Dr John M

cardiac electrophysiologist, cyclist, learner

Shining Bright Spot of 2020 — The RECOVERY Trial

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Take a look at this article in The Times. It tells the story of Oxford professors named Martin Landray and Peter Horby.

When they saw the pandemic unfolding in China and Lombardy, their first thought was to design a proper clinical trial to determine what works for COVID19.

Normally, it takes a year or more to design a medical trial, but they got it done in weeks. This process is super important. You have to write a design first and decide what you will measure. Here is the protocol.

There were two keys to success: one was that the trial had to be simple and the other was that it needed buy-in from hospitals and doctors. Buy-in comes easier in the UK because they have the NHS–a nationalized healthcare system.

The idea behind the RECOVERY trial is that COVID19 is a novel disease, and doctors don’t know what works. The fancy term for this is equipoise.

In the US and other countries, doctors often “throw the kitchen sink” at patients. The problem there is that you can’t figure out what works.

In the UK doctors enrolled patients in the RECOVERY trial. This meant the choice to use a drug like dexamethasone was not up to the doctor but was random.

Some patients got placebo, some got the steroid. Randomization is crucial as it usually balances the groups of patients and allows us to infer causation.

It turns out that the inexpensive and commonly-used drug was beneficial. In a NEJM paper, the authors reported a 17% lower rate of death in the group that got the drug.

In absolute terms the reduction was 2.8%. A rough way to think about that is for every 35 patients treated, one life is saved. Or this: for every one million patients with COVID19 treated with this simple drug, 28,000 lives are saved.

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Readers of this blog and my podcast This Week in Cardiology know how much I believe in the randomized clinical trial. I’ve even said that the the RCT may be the most important medical development of our lifetime.

One hope I have is that COVID19 will help develop the infrastructure needed to do more clinical trials here in the US.

RCTs are not perfect, but they are the best way to know what works and what does not work.

No, Young Adults Should Not Live in Fear from Coronavirus

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What follows is an OpEd that I co-authored with Andrew Foy, MD, from Penn State University. Andrew is an academic cardiologist who studies the quality of scientific evidence.

Two outlets have declined to publish our piece. This is not surprising given that we critique a research letter written by prominent academic leaders. As you read our take, please keep in mind that we oppose only the ideas expressed in the interpretation of data.

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The Journal of the American Medical Association recently published a research letter that reported an excess of nearly 12,000 deaths among younger adults this year. Of these deaths, slightly more than one in three were due to COVID19. 

Three of the authors then explained their findings in an OpEd in the New York Times that ran with the title “People Thought Covid-19 Was Relatively Harmless for Younger Adults. They Were Wrong.” The subtitle doubled down on the fearsome messaging: “New research shows that July may have been the deadliest month for young adults in modern American history.” 

We do not deny the seriousness of COVID19, but we are concerned that prominent medical leaders have potentially misinterpreted their findings. This is remarkable because one of the co-authors is Rochelle P. Walensky, MD the newly appointed head of the CDC. 

We offer four reasons why this study and OpEd do not support the claim that young adults should live in fear from the virus. The point of our critique is not to tell young people to avoid basic measures such as mask wearing and social distancing, but instead to counter the exaggeration of scientific findings—even if the intent is well-meaning. 

The first problem relates to the authors’ choice to assess excess mortality rather than death due directly to COVID19. They state that this was a better way to assess the full burden of the pandemic, as “mortality in young adults may go uncaptured due to uncoded COVID19 and other pandemic-related mortality.”

As doctors who care for patients in the hospital and ICU, we disagree with the premise that undercounting of COVID19 deaths in young adults is common. In an older person with numerous advanced organ diseases, it is sometimes difficult to sort out the true cause of death—especially when death occurs at home. But in a young person, without these chronic diseases, death due to COVID19 pneumonia is much more straightforward to diagnose. 

If under-reporting of COVID19 death is not a major problem in young adults, then one could assess the burden of viral infection by simply counting the number of deaths from the virus. That has been done. A systematic review of more than a hundred studies has shown that the infection fatality rate for young adults is quite low. The authors even cite a study documenting the low case-fatality rate in this age group. 

The second issue relates to the choice to compare excess deaths this year to accidental opioid overdoses from 2018. When we looked at the data presented in the paper and its supplement, we found that with exception of a few scattered months, in a couple of regions, COVID19 deaths were lower than opioid overdose deaths in 2018. An alternative conclusion therefore could be that COVID19 deaths in this age group are much less common than opioid overdose deaths. The authors acknowledge this point in their discussion of the study’s limitations.

