Conversational appraisal of 'liverdoc's article'

[20/02, 8:33 pm] Dr.Dinesh Datta:(Forwarded from other group) Any ayurvedic practitioner on the group, can you pls throw some light on use of heavy metals in medicines? Is it ok to take under medical supervision? I read somewhere about Ras-shastra and Nagarjuna.
[20/02, 8:33 pm] Dr.Dinesh Datta: But then there are reports of heavy metal poisoning too on Pubmed due to ayurvedic preparations, what is the catch??
[20/02, 8:37 pm] Dr Rakesh Biswas: The catch is in dose optimization! 

Holds true for all drugs be it any system of medicine
[20/02, 8:58 pm] +91 93714 56707: My thoughts: the conventional method of preparing ayur drugs i.e. the ras aushadhis which have metallic content is pretty elaborate...eg soak them in lemon juice for x number of days, or triturate together for x hours...these are primarily for those containing the mercury and sulphur combinations....however in current usage Pharma companies may not be diligently following those methods of preparation...and I am not sure of known methods to test them ...so would take them for short durations rather than longer durations under supervision. And also try to procure them from authentic sources
[20/02, 9:11 pm] Dr. Avinash Nepal UDHC: And sharing true pros and cons data for shared decision making. (Transparency)
[20/02, 9:25 pm] Dr Rakesh Biswas: That's difficult as much of it's missing unknown data
[20/02, 9:27 pm] Dr. Avinash Nepal UDHC: Businesses sell pros hide cons, academicians sensationalise pros and cons and worst of all critical appraisal skills are missing (very low).

Truth remain hidden
[20/02, 9:29 pm] Dr. Avinash Nepal UDHC: @⁨Dr.Dinesh Datta⁩ explore india pharma manufacturing and whitelabelling business scenario for allopathy. It will feel as worst as any pathies.
[20/02, 9:45 pm] Dr.Dinesh Datta: Any articles on it mate?
[20/02, 9:46 pm] Dr. Avinash Nepal UDHC: These things won't come in articles
[20/02, 9:48 pm] Dr.Dinesh Datta: Unless we publish an open access blog on it?
[20/02, 9:49 pm] Dr. Avinash Nepal UDHC: Choose a product for which generic version are easily available in india. look for making it's buisness in your area and enquire for 6 months from various sources. You will find most of details.


For other pathies, anyone can pack anything, make it very high price, do some scam marketing and sell in india.
[20/02, 9:50 pm] Dr. Avinash Nepal UDHC: Regulations are very weak here and consumers are clueless, lack critical appraisal skills to even differentiate between medical information and misinformation.
[20/02, 10:05 pm] Dr. Avinash Nepal UDHC: If you follow liver doc, many of the ayurveda drug related heavy metal toxicity cases are products from big brands of ayurveda. Anecdotal 

We need data to clearly understand the risk. Population based
[20/02, 10:05 pm] Dr. Avinash Nepal UDHC: So even choosing big brands doesn't means safe
[20/02, 10:06 pm] Dr.Dinesh Datta: Afaik,any 'branded' ayurveda is sketchy...

Few resorts like Kairali ayurveda etc,they make the medicine then and there and give it to patient..

However,it's practiced in very less places nowadays..
[20/02, 10:07 pm] Dr.Dinesh Datta: Yea,likely 'convenience sampling' or sampling the liver cases.

We wl have to do a population based data collection/study..

How many using ayurveda and how many getting toxicity and admitted..

And do some biostatistics around the data captured
[20/02, 10:09 pm] Dr.Dinesh Datta: Again,will also have to evaluate how the correlation is found
[20/02, 11:25 pm] Dr. Avinash Nepal UDHC: The liver doc have his own research lab and have published various paper. Invested more than 1cr of his own funds afaik. May be he have published some non-anecdotal evidence/ insights there.
[20/02, 11:31 pm] Dr.Dinesh Datta: Any link?
[20/02, 11:35 pm] Dr. Avinash Nepal UDHC: https://www.theliverresearchlaboratory.com/home/publications
[20/02, 11:40 pm] Dr. Avinash Nepal UDHC: you may need to explore a lil to confirm if this is his lab website or any other. I think it is but I couldn't confirm yet..
[20/02, 11:46 pm] Dr.Dinesh Datta: This website is amazing.
It looks like liver research laboratory in JSS medical college..

