Thursday, 5 November 2020

Lunacy in a tertiary ED: A study of the association between moon cycles and violence


Of course, we have all heard the full moon makes people barking mad and creates chaos in the ED.

“It must be a full moon!”

This study out of Melbourne looked at ED patient records over 3 years and compared the rate of “occupational violence and aggression” with the lunar cycle divided into quarters; new moon, first quarter, full moon and third quarter. Then they performed logistic regression to determine the association between the cycle and rates of violence.

In the end, they had 184,059 patients who presented to the ED over three years. It turns out that violence and aggression was NOT associated with a full moon but it was statistically associated with the first quarter (adjusted OR 1.38; P<0.01) and the third quarter (adjusted OR 1.29, P=0.03).

Well, there you have it…

In the discussion, the authors provide physiologic justification for the observed association based on some brilliant quotes from “prominent astrologers Dana Gerhardt and Dane Rudhyar.”

But the rational side of us knows this is completely nuts… just as we know that the transit of Venus doesn’t cause urinary retention and a meteor shower doesn’t cure syphilis.

This article appeared in Emergency Medicine Australasia. It did not appear in a predatory journal or the Christmas edition of BMJ. It was delivered in “dead pan” without even a hint of a wink at the end.

But the authors knew exactly what they were doing. And it provides us with a couple of valuable lessons.

Statistics can get things wrong.

I’m sure if the authors looked at the association of astrological birth signs (i.e. ISIS-2) with violence they would have found some statistically significant results; Capricorn and Leo were hot heads, but Gemini calm as a cucumber.

We need to be reasonably skeptical of the medical literature. Much of what gets published turns out to be false

Thanks to these authors for getting it right… wink… wink…

 

Covering:

Teung T, O’Reilly G, Mitra B, Olaussen A. Lunacy in a tertiary emergency department: A 3 year cohort study of the association between moon cycles and occupational violence and aggression. Emerg Med Aus. https://doi.org/10.1111/1742-6723.13601

 

 

  

Wednesday, 4 November 2020

Comparison of oral ibuprofen and acetaminophen with either analgesic alone for pediatric patients with acute pain. A crash landing...


You would think we should know the answer to this question already. But officially we don’t, and this paper adds absolutely nothing to our understanding.

This single-centre randomised, double-blind trial compared the analgesic efficacy of a combination of ibuprofen (10mg/kg) plus acetaminophen (15mg/kg) to either medication alone for the treatment of mostly acute traumatic pain in children. 

The primary outcome was pain scores at 60 minutes.

They concluded that the reduction in pain scores was similar between all groups. No difference...

The study design was quite good. But like a plane with no wings, there was a fatal flaw.

They only included 30 patients in each treatment arm!!!

Huh?

They provided a crazy power calculation, but it clearly does not pass the sniff test.

30 patients would have only enough power to find large changes in treatment effect making this at high risk for a type II error- or a false negative study. (A quick check of Clinicatrials.gov shows the study was originally intended to enrol 125 patients in each arm.)

I’m surprised the ethics committee approved such a study as it could never adequately answer the research question it proposed. I’m also surprised it got published, albeit in a lesser impact factor journal.

I strongly suspect the peer reviewers snuck the last sentence in to the abstract, “…but the trial was underpowered to demonstrate the analgesic superiority of the combination of oral ibuprofen plus acetaminophen in comparison with each analgesic alone.”

If this was the case, then why was the study conducted?

 

Covering

Motov S, Butt M, Masoudi A, et al. Comparison of oral ibuprofen and acetaminophen with either analgesic alone for pediatric emergency department patients with acute pain. J Emerg Med. 2020;58:725-732.[Link to article]

Monday, 2 November 2020

An RCT comparing antibiotics vs. surgery for appendicitis- the CODA trial


This is a big deal… the largest RCT comparing antibiotics vs. surgery for appendicitis and has closed the lid on this research question.

This non-blinded, pragmatic trial included adults with mostly image proven appendicitis in 25 centers in the USA. They excluded sick patients with shock, diffuse peritonitis, severe phlegmon, free air (microperforations were ok), neoplasm a few other things.

The antibiotic group got IV for 24 hours followed by oral tablets for 10 days.

The primary outcome was an overall health questionnaire at 30 days. Secondary outcomes were rate of appendicectomy in the antibiotic arm, complications, return to work etc.