The third issue is the tiny absolute increase in risk. An excess of 12,000 deaths sounds bad, but Professor Don Boudreaux, from George Mason University, has noted that there are nearly 88 million people in this age group. Thus, the individual risk for a person this age is found by dividing 4,560 (the number dead from COVID19 in this study) by 88 million. This equates to a 0.0052% risk of dying from COVID19. 

While people have different risk thresholds, we struggle squaring a 1 in 20,000 chance of death from the virus with the following statement in the NYT OpED: “Young adults are dying at historic rates.” 

The fourth issue relates to the ratio of virus-related and non-virus-related death. The authors report that 38% were related to COVID19. We ask: what were the causes of the other 62% of excess deaths?

All practicing doctors understand that harm can come from both a disease and its therapies. In this case, the disease is the viral infection; the main therapy is societal interventions. Based on the finding that a higher proportion of deaths occurred from non-viral causes, why wouldn’t an impartial scientist consider the possibility that pandemic interventions have dealt more harm to young adults than the infection itself? 

To prove this thesis would require a deeper look into the data, but we propose that it is reasonable to speculate that economic damage brought by the pandemic could have increased “diseases of despair,” such as depression, suicide and drug overdoses. Another plausible reason for an increase non-COVID19 deaths is avoidance of routine medical care and the postponement of non-emergent procedures. 

In sum, the data in this research letter is inconclusive for drawing conclusions about the risk of dying from COVID19 infection in young adults. The authors noted some of these limitations in the manuscript, but then amplified a fearsome message in the New York Times. 

We understand that the authors’ intention to nudge young adults to adhere to social distancing is benevolent. Our aim in submitting this critical appraisal is not to minimize COVID19 nor to attack the authors, but to uphold the impartial judging of science. Because without impartiality, public trust is lost. And trust will prove crucial for maximizing the benefits of the newly developed vaccines.

The young have many reasons—ethical and moral–to adhere to social distancing during the pandemic. Fear of death is not one of them. In our view, promoting flawed evidence is counterproductive. 

Follow-up on my Eight COVID Assertions

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Yesterday’s post generated some good comments.

Two emergency medicine specialists felt that I was both wrong and insulting in saying that hospitals were not overwhelmed.

What I meant in the word ‘overwhelmed’ is the notion of not being able to support a sick patient in the ICU or on a vent. That didn’t happen, but both doctors make important points.

First I mean no insult to my frontline colleagues. It’s the opposite really. As a specialist who deals mostly on the treatment side of things, I’ve held those who must make diagnoses in the highest regard. Their work in the pandemic has only increased that respect.

Second, the point that there were consequences to the “massive and costly” efforts to shift resources is valid. Data in our (cardiology) journals hint at the fact that heart attacks and stroke admissions were way down during the height of the pandemic.

But it’s hard to believe that heart attacks and strokes stopped happening during this stressful period. Post-pandemic reviews will likely show that the efforts to care for patients with COVID19 will have increased unnecessary non-viral deaths due to lack of care. (The counter is that the pandemic also stopped a lot of low-value, potentially harmful care.)

Nonetheless, “overwhelmed,” was a poor word choice. Sorry.

2. My Twitter friend, Dr. Mike Johansen (who is a super-sleuth when it comes to critical appraisal) pointed out that my comparison to NZ and Australia is problematic.

Dr. Johansen’s first point about not using the dichotomy between NZ and the US is well-taken–especially given the surprise of vaccine development.

Response to the pandemic has clearly been on a continuum. As he wrote, countries such as Canada, Germany, Denmark, Finland have done better than the US. And now that we have vaccines, countries that did better with pandemic control will end up with less death due to COVID19.

It’s interesting, too, that the countries mentioned above all have better safety nets than the US. Though, there are many other factors in a country’s response to the pandemic.

This country has to figure out a way to improve our safety net. I realize that people differ on how to get there. But no one can disagree that it is an existential problem.

3. An anonymous commenter pushed back on my assertion #6.

What evidence is there that reductions in IFR are due to masks and distancing?

My thinking is not that masks or distancing affect the IFR directly, but that delaying getting the infection will reduce one’s chance of dying. For two reasons:

It was a novel virus; it took time to learn stuff. So it is clearly better to get the virus in December than in April.

And now there are vaccines.

For a person with risk factors, therefore, it makes sense, now, to stay hunkered down for a few more months. There is an end in sight.

If you have the means, you use online shopping, you avoid weddings and large gatherings, get an N95 mask, do Zoom Christmas and take the vaccine.

But my commenter is right: Social distancing and masks do not affect the severity of illness–though there is a theory that a mask might lower the severity of illness by reducing the amount of virus that gets in your body.

The pandemic forces everyone to think. This is a good thing.

