Cover image of REBEL Cast
(58)

Rank #117 in Medicine category

Health & Fitness
Medicine

REBEL Cast

Updated 5 days ago

Rank #117 in Medicine category

Health & Fitness
Medicine
Read more

Rational Evidence-Based Evaluation of Literature

Read more

Rational Evidence-Based Evaluation of Literature

iTunes Ratings

58 Ratings
Average Ratings
55
3
0
0
0

Leading the Way!

By flightRNaz - Feb 21 2019
Read more
So excited you have joined IAMED to share your knowledge to even more people!

Awesome Info!

By srezaie79 - Jun 09 2015
Read more
This podcast is doing a great job of bringing cutting edge information in Emergency Medicine from current literature. No biased about what to do, just reviews on the most recent data to help change your practice in real time.

iTunes Ratings

58 Ratings
Average Ratings
55
3
0
0
0

Leading the Way!

By flightRNaz - Feb 21 2019
Read more
So excited you have joined IAMED to share your knowledge to even more people!

Awesome Info!

By srezaie79 - Jun 09 2015
Read more
This podcast is doing a great job of bringing cutting edge information in Emergency Medicine from current literature. No biased about what to do, just reviews on the most recent data to help change your practice in real time.
Cover image of REBEL Cast

REBEL Cast

Updated 5 days ago

Rank #117 in Medicine category

Read more

Rational Evidence-Based Evaluation of Literature

Warning: This podcast is a series podcast

This means episodes are recommended to be heard in order from the very start. Here's the 10 best episodes of the series anyway though!

Rank #1: REBEL Cast Episode 40: Research From the Past Year – Pain Control

Podcast cover
Read more

Welcome back to Episode 40 of REBEL Cast. We have taken some time off but don’t worry, we are back.  In this episode, we will...

The post REBEL Cast Episode 40: Research From the Past Year – Pain Control appeared first on REBEL EM - Emergency Medicine Blog.

Oct 20 2017
16 mins
Play

Rank #2: REBEL Core Cast 4.0 – RSI Cheat Codes

Podcast cover
Read more

Take Home Points Bed Up Head Elevated (BUHE) position is a simple intervention that can reduce the rate of intubation-related complications. The bougie should be...

The post REBEL Core Cast 4.0 – RSI Cheat Codes appeared first on REBEL EM - Emergency Medicine Blog.

Feb 06 2019
6 mins
Play

Rank #3: REBEL Cast Episode 41: Research From the Past Year – Resuscitation

Podcast cover
Read more

Welcome back to Episode 41 of REBEL Cast. In this episode, we will be discussing some studies from the past year that caught our attention...

The post REBEL Cast Episode 41: Research From the Past Year – Resuscitation appeared first on REBEL EM - Emergency Medicine Blog.

Oct 26 2017
18 mins
Play

Rank #4: REBEL Cast Episode 65: Optimal Order of Drug Administration in Rapid Sequence Intubation

Podcast cover
Read more

Background Information: The sequential administration of a sedative and neuromuscular blocking agent (NMBA) to facilitate the passage of an endotracheal tube is a common method of...

The post REBEL Cast Episode 65: Optimal Order of Drug Administration in Rapid Sequence Intubation appeared first on REBEL EM - Emergency Medicine Blog.

May 09 2019
22 mins
Play

Rank #5: REBEL Cast Ep 54: What the Heck is Pseudo-PEA?

Podcast cover
Read more

Background: Pulseless electrical activity (PEA) is an organized electrical activity without a palpable pulse.  1/3 of cardiac arrest cases will be pulseless electrical activity and the...

The post REBEL Cast Ep 54: What the Heck is Pseudo-PEA? appeared first on REBEL EM - Emergency Medicine Blog.

Jun 27 2018
41 mins
Play

Rank #6: REBEL Core Cast 3.0 – Asthma, COPD + PNA

Podcast cover
Read more

Take Home Points Single dose oral dexamethasone is an excellent choice for asthma exacerbations. It takes away the compliance issue for patients who have trouble...

The post REBEL Core Cast 3.0 – Asthma, COPD + PNA appeared first on REBEL EM - Emergency Medicine Blog.

Jan 23 2019
14 mins
Play

Rank #7: REBEL Core Cast 2.0 – Cardiotoxic Drugs

Podcast cover
Read more

Take Homes Calcium Channel Blocker (CCB) toxicity usually present with bradycardia and hypotension, but with preserved mental status. This can help differential from Beta Blocker...

The post REBEL Core Cast 2.0 – Cardiotoxic Drugs appeared first on REBEL EM - Emergency Medicine Blog.

Jan 09 2019
8 mins
Play

Rank #8: REBEL Cast Ep 43: Pain Control and Opioid Sparing Options in the ED

Podcast cover
Read more

Background: In the United States we are not only seeing an opioid epidemic but also a shortage of IV opioid agents. For both reasons, it...

