#Sackett and all that so that's like. the conditions for them to allow closeness is that she's half dead lmaoo

[smiletimeisrunningout]

You'd think, a little part of her thought bitterly, that he'd recoil from my touch as he so often does, and make things easier for me.

So what, it took being a little bit impaled to get closer to him? How was she supposed to return to a normal life now, at distance, knowing how soft he could be? "Hey, I'd stay if you stayed, but I know, I know. Inappropriate," she smiled at him affectionately, because of course he had a point worrying, his reputation was at stake.

She was quick to disrobe enough to clean up while leaving the stitches alone, if only because the sedative wouldn't last long, and Emma had learned the hard way that while she was the type to keep on walking after stabbed, once she settled down, once it was all done, she didn't take the pain too well, easily infuriated by the fact that it wouldn't go away and that it limited her. So she had to do it while she still didn't feel the worst of it, and also because she didn't want Ben and Caleb to walk in on her in a state of undress, bath water turning red fast and reminding her that her clothing needing far more tending than her.

She wrapped the bandage around her waist, washed her undershirt first so she could wear it in case they returned sooner than expected, than the vest that went on top of it, having to slow down because the stabbing pain had returned and kneeling helped only so much. That, and she felt impossibly weak - another infuriating thing to add to the list.

--

By the time Ben and Caleb came, she had been forced to take a break, least she fainted, and was happy to welcome Caleb's hug even if her body protested. "Oh, sweetie, it's alright, I'm fine. You know me," she promised, hugging him as tightly as she could without risking to hurt him, "I'm just glad he attacked me, at least I could kill him on the spot. James' sister Lucy is there often..."

Hell, he had gotten lucky that his death had been quick and nearly painless, because if he had touched another woman, a friend, Emma would have considered well within her powers to rip him apart.

"Sadly, we both know the doctor has nothing to put my pain to sleep..." she answered to Ben, smiling encouragingly, and she recaptured Caleb before he could let her go fully, at least to give him a one armed hug, "Not done with you. But in the morning I'll go see him, if it makes you feel any better. I don't want to use all of my limited medical supplies to avoid infections, I'll take some of his. Otherwise next time I'm getting myself stabbed in the woods I'll kick it. Speaking of which... I apologize, I haven't finished yet. I wanted to wash my cloak but I'm too weak. The blood loss has made me a little faint, I figured you'd rather if I paused before attempting more laundry, and not... pass out over it," she glanced at it, and then at Caleb briefly, because it wasn't exactly a great view - it had collected her blood while Ben stitched her on top of what she had bled before, so it looked very much like part of a murder scene.

With her arm around Caleb, she suddenly found herself leaning more against him, exhausted from the very same thing.

"The ground, too, the water... I'm sorry, I'm leaving your quarters in such a state." She paused, making a face and looking at Caleb, "I'm being responsible about my health. It's a weird feeling. I really don't like it." With a grimace from the pain, she looked up at Ben and gave him a weak smile, "Are you two alright? Everything went well?"

Although Emma was a decidedly soft creature, what with her affinity for sunny smiles, delivering flowers to unsuspecting camp followers, and comforting the stockade horses during storms, her hands belonged to that of a warrior. They were rough and war-torn, and yet once her fingertips brushed along Benjamin's cheek, he took solace in the gesture. He was accustomed to roughness, so the texture of her skin was a kindness, a familiarity that briefly caused his lashes to flutter closed.

"I'll do as you wish."

His eyes lifted again, catching the dancing candleflame within Emma's gaze. He nearly laughed. In all their time knowing one another, she had never once acquiesced so easily, and yet somehow, Benjamin believed her.

"I'll come back," he promised. Seeming to remember that this was his tent, he sheepishly added, "Brewster and I will escort you back to your quarters. You're welcome to stay here until you're well enough, but given how you've already expressed a discontent with this idea, I figured I'd make this as painless for you as possible."

"Thank you."

It was an odd sentiment. Even though Benjamin knew he did a lot in camp, it was rare for anyone, even his very commander and dear friends, to show a hint of gratitude. Unbidden, a lump formed in his throat, and once her lips grazed across his cheek, that painful knot worsened.

Drawing a soft breath, Benjamin rocked back onto his heels and rose on wobbly limbs, the moment forcibly ended. "I'll be back," he promised again. Realizing that he was still holding onto Emma's hand, he released her and rubbed his palm over his thigh, almost as if her very touch had burned him. "Goodnight, Swan."

--

Caleb was uncharacteristically nettled. After they'd buried Randall in the woods, the whaler spat upon the grave and then urinated upon the newly disturbed plot of earth. Benjamin allowed the foul behavior. He, too, held no love in his heart for reprehensible monsters, and once their work was through, they trekked back across camp towards his tent.

"Remember," Benjamin instructed, "Randall defected. This way, no one will ever bother looking for him here in camp."

"As if anyone gives a shite," Caleb snapped. "All I can say is, the bastard's lucky he's already dead."

Benjamin hummed in agreement. And then once they made sure it was safe to enter his quarters, he and his friend stepped inside to check on Emma.

All at once, Caleb gathered the princess into his strong arms, mindful of her wound as he greeted, "Oi, Emma-love, how you doin', uh? I'd offer to kill that lobcock myself, but it seems ya already did the fun part for me."

Benjamin met with Emma's gaze, but he couldn't bring himself to smile. "How's your wound?" he softly asked. "Do we need to wake Dr. Weston, after all?"

[gabriellakirtonblog]

Four Ways to Use Science to Get the Best Results for Your Clients

Let’s say you want to create a fitness and nutrition plan to help a new client get the best possible results. (A typical workday, in other words.) What do you base that plan on?

A.  The best scientific evidence—randomized double-blind placebo-controlled trials are my jam!

B.  Methods I’ve used before and seen work. Real-life results trump the lab any day.

If you pick A, your plan may be too rigid for the demands and challenges of everyday life. Go with B, and your advice may be outdated.

So which option is better? Trick question. There is no better. The only good answer is both.

That’s what “evidence-based training” is all about—integrating your personal judgment based on experience with the best scientific studies. Either one alone can be limiting. But using both empowers you to seek new solutions.

My thinking is inspired by the work of David Sackett, MD, known as the father of evidence-based medicine. Based on his ideas, I’ve found four ways to make the most of this approach.

READ ALSO: “Should Trainers Care About Evidence-Based Training and Therapy?”

1. Keep up on the latest science

Science is always evolving. New discoveries are made; old findings are debunked. Staying on top of it gives you more options. You never know when one of them will come in handy.

Take my client John. (All names have been changed to protect privacy.) He came to me with the goal of building muscle, something he’d been trying to do on his own for many years. But because of an accident two decades earlier, lower-body training caused excruciating knee pain that lasted for days. Naturally, he’d learned to avoid it.

As it happens, I was familiar with occlusion training, a simple lifting technique that involves tying wraps around your limbs to restrict blood flow. Studies show increases in muscle growth with occlusion, even when using surprisingly light loads. Once we cleared it with his doctor, John was finally able to train his legs with little to no knee discomfort the following day.

Had I not been aware of the studies on occlusion training, I likely would’ve tried to build muscle the traditional way, using relatively heavy loads and high volume, which would’ve done nothing but cause him a lot of unnecessary pain.

It’s easy for me to tell you to spend more time reading and analyzing scientific studies. (You know, in all your free time.) You can make it easy on yourself by subscribing to a research review like MASS or Weightology. Certifications are another way to immerse yourself in exercise or nutrition science, although it can take a long time for new research to find its way into official textbooks and courses.

READ ALSO: “A Trainer’s Guide to Building Muscle”

2. Let go of personal bias

We all process information through the filters of our personal experiences and beliefs. Taken to the extreme, these biases can narrow our focus to the point that we only pay attention to information that confirms what we already think is true, while ignoring anything that might challenge those ideas and practices.