The decision to perform appendicectomy in the antibiotic arm was up to the treating clinician.

Results?

1552 patients were enrolled from May 2016 to February 2020.

Antibiotics were non-inferior to appendectomy based on the 30-day health status. In the antibiotic group, 29% underwent appendicectomy by 90 days. (Those with appendicoliths were more likely to eventually get surgery). Half of the patients randomized to antibiotics were discharged from the Emergency Department!

I would imagine that the rate of appendicectomy could have been lower in this study given it was unblinded… the surgeons struggling to put their scalpels down after decades of surgical dogma.

Of course, this is not the first RCT’s looking at antibiotics for appendicitis. The message is consistent and it is clear where we stand. Antibiotics successfully treat acute uncomplicated appendicitis, but a small percentage (30-40%) of patients eventually get their appendix out.

It is now evident that we need to present patients with treatment options for appendicitis in a shared decision-making process

Yes, old habits die hard. But kneejerk surgery for appendicitis is now a stinking corpse.

 

Covering:

Flum DR, Davidson GH, Monsell Se, et al. A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis. N Engl J Med. 2020 Oct 5. doi: 10.1056/NEJMoa2014320. Epub ahead of print. PMID: 33017106. [link to article]

Sunday, 1 November 2020

Haloperidol for the treatment of headache in the Emergency Department... better than nothing

 


Usually randomized, double-blind, placebo-controlled trials are considered the best study design to truly answer a research question. But sometimes they are inappropriate.

Do you ever think we will see placebo used in a study on bacterial meningitis?

When a standard well accepted treatment exists, it is usually thought unethical to use placebo. This is where non-inferiority or equivalence trials come in- i.e. comparing a new drug to existing therapy.

But perhaps they grown them tougher in Michigan…

This randomized, double-blind, placebo-controlled trial compared haloperidol 2.5mg IV to matching placebo for ED patients with acute headache. The primary outcome measure was the change in VAS at 60 minutes.

Results?

118 patients were enrolled at a single large ED in Michigan. The trial was stopped after an unplanned interim analysis. A little bit naughty…

The reported pain dropped 4.77 units in the haloperidol group and only 1.87 in the placebo arm. Treatment with rescue ketorolac 30mg IV was required in 78% of the time with placebo and 31% with haloperidol. There were few side effects of haloperidol that were easily treated.

Ok, I willing to believe that haloperidol is better than nothing...thanks…

 

Covering

McCoy JJ, Aldy K, Arnall E, Peterson J. Treatment of headache in the Emergency Department: haloperidol in the acute setting (THE-HA Study): A randomized clinical trial. J Emerg Med. 2020;59:12-20. [link to article]

 

 

 

Friday, 14 August 2020

Propofol for migraine in the ED: A pilot controlled trial

Migraine – characteristics, recommended treatment

Really?!?

This was an open label pseudo-randomized trial of propofol (1mg/kg) vs. standard therapy for migraine in a single busy ED in Melbourne. 

Patients were included if the treating doctor thought they would require intravenous medication.

Patients were excluded if there was not a resuscitation bay available and a few other things.

The primary outcome was time to discharge from the ED or short stay unit. This is obviously not a patient-oriented outcome and subject to bias due to lack of blinding.

Results?

Over 28 months they enrolled 30 patients (one excluded in analysis due to missing data).

The time to discharge was about 5 hours in the propofol arm and 9 hours in the usual care arm. (P=0.021). The authors conclude that patients go home quicker.

There are some MAJOR problems with this study, mostly to do with study design, safety, efficacy, feasibility, and ethics.

There are substantial challenges to using propofol for migraine. It requires a set up for deep procedural sedation. It needs senior clinicians, airway nurses, and a resuscitation room for probably 30 minutes at a minimum. What are the harms to all the other patients in the ED that we are now potentially neglecting?

It is self-evident that the clinicians considered this as they were only able to enroll one patient a month for a common condition in a busy tertiary hospital.

In addition, with only 30 patients enrolled it cannot make any claims about efficacy or safety. Of the 15 patients who got propofol, six patients required additional medications. Two patients required airway maneuvers to maintain oxygenation & ventilation.

I am a bit surprised this study was granted ethical approval. But obviously there are differing opinions.

