Messages

1

Consequences / Re: COVID-19

« on: March 23, 2020, 06:42:12 PM »

...

Letting it burn thru without masks on is not a plan at all.

The issue is that there is a shortage of masks. There are simply not enough to go around; thus somebody has to go without.

To illustrate this, consider a population of three people: a doctor, a nurse, and yourself. There are only two masks. Who gets the masks?

More importantly, how do you decide who should get them? Should they go to the people who move fastest and speak loudest or should they be allocated according to the best available evidence?

2

Consequences / Re: COVID-19

« on: March 23, 2020, 04:05:06 PM »

There are much better discussions than the usefulness of masks to go at each other's throat for.

Neven, when hospitals run out of PPE nurses and doctors die! They risk their lives for us. Even for people like A. This discussion is really fucking relevant! People need to understand that we are losing our last firewall here.

Everyone who wants a mask can go to youtube and watch a tutorial on how to make them. Medical professionals don't have that luxury. They need to have the masks selfish people like A hoard for themselves.

I can't stress this enough, there is no study claiming what A claims. He is clearly anti-science in this regard.

We need to protect out medial personal in times like this!

Further to this, based on chatter with a number of my colleagues who work in different hospitals in my region there are several units that have already run out masks; doctors and staff are being asked to "borrow" PPE from other units in their hospitals. The main reason for these shortages is theft--presumably motivated by misconceptions regarding their utility outside of healthcare settings.

3

Consequences / Re: COVID-19

« on: March 23, 2020, 04:10:44 AM »

Can everyone cutting and pasting from journal articles please mind their exponents? The quoted "from 103.7 to 100.6" is three orders of magnitude different from the actual change in the article which was from 10^3.7 to 10^0.6 (otherwise known as from 5011 to 4 in linear terms).

4

Consequences / Re: Global recession

« on: March 21, 2020, 07:10:07 PM »

The Global Recession is coming here, but faced with death and life altering disease it's small potatoes until we've broken the back of CV19.


Slowing the onset of CV19 is the only chance we have to come through this without being reduced to animals fighting for our next meal, our last breath. The kids dancing on the beach may return home and inherit their family wealth years earlier than expected. - if they survive until the paperwork has gone through.

...

I'm not sure I agree. COVID-19 is a threat but not one that I would characterize as existential.

As a clinician I must say that as bad as COVID-19 is, the existential threat posed by a second great depression frightens me even more. A pandemic comes but it also goes. The cycle of poverty and its associated diseases--malnutrition, treatable childhood illnesses, tuberculosis, HIV, depression, and many more--is a larger multi-generational threat than a pandemic. Worse, a weakened society burdened by poverty will be even more susceptible to future pandemics.

It is  therefore absolutely necessary that our response be based on consideration of metrics beyond just a simple count of the raw number of deaths directly from COVID-19.


Source: https://idpjournal.biomedcentral.com/articles/10.1186/2049-9957-1-3

5

Consequences / Re: COVID-19

« on: March 21, 2020, 06:08:46 PM »

LA County Shifts From Containing Coronavirus, Advises Doctors to Skip Testing of Some Patients: Report
https://www.latimes.com/california/story/2020-03-20/coronavirus-county-doctors-containment-testing?_amp=true

A surge in coronavirus cases has Los Angeles County health officials telling doctors to give up on testing patients in the hope of containing the outbreak and instructing them to test patients only if a positive result could change how they would be treated, according to a new report.

...

In the USA the window of opportunity for when large-scale testing would have been beneficial in containing the outbreak has long since closed. Large scale testing makes sense if the strategy is containment; it's less helpful and probably wasteful if the strategy is based on mitigation.

There's an old maxim in medicine that states one should not perform a test unless the results of that test are going to change management. Now that containment has failed, the way in which testing affects management has changed and whence the indications for testing are changing. It should come as no surprise that these revised guidelines are quite similar to the guidelines for when testing for influenza should be performed during times of high influenza activity.

6

Consequences / Re: COVID-19

« on: March 20, 2020, 08:43:24 PM »

In the article discussing the "Chinese bus" it was proved that someone contracted COVID-19 by entering a bus 30 minutes after the infected person (who sat in the bus for four hours) disembarked. So the risk is not negligible.

...

Here's the follow-up to the bus article:

Medical journal retracts study on how far coronavirus can spread through droplets

A paper by Chinese researchers suggesting that the coronavirus could spread farther than previously assumed through fine droplets has been retracted.

A study suggesting fine droplets carrying the new coronavirus could linger in the air for at least 30 minutes and travel up to 15 feet has been retracted five days after its publication.

The research on so-called aerosol transmission, by a group of government researchers from the central Chinese province of Hunan, was based on a reconstruction of how the infectious disease Covid-19 spread on a bus on January 22 during the peak Lunar New Year travel season.

...

Source: https://www.inkstonenews.com/health/medical-journal-retracts-study-how-far-coronavirus-can-spread-through-droplets/article/3074449

7

Consequences / Re: COVID-19

« on: March 20, 2020, 03:05:08 PM »

From reddit...

Archimid, as a front-line healthcare worker I appreciate your concern for my welfare. However, since your opinions are obviously based on indiscriminate disregard of evidence I will choose to end this exchange with a simple thank you and best wishes.

8

Consequences / Re: COVID-19

« on: March 19, 2020, 09:53:31 PM »

If you can't rule out the airborne transmission, you must assume airborne transmission. And not only can it not be ruled out, but it has also been confirmed several times. I believe it has been posted in this thread several times.

In an ideal world, perhaps. In the real world we have limited resources that constrain our response: a minimal supply of N95 masks, very few negative pressure rooms, etc. As such we are forced to deploy what resources we have in the most prudent fashion possible as guided by evidence. Reflexively putting every single patient on airborne precautions without assessing the evidence is simply not possible.

