The Worrying State of Medicine

I spent about four hours today at a local Urgent Care facility. Without going into too much detail, the reason I had to do this was because the doctor's appointment I had scheduled for yesterday got canceled because my doctor got sent to cover ER shifts because of labor shortages in the medical industry. The immediate problem I was seeing her for is that my oxygen saturation levels, especially early in the morning, were getting worryingly low, and after starting a new medication I had gained six pounds in a single week, which could be seen as visible swelling in my legs. Since I was measuring my O2 levels with my own pulse/ox, I used the patient portal to say, “This is what I'm measuring. What should I do for the next two weeks before our rescheduled appointment?” Thus, today, I received a call where my doctor informed me I should go to the Urgent Care facility to get examined to make sure there wasn't anything major going on.

Now the fact that my primary doctor wasn't available for a scheduled appointment due to workplace shortages of medical professionals isn't the main focus here. It is certainly worrisome, but I think what might even be more so is the exchange I had with the doctor at the Urgent Care clinic. Since I wasn't getting enough oxygen and had obvious fluid retention from swelling, he ran a litany of tests on me including EKG and a chest X-Ray, even the universal COVID test, all of which came back as “good news” (thank God). But after he got the results back and he was explaining them to me, the doctor mentioned at one point that they'd had a little difficulty with one of the tests because my chest is so large. He then immediately said, “Not that I'm saying there's anything bad about being so large.”

And this is the point I want to bring up. I actually immediately said, “No, I know it's bad. In fact, the increased weight is precisely one of the very things I pointed out to you that had me so concerned.” I immediately saw his demeanor change, as if he was relieved to be able to speak honestly instead of being terrified of offending me, and he said, “Yes, if we could get rid of that weight, it would almost certainly help across the board with everything else here.”

So why did I find this exchange so problematic that I decided to write a blog post about it, especially given that it means I had to divulge (albeit obscurely) some health details I'd rather not talk about? Because I just experienced a doctor telling me something we both knew was a lie because he was afraid that I might be offended had he told me the truth.

There's real danger in this, though. I could have easily come away from that conversation telling everyone, “I went to Urgent Care and the doctor said my weight is fine” when the reality is the exact opposite. If he was so unwilling to state the objective fact that being overweight is detrimental to one's health, then what else are doctors afraid to tell patients? It's extremely worrisome if doctors will lie for the sake of one's ego instead of telling the truth for the sake of one's life.

In the meantime, I still have a case of “We Don't Know”, but at least I know my heart and lungs are sound right now, and I don't have Wuhan Bat Lung either. Prayers would be appreciated that someone in the medical field discovers what the proximate cause is. Or, God could just zap me. I'm fine with that too.

Memento mori

Christina Shenvi recounts her husband Neil Shenvi's seizure, which led to the discovery of his brain tumor, which led to surgery, which led to timely reflection:

"Is daddy going to die?" My 10-year-old son looks up at me. Tears well up in his eyes. He looks anxiously back and forth from me to my husband. He's the spit and image of his dad, with dark brown hair, tan, quarter-Indian skin, and hazel eyes. We've just broken the news that the brain tumor, which has lain dormant for 8 years, is starting to grow again. The younger three kids look to their big brother and to us for their cues.

Ioannidis on COVID-19

"A Conversation with John Ioannidis"

Some coronavirus news

Some coronavirus news. Good news and bad news.

Bad news first.

As many people know, two prestigious medical journals, the Lancet and the New England Journal of Medicine, both had to retract published papers recently. In fact, it's become a scandal.

The Lancet retracted a hydroxychloroquine study, while the NEJM retracted a cardiovascular disease study. The main issue is data integrity; data may have been compromised. Originally data was provided by a company named Surgisphere, but a co-author of both papers co-founded Surgisphere, i.e., Sapan S. Desai, MD, PhD, and Desai's publications history is rife with research misconduct.

Also on the hydroxychloroquine front, a separate study - likewise published in the NEJM but which did not use the Surgisphere database - found that hydroxychloroquine was not significantly different from placebo:

We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.

Now for the good news.

There are still many ongoing studies and trials. Such as one on convalescent plasma which was found to be both safe as well as effective in 19 of 25 (76%) severely ill COVID-19 patients.

In addition, there are several very promising vaccines trials under way. Several in phase 1 trials, a few in phase 2, and a couple moving to phase 3 trials. This includes the much touted vaccine from Moderna which is set to begin phase 3 trials as early as next month in July. The Regulatory Affairs and Professionals Society (RAPS) looks like a good website to track vaccine candidates.

