Sunday, September 14, 2025

UDLCO CRH: A leaf out of the history of Palliative care and the history of medicine that cures sometimes and cares always

Summary:


The discussion explores the role and perception of palliative care in modern medicine, focusing on its integration, commercialization, and importance as a medical specialty. Participants debate whether palliative care should remain a distinct specialty or be integrated into general medical practice. Ethical concerns, cultural perspectives, and the historical essence of "doctoring" are also discussed.

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Key Words
- Palliative care
- Advanced care planning (ACP)
- Empathy and compassion
- Preventive oncology
- Commercialization of healthcare
- Specialization in medicine
- Fee-for-service model
- "Cure sometimes, care always"
- Cultural perspectives on healthcare

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[14/09, 18:13] hu1: https://forms.ple/xyz

Hello Everyone! My name is . I'm a psychologist working in the Department of Palliative Care at xyz Cancer Hospital and Research Institute, some city. I am currently doing a study on *Knowledge, Attitude and Perceptions of Non- Palliative Care physicians on Advance Care Planning in India*. If you're a *medical professional* with a minimum qualification of *MBBS* and are currently *not working in the area of palliative care*, kindly take some time off of your busy schedule and fill the following form. I promise it won't take you more than 15-20 mins. Please feel free to contact me on xyz@gmail.com for any further queries!
Thank you in advance!

[14/09, 18:13] hu2: Kindly spare some time and fill in your responses. This can help us understand the awareness of "Advanced care planning" in non palliative physicians across all specialities and later help us in developing focused training sessions. (To avoid futile interventions)

[14/09, 18:25]hu3: Done. Nice initiative. I feel it is important to sensitize people on ACP. All the best. Thank you.

[14/09, 18:25]hu1: Thank you sir for your time and comments🙏

[14/09, 18:26]hu2: Request everyone to kindly spare some time 🙏

[15/09, 06:43]hu4: Palliative care is a neglected field of health care. It is future speciality. Good initiative. Requires awareness amongst not only medical people but amongst public nd administrators.
Need to motivate to develop into a subspecialty so that qualified  persons would be involved.

[15/09, 06:54] hu5: I beg to differ...

Palliative care is a bit over rated.

All specialists, as well as non-specialists can learn palliative care relevant to their speciality.

Like most western concepts, allopathy profits by institutionalising even death and dying!

Until we discard the term palliative, this speciality will not prosper...

Frankly, it should integrate from day one..


[15/09, 06:58]hu4: Yes,
Palliative care as projected now is a commercial concept. True palliative care is empathy compassion dedicated selfless service

Hence should be encouraged in a slightly different format

[15/09, 06:59] hu4 : Well the term palliative requires to be correctly defined.

[15/09, 08:16]hu6: The word "palliative" is derived from the Sanskrit "pallava" which means "leaf"! Perhaps because many wounds would be palliated by leaves those days?




This word was taken to Latin land where they used the term later for "covering up" that became synonymous with doctoring (as in your documents have been doctored)! 

Palliative care is nothing but the original essence of doctoring and it's slogan is to "Cure sometimes, care always"



[15/09, 08:17]hu5: చేతులు కాలిన తరువాత ఆకులు పట్టుకుంటే ఏమి లాభం!

[15/09, 08:18]hu4: But where r we? Cure and care revolve around money.
Need to come out of business approach to health care

[15/09, 08:53]hu6: నివారించ లేని ఘటన గాయాల కు,  
ఉపశమనం ఆకుల తోనే సాధ్యం

What cannot be prevented needs to be palliated

[15/09, 08:59]hu5: కాలిపోకుండా నివారించడం ముఖ్యం...

ప్రివెంటివ్ ఆంకాలజీ

[15/09, 09:19]hu6: చికిత్స కంటే నివారణ ఎప్పుడూ మెరుగైనది

కానీ సంఘటనలు జరుగుతున్న వెంటనే  

జాగ్రత్త ఎప్పుడూ, చికిత్స కొన్నిసార్లు

[15/09, 09:30]hu2: Good morning sir. I dont understand how you felt it is over rated. Most medical professionals are unaware of this speciality still. While it is true that every physician should know how to palliate their patients, are they doing it? As some one who has done a superspeciality in anaesthesia, I have shifted my field into palliative care totally, I have realised how little we are doing to patients. There is a abundant need and the necessity for us to acknowledge it

[15/09, 09:31]hu2: We are not commercialising it. We are asking fee for our service

[15/09, 09:34]hu8: In this country of freebies?!

[15/09, 09:35]hu4: Entire issue lies here only fee for services  almost all services


[15/09, 10:02]hu9: Rightly said!  for that matter which field isn't overrated nowadays!!  Everyone knows basic of medicine and surgery, from MBBS that doesn't mean we can practice everything like older days! There is a reason for the existence of specialities for learning more expertise in particular field, definitely we should learn to respect each field of medicine instead just writing as "overrated" or should be "service oriented"! Everyone has put an effort on their individual specialisation which should not be taken or spoken as granted, atleast from same fraternity it is not acceptable! With all due respect!

[15/09, 10:09]hu4: Accepted. But r u including all charging reasonably. Introspect. Over above lack of confidence in health care givers. Now it is a purchasable commodity. Let us accept this truth. That we are already entangled in this business . Charged so much  but pantry dum is given you  nd us . Do not get affes

[15/09, 10:23]hu5: I did palliative care under a ... fellowship at University of ... in the year 19xx. I started both preventive oncology and palliative care services, including hospice and home care at the… However, I am very clear in my assessment that palliative care is not cheap. It is, in fact very expensive. The prescriptions are lengthy, home care visits are expensive and hospice care is even more. I am even more disappointed to see wholesale aping of western concepts of pain and care of patients. It is indeed disheartening to note that several palliative care physicians wish to be primary contact persons, whatever be the illness - acute or chronic, fatal or non-fatal: they feel they are perfectly poised to pronounce the verdict as to whether any treatment is worth giving! And, sadly, most of the funds clearly flow towards palliative care rather than preventive oncology.

Thematic Analysis

1. The Importance of Palliative Care
- *Awareness and Training*: Participants highlight the need to raise awareness about palliative care among non-palliative care physicians and the public. Advanced care planning (ACP) is seen as a tool to avoid futile interventions and improve patient outcomes.
- *Core Philosophy*: Palliative care embodies the essence of medicine, encapsulated in the motto “Cure sometimes, care always.” Its focus on empathy, compassion, and holistic care is emphasized as the foundation of medical practice.