I have to imagine ...

You don't have to imagine at all! This has been (and is being) studied. Start with reviewing the current available evidence.

9

Consequences / Re: COVID-19

« on: March 19, 2020, 05:41:05 PM »

First point:

https://www.nejm.org/doi/10.1056/NEJMc2004973

SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours), with a reduction in infectious titer from 103.5 to 102.7 TCID50 per liter of air. This reduction was similar to that observed with SARS-CoV-1, from 104.3 to 103.5 TCID50 per milliliter

For three hours this virus can remain viable in the air if the physics of the room allow it.
Three hours was the limit of the experiment so it could be longer.


The second point, the air is the path of transmission for every nCoV infection unless the patient licks a surface. The virus is excreted in macro and microscopic particles every time a patient exhales, laughs or coughs.  From there it can land on surfaces to be picked up. That's when handwashing can help. But it can never fall to the ground before being breathed by another human.

Archimid, your copy and paste from the NEJM has an important formatting issue: you lost the powers of 10. The titers went from 10^3.5 to 10^2.7 (in linear terms from 3162 to 501) per milliliter of medium.

That said, the findings do indicate that airborne spread is plausible. However, you need to consider how the particles get aerosolized in the first place. It does not appear to happen everytime the patient "exhales, laughs or coughs." Rather,  aerosolization is far more likely to occur in hospital settings during certain procedures such as endotracheal intubation. That is why members of the general public need to stop hoarding N95 masks and allow the healthcare workers who need them to get them.

10

Consequences / Re: COVID-19

« on: March 18, 2020, 11:48:02 PM »

Hot off the presses of the New England journal. Emphasis added.

A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19

BACKGROUND
No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

METHODS
We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao2) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao2) to the fraction of inspired oxygen (Fio2) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir–ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone. The primary end point was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever came first.

RESULTS
A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement (hazard ratio for clinical improvement, 1.24; 95% confidence interval [CI], 0.90 to 1.72). Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (19.2% vs. 25.0%; difference, −5.8 percentage points; 95% CI, −17.3 to 5.7). The percentages of patients with detectable viral RNA at various time points were similar. In a modified intention-to-treat analysis, lopinavir–ritonavir led to a median time to clinical improvement that was shorter by 1 day than that observed with standard care (hazard ratio, 1.39; 95% CI, 1.00 to 1.91). Gastrointestinal adverse events were more common in the lopinavir–ritonavir group, but serious adverse events were more common in the standard-care group. Lopinavir–ritonavir treatment was stopped early in 13 patients (13.8%) because of adverse events.

CONCLUSIONS
In hospitalized adult patients with severe Covid-19, no benefit was observed with lopinavir–ritonavir treatment beyond standard care. Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit. (Funded by Major Projects of National Science and Technology on New Drug Creation and Development and others; Chinese Clinical Trial Register number, ChiCTR2000029308. opens in new tab.)

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2001282

So no panacea seen in this trial. Perhaps larger trials will show a benefit? Eagerly awaiting data on hydroxychloroquine.

11

Consequences / Re: COVID-19

« on: March 18, 2020, 04:14:52 AM »

Better late than never.  Chloroquine (and Kaletra and remdesivir) have been positively recommended by clinicians in China for many weeks.  SKorea has positively recommended hydroxychloroquin and Kaletra.  Both have recommended starting use early in the course of infection.  WHO, CDC, and ECDC have been recommending against antiviral use.

I'm concerned that authorities may have slow-walked these options, in favor of Gilead's remdesivir, an investigational, high-cost, high-profit drug.  It won't be available until it's FDA-approved.  Profit motives may be responsible for the delay.

The other two are already FDA-approved (for other diagnoses) so there's no bureaucratic obstructions to using them immediately.  For other diseases, "off-label" use of medications is routine, when there are expert recommendation to support the use.  Waiting for completion of peer-reviewed, double-blind, placebo-controlled trials is inexcusable.  Many are dying because of this foot-dragging.

We're actively talking about this at a provincial level in Alberta and it's not as simple as it may seem. All of the medications you mentioned are in very limited supply. We only have enough lopinavir/ritonavir to supply the HIV patients their current needs but no more. There's some hydroxychloroquine but not in pandemic amounts as it's largely procured for use in autoimmune disease (Alberta not being a malaria endemic area). There's basically no chloroquine if someone were hoping to use that instead. Needless to say there's also very little remdesivir which is, as you say, expensive and experimental.

There's a lot of constraints on the system, especially for supply lines. We're struggling even with simple things like N95 masks and NP swabs let alone medications. As much as people want to try things that might help, supply lines can't just be easily ramped up overnight. In many cases it may actually be easiest to get medications is through a clinical trial. That obviously doesn't help everyone right away but at least it generates knowledge.

That said, supply lines could be ramped up if there were clear evidence of benefit. However, just being in the somebody's guidelines doesn't cut it. Things actually make it into guidelines all the time without any supporting evidence: just look at what the IDSA guidelines say about the treatment of influenza with oseltamivir then look at the evidence.

12

Consequences / Re: COVID-19

« on: March 18, 2020, 01:03:29 AM »

^ it's a mathematical model based on mobility data, not testing.

That Science paper (which has now been mentioned at least 4 times) is just one of several independent lines of evidence suggesting that there are in fact a large number of undocumented cases.

The fact that the paper in question is based on a model does not in and of itself invalidate its findings. Are you so quick to dismiss evidence stemming from mathematical models in other fields, for example climate science?

13

Consequences / Re: COVID-19

« on: March 17, 2020, 03:53:54 AM »

Edmountain,

Correction. I just saw the most recent log plot of the confirmed count in the US. It shows a 1.35-1.37x/day increase rate for the last several weeks. I had thought with the beginning of public actions that that might have dropped to 1.25x/day. It hasn’t.  At least it hasn’t yet. Beginning now it should. But now won’t show up in the data for 11 days.