Social justice matters more than social distance

"Suddenly, Public Health Officials Say Social Justice Matters More Than Social Distance"

Consciousness in split-brain patients

Striking finding on consciousness:https://t.co/ZMY7gGuyRd pic.twitter.com/0cFCn8PlYP

— Ross Douthat (@DouthatNYT) June 4, 2020

What is the medical impact of the lockdown?

Here's a good interview with an emergency physician as well as lawyer named Simone Gold (MD Chicago Medical School, JD Stanford University):

I was blind, but now I see

"Does Science Support Miracles? New Study Documents a Blind Woman’s Healing"

A severe mercy

Pain relief is an obsession of western medicine because that's something patients demand. And the availability of painkillers is often a blessing. Not to mention anesthesia. 

However, there are worse things than pain. Sometimes a painless sensation can be worse than a painful sensation. But sharp pain of a certain intensity blocks the mind from processing other sensations that may be even more unpleasant. 

So there's a way in which pain can be almost merciful, a kind of unexpected blessing, in that respect. Ironically, sometimes the preferred alternative isn't less pain but more pain. Pain of the right kind and intensity. There are different kinds of pain. But pain of a certain kind, at a certain level, can be distracting in a good way. A "severe mercy". That sheds neglected light on the problem of pain. 

Another advantage is that pain can be controlled in a way that worse sensations can't. Pain can be induced–like taking a cold bath. The chilling effect will make the worse sensation tolerable by blocking it from consciousness. There's a natural fear of death that Christians try to overcome. But this is a reminder that some things are more naturally fearsome than the natural fear of death, which makes that easier to face if handled the right way. It can take the mind off death. And it can be inspiring to take charge of a situation rather than be helplessly passive at its mercy. 

Trump and light therapy

Trump:

Supposing we hit the body with a tremendous - whether it’s ultraviolet or just very powerful - light. And I think you said that hasn’t been checked, but you’re going to test it?

And then I said supposing you brought the light inside the body, which you can do either through the skin or in some other way. And I think you said you’re going to test that too? Sounds interesting.

And then I see the disinfectant, where it knocks it out in a minute. One minute. And is there a way we can do something like that, by injection inside or almost a cleaning, because you see it gets in the lungs and it does a tremendous number on the lungs? So it would be interesting to check that, so that you're going to have to use medical doctors with, but it sounds interesting to me. So we'll see. But the whole concept of the light, the way it kills in one minute, that's pretty powerful.

It seems to me many people are unfairly criticizing Trump on this:

1. Granted, Trump can speak ignorantly, but that's nothing new. In fact, previous politicians including Obama have made many ignorant statements, but do liberals including the mainstream media ever parse and criticize their own side as much as they criticize Trump and conservatives? Many liberals are acting like Trump is telling people to throw themselves onto a burning pyre in order to kill the coronavirus.

2. It's not as if Trump is suggesting it's definitive treatment. He's not acting like Elon Musk did several days ago. Rather Trump is asking medical experts to investigate.

3. For that matter, light has long been used as treatment for some conditions. For example, UV light treatment (e.g. PUVA therapy) is not uncommonly used in certain cases of psoriasis, eczema, vitiligo, lichen planus, cutaneous lymphoma, etc. Ask any dermatologist.

4. Granted, these aren't infectious diseases. Again, Trump doesn't have a medical background (and in fact he's deferring to medical experts on this), so one wouldn't expect Trump to be able to make the distinction. Maybe the criticism should be that Trump shouldn't make apparently impromptu remarks like this. If so, his critics might as well try to rein in what Trump says on Twitter too. /s

5. At the same time, there's some precedence in the use of phototherapy in other coronaviruses. Take the use of phototherapy in the first SARS-1 coronavirus back in 2003 (e.g. here). (Our pandemic is SARS-2.) Also, phototherapy was used in MERS (e.g. here). And even a prestigious science journal like Nature has published on the use of phototherapy against other pathogens. Granted, these aren't all great studies or anything, but it's not like there's zero precedence for phototherapy. Perhaps this is the kind of thing Trump had in the back of his mind.

6. This isn't to suggest phototherapy is a good idea with regard to the coronavirus. Indeed, phototherapy has distinct disadvantages. Not least of which is increased risk of certain cancers (e.g. BCCs, SCCs, melanoma), especially in certain skin types (e.g. Fitzpatrick scale). And I certainly don't think phototherapy should be pursued if it means less focus or attention is placed on other therapies like drug based antivirals and vaccines.

