The Top “Overuse” of 2016

Another entry in JAMA Internal Medicine’s lovely “Less is More” series, this is a “systematic review” of the previous year’s literature regarding potentially unnecessary care. Living here in the asylum, it seems all our fellow inmates and I are consigned to issuing weather reports from the tempest – but, hey, baby steps.

Their “systematic review” is not particularly rigorous.  It’s basically a literature search, followed by a subjective distillation by author consensus to those considered to be the most potentially impactful – but, regardless, their list is worth reviewing. Without further ado, the highlights of their ten selections:

  • Transesophageal echocardiography is more informative than transthoracic in illuminating the etiology of a stroke, but the additive information does not have a clear downstream benefit on outcomes.
  • Patients undergoing computed tomography to rule out pulmonary embolism without algorithm-compliant use of D-dimer suffer from overuse and low-value testing.
  • CT use increased in all Emergency Department patients with respiratory symptoms, with no evidence of downstream change in prescribing, hospital admission, or mortality.
  • Supplemental oxygen does not demonstrate benefit in patients with chronic obstructive pulmonary disease and mild exertional hypoxia.
  • Small improvements in antibiotic prescribing were seen when comparisons to peers were performed.
  • A shared decision-making implementation for Emergency Department patients with chest pain increased patient engagement and demonstrated a secondary effect of diminished admission and cardiac testing.


“2017 Update on Medical Overuse: A Systematic Review”

Morphine Not a Good Adjunct For Pediatric Pain

Treating acute musculoskeletal pain in the Emergency Department is a common occurrence – and even on the docket as a time-to-analgesia quality measure. Where we frequently see failures and delays, however, are in children, with much written regarding oligoanalgesia and the dragging of feet before any sort of pain management. Furthermore, adults are frequently managed with opiate therapy, which, despite its various pitfalls, may be considered to stand above the commonly used ibuprofen and acetaminophen monotherapy in children.

So, does it work better to combine an oral non-steroidal analgesic with opiate therapy in children? Or, perhaps, is even an opiate alone better with regard to adverse effects? That is the question asked by this three-arm, double-blinded, placebo-controlled, randomized trial. Children with painful musculoskeletal injuries were randomized either ti 10mg/kg oral ibuprofen, 0.2mg/kg oral morphine, or the combination of both.

The winner is: not children. With 91 analyzed in the ibuprofen-only arm, 188 in the morphine-only arm, and 177 in the combination arm, there were no reliable differences between analgesia between groups. More disappointingly, the average pain score on the visual analogue scale was ~60mm across all groups, and no group improved more than 20mm within an hour. The authors considered a VAS score of <30mm at 60 minutes to represent adequate pain control, and less than a third from each group achieved this. There were no serious adverse events in any group, but 20% of those receiving morphine complained of mild adverse events, mostly nausea and abdominal pain, compared with 7% of the ibuprofen-only arm.

So, still at square one for oral analgesia – but, at least, this negative trial helps inform our avoidance of the intervention tested here.

“Oral Analgesics Utilization for Children With Musculoskeletal Injury (OUCH Trial): An RCT”

Alas, Abscesses [heart] Antibiotics

“Fake news!” All you need for effective treatment for abscesses is an incision and drainage procedure – adjunctive antibiotics are just unnecessary exposures with only marginal benefit, at best.

Then, unfortunately, two trials have been published in the New England Journal of Medicine showing benefit for antibiotics – either trimethoprim-sulfamethoxazole or clindamycin – improve the rate of clinical cure. The magnitude of benefit was somewhere in the range of a number needed to treat between 7 and 14, with infrequent harms, suggesting the balance of benefit may favor antibiotics. However, the abscesses included in these study tended to be large, suggesting perhaps these results weren’t easily generalizable.