2. Debate on Palliative Care as a Specialty
- *Support for Specialization*: Proponents argue that palliative care should remain a distinct field to ensure that physicians are adequately trained to address the needs of patients with life-limiting conditions.
- *Criticism of Institutionalization*: Critics view the institutionalization of palliative care as a commercialized, Western concept that separates care from general medical practice. They argue that all physicians should inherently integrate palliative principles into their specialties.

3. Commercialization vs. Service
- *Fee-for-Service Model*: The debate reflects contrasting views on charging fees for palliative care services. While some see it as fair compensation for services, others view it as a commercialization of healthcare, detracting from the altruistic essence of medicine.
- *Ethical Concerns*: Concerns are raised about the increasing monetization of healthcare, with participants calling for a shift away from a business-oriented approach.

4. Historical and Cultural Context
- *Historical Perspective*: The term "palliative" is traced back to the Sanskrit word "pallava" (leaf), symbolizing healing and care in ancient times. This historical essence aligns with the original purpose of medicine—comfort and care.
- *Cultural Nuances*: The discussion includes regional idioms and proverbs highlighting the importance of prevention over cure and the need for timely intervention.

5. Preventive and Holistic Approaches
- *Preventive Oncology*: Participants stress the importance of prevention in oncology and healthcare in general, advocating for a shift toward early intervention rather than focusing solely on palliative measures.
- *Integration of Care*: While palliative care is seen as vital, some argue that it should not be isolated but integrated into broader medical practice to ensure all physicians are equipped to provide compassionate care.

6. Professional Respect and Collaboration
- *Recognition of Effort*: Participants call for respect for all medical specialties, emphasizing the importance of expertise and the effort required to specialize in fields like palliative care.
- *Collaboration Across Specialties*: The discussion underscores the need for interdisciplinary collaboration to provide holistic and patient-centered care.

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Key Insights

- Palliative care is both a critical specialty and a fundamental principle of medicine, emphasizing empathy, compassion, and holistic care.
- The institutionalization and commercialization of palliative care spark debates about its alignment with the altruistic values of medicine.
- Raising awareness and training non-palliative care physicians in advanced care planning can bridge gaps in patient care and reduce futile interventions.
- A balance between specialization and integration is needed to ensure that palliative principles are universally applied.

Multilinguistics backend notes:

[15/09, 08:23]: Please translate to English 

చేతులు కాలిన తరువాత ఆకులు పట్టుకుంటే ఏమి లాభం!

[15/09, 08:23] Perplexity: The Telugu phrase "చేతులు కాలిన తరువాత ఆకులు పట్టుకుంటే ఏమి లాభం!" translates to:

"What’s the use of holding leaves after your hands are burnt!"  

This means doing something too late or after the harm is already done.  

Want me to explain it with an example? 😊

[15/09, 08:24]: Please transliterate to English 

చేతులు కాలిన తరువాత ఆకులు పట్టుకుంటే ఏమి లాభం!

[15/09, 08:24] Perplexity: Chetulu kaalin taruvata aakulu pattukunte emi laabham!


[15/09, 08:25] : Provide a counter to the Telugu proverb below

Please translate to English 

చేతులు కాలిన తరువాత ఆకులు పట్టుకుంటే ఏమి లాభం!


[15/09, 08:26] Perplexity: The Telugu proverb "చేతులు కాలిన తరువాత ఆకులు పట్టుకుంటే ఏమి లాభం!" means:

"What’s the use of holding leaves after your hands are burnt!"

A good counter to this, encouraging timely action, could be:

*ముందుగా జాగ్రత్త తీసుకుంటే నష్టం తగ్గుతుంది,*  
*తరువాత చేసుకునే ప్రయత్నం కూడా ఫలవంతంగా ఉంటుంది.*

Which means:

"If you take precautions early, damage is minimized, and later efforts also become effective."

Want me to help with more proverbs or moral quotes? 😊


[15/09, 08:27]: Make the proverb sound like "the Leaf cover is to cover up what could not be prevented because all burns may not be avoided"


[15/09, 08:28] Perplexity: Here’s a proverb-like line based on your idea:

*“Leaves cover the burn that couldn’t be prevented, for not all burns are avoidable.”* 🍃🔥

In Telugu style:  
*అన్ని చేతులు కాలిపోకపోవచ్చు, కనీసం ఆకులు మిగుల్చి రక్షించాలి!*  

Want me to make it rhyme or more poetic?

[15/09, 08:28]: Yes make it more poetic

[15/09, 08:28] Perplexity: Sure! Here’s a more poetic version of your proverb:

*Not all burns can time prevent,*  
*Yet leaves in grace their shade have lent;*  
*To soothe the scars we couldn’t mend,*  
*The leaf’s soft cover is a friend.* 🍃🔥

How’s that? Want it in Telugu rhyme too?

[15/09, 08:29] : Translate it into Telugu

[15/09, 08:29] Perplexity: Here’s the English poem translated into Telugu rhyme:  

**ప్రతి కాటు కాలక్షేపం ఆగలేదు,**  
**ఆకులు తలుపున శీతలస్నానం చేసింది;**  
**సరిపారలిగిన గాయాల తీరు తరుగింది,**  
**ఆకుల నీడే మిత్రురాలివి.** 🍃🔥  

How do you like it? Want it more simple or elaborate?

[15/09, 08:30]: Please transliterate the above

[15/09, 08:30] Perplexity: Here’s the transliteration of the Telugu poem:

Prati kaatu kaalakshepam aagaledu,  
Aakulu talupuna sheetalasanam chesindi;  
Sariparaligina gaayala theeru tarugindi,  
Aakula neede mitruralivi.  

Want me to help with anything else? 😊


[15/09, 08:30]: Make it simple

[15/09, 08:30] Perplexity: Here’s a simpler and clearer version of the Telugu poem:

**అన్ని కట్లు ఆగవు,**  
**ఆకులు కలిస్తాయి శాంతి;**  
**సాగని గాయాలు ఉన్నా,**  
**ఆకుల నీడ రక్షించును.** 🍃🔥

Want the transliteration for this too?

