Month: October 2018

Clinical Policy: Sanity Returns to ACS

This may be the most important recent sentence in modern emergency medicine:

“… based on limitations in diagnostic technology and the need to avoid the harms associated with false-positive test results, the committee based its recommendations on the assumption that the majority of patients and providers would agree that a missed diagnosis rate of 1% to 2% for 30-day MACE in NSTE ACS is acceptable.”

It’s no longer the domain of rogue podcasters and throwaway magazine editorialists to declare our zero-miss culture destructive and self-defeating – it’s finally spelled out in black & white by our speciality society. This is not a license to kill, of course, but it is now utterly reasonable to feel as though the wind is at your back when sending an appropriately-evaluated patient home.

This clinical policy statement does not address terribly many questions, but it does jam a lot of evidence into one document in their review. Specifically, these authors ask:

1. In adult patients without evidence of ST-elevation ACS, can initial risk stratification be used to predict a low rate of 30-day MACE?

In short, yes. These authors recommend HEART as their decision instrument du jour, but also acknowledge other scores that simply do not yet have enough diverse evidence to support their use. Interestingly, they also note clinical gestalt may be just as good as any decision instrument, at least when the ECG and troponin are negative for new ischemia. Again, more prospective evidence would be required to formally enshrine such a recommendation into a clinical policy statement.

2. In adult patients with suspected acute NSTE ACS, can troponin testing within 3 hours of ED presentation be used to predict a low rate of 30-day MACE?

Here the authors have only Level C recommendations, which means their recommendations are based on low levels of evidence. Overall, they are weakly in favor of using of high-sensitivity troponins alone, or repeat conventional troponin testing as part of a risk-stratification or accelerated diagnostic pathway.

3. In adult patients with suspected NSTE ACS in whom acute MI has been excluded, does further diagnostic testing (eg, provocative, stress test, computed tomography [CT] angiography) for ACS prior to discharge reduce 30-day MACE?

Please no: “Do not routinely use further diagnostic testing (coronary CT angiography, stress testing, myocardial perfusion imaging) prior to discharge in low-risk patients in whom acute MI has been ruled out to reduce 30-day MACE.”  Take that, CCTA proponents.  They give an expert consensus recommendation of 1 to 2 week primary care follow-up when feasible, or consideration of observation when no follow-up is possible.

The fourth question posed deals with use of P2Y12 and
glycoprotein IIb/IIIa inhibitors in the ED, and is met basically with a shrug.

So!  Go forth and provide good medical care – specifically, high-value medical care, further freed from the mental oubliette of zero-miss.

“Clinical Policy: Critical Issues in the Evaluation and Management of Emergency Department Patients With Suspected Non–ST-Elevation Acute Coronary Syndromes”
https://www.ncbi.nlm.nih.gov/pubmed/30342745

The Precogs Take On Sepsis

It seems like every week there’s another publicized instance of our impending replacement by artificial intelligence. Big Data, they say, is going to free us of the cognitive burdens of complex thought while maximizing healthcare outcomes. This latest entry is the “AI Clinician”, which has been created as a demonstration for the treatment of sepsis.  Or, rather more narrowly, the AI Clinician tries to prescribe the balance of fluids and vasopressors.

In this predictive feat of strength, decision models were created based on retrospective data sets comprised of tens of thousands of patients meeting Sepsis-3 criteria. Each patient’s clinical trajectory was described by their receipt of intravenous fluids or vasopressors in four-hour blocks, and the ultimate outcome of 90-day survival designated as the reward or penalty for their model. It’s rather beyond the scope of my statistical expertise to precisely describe their value comparison between the AI and clinicians, but suffice to say their results favor their models.

We are rather far from this sort of software being validated as a management adjunct in sepsis, but what’s most interesting is their incidental description of how deviations from their model affected mortality. Effectively by definition, of course, they find patients receiving IV fluids or vasopressors in doses most similar to the AI model had the lowest mortality. Greater variance from these optimal doses tended to increase mortality – most prominently excesses of IV fluids, rather than restrictive IV fluids. Vasopressors, on the other hand, showed a more symmetric distribution of poor outcomes with deviation from the optimal model:

The implication here mostly ties into the oft-repeated concern that high-volume fluid resuscitation is not necessarily the magic bullet in sepsis, and there is likely a point at which returns diminish, or turn harmful. This is virtually the exact hypothesis addressed by the CLOVERS trial. It will be quite interesting to see if these model findings are validated by the trial.

