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Posts: 89
Maloja Snake
Maloja Snake
54 posts
active member
Apr 8, 2020 - 9:10 PM

International Travel May Only Become Practicable after a vaccine is developed, tested, and trusted. That is likely to be anywhere between 12-22 months from now. I live in NYC and the risk and danger is real. This is felt to be palpable in Europe (including Switzerland). Things are going to get worse before they get better; and Swiss travel lovers (like myself) can benefit by being realistic. If you have travel reservations (airline and hotels), it would behoove you to stategise within these parameters. My best advice would be to wait until there is conclusive proof that your trip is impossible, and only then, present your claim for a complete refund to vendors. Accepting future dates is a fools errand, and sets you up for bigger out of pocket losses.

Slowpoke
Slowpoke
7481 posts
expert
Apr 9, 2020 - 1:31 AM in reply to Maloja Snake

Hi Maloja Snake -

<<"International Travel May Only Become Practicable after a vaccine is developed, tested, and trusted. That is likely to be anywhere between 12-22 months from now.">>

I disagree.

The time line constraint will be to have a treatment, not a vaccine. Plus, a serological test to confirm prior exposure/immunity. ( Two were just announced).

Immunogloblin-based treatment ( using immunoglobulin transfusion therapies based on the plasma of cured patients), are likely to be available much faster than a vaccine. Basic biochemistry or physiology, plus the time required to develop and certify safety for a vaccine, are the issues.

That is what I am waiting for, before I travel. In layman's terms- "Have cure in case I catch it."

Slowpoke

Maloja Snake
Maloja Snake
54 posts
active member
Apr 9, 2020 - 5:49 AM in reply to Slowpoke

"The time line constraint will be to have a treatment, not a vaccine. Plus, a serological test to confirm prior exposure/immunity. ( Two were just announced)."

I agree; but only from the standpoint of an individual feeling that they themselves feel immune (and can certify to others that they are safe. But from the standpoint of the vendor (hotels, restaurants, airlines), it will be impossible for them to police whether their customers are safe or not, and so they will not be able to authoritatively represent that infected carriers (disease vectors) aren't on their premises. And 18-22 months is too short of a period to overcome irrational national biases. So in the best case scenario (in my opinion, of course) travel will selectively commence, but will be massively curtailed. This creates all sorts of impracticalities, the ability to retain non-infected employees, and the representation from the vendor that their employees (chefs, stewardesses, hotel housekeepers) are not disease vectors, being the least of them. Add this to community paranoia where the operator of crowded mountain lifts is a danger to his family and community, and is an actual danger of becoming a new community carrier. The current message of the day that lowering the curve ("just stay at home") is creating a shared belief (whether true or not) that makes international travel in the short term (1-3 years) problematic. I hope I'm mistaken; that widespread testing (of all types) changes my above analysis; but judging by the incompetence and stupid arrogance of many of our national leaders (Trump and Johnson first and foremost) I sadly doubt it.

Blig
Blig
4 posts
new member
Apr 9, 2020 - 12:32 PM in reply to Maloja Snake

Flattening the curve is supposed to take the pressure off the health services. It does not mean the crisis us over. It breaks the chain of infection.

I do not think it will be years before people can travel again as apart from tests and vaccines it will depend where you want to go. This year most countries ( like some already) are saying stay and take your holiday inland. Borders are closed to all but essential travel, however life goes on.

Your political remarks , maybe your opinion, but here are out of line. << removed >> I work at an airport so can tell you with some degree of knowledge what will happen there and with subsequent onward travel. That’s my field not running a country.

Stay safe, stay home

Mark
Mark
544 posts
top member
Apr 9, 2020 - 1:06 PM

I am very skeptical that our predictions regarding the future course of the pandemic and subsequent travel effects are very accurate. This is based on a couple of factors. There is no real consensus among the experts, which we are not. Also the track record of the experts has not been so great. Many at first underestimated the severity of the threat, WHO included. More recently the mortality rates and prevalence are somewhat lower than predicted. If the experts are not reliably able to predict the future I’m not sure this forum’s members will fare much better.