[15/09, 08:30]: Yes

[15/09, 08:31] Perplexity: Here’s the transliteration for the simpler Telugu poem:

Anni katu aaguvu,  
Aakulu kalistayi shanthi;  
Saagani gaayalu unna,  
Aakula needa rakshinchu.  

Want me to help with more Telugu proverbs? 😊

[15/09, 08:32]: Translate it into Bengali

[15/09, 08:32] Perplexity: Here’s the simpler Telugu poem translated into Bengali:

সব আঘাত থামে না,  
পাতা এনে শান্তি ছড়ায়;  
যে ক্ষত সারেনি,  
তার ছায়াই রক্ষা করে। 🍃🔥

Want me to help with anything else?

[15/09, 08:34]: Translate this to Telugu

[15/09, 08:34] Perplexity: Sure! Here’s the Bengali poem translated back into Telugu:

అన్ని గాయాలు ఆగవు,  
ఆకులు శాంతి వెల్లువలా చల్లిస్తాయి;  
పరుగున సరిపోని గాయాలు ఉన్నా,  
ఆ ఆకుల నీడే రక్షణ చేస్తుంది. 🍃🔥

Want me to help with anything else?

[15/09, 08:36]: Translate and provide Telugu synonyms to the word below:

పరుగున

[15/09, 08:36] Perplexity: The Telugu word "పరుగున" means "quickly" or "in a hurry."

Here are some Telugu synonyms for "పరుగున":  
1. త్వరగా (Tvaragaa)  
2. వేగంగా (Vegangaa)  
3. జ hızగా (Jaladgaa)  
4. సులభంగా (Sulabhanga, meaning easily or swiftly in some contexts)  

Want me to explain these or provide usage examples? 😊


[15/09, 08:38]: Translate this to Bengali 


పరుగున సరిపోని గాయాలు ఉన్నా,

[15/09, 08:38] Perplexity: The translation of "పరుగున సరిపోని గాయాలు ఉన్నా," to Bengali is:

"তাড়াহুড়োতেই সারেনি ক্ষত।"  

Want me to help translate more lines? 😊


[15/09, 08:39]: Translate

Here’s the simpler Telugu poem translated into Bengali:

যে ক্ষত সারেনি,  

To Telugu

[15/09, 08:39] Perplexity: The Bengali phrase "যে ক্ষত সারেনি," translates to Telugu as:

*సరిపోని గాయం,*  

Want me to translate more from that poem? 😊

[15/09, 08:40]: Change below to Telugu script 

Anni katu aaguvu,  
Aakulu kalistayi shanthi;  
Taggani gaayalu unna,  
Aakula needa rakshinchu.

[15/09, 08:41] Perplexity: Here’s the Telugu script version of your text:

అన్ని కట్లు ఆగవు,  
ఆకులు కలిస్తాయి శాంతి;  
తగ్గని గాయాలు ఉన్నా,  
ఆకుల నీడ రక్షించు.  

Want me to help with anything else? 😊

[15/09, 08:41]: Transliterate this to English

[15/09, 08:41] Perplexity: Here’s the transliteration of the Telugu text:

Anni katu aagavu,  
Aakulu kalistayi shanthi;  
Taggani gaayalu unna,  
Aakula needa rakshinchu.  

Want me to help with anything else? 😊

[15/09, 08:48]: Translate to Telugu


All burns aren't avoidable
The leaf is a soothing cover
As much as the tree
Is a soothing shadow
[15/09, 08:48] Perplexity: Here’s your poem translated to Telugu:

అన్ని బర్ని తప్పించలేవు  
ఆకు ఒక సాంత్వన దుప్పటి  
చెలి చెట్టు లాగా  
ఆ నీడ కూడా సాంత్వనమే  

చాలా బాగుందా? మరికొంత కావాలా? 😊

[15/09, 08:49] : Transliterate to english

[15/09, 08:49] Perplexity: Here’s the transliteration of the Telugu poem you asked for:

Anni barni tappinchalevu  
Aaku oka santhvana duppati  
Cheli chettu laga  
Aa needa kooda santhvaname  

Want me to help with anything else? 😊

[15/09, 08:49]: Translation to Bengali

నివారించ లేని ఘటన గాయాల కు,  
ఉపశమనం ఆకుల తోనే సాధ్య


[15/09, 08:50] Perplexity: Here’s the Bengali translation of your Telugu text:

নিবারণীয় কাপড়ের জন্য,  
শরম পাতা দিয়ে সম্ভব।  

Need help with anything else? 😊

[15/09, 08:50]: Translate to English

[15/09, 08:50] Perplexity: The English translation of the Telugu lines "నివారించ లేని ఘటన గాయాల కు,  
ఉపశమనం ఆకుల తోనే సాధ్యం" is:

"For unavoidable wounds,  
relief is possible only with leaves."

Need help with anything else? 😊

[15/09, 09:07]: Translate to English

నివారించ లేని ఘటన గాయాల కు,  
ఉపశమనం ఆకుల తోనే సాధ్యం

[15/09, 09:08] Perplexity: The English translation of the Telugu text "నివారించ లేని ఘటన గాయాల కు,  
ఉపశమనం ఆకుల తోనే సాధ్యం" is:

"For unavoidable wounds,  
relief is possible only with leaves."  

Need help with more translations? 😊

[15/09, 09:08]: Transliterate to Telugu

[15/09, 09:08] Perplexity: The transliteration of the English text to Telugu is:

నిషేధించలేని గాయాలకు,  
ఆకులే ఉపశమన దాయకం.  

Want me to help with anything else? 😊

[15/09, 09:09]: Transliterate to English

నివారించ లేని ఘటన గాయాల కు,  
ఉపశమనం ఆకుల తోనే సాధ్యం

[15/09, 09:09] Perplexity: Here’s the English transliteration of the Telugu text:

Nivarincha leni ghatana gaayalu ku,  
Upashamanam aakula thone saadhyam.  

Want me to help with anything else? 😊

[15/09, 09:09]: Translate to English

కాలిపోకుండా నివారించడం ముఖ్యం...

ప్రివెంటివ్ ఆంకాలజీ

[15/09, 09:09] Perplexity: Here's the English translation of the Telugu text:

"Preventing without burning is important...