Haven't found liverdoc's name
[20/02, 11:50 pm] Dr. Avinash Nepal UDHC: https://scholar.google.com/citations?user=Gz7g05QAAAAJ&hl=en
[21/02, 12:24 am] Dr.Dinesh Datta: Did you read this?
Let's critically appraise this
[21/02, 12:24 am] Dr. Avinash Nepal UDHC: I didn't. sure, go ahead.
[21/02, 7:08 am] Dr Rakesh Biswas: Let me get the ball rolling. Before I critically appraise it let me praise it first along with respect for the DILIgence liver doc has shown.

DILI is off course known to happen with all drugs from modern medicine too (in fact one of the DILI's we published in BMJ with the queen's college elective students in IQ city was named as "No time to DILI dally by them before I changed it). 

Liver doc has thrown better light on what is happening with AHM's too which is a great thing. 

However we need to realize it's not the system of medicine that is at fault but current stakeholders such as AHM pharma etc who may have been unscrupulous.
[21/02, 7:12 am] Dr Rakesh Biswas: How about hosting this journal club UDLCO link onto liver doc's X platform so that he too can see it. 

We were so impressed by an Indian cardiologist in quora that we referenced his quora write up in our BMJ article with the thought that we may be able to share that link in his quora article reply!
[21/02, 8:08 am] Dr.Dinesh Datta: This is a decent article overall..

However we points I've noted are.

1.Retrospectice study design chosen in this study.While a prospective controlled study are preferable for assessing causality and minimalising bias..
2.RUCAM questionnaire shows 59 possible,19 probable and 0 definite AIH.Can also use another questionnaires,like WHO ones etc..

3.
[21/02, 8:09 am] Dr.Dinesh Datta: 3.clinical,biochem and history findings are evaluated and documented..which may provide valuable insights into AHM spectrum but we don't know the heterogeneity of AHM formulations(how do we know if it's due to heavy metals)
[21/02, 8:12 am] Dr.Dinesh Datta: 4.detection of heavy metals through biochemical methods like chromatography/MS used in this paper,raises concerns over product safety and quality.It doesn't establish causal link.

And there's no control arm as well
[21/02, 8:14 am] Dr.Dinesh Datta: 5.most important..
This study uses statistical methods to identify associations with 'clinical variables','histo' and 'outcomes'..Small sample size and multiple comparisons...

Implies high risk for type 1 errors and falae positive findings
[21/02, 8:15 am] Dr.Dinesh Datta: Histopath findings in this article(inflammation,stasis,necrosis etc) are consistent with DILI(there's literature around it)..attributing them solely to AHM overestimates it's risk potential
[21/02, 8:17 am] Dr Rakesh Biswas: The retrospective nature of the study also makes it cross sectional which is more of a weakness when it comes to joining the dots in DILI as one needs to demonstrate causality by showing association (which they have done) and confirming it with experimental reassociation also known as rechallenge, which they couldn't do for obvious ethical reasons.

Interestingly one cluster of modern medical drugs that we mentioned above in BMJ publication pivoted around it's DILI before I added more spectrum to it, actually doesn't cause DILI on rechallenging and is a standard strategy to address the temporary hiccup in that intervention although many patients have died of that acute DILI!
[21/02, 8:17 am] Dr.Dinesh Datta: Primary outcome measured in this article is 'mortality'..Associating heavy metals to mortality rates may need cautious interpretation..As there's no control for confounding variables and other causes of mortality
[21/02, 8:18 am] Dr Rakesh Biswas: Yes while the effect is well described, the cause isn't!
[21/02, 8:21 am] Dr.Dinesh Datta: It's kinda like this..

Study has nice exclusion criteria to mitigate for confounding variables..That itselves may lead to residual confounding and selection bias..other comprehensive data like diet,lifestyle etc hampers potential confounders
[21/02, 8:23 am] Dr.Dinesh Datta: And also the primary outcome measured in this study is 'mortality'.

Like,lol everyone dies..

It oversimplifies liver injury outcomes,morbidity and other functional impairments
[21/02, 8:24 am] Dr.Dinesh Datta: And also..study detected VOCs in AHMs..raising concerns over heparotoxicity..However the results and interpretations lacks contextualisation..as we don't know the threshold for toxic exposure
[21/02, 8:26 am] Dr Rakesh Biswas: Well I wouldn't be very worried about the fact that there is a claim to causal association with limited evidence, in fact I'm willing to accept that it's true. 

I'm more worried about the thin real time clinical audit in our country that allows anyone to simply get away with poor performance when it comes to dose optimization
[21/02, 8:28 am] Dr.Dinesh Datta: Agreen 
Study highlights the importance for dosage optimisation and collab between multiple stakeholders...
Preferably revolving around the patient in transparent way
[21/02, 8:34 am] Dr Rakesh Biswas: Didn't see that earlier! 

That's definitely a plus



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