Originally Posted by Bwana:
Once again, don't come in this thread with some kind of political agenda, or you will be shown the door. If you want to go that route, there is a thread about this in DC.
Originally Posted by Dartgod:
People, there is a lot of good information in this thread, let's try to keep the petty bickering to a minimum.
We all have varying opinions about the impact of this, the numbers, etc. We will all never agree with each other. But we can all keep it civil.
Thanks!
Click here for the original OP:
Spoiler!
Apparently the CoronaVirus can survive on a inanimate objects, such as door knobs, for 9 days.
California coronavirus case could be first spread within U.S. community, CDC says
By SOUMYA KARLAMANGLA, JACLYN COSGROVE
FEB. 26, 2020 8:04 PM
The Centers for Disease Control and Prevention is investigating what could be the first case of novel coronavirus in the United States involving a patient in California who neither recently traveled out of the country nor was in contact with someone who did.
“At this time, the patient’s exposure is unknown. It’s possible this could be an instance of community spread of COVID-19, which would be the first time this has happened in the United States,” the CDC said in a statement. “Community spread means spread of an illness for which the source of infection is unknown. It’s also possible, however, that the patient may have been exposed to a returned traveler who was infected.”
The individual is a resident of Solano County and is receiving medical care in Sacramento County, according to the state Department of Public Health.
The CDC said the “case was detected through the U.S. public health system — picked up by astute clinicians.”
Officials at UC Davis Medical Center expanded on what the federal agency might have meant by that in an email sent Wednesday, as reported by the Davis Enterprise newspaper.
The patient arrived at UC Davis Medical Center from another hospital Feb. 19 and “had already been intubated, was on a ventilator, and given droplet protection orders because of an undiagnosed and suspected viral condition,” according to an email sent by UC Davis officials that was obtained by the Davis Enterprise.
The staff at UC Davis requested COVID-19 testing by the CDC, but because the patient didn’t fit the CDC’s existing criteria for the virus, a test wasn’t immediately administered, according to the email. The CDC then ordered the test Sunday, and results were announced Wednesday. Hospital administrators reportedly said in the email that despite these issues, there has been minimal exposure at the hospital because of safety protocols they have in place.
A UC Davis Health spokesperson declined Wednesday evening to share the email with The Times.
Since Feb. 2, more than 8,400 returning travelers from China have entered California, according to the state health department. They have been advised to self-quarantine for 14 days and limit interactions with others as much as possible, officials said.
“This is a new virus, and while we are still learning about it, there is a lot we already know,” Dr. Sonia Angell, director of the California Department of Public Health, said in a statement. “We have been anticipating the potential for such a case in the U.S., and given our close familial, social and business relationships with China, it is not unexpected that the first case in the U.S. would be in California.”
It is not clear how the person became infected, but public health workers could not identify any contacts with people who had traveled to China or other areas where the virus is widespread. That raises concern that the virus is spreading in the United States, creating a challenge for public health officials, experts say.
“It’s the first signal that we could be having silent transmission in the community,” said Lawrence Gostin, director of the World Health Organization Collaborating Center on National and Global Health Law. “It probably means there are many more cases out there, and it probably means this individual has infected others, and now it’s a race to try to find out who that person has infected.”
On Tuesday, the CDC offered its most serious warning to date that the United States should expect and prepare for the coronavirus to become a more widespread health issue.
“Ultimately, we expect we will see coronavirus spread in this country,” said Nancy Messonnier, director of the CDC’s National Center for Immunization and Respiratory Diseases. “It’s not so much a question of if, but a question of when.”
According to the CDC’s latest count Wednesday morning, 59 U.S. residents have tested positive for the new strain of coronavirus — 42 of whom are repatriated citizens from a Diamond Princess cruise. That number has grown by two since Messonnier’s last count Tuesday, although the CDC was not immediately available to offer details on the additional cases.
More than 82,000 cases of coronavirus have been reported globally, and more than 2,700 people have died, with the majority in mainland China, the epicenter of the outbreak.
But public health leaders have repeatedly reminded residents that the health risk from the novel coronavirus to the general public remains low.
“While COVID-19 has a high transmission rate, it has a low mortality rate,” the state Department of Public Health said in a statement Wednesday. “From the international data we have, of those who have tested positive for COVID-19, approximately 80% do not exhibit symptoms that would require hospitalization. There have been no confirmed deaths related to COVID-19 in the United States to date.”
CDC officials have also warned that although the virus is likely to spread in U.S. communities, the flu still poses a greater risk.
