You’re Drugged By What You Eat

When you drink sewage, it’s pretty clear what you’re getting: sewage, with all the expect, overt nutritional implications.

When you eat fruit, you expect a tasty and healthy meal.

Unfortunately, as this proof-of-concept study reveals, when you eat fruit watered by sewage, you get a little from Column A and a little from Column B.

This study conducted in Israel evaluated the presence of carbamazapine in healthy university student volunteers.  As carbamazapine is recognized to be excreted as an unchanged active drug, it is ubiquitous in untreated sewage – read "wastewater".  Half the recruited students were then randomized to eat a selection of vegetables acquired from producers watering their fields with wastewater, rather than treated or fresh water.  Unsurprisingly, the various vegetables and leafy greens from the wastewater farm had elevated levels of carbamazepine – and so did the participants randomized to that group.

Just a happy thought for the day – and a reason to think ever so slightly more about from where your food's water comes.

“Human Exposure to Wastewater-Derived Pharmaceuticals in Fresh Produce: A Randomized Controlled Trial Focusing on Carbamazepine”
http://pubs.acs.org/doi/abs/10.1021/acs.est.5b06256

Put the Platelets Away in ICH

Sometimes, medical practice in the setting of uncertainty simply turns out to be futile and low-value.

This is one of those times where we’ve probably been at least futile, and possibly harmful.

Life-threatening or critical intracranial bleeding in the setting of concomitant antiplatelet therapy frequently offers a dire prognosis.  As part of our standard “don’t just stand there!” approach in Emergency Medicine, patients with ICH in this setting are frequently transfused platelets in an effort to provide untainted clotting substrate.  This practice, however, has never been reinforced by substantiated evidence, and the pharmacokinetics of the antiplatelet agents suggests this strategy is unlikely to be efficacious.

This is the PATCH trial, a randomized, open-label trial conducted at 60 hospitals between 2009 and 2015, investigating the utility of platelet transfusion in the setting of ICH.  Patients with normal baseline functional status and ICH while taking aspirin, clopidogrel, or dipyridamole were eligible for inclusion.  Specific excluded ICH were epidural or subdural hematomas, significant intraventricular blood, surgical intervention planned, or those in which death appeared imminent.  Treating clinicians could not be blinded to study arm allocation, but follow-up assessors and data analysis was masked.  The primary outcome is was functional outcome on the modified Rankin Scale, analyzed via ordinal shift analysis.

The authors do not present the number of patients screened for potential enrollment during the study period, but, ultimately, 190 participants were included from 41 centers.  The authors state patients were well-balanced on most demographics, although median ICH volumes were a little higher in the platelet-transfusion group, with 34% of patients having ICH >30mL versus only 21% in the standard-care group.  There were four patients in the platelet-transfusion group who did not receive transfusion, and two in the standard-care that did.

In the end, outcomes were universally dismal.  Only 15 patients in the entire study survived with minimal disability or better.  The vast majority of patients were at least moderately disabled or dead at follow-up.  And, while the confidence intervals for many of their comparisons cross unity, none of the trends favored platelet transfusion.  Generally speaking, there were more deaths, fewer patients with minimal disability, and additional adverse events in the transfusion group.

I tend to feel this is a small enough cohort the heterogeneity between individual patients is enough to effect the overall results – including the apparent harms relating to platelet-transfusion.  However, there is certainly no signal of benefit, and lacking a compelling indication to utilize a scarce resource, I believe this is enough to suggest this practice should be routinely avoided.

“Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)30392-0/abstract

Triaging Large Artery Occlusions

Endovascular intervention for acute stroke can be quite useful – in appropriately selected patients.  However, few centers are capable of such interventions, and the technology to properly angiographically evaluated for large-artery occlusions is not available in all settings.  Thus, it is just as critical for patients to be clinically screened in some fashion to prevent over-utilization of scarce resources.

These authors retrospectively reviewed 1,004 acute stroke patients admitted to their facility since 2008, 328 of which had large-vessel occlusions: ICA, M1, or basilar artery.  They calculated the accuracy, sensitivity, and specificity of multiple different potential clinical scoring systems, cut-offs.  Unfortunately, every score made some trade-off – either in the rate of false-negative results excluding patients from potential intervention, or in the rate of false-positive results serving to simply subject every patient to advanced imaging.  The maximum accuracy of all their various scores topped around around 78%.

The authors’ conclusions are reasonable, if a little limited.  They feel every patient presenting with an acute stroke within 6 hours of symptom onset should undergo vascular imaging.  These are both reasonable, but ignore one of the major uses for simple clinical scoring systems: prehospital triage.  Admitting none of these are perfect, _something_ must be put to use – and, probably, given the current bandwidth for endovascular intervention, something with the highest specificity.

For what it’s worth, we use RACE to triage for CT perfusion, but CPSSS, ROSIER, or just NIHSS cut-offs around 10 would all be fair choices.

“Clinical Scales Do Not Reliably Identify Acute Ischemic Stroke Patients With Large-Artery Occlusion”
https://www.ncbi.nlm.nih.gov/pubmed/27125526

Tying Procalcitonin to Critical Care

It has been hard, over the years, to truly identify a role for procalcitonin.  Generally speaking, its best niche seems to be as a sort of C-reactive protein on steroids – a non-specific infectious or inflammatory marker with better sensitivity than WBC.  This has led to some usage in zero-miss contexts such as neonatal sepsis, as well as a potential role in antibiotic stewardship.

These authors, many of which are supported by the manufacturers of the procalcitonin assay, evaluate its predictive power in the setting of pneumonia hospitalization, attempting to risk-stratify patients for the combined endpoint of vasopressor support or invasive ventilation.  Their goal, they say, is to use procalcitonin levels to better inform level-of-care decisions – both escalated and de-escalated – at the time of hospital admission.

They analyzed 1,770 patients from a prior pneumonia study for whom banked serum samples were adequate for procalcitonin measurement, 115 of whom met their combined critical illness endpoint.  They report risk of critical illness increased approximately linearly with procalcitonin from 4% when procalcitonin was undetectable, to 22.4% when procalcitonin was 10ng/mL or above.  The AUC for procalcitonin alone was 0.69, as compared to WBC at 0.54.  Then, they further go on to add usage of procalcitonin in conjunction with other risk-stratification scores – ATS minor criteria, PSI, and SMART-COP – provided additional discriminatory information.

This could be a potentially useful and interesting application of procalcitonin – except they don’t really make any comparisons to other available tools, other than a straw man comparison with WBC.  Would the venerable CRP have a similar AUC?  Or, better yet, a lab we already use nearly ubiquitously to detect occult severe sepsis – a lactic acid level?  The authors do not present any specific discussion of alternative approaches – of which their friends at BioMerieux probably appreciate.

“Procalcitonin as an Early Marker of the Need for Invasive Respiratory or Vasopressor Support in Adults with Community-Acquired Pneumonia”
https://www.ncbi.nlm.nih.gov/pubmed/27107491