A good trainer learns to recognize her own bias and consider other lines of thought. Instead of becoming comfortable with the status quo, she learns to challenge it. This is how trainers develop their expertise.

Rookie trainers tend to focus on a single methodology of coaching. (I know I did.) One trainer might be interested in athletic performance, so he trains all his clients like competitive athletes. Another might subscribe to the keto diet, so she coaches others to do the same.

I have one client, Sarah, who approached me with a straightforward weight-loss goal. She was young and healthy, so I put her on the same program I use for a lot of my clients: circuits and superset-style workouts to elevate her heart rate. Plenty of research backs up this type of training, and I knew from experience that it works.

But a few months later Sarah was diagnosed with a benign condition called postural orthostatic tachycardia syndrome (POTS). Symptoms include a rapid increase in heartbeat upon standing. Sarah’s heart would race when switching rapidly between moves, and it caused her a lot of anxiety.

We switched to a program emphasizing heavier lifts, with low reps and more rest between sets. The extra recovery time between movements helped her feel more in control.

I’d only used this type of training for clients with serious strength goals. I never would’ve considered it for a fat-loss client. But it was the right choice for Sarah, helping her build confidence while adjusting to the new reality of her diagnosis. It only worked because I was open to trying something new.

READ ALSO: “Stop Training Your Clients Like CrossFitters, Bodybuilders, or Powerlifters”

3. Get to know your client

It’s one thing to have a fully loaded toolbelt, with a mastery of both traditional and new training protocols, all backed by research and practice. But you still need to know how to pick the right tool for the job. That means always factoring in the client’s abilities and limitations, as we just showed, as well as his personal preferences and lifestyle. After all, it doesn’t matter how effective a plan can be if the client can’t or won’t follow it.

What do you know about the client’s job, family life, social activities, sources of stress and anxiety? Does she travel a lot? A workout plan requiring special equipment won’t work. Does she hate doing burpees? Don’t make them an integral part of her program.

Consider Mike, an ER doctor who routinely works 12- to 16-hour shifts. He rarely has time for a sit-down meal at work, and instead fuels himself throughout the day with pizza and vending machine snacks. You can imagine how that affects his ability to lose fat.

Interestingly, he told me that with the stress of the job, he wasn’t all that hungry at work. So I asked Mike if he’d consider modified fasting. He could consume all his calories either before or after his shift, and ignore food entirely while on the job.

There’s no magic to intermittent fasting. It can be a perfectly good way to eat less overall, but in head-to-head studies it isn’t more effective than traditional plans. But it turned out to be the best approach for Mike, allowing him to avoid hospital junk food and achieve a calorie deficit.

So how do you figure out which tool will work for your client? Try this new scientific breakthrough: Ask.

Start with questions like these at your initial consultation:

What are your biggest priorities in life?

Of diets you’ve tried in the past, what did you like and what didn’t you like?

Are you satisfied with just a few bites of dessert, or do you inevitably eat more than you planned?

When you’re on the same page from the beginning, you can suggest a plan that’s realistic for the client’s lifestyle, rather than wasting everyone’s time on strategies that aren’t likely to work.

READ ALSO: “Five Ways to Help Your Clients Lose Weight”

4. Embrace trial and error

Whether you’re a trainer or a scientist, you won’t get far without occasional failure. You won’t learn anything if you never make a mistake or hit a dead end. Failure, on the other hand, gives you a chance to reevaluate, modify, and try something else, this time with more insight into what doesn’t work.

Think of you and your client as a scientific team: You’re monitoring performance, tracking compliance, and seeing what works best. It’s all data, and you’re gathering it together.

One client, Stephanie, is a busy mother with two young children and a demanding job at a large corporation. She regularly opted for convenience food, which was taking a toll.

Her goals were to drop some weight and boost her energy. She seemed like a good candidate for intermittent fasting, which worked so well for Mike. It would free up time early in the day so she could focus on getting the kids off to school and having a productive morning at work. By early afternoon, she could opt for something sensible for her first meal of the day. Even if it wasn’t sensible, I figured a few extra calories would be more than balanced out by eating fewer meals.

But we soon realized it wasn’t working at all. Waiting until midday was giving Stephanie license to eat whatever she wanted. Even if she wasn’t ravenous (which she sometimes was), she convinced herself she had tons of calories banked and could splurge almost daily.

We changed to a more traditional meal frequency, with an emphasis on healthy, easy-to-prepare foods that she could prep ahead of time.

That story illustrates as well as anything what we mean when we talk about evidence-based training. It isn’t about closing off options; it’s about opening them up. If a method is safe and you have good reason to believe it might work, give it a shot.

Just keep in mind that if it works for one client, that means … it works for one client. Fitness and nutrition are too individualized for anything to work for everyone.

      He Said, She Said: Download Our FREE Guide to Analyzing Fitness Research

It’s become commonplace to use cherry-picked, biased and misinterpreted research to back up personal training promises and marketing. Don’t be that fit pro.

Enter your email below for our free guide by Dr. Jonathan Fass, PT, DPT, CSCS. Whether it’s CrossFit or vaccines, Dr. Fass will guide you on how to accurately analyze fitness research so you can better inform your clients.

Get your guide here:

  The post Four Ways to Use Science to Get the Best Results for Your Clients appeared first on The PTDC.

Four Ways to Use Science to Get the Best Results for Your Clients published first on https://onezeroonesarms.tumblr.com/

[kristinsimmons]

The EBM Wars: Manufacturing Equipoise (Part 1)

By ANISH KOKA

The phone rings.  It’s not supposed to be ringing.  It’s 2 am.   The voice on the other line is from an apologetic surgery resident.

Resident: There is this patient..

Me: Yes, go ahead. Please.

Resident: He’s tachycardic.

Me: How fast?

Resident: 160 ?

Me: What’s the blood pressure?

Resident: 130/90

Me: Rhythm?

Resident: An SVT I think.. I gave adenosine.  Nothing happened

Me: Audibly groaning.  I’ll be in..

Forty five minutes later I’m at the bedside of a decidedly ill appearing man.

I want to be triumphant that his heart rate is only 145, and a quick glance at the telemetry monitor above his bed uncovers juicy p waves in a cadence that suggests this is no primary electrical arrhythmia.

Something is very wrong somewhere – the heart in this case is an innocent bystander being whipped into a frenzy to compensate for something.

At the moment the whip is a norepinephrine infusion being used to keep his blood pressure up.

I ask the nurse if the amount of norepinephrine infusing has been stable.  She replies that his dose has been slowly escalating.

Eureka! I think – the heart rate response in this case is being driven by the norepinephrine – a powerful adrenaline that acts on beta receptors and alpha receptors within the body that increase heart rate and constrict the blood vessels to raise blood pressure.  Fix the cause of the low blood pressure, come down on the norepinephrine, and perhaps the heart rate would be better.

But it turns out this particular post surgical patient doesn’t have a medical cause of low blood pressure I can find.  I cycle through cardiac ultrasounds, blood gases, steroid and volume challenges, and try inching down on the norepinephrine.

All of it is to no avail.  I’m growing more and more convinced this problem is surgical in nature. Perhaps an infarcted piece of bowel?  All I know is that the man acts like he has no peripheral vascular tone.

An interesting thing happens shortly after.  The norepinephrine drip runs out.

As one nurse runs to get another bag from the pharmacy – a quick cascade of events unfolds.

The brisk upstroke from the arterial line that marks the pressure wave generated with every beat of the heart starts to dampen.  The color seems to visibly drain from the patients face, and he begins to complain that his vision is getting blurry.  His systolic blood pressure is 70 – an almost forty point drop within a minute of the norepinephrine running out.

I call for help.

I try to keep a level tone.  Project control, not panic.

