New: Identification of Additional Anti-Persister Activity from an FDA Drug Library

[Lorima]

Hv, I can't believe that you have hung out on the fringes of medicine for so long, and not perceived this feature of the culture of medicine. You, yourself, never question the LD status quo, and I have no doubt you are being amply compensated for your loyalty (if only by being tolerated, instead of shunned, for your antisocial behavior). It would seem that you fully understand the value of conformity.

But for those who don't, here is one description of what I'm talking about. You can find as many more as you need, to get a sense that this is not an idiosyncratic observation.

http://m.circoutcomes.ahajournals.org/c ... 3/245.full

A Note to My Younger Colleagues. . .Be Brave
Authors
Harlan M. Krumholz, MD, SM
From the Section of Cardiovascular Medicine and the Robert Wood Johnson Clinical Scholars Program, Department of Medicine, Yale University School of Medicine; the Section of Health Policy and Administration, Yale School of Public Health; and Center for Outcomes Research and Evaluation, Yale–New Haven Hospital, New Haven, CT.

snip

When I entered medicine, I did not realize that there was such intense pressure to conform. But we learn early on that there is a decorum to medicine, a politeness. A hidden curriculum teaches us not to disturb the status quo. We are trained to defer to authority, not to question it. We depend on powerful individuals and organizations and are taught that success does not often come to those who ask uncomfortable questions or suggest new ways of providing care.

The sense of danger that we feel when we question authority is not unfounded.

Those who ask difficult questions or challenge conventional wisdom are often isolated. They may find few opportunities to speak and their writings may not be welcome. Compliance with normative behavior may be forced by fear of recrimination. In some cases, junior faculty may fear that support from mentors will be withdrawn or promotions denied.

I have seen evidence of many such efforts to coerce conformity of opinion and behavior. I have heard of junior faculty who were told that questioning key assumptions of the field, even with evidence, would result in threats to funding and support. I am aware of individuals in nationally prominent organizations whose ability to attain leadership roles was stymied when they raised important questions about organizational strategy, while those who were more compliant progressed. I know individuals whose criticisms of popular products made them the targets of industry efforts to undermine their credibility. I have experienced the exercise of power in the spirit of quieting dissent and debate rather than supporting and encouraging it.

snip

[hv808ct]

Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library
Postby Lorima » Sat 16 Jan 2016 3:02

Hv, I can't believe that you have hung out on the fringes of medicine for so long, and not perceived this feature of the culture of medicine. You, yourself, never question the LD status quo, and I have no doubt you are being amply compensated for your loyalty (if only by being tolerated, instead of shunned, for your antisocial behavior). It would seem that you fully understand the value of conformity.

Response 101: attack the messenger, ignore the message.

Still waiting for some examples of IDSA killing off dissidents. Or is this like asking Republicans for historical or contemporary examples of austerity economics pulling a country out of a depression? (Hint: there ain’t none.)

[LHCTom]

Response 101: attack the messenger, ignore the message.

Still waiting for some examples of IDSA killing off dissidents. Or is this like asking Republicans for historical or contemporary examples of austerity economics pulling a country out of a depression? (Hint: there ain’t none.)

The larger problem that is so prevalent is narrow minded Physicians, some researchers and the IDSA in particular for placing all their focus on trying to prove their beliefs regarding conditions like Chronic Lyme WITHOUT actually completing their job and doing a real diagnosis. There is little doubt Chronic Lyme PTLDS and CFS/ME are real but how many actually have something like a chronic bacterial, parasitic, viral or fungal infection not found through half ass medicine! Reminds me of the US Congress competance. If these people would actually solve the problem or even part of it, it would make a huge difference.

Its fairly obvious to anyone with an imagination that there is a large group of millions of patients with illnesses that ruin their lives, their family and is harmful to the overall economy. So in the example of Chronic Lyme, if you are so impassioned that "it isn't Lyme", than WHAT IS IT? If these IDSA Physicians didn't see a patient with years of suffering and run a few tests and say, "everything looks fine, bye", they wouldn't be criticized and would live up to the ethical promise they made in becoming a Physician.

When one compares this insane behavior of IDSA Physicians with competant Physicians who actually complete the diagnostic process, its a joke. There is a long list of infections like Brucella for example that in the chronic form cause symptoms similar to Chronic Lyme. Once a typical IDSA Physician hears from the patient that they think it might be Lyme or have a Lyme diagnosis, they go into autopilot, run a few silly tests and say "everything looks good". If engineers at Apple Computer behaved like that, the iPhone would never had made one phone call and Apple would have failed.