JMM

What I Got Wrong (and Right) about COVID19

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In May, I wrote a column about COVID19 that got some attention.

My reason for writing was the change in messaging about the strategy of flatten-the-curve. We were first told to flatten-the-curve to prevent overwhelming hospitals. But then the thinking changed to flatten-the-curve to save lives. 

I made eight assertions about COVID19. Let’s see how I did. 

Assertion 1: The virus will not be contained. Verdict: Correct.

You might argue that New Zealand and Australia contained the virus, but I would counter that these are not fair comparisons to the US, Canada, and the EU. 

Assertion 2: Tests will underperform. Verdict: Correct.

The US–which is in the midst of its third spike–is n the top-tier of countries for numbers of tests per million people. Test-and-trace is pure folly. I would not be surprised if some people are actually avoiding being tested–so as to keep working.

Assertion 3: Hospitals are in little danger of being overwhelmed. Verdict: Mostly correct.

There are now places under pressure, some are feeling serious pressure, but we have not nor will we see a Northern-Italy-like situation in the US.

Assertion 4: Americans are not stupid; we will socially distance and take common-sense measures. Verdict: Debatable.

While I stand by my early opinion, I understand those who would point to the third spike and holiday travel as evidence I was wrong. 

A brief comment on the current situation. A colleague recently argued with me that we could have been more like Australia; he said Americans were selfish in failing to take measures to control the virus. In other words, he laid much of the blame on the people.

I don’t entirely blame the people. I lay a lot of the blame on messaging. Consider a doctor who has zero success in getting patients to lose weight, or stop smoking, or take their meds. Maybe it is the messaging.

Apply this thinking to American pandemic messaging: the scolding and scare tactics, mostly from those with the privilege or luck to be able to work at home; the counting of only infections and not the disparate effects of economic shutdowns, and, most of all, the inane rules–like having schools closed for instruction but allowing football.

These have all contributed to a feeling amongst many in the community that goes something like this: screw it, we are done listening.

Assertion 5: Public health surveillance has improved. Verdict: Correct.

While tests have failed to stop the spread of this virus, there are enough tests to inform decision-making at the local level. My hospital has a daily count of cases and have surge plans ready. Indiana, for instance, recently enacted a temporary hold on elective surgeries based on surveillance data. 

Assertion 6: Non-pharmaceutical interventions, such as social distancing and masks, would not lower the infection fatality rate. Verdict: Wrong.

Early on I saw little advantage to delaying infection. I wrote: “the only way fewer people die from COVID19 over time is if the IFR declines.” I then went on to describe the slowness of medical progress.

There have been two major medical developments that (now) argue strongly for delaying infection–especially earlier this year.

First is that clinicians better understand how to care for patients with COVID19 pneumonia. Early intubation is out; steroids have been shown to reduce death in ill patients, and oodles of studies have shown us what not to do.

Second is the huge surprise of vaccine development. I wrote that “COVID19 vaccine development is sobering.” That was dead wrong.

Vaccine development has been intoxicating in its success. With two messenger RNA vaccines with over 90% efficacy, and other vaccines in the works, an optimistic person could have this pandemic ending next year. Adverse effects remain a potential issue, though early data is reassuring.

Assertion 7: The more we test, the lower IFR goes. Verdict: Mostly correct (with caveats).

The US has 16 million known cases. If this number underestimates actual infections by 5, then approximately 80 million Americans have been infected. If you divide by 300,000 deaths, that’s an IFR of 0.3%. 

The two misleading aspects of IFR are the gradient of disease and the morbidity of viral pneumonia. For the young, and those with no risk factors, the IFR is way lower than 0.3%; but for the elderly and the many millions of Americans with obesity, the infection is far riskier. As for COVID morbidity, many survivors of ICU stays face a long road back to normal.

Assertion 8: The harms of pandemic interventions are under-appreciated. Verdict: To be determined.

The intense political divide, the growing intolerance of ideas, the racial unrest, all argue for a pessimistic case that the lives lost from the viral infection will NOT end up being the gravest harm from this contagion.

I do not intend to minimize the loss of life due to viral infection, but I wonder about the degree to which the pandemic interventions have exacerbated the fraying of vital societal bonds. 

A friend sent me this idea via private message: 

The case to be made is the economic consequences of the lockdown on the poorest, and the societal consequences of those economic consequences. It’s not (viral) death vs (non-viral) death. It’s death vs societal collapse. 

I will choose, perhaps naively, to remain optimistic that the pandemic, intolerance and polarization will abate.

JMM

New column and podcast up:

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Last week, I wrote a column on one of the most controversial clinical trials in cardiology.