This is a subgroup analysis of one of these two studies, trying to dredge out a specific population for whom antibiotics weren’t actually of value. And, unfortunately, for the purists among us, the results are bleak. Accounting for the diminishing statistical power and reliability of such an analysis, there are few useful signals within these data. Neither the size of the abscess nor the area of surrounding erythema reliably predicted diminishing returns from adjunctive antibiotics, nor did presence of fever or comorbid illness. The only probably reliable signal in these data, consistent with results in the era prior to MRSA, shows antibiotics are probably unnecessary for those who are not infected with staphylococci. Unfortunately, until that point where the causative agent can be easily ascertained at the time of I&D procedure, these data aren’t terribly useful in a practical sense.

So, the benefit is not universal, but it’s nothing at which to scoff. Perhaps a delayed antibiotic strategy could be considered, but, it seems most patients ought be offered antibiotics following drainage of a clinically significant abscess.

“Subgroup Analysis of Antibiotic Treatment for Skin Abscesses”

CT (Almost) Never Before LP

The guidelines describing the patients with suspected bacterial meningitis for whom neuroimaging is indicated prior to lumbar puncture are quite broad. The Infectious Disease Society of America includes virtually every imaginable mental status or immune system impairment, and guidelines in Europe are similar. The anachronistic concern: cerebral herniation in the setting of increased intracranial pressure leading to an otherwise potentially avoidable death. But, guidelines in Sweden are different. In Sweden, their neuroimaging guidelines suggest only those virtually comatose or with focal neurologic signs should undergo CT prior to LP.

In this review of patients with acute bacterial meningitis from a Swedish registry, the authors attempt to parse out whether a decision to perform CT is not only unnecessary – but also potentially harmful. They analyze 815 patients ultimately diagnosed with bacterial meningitis and stratify them by those who received LP without CT, LP before CT, and CT before LP. Presenting features and comorbid medical conditions were abstracted retrospectively, and the results were analyzed with respect to the varying guideline recommendations, mortality, and functional outcomes.

The clear winner: CT rarely before LP, as in Sweden. By their guidelines, only ~7% of those ultimately diagnosed with bacterial meningitis had indication for CT prior to LP – but, unfortunately, 52% of patients underwent imaging anyway. The reason for “winning” if adherent to the Swedish strategy, however, was not just reduced resource utilization – it was mortality and functional outcomes. Mortality was almost halved in those for whom Swedish guidelines were followed, only rarely CT prior to LP. The authors attribute the signals for the underlying mortality difference to a greater percentage of patients receiving antibiotics within 1 hour or 2 hours when no CT was performed.

This probably overstates the magnitude of harm relating to CT use, as delays in antibiotics are probably more accurately delays in diagnosis, rather than logistics impacting timely delivery of antibiotics. After all, even in those with LP prior to CT, only 41% received steroids plus adequate antibiotics, so I expect the magnitude of effect seen here likely ties more reliably to confounding individual patient factors not easily adjusted for in a retrospective analysis.

That said, I do think the Swedes are doing the right thing – the vast majority of CTs were unhelpful. Their guidelines for neuroimaging – deep coma and/or lateralizing neurologic signs – will probably pick up any relevant findings (like the subdural empyema in this series), and reduce waste while obviating any possible delays in care.

“Lumbar puncture performed promptly or after neuroimaging in adult bacterial meningitis: A prospective national cohort study evaluating different guidelines”

Are We Killing People With 30-Day Readmission Targets?

Ever since the Center for Medicare and Medicaid Services announced their intention to penalize hospitals for early readmissions, folks have been worrying about the obvious consequences: would a focus on avoidance place patients at risk? Would patients best served in the hospital be pushed into other settings for suboptimal care?

That is the argument made in this short piece in the Journal of the American College of Cardiology. They look backwards at the last two decades of heart failure readmissions and short-term mortality, and take issue with the fundamental underlying premise of the quality measure, the inequities associated with the measure, and potential unintended harms. Their most illustrative example: when patients die outside the hospital within 30-days, paradoxically, they contribute to apparent improved performance in healthcare quality, as measured by 30-day readmission.