“Open the code cart, I need a half a milligram of epinephrine”

“You’re going to be ok, sir.  Hang with me.”  I squeeze his hand.

He closes his eyes

The code cart – a fully stocked cabinet on wheels with almost everything you need for resuscitation efforts – is wheeled into the room. The epinephrine vial is handed to the nurse, and hurriedly pushed.

Within seconds, I can see the blood pressure and heart rate rise.  The patient’s grip on my hand relaxes.  Or maybe its my grip on his hand.  I forget which.  His vision returns to normal as his blood pressure ‘normalizes’.

Of course nothing has been fixed.  Why his blood pressure remains low continues to be a mystery.  The bag of norepinephrine soon isn’t enough even at its maximal dose.  The same scenario (hypotension -> pallor -> vision loss ) recurs 30 minutes later, and another bolus of epinephrine aborts a rapid spiral towards pulselessness.

This case is an anecdote, the weakest possible form of evidence apparently.  Yet there are powerful lessons learned that night. Blood flows in pulsatile fashion with a certain pressure head.  Below some threshold of pressure, the end organs of the body stop functioning.  Agents that are active on peripheral vasoconstrictor receptors (norepinephrine, epinephrine) raise blood pressure.  Epinephrine was keeping this patient alive while a team worked to understand why his blood pressure was so low.  My suspicion was that he was in something called distributive shock – a catastrophic life threatening syndrome that requires a furious hunt for cause to save the patient.  Overwhelming infection and an even more aggressive immune response renders normally relatively impervious vasculature to be a sieve.  At the present time the therapy is directed towards replacing the fluid lost in the intravascular space and using medications that act on peripheral vascular receptors that increase peripheral tone.

There is, of course, much that isn’t known about this process.  Hopefully it will come to pass that we will arrive at a better understanding of what specifically creates this mileu so our therapies may be more directed.  But for the time being, our solutions are limited by our current, always imperfect understanding of the world.

The culprit in this case was a leak of intestinal contents into the peritoneal space from two pieces of bowel that should have been exactly apposed.  The body had attempted to tell us this very thing with that high heart rate post-operatively.  It took us, the clinicians, some time to translate.

The uninformed prior: Unlearning what has been learned.

For many, medicine has for too long been an imperfect science.  The history of medicine is replete with physicians acting with certainty in a manner that – in hindsight – was ineffective, or even worse – harmful.  Blood letting to allow the release of bad humors is believed to have hastened the demise of the greatest American – George Washington.  The disconcerting part of this is that the physician players were not motivated by anything but the best intentions.  They relied on their experience, intuition and judgement to deliver exactly the wrong prescription.   Intuition fails.  No matter how many patients died soon after blood letting, operating biases didn’t let physicians link the two events.  After all, the patients may have died even sooner if blood letting hadn’t been done.

The idea that medicine had progressed – by the 1980’s – to the point that doctors were not engaged in the equivalent of blood letting came under heavy fire when it was demonstrated a number of standard practices of the time could indeed be ineffective.  Extra beats (also known as ectopic heart beats) after heart attacks were noted in cardiac units to portend a higher risk of dying suddenly.  The obvious approach to this was to use medications that effectively suppressed ectopic heart beats.  Testing this in a double blind randomized control trial did not just demonstrate ineffectiveness, but harm.  More people randomized to suppression of ectopic beats actually died.  It turns out the anti-arrhythmic drugs being used were actually proarrhythmic as well.  The attack on ‘expertise’ that relied on intuition and experience was on, and it was a rout.

Glue ear – a condition that developed in the middle ears of little kids after ear infections  was treated with insertion of a tube to drain that space.  The trial to determine efficacy using a randomized trial to blindly allocate patients to surgery or no treatment?

Negative.

Many of the children turned out to do just fine if you left them alone.  Given the fact that all procedures have a certain complication rate, the lack of efficacy here was no small matter.

And so it went – the populace had to be on guard not just against the afflictions of disease, but against the intuitions of its doctors.

Uncertainty reigned, and in search of certainty, the field fled to the warm embrace of ever greater empiricism.  In the early ’80s from the McMaster University in Canada, David Sackett gave voice to a new sheriff – Evidence Based Medicine (EBM).

“EBM de-emphasizes intuition, unsystematic clinical expertise, and pathophysiologic rationale . . . and stresses the examination of evidence from clinical research. In 1960, the randomized trial was an oddity. It is now accepted that virtually no drug can enter clinical practice without a demonstration of its efficacy in clinical trials. Moreover the same randomized trial method is increasingly being applied to surgical therapies and diagnostic tests.” (Sackett et. al, Evidence Based Medicine)

The premise as outlined is simple – don’t believe anything that hasn’t been tested in a randomized control trial.  The only real evidence is that found within RCTs or in reviews that amalgamated RCTs.

The usual response from EBM experts can be found below in the response to the statement that real evidence may come from outside an RCT.

It is quite possible Professor Francis is right on here about the specific subject being discussed, but the point is that there is an established hierarchy of evidence on display.  The RCT is king, everything else is no better than the court jester.

While an RCT may certainly be better than anything cobbled together at a pub, the conventional parallel group RCT certainly isn’t always King of the Hill.   As nicely expounded on by the prolific statistician Stephen Senn, there are plenty of potential errors the conventional RCT finds itself humbled by.

The clinician may thus feel somewhat mollified about conclusions drawn about the effect of epinephrine in the earlier anecdote.

The idea that real evidence may live outside the confines of RCTs was also countered by none other than the godfather of EBM, David Sackett:

“Evidence based medicine is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions. To find out about the accuracy of a diagnostic test, we need to find proper cross sectional studies of patients clinically suspected of harboring the relevant disorder, not a randomized trial. For a question about prognosis, we need proper follow up studies of patients assembled at a uniform, early point in the clinical course of their disease. And sometimes the evidence we need will come from the basic sciences such as genetics or immunology. It is when asking questions about therapy that we should try to avoid the non-experimental approaches, since these routinely lead to false positive conclusions about efficacy. Because the randomized trial, and especially the systematic review of several randomized trials, is so much more likely to inform us and so much less likely to mislead us, it has become the “gold standard” for judging whether a treatment does more good than harm. However,some questions about therapy do not require randomized trials (successful interventions for otherwise fatal conditions) or cannot wait for the trials to be conducted. And if no randomized trial has been carried out for our patient’s predicament, we must follow the trail to the next best external evidence and work from there. (Sacket et al, Evidence based medicine: what it is.. )”

Sackett also noted that there were therapies whose ” ‘face validity’ is so great that randomized trials were unanimously judged by the team to be both unnecessary, and, if a placebo would have been involved, unethical”.

In effect, there was always an escape clause to let common sense prevail over EBM.  But as frequently happens in movements, the second generation of followers moves in directions unintended by the founders.  If the safeguards in place involve only areas where equipoise exists, but equipoise is itself determined by fallible judgement, the range of unacceptable experiments becomes very narrow.  This especially applies to new therapies where members of the community not involved in design and development have skeptical prior beliefs.  This is, of course, not a bad thing – it is entirely possible that the usually overoptimistic prior of the developers of a new therapy are farther from the truth than the skeptics.  But it is a major problem if we ask doctors to discard their prior beliefs that are not based in RCTs.  In doing so, we are manufacturing equipoise.  This means travel in dangerous ethical waters for physicians and their patients that is at best unwise, and at worst willfully foolish.

The EBM Wars: Manufacturing Equipoise (Part 1) published first on https://wittooth.tumblr.com/

[kristinsimmons]

The EBM Wars: Manufacturing Equipoise (Part 1)

By ANISH KOKA

The phone rings.  It’s not supposed to be ringing.  It’s 2 am.   The voice on the other line is from an apologetic surgery resident.

Resident: There is this patient..

Me: Yes, go ahead. Please.

Resident: He’s tachycardic.

Me: How fast?