Correcting for that, I suspect that we now have 135,000-150,000 people infected in the US. That should show up as confirmed numbers 11 days from now, by which time the count of infected (not the confirmed count, but the actually infected count) will be about 800,000 to 1 million. - give or takes a lot due to uncertainties. 7 days later that should be counted as 160-200 thousand hospital admissions for critical care, about April 3-4. That will likely then double over the next week - reaching perhaps 700,000 by tax day - April 15. Said differently - the US may have no available ICU beds then.

I really really want to be wrong with this swag estimate.

Sam

Sam, I have little doubt that you are correct and that there will be about 140K confirmed cases in the US in 11 days.

In addition to this, there is (in my opinion) a large number of undocumented cases in the US as suggested by multiple lines of evidence. The Science study I linked to is an example of some of the more rigorous evidence as to the magnitude of this effect; the anecdotal stories that vox posted of people being turned away from testing suggests how this has been allowed to happen.

Bottom line is, the US has botched the testing so badly that it's hard to believe they've captured anything other than a small minority of the cases. The possible pool of undocumented cases does have significant public health implications. However, at the end of the day, I don't really care too much about the denominator; that's for epidemiologists. As a clinician, I care much more about the numerator. And the numerator is, as you point out, frightening.

Edit: numerator and denominator being ratio of confirmed to unconfirmed cases.

14

Consequences / Re: COVID-19

« on: March 17, 2020, 12:04:12 AM »

...

As he notes, the caveat is that in many places the official numbers may greatly underestimate the true number of infections, due to limited testing.

...

On that note there was a paper published online in Science today providing evidence that in China during the period January 10-23, i.e. prior to the implementation of widespread testing and travel restrictions, that more than 80% of cases went undocumented.

I think this furthers the case that there is likely substantially more infection in places where access to testing has been limited. For example, if we extrapolate these numbers to the USA could there actually be 32,000 cases in the US rather than the documented 4,600?

https://science.sciencemag.org/content/early/2020/03/13/science.abb3221

15

Consequences / Re: COVID-19

« on: March 16, 2020, 05:06:21 PM »

...

U.S. May Need 6-8 Weeks to Get Over the Worst (7:30 a.m. NY)
https://www.msn.com/en-us/finance/markets/health-agency-hit-by-cyber-attack-airline-warning-virus-update/ar-BB11e57K

U.S. Surgeon General Jerome Adams says the nation may need six to eight weeks to get over the majority of coronavirus-related pain, if the situation develops as it did in China and South Korea.

Adams, speaking on Fox News, acknowledged there is a chance the U.S. does worse than South Korea, and that the situation could get as bad as in Italy.

...

Given that testing in the US has been so badly botched they will be extremely lucky to get an outcome anywhere near that of China or South Korea. Based on deaths, which are presumably easier to track than cases, it seems likely that the current number of cases in the US is at least the same as South Korea, i.e. around 8,000. Frankly, even that may be an underestimate: it's possible people have died in the US without having been tested so the actual number of deaths could be even higher.

16

Consequences / Re: COVID-19

« on: March 15, 2020, 09:58:04 PM »

Edmountain,

The difference in 1-4% fatal isn’t with medical folks. They get it. They focus on what is right before them and what is important.

The importance is with the political leaders. When they fall into the threshold belief that this is just another flu, that is when they fail to act and fail to act quickly enough or massively enough. That is when a simple disease outbreak becomes an epidemic and when an epidemic becomes a pandemic.

In the end, the CFR will be a footnote. Unfortunately it will be a footnote to a paragraph that explains how leaders were so stupid as to allow a pandemic to ravage the world killing untold millions, and about how unnecessary those deaths were, and where it was that they got this idea from.

That is why and where the CFR argument has any importance at all. That - and the lives destroyed by all of those individual unnecessary deaths.

Sam

Sam, I think we're both on the same side in that we're each trying to achieve the best possible outcome under the circumstances. Your concerns are clearly genuine, heartfelt, and admirable. However, I feel our personal and professional circumstances are leading to different approaches as to how a good outcome could be achieved.

I don't want to be self-aggrandizing but I feel compelled to reiterate that I work within the medical system on the front lines clinically, at the operations level through management, and in my academic role. Through my work and research I know firsthand what the scientific consensus on this issue is. The consensus is that the CFR is only one small piece of the puzzle. Whatever its eventual value, it is clearly dangerously high; I have not a single colleague who believes that this is "just another flu".

More important than the numerical value of the CFR though is the realization that it is modifiable through application of evidence-based interventions [see edit below]. Discussion focused on the response and the evidence available to guide this response is, in my opinion, of far greater value than continual bidding wars about a fuzzy number.

Edit: what I should have said above is that the total number of cases and whence the number of deaths is modifiable; the CFR in and of itself is not modifiable. Apologies for the error.

17

Consequences / Re: COVID-19

« on: March 15, 2020, 07:13:54 PM »

...

Any references on the upregulation of ACE2 by ACE-inhibitors and ARBs?  I'm not doubting you, but I'd looked into this question and didn't find a clear answer.

It's of more than academic interest, as I have HTN and am on an ACE inhibitor.  I'm probably not alone on this forum in this regard.