Of course that being said I will still add my 2 cents worth, given that my opinion and $2.50 will buy you a cup of coffee at McDonalds.

I think the stay at home measures and social distancing are moderately good at flattening the curve. This will definitely help reduce the surge of ICU admissions. But I afraid this will also prolong the duration of the pandemic. As the restrictions are eased I expect there will be some resurgence in infections and we may see recurring cycles of decreased then increased disease occurrence. Will it be safe to travel in 3 months? 6 months ? I hope so as i have a trip to Switzerland planned for September. But I truly have no idea if that will be feasible, nor do I believe does anyone else.

Mark

Maloja Snake
Maloja Snake
54 posts
active member
Apr 9, 2020 - 1:32 PM in reply to Blig

"Flattening the curve is supposed to take the pressure off the health services. It does not mean the crisis us over. It breaks the chain of infection."

I agree that flattening the curve seems to be the first step, but, as we saw in Singapore and other places is that when we relax the social distancing guidelines, the curve, and transmission rate can shoot up again. And I'm just not sure how to travel to international destinations while maintaining distancing guidelines. Crowded airports, crowded trains and stations, crowded ski lifts, crowded dining rooms, and even crowded hiking trails, all seem to be problematic regarding maintaining a low curve.

What is your take, as an airport worker, is the near term prognosis (1-6 months) of air travel. Seeing photos of Kloten suggest an almost total shutdown.

Good luck and stay safe!

Slowpoke
Slowpoke
7481 posts
expert
Apr 9, 2020 - 1:50 PM in reply to Blig

Hi Blig -

Yeah, I also made the mistake of putting a bit of politics in one of my comments in another thread. It's better to deal with that elsewhere.

I am not a world class virologist, or, more particularly, also not any class of epidemiologist.

So, although, I'd be ready to travel once there is a cure, I agree that factors other than my personal situation would likely be controlling.

And, to point out a corollary of "flattening the curve," the consequences will be most likely to prolong the epidemic, and alternate norms of behavior, until an effective vaccine is available. I'd submit that no matter how good or how bad the predictive capability of the experts, that conclusion will hold.

Just read Mark's comments about the poor accuracy of predictability from the experts. I agree. I'll also suggest that it is hard to do accurate work of that sort without data. A high rate of testing would provide a firmer base for calculations. It seems to me that quantitative work like that needs good input data.

Slowpoke

Slowpoke

Last modified on Apr 9, 2020 - 1:58 PM by Slowpoke
Mark
Mark
544 posts
top member
Apr 9, 2020 - 5:16 PM

Hi All

BTW in my above post I should have said incidence instead of prevalence. I’m a little rusty as my medical school classes in statistics and epidemiology were 40 years ago.

I believe travel within the US will be mostly determined by the Governors of each state with recommendations from the Federal government. Their unenviable job is to weigh the health risk vs the effects on the local economy (skyrocketing unemployment and bankruptcies). Perhaps that’s a no brainer now but may not be in 3 months as the pandemic lessens (hopefully) and the damage to our economy becomes critical. Tough choices. International travel will likely be determined by the national governing institutions of each country. But they will have a similar delemma. How many businesses in Wengen can last without tourists for a year?

As for treatment. Who knows ! As of now the most promising look to be Azithromiacin, Plaquinil (hydroxychlorquin), convalescent serum, and the Ebola drug. These are mostly being given to the sickest of patients who are already experiencing respiratory failure and or organ failure. The medical community is for the most part (either wisely or not) stuck on clinical trials often with double blind controls. This takes a lot of time to determine risk/benefit ratios and appropriate usage guidelines. It can only be hurried to a limited extent. As an example I do eye exams on people taking Plaquinil weekly for eye damage screening. Blindness is a rare side effect but Liver damage is fairly common place. Should we prescribe Plaquinil to everyone who has Covid-9 symptoms and hope their liver survives?