The EXCEL trial pitted stents vs bypass surgery for people who have left main coronary artery disease. The trial has been beset with controversy.

The three areas of debate surround the definition of MI (or heart attack), the increased risk of death in the stent arm, and selective publishing of data.

Here is the column: Latest EXCEL MI Analysis Settles Nothing; Flaws Remain

You should study this one because it hints at how precarious medical evidence can be.

On the This Week in Cardiology podcast, I discuss EXCEL, but also the issue of trust in science.

This includes a few words on the matter of silly studies that still garner media attention. I’ve come to name these studies, howlers.

One of the reasons behind this is the business model of medical publishing. Medical journals, like any media outlet, need attention. Coffee studies bring attention; statistics studies not so much.

The pandemic has brought oodles of silly studies.

A classic example is the broken study on cardiac MRI in recovered COVID patients. This one had to be corrected due to a slew of errors and now shows no concerning signal of cardiac harm from COVID. But it has hundreds of thousands of page views and will surely bump up the impact factor of the journal that published it.

I discussed CMR, COVID and sports participation a few weeks ago.

The problem with howlers is that they hurt public trust in science. One week coffee is good, the next it is not. Don’t wear masks, do wear masks.

I also discuss the Vitamin D and COVID19 issue. Teaser: it’s folly.

Science leaders, I think, ought to be more candid about the limits of science, the uncertainty. Let the public in on the truth.

You know, a Karl Popper-like message.

Finally, there was big news in nutrition science: a group at the UCSF actually did a randomized controlled trial. This is huge because most nutrition science stems from flawed observational studies.

Here is the pod link: https://podcasts.apple.com/us/podcast/this-week-in-cardiology/id991125169

Let me know what you think. Remember, if you like the pod, give it a good rating so others can find it.

JMM

Deeper Worries in America

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I worry about the coronavirus. It’s already killed more than 100,000 Americans. The recent protests have created a nerve-wracking public-health situation for the next weeks.

I really worry about racism. Not only racism in police systems but more systemic racism in our culture.

My friend Dr. Andrew Foy sent me this slide and post showing the large disparity in black and hispanic representation in medical education.

There can be no rest so long as a man like Dr. Otis Brawley, a distinguished professor of medicine,

“can get thrown to the ground, handcuffed and questioned at gunpoint for looking suspicious in a nice part of Montgomery County. That would be yours truly a few years ago.

My real offense: standing in the garage of my own home.”

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But I think there may be another great threat to this country.

Last night I read a story describing a situation in which the writer Andrew Sullivan would not be allowed to publish his column on the protests in the New York Magazine.

Sullivan is not just forbidden from writing for the New York magazine about the riots; his contract means he cannot write on the topic for another publication.

From Wikipedia: Andrew Sullivan is an openly gay Roman Catholic conservative intellectual. He has voted for Bill Clinton, and endorsed Barak Obama. And in 2006, Sullivan was named as an LGBT History Month icon.

The reason I am writing here is that my colleague in cardiology Usman Qayyum asked ….with so many problems right now, how is this important?

This is important because it indicates what could become a dangerous problem: the fall of classic liberalism.

If a sane calm intellectual like Andrew Sullivan can be silenced, what does that say for others?

Then there was the civil war within the NYT about the Tom Cotton editorial. I disagree strongly with the Senator’s view, but as a leading senator, should he not be allowed to make his argument?

Intolerance of ideas also extends into science:

Liz Neporent, the social media director at Medscape, had an important story on how YouTube initially removed a video on coronavirus from British oncologist and former chief of The WHO for violating guidelines. Initial efforts to have the video reinstated failed. It took more intervention from Medscape Medical News to get it put back up.

What was the problem? The scientist dared to express a view of the coronavirus that ran counter to the prevailing “consensus.” As if there could be any consensus with a months-old novel virus.

Hospital-employed doctors and nurses have grown used to not speaking publicly on anything contentious. So have many corporate workers.

But when this degree of illiberalism reaches the opinion pages of media, college campuses or social medial platforms, we have a big problem.

The obvious issue with deplatforming an idea is that if it can’t be debated, it cannot be proven wrong.

The late Christopher Hitchens, who we dearly miss now, once said or wrote: “time spent in argument is hardly ever time wasted.”

If the opposition to the current authoritarian regime, one that seeks to divide us, is an illiberal group that does not tolerate free public debate, I think we should be very worried.

JMM

P.S. After a thoughtful online discussion with Professor Alok Khorana, I have changed my choice of words in the seventh and eleventh paragraphs.

In the seventh paragraph, I changed the wording from ‘even greater ‘ to ‘another’ to define a threat to our country. In the eleventh paragraph, I changed ‘what could become a much more dangerous problem’ to ‘what could become a dangerous problem.’

