Lorima: In view of your extensive and intimate experience in dealing with patients with Lyme disease and your distrust of 2T testing, what would be your enrollment criteria for a clinical study on the benefit of a specific treatment regimen for early, disseminated, late Lyme disease, or chronic Lyme disease ? Please guide us through that process. And, please be as specific as possible in defining the patient cohort.
Duncan: You may help Lorima out and join in if you wish.
My Lord! Henry, this is about as zany a response as I've seen in quite sometime.
So, if I watch a plane crash, and the same model plane crashes 25% of the time, and if some of its victims are family members of mine, and I say there is something terribly, dangerously wrong with that plane model - your response to that is: Well, if you don't like it, build one of your own?
Yes, that's about the size of it.
It's absurd to expect Duncan and me to produce a specific clinical trial enrollment protocol in two days - or even two months.
A lot of preparation would go into it, including having discussions with clinicians who see a lot of late LD patients along with their complete Western blot and other test results, and discussion with a lot of their late LD patients who have lab documentation. Then I'd want to talk to some smart non-LD-involved neurologists and psychiatrists, in both high and low endemic areas, to see what signs and symptoms they see, in patients with illnesses that are puzzling and have required resort to "diagnoses of exclusion" or a psychiatric interpretation of "medically unexplained symptoms." I suspect it would not be too difficult to generate a list of some stand-out, fairly unusual signs and symptoms worth including.
The literature on diseases which have neurological signs and symptoms is vast, but it would have to be surveyed by unbiased and insightful readers, to look for clues, and to be aware of all current diagnostic categories that overlap with LD, and to evaluate which ones seem well-grounded in physical reality, and which ones are make-do descriptions cobbled together so neurologists can say something, anything, to their patients with conditions that are currently not understood. There are plenty of idiopathic (cause not known) conditions, in medicine, and there are a lot of story-telling papers with graphs and tables published, that look science-y and evidence-y, but are just provisional categorizing and explanation, used for lack of anything better. I'm not necessarily deploring this; doctors really do have to have something to tell their patients, and names for certain collections of symptoms so they can discuss them with each other. I'm just pointing out that in these cases, there are any number of stories that could be told to serve the purpose, and it takes detailed and critical reading to sort out the relative proportion of spurious, or should I say provisional, assertion in each disease field, which is there for social rather than scientific reasons.
The symptoms and signs on any generated list for signs and symptoms that occur in late LD wouldn't each
be specific to LD. It would have to be one of those lists on which the prospective research subjects accumulate points, that are useful for diseases that don't happen to have one convenient, completely specific marker. This includes a lot of diseases and conditions - which fact speaks to our relative paucity of tools, not to anything that should lead one to question the existence of these conditions. That error is akin to the one called WYSIATI by Danial Kahneman (Nobelist author of Thinking, Fast and Slow
): What You See Is All There Is. But it's worse; the medical version would be What You Can Measure Is All There Is.
I suspect that uncertainty in diagnosis, may apply to a significant proportion of patients with illnesses in the internal medicine field (as opposed to surgery for trauma, say). Anyone over, say, 40, who doesn't know people (not with LD) who have been misdiagnosed for some set of symptoms because of this fact, is not paying attention. The idea that patients typically
present like a contrived true-false, or multiple choice quiz, where there is one right answer and all the others are detectably wrong, is a fantasy. There is a lot of guesswork in medicine. I always chuckle when somebody complains about a doctor using "unproven" therapies, now that I know how iffy the whole process of diagnosis and treatment typically is. It's true that some are proven, and some are more plausible than others. But expecting certainty as the norm, is absurd.
Off the top of my head (which is not how I'd design a clinical trial, or any experiment, despite Henry's quixotic request) bradycardia (slow heart beat) attributable to heart block comes to mind; I personally know three officially diagnosed LD patients who had that. Here's the WebMD link to that:
http://www.webmd.com/a-to-z-guides/hear ... c-overview
It occurs to me that you might want to exclude people over, say, sixty-five from the study, just because of the rise of age-related symptoms. This is unfortunate, because people of retirement age are in a high-risk group due to having more free time to be outside. I'd have to consider the pros and cons of this, carefully.