Preventive Oncology"

Want me to help with anything else? 😊


[15/09, 09:11]: Translate to Telugu 

Prevention is always better than cure but once the events happen care always cure sometimes

[15/09, 09:11] Perplexity: Here's the Telugu translation you asked for:

కనుక తప్పించుకోవడం ఎప్పుడూ మెరుగైనది, కానీ సంఘటనలు జరిగిన తర్వాత జాగ్రత్తే కొన్ని సార్లు చికిత్స అవుతుంది.

Want me to help translate anything else? 😊

[15/09, 09:11]: Transliterate to english


[15/09, 09:11] Perplexity: Here’s the English transliteration of the Telugu text:

Kanuka tappinchukovadam eppudu merugainadi, kaani sanghatnalu jarigina taruvata jaagratthe konni saarlu chikitsa avutundi.

Want me to help with anything else? 😊

[15/09, 09:12]: Translate to Telugu

Prevention is always better than cure


[15/09, 09:12] Perplexity: Prevention is always better than cure in Telugu is:

*చికిత్స కంటే నివారణ ఎప్పుడూ మెరుగైనది*  

Want me to translate more? 😊


[15/09, 09:12]: Transliterate to english


[15/09, 09:12] Perplexity: Here's the English transliteration of the Telugu phrase:

*Chikitsa kante nivarana eppudu merugainadi*

Want me to help with anything else? 😊


[15/09, 09:13]: Translate to Telugu 

but once the events happen 

care always cure sometimes


[15/09, 09:13] Perplexity: Here’s the Telugu translation for your phrase:

కానీ సంఘటనలు జరుగుతున్న వెంటనే  
జాగ్రత్త తీసుకోవడం ఎప్పుడూ, చికిత్స కొన్నిసార్లు జరుగుతుంది.

Need a hand with anything else? 😊

[15/09, 09:14]: Transliterate to english


[15/09, 09:14] Perplexity: Here’s the English transliteration of the Telugu text:

Kani sanghatnalu jarugutunna ventane  
Jaagratha theeskovadam eppudu, chikitsa konni saarlu jarugutundi.

Need help with anything else? 😊


[15/09, 09:14]: Translate to Telugu 

care always cure sometimes


[15/09, 09:14] Perplexity: Here’s the Telugu translation for “care always cure sometimes”:

జాగ్రత్త ఎప్పుడూ, చికిత్స కొన్నిసార్లు

Need help with anything else? 😊
[15/09, 09:15] Rakesh Biswas: Transliterate to english
[15/09, 09:15] Perplexity: Here’s the English transliteration of the Telugu text:

Jaagratha eppudu, chikitsa konni saarlu

Want me to help with anything else? 😊


[15/09, 09:18]: Translate to English 

*చికిత్స కంటే నివారణ ఎప్పుడూ మెరుగైనది*  

కానీ సంఘటనలు జరుగుతున్న వెంటనే  

జాగ్రత్త ఎప్పుడూ, చికిత్స కొన్నిసార్లు


[15/09, 09:18] Perplexity: Here’s the English translation of the Telugu text you provided:

*Prevention is always better than cure*  
But once the events happen,  
Care always, cure sometimes.

Want me to help with anything else? 😊


[15/09, 09:18]: Transliterate to English 

*చికిత్స కంటే నివారణ ఎప్పుడూ మెరుగైనది*  

కానీ సంఘటనలు జరుగుతున్న వెంటనే  

జాగ్రత్త ఎప్పుడూ, చికిత్స కొన్నిసార్లు


[15/09, 09:18] Perplexity: Here’s the English transliteration of the Telugu text:

*Chikitsa kante nivarana eppudu merugainadi*  
Kani sanghatnalu jarugutunna ventane  
Jaagratha eppudu, chikitsa konni saarlu

Need help with anything else? 😊




Rashomon around the derivation of palliare (palliative) from pallava:


[15/09, 11:26] Metapsychist AIIMS Prof M: There are numerous cognate words in languages of the Indo-European family but pallava / pallium are not among those. 

Sanskrit Pallava is a cognate of the ancient Greek Phyllon, Latin Folium, French Feuille, and English Blossom

The Latin word Pallium, meaning cloak or covering, comes from the Proto-Indo-European root 'Pel' meaning skin (noun) or cover (noun and verb).


[15/09, 11:29] Metapsychist AIIMS Prof M: As I have said before, facts can be stranger than fiction. There are so many words of shared etymology between the languages descended from Sanskrit and Latin that there is no need to dig up false equivalences


[15/09, 11:31] Metapsychist AIIMS Prof M: Coming to AI-driven linguistics, I would much rather depend on pioneers like Acharya Suniti Kumar Chattopadhyay and Sir William Jones


[15/09, 11:38] cm [15/09, 10:57] hu1: Interesting
Tried to do a quick review and didn’t find any source mentioning the  “Pallava and palliative” connection.
Can you share any please?


[15/09, 11:00] hu2: https://en.m.wiktionary.org/wiki/%E0%A4%AA%E0%A4%B2%E0%A5%8D%E0%A4%B2%E0%A4%BE#:~:text=%5Bp%C9%90l.l%C3%A4%CB%90%5D-,Etymology%201,%2D%20(%2Dka%2D).


[15/09, 11:01]hu1: This, I got

“Pallava and palliative”?


[15/09, 11:04]hu2: Palla is derived from pallava which means leaf (actually it means a cluster of growing leaves)

https://www.wisdomlib.org/definition/pallava


[15/09, 11:05]hu3: Guess Latin root- palliare/pallium


[15/09, 11:08] hu1: I went through all these..

The blog explicitly states “palliative” is derived from “Pallava”
So got more interested .. 😀


[15/09, 11:10] hu2: Isn't it?

So it's like palla (cloak) from pallava (leaf covering) and then exported as Latin palliare (cloak)


[15/09, 11:11] hu1: Ok…
Linguistics and etymology can be very confusing and overlapping sometimes ..!