By expressing my concern over the intolerance of ideas in policy and science, I did not intend to minimize racism.

P.P.S: Another edit. I cut the line “As a doctor, I am always looking for upstream causes of bad things.” I did not mean to imply the intolerance of ideas caused systemic racism.

Stopping COVID19 in Nursing Homes is No Easy Task

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My city, Louisville KY, recently had a spike in COVID19 infections. It came from a handful of nursing homes.

That nursing home and long-term care facilities account for large percentages of COVID19 cases has been well documented. In some cities, the majority of cases come from these facilities.

These facts have sprouted platitudes about “protecting our elderly.” What makes this a platitude is that it belies the challenges faced by nursing facilities.

Two recent papers shed light on these challenges.

First is an article by Chris Pope in the City Journal. Second is an academic-like defense of Stockholm City’s elderly care. The latter paper came in response to the former chief epidemiologist of the Public Health Agency of Sweden Johan Giesecke who bluntly said that Sweden has failed in protecting those in elderly care.

My wife spent a handful of years practicing palliative care and hospice in nursing homes. Her stories confirm the challenges brought out in both these papers.

I don’t think many people get the reality of life in nursing facilities.

Taken from these two articles, here are 7 challenges for protecting people from COVID19 who live in nursing facilities:

  • Residents spend most of their day in close contact with others, indoors, eating meals together, often sharing rooms, and needing high-touch care from caregivers who move room to room.
  • How can you social distance when residents need on average of four hours daily of personal care? Why so much? Almost half of residents have dementia, 2/3rds have bladder incontinence, 1/3rd require rehab, 2/3rds are chair-bound and 15% require respiratory therapy.
  • Healthy people do not get admitted to nursing homes. The vast majority of residents have not one but multiple chronic conditions, such as high-blood pressure, heart disease, diabetes and lung disease. (All risk factors for COVID19 mortality).
  • People in nursing homes are already near death. [I]n 2016, while nursing-home residents made up just 0.4 percent of the U.S. population, they accounted for 19 percent of deaths.”
  • Because of the last two points, residents of nursing facilities travel back and forth from hospitals–further increasing the risk of being infected with serious pathogens.
  • Work in nursing home is neither glamorous nor well-paid. “Nursing-home staff often work in multiple facilities, share housing with those who work at other care homes, and rely on public transportation.”
  • While many nursing residents have advanced dementia, many do not. The isolation of people from other people, including their loved ones, is hardly an easy intervention.

While these words lay out problems not solutions, I do so in hopes to provide some reality to the difficulties in protecting the most vulnerable.

Often heard on our hospital wards is something like this: “Mrs Jones is going to the nursing home to get stronger.”

While this is true for a select few elders who’ve had a recent surgery or brief illness, for many elders, the truth is they are going to the nursing home because they are too frail to be home. And that frailty is a result of their long life.

I’ve said before that I hate this virus. I wish it never came.

But its presence does seem to be teaching us a lot.

One lesson has been the dangers of accepting shoddy medical evidence (hydroxychloroquine); another is the limits of epidemiological models, and a third may be the stark realities of protecting older vulnerable patients who are close to the end-of-life.

We can hope that advances, say, better testing, more protective gear for nursing home workers, a vaccine, or even smarter policy changes will help reduce the effect of COVID19 on nursing home residents.

But it won’t be easy. We will have to be careful with what we consider success and failure.

JMM

P.S. I wonder if mandatory 2-month rotations in nursing facilities for medical trainees might help doctors better understand the realities faced by older patients.

More on COVID19 Testing and How This Virus Makes Us Use Our Noggins

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My friend Anish Koka, a cardiologist, wrote a beautiful review of COVID testing over at the HealthCareBlog.

The great pandemic is wreaking havoc, we are told, because the nation is not testing enough.  The consensus from a diverse group that includes public health experts, economists, and silicon valley investors is that more testing will allow the country to restart the economy and do it safely. 

No, it’s not quite that easy, Anish writes. You will learn a lot from his long column.

You might wonder why a COVID post from a cardiologist is worth reading. First, since COVID is novel, there are few true experts. Second, COVID tests are similar to cardiology tests in many ways.

Take a stress test; these are not black and white. A young patient with no risk factors and unusual symptoms who has a positive stress test probably has a false positive. A patient who smokes and has diabetes and typical chest pain who has a positive stress test probably has a true positive.

COVID tests are like that too. You have to think about likelihoods. You have to know the viral swab has problems with false negatives–you could have COVID infection and still test negative. The antibody tests have the other problem: you could test positive and not actually have the antibodies.