Resident: 160 ?

Me: What’s the blood pressure?

Resident: 130/90

Me: Rhythm?

Resident: An SVT I think.. I gave adenosine.  Nothing happened

Me: Audibly groaning.  I’ll be in..

Forty five minutes later I’m at the bedside of a decidedly ill appearing man.

I want to be triumphant that his heart rate is only 145, and a quick glance at the telemetry monitor above his bed uncovers juicy p waves in a cadence that suggests this is no primary electrical arrhythmia.

Something is very wrong somewhere – the heart in this case is an innocent bystander being whipped into a frenzy to compensate for something.

At the moment the whip is a norepinephrine infusion being used to keep his blood pressure up.

I ask the nurse if the amount of norepinephrine infusing has been stable.  She replies that his dose has been slowly escalating.

Eureka! I think – the heart rate response in this case is being driven by the norepinephrine – a powerful adrenaline that acts on beta receptors and alpha receptors within the body that increase heart rate and constrict the blood vessels to raise blood pressure.  Fix the cause of the low blood pressure, come down on the norepinephrine, and perhaps the heart rate would be better.

But it turns out this particular post surgical patient doesn’t have a medical cause of low blood pressure I can find.  I cycle through cardiac ultrasounds, blood gases, steroid and volume challenges, and try inching down on the norepinephrine.

All of it is to no avail.  I’m growing more and more convinced this problem is surgical in nature. Perhaps an infarcted piece of bowel?  All I know is that the man acts like he has no peripheral vascular tone.

An interesting thing happens shortly after.  The norepinephrine drip runs out.

As one nurse runs to get another bag from the pharmacy – a quick cascade of events unfolds.

The brisk upstroke from the arterial line that marks the pressure wave generated with every beat of the heart starts to dampen.  The color seems to visibly drain from the patients face, and he begins to complain that his vision is getting blurry.  His systolic blood pressure is 70 – an almost forty point drop within a minute of the norepinephrine running out.

I call for help.

I try to keep a level tone.  Project control, not panic.

“Open the code cart, I need a half a milligram of epinephrine”

“You’re going to be ok, sir.  Hang with me.”  I squeeze his hand.

He closes his eyes

The code cart – a fully stocked cabinet on wheels with almost everything you need for resuscitation efforts – is wheeled into the room. The epinephrine vial is handed to the nurse, and hurriedly pushed.

Within seconds, I can see the blood pressure and heart rate rise.  The patient’s grip on my hand relaxes.  Or maybe its my grip on his hand.  I forget which.  His vision returns to normal as his blood pressure ‘normalizes’.

Of course nothing has been fixed.  Why his blood pressure remains low continues to be a mystery.  The bag of norepinephrine soon isn’t enough even at its maximal dose.  The same scenario (hypotension -> pallor -> vision loss ) recurs 30 minutes later, and another bolus of epinephrine aborts a rapid spiral towards pulselessness.

This case is an anecdote, the weakest possible form of evidence apparently.  Yet there are powerful lessons learned that night. Blood flows in pulsatile fashion with a certain pressure head.  Below some threshold of pressure, the end organs of the body stop functioning.  Agents that are active on peripheral vasoconstrictor receptors (norepinephrine, epinephrine) raise blood pressure.  Epinephrine was keeping this patient alive while a team worked to understand why his blood pressure was so low.  My suspicion was that he was in something called distributive shock – a catastrophic life threatening syndrome that requires a furious hunt for cause to save the patient.  Overwhelming infection and an even more aggressive immune response renders normally relatively impervious vasculature to be a sieve.  At the present time the therapy is directed towards replacing the fluid lost in the intravascular space and using medications that act on peripheral vascular receptors that increase peripheral tone.

There is, of course, much that isn’t known about this process.  Hopefully it will come to pass that we will arrive at a better understanding of what specifically creates this mileu so our therapies may be more directed.  But for the time being, our solutions are limited by our current, always imperfect understanding of the world.

The culprit in this case was a leak of intestinal contents into the peritoneal space from two pieces of bowel that should have been exactly apposed.  The body had attempted to tell us this very thing with that high heart rate post-operatively.  It took us, the clinicians, some time to translate.

The uninformed prior: Unlearning what has been learned.

For many, medicine has for too long been an imperfect science.  The history of medicine is replete with physicians acting with certainty in a manner that – in hindsight – was ineffective, or even worse – harmful.  Blood letting to allow the release of bad humors is believed to have hastened the demise of the greatest American – George Washington.  The disconcerting part of this is that the physician players were not motivated by anything but the best intentions.  They relied on their experience, intuition and judgement to deliver exactly the wrong prescription.   Intuition fails.  No matter how many patients died soon after blood letting, operating biases didn’t let physicians link the two events.  After all, the patients may have died even sooner if blood letting hadn’t been done.

The idea that medicine had progressed – by the 1980’s – to the point that doctors were not engaged in the equivalent of blood letting came under heavy fire when it was demonstrated a number of standard practices of the time could indeed be ineffective.  Extra beats (also known as ectopic heart beats) after heart attacks were noted in cardiac units to portend a higher risk of dying suddenly.  The obvious approach to this was to use medications that effectively suppressed ectopic heart beats.  Testing this in a double blind randomized control trial did not just demonstrate ineffectiveness, but harm.  More people randomized to suppression of ectopic beats actually died.  It turns out the anti-arrhythmic drugs being used were actually proarrhythmic as well.  The attack on ‘expertise’ that relied on intuition and experience was on, and it was a rout.

Glue ear – a condition that developed in the middle ears of little kids after ear infections  was treated with insertion of a tube to drain that space.  The trial to determine efficacy using a randomized trial to blindly allocate patients to surgery or no treatment?

Negative.

Many of the children turned out to do just fine if you left them alone.  Given the fact that all procedures have a certain complication rate, the lack of efficacy here was no small matter.

And so it went – the populace had to be on guard not just against the afflictions of disease, but against the intuitions of its doctors.

Uncertainty reigned, and in search of certainty, the field fled to the warm embrace of ever greater empiricism.  In the early ’80s from the McMaster University in Canada, David Sackett gave voice to a new sheriff – Evidence Based Medicine (EBM).

“EBM de-emphasizes intuition, unsystematic clinical expertise, and pathophysiologic rationale . . . and stresses the examination of evidence from clinical research. In 1960, the randomized trial was an oddity. It is now accepted that virtually no drug can enter clinical practice without a demonstration of its efficacy in clinical trials. Moreover the same randomized trial method is increasingly being applied to surgical therapies and diagnostic tests.” (Sackett et. al, Evidence Based Medicine)

The premise as outlined is simple – don’t believe anything that hasn’t been tested in a randomized control trial.  The only real evidence is that found within RCTs or in reviews that amalgamated RCTs.

The usual response from EBM experts can be found below in the response to the statement that real evidence may come from outside an RCT.

It is quite possible Professor Francis is right on here about the specific subject being discussed, but the point is that there is an established hierarchy of evidence on display.  The RCT is king, everything else is no better than the court jester.

While an RCT may certainly be better than anything cobbled together at a pub, the conventional parallel group RCT certainly isn’t always King of the Hill.   As nicely expounded on by the prolific statistician Stephen Senn, there are plenty of potential errors the conventional RCT finds itself humbled by.

The clinician may thus feel somewhat mollified about conclusions drawn about the effect of epinephrine in the earlier anecdote.