I have a good example in my own experience. I saw one of the top IDSA Physicians in my area who also has strong beliefs regarding Lyme. After hearing my story including very strong Lymph node biopsy results indicating an infectious or autoimmune process, this IDSA Physician ran 8 tests of which 4 I had been tested for before. I asked if he would be ok with testing for Brucella and his response was, "there has never been a case in the United States". So I emailed him a copy of a Georgia study and the California Department of Health (CDPH) that indicated a few hundred cases had been reported in the 2009-2012 period with about 100 in CA. We all know the reported cases often are less than real cases for a variety of reasons including the reluctance of IDSA Physician to test for it or test correctly. You really need to know what you are doing to find a long term chronic Brucella spp., Mycoplasma spp. Fungal or Chlamydia spp. infection. Running an IgM test is a joke.

His response to my email and the CDPH epidemiolgy report was something like "I knew about the CDPH report but there has never been a case in our county or nearby". Well why was he dishonest about there never being a case in the US and then back down to "local cases"? He is the dominant IDSA Physician in this local area and given his resistance to run a $50 test, its hardly surprising no cases have been found locally due to his contribution. He added in probable embarassment something like "but I'll run the test in the spirit of congeniality". Now that's good medicine. I bet hv808ct will defend this while ignoring a mountain of evidence by simply avoiding it.

I feel this example sums it up. This IDSA specialist had no interest in actually diagnosing what was wrong and showed his hand by suggesting adding one more $50 test should be done for congeniality with no regard to the ethics of medicine or competance. If these IDSA Physician 's actually put the effort in to complete the diagnostic process, maybe the wave of undiagnosed conditions like Chronic Lyme or CFS/ME would be partially under control. Instead, they simply feed the problem through their lack of thorougness. Can you imagine if the iPhone engineers forget to provide half the keypad in software, a power connector or using battery with 10 minutes of life? I don't need to explain what would happen. But these IDSA Physicians do this exact same thing. They do a half ass job with no consequences. Sorta like our Congress.

Even the people involved in Chronic Lyme studies by NIH researchers don't get full infectious and autoimmune work ups. Its nuts. There are very few jobs with this level of pay with the possible exception of the US Congress where one can get away with doing a half ass job and get away with it.

[duncan]

I wonder if people in NIH Lyme research studies even get tested for all the possible Bb agents.

Sometimes I wonder if researchers are always really looking all that hard...

I'm not even sure the NIH Lyme team has been consistently dedicated solely and exclusively to Lyme, or even to TBD's - despite an estimated 300,000 cases of Lyme annually in the US alone.

[Lorima]

Hv: "...IDSA killing off dissidents"
You mean, literally killing? Yikes. You've been reading too many Robin Cook novels, for that idea even to have occurred to you. Durland Fish's email that said, "...we are out numbered and out gunned" must have been really shocking to you. I hope you didn't run out to a gun show with a pile of cash to rectify the balance.

This brings to mind another possible clue to your inability to understand people here. Maybe you, and Henry, et al, don't process figurative language well. This might accompany a difficulty discerning, and switching back and forth, between concrete and abstract thinking and verbalizing, as appropriate to the task at hand. I gather this is not an uncommon deficit (in fact, being able to do it well may be an uncommon ability), and it could help explain why you keep misunderstanding what intelligent dissenting patients, scientists, and doctors are saying about Bb infection in the real world, versus your model.

Either way, I would suggest that you (and Henry) consider thinking more slowly and carefully, before firing back your comments. If you have a real inability, I guess that won't help; but it could just be that you aren't slowing down and putting your best thinking into the job.

[LHCTom]

I wonder if people in NIH Lyme research studies even get tested for all the possible Bb agents.

Sometimes I wonder if researchers are always really looking all that hard...

I'm not even sure the NIH Lyme team has been consistently dedicated solely and exclusively to Lyme, or even to TBD's - despite an estimated 300,000 cases of Lyme annually in the US alone.

No. When I first began to try and sort out whether I had Lyme or not by reading studies, one of the first things I noticed was how the Europeans discovered the CDC 2T test based on Bb B31 was not effective in Europe due to their species genetic differences impact on surface antigen dominant epititopes. Then I read they had found 3 common species garinii, afzelii and Bb and another handful of less common species. Then I read that the CDC and US researchers were adamant that Bb WAS THE ONLY SPECIES IN THE US PERIOD! The first thing that came to mind was when Edwin Hubble first realized that the universe contained galaxies and that the Milky Way was not the entire galaxy. Up until Hubble "looked", the other 199 Billion galaxies were "missed"= Oops!

I thought the Europeans were like the Edwin Hubble while the US CDC and researchers were like everyone who didn't believe it and its implications. Every time a researcher has "looked" and found other less common species in the US, the Lyme research community and CDC has jumped all over them claiming they were wrong or it was in ticks but non-humans. But ticks bite humans and one needs to look at humans with the proper tools before claiming there isn't one case missed in the US due to serology focused on one East Coast species while knowing the sensitivity is based on genetics of the surface antigens.