One of my hopes from this terrible pandemic is that it makes patients and doctors smarter about uncertainty. COVID19 is one giant thinking exercise. And if we think a lot we may collectively become smarter about healthcare.

The next time the doctor says you “need” some test, you might think about asking about the rates of false negatives or false positives. You might think what if I don’t get this test?

And since your mind is so sharp from all this thinking, you might think: what are the potential downsides, the unintended consequences of having this test? I have seen a simple $25 dollar ECG lead people into an odyssey of healthcare folly.

Dan Morgan, MD and I wrote about the pitfalls of cascades from testing in the open access journal JAMA Network Open.

JMM

COVID19 and Finding Effective Medical Therapies

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This post introduces a column I wrote over at TheHeart.org | Medscape Cardiology

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The good news is that most people infected with coronavirus don’t need a hospital or doctor. But some do. Some get very ill.

The maddening thing is that doctors don’t have an effective treatment for the virus. There are no cures. The Worldmeter today shows nearly 5 million infections and more than 300,000 deaths. And no effective therapy.

Excluding a possibly modest effect of Remdesivir, our care is supportive, which is medical jargon for giving simple things like oxygen, acetaminophen, IV fluids and letting the body do the rest.

That sentence makes supportive care seem simple, but it is not so with COVID19. The virus can cause havoc in the body. Damage to the lungs (pneumonia) gets most of the attention, but other organs can be harmed.

COVID19 and Clotting:

One system in particular that can go haywire is the clotting system (medical term is coagulation). Many studies have shown that patients ill with COVID19 can have excess clotting.

(It’s not well known, but our bodies do this elegant dance to keep the blood clotting factors and thinning factors in balance. Medical people call this equilibrium or homeostasis of the coagulation system.)

We now have blood tests that give us a window, albeit a somewhat opaque one, onto the clotting system. Also imperfect is the observation that patients with COVID19 can clot off intravenous lines, or on autopsy, clots can be seen in organs.

The worry about excess clotting (medical term is thrombosis) causes doctors to consider using drugs called anticoagulants, which come in many different forms–heparin (IV), low-molecular weight heparin (sub-q shots) and direct-acting oral anticoagulants (DOACs).

“If there are too many clots, you give clot-blocking drugs”…goes the Cartesian body-as-a-machine thinking.

Alas, the problem is a) infection control issues often makes it impossible to scan COVID19 patients, so we don’t know if they actually have clots in their organs, and b) anticoagulants can accentuate bleeding, which can be horrific.

Anticoagulants Work in Some Diseases:

In non-COVID19 patients, we know anticoagulant drugs work because we have done proper trials.

Take anticoagulants for patients with atrial fibrillation. We know these drugs work because in trials with thousands of AF patients who take the drug compared to thousands who take placebo, fewer people have strokes while taking anticoagulants. These trials also tally bleeds and thus doctors can know the net benefits, which favor the anticoagulants in selected patients.

Proper Trials = Knowledge:

The essential part of a proper trial is that the choice to use the drug or not (placebo) is random. That means in a randomized controlled trial (RCT) you end up with two balanced groups of patients. (Well, mostly balanced). This is crucial because if one group does better, you know it was drug, and not because one group was healthier, or sicker.

Trials, of course, take effort. You have to write a protocol, specify what you will measure and the types of patients to include or exclude, get ethical approval, recruit sites, consent patients, to name just a few tasks. You also have to blind the patients and doctors so they don’t know the treatment arms. This takes money and time. RCTs don’t make themselves.

The Limits of Observation:

In the COVID era, people don’t want to wait. So instead, investigators are recording outcomes on what happens to patients who have been treated.

These are called observational studies; people simply observe what happens after the fact.

Observational studies are deeply problematic for deciding what caused what.

A simple example: a heart surgeon decides to do an extra procedure during routine valve surgery, say, a closure of the left atrial appendage in the heart. It takes an extra few minutes and the idea is that closure of the appendage will reduce clots and that will reduce future stroke.

Then researchers look back, and voila, patients who had the extra procedure during valve surgery had fewer strokes than patients who did not have it. The procedure must work. Wrong.

The problem is that the surgeon’s decision to close the appendage was not random: thus, she may have chosen healthier patients to do the procedure on. And that is why the intervention looked good. We call this selection bias.

The Pressure of COVID:

My post over at TheHeart.org | Medscape Cardiology critiqued a study published in an influential cardiology journal. A group of researchers from Mt. Sinai hospital system in New York City looked back on about 3000 patients with COVID19.

They studied the association between the use of anticoagulants (or non-use) and death in the hospital. They specifically considered patients sick enough to require ventilators.

