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”

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.

“‘Top 5’ Lists Top $5 Billion”
http://www.ncbi.nlm.nih.gov/pubmed/21965814

When Parents Refuse a Septic Workup

This is a brief commentary and discussion regarding the implications of parental refusal of hospitalization and evaluation of a potentially septic neonate.  It is absolutely an issue we all hope to never face, but probably will at some point in our careers.

Two pediatricians offer differing opinions on the extent to which social work and child protective services need be involved, raising such issues as the threshold percentage for likelihood of serious bacterial infection/bacteremia should be for “imminent harm” to the child, and the perceived benefits of therapy.  No specific answers are gleaned from the article, but it is worth reading and thinking through the discussions you would have in a similar situation.

“When Parents Refuse a Septic Workup for a Newborn”
www.ncbi.nlm.nih.gov/pubmed/22025599

Ethanol – Miracle Drug (For Stroke)

From China, in Stroke, an animal model (poor rats, as usual) of MCA ischemia, collagenase-induced ICH, and post-TPA ICH.  Rats received either 0.5 mg/kg, 1.0 mg/kg, or 1.5 mg/kg ethanol after two hours of MCA occlusion.  Performance on various foot, balance, and parallel behavioral testing significantly favored the ethanol treatment group with initial and sustained reduction in errors as compared to the no-treatment group.

No difference was found between groups in induced ICH volume, and in their (small) series, no increase in ICH after TPA administration.  A transient increase in expression of hypoxia-inducible factor 1-alpha favoring ethanol was seen at 3 hours after reperfusion, gone by 24 hours.

I cannot wait to see the day where we give IV ethanol for acute stroke.

“Beer, the cause and solution to all the world’s problems.”

“Neuroprotective Effect of Acute Ethanol Administration in a Rat With Transient Cerebral Ischemia”

Computers – Probably Better Doctors for UTI

Uncomplicated urinary tract infections are probably one of the diagnoses that Emergency Physicians handle the worst – if they come to the ER, they’re likely to get some sort drawn-out testing, whereas, if they went to their regular physician or called the nurse hotline, there would be antibiotics waiting for them at the pharmacy before they finished talking.

This is a prospective study in which patients with possible UTI were referred to a triage kiosk to complete a standardized computer questionnaire.  624 patients with possible UTI interacted with the kiosk – and unfortunately, only 103 qualified for the study by having enough features of typical, low-risk illness.  Patients were then randomized to protocolized antibiotic prescription as reviewed by a triage physician or usual care.

The good news – the kiosk saved a lot of time (89 minutes vs. 146 minutes).  The bad news – there were only 41 patients  followed-up in the intervention group and 26 followed-up in the control group, so we end up with only a tiny number of patients in each arm.  The kiosk group received more antibiotics for negative urine cultures than the control group (93% vs. 67%), so there is some additional element of harm secondary to antibiotic exposure – and, with a limited protocol, there are potential misses – and this study isn’t large enough to identify them.

But, really, uncomplicated, typical UTI symptoms in women shouldn’t be rocket science – and you shouldn’t necessarily be doing any testing.  I would say the computer is a better physician – except, it would be absolutely simple for a physician to simply narrow their approach to match the efficiency of the kiosk with, in theory, some added skill.

“A Randomized Trial of Computer Kiosk–expedited Management of Cystitis in the Emergency Department”

Conflict of Interest in TPA Literature

Another tiny bit of self-promotion – a new publication published today.  Stems essentially from a literature review I did after clawing through ECASS-III and noting that 12 of the 14 investigators were paid, sponsored, or employed by the manufacturers of alteplase – which muddied my estimation of the reliability of the conclusions.  Turns out, ECASS-III wasn’t the only one….

Pharmaceutical Sponsorship Bias Influences Thrombolytic Literature in Acute Ischemic Stroke”

Resident Productivity Does Not Predict ABEM Scores

Simple, single-institution study of 11 years of resident in-service scores, patients-per-hour, and ABEM qualifying examination scores – and, as previously shown, only PGY-3 in-service examination scores predicted ABEM oral and written examination scores.
Simulated oral board examination scores did not correlate with ABEM oral examination scores, and the relative number of patients-per-hour had no significant correlations between any testing.
I would say that bears out my observational experience – doing more has no bearing on whether you might be doing more incorrectly.
Outcome Measures for Emergency Medicine Residency Graduates: Do Measures of Academic and Clinical Performance During Residency Training Correlate With American Board of Emergency Medicine Test Performance?”
www.ncbi.nlm.nih.gov/pubmed/21999560

Good luck to everyone taking their ABEM exam today!

CTA Contrast Probably Increases ICH With TPA

…although the authors of this study draw the opposite conclusion.

