Just a couple thoughts from the realm of COVID-19 trials. 1. We are honestly very excited that fewer patients are afflicted by COVID-19. We will work as hard as we can to make sure trials are available to patients wherever they are in the world AND we will celebrate the fact that this is becoming a rarer disease.

2. This really looks to be a disease of unvaccinated people now. It's striking how little ARDS we are seeing among vaccinated people. Not sure whether any specific line of evidence is helpful, but, wow. In the big COVID ARDS trial we're

In case the story about full-dose anticoagulation in critically ill patients is confusing, a quick comment about the design and the reason what looks like harm is being called futility. Recall that in the prespecified Bayesian model, they used a threshold of 99% probability that the OR was > 1 or < 1. This is an appropriate move. If you drop the probabilities lower, the Bayesian approach starts to look a lot more like an error-inflation machine. So if you're being rigorous, you want for 99% probability before you declare superiority or inferiority.

I'm thinking more about the Pfizer vaccine (and grateful for those who have clarified some key points). First, I agree that early efficacy (right after the second injection) prevents infection in this patient population. That seems statistically certain. Second, the population is those the investigator deems to be at high risk. I know that we've all wanted "wiggle room" in our inclusion criteria and that's not wrong. But for generalizability we want to know what "high risk" really means. In the event, it looks like "high-risk"

I've been hearing and thinking more about the Pfizer mRNA vaccine this morning. It does seem like this signal is likely to be real (there's not enough data in the news release to know, but most credible back calculations suggest that the efficacy signal is real). So I've been trying to think what bothers me about it. And it's the ways that the culture of interim analyses seems to be shifting. Instead of the clear boundaries keeping the businesspeople from interfering with trials while they're being run, we're now seeing premature breaking of

HAHPS trial also published--atsjournals.org/doi/abs/10.151…. I'm incredibly proud of @Research_Inter ability to run a pragmatic controlled trial in context of ORCHID to allow us to move more efficiently through candidate agents. There's an early suggestion that azithromycin may be useful (looking forward to RECOVERY results in that regard). If anyone can remember back to March, there was a plan to provide HCQ with essentially no oversight, consent, or monitoring. With retrospect, HAHPS (and its sister trial HyAzOUT) were exactly the right response.

Once a year I give a lecture to the 2d year medical students on humanizing intensive care. It's fun to be with these bright young people moving toward careers as physicians. One asked me an interesting and important question that seems like it's worth reflection. Specifically, how do we engage people in positive and respectful ways if we don't have an authentic connection with the patient/family member? We know from RCTs that rote condolence letters after a death seem to raise and then disappoint expectations of intimacy, so how do we

The letter from the treating physician for the US president is emblematic of “VIP medicine”. Almost none of it is a good idea even on its own, and no one has a clue what happens when you throw all these therapies together in one giant bag of too much. Monoclonal antibodies (not polyclonal antibodies, as the letter indicates) are a promising therapy and we have two very early hints from premature soft reports. So that’s outstripping the evidence, but it’s not crazy.The vitamin D and famotidine are crazy town,

I’ve been trying to support the restaurant industry better lately. The thing that strikes me is what appears to be widely held misconceptions about how to prevent spread. I think they’re used to Salmonella and pathogenic E. coli. So the scrub down the surfaces a lot. But that’s not how sars2 is transmitted (you should still keep surfaces clean because it’s not like Salmonella died of COVID; plus there’s some small risk for COVID transmission associated with contamination of shared surfaces). It’s transmitted by being near people w/o mask

We're all a bit worried about the two neurological disorders seen in the AstraZeneca vaccine trial. In the media, one is being called multiple sclerosis; the other is being called transverse myelitis. These diseases can happen spontaneously, can happen as a result of a viral infection (we think) and could possibly be an immune response to a vaccine. With the whole world watching and hoping, I have only sympathy for the trialists and sponsors and of course the participants. I'm seeing calls for "opening the books" and breaking blinds and increasing

A friend asked me about school this fall--someone told her it would be perfectly safe because hospitals were safe. We are cautious because we have a high-risk family member. These were my thoughts. Glad to hear where I've missed something.

we're doing online only. the evidence suggests that universal masking makes hospitals mostly pretty safe. The rates of mask compliance are >90% at hospitals, people don't hang out in crowded environments, and very few people engage in communal eating.

This CDC thing about a small minority of the COVID deaths being among previously healthy individuals? A few thoughts. First, we already knew that SARS-CoV-2 is ruthlessly Darwinian in its assault on human beings. Our responsibility in the battle with COVID is overwhelmingly to protect people who are vulnerable.