They found that patients who received the anticoagulants had better survival. One of the authors was actually the editor-in-chief of the journal that published the study. His name is Dr. Valentin Fuster and he is one of the most-cited most influential voices in cardiology today.

Dr. Fuster was impressed with the results and went to the media to say:

I can tell you any family of mine who will have this disease absolutely will be on antithrombotic therapy and, actually, so are all of the patients at Mount Sinai now.

The problem was that these observations were biased. The choice to use anticoagulation was not random. So you can’t know if the drugs made survival better or whether it was something else.

Multiple experts, writing on Twitter, identified a well-known bias called immortal time bias. The last link explains the problem. But this was only one of the many biases in this observational study.

The Harm of Observational Studies:

Remember in the beginning I wrote that there was no known therapy for COVID19? One of the main reasons is observational studies.

Take the case of Mt. Sinai hospital. Because of this study, and the influence of the researchers, and publication in a big journal, there is a protocol in which sick patients get treated with anticoagulants. A treatment is codified as standard of care. And if it is codified at a big hospital in NY, it will likely be codified in other hospitals.

Here is the issue: now you want to do a study to find out whether anticoagulants work. A patient is asked to participate, which means they could receive placebo. The patient does a Google search and up pops Dr. Fuster’s comments to the Washington Post alongside a headline saying anticoagulants have promise in COVID19.

In this setting, the patient as well as many doctors will no longer have that feeling of uncertainty about the use of anticoagulants. We call this equipoise. And without it, you can’t ethically do trials.

The lack of equipoise causes us to persist with unproven therapies. Take Hydroxychloroquine–we still don’t have a proper trial.

Smart people, people whom I respect, say that the desperation of COVID19 is such that we should use the data we have.

I do not agree. In my column, I argue that observational data may actually be worse than no data.

The title of it is: Some Data May Be Worse Than No Data in the COVID Era

JMM

The Case for Opening (some) Pools In COVID19 Pandemic

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The COVID crisis has decimated water exercise. Can we rethink pool closures?

A significant number of my older patients relied on pools for their fitness. During a pandemic, you can stay active or fit only if you have good legs and joints. Walkers, runners, and cyclists have no problem; they play outside in the Spring weather.

People with bone/joint problems, fitness swimmers, and young children who normally take swim lessons this time of year are out of luck.

Consider the place I swim—the Mary T Meagher Natatorium, named after Mary T, a Louisville native, who won Olympic gold in 1984. The place is an ode to Sparta. The expansive no-frills public facility has tons of space to socially distance. 

Before I tell you my proposal, let’s set out some givens on May 13.

  • Three months into this crisis literally everyone knows the deal: the coronavirus is not going away. It will be as dangerous next year as this year; 
  • Older people are more vulnerable, and they know it;
  • The virus travels via droplets so distance reduces your odds of infection;
  • Other health conditions, such as mental stress, heart disease, obesity, diabetes, immobility and arthritis, do not become less problematic during a pandemic;
  • People differ in their risk tolerance; some people see a 0.5% infection fatality rate as scary as heck, others see a 99.5% chance of survival. 
  • Hand washing reduces transmission. Masks might also reduce transmission.
  • Finally, and this is key, the community-level risk for the virus differs greatly across the US. Policy in New York City or Chicago ought not be the same for rural Kansas or Texas. 

I’ve said before that Americans are not stupid. We can, and we must, rely on people to make good decisions for themselves and their community.

Now to the proposal to open some public pools: 

Start with a big sign in front that says we are open but these are not normal times. 

You place a bunch of hand-sanitizer stations at the entrance.

Tell people to wear a mask and leave it at the poolside. 

Then let them swim, do water aerobics at a distance, and allow teenagers to teach toddlers to swim. 

After the workout, people put their mask on and leave. If they have to use a locker room or shower, that’s fine. I don’t know about women, but in the men’s locker room, social distancing comes naturally whilst being naked.

When schools open in the fall, and they must open, kids should play sports. This includes the swim teams. Teenagers have minimal risk from the virus. If they are mixing in schools, there is no reason not to let them mix on the field and in pools. 

Caveat: I realize that summer scenes of hundreds of children mixed with adults in public pools is more problematic. My proposal applies to opening pools for the purpose of fitness. 

An unintended positive externality: the act of allowing people to exercise in water would be a small step towards making peace with the virus. If people don’t want to risk catching the virus, they can stay away. 

If we let people go to the grocery, walk in crowded parks or shop at gardening stores, we ought to let them enjoy the water. 

JMM 

Conflict of Interest: After fracturing my foot 2 years ago, I rediscovered the joys of swimming. Before the pandemic I often recommended swimming to my patients because there is something soothing about immersion in water.