Ultimately I agree with Slowpoke, a vaccine is probably the only long term solution. As of today the estimate of widespread availability is 10-12 months (not 1- 3 years). But as I’ve said before these predictions are at best guesses (my opinion). Lord help us till then.

Mark

Last modified on Apr 9, 2020 - 5:17 PM by Mark
Slowpoke
Slowpoke
7481 posts
expert
Apr 9, 2020 - 9:43 PM in reply to Mark

Hi Mark -

<<"As of now the most promising look to be Azithromiacin, Plaquinil

(hydroxychlorquin), convalescent serum, and the Ebola drug. These are

mostly being given to the sickest of patients who are already

experiencing respiratory failure and or organ failure.">>

"Convalescent serum" is what I was referring to as an "immunoIogical approach." The concept is well-known and in practical use for other diseases, and from a theoretical basis ought to be effective, according to the company who has commercial products of this type. Takeda Pharmaceuticals, in Georgia, I believe, is expert in that technology, and his written that they are trying to develop a therapy based on this concept. Their comments indicate that some stages of clinical trials can be shortened or eliminated due to knowledge from existing similar products. For what it is worth.....

There may be a 5th route to pay attention to, also. I recently read about trials of an approach that has been tested and used when some patients experience an over-active immune system response. I believe that this is sometimes called a "cytokine storm"....but I don't really know what I'm talking about when I use words like that. However, you may be able to refine my comment, if necessary.

Here is quote from the magazine ( not a technical journal) Chemical and Engineering News, March 23, page 13

<<" Doctors in China noted that in some of those really sick patients, [major respiratory distress and organ failure] viral levels dropped, but levels of IL-6 - one of the distress signals used to call the immune system to action - remained high. A small study tested whether Actemra [ a drug used to treat rheumatoid arthritis, which is an IL-6 blocker] could stop the immune overreaction.

Paraphrasing further comments in the article-

A high percentage of of the patients in the small study reduced their need for supplemental oxygen....then there are some thoughts about the somewhat complicated implication of these results for actual treatment regimens.

This result is leading to controlled trials with larger numbers of participants of two such drugs. Actemra and Kevzara.

Speaking as a laymen, this sounds like an approach in addition to the 4 that you mentioned.

Extensive reading about early stage clinical trials when I was helping out a family member who was ill reminded me that such small trials may often give helpful results, which don't hold up in larger, better controlled studies. Nonetheless, in desperate times, "off-label trials" may well be explored, without a double-blind protocol. I believe that is what is going on with the (hydroxy)chloroquine treatments now being used with an intent to cure.

I don't pretend to sufficient knowledge to make judgements or predictions of any value about these approaches. You are much better qualified than I to make comments about "promising." I'm simply adding to your list an example of another creative approach being tried.

There is one very important feature to watch for, with many of the different approaches. If they use drugs that have been approved for another disease, they can be used immediately in so-called "off-label " studies or treatments. That much I am pretty sure of. I'm also sure that such uses ordinarily have a high risk of failure or undesirable side effects. But, they can be used legally by a physician without the time-consuming studies to prove safety and efficacy required for a completely new medicine.

If they work, they shorten the times we have been talking about.

Slowpoke

PS- meanwhile, we should all remember that a layman who took chloroquine ( or a close relative) on his own killed himself.

Mark
Mark
544 posts
top member
Apr 10, 2020 - 1:31 AM

Hi Slowpoke

You raise some valid points. My field of Ophthalmology is pretty far removed from much of what you brought up so I’m probably only marginally more informed than an average layperson. But here are some general comments you might find helpful. The field of immunology is unbelievably complex. Actually I can think of no other branch of medicine as complicated or difficult to grasp. Much of it deals with the body’s inflammatory response to injury or disease. This inflammatory response helps the body to fight injury or disease but sometimes as you states it can go too far and cause damage even worse than the disease. The inflammatory response is triggered by an array of complicated pathways and chemical mediators. When the response is too overactive to become harmful a number of agents are used to interrupt the chain of events at various points. This would apply to the drugs you mentioned affecting the cytokines pathway. It would also apply to hydroxychlorquine as well. It is most commonly given to patients with Lupus and Rheumatoid Arthritis to reduce their overactive inflammatory response. Steroids like Prednisone are another example (apparently it has been tried and made the Covid-19 worse). And the new class of drugs, biologics, as Humera for psoriasis are yet another example. All these drugs lessen inflammation from different points and pathways. They help some diseases and make others worse. They all have side effects, some life threatening.