“The Artificial Intelligence Clinician learns optimal treatment strategies for sepsis in intensive care”
https://www.nature.com/articles/s41591-018-0213-5

HEART Outcomes in the “Real World”

There are two parallel universes in medicine – the “real world”, where most physicians practice, and the “academic world”, where most research is performed. Then, these disparate universes are scattered across the physical world, with its rich tapestry of cultures, further complicating the generalizability of any one set of observations.

This example demonstrates this effect on outcomes from the HEART Score, typically applied for its utility in disposition of those with Low (0-3) scores. Scores in this range have been generally observed to have a 6 week rate of Major Adverse Cardiac Events in the 0.7 to 1.7% range. However, these outcomes are subject to those aforementioned limitations – mostly academic centers, frequently across the pond.

These results are from a prospective evaluation of practices and outcomes regarding the approach to chest pain in the Emergency Department, ongoing at Kaiser Permanente Southern California. In this study, clinicians have been routinely recording the HEART Score in the context of chest pain evaluation since May 2016, allowing for the abstraction of this score in structured data. This analysis captured all Kaiser members evaluated in the ED who were not diagnosed with an acute myocardial infarction at the index visit, and gathered outcomes from their data warehouse.

Based on 29,196 ED encounters, 59% were “low risk”, and most of the remainder were “intermediate risk” (4-6). The overall rate of 6 week MACE was only 0.4% in the low risk group and 2.4% for intermediate risk, with most MACE being driven by revascularization. Only 0.2% of low risk and 1.0% of intermediate risk suffered death or acute myocardial infarction within 30-days. These authors then go on to suggest a HEART Score of 5 should rather be considered the cut-off for safe discharge from the ED, the maximum at which 30-day death or AMI was ~1% , which would represent ~89% of ED visits.

These data may represent our best insight yet into the pragmatic application of HEART in U.S. EDs, where certain semi-subjective aspects or misinterpretation of score elements serve to skew the scores higher.  Rather than 0-3 representing a low-risk cohort, it is probably more likely 0-5 as these authors report.  This ties into our general risk-averse nature, which tends to result in virtually universal over-triage of most complaints in the ED, as our other over-testing trends would indicate.  These data also probably serve as a lesson to those who promote the application of other decision instruments in the ED, as we’ve recently seen with the Canadian Head CT Rule for minimal risk head injury, or potential indication creep from the Ottawa Subarachnoid Rule – we must exercise caution regarding downstream unintended consequences and low-value care as a result.

“The HEART Score for Suspected Acute Coronary Syndrome in U.S. Emergency Departments”
https://www.ncbi.nlm.nih.gov/pubmed/30286933

Who Wants to Be Famous!

And by fame, I mean Twitter fame.

Based on SCIENCE!

This is a retrospective study of you, all you, you lab rats you, spinning your wheels about on the Twitter. This lovely study took four years of #FOAMed, chopped up all the tweets into little pieces, and ran the pieces through R. Specifically, they chopped up the tweets of a cluster of 238 heavily-retweeted tweeters (twits?), and analyzed their various attributes and flavors to determine those with the greatest likelihood of being retweeted.

And, the #1 determinant of whether a tweet would be retweeted and make you famous …

… was to be famous already, specifically, a tweet from one of 21 accounts with large (mostly >15,000) amounts of Twitter followers.

For the rest of us on the fringe of fame or worse, here were predictors of high retweet volume:

  • Tweets on resuscitation, trauma, neurology, infectious disease, pulmonary topics, and ultrasound.
  • Tweets with images, advertisements, or research critiques.
  • Avoidance of mental health topics, blog links, or “questions”.

The appendices are full of entertaining nuggets, including the top tweets of the study period – dominated by @EM_RESUS. Splendid work!

“Trends and Predictors of Retweets in Free Open Access Medical Education (#FOAMed) on Twitter (2013-7)”
https://www.ncbi.nlm.nih.gov/pubmed/30343518

Just Stand There! Bacterial Vaginosis Edition

There has long been considered to be a causative association between bacterial vaginosis and preterm delivery – with increasing risk of delivery when BV is identified earlier in pregnancy. Clearly, of course, early antibiotic treatment would eradicate the pathology and improve pregnancy outcomes. It just makes sense.

But, no.

In this large, multicenter trial performed in France, 84,530 pregnant women were screened before 14 weeks gestation, resulting in 5,630 diagnoses of BV. Patients deemed “low-risk” for preterm delivery were treated with one of regimens of clindamycin or placebo, while those few deemed “high-risk” were excluded from placebo randomization. The primary outcome was late miscarriage or early preterm birth, a range of preterm delivery spanning 16-32 weeks gestation.