Gostin said the news of potential silent transmission does not eliminate the possibility of containing the virus in the U.S. and preventing an outbreak.
“There are few enough cases that we should at least try,” he said. “Most of us are not optimistic that that will be successful, but we’re still in the position to try.”
I actually play a game every time I travel to see how long it takes someone to annoy me once I get to the airport. It's usually when I get on and off the elevator from the parking garage. But, on occasion, it takes as long as getting to the Clear or TSA Pre lanes. [Reply]
Originally Posted by BWillie:
Nonetheless, those of you trying to figure out the mortality rate based on active cases and deaths are doing it wrong. Active cases do not mean anything. They are still active and ongoing and have no effect on mortality rate until they are either recovered or dead.
The real question is how many total infections have occurred. Is it twice the 5K in the US? Ten times? 100 times? If the number of people who have contacted this is actually 50,000 instead of 5,000 then the 1.5% mortality rate is really .15%.
Heck, Ohio estimated they had 100,000 cases just in that state based on some model created by someone smarter than me.
Not saying we shouldn’t be doing all we can to stop it or the impact this has on our health care system by happening all at once, but it also won’t surprise me if this ends up killing a smaller percentage of people than the flu. Not diminishing it, just saying the data conclusions are probably not as bad as they look right now. [Reply]
This this same treatment has been used elsewhere. Hamas the pharmacist, thoughts? My pharmacist buddy was intrigued by it.
It's chloroquine along with lopinavir+ritonavir (Kaletra)
My thoughts about trial design and potential issues are explained here:
Spoiler!
Originally Posted by 'Hamas' Jenkins:
The short answer is that it's complicated. The long answer will follow:
1) The evidence is only as good as the trial design. In a situation like this, you aren't going to have good trial design, because people deteriorate quickly, there are no known beneficial treatments, and the need is so great that you aren't going to be able to blind patients and/or investigators as there is no standard of care to compare against. Ideally, you would want a large, multicenter trial with thousands of patients from a variety of demographics. They would need a random distribution between the intervention and the control group that is also consistent within subgroups. The trial should also be forward-looking (prospective) rather than collecting data from old cases and compiling it together (retrospective). The more patients you have, the greater your predictive power of the trial can be. Blinding helps prevent the placebo effect and reporter bias, but that really can't be done at this stage either.
2) In order to pass muster, most operators have agreed that a p-value of greater than two standard deviations is necessary to reduce the chances of it being a statistical anomaly. What that means is that there has to be less than a five percent chance the effects are random for it to be statistically significant. However, this is also complicated--what is the difference between clinical and statistical significance? Let's say I have a blood pressure drug I'm bringing to market and it lowers BP by an average of 2mmHg compared to a popular ACE-inhibitor, like lisinopril. Is that statistically significant? Yes. Is it clinically significant? Not likely. So the other thing I have to do is consider how much of a clinical impact this drug may have. That's why Tamiflu is overused in my opinion. Unless you are very young or old/immunocompromised, Tamiflu only shortens the duration of flu symptoms by about 8 hours, and that's only if you begin treatment within the first 40 hours of symptom onset.
3) Trials normally progress through three distinct phases (ignoring the preclinical trials with animal and computer models). The first is a dose escalation study--what can the body handle. Usually this is done in healthy volunteers depending upon the drug, but in more emergent cases, it is applied to individuals with the illness. The second phase is generally a placebo comparison--is this better than nothing at all? The third phase is comparison against an active comparator. Is this better than the current standard of care? As you can see, a trial for a COVID-19 agent isn't going to be able to meet these standards very well, either.
So, let's apply this to COVID-19:
What am I looking for first: a mortality benefit. What am I looking for next: morbidity benefits: decreased hospitalization length, reduced clinical sequelae, etc.
So, what are these studies like: the favipravir study you mention is just a dose escalation study of about 60 people. You can get enough data with a sample size that small to meet statistical significance, but the confidence intervals will be broad and uncertainty high due to the small sample size.
Also, what are the impacts of polypharmacy? Generally, multiple agents are needed in the case of antivirals, whether it's Hep C or HIV. However, one must be careful in choosing those agents due to drug interactions.
Protease inhibitors are a great example. Their use revolutionized treatment for HIV, but protease inhibitors are among the strongest inhibitors of an enzyme in your body called cytochrome p450 3A4, which metabolizes more drugs than any other drug type. Well, what does this mean? Let's say that I'm taking carbamazepine for seizures and I start a protease inhibitor. What happens? The inhibition of 3A4 causes carbamazepine levels in my system to build up to toxic levels because I'm not clearing the drug quickly enough.