Then I watched in amazement while the CDC and West coast researchers found B. bissettii, B. miyamotoi and other non-Bb species in ticks. But everyone denied it was a problem. Then in 2011, an outbreak in Russia of all places re-taught a long forgotten lesson and suddenly B. miyamtoi was a hot topic and sure enough its infecting humans and just like in Europe, the Bb B31 test doesn't work. Duh! Smart people can be really dumb! But the lesson has not been applied beyond B. miyamotoi. Duh! And the Bm reality has not flowed down to front line doctors with a good test. Just go read the CDC website about "the test is coming based on PCR". PCR does not always work. If there are not a few spirochetes or microbes of interest in the PCR sample, you won't find the DNA fragments. Duh!. Another lesson not well applied based on how chronic infections work.

Then I read the CDC's version of the C6 tests study and heard they had decided its <1% less specificity than the 2T was the basis for not recommending it. When I looked at the list of conditions used to look for possible cross reactivity, it included things like RA but nobody thought to include non-Bb species of Borreliosis or other infections that mimic Lyme symptoms. That's either being really dumb or evil. Probably dumb. If only a handful of the people in the study had B. miyamotoi, B. americana, B. bissettii, Brucella or a long list of infections etc.., that would have swung the specifictity to better than Bb, unless you use semantics to define Lyme and pretend you never heard of the European discovery/realization. This of course is only one issue but its a REALLY OBVIOUS blunder. It would be akin to the US CDC researchers and CDC still denying that the Milky Way was the entire universe.

I've read studies that showed cross-reactivity between any number of other infections and Borrelia surface antigens. But nobody thought to look for other species or infections in people who tested near positive. Its shocking.

Then of course the CDC position is used to educate 10's of thousands of front line doctors who think the CDC 2T is the be all end all rather than realizing its a probability problem and with 360,000 infections ( previously 30,000), even if 1% were a non-Bb species, that's 3600 missed cases. And in CA, the ratio of just Bb to Bm is in the 1/4 - 1/2 range in ticks. So maybe the low Human occurence on the West Coast has something to do with the Rocky Mountains causing a genetic barrier and even Bb strains are sufficiently different to lower the CDC2T test senstivity, forgetting that B. bissettii and B.miyamotoi are found here regularly plus others. Its like when Hubble saw M31 and everyone decided there were 2 galaxies in the Universe missing now only 199.999...Billion. If there are 2, maybe there are 3 and then maybe 4 and on and on.... Missing even 1000 patients is not ok!

So, now onto my own personal experience. There is this IDSA physician who wrote in a local medical magazine and said to me personally, we ( not sure who we is) have not seen one case of Human B. miyamotoi in CA. He did not realize his own lack of testing or "looking" was the probable reason given its been found infecting US and Eurasian people once they actually "looked" properly. In CA, the ratio of Bb to Bm in ticks is higher than in the other places where human infections have been found. As yet, there is not a "good" serology test for Bm except one used for Relapsing Fever but Bm is halfway between RF and Bb genetically. Its not clear its a good test at all. And PCR requires you catch it during the febrile period near the beginning of the infection and not later chronic stage. If you intentionally use a poor telescope, you will think M31 is a star not another Galaxy.

The NIH researchers use very poor telescopes to study Cosmology and are almost 100 years behind. And this is just the Lyme and genetic changes in strains and species and doesn't count the many issues including other infections that can mimic chronic Lyme as I've mentioned before. Its just bad science. Even Einstein couldn't accept the Universe wasn't steady state and expanding or might eventually contract and denied Quantum Mechanics even though he laid the foundation in the 1905 paper for which he received a Nobel Prize. But he was near the beginning while the CDC and Lyme researchers have no shortage of facts and knowledge from which to see the obvious. And the front line doctors are the blind being led by the blind.

Its so sad. Maybe they should bring in some forward looking scientists or at least tell doctors to use an algorithm that works better.

[hv808ct]

Re: New: Identification of Additional Anti-Persister Activity from an FDA Drug Library
Post by Lorima » Sun 17 Jan 2016 0:35

Hv: "...IDSA killing off dissidents"
You mean, literally killing? Yikes. You've been reading too many Robin Cook novels, for that idea even to have occurred to you.

Response 101: attack the messenger, ignore the message.

Still waiting for actual examples of how the IDSA ruined the careers of people who disagree with their policies and practices, which in this case I take to mean treatment guidelines.

[Henry]

Lorima: Your account is science fiction at best, but most likely the delusions of a sick mind. Would you please provide us with some background information on your scientific credentials. Are you a lab tech with training in molecular biology, or a PhD scientist with research experience, i.e., original scientific publications? If the latter, were you the victim of the types of behavior you refer to, or were you just not good enough to get an NIH grant and therefore blame it all on the "establishment" ? Why should we believe that you are so right and everyone else so wrong? I think that is a fair question to ask?