Approximately 2/5ths of those approached for enrollment declined to participate, leaving 2,869 for randomization into one of the three low-risk arms. There were no important baseline differences between the three cohorts. The results: no difference. About 1% of each group met the primary outcome, and there were no signals of even a small magnitude of benefit to treatment with clindamycin in the low-risk cohorts. Adverse events, of course, clearly favored placebo – as befitting clindamycin’s known propensity for gastrointestinal effects, but no effects on fetal outcomes were apparent.

This is not specifically relevant to Emergency Medicine other than to demonstrate the need to rigorously test even what seems obvious. Widespread screening and aggressive, proactive treatment – even when all signs point to an expected positive result – represented low-value, and potentially harmful care.

“Early clindamycin for bacterial vaginosis in pregnancy (PREMEVA): a multicentre, double-blind, randomised controlled trial”

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31617-9/fulltext

All Hail the Female Resuscitationist

There has been more than one instance recently of observed associations between female gender and improved outcomes. Female physicians have lower rates of 30-day mortality and readmission rates for hospitalized elderly, and have better outcomes among female patients with acute myocardial infarction.

Now, another set of data showing improved survival after in-hospital cardiac arrest.

This is a retrospective review of 1,082 in-hospital cardiac arrests between 2005 and 2017 in which the gender of the code team leader could be ascertained. The minority – 30.2% – were led by a female physician. Location within the hospital, shockable rhythm, time of day, and patient age were similar between the male and female physician-led cardiac arrest cohorts. With male physicians, ROSC was 71.7% and survival to discharge was 29.8%, bested by female physicians with 76.8% ROSC and 37.3% survival. In a sample size this small, there are many potentially unmeasured confounders regarding the underlying health and type of arrest that may have contributed to the baseline likelihood of ROSC and survival – but this is still quite the interesting association.

Unfortunately, this brief analysis cannot tweeze out specifically why the female physician-led cohort had better outcomes. Their data set recorded compression depth and rate, and these were effectively the same – but they do not have medication use, timing, and other relevant attributes for evaluation. They make some further associations between physician and nurse gender, but the confidence intervals simply explode regarding whether any observed survival advantage may have occurred by chance alone.  I expect other inpatient cardiac arrest registries or databases may have more granular data to either confirm or refute this association – and, hopefully, if such an association continues to be observed, to better determine the practice patterns associated with any increased survival.

Lastly, it is reasonable to be concerned regarding publication bias relating to these such reports of gender-based outcomes.  It is probably editorially more interesting – and certainly seems more likely to get picked up by the lay press – to report associations favoring the female gender than the other way around.  Perhaps a bit more research seems warranted before condemning men to the scrap heap of history.  I hope, for my own sake!

“Female Physician Leadership During Cardiopulmonary Resuscitation Is Associated With Improved Patient Outcomes”
https://journals.lww.com/ccmjournal/Abstract/onlinefirst/Female_Physician_Leadership_During_Cardiopulmonary.96124.aspx

Five-Stars is Bad Medicine

In modern medicine, the patient is the customer. Medical services are customer services. Measures of patient – nay, customer – satisfaction are tied to reimbursement and, by association, contracts and employment. We’ve often remarked this perceived or overt emphasis on satisfaction is an incentive for bad medicine – specifically the “Where’s my Z-pack variety?”, and this is one of the few studies to actually show such an effect.

These authors reviewed three years of data from their direct-to-consumer telemedicine program and assessed the correlation between receiving a 5-star patient rating and various physician-related features. There were 85 physicians included across 8,437 patient visits for respiratory tract complaints, mostly sinusitis, but also pharyngitis, bronchitis, and “other” categories. While adjusted ORs showed a variety of small associations with 5-star service just barely clearing statistical significance, there were clear ORs favoring those who gave out candy. Antibiotics were provided in 66% of all visits, and the aOR for a 5-star rating was 3.23 (2.67-3.91) as compared to no antibiotic, and a non-antibiotic prescription bestowed an aOR of 2.21 (1.80-2.71). No other aOR exceeded 1.30, except the “free coupon” visits at 1.58 (1.31-1.90). They also noted it was not possible to be in the 90th percentile for patient satisfaction unless you were basically in the top half of antibiotic prescribing.

There were a couple physicians who were above the 50th percentile for patient satisfaction while maintaining some semblance of antibiotic stewardship. The authors do not provide any qualitative evaluation of those physicians but – thank you good sirs, please share your wisdom with us all.