As you pointed out off label use of drugs by physicians enables us to use drugs for purposes that the FDA has not approved them for. It is actually quite common place in medicine but we must do it with caution. We are certainly liable for any adverse effect or damage off label use causes. Consequently off label use in life or death situations is a heavy responsibility. Of course if I was in respiratory failure I would want to try Plaquinil or Azithramicin. But it quickly becomes complicated. What dose? How long? At what stage?When to stop? Did I get better or worse because of the drug or just the natural course of the disease? My livers dead, was it worth it now that I need a transplant? Well you see what i mean that it can get complicated. It is also a balancing act. The inflammatory response is necessary to fight Covid-19 so you can’t eliminate it. Rather reduce the harmful aspects in the lungs and leave the rest intact. Not so easy.

I certainly don’t want to paint an overly pessimistic picture. I don’t think clinical trials can be eliminated but they can absolutely be shortened. If a drug or treatment clearly shows good efficiency with acceptable risk, I would expect the trial would be cut short and the treatment widely implemented to some degree. Unfortunately in medicine the results are often equivocal and unclear. Let’s hope this time we discover the miracle we all want to see happen. Some of our greatest discoveries have been serendipity. Azithromicin for example is a common antibiotic (often given for sinus infections)which we know doesn’t kill viruses but as a side effect it may inhibit Covid by changing the pH of the cells the virus attacks ( a completely off label, unforeseen action ).

Mark. PS if this doesn’t get a slap on the hand from a moderator I’ll be surprised !!

Last modified on Apr 10, 2020 - 1:36 AM by Mark
Annika
Annika
6251 posts
expert &
moderator
Apr 10, 2020 - 8:42 AM

Hi all! No, no slap on the hand as predicted by Mark :-). It's perfectly understandable that this situation raises deep questions and concerns, and this will inevitably effect (international) travel for quite a while. So it's legitimate to discuss concerns and possible scenarios here. I do urge everyone to remain friendly and respectful, as requested in the forum rules.

Let's understand that we all have different views, hopes and expectations of how this will further develop, depending on our backgrounds, expertise, personality and political situations. Respecting those differences is most important. As long as that's the case, this thread can continue.

Slowpoke
Slowpoke
7481 posts
expert
Apr 10, 2020 - 12:38 PM in reply to Mark

Hi Markj-\

Thanks for filling in the gaps and putting my thoughts in order.

A little knowledge can be a dangerous thing.

In spite of having read comments about using chloroquine for immune deficiency diseases like rheumatoid arthritis, I i did not recognize that it was conceptually in the same category as the Chinese study of IL-6 blockers, that I had mentioned as a 5th approach. Certainly, the concerns you mention with those approaches were, indeed,mentioned in the C&EN article. As Ilearnedmany years ago, in work scaling up lab preps to pilot scale an full production, nothing is simple or easy as it first seems. .

It is nice to have confirmation that off-label studies of various therapeutic approaches offers at least some potential to shorten the period before widespread usage or trials might be possible.

Slowpoke

Mark
Mark
544 posts
top member
Apr 11, 2020 - 2:48 PM in reply to Slowpoke

Hi Slowpoke

I saw a report yesterday you might find interesting and illustrative. I’ll have to paraphrase it and the numbers may not be exact but they are close (I’m doing it from memory). It was a small study using the Ebola drug, Ranitidine, which scientists have high hopes it can reduce the replication of the virus. Apparently about 10 patients got remarkably better in a shorter than expected time. About 20 had a typical prolonged recovery. And 5 died. Their conclusion was there needed to be a controlled study with placebo to determine efficacy but the results looked promising.