They back up their point by using the aggregate data analyzing readmissions between 2008 and 2014, published previously in JAMA, and focusing primarily on the heart failure component. In the original JAMA analysis, the evaluation paired individual hospital monthly readmission and risk-adjusted mortality, and were unable to identify an increased risk of death relating to reductions in 30-day readmissions. These authors say: too much tree, not enough forest. In the decade prior to announcements of 30-day readmission penalties, 30-day heart failure mortality had dropped 16.2%, but over the analysis period, 30-day heart failure mortality was back on the rise. In 2008 the 30-day mortality was 7.9% and by 2014 it was up to 9.2%, a 16.5% increase, and an even larger increase relative to the pre-study trend with decreasing mortality.

These are obviously two very different ways of looking at the same data, but the implication is fair: those charged with developing a quality measure should be able to conclusively demonstrate its effectiveness and safety. If any method of analysis raises concerns regarding the accepted balance of value and harm, the measure should be placed on a probationary status while rigorous re-evaluation proceeds.

“The Hospital Readmission Reduction Program Is Associated With Fewer Readmissions, More Deaths”

The Lifespan of the Torsed Testicle

Depriving an organ of its blood supply is invariably fatal in the local context. And, just as supposedly “time is brain”, “time is testicle” in the case of torsion. But, while we have our various time-based targets and thresholds for the acute treatment of cerebral ischemia, how long ought we be urgently concerned about the potential for testicle salvage after the onset of symptoms?

These authors undertook a systematic review of case series reports of testicular salvage following torsion, stratified by time of symptom onset. The quality of their evidence is, admittedly, low, and subject to the flaws of retrospective series and publication bias. That said, however, they identified a cumulative accounting of outcomes for 2,114 patients undergoing surgical exploration for potential salvage.

Earlier is, obviously, better. It is reasonable to estimate the likelihood of finding a salvageable testicle at ~95% if symptoms have been present for six hours or fewer. As time ticks by, rates of salvage decreased: ~77% between 6-12 hours, ~50% in the 13-24 hour timeframe, and, finally, ~25% and below in smaller samples beyond 24 hours. Even though these rates of salvage are lower, they remain substantial, and certainly beyond the traditional 6-8 hour viability teaching.

The authors do not have a conclusive unifying hypothesis as to why many cases were still salvageable despite extended time windows, but simply use these weak data to suggest timely evaluation and consultation remains important even beyond acute symptom onset.

“A Systematic Review of Testicle Survival Time After a Torsion Event”

Take Large-Vessel Strokes Directly to Endovascular Centers

This isn’t exactly “news” – or it shouldn’t be – because the basic underlying hypotheses for care in cerebral ischemia are: 1) identify or assume viable brain tissue, and 2) effectively reperfuse said tissue. So, of course, delays in 2 will lead to reductions in remaining viable 1 – the so-called “time is brain”.

This is a review of a mechanical thrombectomy registry, STRATIS, set up mostly just to record outcomes and usage in the “real world”. Registries are great for retrospective analysis fraught with bias, but, if high-quality evidence were cheap and easy to come by, we would have that instead. These authors performed an analysis associating onset-to-revascularization times with outcomes, stratifying their analysis by direct presentation to an endovascular center versus those requiring intra-hospital transfer. Unsurprisingly, onset-to-revascularization times are longer in those who presented to an outside facility prior to transfer. Unadjusted functional outcomes favored those with direct presentation (mRS 0-2 in 60.0% vs 52.2%), with no change in mortality. Statistical analysis of the impact of receiving tPA did not demonstrate any effect on outcomes.