The idea that real evidence may live outside the confines of RCTs was also countered by none other than the godfather of EBM, David Sackett:

“Evidence based medicine is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions. To find out about the accuracy of a diagnostic test, we need to find proper cross sectional studies of patients clinically suspected of harboring the relevant disorder, not a randomized trial. For a question about prognosis, we need proper follow up studies of patients assembled at a uniform, early point in the clinical course of their disease. And sometimes the evidence we need will come from the basic sciences such as genetics or immunology. It is when asking questions about therapy that we should try to avoid the non-experimental approaches, since these routinely lead to false positive conclusions about efficacy. Because the randomized trial, and especially the systematic review of several randomized trials, is so much more likely to inform us and so much less likely to mislead us, it has become the “gold standard” for judging whether a treatment does more good than harm. However,some questions about therapy do not require randomized trials (successful interventions for otherwise fatal conditions) or cannot wait for the trials to be conducted. And if no randomized trial has been carried out for our patient’s predicament, we must follow the trail to the next best external evidence and work from there. (Sacket et al, Evidence based medicine: what it is.. )”

Sackett also noted that there were therapies whose ” ‘face validity’ is so great that randomized trials were unanimously judged by the team to be both unnecessary, and, if a placebo would have been involved, unethical”.

In effect, there was always an escape clause to let common sense prevail over EBM.  But as frequently happens in movements, the second generation of followers moves in directions unintended by the founders.  If the safeguards in place involve only areas where equipoise exists, but equipoise is itself determined by fallible judgement, the range of unacceptable experiments becomes very narrow.  This especially applies to new therapies where members of the community not involved in design and development have skeptical prior beliefs.  This is, of course, not a bad thing – it is entirely possible that the usually overoptimistic prior of the developers of a new therapy are farther from the truth than the skeptics.  But it is a major problem if we ask doctors to discard their prior beliefs that are not based in RCTs.  In doing so, we are manufacturing equipoise.  This means travel in dangerous ethical waters for physicians and their patients that is at best unwise, and at worst willfully foolish.

The EBM Wars: Manufacturing Equipoise (Part 1) published first on https://wittooth.tumblr.com/

[kristinsimmons]

The EBM Wars: Manufacturing Equipoise (Part 1)

By ANISH KOKA

The phone rings.  It’s not supposed to be ringing.  It’s 2 am.   The voice on the other line is from an apologetic surgery resident.

Resident: There is this patient..

Me: Yes, go ahead. Please.

Resident: He’s tachycardic.

Me: How fast?

Resident: 160 ?

Me: What’s the blood pressure?

Resident: 130/90

Me: Rhythm?

Resident: An SVT I think.. I gave adenosine.  Nothing happened

Me: Audibly groaning.  I’ll be in..

Forty five minutes later I’m at the bedside of a decidedly ill appearing man.

I want to be triumphant that his heart rate is only 145, and a quick glance at the telemetry monitor above his bed uncovers juicy p waves in a cadence that suggests this is no primary electrical arrhythmia.

Something is very wrong somewhere – the heart in this case is an innocent bystander being whipped into a frenzy to compensate for something.

At the moment the whip is a norepinephrine infusion being used to keep his blood pressure up.

I ask the nurse if the amount of norepinephrine infusing has been stable.  She replies that his dose has been slowly escalating.

Eureka! I think – the heart rate response in this case is being driven by the norepinephrine – a powerful adrenaline that acts on beta receptors and alpha receptors within the body that increase heart rate and constrict the blood vessels to raise blood pressure.  Fix the cause of the low blood pressure, come down on the norepinephrine, and perhaps the heart rate would be better.

But it turns out this particular post surgical patient doesn’t have a medical cause of low blood pressure I can find.  I cycle through cardiac ultrasounds, blood gases, steroid and volume challenges, and try inching down on the norepinephrine.

All of it is to no avail.  I’m growing more and more convinced this problem is surgical in nature. Perhaps an infarcted piece of bowel?  All I know is that the man acts like he has no peripheral vascular tone.

An interesting thing happens shortly after.  The norepinephrine drip runs out.

As one nurse runs to get another bag from the pharmacy – a quick cascade of events unfolds.

The brisk upstroke from the arterial line that marks the pressure wave generated with every beat of the heart starts to dampen.  The color seems to visibly drain from the patients face, and he begins to complain that his vision is getting blurry.  His systolic blood pressure is 70 – an almost forty point drop within a minute of the norepinephrine running out.

I call for help.

I try to keep a level tone.  Project control, not panic.

“Open the code cart, I need a half a milligram of epinephrine”

“You’re going to be ok, sir.  Hang with me.”  I squeeze his hand.

He closes his eyes

The code cart – a fully stocked cabinet on wheels with almost everything you need for resuscitation efforts – is wheeled into the room. The epinephrine vial is handed to the nurse, and hurriedly pushed.

Within seconds, I can see the blood pressure and heart rate rise.  The patient’s grip on my hand relaxes.  Or maybe its my grip on his hand.  I forget which.  His vision returns to normal as his blood pressure ‘normalizes’.

Of course nothing has been fixed.  Why his blood pressure remains low continues to be a mystery.  The bag of norepinephrine soon isn’t enough even at its maximal dose.  The same scenario (hypotension -> pallor -> vision loss ) recurs 30 minutes later, and another bolus of epinephrine aborts a rapid spiral towards pulselessness.

This case is an anecdote, the weakest possible form of evidence apparently.  Yet there are powerful lessons learned that night. Blood flows in pulsatile fashion with a certain pressure head.  Below some threshold of pressure, the end organs of the body stop functioning.  Agents that are active on peripheral vasoconstrictor receptors (norepinephrine, epinephrine) raise blood pressure.  Epinephrine was keeping this patient alive while a team worked to understand why his blood pressure was so low.  My suspicion was that he was in something called distributive shock – a catastrophic life threatening syndrome that requires a furious hunt for cause to save the patient.  Overwhelming infection and an even more aggressive immune response renders normally relatively impervious vasculature to be a sieve.  At the present time the therapy is directed towards replacing the fluid lost in the intravascular space and using medications that act on peripheral vascular receptors that increase peripheral tone.

There is, of course, much that isn’t known about this process.  Hopefully it will come to pass that we will arrive at a better understanding of what specifically creates this mileu so our therapies may be more directed.  But for the time being, our solutions are limited by our current, always imperfect understanding of the world.

The culprit in this case was a leak of intestinal contents into the peritoneal space from two pieces of bowel that should have been exactly apposed.  The body had attempted to tell us this very thing with that high heart rate post-operatively.  It took us, the clinicians, some time to translate.

The uninformed prior: Unlearning what has been learned.

For many, medicine has for too long been an imperfect science.  The history of medicine is replete with physicians acting with certainty in a manner that – in hindsight – was ineffective, or even worse – harmful.  Blood letting to allow the release of bad humors is believed to have hastened the demise of the greatest American – George Washington.  The disconcerting part of this is that the physician players were not motivated by anything but the best intentions.  They relied on their experience, intuition and judgement to deliver exactly the wrong prescription.   Intuition fails.  No matter how many patients died soon after blood letting, operating biases didn’t let physicians link the two events.  After all, the patients may have died even sooner if blood letting hadn’t been done.

The idea that medicine had progressed – by the 1980’s – to the point that doctors were not engaged in the equivalent of blood letting came under heavy fire when it was demonstrated a number of standard practices of the time could indeed be ineffective.  Extra beats (also known as ectopic heart beats) after heart attacks were noted in cardiac units to portend a higher risk of dying suddenly.  The obvious approach to this was to use medications that effectively suppressed ectopic heart beats.  Testing this in a double blind randomized control trial did not just demonstrate ineffectiveness, but harm.  More people randomized to suppression of ectopic beats actually died.  It turns out the anti-arrhythmic drugs being used were actually proarrhythmic as well.  The attack on ‘expertise’ that relied on intuition and experience was on, and it was a rout.

Glue ear – a condition that developed in the middle ears of little kids after ear infections  was treated with insertion of a tube to drain that space.  The trial to determine efficacy using a randomized trial to blindly allocate patients to surgery or no treatment?

Negative.

Many of the children turned out to do just fine if you left them alone.  Given the fact that all procedures have a certain complication rate, the lack of efficacy here was no small matter.