To me this also illustrates a very common outcome in drug studies that results are often equivocal and often drug companies rely on statistics (as they should ) to draw conclusions. But it also reminds me of an experience i had several years ago. I was on a medication for a fairly short time that had an annoying side effect. My doctor gave me a sample of another drug (brand new) to counter the side effect. I couldn’t tell much difference but when the sample ran out I went to have it filled at the local pharmacy. A 2 week supply was $400 ! I declined the prescription and went home and read the product insert. It turned out the drug was effective in only 1 in 10 patients according to the insert. But that was apparently statistically significant enough to be approved by the FDA. Interesting.

Last, there has been a lot of information recently about the role of the cytokines storm especially with regard to lung damage. Hopefully the drugs you mentioned will be the answer we are looking for. Certainly if they cure a high percentage of patients they will hopefully be widely available and used. But what would constitute a high percentage? 100%( miracle drug), 80-90 % (great drug), 10-20% (still very useful). Actually I would think they sound very promising. Let’s hope!

Mark

Slowpoke
Slowpoke
7481 posts
expert
Apr 11, 2020 - 4:07 PM in reply to Mark

Hi Mark-

Thanks. I do find it interesting and informative.

Due to family history,I keep track of oncology publications, via the Elsevier web site.

The heavy reliance on statistics so often reported in the results from clinical trials is a problem, in my opinion. Not that I have any answers to the problem. Maybe ability to choose what is best for a person via genetic analyses is staring to do that job...it seems to be in breast cancer....hormone receptor positive or negative...

You have made the point exactly.

<<"It turned out the drug was effective in only 1 in 10 patients according

to the insert. But that was apparently statistically significant enough

to be approved by the FDA. Interesting.">

In that Ranitidine study, at first glance, 40 % of the patients have some feature that made the drug effective, 60% did not. Not an unusual results in small studies...which may or may not be replicated as larger studies are done. So, the drug may never achieve FDA approval for treating that particular disease. However, your 10% example makes me hopeful that the FDA may indeed be able to see past statistics if there is a real need for the drug.

If I had zero chance of being cured of a fatal disease by any "usual" therapy, I'd believe that a drug that gave 40% success would be worth a try. Or 10%. I think the hopes for hydroxychloroquine that is getting so much press is in that category.

But, 40% of that Ranitidine study got well in a fashion that implies that the drug made no difference. and, another perspective is that 20 % died.....

How is physician in the front lines to decide whether to try Ranitidine on a patient? What test can she do to guide the decision? I don't know if one exists, or is being developed based on that clue, plus knowledge of the mechanism by which Ranitidine usually works. . .. Or, for that matter, how can a government official or television reporter with no medical training even begin to make a choice?

Here is an example for hydroxychloroquine -

<<"Patients who are genetically deficient in a certain enzyme, called G6PD, can develop a severe anemia resulting from the rupture of red blood cells.">>

And, you know about the potential for eye damage.

I'm glad I'm a chemist. We are usually able to isolate our variables when we carry out experiments, and we usually have some idea what variables to examine.

Meanwhile, in Connecticut, there are faint hints that the rate of appearance new patients needing hospitalization is maybe possibly hopefully leveling out. And, so far, apart from the shoreline suburbs near NY City, the hospitals are not running out of capacity. Yet. Friends in Switzerland have said that to me about their situation, too.

Slowpoke

Last modified on Apr 11, 2020 - 4:15 PM by Slowpoke
Maloja Snake
Maloja Snake
54 posts
active member
Apr 11, 2020 - 4:59 PM

I appreciate the very interesting, detailed, and considerable scientific analysis. But I have a pure layman's question regarding the study of the efficacy of the drugs discussed.

Is is possible to do drug efficacy analysis on Covid 19 (a completely new human virus emerging in the last few months) before knowing population testing results (both kinds) or at least sample results that could be statistically projected to larger groups. For example, do we have any idea what percentage of people contract and survive Covid 19 without knowing it; ie asymptomatically? Wouldn't we need this knowledge prior to doing any effective drug testing?