In an effort to decrease the administration of TPA to stroke mimics and TIAs, some institutions are moving to the use of CT angiographic and perfusion studies after the initial non-contrast scan.  Previous studies have suggested an association between iodinated contrast administration and ICH after TPA.

These authors beg to differ.  In their study cohort, they retrospectively evaluate 319 patients receiving TPA for acute stroke, 69 of whom receive contrast and 243 who do not.  Depending on whether the ECASS or SITS-MOST definition of symptomatic ICH is used:
 ECASS – 4 of 69 (5.8%) with contrast, 12 of 243 (4.9%) without contrast
 SITS-MOST: 3 of 69 (4.4%) with contrast, 9 of 243 (3.7%) without contrast

…and that small absolute difference does not reach statistical significance because their numbers are so small.  This does not prevent the authors from stating “we found no association of either IV contrast administration or contrast dose with SICH in our series of patients treated with IV rtPA.”  They’re not wrong – but they barely address how underpowered their study is, or how every baseline characteristic (age, stroke severity, comorbid conditions) favored their contrast group, yet they still trended towards increased ICH.

Does the author of every TPA article live in a distortion field that blinds them to reasonable consideration of safety issues and study limitations?

“Iodinated Contrast Media and Cerebral Hemorrhage After Intravenous Thrombolysis”
http://stroke.ahajournals.org/content/42/8/2170.short?rss=1

Predicting Deterioration After Admission

This is a decidedly unsexy topic that I guarantee your Medical Director or QI committee cares about a lot.  Particularly where I work, we occasionally have a prolonged boarding event, the patient isn’t reassessed in a certain time frame, the patient is transported out of the ED – and they arrive on the floor or step-down and Rapid Response is called for an unanticipated escalation in care.

This is apparently a bigger deal in the United Kingdom, because it is recommended by their government hospital body to employ a risk-stratification system to predict patient deterioration.  These two articles discuss the derivation in the UK and the validation in Canada of the “ViEWS” score, which is named in part by from their electronic health record that stores their physiologic data.  The general gist of the system is that the authors of the first article derived a score incorporating pulse, respiratory rate, temperature, systolic BP, O2 saturation, whether patient was on oxygen, and a measure of CNS alertness.  They then compare it do several other scoring systems and amazingly enough, the scoring system they derive – using the system from the company the authors’ wives work for and in which they own shares of stock – works better than the other systems.

An abbreviated version of this is put into validation at a Canadian hospital that does not use any of the equipment, or have any financial conflict of interests.  They found equally good results – which, in summation they give as four risk-stratification groups:
 – < 3 points: 65% of all patients, only 0.02% died within 48 hrs.
 – 3-6 points: 28% of all patients, 0.41% died within 48 hrs.
 – 7-10 points: 6% of all patients, 3% died within 48 hrs.
 – >11 points: 0.7% of all patients, 13.8% died within 48 hrs.

So, yes, we all can probably look at the patients scoring >11 and know they’re sick without a scoring system.  However, this might be a model to look at with nursing staff to help change the parameters for floor beds or to reassess which patients can be downgraded in order to free up more intensive resources upstairs.  Just don’t necessarily buy the product being hawked by the original authors.

“ViEWS—Towards a national early warning score for detecting adult inpatient deterioration.”
www.ncbi.nlm.nih.gov/pubmed/20637974

“Validation of an abbreviated VitalpacTM Early Warning Score (ViEWS) in 75,419 consecutive admissions to a Canadian Regional Hospital”
www.ncbi.nlm.nih.gov/pubmed/21907689

Medication Errors During Resuscitation

According to previous literature from 2002, up to 19% of medication doses are administered in error to hospitalized patients.  Presumably, we’ve improved.

Apparently, we haven’t.  This is a prospective observational study by pharmacists in Pittsburgh who observed the inpatient Medical Emergency Team in operation – which in this instance, was a physician-led team with “full” critical care capabilities, as opposed to their non-physician Rapid Response Team.  They observed medication administration during 50 of these calls and found that there were 1.6 errors per medication administration.  Yes, they really observed more than one error per dose – but 66% of those issues involved aseptic technique.  Subtracting those, they observed an error merely every other dose.  46% were prescribing errors, 28% administration technique, 14% mislabeling, 10% preparation, and 2% improper doses.  The authors eventually conclude that 14% of the total non-aseptic errors were truly harmful, not just “errors”.

Despite the small sample size, I think it’s a fair assessment that “medical emergency” situations can be chaotic and error-prone – and we still have a ways to go to implement systemic changes to prevent errors.

In the end, the pharmacists’ solution is – more pharmacists.  Hmmm….

“Medication Errors During Medical Emergencies in a Large, Tertiary Care, Academic Medical Center”
www.ncbi.nlm.nih.gov/pubmed/22001000