The post REBEL Cast Ep 43: Pain Control and Opioid Sparing Options in the ED appeared first on REBEL EM - Emergency Medicine Blog.

Jan 08 2018
25 mins
Play

Rank #9: REBEL Core Cast 6.0 – Traumatic Arrest

Podcast cover
Read more

Take Home Points: If the patient is a clear traumatic arrest, compressions aren’t indicated and, instead we should focus on the important interventions that need...

The post REBEL Core Cast 6.0 – Traumatic Arrest appeared first on REBEL EM - Emergency Medicine Blog.

Mar 06 2019
8 mins
Play

Rank #10: REBEL Cast Ep 46b: Vent Management in the Crashing Patient with Haney Mallemat

Podcast cover
Read more

In Episode 46a we discussed respiratory failure and NIV.  In episode 46b we are going move on to the patient where you have tried NIV...

The post REBEL Cast Ep 46b: Vent Management in the Crashing Patient with Haney Mallemat appeared first on REBEL EM - Emergency Medicine Blog.

Mar 12 2018
18 mins
Play

Rank #11: REBEL Core Cast 11.0 – Epiglottitis

Podcast cover
Read more

Take Home Points on Epiglottitis Epiglottitis has demonstrated a resurgence in the adult population. It is no longer a pediatric only disease. The classic presentation...

The post REBEL Core Cast 11.0 – Epiglottitis appeared first on REBEL EM - Emergency Medicine Blog.

May 15 2019
14 mins
Play

Rank #12: REBEL Cast Ep 61: Diagnostic Questions in Urinary Tract Infections in the Elderly

Podcast cover
Read more

Introduction: Beyond the Data The evolution from eminence-based to evidence-based care has come to define bedside emergency medicine, with rigorous skepticism and scholarly consideration accelerated...

The post REBEL Cast Ep 61: Diagnostic Questions in Urinary Tract Infections in the Elderly appeared first on REBEL EM - Emergency Medicine Blog.

Jan 03 2019
18 mins
Play

Rank #13: REBEL Cast Ep 48: Octreotide and Somatostatin for Undifferentiated Upper Gastrointestinal Bleed

Podcast cover
Read more

Recently I was asked to speak at the Texas College of Emergency Physicians (TCEP) conference April 2018.  The particulars of this session were, five, 10...

The post REBEL Cast Ep 48: Octreotide and Somatostatin for Undifferentiated Upper Gastrointestinal Bleed appeared first on REBEL EM - Emergency Medicine Blog.

Apr 13 2018
6 mins
Play

Rank #14: REBEL Cast Episode 67: EXTEND-ing Times for Systemic Thrombolysis in Acute Ischemic Stroke?

Podcast cover
Read more

Background: Despite the lack of replication of the NINDS & ECASS-3 trials, guidelines recommend the use of tPA in the ≤4.5hr window after the onset of symptoms of acute ischemic stroke [2]. These recommendations used non-contrast computed tomography (NCHCT) for the selection of patients.  More recent endovascular studies have shown that perfusion-based imaging can show potential viable brain tissue beyond the 4.5 hour mark in patients with large vessel occlusions and result in good neurologic outcomes.  This advance has prompted investigators to look at perfusion-based technology to identify a larger cohort of patients without large vessel occlusion that may be candidates for systemic thrombolysis.  One of the big fears in stroke management is the concept of indication creep: finding more uses for a medication or product without strong evidence to support its use. The bigger question is, does this increase in use help the company’s bottom line or the patient? It is no wonder physicians are skeptical of industry sponsored trials, as we sometimes question the motives behind the study.  Now we have another industry sponsored trial: EXTEND. In this trial.

REBEL Cast Episode 67: EXTEND-ing Times for Systemic Thrombolysis in Acute Ischemic Stroke?

Click here for Direct Download of Podcast

What They Did:

  • Phase 3, multicenter, randomized, placebo-controlled trial
  • Patients with ischemic stroke with hypoperfused but salvageable regions of the brain on perfusion imaging in the 4.5 – 9.0 hr window after onset of stroke or on awakening with stroke (if within 9 hrs from the midpoint of sleep)
  • Randomized to systemic tPA vs placebo
    • Alteplase = 0.9mg/kg of body weight (maximum = 90mg) administered IV as a 10% bolus and 90% infusion over 1hr

Outcomes:

  • Primary: mRs of 0 or 1 at 90 days
    • The risk ratio was later adjusted for age and clinical severity at baseline
  • Secondary:
    • mRs score at 90days using an ordinal analysis to assess functional improvement
    • mRs score of 0 – 2 at 90 days (functional independence)
    • Percentage of reperfusion of at least 50% and of at least 90% at 24hrs after the intervention
  • Tertiary:
    • Recanalization at 24hrs after stroke
    • Major neurologic improvement (defined as a reduction in the NIHSS score of ≥8 points or a score of 0 or 1 within 24 hours, 72 hours, and 90 days after intervention)
  • Safety:
    • Death within 90 days after intervention
    • Symptomatic ICH (confluent blood clot occupying >30% of the infarct with substantial mass effect) within 36hrs after intervention with an increase of at least 4 points in the NIHSS score from baseline

Inclusion:

  • ≥18 years of age
  • Excellent functional status prior to enrollment (defined as a score of <2 on the modified Rankin scale)
  • Had a stroke with a clinical severity score at presentation of 4 to 26 on the NIHSS
  • Had hypoperfused but salvageable regions of brain detected on automated perfusion imaging
    • Defined as an estimated volume of irreversibly injured ischemic-core tissue of <30%)
    • Perfusion lesion-ischemic core mismatch was defined as a ration >1.2 between the volume of hypoperfusion and the volume of the ischemic core, an absolute difference in volume greater than 10mL, and an ischemic core volume of less than 70mL
  • Occlusion of a large cerebral vessel was not a prerequisite for inclusion

Exclusion:

  • Patients considered for endovascular thrombectomy at the time of enrollment
  • Rapidly improving symptoms, in the judgment of the managing clinician
  • Eligible for Endovascular Clot Retrieval
  • Pre-Stroke mRs of ≥2
  • Contraindication to contrast agents
  • Ischemic core >1/3 MCA territory
  • Pregnancy
  • Previous stroke within last 3 months
  • Recent history or clinical presentation of ICH, SAH, AVM, Aneurysm, or Cerebral neoplasm
  • Use of oral anticoagulation and INR >1.7
  • Clinically significant hypoglycemia
  • Uncontrolled HTN (SBP >185mmHg or DBP >110mmHg) on at least 2 separate occasions at least 10 minutes appart or requiring aggressive treatment to reduce BP
  • Major surgery within the preceding 14 days
  • Thrombolysis within previous 72hrs

Results:

  • Original sample size was supposed to be 400 patients
    • Later sample size modified to 310 patients
    • Only 225 of planned 310 patients enrolled due to early stoppage
    • 25% of patients received assigned intervention in >6.0 – 9.0hr window
    • 10% of patients received assigned intervention in the >4.5 – 6.0hr window
    • 65% of patients woke up with their stroke symptoms with an unknown time of onset
  • Initial NIHSS Score at Enrollment:
    • tPA: 12 (Range 8.0 – 17.0)
    • Placebo: 10 (6.0 – 16.5)
  • Primary Outcome of mRs of 0 or 1 at 90d:
    • tPA: 35.4%
    • Placebo: 29.5%
    • aRR 1.44; 95% CI 1.01 – 2.06; p = 0.04
    • The unadjusted risk ratio did NOT show a significant difference between groups (RR 1.2; 95% CI 0.82 – 1.76; p = 0.35)
  • Symptomatic ICH:
    • tPA: 6.2%
    • Placebo: 0.9%
    • aRR 7.22; 95% CI 0.97 – 53.5; p = 0.05
  • No improvement in functional status or functional independence at 90days
  • No statistical difference in mortality within 90 days after intervention (11.5% with tPa vs 8.9% with placebo)

Strengths:

  • Randomization was performed through a centralized website with stratification according to geographic region and time of intervention (>4.5 – 6.0hrs & 6.0hrs – 9.0hrs after stroke onset), or on awakening with stroke symptoms
  • Symptomatic ICH was adjudicated by a central panel of stroke neurologists and neuroradiologists

Limitations:

  • Trial terminated early because of a loss of equipoise after the publication of positive results from the WAKE UP trial published in May 2018. This is a methodological issue, as most trials that go to completion have a regression to the mean, meaning trials stopped early, tend to be hyperinflated in their results.
  • The design of the trial, the analysis and collection of the data were performed by members of the executive committee and by the investigators at trial sites who had multiple financial conflicts of interest, including Boehringer Ingelheim the manufacturer of alteplase, which again does not negate the results, but should cause one to be skeptical of the results.
  • Unclear if patients were consecutively enrolled (i.e. a convenience sample)
  • Advances in stroke care occurred during enrollment of this study, so it is difficult to know how that affected the study
  • Few patients enrolled at each site hinting that this only applies to a small group of patients overall

Discussion:            