So, yes, patients should be triaged in the field as best as possible to detect a large vessel stroke possibly amenable to intervention, and transported directly to capable centers. The only apparent negative impact is a delay to tPA, but the entire existence of the endovascular industry is predicated on the fact tPA just doesn’t work for large vessel strokes – the reperfusion rate is probably <10%, and it probably leads to increased post-procedural hemorrhage. There is essentially no value to stopping at the closest hospital just to give tPA when definitive therapy is delayed by, as these authors modeled, up to an hour and a half. The collateral circulation does usually give out eventually, so, while the magnitude of time-based treatment effect from this retrospective analysis isn’t reliable, it probably reflects some underlying truths – and stopping anywhere sooner is just a waste.

“Interhospital Transfer Prior to Thrombectomy is Associated with Delayed Treatment and Worse Outcome in the STRATIS Registry”

When Aggressive Sepsis Treatment Kills

Much has been made of efforts to detect and treat sepsis as early as possible after presentation, with many post-hoc analyses seeming to demonstrate time-sensitive mortality benefits associated with receiving the various components included in our “quality” measures. However, just like early goal-directed therapy back in the day, it has never truly become clear which element of early sepsis care confers the survival benefit. Absent specific data regarding how to best tailor therapy to the individual patient, we simply bludgeon everyone with the same sepsis bundle.

And, as we see here, that generalization is likely harmful.

This is a small randomized trial from Zambia – not to be confused with Nambia – in which 212 patients presenting with suspected infection, at least 2 systemic inflammatory response syndrome criteria, and hypotension were randomized to an early resuscitation protocol or “usual care”. The early resuscitation protocol sounds, generally speaking, similar to our modern approach to sepsis care – early intravenous fluid boluses with frequent intravascular volume assessment, vasopressors, and transfusions for severe anemia. The usual care cohort received, essentially, the same, only less so.

The two groups enrolled were roughly equivalent – but nothing like our sepsis cohort here in the United States. Approximately 90% of the patients enrolled were positive for the human immunodeficiency virus, half of the positive culture results were tuberculosis, the mean hemoglobin was 7.8 g/dL, and the majority of patients had been bedridden for over a week prior to presentation. Intravascular volume status and response to resuscitation was assessed by evaluating jugular venous pressure, tachypnea, and peripheral oxygenation. Finally, unlike many modern settings, most patients received dopamine as their vasopressor of choice and were admitted to general medical wards rather than intensive care units. In short, these are patients and care settings unlike in most industrial nations.

Mortality, not unexpectedly, was high – but it was much higher in those randomized to the early resuscitation cohort. Mortality in those receiving early resuscitation was 48.1%, compared with 33.0% in those receiving usual care. This mortality different then persisted out to 28 days, with over 60% mortality in the early resuscitation group at that time, compared with just over 40% in usual care.

This trial does not necessarily call into question the general principles of modern sepsis care, but it certainly provides a couple valuable lessons. The first, and most obvious, is the cautionary tale regarding generalizing research findings from one setting to another. Even a reasonably important, beneficial effect size can be transformed into a greater magnitude of harm if applied in another clinical setting. Then, this should clearly make us re-examine our current approach to sepsis care to ensure there is not a subgroup for whom early resuscitation is, in fact, the wrong answer. Our blind pursuit of checking boxes for quality measures, while generating an overall beneficial effect, is probably resulting in waste and harms for a substantial subgroup of those presenting with sepsis and septic shock.

“Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension”

The End of the “Emergency” Pelvic Exam

Enthusiasm, as measured by time-to-provider, for performing a pelvic examination in the Emergency Department is low. The logistics of a comfortable, adequate examination can be time consuming and detract from patient throughput. The yield of such examination is thought to be poor – enough so many providers, even absent sufficient evidence, choose to forgo the examination whenever reasonable, and depend on symptoms or advanced imaging to complete the evaluation.