So, what happens if one agent is a substrate and the other is an enzyme inducer? The second drug wipes out the efficacy of the first drug. In other cases, the inhibition (carbamazepine example) can actually be a benefit. Ritonavir is a potent 3A4 inhibitor, and is used to actually boost the level of other protease inhibitors (as they are also 3A4 substrates). Thus, when weighing such therapy, I must consider those effects as well.
Also, I have to think about the side effects of each drug. For years, patients coming into the hospital who may have had an infection were given broad spectrum antibiotic coverage often with vancomycin and piperacillin-tazobactam (Zosyn). This would cover gram-positive bugs, gram-negative bugs and anaerobes. However, both agents are harmful to the kidneys, and the rate of acute kidney injury from their concurrent use is high, especially in an elderly population. This is also why you should avoid the use of fluoroquinolone antibiotics in the elderly. They increase the QT interval in the heart (old people are already prone to arrhythmias) and increase the risk of tendon rupture. So, who am I giving my new therapy to? What are its side effects? How do those side effects affect that person? What are their comorbidities?
However, there's a reason why HAART works. In the case of HIV, which is prone to rapid mutation, suppression of one target (reverse transcriptase was the first and only target for almost a decade) leads to rapid development of resistance. Suppression of multiple targets (reverse transcriptase *2 plus viral protease) lead to a revolution in therapy, although not an elimination of resistance. We are still learning about SarsCoV2. Sites of attachment, entry, etc. More time will provide greater clarity on the viral life cycle, which will better elucidate treatments. Time, unfortunately, is not on our side in this case.
Key takeaways:
There is no magic number of patients, but more (hundreds to thousands) is always better and far, far more predictive than dozens.
Polypharmacy may work if the mechanisms of action are synergistic or additive, but the risk of drug interactions and drug-disease interactions also increases.
I'll also add that many initially promising therapies usually don't bear fruit. There's a reason why the success rate of small molecule drugs is around 1:5000.
With that said, if there aren't drug-drug or drug-disease interactions, then if it appears safe and there are no other options, you have to try something. [Reply]
Originally Posted by BWillie:
Nonetheless, those of you trying to figure out the mortality rate based on active cases and deaths are doing it wrong. Active cases do not mean anything. They are still active and ongoing and have no effect on mortality rate until they are either recovered or dead.
One of the most significant "unknowns", Mr. BWillie is this; How many people have contracted the virus? We know that you can be a carrier and show no symptoms. We know that because many people who have tested positive have no symptoms ... and never presented symptoms.
Those who are asymptomatic aren't even being counted by the CDC unless or until they are tested. They don't know who they are so they couldn't count them if they wanted to.
So, if the mortality "rate" doesn't include the entire population, at a minimum it should include all those with the virus ... not simply those who have tested positive, right?
Not to mention the problem of weighting the mortality rate numbers against only those who have contracted the virus and are "at higher risk" due to complicating health issues.
Originally Posted by BWillie:
Nonetheless, those of you trying to figure out the mortality rate based on active cases and deaths are doing it wrong. Active cases do not mean anything. They are still active and ongoing and have no effect on mortality rate until they are either recovered or dead.
But we do have a ratio of 'completed' cases and I wonder if you're not conflating those a little with the mortality rate.
Right now 8% of 'closed' cases ended in death, 92% ended in recovery. And those are closed cases. But remember that the spike is still working its way through the system and the trends have been improving for weeks. It's started to bow back up a little bit as more countries are hit and figuring out their own way through it, but those too shall stabilize.
So yes, there are projections in the numbers, but when you can see that even in 'confirmed' cases where we were still putting up with lag in the denominator, the ratio of closed cases that ended in death vs. recovery had whittled its way all the way down to about 95% to 5% before the global spread geared up about 10 days ago.
When the math sorts itself out I'd be surprised if the CFR stayed greater than 1%. [Reply]
Originally Posted by BDj23:
I plan on laying low for the next couple of weeks. I'll probably venture out to get food and booze, but other than that just relax at home.
Helps that I hate almost everyone in the general public.
Same here. I could go all year without having to interact with John Q Fuckstick and be perfectly fine with it. [Reply]
Suspending all commerce except for food/health care isn’t a bad idea if you’re determined to mostly suspend all commerce piecemeal. If Trump came out and shut down everything for a month we’d all have a date circled on our calendar and wouldn’t much care about anything since we wouldn’t have any bills until next month.
Reminds me of the Wall Street Do-Over in Red Storm Rising. [Reply]