  • Recruitment for this trial occurred from 2010 through February 2018. Stroke management with endovascular therapy had changed quite a bit from 2010 to 2018. MR CLEAN, the 1st positive endovascular therapy study was published in January 2015.
  • Trial required a sample size of 400 patients to provide a 80% power to detect a between-group difference of 15% in the primary outcome of mRs of 0 or 1 at 90 days.According to the authors after a blinded review, the sample size was revised to 310 patients, which again was not met after the trial was stopped early.
  • The original pre-specified analysis of the primary outcome was supposed to be with the more standard logistic-regression model, however with no explanation the authors used a covariate-adjusted modified Poisson regression instead, which has not traditionally been used in previous stroke trials (Don’t stress about what each of these mean. Simply put regression modeling is used to adjust for confounding variables.) What is interesting is the original logistic regression modeling can be found in the supplementary appendix, which found no difference between groups, however the covariate-adjusted modified Poisson regression model which is what was published in the manuscript did find a small difference.
  • Despite having 16 centers in Australia, 1 center in New Zealand, 10 centers in Taiwan, and 1 center in Finland, the authors were only able to recruit 225 patients from 2010 to 2018

Author Conclusion: “Among the patients in this trial who had ischemic stroke and salvageable brain tissue, the use of alteplase between 4.5 – 9.0 hours after stroke onset or at the time the patient awoke with stroke symptoms resulted in a higher percentage of patients with no or minor neurologic deficits than the use of placebo.  There were more cases of symptomatic cerebral hemorrhage in the alteplase group than in the placebo group.”

Clinical Take Home Point: This study should in no way change practice and is a ridiculous display of statistical hocus pocus (i.e. multiple regressions ran, and the one that worked for the authors was the one selected for the manuscript). Another example of a small study, stopped early, with frank manipulation of data to help promote one thing…more money in the pockets of the company making the medication.

References:

  1. Ma H et al. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. NEJM 2019. [Epub Ahead of Print]
  2. Powers WJ et al. 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2018. PMID: 29367334

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

The post REBEL Cast Episode 67: EXTEND-ing Times for Systemic Thrombolysis in Acute Ischemic Stroke? appeared first on REBEL EM - Emergency Medicine Blog.

Jun 03 2019
29 mins
Play

Rank #15: REBEL Cast Ep 47: Blood Transfusions, Lidocaine for Kidney Stones, and Stop Using So Much Oxygen

Podcast cover
Read more

Background: Welcome back to REBEL Cast episode 47.  In this issue we are going to talk about some recent trials published in the past year...

The post REBEL Cast Ep 47: Blood Transfusions, Lidocaine for Kidney Stones, and Stop Using So Much Oxygen appeared first on REBEL EM - Emergency Medicine Blog.

Mar 26 2018
27 mins
Play

Rank #16: REBEL Core Cast 7.0 – Oncologic Emergencies

Podcast cover
Read more

Take Home Points on Oncologic Emergencies: Hyperviscosity Syndrome happens when elevated WBCs or severe hyperproteinemia cause high serum viscosity and micro-circulatory problems in patients with Waldenstrom’s macroglobulinemia, multiple myeloma or...

The post REBEL Core Cast 7.0 – Oncologic Emergencies appeared first on REBEL EM - Emergency Medicine Blog.

Mar 20 2019
9 mins
Play

Rank #17: REBEL Core Cast 12.0 – Tracheostomy Emergencies

Podcast cover
Read more

Take Home Points on Tracheostomy Emergencies Track is mature in 7 days – don’t blindly replace before then because concern for false track creation All...

The post REBEL Core Cast 12.0 – Tracheostomy Emergencies appeared first on REBEL EM - Emergency Medicine Blog.

May 29 2019
9 mins
Play

Rank #18: REBEL Cast Ep56 – PARAMEDIC-2: Time to Abandon Epinephrine in OHCA?

Podcast cover
Read more

Background: Epinephrine(adrenaline) has been used in advanced life support in cardiac arrest since the early 1960s. Despite the routine recommendation for its use, evidence to support...

The post REBEL Cast Ep56 – PARAMEDIC-2: Time to Abandon Epinephrine in OHCA? appeared first on REBEL EM - Emergency Medicine Blog.

Jul 20 2018
27 mins
Play

Rank #19: REBELCast Ep62 – US Guided PIVs with Jacob Avila, MD

Podcast cover
Read more

Welcome back to REBELCast.  In this episode we talked with Jacob Avila about US guided PIVs. Difficult IV access in an already busy department can be...

The post REBELCast Ep62 – US Guided PIVs with Jacob Avila, MD appeared first on REBEL EM - Emergency Medicine Blog.

Feb 07 2019
45 mins
Play

Rank #20: REBEL Cast Episode 49: Pediatric Pain Management Pearls with Sebrina Perkins

Podcast cover
Read more

Background: There has been lots of research published in past years on how to minimize pain and anxiety in children brought to the ED.  Unfortunately,...

The post REBEL Cast Episode 49: Pediatric Pain Management Pearls with Sebrina Perkins appeared first on REBEL EM - Emergency Medicine Blog.

Apr 26 2018
25 mins
Play

Similar Podcasts