Most of the evidence is based on extrapolation from animal models:

https://www.ahajournals.org/doi/10.1161/01.HYP.0000237862.94083.45
https://www.ahajournals.org/doi/full/10.1161/01.HYP.0000124667.34652.1a
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-1681.2009.05302.x
https://www.ahajournals.org/doi/full/10.1161/circulationaha.104.510461


For humans the evidence is less clear and somewhat contradictory:

https://www.sciencedirect.com/science/article/abs/pii/S0196978110001257
https://link.springer.com/article/10.1007/s00726-014-1889-6
https://academic.oup.com/europace/article/19/8/1280/2194467
https://academic.oup.com/eurheartj/article/39/suppl_1/ehy566.P6430/5082261


It's probably not as cut-and-dry as the Lancet Respiratory letter suggested and that's a valid criticism of their position--and a weakness that I further perpetuated by reposting it verbatim here! This is an active area of inquiry that's moving at a pace not general seen in the internal medicine community. Matthew Sparks from Duke and Swapnil Hiremath out of Ottawa are doing their best to stay on top of things over at the nephrology journal club.

Take home message is: don't listen to some hack on the internet. Instead, speak to your doctor.

18

Consequences / Re: COVID-19

« on: March 15, 2020, 04:39:21 PM »

...

One thing I wish would stop is arguing over numbers and who is more right and wrong.

...

Thank you.

I am someone whose job involves both clinical front-line work and pandemic planning for my hospital. I can assure you that very few of us personally involved in this struggle care all that much right now whether the CFR is 1%, 2%, 4%, or anywhere in between. We all recognize this disease is dangerous enough to wreak havoc. It crosses a threshold; a deluge is coming. By the time we emerge on the other side the actual CFR will be an historical footnote.

That said, I strongly believe that our struggle has the highest chance of success when guided by the best available evidence. The scientific consensus (remember that term?) does not suggest that this disease will be fatal to 4% of the general population; perpetuation of such inflated death rates is likely counterproductive. See, for example, the critical shortages of PPE and hand sanitizer faced by front-line workers (including myself) because of gratuitous hoarding by the general public fed by panic.

19

Consequences / Re: COVID-19

« on: March 15, 2020, 03:53:28 PM »

...

Many presume that being a fit, active 72 year-old makes them lower risk than a sedentary 72 year-old.  I'm not aware of any data to support that presumption.

My impression is that most of the risk factors for bad outcome derive from higher levels of ACE2 expression in tissues.  ACE2 is the portal of entry for the virus.

I'm not aware that being fit lowers ACE2 receptor expression.  Perhaps it does.  I wouldn't gamble on that.

If society would suffer from all the over 70s sequestering themselves for some months, imagine if many of them would disappear from their jobs and communities forever. 

I think the suggestion is prudent.  Avoiding contact with others doesn't mean losing fitness, though it would, admittedly, make that more common.

Your thoughts raise some fascinating questions because ACE2 expression is upregulated by two very common classes of medications: ACE inhibitors and angiotensin receptor blockers (ARBs).

One of the most interesting aspects of covid is the degree to which cardiovascular disease and CV risk factors are bad prognostic factors. Specifically, it seems hypertension, diabetes, and associated CV disease are bigger risk factors than a history of pulmonary disease such as COPD, asthma, or ILD. For example, see the following two papers, one being a case series out of Wuhan the other being a larger series in all of mainland China.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext
https://www.nejm.org/doi/full/10.1056/NEJMoa2002032

Subsequent to this there was a letter to Lancet Respiratory Medicine on Wednesday speculating that these observations were real and that the mechanism was increased expression of ACE2 mediated by the use of ACE inhibitors and ARBs in these patients. The authors wondered weather clinicians should consider discontinuing ACEs and ARBs in favour of CCBs or other medications in order to reduce the risk associated with covid infection.

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext

It's fascinating because ACEs and ARBs haven proven mortality benefits in many patients with cardiovascular disease and cardiovascular disease itself is so common. If the millions of high-risk patients on ACEs or ARBs were to discontinue those medications would the inevitable uptick in CV mortality be counterbalanced by a reduced risk of severe covid infection? Nobody knows the answer right now.

20

Consequences / Re: COVID-19

« on: March 15, 2020, 05:41:41 AM »

...

The point is that a rapid influenza test is simple, easy, and quick.  A positive test then obviates the need for Covid testing, which is slow, expensive, and in short supply.  Influenza can be treated with approved medications.

If the influenza test is negative, the probability of Covid is higher.  This affects how such patients are managed until test results are back, and affects one's confidence that a negative result isn't a false-negative.  Re-testing the negatives then becomes a more reasonable course of action.

Point-of-care influenza tests may be easy and quick but their interpretation is not so simple. Just as with any other diagnostic test, it's not a binary "yes" or "no" because every test has limited sensitivity and specificity. Interpretation of the result is heavily reliant upon the pretest probability which, in the case of influenza, corresponds to the degree of influenza activity in the community.

My concern with your strategy is therefore that all influenza tests, whether it's molecular assays or RIDT at point-of-care or RT-PCR in a lab, suffer from poor positive predictive power when influenza activity is low. So while influenza activity is currently high it's already decreasing in both the USA and Canada. At some point soon the risk of a false positive test will become unacceptably high leading to false reassurance that a patient with ILI symptoms is suffering from influenza when in fact they have another disease.

21

Consequences / Re: COVID-19

« on: March 15, 2020, 03:18:44 AM »

...

We do have rapid tests for influenza (and other respiratory tract pathogens).  I would suggest that anyone anywhere with fever+cough deserves a rapid influenza test.  If negative, a Covid test.

The appropriate testing depends on the setting.

In the case of an ambulatory outpatient only the covid test is of any real value at this point. That's because for any other pathogen the advice is go home until you feel well then return to work. This advice does not change regardless of the non-covid pathogen found. However, for covid the advice is to isolate for 14 days (minimum) and initiate contact tracing. The covid test thus has important implications both for patient disposition and public health. Again, this is all for ambulatory outpatients: the walking well if you will.