7. I should be clear: I'm not defending Trump's proposal so much as I'm criticizing his critics.

It's challenging to compare nations over coronavirus response

I think many people simply assume it's a fairly straightforward comparison to compare how the US is doing vs. how other nations are doing in terms of responses to the coronavirus or COVID-19. Many people simply look at the total case numbers and the total deaths between nations without considering other factors involved. However, consider the following variables:

1. Population density

   Nations could have significantly different population densities. Indeed, cities within nations could have significantly different population densities. All things equal, the more dense a population is, the more challenging it is to maintain a certain distance from one another. Not to mention population density may impact a city or nation's access to its health care system as well as delivery of health care to the general population.

2. Health demographics

   Nations could have significantly different population demographics which impact their health. Some nations may have a higher median age than other nations (e.g. China is 37.4, Italy is 45.5, USA is 38.1). Some nations may have "sicker" people at baseline than other nations (e.g. higher rates of obesity, higher rates of hypertension, higher rates of diabetes).

3. Health care systems

   Nations could have significantly different health care systems. Take the quantity and quality of its health care providers and workers (e.g. some nations have more physicians per capita than other nations, some nations have better medical education and training than other nations). Take people's access to health care and a nation's delivery of health care to people. Some nations don't have a primary care system that stands in-between the general population and hospital systems like the US does, but instead the general population goes directly to the hospital, which could more easily overwhelm hospital systems. Some nations have socialized medicine which comes with its own complex sets of challenges.

4. Private enterprise

   Some nations' health care systems allow for better cooperation with private enterprise than other nations. Some nations can better mobilize private industry to help. Some nations are more advanced in prior research and development of medical technologies (e.g. pharmaceutical therapies), though to be fair R&D isn't necessarily primarily a private enterprise. However, at the very least, R&D is often closely tied to private industry in Western-style democratic nations.

5. Testing

   Some nations have done more and/or better testing of their populations than other nations. As Samuel Shem (pseudonym) points out in his satirical novel The House of God: if you don't take a temperature, you can't find a fever!

Of course, this isn't to suggest we can never reliably compare nations. This isn't to suggest we can't learn from other nations when they have failed. This isn't to suggest we can't adopt strategies from other nations when they have succeeded. Rather I'm simply pointing out that comparisons between nations can be more complicated and challenging than at first glance.

What's the harm?

What's the harm with trying a drug like hydroxychloroquine? For example:

There has been a lot of “what’s the harm” logic for #COVID19 therapeutics going around like @ChrisCarrollMD pointed out.

Let’s talk specifics, here’s the harm that comes from various Rx being evaluated currently. This is why the evidence of benefit is critical 👇🏽👇🏽

— Viren Kaul, MD (@virenkaul) April 7, 2020

Hydroxychloroquine:
🚨Cardiomyopathy and ventricular arrhythmias: ❤️ damage
🚨 Bone marrow suppression: Compromised immunity and bleeding risk
🚨 Hypoglycemia: Low blood glucose

Here’s @US_FDA’s fact sheet: https://t.co/dI40HwZbh4#COVID19

— Viren Kaul, MD (@virenkaul) April 7, 2020

Lopinavir/ritonavir:
🚨QTc prolongation & heart blocks: affects electricity in ❤️
🚨Risk of MI: ie heart attacks esp with previous structural heart diseases
🚨Hepatotoxicity: Liver injury. Critically ill pts can develop liver injury by other mechanisms, so added damage #COVID19

— Viren Kaul, MD (@virenkaul) April 7, 2020

Tocilizumab:
🚨Increased liver enzymes in 20-30%
🚨Liver injury resulting in transplant or death has been reported
🚨Low neutrophil and platelet counts
🚨 Anaphylaxis: Could be life threatening in sick patients
🚨 High TG level’s: makes using propofol (sedative) hard #COVID19

— Viren Kaul, MD (@virenkaul) April 7, 2020

IVIG:
🚨Low BP in 15%
🚨Anaphylactic reactions
🚨Pulmonary edema: fluid in lungs
🚨Aseptic meningitis
🚨Hemolysis: breakdown of 🩸 cells
🚨Kidney failure
🚨Thromboembolism: Increased clotting , which is already an issue with #COVID19

— Viren Kaul, MD (@virenkaul) April 7, 2020

My goal is not to create a scare but provide education on why just using therapies isn’t as simple. The risks need to be weighed against the benefit.

Problem is we don’t have good data to suggest benefit. And we do know the risks.

To deal with this pandemic ...

