Month: August 2019

Let’s Not Treat the Asymptomatic (Urine)

It’s a fairly common picture: the altered/declining/demented/elderly, with a small leukocytosis, and some positive elements on a urinalysis – but no clear symptoms of urinary tract infection. For lack of a better explanation, perhaps, treatment is begun with antibiotics. The benefit is uncertain, but, at the least it is more likely to benefit than harm?

This retrospective study, within the scope of its limitations, finds no reliable benefit to treatment, and more likely harms. This study performed chart reviews on 2,733 hospitalized patients with “asymptomatic bacteriuria”, as defined as a positive urine culture in the absence of documented Infectious Diseases Society of America criteria for UTI. Constitutional or non-specific symptoms in those unable to specifically report (e.g, dementia, AMS) were not considered as consistent with UTI unless multiple systemic signs of infection were also present.

Not only did nearly 80% of patients identified as ASB receive antibiotics, these authors were unable to shed light on any value of treatment. Treatment of ASB was more common in the scenario above, but was also widespread in patients capable of reporting symptoms yet having none documented. The dependence on retrospective chart abstraction limits the accuracy of their observations, but they have face validity.

Patient-oriented outcomes associated with either antibiotic treatment or non-treatment were 30-day mortality, 30-day readmission, 30-day post-discharge Emergency Department visit, C. diff infection, and duration of hospitalization. Most adjusted and unadjusted odds ratios for poorer outcomes were associated with treating ASB, but these differences were generally not statistically significant. Duration of hospitalization, however, was statistically associated with antibiotic treatment. This may be a spurious finding relating to contextual clinical confounders, but it may also represent an element of diagnostic inertia distracting from the true underlying etiology relating to hospitalization.

Regardless, consistent with this journal’s series feature “Less is More”, yet another instance in which common practice does not easily lend itself to confirmation of value.

“Risk Factors and Outcomes Associated With Treatment of Asymptomatic Bacteriuria in Hospitalized Patients”

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2748454

Women are Just as Typical as Men?

It’s somewhat dogmatic in medicine to teach men and women present with differing symptoms during myocardial infarction. Women are, as they say, more likely to have “atypical” symptoms.

This study differs slightly from previous accounting of the presenting symptoms of men and women with potential cardiac ischemia. This is a pre-planned, prospective analysis accompanying the High-STEACS trial, featuring in part an evaluation of gender-specific cut-offs for high-sensitivity troponin. As part of this trial, rather than using a typical “conventional” troponin cut-off for the 99th percentile of 50 ng/L, they used 16 ng/L for women and 34 ng/L for men. These cut-offs were correlated with clinical information to determine the diagnosis of type I myocardial infarction, generating a prevalence of 16% for men and 12% for women among the 1,941 included in the analysis.

Among these, authors found similar prevalence of “typical” symptoms – dull, tight, pressure, aching, crushing, in the chest, arm or jaw – in women as men considered for potential acute coronary syndrome. Among those ultimately diagnosed with type I MI, women were actually slightly more likely to manifest “typical” symptoms – 77% versus 59%. The authors did not find the presence of multiple “typical” symptoms to have a terribly useful positive likelihood ratio for MI in either women or men.

Unfortunately, these data run into unavoidable selection bias: “All patients over 18 years of age in whom the attending clinician requested cardiac troponin for suspected acute coronary syndrome were eligible for inclusion.” Therefore, the so-called “atypical” presentation in which ACS was not suspected – i.e., the women with “atypical” presentations – would be, by definition, missed. It may be the difference between men and women is not as great as originally thought – but these data cannot definitively answer the question.

“Presenting Symptoms in Men and Women Diagnosed With Myocardial Infarction Using Sex-Specific Criteria”
https://www.ahajournals.org/doi/10.1161/JAHA.119.012307

Wednesday is for Stroke

It had been a few weeks since I perused the recently published articles in Stroke – and there were so many: 1) not quite enough for their own angry post, but 2) worth noting, so, here we are:

Emergency Department Door-to-Puncture Time Since 2014: Observations From the BEST-MSU Study
https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.025106

This one comes with the nonsensical medical lay press article entitled “Mobile stroke units get patients to hospital faster than ambulances“. No, mobile stroke units do not warp the fabric of space-time. They are bound by the same laws of physics and traffic as the rest of us.

What this study actually shows is the difference between door-to-groin-puncture time in patients arriving via the MSU versus regular EMS. The result: it saved about 10 to 15 minutes to have the pre-hospital neurologist evaluation in-person or via telemedicine. Considering the observational evidence regarding the fragility of collateral circulation within the first few hours of large-vessel stroke, this is obviously favorable – but the actual clinical effect of a few minutes can only be minimal at best.

Functional Outcome Following Stroke Thrombectomy in Clinical Practice
https://www.ahajournals.org/doi/10.1161/STROKEAHA.119.026005

A huge German registry of stroke thrombectomy provides some insights into the “real world” outcomes. These authors spend a little time comparing their outcomes to those observed in the meta-analysis of the trials, but this comparison is obviously challenging due to the entry and perfusion imaging selection criteria of the trials. The big takeaway, however: real world mortality was 28.6% compared with the trial mortality of 15.3%. These findings should prompt further investigation into strategies to reduce risk for death.