Last modified on Apr 11, 2020 - 5:01 PM by Maloja Snake
Slowpoke
Slowpoke
7481 posts
expert
Apr 11, 2020 - 10:12 PM in reply to Maloja Snake

Hi Maloja Sake-

Glad that you are enjoying our conversation.

I'm just trying to get a sense of the possible paths forward on the cure for the virus itself + immunization + treatments for side effects, etc.. That for guidance on when partially or unrestricted travel might begin. Mark's perspective as a practicing physician is extremely valuable for me because, as I noted before -

"A little knowledge can be dangerous."

<<"Is is possible to do drug efficacy analysis on Covid 19 (a completely

new human virus emerging in the last few months) before knowing

population testing results (both kinds) or at least sample results that

could be statistically projected to larger groups. ">>

I certainly don't know the answer. However, I think that the answer is "Yes." You may question my credentials, of course. They are a bit thin.

I do know that this virus is only "new" in the sense that there is apparently no native immunity in the majority of the population, as exists for some other viruses. However, it is in one sense not a completely new virus causing disease in humans and animals.

This well written article offers a useful perspective on the point of novelty, and on the last sentence of your questions, as well:

www.niaid.nih.gov/diseases-conditions/coronaviruses

<<" For example, do we

have any idea what percentage of people contract and survive Covid 19

without knowing it; ie asymptomatically? Wouldn't we need this knowledge

prior to doing any effective drug testing?">>

In theory, one can argue it would be required. But,that is a purist's approach. The best question, IMHO, is-

How well we can do with only partial information?

That data base is certainly growing rapidly, by the way.

I'll add an opinion purely as a layman in medical issues. I speak as a scientist, a discipline in which I worked at chemical research and development at a professional level. And, although no longer gainfully employed in that work, I still have a useful perspective on creation of "new" technology. Even after I'm retired.

Just as engineers can design and create things without perfect knowledge of all of the fundamental aspects of the needed technologies, some of which knowledge may not exist, I submit there there is enough relevant knowledge to get started effectively on this problem. I'd like to have that opinion refined or refuted by anyone more knowledgeable in the field than I.

Since the time for results of tests is measured in days or weeks, not just in months or years, a lot of knowledge-based empiricism can be quickly applied, tested, published, tested again, and discarded or pursued. The various studies mentioned in this thread testify to that belief. The gold standard of statistically valid large double blind studies with perfect test equipment may well be involved for a "final" solution. But, a less than perfect solution can be sufficient. In my opinion.

You are certainly correct that the best way to understand results is to have testing. Chemists are lucky...they have that luxury, in general. Physicians may have to practice without it. In this Covid-19 case, excellent tests suitable for clinical research already exist. Further, Abbott Labs - a substantial and highly capable provider of lab test technology - has commercialized a kit for use with the existing installed base of their test equipment. Also, they have introduced a faster test/kit/apparatus, that can give results in 5 minutes or so, and more thorough results in 15 minutes or so. Even though this is not suitable for mass screening of thousands of patients per day or hour...not enough of the equipment, yet........patients in trials can be tested frequently as therapies are tested. (That is being done in the tests of off-label drugs such as the much-hyped hydroxychloroquine). They were being deployed in Asia and Europe while the USA was failing at developing its own test. [In that case it seems that the initials NIH stand for "Not Invented Here" syndrome instead of "National Institutes of Heath."] Specifically apropos your question, two serological tests also have been announced that allow determination of whether a patient has been exposed to the virus. That helps answer your question, too.

And, the symptoms of a case of the Covid-19 disease can certainly be observed often in patients of normal good health, once they have the disease. Most of them survive, possibly needing supportive therapy, some without hospitalization. Even if there exists a percentage of asymptomatic people ( many of whom have been shown to eventually develop symptoms), they can be treated with a test drug and tested to see if the viral infection is eliminated. Tests exist, and I believe that are available in sufficient quantity for that purpose. That narrow purpose needs less testing capability than does mass screening...which , as you imply, is also needed eventually ( or sooner). So, to answer your last question, with limited knowledge of the specifics, I still believe that practical success can be achieved by the methods in place, or coming into place. Eventually, more tests will add to the precision, but there are enough now to do the clinical trials...as far as I can tell from my reading. I'm a layman in medical issues, remember.