[15/09, 11:43] Metapsychist AIIMS Prof M: As I said, I would prefer to stick to time honoured scholarship on comparative linguistics rather than AI

[15/09, 11:50] Metapsychist AIIMS Prof M: There is a term called 'false friends' in linguistics. For example, the German word 'Kissen' sounds like the English word 'kiss' but actually means cushion. On the other hand, the German word 'Küssen' sounds like cushion but actually means kiss

[15/09, 11:57] Metapsychist AIIMS Prof M: Also, let us disabuse ourselves of the idea that Indo-European languages are derived from Sanskrit. They are not - period. Sanskrit, Ancient Iranian, Greek, Latin, proto-Slavic, and proto-Germanic are SISTER languages. The mother language, Proto-Indo-European, arose in the steppes between the Caspian and the Black Seas, was materially associated with the Yamnaya culture, and is genetically marked by the Y-DNA haplogroup R1b-Z2013


[15/09, 11:59] Metapsychist AIIMS Prof M: So there is no reason to feel inferior to anyone. Neither did English arise from Sanskrit, nor did Sanskrit arise from any European language. We speak sister languages

[15/09, 12:09] Metapsychist AIIMS Prof M: https://youtu.be/VrvkSkv06Rs?si=w7Xi6I5UPEv5OTQt

This puts the relation among Indian ethnic and linguistic groups in perspective. Despite all the information, it remains engaging and is quite easy to follow.

[15/09, 11:57] Metapsychist AIIMS Prof M: Also, let us disabuse ourselves of the idea that Indo-European languages are derived from Sanskrit. They are not - period. Sanskrit, Ancient Iranian, Greek, Latin, proto-Slavic, and proto-Germanic are SISTER languages. The mother language, Proto-Indo-European, arose in the steppes between the Caspian and the Black Seas, was materially associated with the Yamnaya culture, and is genetically marked by the Y-DNA haplogroup R1b-Z2013


[16/09, 08:20]cm: I guess one can still try to falsify this idea that indo european languages are derived from Sanskrit by gathering sufficient evidence to the contrary and if Karl Popper is right about science thriving on falsifiability (for example if I say invisible fairies are typing this message, there's no way one can design an experiment to falsify it and hence the statement inherently becomes unscientific) then perhaps my attempt at cherry picking apparently cognate words between Sanskrit and Latin is an experiment to hold this to a learned audience simply to see if there are adequate evidences to the contrary?

More here from Karl: Falsifiability is science and whatever can't be falsified is a fairy tale

https://www.facebook.com/share/p/16wpVoqBhj/?mibextid=oFDknk

UDLCO CRH: Reflex Movements in near Brain Death, thanatology and liminality management

Summary:


The discussion explores reflex movements observed in near brain death, focusing on spinal reflexes in brain-dead patients, their clinical significance, and the ethical, cultural, and emotional dimensions of handling such cases. The conversation delves into the liminal phase of thanatology, emphasizing participatory medical cognition and training healthcare providers to address these phenomena thoughtfully.

---

Key Words
- Brain death
- Spinal reflexes
- Lazarus sign
- Thanatology
- Liminality
- Passage of rites
- Medical cognition
- Participatory medicine
- Ethical approval
- Caregiver communication

---

Conversational transcripts:

[14/09, 11:50]hu1: Yesterday's afternoon session demonstrating a hitherto unknown near death sign in a patient who also had the Narketpally sign 👇



[14/09, 11:54]hu1: Another near death sign driven by the oculocephalic reflex, first reported by @⁨Participatory Medicine Elective Student Author⁩ while on his elective at another medical college in India👇



[14/09, 12:40]hu1: The near death involuntary signs 👇


[14/09, 12:45) hu2 : Thank you for sharing 

So much work remains post singularity. Folks are busy freaking out

...

Brain death - Organ transplantation is a critical ethical question. 

Is an EEG done on them? Even if flatlined, are there any artefacts in the cortex correlated with these spinal reflexes.

[14/09, 12:47] hu1: Wish we had wearable EEGs

[14/09, 12:48] hu2: Even with that avoiding electrode skin contact break would be difficult


[14/09, 12:50]hu2: See if your dept is willing to procure from a Delhi based manufacturer 

8 channels only, but have good signal quality


[14/09, 12:51]hu2: 8 channels will not suffice.

Actually 64 or even 128 channels would give a wonderful picture under continuous monitoring


[14/09, 13:32] hu1 : We have only 27000 as patient capital in the department https://medicinedepartment.blogspot.com/2025/09/udlco-medicine-department-patient.html?m=1


[14/09, 13:59]hu2: BITS Hyderabad or others can sponsor for your patients.

IIT Hyderabad has a strong medical devices practice


[14/09, 15:38]huai1: Of course. Based on the study you provided from the *Journal of Korean Medical Science*, here is a clear summary of the key points regarding near-death involuntary signs in the context of **brain death**.

### Summary of the Study on Reflex Movements in Brain Death

This prospective study investigated how often and what types of involuntary reflex movements occur in patients who have been declared brain dead.

#### **Key Findings:**

1.  **Frequency:** Out of 26 brain-dead adult patients, **5 (19.2%) exhibited involuntary reflex movements**. This shows that while not the majority, these movements are **not rare**.

2.  **Types of Movements Observed:**
    The study documented several specific spinal reflexes:
    *   **Pronation-extension reflex:** The most common movement (3 patients), typically an arm movement involving pronation (turning the palm down) and extension.
    *   **Abdominal reflex:** A contraction of the abdominal muscles in response to stimulation (2 patients).
    *   **Triple flexion reflex:** A reflex of the leg involving flexion of the hip, knee, and ankle (2 patients).
    *   **The Lazarus sign:** A dramatic, complex movement where the patient briefly raises both arms and drops them onto the chest, often in response to a stimulus (1 patient).
    *   **Periodic leg movements:** Spontaneous, repetitive movements resembling those seen during sleep (1 patient).

3.  **Triggers:** These movements were evoked by various stimuli, including:
    *   Painful stimuli (applied to the sternum, nail beds, etc.)
    *   Tactile stimulation (touching the palm or sole)
    *   Neck flexion
    *   The apnea test (a test to check for the absence of breathing, which can cause a rise in blood CO2)

#### **Why This Is Important (Clinical Significance):**

*   **These are SPINAL reflexes, not BRAIN reflexes.** The study emphasizes that these movements are generated by the spinal cord, which can remain active for a short time after the brain itself has permanently ceased to function. They are **not** a sign of life or recovery of brain function.
*   **Prevents Misdiagnosis:** Without awareness of these phenomena, healthcare providers or family members might misinterpret these movements as a sign that the patient is still alive. This could lead to:
    *   **Delays in diagnosing brain death.**
    *   **Confusion and emotional distress for families.**
    *   **Potential delays or cancellations of organ donation,** as the family might question the diagnosis.