Blood Pressure and Outcome After Mechanical Thrombectomy With Successful Revascularization
https://www.ncbi.nlm.nih.gov/pubmed/31318633

This is just an observational series – with a lot of missing data – looking for any association between blood pressure and outcomes following mechanical thrombectomy. The general trend: higher is worse. Something like the normotensive range is associated with the best outcomes and fewest complications. However, such observations cannot be assumed to suggest improving blood pressure control will reduce the frequency of downstream complications. More likely, the blood pressure is rising as a result of the complications – intracranial hemorrhage and cerebral edema – and it is only hypothesis-generating at this stage to say strict control will improve outcomes.

Magnitude of Benefit of Combined Endovascular Thrombectomy and Intravenous Fibrinolysis in Large Vessel Occlusion Ischemic Stroke
https://www.ncbi.nlm.nih.gov/pubmed/31311465

Very few analyses truly spur a full rolling-of-the-eyes, but this is one of them: taking matched cohorts from NINDS and SWIFT-PRIME to conjure up some sort of quantification of the benefit of endovascular therapy in large-vessel occlusion. It isn’t so much the basic principle of the analysis with which I quibble – but the fact they are only able to roll with 80 patients each from their NINDS tPA, NINDS placebo, and SWIFT-PRIME cohorts. Of course, if you recall, large-vessel occlusions were not specifically identified in NINDS, so these authors are imputing their presence based on NIHSS and deficit patterns, which is hardly a reliable means of identification. Then, with only 80 patients in each cohort, the imprecision of each comparison is so great it’s virtually pointless to rely on these findings in the patient-facing shared-decision-making information graphics they created. Without reading too much between the lines regarding why this nonsense was ultimately published, it should be noted the lead author is Jeff Saver’s son.

Pulmonary Embolism in Syncope, Forever

For about the zillionth time – the Prandoni observations of 16% prevalence of pulmonary embolism in syncope are not not generalizable.

This is the BASEL IX study (BAsel Syncope EvaLuation Study) whose primary purpose is to gather observational data regarding the outcomes of patients with syncope. These authors pulled a chunk of their data to address the question of whether PE was highly prevalent among those with syncope, as well as to describe the timing of such any downstream “missed” diagnoses.

The data presented comes from 1,895 patients enrolled in the main study, 1,397 of whom were eligible via being clinically stable enough to provide informed consent, and in whom a D-dimer result was available. Patients underwent clinical assessment by treating physicians without influence by the study.

Overall, only 14% underwent imaging for PE, with PE ultimately found in 1.4% of the cohort at initial presentation. About half the remaining patients who did not undergo imaging had normal D-dimer results and were retrospectively calculated to have low pre-test probability. By logical conclusion, however, that means half the remaining cohort was either non-low pretest or had elevated D-dimer – but still did not undergo imaging.

The follow-up period was up to two years in 83% of this cohort, and only 12 events occurred in follow-up, all in the non-low/elevated D-dimer group not undergoing initial imaging evaluation. Eight of these were PEs and 4 were cardiovascular deaths. The good news: the earliest subsequent PE diagnosis was 55 days, and earliest death was almost a year later.

So, no, again, no – no need to pursue PE in syncope unless otherwise clinically indicated, even if the patient may be at incidentally elevated risk.

“Prevalence of Pulmonary Embolism in Patients With Syncope”
http://www.onlinejacc.org/content/74/6/744.full

If You Guessed “Definitely Not ACS” …

This little observational study, part of a larger troponin-centric evaluation, looked at the predictive value of clinician gestalt for acute coronary syndrome. This has been evaluated before – including by this same group – but this cohort is three times the size of their prior effort.

Of the 1,391 patient encounters included, 207 had an acute MI, and another 33 died or underwent coronary revascularization within 30 days. Only 60 patients actually fell into the category of “definitely not ACS”, and 3 of those turned out to actually have an AMI. However, adding an ECG and a troponin to the initial gestalt was ultimately 100% sensitive for acute MI said “definitely not” cohort.

The other end of the spectrum – the “definitely ACS” side – was similar, with gestalt requiring supplementation by troponin and ECG testing to confirm.

One of the authors’ takeaways: a label of “definitely not” isn’t safe enough to forgo troponin testing. However, this comes with a big caveat: the enrolled patient cohort was specifically chosen for the main study because the treating clinician judged they required evaluation for ACS. Thus, effectively by definition, “definitely not” is incompatible with the study population.

You should not use this study to justify evaluation with additional or definitive testing in those who are truly “definitely not” ACS – the cohort here was enriched by 60 year old patients with hypertension, hyperlipidemia, prior MIs, smokers, and diabetes, and it would truly be the exception for one of these patients to “definitely not” have ACS. The 28 year-old for whom you think “definitely not” can still be evaluated as you feel appropriate.

“Can emergency physician gestalt “rule in” or “rule out” acute coronary syndrome: validation in a multi-center prospective diagnostic cohort study”
https://www.ncbi.nlm.nih.gov/pubmed/31338902