— Viren Kaul, MD (@virenkaul) April 7, 2020

How to treat coronavirus

In general, there are 4 or 5 main ways to "treat" Covid-19:

1. Vaccine.

This would be the best. However, it's also the one that takes the longest time to develop, involves the most extensive research, costs the most money, and so on. It's at least a year away. And that would be extremely fast. By comparison, consider that a vaccine was eventually developed against Ebola, but it took approximately 5 years. If I recall, I think it only arrived last year in 2019. Yet 5 years is more typical of the timeframe in vaccine development.

2. A new drug.

This would take slightly less research effort and time than a vaccine. Even if we accelerate it.

3. An old drug.

By this I mean a drug that has been used in other diseases or conditions but is re-purposed for the use in Covid-19. This is where most of the drugs we hear about in the news would be categorized. Such as chloroquine and hydroxychloroquine. These drugs were anti-malarial drugs and also used in rheumatoid diseases like lupus. Today medical experts are trying to re-purpose them for use in Covid-19. However, contrary to what most the media is reporting, there isn't much good evidence that these drugs will work - at least not yet. There is promise and hope, but only time will tell. By the way, in case anyone is interested, here is a summary of all the clinical trials we are working on to date. It's not comprehensive, but it's close.

4. Covalescent plasma therapy.

This is a treatment that's been around for years. In a general sense, it's been around even as far back as the Spanish flu in 1918. It was used to some degree in the first SARS pandemic or SARS-1; our pandemic is SARS-2. Many medical experts working in infectious disease and vaccine development have been pushing convalescent plasma therapy (e.g. Peter Hotez at Baylor, Arturo Casadevall at Johns Hopkins, Ian Lipkin at Columbia University). Basically it's just transferring the antibodies (in blood plasma) from someone who has recovered from Covid-19 to someone who has been infected with Covid-19 (as treatment) or to someone who is at high risk of infection (as prophylaxis). So the elderly, the immunocompromised, health care providers. There wouldn't likely be enough for the general population, but we can target at-risk groups and perhaps even areas that are seriously affected (e.g. NYC, Seattle). This could help diminish the virus' spread so that we can get a better handle on things. Clinical trials are already under way. It should move much faster than vaccine development. The medical technology is available today and as such comparatively easy to implement. The major issue is rolling it out. I'm referring to logistics like setting up blood banks, asking for blood donors (though the donation would require much less effort on the donor than, say, donating blood at the Red Cross), and so on.

5. Supportive care.

This is primarily what we're doing now. For the sickest patients, i.e. patients in the ICU with acute respiratory distress syndrome (ARDS) which is the leading cause of death in Covid-19 patients, it's basically just trying to give them oxygen, help them breathe better via mechanical ventilation, make sure they stay well-hydrated with fluids, maintain their nutritional status, put them in a prone position (i.e. lying face down) which has been shown to significantly help reduce mortality from ARDS, etc. All this is far better than we had, say, in 1918 with the Spanish influenza, but it falls short of an effective treatment against the SARS-2 virus itself.

References

Ian Lipkin on convalescent plasma therapy

Peter Hotez on convalescent plasma therapy

"A Seattle Intensivist’s One-pager on COVID-19"

"Should we use #hydroxychloroquine (HCQ) +/- azithromycin to treat #COVID19?"

"Lord Sumption explains national overreaction to coronavirus"

(Credit to Steve from whom I first saw this.)

Is the coronavirus a bioweapon?

There's a conspiracy theory floating around that claims the coronavirus (SARS-CoV-2/COVID-19) was a bioweapon engineered by China.

I don't know how or when it started. Tom Cotton broached the theory back in January:

We still don’t know where coronavirus originated. Could have been a market, a farm, a food processing company.

I would note that Wuhan has China’s only biosafety level-four super laboratory that works with the world’s most deadly pathogens to include, yes, coronavirus. pic.twitter.com/CtuU2czBLp

— Tom Cotton (@SenTomCotton) January 30, 2020

I would add: BSL-4 labs represent the highest level of containment for deadly pathogens. There are only about 50 BSL-4 labs in the world.

My thoughts:

Drugs against coronavirus

I see a lot of people strongly urging doctors to use the drug hydroxychloroquine/azithromycin as a remedy against the coronavirus or Covid-19. I guess that's in large part because Pres. Trump has been pushing the same drug quite a bit. However:

1. The evidence for the drug in human beings - not in vitro ("test tubes"), nor in vivo in animals (e.g. mice), but in human beings - is still predominantly anecdotal or low quality studies (e.g. here).

Sure, there may seem to be hundreds of coronavirus sufferers who have dramatically improved thanks to this drug combination, but one could say similar things for homeopathy, Chinese medicines, chiropractic manipulation, and so on.