For hospitalized patients it's totally different. In this setting you want to test for both covid and non-covid pathogens so that patients can be properly cohorted. You would not want to cohort an influenza patient with a covid patient, for example. There may also be treatment implications, e.g. antiviral choices, although that's a whole other conversation. In Alberta hospitals we use the Luminex RPP for non-covid pathogens and a non-commercial test for covid that's been validated against the test created at the National Micro Lab in Winnipeg.

22

Consequences / Re: COVID-19

« on: March 15, 2020, 02:12:59 AM »

The test are useful for contact tracing and epidemic management. If contact tracing is not possible, then a quarantine is the answer. Take the hit for a 3-4 weeks, start tracing again when the numbers go down.

Right now they are taking the most costly route in terms of lives and money. Is not that they are greedy. They just don’t know what they are doing.

Testing has another important role which is to exclude covid-19 in those patients presenting with an influenza-like illness so that they can avoid being in isolation for 2 weeks or more and get back to being productive members of society. This is particularly important for health care workers.

However, the test is only useful in this regard for low pretest probabilities. If the numbers from New York that Alexander posted are accurate then the pretest probability in that sample is actually quite high; the test is therefore not helpful at excluding the disease in those individuals.

As you suggested: they seem to have botched it.

23

Consequences / Re: COVID-19

« on: March 15, 2020, 01:04:43 AM »

...

If the testing capability is very low, then testing of someone probably only happens given the most alarming symptoms. So the data is of just about zero use and liable to confuse.

Exactly. For a high enough pre-test probability, false negatives outnumber true negatives. Negative results are therefore not to be believed. Moreover, false positives are relatively rare. Thus, the test does not alter management.

24

Consequences / Re: COVID-19

« on: March 14, 2020, 11:57:50 PM »

On the flip side... if the tests are correct, we will know in about a week as a large percentage of those 500 become hospital patients.

...

My point was that the number of patients with the disease is likely larger (possibly much larger) than 500 because the apparent high pre-test probability and limited sensitivity of the test create many false negatives.

The flip side concerns the specificity of the test. However, with a large pre-test probability even a test with a modest specificity can have a high positive predictive value. As such, it's highly likely that many of the 500 do, in fact, have the disease; no need to wait a week to find out.

25

Consequences / Re: COVID-19

« on: March 14, 2020, 10:44:17 PM »

So far 700 people have been tested in New-York, 500 of them tested positive.

That is an insane number of positive results for what is at this point essentially a screening test. Contrast this with where I work in Alberta where as of this morning there have been 7,108 tests done with 39 positives (source; accessed March 14).

In practice in New York this means the pre-test probability at the time the test is exceptionally high; in this setting it's impossible to conclude that a negative result is a true negative (barring a test with 100% sensitivity--and we know that's not the case).

26

Consequences / Re: COVID-19

« on: March 09, 2020, 01:31:52 PM »

For people here following the science side of this virus, the best two resources are biorxive (hasty preprints) and pubmed (final peer-reviewed), not so much press releases from know-nothing campus publicists or pharma marketing promotions of pre-existing repurposed miracle drugs (possibly with rush-rush clinical trials and carcinogenic side effects).

https://www.biorxiv.org/search/
https://pubmed.ncbi.nlm.nih.gov/

...

Thanks.

For those of us who deal with the clinical side of things there's also the medRxiv preprint server.

https://www.medrxiv.org/

27

Consequences / Re: COVID-19

« on: March 09, 2020, 03:13:11 AM »

Linear growth in South Korea rather than exponential for a week now, that's some glimmer of hope at least.

28

Consequences / Re: COVID-19

« on: March 08, 2020, 11:47:10 PM »

...

Oil now a ‘bigger problem for markets than the coronavirus,’ analyst says
https://www.cnbc.com/2020/03/08/coronavirus-live-updates-grand-princess-to-disembark-passengers.html

Oil prices plunged last week as OPEC and its allies failed to reach an agreement on production cuts, and as prices look set to continue cratering, some are warning about the impact on the broader economy.

“Crude has become a bigger problem for markets than the coronavirus,” Vital Knowledge founder Adam Crisafulli said Sunday. “It will be virtually impossible for the [S&P 500] to sustainably bounce if Brent continues to crater,” he added.

...

Oil has absolutely tanked as Asian markets opened. This is incredible... Down more than 20%!


Source: https://www.theglobeandmail.com/investing/markets/commodities/CL*0

29

Consequences / Re: COVID-19

« on: March 07, 2020, 04:29:27 AM »

The US CDC is now recommending that those over 60 or with serious health conditions stay home.

https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/high-risk-complications.html

...

Let's hope people follow their advice! Although their actual advice was "stay at home as much as possible" so rather open-ended. And they didn't actually specify the age of 60, just "older adults". Most people would probably just interpret that as "anyone older than me".

30

Consequences / Re: COVID-19

« on: March 07, 2020, 04:20:30 AM »

'Wildly Unprepared’: Survey of US Nurses Highlights Coronavirus Concerns
https://www.theguardian.com/world/2020/mar/06/us-coronavirus-outbreak-nurses-cdc

...

Just 63% of nurses surveyed had access to N95 respirators in their units, while a mere 27% had access to powered air purifying respirators.

...

The clamor over N95 masks is a good example of the problems that arise when decisions are made based on fear rather than on evidence. In my health region we are faced with a growing concern regarding the supply of N95 masks--a looming shortage that would possibly be completely avoidable if their use elsewhere were reserved only for when they are really needed rather than universally.

Elsewhere in Canada, the Ontario Ministry of Health was recently taken to task by ID doctors over similar concerns.

Ontario’s coronavirus policy for health workers not supported by evidence, experts warn

Ontario’s policy for protecting health-care workers against COVID-19 wastes precious resources and leaves hospitals unable to safely cope with an expected rise in coronavirus patients in the coming days, infectious disease experts warn.

...