And so it went – the populace had to be on guard not just against the afflictions of disease, but against the intuitions of its doctors.

Uncertainty reigned, and in search of certainty, the field fled to the warm embrace of ever greater empiricism.  In the early ’80s from the McMaster University in Canada, David Sackett gave voice to a new sheriff – Evidence Based Medicine (EBM).

“EBM de-emphasizes intuition, unsystematic clinical expertise, and pathophysiologic rationale . . . and stresses the examination of evidence from clinical research. In 1960, the randomized trial was an oddity. It is now accepted that virtually no drug can enter clinical practice without a demonstration of its efficacy in clinical trials. Moreover the same randomized trial method is increasingly being applied to surgical therapies and diagnostic tests.” (Sackett et. al, Evidence Based Medicine)

The premise as outlined is simple – don’t believe anything that hasn’t been tested in a randomized control trial.  The only real evidence is that found within RCTs or in reviews that amalgamated RCTs.

The usual response from EBM experts can be found below in the response to the statement that real evidence may come from outside an RCT.

It is quite possible Professor Francis is right on here about the specific subject being discussed, but the point is that there is an established hierarchy of evidence on display.  The RCT is king, everything else is no better than the court jester.

While an RCT may certainly be better than anything cobbled together at a pub, the conventional parallel group RCT certainly isn’t always King of the Hill.   As nicely expounded on by the prolific statistician Stephen Senn, there are plenty of potential errors the conventional RCT finds itself humbled by.

The clinician may thus feel somewhat mollified about conclusions drawn about the effect of epinephrine in the earlier anecdote.

The idea that real evidence may live outside the confines of RCTs was also countered by none other than the godfather of EBM, David Sackett:

“Evidence based medicine is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions. To find out about the accuracy of a diagnostic test, we need to find proper cross sectional studies of patients clinically suspected of harboring the relevant disorder, not a randomized trial. For a question about prognosis, we need proper follow up studies of patients assembled at a uniform, early point in the clinical course of their disease. And sometimes the evidence we need will come from the basic sciences such as genetics or immunology. It is when asking questions about therapy that we should try to avoid the non-experimental approaches, since these routinely lead to false positive conclusions about efficacy. Because the randomized trial, and especially the systematic review of several randomized trials, is so much more likely to inform us and so much less likely to mislead us, it has become the “gold standard” for judging whether a treatment does more good than harm. However,some questions about therapy do not require randomized trials (successful interventions for otherwise fatal conditions) or cannot wait for the trials to be conducted. And if no randomized trial has been carried out for our patient’s predicament, we must follow the trail to the next best external evidence and work from there. (Sacket et al, Evidence based medicine: what it is.. )”

Sackett also noted that there were therapies whose ” ‘face validity’ is so great that randomized trials were unanimously judged by the team to be both unnecessary, and, if a placebo would have been involved, unethical”.

In effect, there was always an escape clause to let common sense prevail over EBM.  But as frequently happens in movements, the second generation of followers moves in directions unintended by the founders.  If the safeguards in place involve only areas where equipoise exists, but equipoise is itself determined by fallible judgement, the range of unacceptable experiments becomes very narrow.  This especially applies to new therapies where members of the community not involved in design and development have skeptical prior beliefs.  This is, of course, not a bad thing – it is entirely possible that the usually overoptimistic prior of the developers of a new therapy are farther from the truth than the skeptics.  But it is a major problem if we ask doctors to discard their prior beliefs that are not based in RCTs.  In doing so, we are manufacturing equipoise.  This means travel in dangerous ethical waters for physicians and their patients that is at best unwise, and at worst willfully foolish.

The EBM Wars: Manufacturing Equipoise (Part 1) published first on https://wittooth.tumblr.com/

[kristinsimmons]

The EBM Wars: Manufacturing Equipoise (Part 1)

By ANISH KOKA

The phone rings.  It’s not supposed to be ringing.  It’s 2 am.   The voice on the other line is from an apologetic surgery resident.

Resident: There is this patient..

Me: Yes, go ahead. Please.

Resident: He’s tachycardic.

Me: How fast?

Resident: 160 ?

Me: What’s the blood pressure?

Resident: 130/90

Me: Rhythm?

Resident: An SVT I think.. I gave adenosine.  Nothing happened

Me: Audibly groaning.  I’ll be in..

Forty five minutes later I’m at the bedside of a decidedly ill appearing man.

I want to be triumphant that his heart rate is only 145, and a quick glance at the telemetry monitor above his bed uncovers juicy p waves in a cadence that suggests this is no primary electrical arrhythmia.

Something is very wrong somewhere – the heart in this case is an innocent bystander being whipped into a frenzy to compensate for something.

At the moment the whip is a norepinephrine infusion being used to keep his blood pressure up.

I ask the nurse if the amount of norepinephrine infusing has been stable.  She replies that his dose has been slowly escalating.

Eureka! I think – the heart rate response in this case is being driven by the norepinephrine – a powerful adrenaline that acts on beta receptors and alpha receptors within the body that increase heart rate and constrict the blood vessels to raise blood pressure.  Fix the cause of the low blood pressure, come down on the norepinephrine, and perhaps the heart rate would be better.

But it turns out this particular post surgical patient doesn’t have a medical cause of low blood pressure I can find.  I cycle through cardiac ultrasounds, blood gases, steroid and volume challenges, and try inching down on the norepinephrine.

All of it is to no avail.  I’m growing more and more convinced this problem is surgical in nature. Perhaps an infarcted piece of bowel?  All I know is that the man acts like he has no peripheral vascular tone.

An interesting thing happens shortly after.  The norepinephrine drip runs out.

As one nurse runs to get another bag from the pharmacy – a quick cascade of events unfolds.

The brisk upstroke from the arterial line that marks the pressure wave generated with every beat of the heart starts to dampen.  The color seems to visibly drain from the patients face, and he begins to complain that his vision is getting blurry.  His systolic blood pressure is 70 – an almost forty point drop within a minute of the norepinephrine running out.

I call for help.

I try to keep a level tone.  Project control, not panic.

“Open the code cart, I need a half a milligram of epinephrine”

“You’re going to be ok, sir.  Hang with me.”  I squeeze his hand.

He closes his eyes

The code cart – a fully stocked cabinet on wheels with almost everything you need for resuscitation efforts – is wheeled into the room. The epinephrine vial is handed to the nurse, and hurriedly pushed.

Within seconds, I can see the blood pressure and heart rate rise.  The patient’s grip on my hand relaxes.  Or maybe its my grip on his hand.  I forget which.  His vision returns to normal as his blood pressure ‘normalizes’.

Of course nothing has been fixed.  Why his blood pressure remains low continues to be a mystery.  The bag of norepinephrine soon isn’t enough even at its maximal dose.  The same scenario (hypotension -> pallor -> vision loss ) recurs 30 minutes later, and another bolus of epinephrine aborts a rapid spiral towards pulselessness.

This case is an anecdote, the weakest possible form of evidence apparently.  Yet there are powerful lessons learned that night. Blood flows in pulsatile fashion with a certain pressure head.  Below some threshold of pressure, the end organs of the body stop functioning.  Agents that are active on peripheral vasoconstrictor receptors (norepinephrine, epinephrine) raise blood pressure.  Epinephrine was keeping this patient alive while a team worked to understand why his blood pressure was so low.  My suspicion was that he was in something called distributive shock – a catastrophic life threatening syndrome that requires a furious hunt for cause to save the patient.  Overwhelming infection and an even more aggressive immune response renders normally relatively impervious vasculature to be a sieve.  At the present time the therapy is directed towards replacing the fluid lost in the intravascular space and using medications that act on peripheral vascular receptors that increase peripheral tone.