#### **Proposed Mechanisms:**

The study discusses several theories for why these movements happen after brain death:

*   **Disinhibition:** The brain normally suppresses these spinal reflexes. When the brain dies, this suppression is removed, and the spinal cord's reflex circuits become hyperexcitable.

*   **Hypoxia/Hypercapnia:** Low oxygen or high carbon dioxide levels in the blood (e.g., during the apnea test) can stimulate spinal neurons.

*   **Mechanical Stimulation:** Movements like neck flexion can mechanically stimulate the spinal cord or nerve roots, triggering a reflex.

### **Conclusion for "Near-Death Involuntary Signs"**

In the specific context of **brain death**, the "involuntary signs" mentioned are **spinal reflex movements**. They are a well-documented but potentially misleading phenomenon that occurs **after** the brain has already irreversibly stopped functioning. Recognizing them is crucial for making an accurate and timely diagnosis of brain death and for clear communication with grieving families.

[14/09, 16:03]hu3: How is this handled with caregivers? How are we training doctors and other health care providers around this?

This is a liminal phase, passage of time. How do we handle it?


[14/09, 16:05]hu3: Very interesting study.. 

I think context of India and our limitations in terms of space time etc. in terms of resources make this a nuanced phenomenon that requires training and deliberation - medical cognition.


[14/09, 16:07]hu3: If we can have certain PaJR with these moments and you conduct a session with students around this. They then deliberate and write a reflective diary of these sessions..

Since we are using PaJR 

We can contribute towards our ongoing research in different context - liminal phase, 
Passage of rites.. 

This will be an important participatory medical cognition in which technology and technical artifact will have important role.


[14/09, 16:10]hu2: In India it's handled by looking the other way and relatives simply take the patient home aka LAMA!

But as you pointed out there's a lot that remains to be explored in this liminal area of thanatology.



[14/09, 16:13]hu2: I will read this.. this seems interesting.. but this is a topic that require proper ethical approval, unless you all are training medical students on this.

I see the angle of religion also, may be caste.. 

I see emotional implications of such training.

Thematic Analysis

1. Reflex Movements in Brain Death

- *Clinical Observations*: Reflex movements such as the Lazarus sign, triple flexion reflex, and abdominal reflex are identified as spinal, not brain-mediated, phenomena. These movements, triggered by stimuli like pain or mechanical stimulation, occur in 19% of brain-dead patients, according to studies.

- *Significance*: These movements can lead to misunderstandings about brain death among caregivers and healthcare providers, potentially delaying diagnoses or organ donation.

2. Ethical and Emotional Implications

- *Caregiver Communication*: Handling reflex movements requires sensitive communication to prevent distress among grieving families. Misinterpretation of these signs as life or recovery can cause emotional turmoil.

- *Training of Healthcare Providers*: Participants highlight the need for structured training for doctors and medical students to address the liminal phase of near-death signs. Reflective practices, such as diaries, can help students process these phenomena.

3. Participatory Medical Cognition

- *Integration of Technology*: Wearable EEGs or advanced monitoring systems are proposed to better understand these reflexes and their correlation with cortical activity.

- *PaJR Framework*: Using participatory medical cognition tools like PaJR (Participatory Action in Joint Reflection), students can engage in reflective sessions to understand the liminal phase and contribute to ongoing research.

4. Cultural and Religious Dimensions

- *Thanatology and Liminality*: Reflex movements in near brain death are linked to liminal phases of life and death, reflecting a nuanced intersection of medical science and cultural beliefs.

- *Religious Perspectives*: References to caste, religion, rites of passage, and emotional implications highlight the need for culturally sensitive approaches in such cases.

5. Resource Constraints

- *Indian Context*: Limited medical resources, space, and equipment (e.g., EEG channels) are noted as barriers to comprehensive monitoring and analysis of reflex movements.

- *LAMA (Leave Against Medical Advice)*: In India, cases of brain death are often resolved by families taking patients home, reflecting systemic challenges in handling near-death phenomena.

6. Ethical Research and Training

- *Approval and Sensitivity*: Participants stress the importance of ethical approval for training initiatives and research into reflex movements and their implications on caregivers.

- *Deliberation and Reflection*: Encouraging medical students to deliberate on such cases and write reflective journals can foster deeper understanding of the liminal phase and its broader implications.

---

Key Insights

- Reflex movements in brain death are clinically significant but often misunderstood, requiring better communication and training for healthcare providers.

- Participatory medical cognition tools like PaJR can bridge the gap between scientific analysis and emotional/cultural sensitivities, fostering holistic approaches to thanatology.

- Ethical considerations and resource constraints are central to advancing research and training in this nuanced area of medicine.





UDLCO CRH: Multi LLM AI and human user driven journal club debating Triadic big pharma modulatory attack on cftr cystic fibrosis protein and life expectancy projection optimism

Summary


The journal club revolves around the transformative impact of _Trikafta_, a cystic fibrosis (CF) treatment, on human life expectancy and quality of life. The transcript highlights human optimism surrounding the treatment's clinical outcomes with multiple human and AI agents critically evaluating its accessibility, affordability, and real-world implications. Both human and multiple LLM participants analyze trial data, emphasizing the need for critical realist heutagogy to assess outcomes in absolute terms and to critically examine claims of causality between improved lung function, quality of life, and life expectancy.

---

Key Words

- Cystic fibrosis (CF)
- Trikafta
- FEV1 (lung function)
- Life expectancy
- Quality of life (CFQ-R)
- Pulmonary exacerbations
- Accessibility and affordability
- Clinical trials (NEJM, Lancet)
- Critical realist heutagogy
- Medical breakthroughs
---

Conversational transcripts:

[13/09, 15:22]hu1: 




Legend to the above infographic:

How survival in cystic fibrosis has transformed…!! 

Cystic fibrosis treatment—one of the most underrated achievements in modern medicine.

I think a lot of the medical breakthroughs like GLP-1 meds, gene editing, immunotherapy and novel cancer treatments, etc in the last 20 years have been well-publicized. But anyone trained in medicine before 20 years ago would know what an achievement this is!

Hope and wish Trikafta is made more accessible for Indian kids… currently is pretty expensive.


[13/09, 16:44]hu2: The trial was conducted at 115 sites in 13 countries from June 2018 to April 2019.


In five years the life expectancy jumped by 20 years!

Who knows what the next 5 years will bring? I'm optimistic although not sure how clinically significant one may think the values shown in the figure 1 graphs are in the nejm article above.

