Month: March 2017

All Aboard the tPA Hype Bus

Indiscriminate use of tPA in those with undifferentiated stroke is a low-value proposition – even if you find the evidence reliable. The utility of tPA for stroke depends on anatomy, time, and tissue status – information the traditional non-contrast head CT does not usually provide. Unfortunately, one of the latest “innovations” in stroke care is simply to do this useless test faster – in a bus, down by the river.

This is the PHAST project out of Cleveland, which, like similar efforts in Berlin, Chattanooga, and Houston, puts a CT scan machine in an oversized ambulance. Many of the initial phases of these projects included a stroke physician physically in the vehicle – but this, as you would expect, takes advantage of telemedicine technology to provide consultation from afar.

The stated hypothesis of this project is “that the MSTU will allow significant reductions in time to evaluation and treatment of patients when compared to a traditional ambulance model in an American urban environment”, which is just mind-numbingly infantile. Of course, pre-hospital administration will be faster than in-house thrombolysis – the interesting data would be with regard to safety and misdiagnosis.

This report is of the first 100 patients evaluated – generated by 317 system alerts. Of these, 33 were given a preliminary diagnosis of probable stroke, 30 possible stroke, 4 transient ischemic attacks, 5 intracerebral hemorrhages, and 28 non-cerebrovascular. Of the 33 probable strokes, 16 received thrombolysis – and, by most of their various metrics, care was accelerated by 20-40 minutes. And, then, no outcomes, safety, or follow-up data is presented – apparently we are simply supposed to operate under the assumption this resource outlay and rush to provide the substrate for potential tPA administration is obviously prudent and effective care.

Probably the only interesting tidbit from this paper was with regard to one of the cases of ICH diagnosed by CT in the prehospital setting. One patient was identified as taking anticoagulation, and prothrombin concentrate complexes were initiated in the pre-hospital setting. The timeliness of anticoagulation reversal is almost certainly beneficial, although the magnitude of effect for the few minutes saved is uncertain.

“Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis”

http://www.neurology.org/content/early/2017/03/08/WNL.0000000000003786.abstract

Vitamin C for Sepsis

This is just a quick post in response to a tweet – and hype-machine press-release – making the rounds today.

This covers a before-and-after study regarding a single-center practice change in an intensive care unit where their approach to severe sepsis was altered to a protocol including intravenous high-dose vitamin C (1.5g q6), intravenous thiamine (200mg q12), and hydrocortisone (50mg q6). Essentially, this institution hypothesized this combination might have beneficial physiologic effects and, after witnessing initial anecdotal improvement, switched to this aforementioned protocol. This report describes their outcomes in the context of comparing the treatment group to similar patients treated in the seven months prior.

In-hospital mortality for patients treated on the new protocol was 8.5%, whereas previously treated patients were subject to 40.4% mortality. Vasopressor use and acute kidney injury was similarly curtailed in the treatment group. That said, these miraculous findings – as they are exhorted in the EVMS press release – can only be considered as worthy of further study at this point. With a mere 47 patients in both treatment groups, a non-randomized, before-and-after design, and other susceptibilities to bias, these findings must be prospectively confirmed before adoption. When considered in the context of Ioannidis’ “Why Most Published Research Findings Are False”, caution is certainly advised.

I sincerely hope prospective, external validation will yield similar findings – but will likewise not be surprised if they do not.

“Hydrocortisone, Vitamin C and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study”
https://www.ncbi.nlm.nih.gov/pubmed/27940189

Making Urine Cultures Great Again

As this blog covered earlier this month, the diagnosis of urinary tract infection – as common and pervasive as it might be – is still fraught with diagnostic uncertainty and inconclusive likelihood ratios. In practice, clinicians combine pretest likelihood, subjective symptoms, and the urinalysis to make a decision regarding treatment – and invariably err on the side of over-treatment.

This is an interesting study taking place in the Nationwide Children’s Hospital network regarding their use of urine cultures. In retrospect, these authors noted only half of patients initially diagnosed with UTI had the diagnosis ultimately confirmed by contemporaneous urine culture. Their intervention, then, in order to reduce harm from adverse effects of antibiotics, was to contact patients following a negative urine culture result and request antibiotics be stopped.