Multiple peripheral dysesthesias, or radicular neuropathies, with no other discernable cause, also comes to mind, as promising items to list. It might be a good idea to not count "LD suspicion points" for those types of back pain that are so common as to be confounding, like lower back pain, or sciatica, though some of these cases are likely due to LD. Patients with these manifestation would have to have some other, less common, signs and symptoms in addition to the lower back pain or sciatica, in order to be included.
Because late LD is so heterogeneous in expression, the list would have to be pretty long. And you couldn't take the attitude that "subjective" symptoms like numbness, tingling, and pain have to be ignored, because some proportion of patients might be lying or deluded. Our available objective imaging capacities for neurological dysfunction are mostly nonspecific and insensitive, so there is no avoiding listening to the patients about their bodily sensations. Anyone with a degree of mistrust that doesn't allow that, should go into a different field than medicine - maybe mechanical engineering, or accounting.
To me, the political block to doing any realistic LD research (due to the successful spreading of the illusion that LD diagnosis and treatment presents no problem) is far more urgent that designing trials that can never be funded, and that wouldn't be believed even if they were accomplished. As a scientist, I've done original work and made some discoveries, some of which were surprising. But there wasn't a team of people devoted to stopping progress in my field, in order to defend the status quo, as there is in the LD field. In my field, people understood that progress and correction of errors was desirable.
We shouldn't cultivate the illusion that doctors can do clinical trials without the cooperation of multiple agencies and institutions. You can (in fact, Henry, hv808ct, and their team do) block good clinical research, using institutional barriers.
Henry wrote:Duncan: Use what ever criteria YOU deem appropriate to identify patients YOU believe to be eligible for enrollment in the study. I'm asking YOU to identify the patients. WHO has early acute, disseminated, late stage or chronic Lyme disease by the criteria YOU and LORIMA believe is appropriate? You should be able to do this. Who are these patients you and Lorima have been talking about? Who are the ones both of you are trying to help and provide care for?
I take it since you think all currently used diagnostic tests are worthless, you are left only with symptoms. OK, what symptoms are you going to use for enrollment criteria?
Your memory is playing tricks on you again. I never said all serology is worthless, just the arbitrary criteria used to interpret them. How many times do I have to say that, before you get it? Furthermore, in this case, I specifically suggested a possible criterion to use:
These low-IgG patients often have enough, and varied-enough, IgM antibodies specific to Bb, to be identified and diagnosed accurately as having LD. Not by the current arbitrary rules, mind you, but by criteria that are nonetheless ( I would even say more) scientifically acceptable. The argument that IgM is too "sticky" to be used reliably for diagnosis, is an excuse for shoddy technique, in my view. A research lab, if not a commercial lab, would be able to overcome this problem, if it really is a problem.
Henry, I think this recurring memory problem, which may or may not be caused by your desire to maintain your belief system, is interfering with your ability to participate in a meaningful discussion. Demanding that others be specific (which implies that you think they aren't) and then forgetting or ignoring what people have specifically said
in your responses to them, is a waste of time (which may be your actual goal here, I realize - when we're writing to you, we're not writing to the media, etc.) The fact that it is all written down here, and that you could re-read it whenever you forget, makes it all the worse. It's not as if it were an unrecorded verbal conversation and no one took notes.
It reflects badly on you and your team. If you are all this careless and/or confused, no wonder the field is such a mess. It's like a political machine in which only people with certain mental and emotional disabilities are invited to participate.
Then Duncan wrote:
Personally, I would enroll individuals who have a history of an EM, and/or are IgM positive or have two or three bands IgG positive, and are symptomatic, despite treatment. I would base enrollment on that - that doesn't mean others who don't satisfy those criteria don't have active Lyme. I think there is an argument that if someone has even one band positive that is specific to Bb, and are symptomatic, they should be considered for inclusion.
So, we both have suggested specific criteria. These are open to discussion, as you can tell from our tone.
I wrote my original post in this thread because of the suggestion that new trials on late LD patients be done, using the old 5-band IgG western blot as an entry requirement. I think that is unrealistic scientifically, though impossible to avoid at present, politically. In other words, there is a political block to studying late LD except Steere's type of arthritis, and so it's silly to simply call for "more science," until that block is removed.