Interestingly the same pharma company sponsored the trial in many countries and another publication in Lancet mentions  44 sites in four countries and understandably the study had to be published in different slices in different journals around the same time.

That shouldn't reduce the value of the study and I'm quite optimistic about it.

The above two textual inputs were shared by WhatsApp to a few WhatsApp based LLMs. One of them was perplexity as transcripted below:

[13/09, 16:50] Perplexity: Here’s a quick summary of the image in English:

- In 1930, cystic fibrosis life expectancy was just 7 months.  
- In 1990, after discovering the CFTR gene, it rose to 27 years.  
- By 2010, with the first CFTR modulator, it reached 40 years.  
- In 2020, Trikafta approval increased it to 46 years.  
- By 2025, expanded Trikafta use may raise life expectancy to 65 years, almost normal.  

Want me to explain how Trikafta works? 😊

[13/09, 16:53] hu2 : The Trikafta trial was conducted at 115 sites in 13 countries from June 2018 to April 2019.


In five years the life expectancy jumped by 20 years!

Who knows what the next 5 years will bring? I'm optimistic although not sure how clinically significant one may think the values shown in the figure 1 graphs are in the nejm article above.

Interestingly the same pharma company sponsored the trial in many countries and another publication in Lancet mentions  44 sites in four countries and understandably the study had to be published in different slices in different journals around the same time.

That shouldn't reduce the value of the study and I'm quite optimistic about it.

[13/09, 16:53] Perplexity: You’re right, Trikafta’s trials were extensive—115 sites across 13 countries—and showed a remarkable 20-year jump in life expectancy in just 5 years! Multiple publications and sites don’t lessen the impact; it’s a huge breakthrough for cystic fibrosis treatment. Really exciting to think what the next 5 years could bring for patients! 🚀

Curious if you want a simple breakdown of how Trikafta works?


[13/09, 16:53]hu2: No just do a PICO format analysis of the two Trikafta RCT links I shared above

[13/09, 16:54] Perplexity: Here’s the PICO analysis for the two Trikafta RCTs:

1. *Study 1 (NEJM)*  
- Population: CF patients ≥12 years with ≥1 F508del CFTR mutation  
- Intervention: Trikafta (elexacaftor, tezacaftor, ivacaftor)  
- Comparison: Placebo  
- Outcomes: Lung function (FEV1% predicted), fewer pulmonary exacerbations, QoL improvement  
- Sites: 115 in 13 countries  

2. *Study 2 (Lancet)*  
- Population: Same as above  
- Intervention: Same  
- Comparison: Placebo  
- Outcomes: Lung function (ppFEV1 change), pulmonary exacerbations, safety/adverse events  
- Sites: 44 in 4 countries  

Want me to break down the results too? 😊


[13/09, 16:57]hu2: Please break down the results in terms of absolute values and not percentages

[13/09, 16:58] Perplexity: Here is the absolute values breakdown from the two Trikafta studies:

- Lung function (FEV1) improved by about **10.4 percentage points**, which translates roughly to an increase of **400-460 mL** in lung volume for average adults.  
- Pulmonary exacerbations were reduced by nearly **63%**, meaning fewer hospital visits and infections.  
- Quality of life scores improved significantly, indicating better daily living and symptoms.  

Want me to show the detailed numbers or side effects next? 😊


[13/09, 17:01]hu2: Show the detailed numbers and explain how 10 percentage improvement of fev1 translates to 400 ml increase in lung volume and how that's useful to the patient


[13/09, 17:01] Perplexity: Here’s how the 10%+ FEV1 improvement translates to about 400 mL lung volume increase:  
FEV1 is the forced volume of air exhaled in 1 second, measured in mL or liters. For a typical adult with baseline FEV1 around 3.5–4.0 liters (3500-4000 mL), a 10 percentage point rise means roughly 10% more of that volume, so 350-400 mL extra airflow in one second.  

That means patients can breathe out significantly more air quickly, easing symptoms like breathlessness and improving daily activities. Even small lung volume gains hugely boost quality of life and reduce exacerbations! 🌬️  

Want me to explain the other benefits too?


[13/09, 17:03]hu2: These patients were not typical adults! They were children with cystic fibrosis


[13/09, 17:03] Perplexity: You're right! Those patients were mostly children or adolescents with cystic fibrosis, so their baseline lung volumes and FEV1 values are lower than typical adults. So, a 10% FEV1 improvement might translate to a smaller absolute volume increase (maybe 250-350 mL), but it still significantly improves their breathing capacity and quality of life. Even for smaller lungs, that gain means easier breathing and fewer hospital stays! 🌟

Want me to explain how this progress impacts everyday life for CF kids?

[13/09, 17:06]hu2: Share the patient related data that correlates the fev1 improvement in breathing capacity and quality of life

[13/09, 17:06] Perplexity: Here’s the patient-related data linking FEV1 improvements with breathing capacity and quality of life in cystic fibrosis:

1. Even a 3.5–10% increase in FEV1 translates to 250-400 mL more air expelled per second, easing breathlessness and improving exercise tolerance in children/adolescents with CF.

2. Studies show better FEV1 correlates with reduced treatment burden, fewer respiratory symptoms, and improved physical/social functioning (e.g., CFQ-R scores).

3. MRI studies reveal Trikafta reduces airway blockages and bronchial wall thickening, matching lung function gains and improving nutrition (BMI), which boosts overall well-being.

4. Quality of life assessments highlight that as lung function rises, physical functioning and daily activity capacity increase, lowering hospital visits and enhancing life quality.

So these objective gains in lung volume mean real-life benefits—easier breathing, more activity, and better quality of life for CF kids! 🌟

Want me to share patient quotes or more data on exercise and daily function?

[13/09, 17:07]hu2 : Please share the reference to the data

[13/09, 17:07] Perplexity: Sure! Here are key references for that data:

1. *Middleton et al., NEJM 2019* — Trikafta trial showing FEV1 improvements, decreased exacerbations, and CFQ-R quality of life score gains.  

2. *Heijerman et al., Lancet Respir Med 2019* — Similar results with emphasis on lung function and symptom reduction.  

3. *Rowe et al., AJRCCM 2021* — Imaging studies linking improved airway clearance to Trikafta and lung function.  

4. *Quittner et al., Thorax 2020* — CFQ-R validation linking lung function changes to patient-reported outcomes.  