As we think about convalescent plasma (CP), I thought it was worth looking at the actual data in other diseases. As best I can tell, the only actual trial showing efficacy for CP is in Argentine hemorrhagic fever, published in Lancet in 1979. It's an elegant study from 1974–1978 pubmed.ncbi.nlm.nih.gov/92624/

I finished the Brazilian HCQ +/- Azithro trial. ( nejm.org/doi/full/10.10… ) Good on them for meeting a tsunami of demand for an unproven therapy with randomization. This is a very pragmatic trial with a relatively modest sample size, but I think it provides important observations, which can be best interpreted in the context of forthcoming placebo controlled trial reports. For now, there's no promising signal for benefit or harm, there's a suggestion that HCQ may be harmful >7d after symptom onset. The AEs were pretty rare. Not clear whether

A quick experiment. First make a list of everybody you love. Not like civic-or-religious duty love, but tangible love: you'd be personally legitimately sad if they were harmed or killed. Spend some time with the list because that's the good stuff in life. Count your blessings! Second, run through the list and mark which of those people fall into a high-risk category. These include (1) age > ~60 years, (2) kidney or heart or lung disease, (3) obesity (BMI > ~30), (4) diabetes, (5) cancer, (6) immune diseases on treatment like Crohn's or lupus

We don't talk about lawsuits much in medicine. Too painful. I got sued when I was a resident. An intern had written a note that was misinterpreted to mean that I had arrogated to myself the role of the attending. The patient had died, and it had been a terrible, sad situation. There was no malpractice committed, although of course I searched my mind and heart with relentless self criticism. I lost my self confidence for about 6 months and struggled to find my rhythm clinically, second- and third- and fourth-guessing every decision I made.

The Italian investigator-initiated trial of tocilizumab had a readout via AIFA ( aifa.gov.it/documents/2014… ). It's being covered, with little relevant insight, in various media channels. With the help of Google Translate, the story seems pretty straightforward and doesn't add new information to the sarilumab phase 2 data (topline released). This was a trial of pre-ICU patients with only moderate illness. It wasn't really funded, but it was supported by the passion and good will of local clinicians. They should be proud of their hard work. After enrolling

I'm hearing from credible sources that asymptomatic positives are in the range of 4-5% in Utah right now. (>650 new positives today statewide). Let's say that this is an overestimate, just to be conservative, and it's really 3%. So then let's think about your risk if people get close to you for ~10min without their mask on (your mask will help some too, but theirs is most important), especially indoors. If you encounter one person, the chance that you'll be exposed is only 3% (1-0.97^1). If you encounter two people, it's just under 6% (1-0.97^1).

I've been grateful for the push for me to review the old steroids ARDS papers and meta analyses. I started with the ESICM/CCM statement led by Annane (a long-time advocate of steroids in general)--journals.lww.com/ccmjournal/Ful…. They include a meta-analysis for ARDS. Here's their forest plot. Note that there are three decent-sized trials and then tiny trials, the ones most likely to be false positive (unknown how many small negative trials were excluded). Let's look at the three decent-sized trials.

I wonder whether we could think about clinician or patient optimism in the ICU. My guess is that we many of us weigh multiple factors, often without knowing all of them consciously. Some are good--high-quality quantitative risk models, a patient's clearly stated values and priorities. Some are bad--unintended racism, personal emotional conflict with the patient or family. Some are more complex--the degree of emotional resonance with the patient, recent vivid experiences, gut instinct, the desire to let a new therapy have an effect, beliefs

A quick comment about death and placebos before diving back into work for the day. In many settings (young healthy people without depression), the placebo effect is unlikely to lead to changes in mortality. But in settings where beliefs and attitudes dominate mortality ( advanced dementia, intensive care, suicide-susceptible mental illness), placebos can have a dramatic effect on mortality. It's true that mortality is the ultimate objective endpoint (not much dispute among physicians over whether a patient has in fact died), but we have to be

Some thoughts about the RECOVERY-DEX preprint. First, some more clarity about why it stopped--it hit the target sample size. Oddly, no discussion about alpha spend or what the DSMB reviewed. Second, post hoc analyses that control for age only in their primary analysis. This is confused and confusing, since they should have had a prespecified model that included more factors (table S2). The primary analysis, flawed as it was, looked a bit worse for non-oxygen patients (unadjusted p = 0.05), less impressive for the oxygen group (unadjusted p=0.014), but