There is, of course, much that isn’t known about this process.  Hopefully it will come to pass that we will arrive at a better understanding of what specifically creates this mileu so our therapies may be more directed.  But for the time being, our solutions are limited by our current, always imperfect understanding of the world.

The culprit in this case was a leak of intestinal contents into the peritoneal space from two pieces of bowel that should have been exactly apposed.  The body had attempted to tell us this very thing with that high heart rate post-operatively.  It took us, the clinicians, some time to translate.

The uninformed prior: Unlearning what has been learned.

For many, medicine has for too long been an imperfect science.  The history of medicine is replete with physicians acting with certainty in a manner that – in hindsight – was ineffective, or even worse – harmful.  Blood letting to allow the release of bad humors is believed to have hastened the demise of the greatest American – George Washington.  The disconcerting part of this is that the physician players were not motivated by anything but the best intentions.  They relied on their experience, intuition and judgement to deliver exactly the wrong prescription.   Intuition fails.  No matter how many patients died soon after blood letting, operating biases didn’t let physicians link the two events.  After all, the patients may have died even sooner if blood letting hadn’t been done.

The idea that medicine had progressed – by the 1980’s – to the point that doctors were not engaged in the equivalent of blood letting came under heavy fire when it was demonstrated a number of standard practices of the time could indeed be ineffective.  Extra beats (also known as ectopic heart beats) after heart attacks were noted in cardiac units to portend a higher risk of dying suddenly.  The obvious approach to this was to use medications that effectively suppressed ectopic heart beats.  Testing this in a double blind randomized control trial did not just demonstrate ineffectiveness, but harm.  More people randomized to suppression of ectopic beats actually died.  It turns out the anti-arrhythmic drugs being used were actually proarrhythmic as well.  The attack on ‘expertise’ that relied on intuition and experience was on, and it was a rout.

Glue ear – a condition that developed in the middle ears of little kids after ear infections  was treated with insertion of a tube to drain that space.  The trial to determine efficacy using a randomized trial to blindly allocate patients to surgery or no treatment?

Negative.

Many of the children turned out to do just fine if you left them alone.  Given the fact that all procedures have a certain complication rate, the lack of efficacy here was no small matter.

And so it went – the populace had to be on guard not just against the afflictions of disease, but against the intuitions of its doctors.

Uncertainty reigned, and in search of certainty, the field fled to the warm embrace of ever greater empiricism.  In the early ’80s from the McMaster University in Canada, David Sackett gave voice to a new sheriff – Evidence Based Medicine (EBM).

“EBM de-emphasizes intuition, unsystematic clinical expertise, and pathophysiologic rationale . . . and stresses the examination of evidence from clinical research. In 1960, the randomized trial was an oddity. It is now accepted that virtually no drug can enter clinical practice without a demonstration of its efficacy in clinical trials. Moreover the same randomized trial method is increasingly being applied to surgical therapies and diagnostic tests.” (Sackett et. al, Evidence Based Medicine)

The premise as outlined is simple – don’t believe anything that hasn’t been tested in a randomized control trial.  The only real evidence is that found within RCTs or in reviews that amalgamated RCTs.

The usual response from EBM experts can be found below in the response to the statement that real evidence may come from outside an RCT.

It is quite possible Professor Francis is right on here about the specific subject being discussed, but the point is that there is an established hierarchy of evidence on display.  The RCT is king, everything else is no better than the court jester.

While an RCT may certainly be better than anything cobbled together at a pub, the conventional parallel group RCT certainly isn’t always King of the Hill.   As nicely expounded on by the prolific statistician Stephen Senn, there are plenty of potential errors the conventional RCT finds itself humbled by.

The clinician may thus feel somewhat mollified about conclusions drawn about the effect of epinephrine in the earlier anecdote.

The idea that real evidence may live outside the confines of RCTs was also countered by none other than the godfather of EBM, David Sackett:

“Evidence based medicine is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions. To find out about the accuracy of a diagnostic test, we need to find proper cross sectional studies of patients clinically suspected of harboring the relevant disorder, not a randomized trial. For a question about prognosis, we need proper follow up studies of patients assembled at a uniform, early point in the clinical course of their disease. And sometimes the evidence we need will come from the basic sciences such as genetics or immunology. It is when asking questions about therapy that we should try to avoid the non-experimental approaches, since these routinely lead to false positive conclusions about efficacy. Because the randomized trial, and especially the systematic review of several randomized trials, is so much more likely to inform us and so much less likely to mislead us, it has become the “gold standard” for judging whether a treatment does more good than harm. However,some questions about therapy do not require randomized trials (successful interventions for otherwise fatal conditions) or cannot wait for the trials to be conducted. And if no randomized trial has been carried out for our patient’s predicament, we must follow the trail to the next best external evidence and work from there. (Sacket et al, Evidence based medicine: what it is.. )”

Sackett also noted that there were therapies whose ” ‘face validity’ is so great that randomized trials were unanimously judged by the team to be both unnecessary, and, if a placebo would have been involved, unethical”.

In effect, there was always an escape clause to let common sense prevail over EBM.  But as frequently happens in movements, the second generation of followers moves in directions unintended by the founders.  If the safeguards in place involve only areas where equipoise exists, but equipoise is itself determined by fallible judgement, the range of unacceptable experiments becomes very narrow.  This especially applies to new therapies where members of the community not involved in design and development have skeptical prior beliefs.  This is, of course, not a bad thing – it is entirely possible that the usually overoptimistic prior of the developers of a new therapy are farther from the truth than the skeptics.  But it is a major problem if we ask doctors to discard their prior beliefs that are not based in RCTs.  In doing so, we are manufacturing equipoise.  This means travel in dangerous ethical waters for physicians and their patients that is at best unwise, and at worst willfully foolish.

The EBM Wars: Manufacturing Equipoise (Part 1) published first on https://wittooth.tumblr.com/

[kristinsimmons]

The EBM Wars: Manufacturing Equipoise (Part 1)

By ANISH KOKA

The phone rings.  It’s not supposed to be ringing.  It’s 2 am.   The voice on the other line is from an apologetic surgery resident.

Resident: There is this patient..

Me: Yes, go ahead. Please.

Resident: He’s tachycardic.

Me: How fast?

Resident: 160 ?

Me: What’s the blood pressure?

Resident: 130/90

Me: Rhythm?

Resident: An SVT I think.. I gave adenosine.  Nothing happened

Me: Audibly groaning.  I’ll be in..

Forty five minutes later I’m at the bedside of a decidedly ill appearing man.

I want to be triumphant that his heart rate is only 145, and a quick glance at the telemetry monitor above his bed uncovers juicy p waves in a cadence that suggests this is no primary electrical arrhythmia.

Something is very wrong somewhere – the heart in this case is an innocent bystander being whipped into a frenzy to compensate for something.

At the moment the whip is a norepinephrine infusion being used to keep his blood pressure up.

I ask the nurse if the amount of norepinephrine infusing has been stable.  She replies that his dose has been slowly escalating.

Eureka! I think – the heart rate response in this case is being driven by the norepinephrine – a powerful adrenaline that acts on beta receptors and alpha receptors within the body that increase heart rate and constrict the blood vessels to raise blood pressure.  Fix the cause of the low blood pressure, come down on the norepinephrine, and perhaps the heart rate would be better.

But it turns out this particular post surgical patient doesn’t have a medical cause of low blood pressure I can find.  I cycle through cardiac ultrasounds, blood gases, steroid and volume challenges, and try inching down on the norepinephrine.

All of it is to no avail.  I’m growing more and more convinced this problem is surgical in nature. Perhaps an infarcted piece of bowel?  All I know is that the man acts like he has no peripheral vascular tone.

An interesting thing happens shortly after.  The norepinephrine drip runs out.

As one nurse runs to get another bag from the pharmacy – a quick cascade of events unfolds.

