Activated Protein C, also known as Xigris, which has had an infamous and circuitous career of sorts, is back.
After a short life of use in severe sepsis, the continued investigations into its efficacy have finally been unable to establish its benefit. Although many expensive therapies without conclusive benefit are still in use in medicine, we’ll score this one (belatedly) for the good guys.
This early animal research, published as a letter in Nature Medicine, reports on interventions targeting the aPC pathway to prevent lethal radiation injury to hematopoietic cells. They say that starting infusions of aPC within 24 hours of lethal radiation exposure mitigated radiation mortality in mice. Probably quite a long way off for real-world usage, but any potential treatment is better than none.
“Pharmacological targeting of the thrombomodulin–activated protein C pathway mitigates radiation toxicity”
A brilliant piece that eloquently states many of the ideas espoused on this blog, focusing on pulmonary embolism as the poster child for over-testing, over-diagnosis, and lack of sound evidence underlying treatment.
These authors, in the Archives of Internal Medicine, accurately describe the chimeric nature of pulmonary embolism – historically described as a dreaded disease, diagnosed clinically from the manifestations of pulmonary infarction, to the modern manifestation of filling defects noted on CTA during an episode of pleuritic chest pain. They discuss the handful of patients who benefited from the first heparinization for treatment, and argue the disease for which anticoagulation is the treatment is not the disease we are diagnosing today.
This article covers so many excellent points, and ties the clinical problems so tightly into the underlying principles, that it’s almost the sort of must-read article to which medical students should be exposed – in order to bring about that frightening moment of maturity in medicine in which you realize the emperor is distinctly lacking in clothes.
“The Diagnosis and Treatment – of Pulmonary Embolism: A Metaphor for Medicine in the Evidence-Based Medicine Era”
This article I dredged up from the archives is mostly of sentimental value – although, I could claim it’s related to Olympic sport-related trauma with the upcoming Games.
This is from the series “Case records of the Massachusetts General Hospital”, which run the gamut all the way out to some of the most esoteric diagnoses possible. This particular article describes the management and outcomes of a man impaled by a rowing shell while on the Charles River. Eight-person rowing shells are ~17 meters in length, have a crewed weight of nearly 1,000 kg, and travel fast enough that a water skier may be towed behind. There is a small rubber bumper affixed to the, otherwise sharp, wooden or carbon-fiber bow that is meant to reduce the potential for injury in event of a collision. In this incident, the momentum of a head-on impact dislodged the bow ball and resulted in the unfortunate impalement incident described. A fascinating little read.
Rowing collisions are uncommon, injuries are rare, and this is probably nearly unique.
“Case records of the Massachusetts General Hospital. Case 10-2007. A 55-year-old manimpaled in a rowing accident.”
It’s Jeff Kline Week at EMLitOfNote, with the second Carolinas paper this week – and, as a Patient Safety and Quality Fellow, I just can’t help but cite articles that deal with the consequences of otherwise well-meaning practice.
This small study followed 174 patients undergoing CTPA demonstrated a yield of 7% for PE. On the other hand, this same cohort demonstrated a yield of 14% for contrast-induced nephropathy – as defined by an increase in serum Cr of 0.5 mg/dL or >25%. Three of the 24 patients with CIN progressed to severe renal failure, two of whom died. The proportion of CIN and renal failure were similar to the outcomes observed in the additional 459 patients they followed for CT imaging on other contrast protocols.
So, the rate of CIN is not insignificant – particularly compared to the rate of diagnosis of PE at this institution. It seems to be suggested by this study, although not shown, that the relative risk of death conferred by receiving contrast and developing CIN might even exceed the number of adverse events that might have occurred from PE if left undiagnosed or untreated.
“Prospective Study of the Incidence of Contrast-induced Nephropathy Among Patients Evaluated for Pulmonary Embolism by Contrast-enhanced Computed Tomography”
In the United States, a quarter of our medical malpractice payments result from missed myocardial infarctions. Therefore, in states with sub-optimal liability environments, emergency physicians are stuck in a quagmire of conflicted interests and fear of litigation if a discharged patient has an MI.
Therefore, a common strategy is to make low-risk chest pain Someone Else’s Problem. And, this article from Archives of Internal Medicine shows the internist evaluating the patient simply makes the same surrender to defensive medicine. In this retrospective cohort, 2,107 admitted patients underwent 1,474 stress tests during their two-year study period. Of those 1,474, 12.5% were abnormal. Of those 184 patients, only 11.6% underwent cardiac catheterization, and a grand total of 9 patients received a revascularization.
So, the authors suggest two salient points:
– 2,107 admissions to yield 9 (supposedly) beneficial interventions – how crazy is that?
– What about the 88.4% of patients with abnormal stress tests that didn’t undergo an invasive test within 30 days – why are we using an evaluation strategy we don’t act on?