“Association Between Antibiotic Prescribing for Respiratory Tract Infections and Patient Satisfaction in Direct-to-Consumer Telemedicine”
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2705078

I Choose You! Observation, I Hope.

We’re back with another patient-oriented clinical decision aid from the folks who brought you Chest Pain Choice – Pediatric Head CT Choice! In this episode, our noble heroes are out to educate parents regarding the risk of intracranial injury in children who are at “intermediate risk” for clinically-important traumatic brain injury by PECARN criteria.

In this multicenter, cluster-randomized, controlled-trial, these authors tested an information graphic and educational tool against usual care, with a primary outcome of parental knowledge. Additional measures of engagement in the decision-making processes, decisional conflict, and parental trust were measured as secondary outcomes related to the cognitive aspects, along with patient-oriented outcomes such as ciTBI and imaging utilization. They included 172 clinicians at 7 sites, and enrolled 971 patients, including 516 patients who consented for recording of their discussion regarding imaging. Follow-up by telephone was obtained in 890 (92%) of patients, with the remainder of outcomes assessment limited to electronic health record and vital records follow-up.

The results are mostly good news regarding the decision aid. Parents in the intervention arm could answer 6 of 10 questions about their choice correctly, compared with 5 of 10 receiving usual care. Secondary cognitive outcomes also favored the decision instrument, and physicians surveyed were generally in favor of the decision aid, as well. Imaging at the index visit was similar between the two groups, but downstream healthcare resource use and subsequent imaging was lower in the decision aid cohort.

There are findings here to critique, of course. There was only one ciTBI in the entire cohort, and they were imaged at the index visit. The expectation – and the tool – were constructed based on a 0.9% ciTBI rate, when the actual observed incidence was 0.1%. It is reasonable to consider the practical implementation of PECARN over-classifies patients into the “intermediate risk” cohort, placing additional children at risk for unneeded imaging – which, in turn, renders their “1 in 100” information graphic misleading. Then, clinicians spent an extra 2 minutes – 38% longer – with parents when using the decision aid. How much of the improved knowledge and trust stems from the decision aid, and how much from simply spending more time in the discussion? Finally, there are uncertain manifestations of the Hawthorne effect, particularly considering over half the encounters were recorded.

Overall, however, I have few quibbles with this decision aid. At the least, it is unlikely to exert a negative effect on parental knowledge or paradoxically increase unnecessary scanning.

“Effect of the Head Computed Tomography Choice Decision Aid in Parents of Children With Minor Head Trauma”
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2703135

New Anti-Flu, Just Like the Old Anti-Flu

Mitigating the harm of influenza pandemic is certainly an important endeavor. Despite the clinical importance, however, we’ve simply been kicking the oseltamivir can down the road for over a decade. Given the ongoing controversy over its usefulness, this is suboptimal – and winter, of course, is coming.

The newest agent to the scene is baloxavir marboxil, being developed in Japan. Baloxavir is a selective inhibitor of influenza endonuclease, rather than a neuraminidase inhibitor like oseltamivir. This recent article details the phase 2 dose-ranging study and subsequent phase 3 placebo and oseltamivir-controlled trial, CAPSTONE-1.

There were 1,436 patients enrolled in CAPSTONE-1, 1,064 of whom were ultimately confirmed to have influenza A or B. Most of the patients (~85%) had influenza A. The results are – well, “favorable”, by which I mean most likely “profitable”. Symptom duration in the infected population was attenuated by the the same length of time as oseltamivir, which in turn was about a day shorter than placebo. Various measures of viral expression were improved by baloxavir, which seemed to virtually eliminate detectable infective activity within the first 24 hours. There were a small number of extra treatment-related adverse events in the baloxavir cohort, but there were only a handful in each cohort overall, and it remains to be seen in further surveillance the true incidence.

As anyone who has been afflicted by influenza can tell you, a day’s shorter illness is no small feat.  of course, this is just a single, sponsored trial, with all the advantages to the “home team”, as it were.  Whether treatment with baloxavir can be demonstrated to decrease clinically important deterioration remains to be seen – as has been a persistent struggle for other antivirals, given the low rate of complications, overall.  Then, even with rigorous screening, a third of those treated did not have influenza.  Real-world use would almost certainly include a greater proportion of patients without influenza.  Lastly, baloxavir-treated patients were observed to develop resistance mutations in substantial numbers, leading to questions whether this medication will provide durable efficacy in widespread use.

“Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents”
https://www.nejm.org/doi/full/10.1056/NEJMoa1716197