To summarize, there are two kinds of needs for test. Small volume for clinical trials (which I believe exists, and large volume for mass screening ( which as been delayed more than it should be). The distinction is meaningful.

The part of this situation that particularly worries me is the group of patients whose immune symptoms become overactive, as the body "fights' the virus, and consequently die of autoimmune destruction of vital organs. ( Hydroxychloroquine and the IL-6 blockers being tested are aimed at curing that category of patient). Other patients die of bacterial infections (such as some kinds of pneumonia) that would normally be treatable with antibiotics, but whose immune systems cannot help contribute to a cure.

Those are deaths that are not caused by the virus infection, per se. And, if a population known to carry the virus (even if asymptomatic) is treated empirically, and a high percentage survive, especially in the class of patients with compromised immune systems, that in fact that is a success. In the Ranitidine trial mention by Mark, about 30% were cured quickly, a bit less than 60% had normal progression, and about 15% died. Although Mark did not say, I am sure that people chosen for that study were all clearly infected and had symptoms of the infection and/or positive tests for the virus, in order to be allowed into the study.

So, in any trials of a population that test positive for the presence of the virus result in zero deaths ( or as Mark pointed out "few" deaths), or normal progression of the viral infection or its consequent symptoms/ conditions is arrested in "most" , that is a success. How much is enough? Opinions will shift as success approaches.

Compared to what I have seen in chemistry, there is a lot of empiricism in medicine, and it works. Medicine is an art, as well as a science. And, there are a lot of knowledgeable and motivated people working on the problems. I don't lack optimism about eventual success,which will followed by years of greater understanding arising from all of the studies - fundamental or empirical. It will help get ready for the next one. I'm just hoping that the systems get in place to allow safe travel/normal life for old people like myself. In simple terms, that means that a cure is readily available wherever I happen to be. For a start, I'd like that to be Connecticut, New Hampshire (relatives), a small part of Massachusetts ( the highway between those other two states). Then Switzerland, and airline routes to and from.

The broader social issues will have to be solved, as well...probably means a vaccine, as you have discussed.

Slowpoke

Last modified on Apr 11, 2020 - 10:30 PM by Slowpoke
Slowpoke
Slowpoke
7481 posts
expert
Apr 12, 2020 - 12:04 AM

Added for Maloja Snake..

One more thought. As a philosopher, you know a specific definition of Empiricism.

In fact, practice of the so-called scientific method, beloved by laboratory scientists, and as as used routinely in my work as a chemist, actually falls within the classical definition of Empiricism, as espoused by Locke, Berkeley, and Hume.

So, maybe in that sense, scientists and physicians are not so far apart. ;-)

Words...

Slowpoke

Mark
Mark
544 posts
top member
Apr 12, 2020 - 12:41 AM

Hi Slowpoke and Maloja Snake

In response to Maloja Snake’s question regarding the need for more information on asymptotic subjects to evaluate drug and treatment efficacy, I would say that’s not too important. Data on asymptotic patients is necessary to accurately evaluate prevalence (how many have the disease at any given time). Prevalence is important to predict the spread of the disease and thus the resources that may be needed. It is also essential to get accurate morbidity and mortality rates (currently the prevalence is probably much higher than reported which would make the morbidity and mortality rates lower). However the question of treatment efficacy is a different matter. Those who are asymptotic or only have mild “cold like” symptoms don’t need any treatment (quarantine is not really a treatment) and efficacy for them is immaterial. Those with more severe “flu like” symptoms but that will eventually fully recover may benefit from treatment making the course of the disease shorter and milder. For them efficacy is important but not critical. But for those with severe , life threatening symptoms that require hospitalization and perhaps ventilator intervention then treatment efficacy is critical (life or death). So really it is only the treatment success in these last 2 sub- groups that matter. In this last group almost any improvement over baseline no matter how small would be welcome and lifesaving. Of course what is “baseline” or the natural course of the disease in those more severely affected is a critical piece of information. That is answered by placebo studies. Of course that’s the rub. If my wife has severe symptoms that may progress to death I don’t want her getting a sugar pill. I’d want her to get the Plaquinil or whatever the doctor’s best guess would save her life. This kind of dilemma comes up all the time in evaluating cancer drugs. Widespread testing for the Covid 19 disease will help answer several questions but I don’t think it critical in treatment evaluation except to confirm they have the disease and possibly if they’re immune after recovering.