The authors think we might be able improve upon this practice pattern.
“Outcomes of Patients Admitted for Observation of Chest Pain”
The overuse of CTA in the Emergency Department and the over-diagnosis of pulmonary emboli of non-physiologic significance has been demonstrated as a significant societal harm. In response to this, the National Quality Forum has been looking at developing a quality measure aimed at reducing CTA use in the Emergency Department.
The NQF estimated 7 to 25% of CTAs in the ED might be unnecessary. From Jeff Kline’s shop at Carolinas, they prospectively gathered data on all their potential pulmonary emboli and attempted to determine which scans were “inappropriate.” For their purposes, a scan was “inappropriate” if it was a low-risk patient with a negative D-dimer assay, or it was a low-risk patient without D-dimer testing. 11% were D-dimer negative and 22% were low-risk without D-dimer testing performed, which sums to 32% potentially avoidable imaging.
Of the 1,205 “potentially avoidable” scans, there were 58 positives. The clinical significance of these potential misses is uncertain. Whether this represents an acceptable miss rate for a quality measure in a liability prone environment is another matter entirely.
“Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure”
The summer is a great time for swimming – and, luckily, there’s an evidence-based systematic review of treatment of jellyfish stings available from Annals of Emergency Medicine. Unfortunately, it’s only the relatively benign and inconvenient species from North America, rather than the life-threatening species found more commonly in the southern hemisphere.
Literally, everything has been tried on jellyfish stings in an attempted in treatment, from vinegar, to ammonia, to ethanol, to meat tenderizer, to magnesium chloride, and the list goes on. Essentially, the attempted treatments fall into two camps – wash off the nematocysts without inducing discharge, or simply to treat the pain and tissue damage from the venom itself.
The American Red Cross First Aid consensus suggests the use of vinegar – which, according to this review, induces nematocyst discharge in everything but some Physalia species. The real answer is…no single agent reliably inactivates nematocysts from every organism. The authors recommend simply using readily available saltwater to wash the affected area. For post-envenomation pain, topical anesthetics such as lidocaine and hot water were found to be most reliably effective. Given the limited availability of anesthetics to laypersons, the best treatment is likely to be hot water submersion to help inactivate the toxins.
“Evidence-Based Treatment of Jellyfish Stings in North America and Hawaii”
It is popular to worry about the harms of CT scans in small children. A retrospective Swedish study suggests decreased intelligence. And, our models based on nuclear weapon exposure data combined with dummy CT exposure suggest these scans are likely to result in an increased risk of malignancy.
This is another retrospective study in the National Health Service of Britain comparing malignancy outcomes with their exposure to CT in childhood. The scary headline: CT scan radiation triples the risk of leukemia and primary brain malignancy. Of course, triple the risk is essentially 1 additional case of leukemia and 1 additional case of primary brain malignancy in the first 10 years after exposure. So, this is potentially another study you can use to discuss the Number Needed to Harm with families when discussing the need for CT radiation in pediatric cases.
Now, whether articles like this trigger a wave of legal trolling for malignancies preceded by CT remains to be seen….
“Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study”
It’s a little more insightful than my cynical title indicates, but it is, essentially an article that tries to quantify what we already know – blood tests, MRI, and CT all add to ED length-of-stay.
While the article isn’t specifically earthshaking, it interests me in the context of patient flow through the Emergency Department and the utilization of finite ED resources. Every ED has a waiting room – and, if you’re like me, sometimes you look at the board and there are 34 waiting – on a good day. In that sense, one becomes acutely aware of the value of space in the ED with which to evaluate new patients. If blood tests and imaging tests are adding over an hour to ED LOS for each of your bed, then it would seem prudent to minimize those tests whenever possible. It might also, perhaps, even be feasible to consider “standard of care” to be a malleable concept based on a need to ration testing specifically to increase patient flow, balancing the risks of diagnostic uncertainty against the risks of prolonged waiting room times.
Just brought to mind some interesting issues.
“Effect of Testing and Treatment on Emergency Department Length of Stay Using a National Database”
Patients with cardiovascular disease are routinely placed on daily, low-dose aspirin for primary prevention of cardiac events.
Unfortunately, antiplatelet effects promote other types of bleeding, while the cyclooxygenase pathway has a deleterious effect on the gastric mucosal. This 4.1 million patient propensity matched retrospective database study from Italy demonstrated approximately 2 excess cases of major bleeding events – whether intracranial or gastrointestinal – per 1000 patients treated per year.
Which is approximately the number of major cardiovascular events prevented by the daily aspirin use during the same time period.
Not specifically relevant to Emergency Medicine, but yet another example of how it’s naive to think many treatments in medicine – even those (or particularly those!) that have been part of routine practice for eons – are benefiting patients without a significant risk of harms.
“Association of Aspirin Use With Major Bleeding in Patients With and Without Diabetes”