This tied into an entire quality-improvement procedure simply to use the electronic health record to accurately follow-up the urine cultures, but over the course of the intervention, 910 patients met inclusion criteria. These patients were prescribed a total of 8,648 days of antibiotics, and the intervention obviated 3,429 (40%) of those days. Owing to increasing uptake of the study intervention by clinicians, the rate of antibiotic obviation had reached 61% by the end of the study period.

There are some obvious flaws in this sort of retrospective reporting on a QI intervention, as there was no reliable follow-up of patients included. The authors report no patients were subsequently diagnosed with a UTI within 14 days of being contacted, but this is based on only 46 patients who subsequently sought care within their healthcare system within 14 days, and not any comprehensive follow-up contact. There is no verification or antibiotics actually being discontinued following contact. Then, finally, antibiotic-free days are only a surrogate for a reduction the suspected adverse events associated with their administration.

All that said, this probably represents reasonable practice. Considering the immense frequency with which urine cultures are sent and antibiotics prescribed for dysuria, the magnitude of effect witnessed here suggests a potentially huge decrease in exposure to unnecessary antibiotics.

“Urine Culture Follow-up and Antimicrobial Stewardship in a Pediatric Urgent Care Network”
http://pediatrics.aappublications.org/content/early/2017/03/14/peds.2016-2103

Troponin Sensitivity Training

High-sensitivity troponins are finally here! The FDA has approved the first one for use in the United States. Now, articles like this are not for purely academic interest – except, well, for the likely very slow percolation of these assays into standard practice.

This is a sort of update from the Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) consortium. This consortium is intended to “advance the early diagnosis of [acute myocardial infarction]” – via use of these high-sensitivity assays for the benefit of their study sponsors, Abbott Laboratories et al. Regardless, this is one of those typical early rule-out studies evaluating the patients with possible acute coronary syndrome and symptoms onset within 12 hours. The assay performance was evaluated and compared in four different strategies: 0-hour limit of detection, 0-hour 99th percentile cut-off, and two 0/1-hour presentation and delta strategies.

And, of course, their rule-out strategies work great – they miss a handful of AMI, and even those (as documented by their accompanying table of missed AMI) are mostly tiny, did not undergo any revascularization procedure, and frequently did not receive clinical discharge diagnoses consistent with acute coronary syndrome. There was also a clear time-based element to their rule-out sensitivity, where patients with chest pain onset within two hours of presentation being more likely missed. But – and this is the same “but” you’ve heard so many times before – their sensitivity comes at the expense of specificity, and use of any of these assay strategies was effective at ruling out only half of all ED presentations. Interestingly, at least, their rule-out was durable – 30-day MACE was 0.1% or less, and the sole event was a non-cardiac death.

Is there truly any rush to adopt these assays? I would reasonably argue there must be value in the additive information provided regarding myocardial injury. This study and its algorithms, however, demonstrates there remains progress to be made in terms of clinical effectiveness – as obviously far greater than just 50% of ED presentations for chest pain ought be eligible for discharge.

“Direct Comparison of Four Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I”
http://circ.ahajournals.org/content/early/2017/03/10/CIRCULATIONAHA.116.025661

Done Fall Out

Syncope! Not much is more frightening to patients – here they are, minding their own business and then … the floor. What caused it? Will it happen again? Sometimes, there is an obvious cause – and that’s where the fun ends.

This is the ACC/AHA guideline for evaluation of syncope – and, thankfully, it’s quite reasonable. I attribute this, mostly (and possibly erroneously) to the fantastic ED syncope guru Ben Sun being on the writing committee. Only a very small part of this document is devoted to the initial evaluation of syncope in the Emergency Department, and their strong recommendations boil down to:

  • Perform a history and physical examination
  • Perform an electrocardiogram
  • Try to determine the cause of syncope, and estimate short- and long-term risk
  • Don’t send people home from the hospital if you identify a serious medical cause

These are all straightforward things we already routinely do as part of our basic evaluation of syncope. They go on further to clearly state, with weaker recommendations, there are no other mandated tests – and that routine screening bloodwork, imaging, or cardiac testing is likely of no value.

With regard to disposition:

“The disposition decision is complicated by varying resources available for immediate testing, a lack of consensus on acceptable short-term risk of serious outcomes, varying availability and expertise of outpatient diagnostic clinics, and the lack of data demonstrating that hospital-based evaluation improves outcomes.”

Thus, the authors allow for a wide range of possible disposition decisions, ranging from ED observation on a structured protocol to non-specific outpatient management.

