Determinants of persistent symptoms after treatment for Lyme borreliosis: a prospective observational cohort study 2023 Vrijmoeth, Knoop et al

Summary
Background
Patients treated for Lyme borreliosis (LB) frequently report persistent symptoms. Little is known about risk factors and etiology.
Methods
In a prospective observational cohort study with a follow-up of one year, we assessed a range of microbiological, immunological, genetic, clinical, functional, epidemiological, psychosocial and cognitive-behavioral variables as determinants of persistent symptoms after treatment for LB. Between 2015 and 2018 we included 1135 physician-confirmed LB patients at initiation of antibiotic therapy, through clinical LB centers and online self-registration. Two reference cohorts of individuals without LB (n = 4000 and n = 2405) served as a control. Prediction analyses and association studies were used to identify determinants, as collected from online questionnaires (three-monthly) and laboratory tests (twice).
Findings
Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms. The primary prediction model correctly indicated persistent symptoms in 71.0% of predictions (AUC 0.79). In patients with symptoms at baseline, cognitive-behavioral responses to symptoms predicted symptom persistence. Of various microbiological, immunological and genetic factors, only lower IL-10 concentrations in ex vivo stimulation experiments were associated with persistent symptoms. Clinical LB characteristics did not contribute to the prediction of persistent symptoms.
Interpretation
Determinants of persistent symptoms after LB were mainly generic, including baseline functioning, symptoms and cognitive-behavioral responses. A potential role of host immune responses remains to be investigated.

Determinants of persistent symptoms after treatment for Lyme borreliosis: a prospective observational cohort study - eBioMedicine (thelancet.com)

 

"No evidence was found for microbiological or LB-specific clinical determinants of persistent symptoms, but an association of host immune responses with persistent symptoms was observed."

No evidence at all? None? With close to 300 Lyme patients?

I'd have thought there might be some somewhere along the line .


"Main predictors of persistent symptoms were baseline poorer physical and social functioning, higher depression and anxiety scores, more negative illness perceptions, comorbidity, as well as fatigue, cognitive impairment, and pain in 295 patients with persistent symptoms."

They place social functioning, depression, anxiety, and negative illness perceptions before mentioning pain, cognitive impairment and fatigue.

 

It's kind of missleading to call it prospective. You cannot obtain reliable baseline data for someone who is already sick, what they have measured might as well be correlated to the severity of the infection. Looking at table 3 in the paper, both use of anti-inflammatory drugs and physical functioning points toward preexisting somatic conditions being a risk factor, but there is no mention of the fact that depression and anxiety may as well be a function of exactly that. Nothing about the fact that 'illness-beliefs' may as well be quite rational, based on experience.

In the discussion they write:

"The association of depression and anxiety scores with persistent symptoms after LB does not prove a direct relation, but rather indicates that psychological distress from any origin may be accompanied by long-lasting symptoms.". Which I presume is just a game of syntax and semantics to pass the peer review, while still leaving the reader with the impression of a causal relationship between the two.​

This part is quite interesting, and sort of undermines the usual inference of psychology being the master volume knob:

"We analysed a subgroup of patients who self-attributed symptoms during follow-up to LB, and found association with a MBL polymorphism, a C-type lectin involved in complement activation after pathogen recognition. MBL2-deficiency in mice has been associated with a more severe course of various infectious diseases..."​

and

"Polymorphisms in MBL and two IL-1β promotor genes,39,40 and disseminated LB were significantly associated with attribution of persistent symptoms to LB.".​

It's almost as if a BPS large language model has been fused with a biomedical one, still giving the BPS part more weight in setting the tone, always having the last say.

 

This seems very confused. Their definition of having persistent symptoms is:

This looks very broad, so of course it would be associated with baseline symptoms. And as @sneyz says, the baseline isn't even a baseline, it's while they are receiving antibiotic treatment for acute Lyme. So people who were sicker initially were more likely to be sicker later. And of course people who had pre-existing lower functioning scores were likely to be sicker later too.

 

The primary determinant should be having clinically demonstrated LB. If you're going to talk causes of persistent symptoms, first order of business is being able to prove, unconditionally, Lyme and/or its co-infections (which can cause similar sequelae) have been eradicated - this in order to rule out continued infection.

Until you unequivocally can do that, you're potentially just chasing windmills. Or being perceived as enjoying sleight of hand. Or biased.

The TBD medical world straddles a gaping split, and like Congress, it's dysfunctional because of that schism. It's not hard to figure out which side of the aisle researchers sit.

This is worse than grinding to a standstill.

FFS, why are they biopysing EMs?

 

Studies like this don't seem for me to be so much about science as they do churning out party-line rhetoric.

Anybody here who's familiar with typical Lyme symptoms, check out Table 2 Baseline Patient Characteristics and see if that might be coming up short.

And what does this even mean?:
"Determinants identified in patients treated for physician-confirmed LB were assessed in a separate cohort of 65 patients who at baseline reported chronic (≥six months) symptoms of unknown origin that were attributed to LB, without clinical or laboratory confirmation. Criteria for persistent fatigue, cognitive impairment or pain in the one year after enrollment were met by 80.7% (46/57) of patients. Random forest analysis in this cohort lacked a clear ranking of importance (pmc 0.47, sensitivity 0.48, specificity 0.73), probably due to low numbers. The only significant association with persistent symptoms was absenteeism from paid work at baseline. Therefore, comparison with the primary analysis in patients with confirmed LB was deemed inappropriate."

So at baseline they'd had symptoms for at least 6 months? The only significant association with persisitent symptoms with, what, fatigue. cognitive impairment or pain, was too sick to work at times? And if these patients were physician-confirmed, isn't that clinically confirmed? Were there no labs performed at all (if so, what were the particulars since these can matter)?

I can go on, but seriously, to me this feels just like a school exercise to catch a glimpse of BPS expression. How do such field trips help Lyme patients?

 

It's pretty much 9 parts medical theology and 1 part medical politics. Science doesn't factor in at all. Even by the standards of political science it's excessively biased. Party ideology is the only proper framing for this, this stuff doesn't even get published in political science, it's for party faithful.

The fact that you can get 'prospective' and 'baseline' through a journal in a paper of acute patients is just beyond silly, let alone how every single "affect" and "mood" and "belief" they ascribe here is fully consistent with the misery of being ill. Medicine truly has learned nothing useful about illness and the journals play a significant role in it. Only disease matters, they know nothing about illness. It's just baffling.

 

Enough of them know better. It's not all blind filial chanting.

Although this study comes close, in my estimation.

If you research Lyme, truly study its landscape for a long time, you realize there are no pat answers yet about persistence. That is criminal after more than 40 years. It's a pathogen! In my country hundreds of thousand are being infected each year. Between 10 and 20 % stay sick, even with some kind of treatment.

Irrespective of that fact, if you immerse yourself in Lyme, you know nobody knows. Efforts like this study seem to presuppose they know something. That's dangerous in general. In cases like this, it could be incredibly detrimental to finding out what's actually happening. Worse, it could be damaging to how literally millions of patients are perceived and treated by the greater medical community..

No one should claim to research Lyme if they cannot pass Lyme 101. And Lyme 101 says everything is moot until we prove the spirochete is gone, remnants and all. Pretty much everything else is posturing, taking a side, or trying to capitalize on the disease and those it claims.