Will the Uncertainties of COVID Science Resurrect Blogs?

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Health news was popular before the pandemic. Now, almost all news is health news.

It’s not only a rapt audience contributing to the deluge of COVID19 news. Two other factors: 1) the availability of preprint servers, digital archives where a scientific paper can be published without formal peer-review and 2) the attention economy.

Attention is currency. Since the business model of both scientific journals, internet-based medical news sites and mainstream media is attention (citations, views), both groups are eager to publish all that is COVID.

The slew of COVID papers are outpacing the normal vetting process. It happened with hydroxychloroquine. In normal times, a study as weak as the one which launched this unproven drug would have never passed muster.

Media has the same problem as medical journals. They struggle to keep up with the public’s need for COVID information. Vetting was far from perfect before COVID, but there used to be more time to assess a study, seek expert opinion and add a bit of caution.

For instance, pre-COVID, journalists would often get an embargoed copy of a study days before it was published. The luxury of time does not exist during the pandemic.

Enter blogs

Blogs were hip 10-15 years ago, but have given way to Instagram, Twitter, and podcasts. Content consumption via the printed word seems quaint.

But these days I find myself increasingly drawn to the raw and candid nature of un-edited blogs. Here is why: A study gets covered in mainstream media. It fits an anointed narrative. Once one media site covers it, others feel like they have to cover it as well. Then Twitter and Facebook amplify it.

Boom, a message becomes accepted, often codified. If slow science pre-COVID was imperfect, the fast science of COVID can be deeply problematic. I’ve already mentioned hydroxychloroquine.

Another example is a study showing that cities that started social distancing earlier and stayed with it longer had better economic outcomes during the 1918 flu pandemic.

That narrative aligned well with the notion that stricter/longer lockdowns were the right choice. Keeping the virus from spreading is good for health and good for the economy.

Here’s the problem: other researchers could not reproduce it. When they tried, they found noise instead of signal.

Where did I read that? No, not in the NYT or WashPo or NPR; they don’t have the time or the incentive to correct a story. I read it on a blog from a distinguished professor of statistics at Columbia.

Professor Andrew Gelman writes;

The larger issue is that there seem to be more outlets for positive claims than negative claims. “We found X” can get you publication in a top journal and major media coverage—in this case, even before publication. “We didn’t find X” . . . that’s a tougher sell.

Another example, one which I may opine on in coming days:

A prominent group of researchers in cardiology published an observational study of patients with COVID who received clot-blocking drugs called anticoagulants. The top-line result was that patients who got the anticoagulants did better.

One of the authors of the study is the editor-in-chief of the journal that published the paper. He’s influential. Mainstream media covered the story. The WashPo used an upbeat headline and weaved a positive narrative.

This, too, fits with another common theme: keep socially distancing because if you get the virus later rather than sooner doctors will have found better treatments. And this may be true, but the study on anticoagulants was far too flawed to make any such conclusion.

Where did I get that? Well, since this is cardiology, I could critically appraise it myself. But say I wasn’t a cardiologist.

I, or you, or anyone, could have read the blog of intensive-care doctor, Josh Farkas, who writes on topics related to ICU medicine. Here is his assessment of the study’s fatal problem, including something technical called immortal time bias.

Numerous sources of bias exist.  Perhaps most notable is immortal time bias – patients who live longer may survive long enough to be diagnosed with DVT/PE and be treated with anticoagulation (whereas other patients may die rapidly, before being able to be prescribed anticoagulation).

You might wonder how one is supposed to know if information from a blog is reliable. This is where thinking comes in; it’s under-rated. You start with the content. Make a judgement.

You can also use meta-data: for instance, a blog with adverts for life-hacks or proprietary supplements might downgrade your confidence. Keep in mind, though, that many medical journals make you watch an ad before looking at a study.

One of my favorite American heroes, Mr Rogers, famously said when you are scared look for the helpers. I wonder… in this scary pandemic will more people start looking for help from the doctors, professors and thinkers taking time to write online. One of my recent favorites is Marginal Revolution.

Medical studies often get discussed on Twitter on the day of publication. Indeed, it is a great place for watching and conversing in realtime, but, as Doctor Bryan Vartabedian writes, in a blog, the ephemeral nature of Twitter makes it a lousy place to park ideas.

Finally, and this is big: science is not supposed to be held up as law; it’s supposed to be corrected. Being wrong in science is normal. Humility is essential. More and more, I am interested in how we communicate that core tenet to the public.

The tension, of course, is that the public can’t handle uncertainty.

I wonder if that is true. Perhaps it is the opposite: is it the faux certainty that bolsters distrust and division?

JMM