The rest of the document provides recommendations more relevant to cardiology management of those with specific medical causes identified, although tables 5, 6, and 7 do a fairly nice job of summarizing some of the risk-factors for serious outcomes, and some of the highlights of syncope risk scores.  While it doesn’t provide much concrete guidance, it at least does not set any low-value medicolegal precedent limiting your ability to make appropriate individual treatment decisions.

“2017 ACC/AHA/HRS Guideline for the Evaluation and Management of Patients With Syncope”
http://circ.ahajournals.org/content/early/2017/03/09/CIR.0000000000000499

The Failing Ottawa Heart

Canada! So many rules! The true north strong and free, indeed.

This latest innovation is the Ottawa Heart Failure Risk Scale – which, if you treat it explicitly as titled, is accurate and clinically interesting. However, it also masquerades as a decision rule – upon which it is of lesser standing.

This is a prospective observational derivation of a risk score for “serious adverse events” in an ED population diagnosed with acute heart failure and potential candidates for discharge. Of these 1,100 patients, 170 (15.5%) suffered an SAE – death, myocardial infarction, hospitalization. They used the differences between the groups with and without SAEs to derive a predictive risk score, the elements of which are:

• History of stroke or TIA (1)
• History of intubation for respiratory distress (2)
• Heart rate on ED arrival ≥110 (2)
• Room are SaO2 <90% on EMS or ED arrival (1)
• ECG with acute ischemic changes (2)
• Urea ≥12 mmol/L (1)

This scoring system ultimately provided a prognostic range from 2.8% for a score of zero, up to 89.0% at the top of the scale. This information is – at least within the bounds of generalizability from their study population – interesting from an informational standpoint. However, they then take it to the next level and use this as a potential decision instrument for admission versus discharge – projecting a score ≥2 would decrease admission rates while still maintaining a similar sensitivity for SAEs.

However, the foundational flaw here is the presumption admission is protective against SAEs – both here in this study and in our usual practice. Without a true, prospective validation, we have no evidence this change in and its potential decrease in admissions improves any of many potential outcome measures. Many of their SAEs may not be preventable, nor would the protections from admission be likely durable out to the end of their 14-day follow-up period. Patients were also managed for up to 12 hours in their Emergency Department before disposition, a difficult prospect for many EDs.

Finally, regardless, the complexity of care management and illness trajectory for heart failure is not a terribly ideal candidate for simplification into a dichotomous rule with just a handful of criteria. There were many univariate differences between the two groups – and that’s simply on the variables they chose to collect The decision to admit a patient for heart failure is not appropriately distilled into a “rule” – but this prognostic information may yet be of some value.

“Prospective and Explicit Clinical Validation of the Ottawa Heart Failure Risk Scale, With and Without Use of Quantitative NT-proBNP”

http://onlinelibrary.wiley.com/doi/10.1111/acem.13141/abstract

The Solution to Dilution is ….

Do we order a lot of urinalyses? Does the sun rise in the east? Does a bear ….

For a test we order with great frequency, there is actually quite a bit of complexity in its interpretation. The combination of symptoms, clinical context, the balance between sample contamination and presence of white blood cells, of nitrites and/or leukocyte esterase, and so on, can make it a relatively tricky test to interpret. The gold standard remains a urine culture.

Now – if you haven’t been already – you probably ought to be taking into account the urine specific gravity, as well.

This retrospective analysis of 14,971 children for whom paired urinalyses and urine cultures were available describes the test characteristics of WBCs/hpf, LE, and nitrites as stratified by urine specific gravity. There are a lot of numbers in this article – a “zillion” to be precise – across eighteen dense tables of +LR/-LR, sensitivity/specificity, and PPV/NPV, but the basic gist of the matter is: variations in urine concentration diminish the value of the test in different ways. As urine specific gravity increases, it becomes more likely a patient will not have a positive urine culture despite having typically diagnostic amounts of WBCs/hpf, +LE, and/or +nitrites. Likewise, with dilute urine, a lower threshold for WBCs/hpf may be needed to have adequate sensitivity.

Just one more layer to consider in this frequently used test of under-appreciated complexity.

“The Importance of Urine Concentration on the Diagnostic Performance of the Urinalysis for Pediatric Urinary Tract Infection”
https://www.ncbi.nlm.nih.gov/pubmed/28169050