At best, at this point, hydroxychloroquine/azithromycin may indeed be promising, and perhaps it will be proven to be safe and effective in treating Covid-19 in the near future, but there remains much work to be done in order to demonstrate these hypotheses.

2. I realize people are demanding a fix stat. It looks like governments have fast-tracked a lot of the trials. Indeed, it seems to me like we're moving about as fast as we can. However, there are limits to how fast trials can move. We can't time travel.

3. Suppose we have several friends who are badly injured and need to go to the emergency department. So we get them into a car and drive them to the ED as quickly as we can. Suppose we speed, run red lights, and zigzag through traffic to do all we can to get our friends to the ED as soon as possible.

Nevertheless if we're decent people then I presume we wouldn't attempt to run over pedestrians or drive through stores with people shopping or anything like that. As much as we wish to save our friends, all things equal, we wouldn't necessarily want to endanger other people's lives in order to do so.

I realize the analogy is not entirely analogous, but dropping the analogy my point is simply that we may believe this drug will save our friends and family. However, in this case, we wouldn't (or shouldn't) wish to endanger the lives of others in case it doesn't work in other coronavirus patients even if it works in the ones we happen to know.

(Of course, I'm sure we could concoct hypotheticals where it might be morally licit to risk the lives of others in order to save our loved ones.)

4. Finally, as I mentioned in a previous post, there are about 40 other coronavirus therapies doctors and scientists are currently working on spread out across approximately 200 trials. So I don't understand why the focus on this one particular drug when we have about 40 other coronavirus drugs or therapies we are trying. It's not as if this drug hydroxychloroquine/azithromycin is head and shoulders better proven than several of the other drugs or therapies (e.g. here).

The course of coronavirus

It doesn't look like the numbers or percentages are entirely accurate. However it's still useful as a generic schema for how the coronavirus seems to be playing out.

Summary of clinical trials for coronavirus

There are several different treatment options that physicians and scientists are looking into for the coronavirus. Such as antivirals and vaccines. These aren't necessarily mutually exclusive.

I've posted on a few of these in the past (e.g. convalescent plasma therapy, remdesivir, hydroxychloroquine/azithromycin).

Here's a more comprehensive list so people can see what's being worked on around the world to combat the coronavirus:

(Source)

Confirmation bias

Coram Deo asks a good question here:

I don't know if either Hawk or steve (or another active T-blogger) would be willing to take up the question, but both here and elsewhere I'm seeing what I perceive as rampant confirmation bias swirling amidst the current coronavirus pandemic and I'm wondering if it's possible to implement guards or filters in our critical thinking to avoid this to some extent.

This assumes of course that folks wish to avoid or mitigate this feature, indeed many seem to rush to pick out this or that expert, model, or theory which bolsters their preconceived notions.

Thanks, CD. That's a good point and a good question! What you've said is important to keep in mind. If I can offer my random thoughts:

We're not shooting in the dark

1. On the one hand, the coronavirus (i.e. SARS-CoV-2/COVID-19 or simply COVID-19) is a novel virus. That poses many challenges for us. For example, take the fact that it's constantly mutating. Indeed, there are at present approximately two different groups of the coronavirus - i.e. L and S haplotypes. As such, its virulence and transmission can shift over time in unpredictable ways. In fairness, the coronavirus seems to be reaching some genetic stability now. Hopefully it won't significantly change before we can find a vaccine. (By the way, if anyone wishes to see the mapping of the various strains of the coronavirus' genomic evolution, this website is a good resource.)

2. On the other hand, the leading disease that's killing people from coronavirus is acute respiratory distress syndrome (ARDS). Yet ARDS is an utterly familiar disease to physicians today. In other words, yes, we have to wait for therapies like antivirals and vaccines for the coronavirus. However, it's not as if we're wildly shooting in the dark. We know how to treat ARDS. We know how to protect the lungs. We know how to intubate patients. We know how to put patients on mechanical ventilation. We know how to prone people early to help increase their survival chances. We know how to use empiric antibiotics. We know how to use inhaled prostacyclins and neuromuscular blockers. We know the seven Ps for the care of ARDS patients. Indeed all these (and other) strategies work very well for ARDS.

3. It's just that, even absent the coronavirus, ARDS has high mortality rates:

ARDS is associated with appreciable mortality, with the best estimates from a multicenter, international cohort study of 3022 patients with ARDS, suggesting an overall rate of death in the hospital of approximately 40 percent [1-4]. Mortality increases with disease severity; unadjusted hospital mortality was reported to be 35 percent among those with mild ARDS, 40 percent for those with moderate disease, and 46 percent for patients with severe ARDS [4].