But numerous infectious disease experts say mounting evidence shows COVID-19 spreads through droplets, such as when an infected person sneezes and coughs, and that airborne precautions are not appropriate nor are they supported by evidence. Instead, they say health professionals should use “droplet precautions,” which refer to gowns, eye guards, gloves and regular surgical masks.

...

https://www.theglobeandmail.com/canada/article-ontarios-coronavirus-policy-for-health-workers-not-supported-by/

In other news, my region is about to start testing all patients presenting with ILI symptoms for SARS-CoV-2; no longer will a travel history or epidemiological link be required. I expect a big increase in cases soon (source: inside information).

31

Consequences / Re: COVID-19

« on: March 04, 2020, 03:14:34 AM »

WHO chief, arguably the world's top 'authority' in such matters:

"We are in unchartered territory.

We have never before seen a respiratory pathogen that is capable of community transmission..."

That is an extremely misleading selective quotation you have just provided. The full statement from Director-General Ghebreyesus was:

"We have never before seen a respiratory pathogen that is capable of community transmission but which can also be contained with the right measures."

Source: https://www.npr.org/sections/goatsandsoda/2020/03/02/811271217/coronavirus-update-we-are-in-unchartered-territory-who-says

32

Consequences / Re: COVID-19

« on: March 03, 2020, 09:18:59 PM »

Health system in northern Italy stretched to the limit. 10 % of medical staff already infected. https://the-japan-news.com/news/article/0006393527

From the article:

Alarmingly, 10% of Lombardy’s doctors and nurses cannot work because they tested positive for the virus and are in quarantine, the region’s top health official, Giulio Gallera, said Monday.

I can't help but think that something was lost in translation. Italy has about 10.7 doctors and nurses per 1,000 people (source), hence probably about 107,000 doctors and nurses among Lombardy's 10 million inhabitants. If 10% have tested positive that's more than 10,000 cases just from doctors and nurses!

33

Consequences / Re: COVID-19

« on: March 03, 2020, 03:42:11 PM »

That is perhaps true if you are a health care worker who will be repeatedly exposed thousands of times, and who doesn’t mind risking ultimate exposure, illness, heart damage, lung damage, kidney damage, and death.

Yes sure, in that case, by all means use the piss poor protective recommendations from CDC. While you are at it, rely on their seemingly mostly ineffective test. 

Sam

What a strangely angry response. If the CDC IPC guidelines are "piss poor" I am curious what you think of the guidelines from the WHO, Health Canada, and other jurisdictions which are actually less strict than those from the CDC.

34

Consequences / Re: COVID-19

« on: March 03, 2020, 04:26:23 AM »

Use Standard Precautions, Contact Precautions, and Airborne Precautions and eye protection when caring for patients with confirmed or possible COVID-19

https://www.cdc.gov/coronavirus/2019-ncov/hcp/caring-for-patients.html

(my emphasis)

Yes, however as noted above that's different from most of jurisdictions who recommend airborne precautions only when aerosolizing procedures are being performed.

35

Consequences / Re: COVID-19

« on: March 03, 2020, 03:14:36 AM »

Archimid's picture is probably all too real . I watched in disbelief what was obviously someone being transferred from old folks home to ambulance in Washington 24+ hours ago .. pretty sure it was on bbc .. again no precautions beyond basic masks . If that's the USA's preparedness I guess someone has calculated if you are going to lose the pensioners , may as well get the carers off the payroll too .. b.c.

Interestingly the CDC guidelines for infection prevention and control for COVID-19 seem to be more strict than most other jurisdictions. CDC recommend N95 masks and negative-pressure isolation at all times. WHO guidelines recommend N95 masks and negative-pressure isolation only when aerosolizing procedures (e.g., endotracheal intubation) are being performed; at other times a regular medical mask can be used. Canadian guidelines are roughly parallel to WHO guidelines.

The WHO guidelines actually make more sense given what we know about the mechanism of transmission of this disease. N95 masks and negative-pressure isolation rooms are valuable resources and need to be used rationally.

WHO guidelines for IPC:
https://www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125

Health Canada:
https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/health-professionals/interim-guidance-acute-healthcare-settings.html#a4.10

CDC:
https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fhcp%2Finfection-control.html

36

Consequences / Re: COVID-19

« on: March 02, 2020, 10:52:39 PM »

That did not come out of nowhere. Read some of the earlier posts about the US healthcare on this thread. Get tested for flu costs 4k$ and many can not pay that which will make the outcome worse also because of additional community spread.

Yes, to us on this thread it did not come out of nowhere, but for the general public it did. Death rate for confirmed US mainland cases is now over 10%.  And yes, the real death rate if probably much lower due to more cases out their waiting to be confirmed.

All six deaths occurred at EvergreenHealth Health hospital in Kirkland including two clients of the Life Care long-term care centre where an outbreak was confirmed. There's a pretty good chance that all deaths end up being connected to the long-term care centre somehow. Regardless, there's very soon going to be a large uptick in the number of cases both confirmed and unconfirmed in the Seattle area.

Also given, what we know about who disease affects most, there's likely to be a quick uptick in the number of fatalities. Residents of long-term care facilities are vulnerable at the best of times.

https://www.seattletimes.com/seattle-news/health/king-county-now-has-14-coronavirus-cases-including-5-deaths/

37

Consequences / Re: COVID-19

« on: March 02, 2020, 02:40:45 AM »

I am not an expert but I think your logic is flawed.
If a reduced immune response is partly why children are less affected is the reason they are okay, then it stands to reason that those with suppressed immunity would be the same way and it would also hit those with health immunity harder.

The immune system is not a single anti-infectious process, it's more a collection of processes some of which are pro-inflammatory causing cellular injury and some of which are anti-inflammatory and promote cellular repair. In health, these processes balance each other out. In sepsis, this balance is disturbed leading to loss of homeostasis, multi-organ failure, and, frequently, death.

