6.7 billion in these consensus not-recommended activities.

Fortunately for our Internal Medicine and Family Medicine colleagues, they actually weren't ordering a lot of unnecessary tests - $175 million for low back pain and $527 million for DEXA are a lot of money, but still a drop in the bucket.  The majority of the unnecessary activities, $5.8 billion of the total $6.7 billion, was writing for a brand-name statin (atorvastatin or rosuvastatin) instead of one of the generics.

Certainly just the tip of the iceberg.  Drug reps are more than earning their salaries, apparently.

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