The brisk upstroke from the arterial line that marks the pressure wave generated with every beat of the heart starts to dampen.  The color seems to visibly drain from the patients face, and he begins to complain that his vision is getting blurry.  His systolic blood pressure is 70 – an almost forty point drop within a minute of the norepinephrine running out.

I call for help.

I try to keep a level tone.  Project control, not panic.

“Open the code cart, I need a half a milligram of epinephrine”

“You’re going to be ok, sir.  Hang with me.”  I squeeze his hand.

He closes his eyes

The code cart – a fully stocked cabinet on wheels with almost everything you need for resuscitation efforts – is wheeled into the room. The epinephrine vial is handed to the nurse, and hurriedly pushed.

Within seconds, I can see the blood pressure and heart rate rise.  The patient’s grip on my hand relaxes.  Or maybe its my grip on his hand.  I forget which.  His vision returns to normal as his blood pressure ‘normalizes’.

Of course nothing has been fixed.  Why his blood pressure remains low continues to be a mystery.  The bag of norepinephrine soon isn’t enough even at its maximal dose.  The same scenario (hypotension -> pallor -> vision loss ) recurs 30 minutes later, and another bolus of epinephrine aborts a rapid spiral towards pulselessness.

This case is an anecdote, the weakest possible form of evidence apparently.  Yet there are powerful lessons learned that night. Blood flows in pulsatile fashion with a certain pressure head.  Below some threshold of pressure, the end organs of the body stop functioning.  Agents that are active on peripheral vasoconstrictor receptors (norepinephrine, epinephrine) raise blood pressure.  Epinephrine was keeping this patient alive while a team worked to understand why his blood pressure was so low.  My suspicion was that he was in something called distributive shock – a catastrophic life threatening syndrome that requires a furious hunt for cause to save the patient.  Overwhelming infection and an even more aggressive immune response renders normally relatively impervious vasculature to be a sieve.  At the present time the therapy is directed towards replacing the fluid lost in the intravascular space and using medications that act on peripheral vascular receptors that increase peripheral tone.

There is, of course, much that isn’t known about this process.  Hopefully it will come to pass that we will arrive at a better understanding of what specifically creates this mileu so our therapies may be more directed.  But for the time being, our solutions are limited by our current, always imperfect understanding of the world.

The culprit in this case was a leak of intestinal contents into the peritoneal space from two pieces of bowel that should have been exactly apposed.  The body had attempted to tell us this very thing with that high heart rate post-operatively.  It took us, the clinicians, some time to translate.

The uninformed prior: Unlearning what has been learned.

For many, medicine has for too long been an imperfect science.  The history of medicine is replete with physicians acting with certainty in a manner that – in hindsight – was ineffective, or even worse – harmful.  Blood letting to allow the release of bad humors is believed to have hastened the demise of the greatest American – George Washington.  The disconcerting part of this is that the physician players were not motivated by anything but the best intentions.  They relied on their experience, intuition and judgement to deliver exactly the wrong prescription.   Intuition fails.  No matter how many patients died soon after blood letting, operating biases didn’t let physicians link the two events.  After all, the patients may have died even sooner if blood letting hadn’t been done.

The idea that medicine had progressed – by the 1980’s – to the point that doctors were not engaged in the equivalent of blood letting came under heavy fire when it was demonstrated a number of standard practices of the time could indeed be ineffective.  Extra beats (also known as ectopic heart beats) after heart attacks were noted in cardiac units to portend a higher risk of dying suddenly.  The obvious approach to this was to use medications that effectively suppressed ectopic heart beats.  Testing this in a double blind randomized control trial did not just demonstrate ineffectiveness, but harm.  More people randomized to suppression of ectopic beats actually died.  It turns out the anti-arrhythmic drugs being used were actually proarrhythmic as well.  The attack on ‘expertise’ that relied on intuition and experience was on, and it was a rout.

Glue ear – a condition that developed in the middle ears of little kids after ear infections  was treated with insertion of a tube to drain that space.  The trial to determine efficacy using a randomized trial to blindly allocate patients to surgery or no treatment?

Negative.

Many of the children turned out to do just fine if you left them alone.  Given the fact that all procedures have a certain complication rate, the lack of efficacy here was no small matter.

And so it went – the populace had to be on guard not just against the afflictions of disease, but against the intuitions of its doctors.

Uncertainty reigned, and in search of certainty, the field fled to the warm embrace of ever greater empiricism.  In the early ’80s from the McMaster University in Canada, David Sackett gave voice to a new sheriff – Evidence Based Medicine (EBM).

“EBM de-emphasizes intuition, unsystematic clinical expertise, and pathophysiologic rationale . . . and stresses the examination of evidence from clinical research. In 1960, the randomized trial was an oddity. It is now accepted that virtually no drug can enter clinical practice without a demonstration of its efficacy in clinical trials. Moreover the same randomized trial method is increasingly being applied to surgical therapies and diagnostic tests.” (Sackett et. al, Evidence Based Medicine)

The premise as outlined is simple – don’t believe anything that hasn’t been tested in a randomized control trial.  The only real evidence is that found within RCTs or in reviews that amalgamated RCTs.

The usual response from EBM experts can be found below in the response to the statement that real evidence may come from outside an RCT.

It is quite possible Professor Francis is right on here about the specific subject being discussed, but the point is that there is an established hierarchy of evidence on display.  The RCT is king, everything else is no better than the court jester.

While an RCT may certainly be better than anything cobbled together at a pub, the conventional parallel group RCT certainly isn’t always King of the Hill.   As nicely expounded on by the prolific statistician Stephen Senn, there are plenty of potential errors the conventional RCT finds itself humbled by.

The clinician may thus feel somewhat mollified about conclusions drawn about the effect of epinephrine in the earlier anecdote.

The idea that real evidence may live outside the confines of RCTs was also countered by none other than the godfather of EBM, David Sackett:

“Evidence based medicine is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions. To find out about the accuracy of a diagnostic test, we need to find proper cross sectional studies of patients clinically suspected of harboring the relevant disorder, not a randomized trial. For a question about prognosis, we need proper follow up studies of patients assembled at a uniform, early point in the clinical course of their disease. And sometimes the evidence we need will come from the basic sciences such as genetics or immunology. It is when asking questions about therapy that we should try to avoid the non-experimental approaches, since these routinely lead to false positive conclusions about efficacy. Because the randomized trial, and especially the systematic review of several randomized trials, is so much more likely to inform us and so much less likely to mislead us, it has become the “gold standard” for judging whether a treatment does more good than harm. However,some questions about therapy do not require randomized trials (successful interventions for otherwise fatal conditions) or cannot wait for the trials to be conducted. And if no randomized trial has been carried out for our patient’s predicament, we must follow the trail to the next best external evidence and work from there. (Sacket et al, Evidence based medicine: what it is.. )”

Sackett also noted that there were therapies whose ” ‘face validity’ is so great that randomized trials were unanimously judged by the team to be both unnecessary, and, if a placebo would have been involved, unethical”.

In effect, there was always an escape clause to let common sense prevail over EBM.  But as frequently happens in movements, the second generation of followers moves in directions unintended by the founders.  If the safeguards in place involve only areas where equipoise exists, but equipoise is itself determined by fallible judgement, the range of unacceptable experiments becomes very narrow.  This especially applies to new therapies where members of the community not involved in design and development have skeptical prior beliefs.  This is, of course, not a bad thing – it is entirely possible that the usually overoptimistic prior of the developers of a new therapy are farther from the truth than the skeptics.  But it is a major problem if we ask doctors to discard their prior beliefs that are not based in RCTs.  In doing so, we are manufacturing equipoise.  This means travel in dangerous ethical waters for physicians and their patients that is at best unwise, and at worst willfully foolish.

The EBM Wars: Manufacturing Equipoise (Part 1) published first on https://wittooth.tumblr.com/