People with immune dysfunction, such as those with increased age, chronic disease, malignancy, etc are more prone to sepsis not necessarily because their immune systems are "reduced" but because their equilibrium between pro- and anti-inflammatory processes is more unstable.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701539/

38

Consequences / Re: COVID-19

« on: March 01, 2020, 05:32:46 AM »

For those interested in reviewing the peer-reviewed literature describing the clinical characteristics of this virus, most major journals are allowing free access to relevant papers. For example, yesterday the New England Journal of Medicine published data from a series of 1099 hospitalised and confirmed cases through January 29.

RESULTS
The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2002032

39

Consequences / Re: COVID-19

« on: February 26, 2020, 02:52:20 AM »

If that is true (I.e. that the blue and gold bars represent the same set of patients), then it is clear that a large subset of patients not counted in these bars and represented by the as yet missing right tail of the gold bars will when counted increase the counts in the blue bars shifting the distribution to the right as they are counted.

The data as presented in the synopsis is not (at least at first reading) absolutely clear which case is true. 1) that the blue bars represent all cases reporting with symptoms, or 2) that the blue bars only represent those cases presenting with symptoms that are later confirmed.

The rest of the analysis is unchanged. The death count is incomplete, as is the recovery count.

Sam

The graph represents 44,672 confirmed cases. Of these almost 90% had onset of illness by January 31. The "death count" while not complete is going to be pretty close.

40

Consequences / Re: COVID-19

« on: February 25, 2020, 10:52:06 PM »

[
Edmountain,

In a word - wrong.

Note that the blue bars are about new incidence. And yes for this cohort, new incidence is nearing an apparent end.

But note then the gold bars - confirmed. That count is about 2/3rds complete due to the delay in testing compared to symptomoligy.

...

Sam, you misread the graph. All cases are confirmed.

41

Consequences / Re: COVID-19

« on: February 25, 2020, 10:00:38 PM »

I too find the poll rather shameful and wish it were taken down.

With respect to the earlier discussion about the case fatality rate (CFR), it's safe to say that the authors of that JAMA paper are well and truly aware of the pitfalls of measuring the CFR when things are still evolving. That said, the CFR estimate they provide is specifically for that series of cases and for that series the number of new cases was virtually nil by February 11 as evidenced by the height of the blue bars from their Figure 1.


Source: https://jamanetwork.com/journals/jama/fullarticle/2762130

Whence given what we know about the duration of the disease I think it's unlikely the overall CFR will be significantly higher than the 2.3% for this series of cases. Indeed, the authors discuss the foibles of estimating the CFR and provide good reasons why it might actually be lower than this:

As of the end of February 18, 2020, China has reported 72 528 confirmed cases (98.9% of the global total) and 1870 deaths (99.8% of the global total). This translates to a current crude CFR of 2.6%. However, the total number of COVID-19 cases is likely higher due to inherent difficulties in identifying and counting mild and asymptomatic cases. Furthermore, the still-insufficient testing capacity for COVID-19 in China means that many suspected and clinically diagnosed cases are not yet counted in the denominator. This uncertainty in the CFR may be reflected by the important difference between the CFR in Hubei (2.9%) compared with outside Hubei (0.4%). Nevertheless, all CFRs still need to be interpreted with caution and more research is required.

Source: https://jamanetwork.com/journals/jama/fullarticle/2762130

42

Consequences / Re: COVID-19

« on: February 09, 2020, 08:17:05 PM »

...

If for example we take the current daily growth factor as being 1.32 and the mean time from confirmed status to death, we would expect the value of the ratio of the number dying each day to the number confirmed each day to be about equal to the inverse of 1.32^6 times the case fatality rate. 1/(1.32^6) equals 0.189.  If as we seem to be seeing, the mean death rate is 10-12% of those infected and reporting to hospital, then we would expect the ratio of daily deaths to daily confirmations to be about 0.019 to 0.023 (1.9%-2.3%). If the CFR is 11%, the ratio would be ~2.1%

...

Thank you for this helpful post.

When calculating the CFR I'm not sure it's necessary to estimate an exponential growth rate which is then used to calculate the number of cases 6 days ago. Rather, one can simply use the directly measured number of cases from 6 days ago. This would reduce the number of parameters in your model to just one, i.e. the estimate of the 6 days for the time from confirmation to death.

43

Consequences / Re: COVID-19

« on: February 09, 2020, 01:09:08 AM »

The contagiousness and significant lethality of this virus are roughly comparable to the 1918 influenza pandemic.  Similarly to that episode, there is currently no available vaccine or antiviral treatment.  Unlike that episode, we have a good diagnostic test, though test availability is still terribly limited.

Also unlike 1918 pandemic, we have prospects of finding effective anti-viral treatment in a matter of perhaps weeks.  But actually making a new medication available around the world to all who become sick will takes many months of dedicated, funded, herculean efforts.  Wealthy nations and individuals will, of course, be first in line.

One interesting thing about the 1918 influenza epidemic was a disproportionate number of deaths among seemingly-healthy 20-40 year-old individuals; the mortality curve was W-shaped rather than U-shaped. These deaths accounted for the majority of "excess" influenza deaths over the course the pandemic (source).

Thus far it seems as if the Wuhan coronavirus is not following this 1918 influenza pattern: the most severely ill and the most fatalities seem to be older or comorbid individuals. See, for example, this case series of 138 hospitalized patients recently published in JAMA.

Also unlike 1918 pandemic, we have prospects of finding effective anti-viral treatment in a matter of perhaps weeks.  But actually making a new medication available around the world to all who become sick will takes many months of dedicated, funded, herculean efforts.  Wealthy nations and individuals will, of course, be first in line.