For now, please do NOT give propofol for migraine!

 

Covering:

Mitra B, Roman C, Mercier E, et al. Propofol for migraine in the emergency department: A pilot randomised controlled trial. Emerg Med Aus 2020;32:542-547. [link to article]

 

 

 

Dexamethasone in Hospitalized Patients with COVID-19- Preliminary Report

COVID-19 and the cheap, old, boring drug that could treat it

Beyond supportive care, we currently don’t have much to treat COVID-19. Remdesivir might decrease hospital length of stay. But we have found no medications that save lives.

The unprecedented RECOVERY trial involves 176 NHS organizations in the UK and are answering clinical questions at an lightning pace. This adaptive RCT has been looking at the use of dexamethasone, hydroxychloroquine, lopinovir/rotonavir, tocilizumab, and convalescent plasma.

This “preliminary report” is publishing the data on dexamethasone.

The background is COVID-19 often results in some immune mediated lung injury. Could steroids mitigate this? Or might they may cause harm by inducing immunosuppression?

6425 hospitalized patients with COVID-19 were randomized in a 1:2 fashion to dexamethasone vs. usual care.

The primary outcome was all-cause mortality at 28 days. They had a bunch of prespecified secondary outcomes.

The dose of dexamethasone was 6mg/day for 10 days.

Results?

Mean age was 66. Median days from symptom onset was 8 days. 16% of them were intubated and 60% were getting supplemental oxygen. 24% had no oxygen requirements.

Overall, 23% of patients randomized to dexamethasone died while 25% died in the usual care group for a number needed to treat (NNT) of about 35. (Rate ratio 0.83, 95% CI 0.75-0.93; P less than 0.001)

But it seemed to work the best in the sickest patients. Those who were intubated had an absolute mortality reduction of 12% for an NNT of 8. Those only on supplemental oxygen derived small benefit at a 3% reduction.

Unfortunately, it appears there is a trend toward harm in patient not requiring oxygen with a number needed to kill of about 26.

With the multitude of crap quality studies being rushed to publication, this is an absolute breath of fresh air. Prior to the final manuscript, this study has already changed the guidelines around the world.

Bottom line?

Intubated patients should get dexamethasone. We should probably give it to sicker patients on oxygen, but avoid it in everyone else.

Of course, this could all change tomorrow…

 

Covering:

Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with COVID-19- Preliminary Report. NEJM. 2020,  DOI: 10.1056/NEJMoa2021436 [link to full text article]

 

Thursday, 13 August 2020

Five-year follow-up of antibiotic therapy for uncomplicated appendicitis in the APPAC Randomized Clinical Trial

Long term outcomes are important when trying to understand the usefulness of a non-surgical approach to appendicitis. If all the patients eventually fail and have an appendicectomy, then what is the point?

The Appendicitis Acuta (APPAC) trial out of Finland randomized 530 patients with CT proven uncomplicated acute appendicitis to antibiotics vs. open appendicectomy. Now we have some 5-year data.

The cumulative incidence of appendicitis was 27% at year one, 34% year two, 35% year three, 37% year four and finally 39% by 5 years.

The five year overall surgical complication rate (SBO, surgical infection, incisional hernias, and abdominal pain) was 24%.

These are good statistics to consider when considering shared decision-making.

But there are a few things to remember.

  • All patients got CT prior to randomization to ensure uncomplicated illness. (i.e no perforation, abscess, appendicolith or suspicion of tumor.)
  • They excluded children and adults over the age of 60
  • They used some crazy C diff inducing doses of antibiotics including an IV carbapenem for 3 days followed by an oral fluoroquinolone and metronidazole. (But Augmentin has been used in other studies.)
  • Patients had open appendicectomies. Laparoscopic surgery would be expected to have a lower surgical complication rate.

What’s the take home?

There is now more and more literature consistently demonstrating the decent efficacy of antibiotic therapy for uncomplicated appendicitis. Decades of surgical tradition is hard to change. But it is getting to the point where patients will need to participate in discussions regarding treatment options.

 

Covering:

Salminen P, Tuominen R, Paajanen H, et al. Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. JAMA. 2018;320:1259-65. [link to article]

 How to Tell If That Pain Is Your Appendix – Health Essentials from  Cleveland Clinic