This study aims to determine the acceptableness of the practice of forgoing the pelvic examination in a subset of vaginal complaints, those presenting with vaginal bleeding or abdominal pain in early pregnancy. From an ED standpoint, the typical most worrisome consideration is an ectopic pregnancy, with other diagnostic considerations important, but less salient. These authors developed a protocol in which women of fewer than 16 weeks gestation could be randomized to assessment with pelvic examination omitted or not. Their primary outcome was a composite pregnancy morbidity and utilization outcome at 30 days, with the trial designed to evaluate statistical equivalence between the two strategies.

Unfortunately, we have to give this trial a grade of “incomplete” for its ability to answer the research question – not the least because they under-enrolled their study cohort by over 500 patients. Of a planned enrollment of 720, they were only able to capture 202 due to slow enrollment due to a variety of factors. Furthermore, even if they had met their enrollment, I’m uncertain whether their composite outcome – chosen, almost certainly, to reduce the sample size needed to detect already rare outcomes – is clinically meaningful. Some elements of their composite morbidity outcome – unscheduled ED visits, hospital admissions, procedures relating to pregnancy – are of uncertain relationship to the decision to provide or withhold a pelvic examination at the time of first encounter. The most relevant of their composite is undoubtedly the identification of an alternative symptom source, but, again, this would require additional enrollment to detect a difference in such an infrequent outcome. Of the 202 patients included, 2 of 100 in the pelvic examination cohort had an alternative source for symptoms identified, but these are not specifically commented upon in the text.

Secondary outcomes relating to ED throughput and patient satisfaction favored the cohort omitting the pelvic examination, only ED length of stay suggests a potentially meaningful difference of approximately 20 minutes (not reaching statistical significance). Patient perceptions and concerns over embarrassment were not consistent across measures and assessment and probably not reliable.

Generally speaking, this study probably provides evidence supporting a strategy in which pelvic examinations are omitted, but this evidence is quite weak. The clinical significance of the information gleaned from a pelvic examination is unlikely to be of substantial clinical interested except in rare cases, and I would suggest the next steps in observational research to be to evaluate the clinical features of patients whose diagnosis or plan of care is changed by the pelvic examination.

“Is the Pelvic Examination Still Crucial in Patients Presenting to the Emergency Department With Vaginal Bleeding or Abdominal Pain When an Intrauterine Pregnancy Is Identified on Ultrasonography? A Randomized Controlled Trial”


It’s Sepsis-Harassment!

The computer knows all in modern medicine. The electronic health record is the new Big Brother, all-seeing, never un-seeing. And it sees “sepsis” – a lot.

This is a report on the downstream effects of an electronic sepsis alert system at an academic medical center. Their sepsis alert system was based loosely on the systemic inflammatory response syndrome for the initial warning to nursing staff, followed by additional alerts triggered by hypotension or elevated lactate. These alerts prompted use of sepsis order sets or triggering of internal “sepsis alert” protocols. Their outcomes of interest in their analysis were length-of-stay and in-hospital mortality.

At first glance, the alert appears to be a success – length of stay dropped from 10.1 days to 8.6, and in-hospital mortality from 8.5% to 7.0%. It would have been quite simple to stop there and trumpet these results as favoring the alerts, but the additional analyses performed by these authors demonstrate otherwise. In the case of both length-of-stay and mortality, both of those measures were trending downward independently regardless of the intervention, and in their adjusted analyses, none of the improvements could be conclusively tied to the sepsis alerts – and some relating to diagnoses of less-severe cases of sepsis probably prompted by the alert itself.

What is not debatable, however, is the burden on clinicians and staff. During their ~2.5 year study period, the sepsis alerts were triggered 97,216 times – 14,207 of which in the 2,144 subsequently receiving a final diagnosis of sepsis. The SIRS-based alerts comprised most (83,385) of these alerts, but only captured 73% of those with an ultimate diagnosis of sepsis, while having only a 13% true positive rate. The authors’ conclusion gets it right:

Our results suggest that more sophisticated approaches to early identification of sepsis patients are needed to consistently improve patient outcomes.

“Impact of an emergency department electronic sepsis surveillance system on patient mortality and length of stay”