Another interesting thing about the 1918 influenza pandemic was that a large part of excess influenza deaths were caused secondary bacterial pneumonias (source, and references therein) for which no effective treatment, i.e. antibacterials, existed in 1918. If secondary bacterial pneumonias comprise an important complication of the current infection then antibacterials may be of benefit. This is of course a big if but it's notable that most of the patients in the JAMA case series above received antibacterials. Obviously antibacterials have no role in treating the primary infection

What this means exactly for the future transmission of the Wuhan virus remains to be seen. As you suggest, there are many reasons to believe that the current outbreak will not automatically be a repeat of 1918.

44

Arctic sea ice / Re: The 2019/2020 freezing season

« on: February 07, 2020, 10:52:22 PM »

Not often you see a 100% expectation of below normal temperatures over such a large swath of the Canadian far North

I think it's technically in the 90-100% range. But still unusual for sure.

45

Arctic sea ice / Re: The 2019/2020 freezing season

« on: February 06, 2020, 07:32:50 PM »

Snow area in January ranked third in the 21st century after 2007 and 2014.

I assume you mean third lowest? What's the source of the data?

46

Consequences / Re: Weird Weather and anecdotal stories about climate change

« on: February 04, 2020, 10:52:09 PM »

January 2020 Warmest On Record: EU Climate Service
https://phys.org/news/2020-02-january-warmest-eu-climate.html

Last month was the warmest January on record globally, while in Europe temperatures were a balmy three degrees Celsius above the average January from 1981 to 2010, the European Union's climate monitoring system reported Tuesday.

...

These data would seem to be more empiric and less "weird and anecdotal"--which makes it all the more concerning.

47

Policy and solutions / Re: Oil and Gas Issues

« on: February 04, 2020, 08:34:25 PM »

Meanwhile in Canada, the federal government continues its headlong rush into building a pipeline using billions of dollars of public money. A pipeline that by the government's own assessment will release between 21 and 26 megatonnes of carbon dioxide equivalent per year counting only upstream emissions--let alone downstream.

The federal government maintains this disastrous pipeline is in the "public interest". Today, the Federal Court of Appeal ruled that the government's consultation with indigenous peoples was "reasonable" and "meaningful".

Court upholds Trans Mountain pipeline approval

Prime Minister Justin Trudeau’s government fulfilled its obligations to consult with Indigenous people when it re-approved the expansion of the Trans Mountain oil pipeline last year, a panel of the Federal Court of Appeal has ruled.

“We conclude that there is no basis for interfering with the [cabinet’s] second authorization of the Project,” the judgement states, dismissing an application by four Indigenous groups seeking to halt the project.

The decision strips away one more layer of uncertainty over the $10-billion project which is now owned by the government of Canada. The expansion will triple the capacity of the existing pipeline from Alberta’s oilsands to a shipping terminal in Burnaby, allowing Alberta greater access to overseas markets.

...

Source: https://www.theglobeandmail.com/canada/article-court-upholds-trans-mountain-pipeline-approval/

48

Policy and solutions / Re: Coal

« on: February 04, 2020, 08:11:47 PM »

A New York Times article released yesterday describing Japan's move towards coal instead of away from it has been widely picked up.

Japan to build up to 22 new coal power plants despite climate emergency

Just beyond the windows of Satsuki Kanno’s apartment overlooking Tokyo Bay, a behemoth from a bygone era will soon rise: a coal-burning power plant, part of a buildup of coal power that is unheard of in an advanced economy.

It is one unintended consequence of the Fukushima nuclear disaster almost a decade ago, which forced Japan to all but close its nuclear power program. Japan now plans to build as many as 22 new coal-burning power plants - one of the dirtiest sources of electricity - at 17 different sites in the next five years, just at a time when the world needs to slash carbon dioxide emissions to fight global warming.

...

Source: The New York Times via The Independent
https://www.independent.co.uk/news/world/asia/japan-new-coal-power-plant-climate-change-tokyo-a9316271.html

49

Science / Re: Where are we now in CO2e , which pathway are we on?

« on: February 04, 2020, 05:30:51 PM »

I don’t think there’s any way to get around using time horizons when discussing CO2 equivalents. This is because the very definition of GWP is based on integration over time. From the IPCC AR5 report:

The Global Warming Potential (GWP) is defined as the time-integrated RF due to a pulse emission of a given component, relative to a pulse emission of an equal mass of CO2 (Figure 8.28a and formula).

Source: https://www.ipcc.ch/site/assets/uploads/2018/02/WG1AR5_all_final.pdf

The absolute GWPs (AGWP) of hypothetical gases are the areas under the curves red and green curves in Figure 8.28a from the same report as shown below. The AGWP for CO2 is the area under the blue curve. GWP for a gas is the AGWP for that gas divided by the AGWP for CO2.


CO2 equivalents are essentially a unit of measure of GWP (analogous to how meters are a measure of distance). As such, time horizons are inseparable from the definition of CO2 equivalents. I’m not sure how to interpret the instantaneous ratio of RF that Ken refers to other than being some measure of relative fluxes.

50

Policy and solutions / Re: Coal

« on: February 03, 2020, 11:41:14 PM »

^Colour me skeptical: later on in the same article it also says "Coal, however, is still expected to make up the majority of Indonesia’s power mix, at least up until 2028." So much for starting today.

Also, just the day before Reuters described how the very same Indonesian minister was busy incentivizing the coal industry:

Indonesia to set cheaper coal prices for future gasification plants - minister

JAKARTA, Jan 30 (Reuters) - Indonesia plans to set cheaper prices for coal to be sold to future gasification facilities as part of incentives for investors, Energy and Mineral Resources Minister Arifin Tasrif told reporters on Thursday.

The government is promoting the development of the coal gasification industry to take advantage of Indonesia’s large coal output and is offering incentives to attract investments.

...

https://af.reuters.com/article/commoditiesNews/idAFL4N29Z396