Slowpoke brings up a somewhat different topic in genetic testing and manipulation. It could very well play an important roll in this pandemic, I just don’t know enough to comment. I am very aware of how important and exciting it is in the field of oncology (cancer treatment). My wife was diagnosed with breast cancer 3 years ago. Hormone receptor testing and genetic patient testing have been around for a while and are critically important. But a much newer and still ongoing area of research is genetic testing on the tumor itself. The MindAct study had been out less than a year but the specific tumor genetic test it analyzed showed chemotherapy would improve her outcome only 2%(98% cure vs 96%) So no chemotherapy was needed. Just 1 year prior she would have been strongly advised to have chemo. There are multiple studies like this ongoing in just about every type of cancer and I firmly believe it will revolutionize the treatment of cancer.

For doctors and other medical personnel (and laypeople as well) the most respected source on cancer diagnosis and treatment is nccn.org (national comprehensive cancer network). I have found the multidisciplinary approach to be very current and informative on all types of cancers (although it can be somewhat technical). The exception to this is I tried to get a feeling for the benefits (or lack of)proton beam therapy for prostate cancer (I’m ok now but after all i am 67 yo). If you get 5 urologist in a room you’ll have 6 different opinions on this subject. It is a quagmire of different opinions from some very smart people. Of course there is A LOT of money involved for both sides. Perhaps I’m too cynical but I’m suspicious that may play a roll.

Sorry I got way off subject but my social calendar is empty and I have a lot of free time !! Mark

Slowpoke
Slowpoke
7481 posts
expert
Apr 12, 2020 - 9:52 AM in reply to Mark

Hi Mark, and Maloja Snake-

Mark wrote :

<<"Of course if I was in respiratory failure I would want to try Plaquinil

or Azithramicin. But it quickly becomes complicated. What dose? How

long? At what stage?When to stop? Did I get better or worse because of

the drug or just the natural course of the disease? My livers dead, was

it worth it now that I need a transplant? Well you see what i mean that

it can get complicated. It is also a balancing act. The inflammatory

response is necessary to fight Covid-19 so you can’t eliminate it.

Rather reduce the harmful aspects in the lungs and leave the rest

intact. Not so easy.">>

This article in the Lancet directly addresses those issues:

www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext

Among other comments, it notes, as you commented:

<<"As during previous pandemics (severe acute respiratory syndrome and Middle East respiratory syndrome), corticosteroids are not routinely recommended and might exacerbate COVID-19-associated lung injury.7">>

Appropriate therapies are discussed. The implication for me is that there are existing therapies known for the "cytokine storm " condition. Although not exactly answering Maloja Snake's questions, it makes clear that this "new" virus has precedents, which offer guidance for tackling COVID-19.

FYI, Elsevier has started a weekly journal abstract service focusing on COVID-19. I found it when the oncology abstracts page that I subscribe to arrived today. In this edition, several relevant articles about COVID-19 in the Lancet are referenced.

The link is terribly long, and seems to involve my e-mail. So, if you care to go further, a search of the internet might be a useful exercise.

Slowpoke

Mark
Mark
544 posts
top member
Apr 12, 2020 - 12:54 PM in reply to Slowpoke

Hi Slowpoke

i have been mostly using the website Doximity to try to keep up to date. It is geared towards health care professionals and in regard to Covid 19 it accesses articles from a number of sources. I noticed of the articles today on Doximity about half were from the Lancet.

Mark

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