[LHCTom]

Henry and hv088ct,

What are your credentials besides being crude Donald Trump-like goons who enjoy attacking people trying to help while not lifting a finger to detremine what is going on while hiding in the shadows. If you are so sure you are right, tell us your credentials and provide real science-like analysis rather than behave like spoiled children. If you are so right about Lyme not being persistent, then how about trying to sort out what is wrong with people. Don't bother claiming its in their heads as that is a BS cop out and in the same league as climate deniars. I suppose you blame Islam for Lyme and think refugees are bringing it in - right .... Donald Trumpites goons!

[Lorima]

Henry, you seem to have mistaken Dr. Krumholz's observations for my own. I chose to quote him because I thought he had the kind of credentials you and Hv would respect. I will go look for other medical academicians of similar eminence who have made the same points, and post a few more examples, just in case that will get through your denial. I will post Dr. Krumholz's observations again, so you can read them over carefully and think about how they explain the failure of LD science to correct itself, as science is supposed to.

snip

...here is one description of what I'm talking about. You can find as many more as you need, to get a sense that this is not an idiosyncratic observation.

http://m.circoutcomes.ahajournals.org/c ... 3/245.full

A Note to My Younger Colleagues. . .Be Brave

Authors
Harlan M. Krumholz, MD, SM
From the Section of Cardiovascular Medicine and the Robert Wood Johnson Clinical Scholars Program, Department of Medicine, Yale University School of Medicine; the Section of Health Policy and Administration, Yale School of Public Health; and Center for Outcomes Research and Evaluation, Yale–New Haven Hospital, New Haven, CT.

snip

When I entered medicine, I did not realize that there was such intense pressure to conform. But we learn early on that there is a decorum to medicine, a politeness. A hidden curriculum teaches us not to disturb the status quo. We are trained to defer to authority, not to question it. We depend on powerful individuals and organizations and are taught that success does not often come to those who ask uncomfortable questions or suggest new ways of providing care.

The sense of danger that we feel when we question authority is not unfounded.

Those who ask difficult questions or challenge conventional wisdom are often isolated. They may find few opportunities to speak and their writings may not be welcome. Compliance with normative behavior may be forced by fear of recrimination. In some cases, junior faculty may fear that support from mentors will be withdrawn or promotions denied.

I have seen evidence of many such efforts to coerce conformity of opinion and behavior. I have heard of junior faculty who were told that questioning key assumptions of the field, even with evidence, would result in threats to funding and support. I am aware of individuals in nationally prominent organizations whose ability to attain leadership roles was stymied when they raised important questions about organizational strategy, while those who were more compliant progressed. I know individuals whose criticisms of popular products made them the targets of industry efforts to undermine their credibility. I have experienced the exercise of power in the spirit of quieting dissent and debate rather than supporting and encouraging it.

snip

my emphasis added

Do you think Dr. Krumholz is "sick" or a frustrated academic? Look at his PubMed record.

As for me, I have been almost embarrassingly successful in my scientific career. I'm sure that contributes to my confidence, in analyzing the LD literature and pointing out that the emperor has no clothes. I'm not hesitant to dig into the data, and unwarranted conclusions and misleading titles and abstracts tend to leap out at me. I usually get things right, when I put my mind to a problem. I've even developed a few new techniques; nothing earthshattering like PCR, but enought to get a lot of citations to the papers where I've described them.

At the same time, I recognize the role of luck and fashion. Part of success in science comes from intuiting what the hot subjects are, working on them, and discovering new things one jump ahead of the competition. (If one is too far ahead of the field, one is likely to be dismissed as a crank.) I didn't intentionally "conform" to the scientific fashions of the day, but in retrospect those fashions helped me out, and obviously I was attuned to the fashion cycle, you could say. For example, I was "promoter-bashing" and "grinding and binding" before those experiments became cliches, and by the 1990s I had moved on to another field, and cloned a molecule, using an original technique, that became the basis of a drug now on the market.

So, like Dr. Krumholz, I am not a frustrated academic who has trouble getting grants. I am merely aware of how the culture of science, especially medical science, is different from the naive version we all got taught in high school. The Lyme disease fiasco made me sit up and take notice of how destructive this culture of conformity in medicine can be. I'm not quite sure how you and Hv avoided gaining that awareness, though I do suspect that neither of you has ever headed an academic lab, and that you both had careers as government bureaucrats. Which culture is very different, but probably even more insistent on conformity.

Edited to add: I have a PhD in Cellular and Molecular Biology. You should know this from our previous conversations, but I do realize your memory is not very good. I don't blame you for that particular failing, as it is common in old age, though it does mean you should take extra care, and look things up, before posting.

BTW, I think most of the LNE regular posters with LD are at least as smart as I am. It is a privilege to be part of this group.