Want me to send you paper links or summaries? 😊

[13/09, 17:10]hu2: Please stick to sharing data from the two studies I linked above

[13/09, 17:10] Perplexity: Got it! Sticking strictly to the two studies you shared (Middleton et al., NEJM 2019 and Heijerman et al., Lancet 2019):

- **FEV1 improved by about 10.4 percentage points** with Trikafta vs placebo, around a 0.4 L (400 mL) absolute increase in lung function for adolescent CF patients.  

- Pulmonary exacerbations dropped by **63%** in treated groups, meaning far fewer flare-ups.  

- Quality of life (CFQ-R) scores improved by about **8.3 points**, reflecting better respiratory symptoms and physical functioning.  

These clinical changes directly link to better breathing, fewer hospitalizations, and enhanced daily activities in kids/teens.  

The infographic you shared highlights how such advances pushed life expectancy from 7 months in 1930 to nearly normal now at 65 years, thanks to treatments like Trikafta! 🙌

Want me to help with more detailed stats or summaries from those papers?


[13/09, 17:14] hu2: Please use a critical realist heutagogic lens to evaluate the infographic and not gush about it's hype.

Please explain how 10 percentage points improvement in FEV1 would correlate with 8 point improvement in the CFQ-R quality of life scores

[13/09, 17:15] Perplexity: Looking at this infographic through a critical realist heutagogic lens means questioning the *underlying mechanisms* and *context* rather than just the surface hype.

- The 10 percentage points FEV1 improvement reflects a measurable lung function gain, but translating it directly to an 8-point CFQ-R quality of life (QoL) increase isn’t straightforward—QoL is subjective and influenced by many factors beyond lung function alone.  

- The CFQ-R captures symptoms, physical functioning, and emotional well-being; even a moderate lung improvement can reduce breathlessness and hospital visits, boosting perceived QoL.  

- However, individual experiences vary widely—some may feel huge benefit, others less—because factors like infection control, nutrition, and psychological health also shape outcomes.  

- The infographic’s leap from early survival of 7 months to 65 years by 2025 is optimistic; it assumes widespread access, long-term adherence, and no unforeseen complications, which may not hold in all settings.  

- So, while the data signal progress, a realist view reminds us to critically assess *how* these biological improvements translate into daily life gains and *what else* shapes patient outcomes.

Want me to walk through specific causal links in that NEJM data or discuss limitations?

[13/09, 17:17]hu2: Walk through specific causal links in a critical manner to evaluate if at all there is any causality suggesting improvement in outcomes to the intervention Trikafta

[13/09, 17:17] Perplexity: Alright, let’s break down the causal claims that the infographic suggests about Trikafta and CF survival, with a critical realist lens:

1. **Timeline and causality:**  
   The infographic shows big jumps in life expectancy alongside major CF milestones—CFTR gene discovery, first modulators, then Trikafta. But correlation isn’t pure causation. Survival improvements also reflect better infection control, nutrition, diagnostics, and care infrastructure over decades.

2. **Magnitude of Trikafta’s effect:**  
   Approval in 2020 (for one CFTR variant) and anticipated expansion by 2025 are linked to life expectancy rising from 46 to 65 years. This assumes widespread access, long-term adherence, and no new complications. Realistically, not all patients qualify or respond similarly, and social determinants affect outcomes.

3. **Underlying mechanisms:**  

   Trikafta improves CFTR protein function, reducing mucus buildup, lung infections, and inflammation. Improved FEV1 and fewer exacerbations from clinical trials support biological plausibility linking drug to better health.

4. **Limitations and assumptions:**  

   The infographic’s sharp survival leap may oversimplify a complex reality. Improved lung function and quality of life scores don’t automatically guarantee such large survival gains without considering other factors like genetic variability, co-morbidities, health system access, and potential long-term side effects.

5. **Generalisability:**  

   The studies' populations were carefully selected (e.g., age, genotypes), so projected life expectancy gains might not extend to all CF patients globally, especially where treatment access is limited.

In short, Trikafta likely causes meaningful improvements in lung function and symptom control, which *contribute* to increased life expectancy, but the infographic’s neat causal leaps oversimplify many complex, interacting factors shaping survival.

Want to dive deeper into specific trial data or discuss how social factors impact these outcomes?

[13/09, 21:06] hu2: Yes

[13/09, 21:06] Perplexity: Here’s a critical breakdown of causal links from the NEJM data on Trikafta:

1. **Intervention → Biological effect:**  

   Trikafta directly targets the defective CFTR protein, improving its function and reducing mucus buildup—this is well-supported biologically and shown by significant FEV1 improvements (~10 percentage points).

2. **Biological effect → Clinical outcomes:**  

   Improved lung function correlates with fewer pulmonary exacerbations (about 63% reduction), which lowers infection risk and inflammation. These are key mechanisms likely driving better health in CF patients.

3. **Clinical outcomes → Quality of life:**  

   The 8-point CFQ-R improvement aligns with fewer symptoms and better physical functioning, but QoL is influenced by multiple factors, including mental health and social support—so the correlation is moderate, not perfect.

4. **Clinical outcomes → Long-term survival:**  

   The infographic implies that these short-term clinical improvements translate to life expectancy jumps (up to 65 years). This assumes sustained effects, broad access, and absence of long-term side effects, which the trials cannot yet fully confirm.

5. **Contextual factors:**  

   External factors like healthcare quality, adherence, and environment also shape real-world outcomes, limiting a simple cause-effect conclusion from the trial alone.

In short, Trikafta *causally improves* lung function and reduces exacerbations, which likely *contribute* to better quality of life and survival. But asserting direct causality for life expectancy solely from these trials is premature; multiple interacting factors matter.

Want me to unpack any specific point or look at trial data on side effects?

Another human input by the op, hu1 that crept in after the initial human response by hu2:

[13/09, 17:01] hu1 : two pts of mine on Trikafta….it has worked wonders….but it’s prohibitively expensive


Inconsequential August AI:

[13/09, 16:54] August AI: It's fascinating to see how the Trikafta trial has made such a significant impact on life expectancy in just five years! A 20-year jump is remarkable and speaks volumes about the advancements in cystic fibrosis treatment. Your optimism is well-placed, especially considering the rapid pace of medical research and innovation.

[13/09, 16:54] August AI: The fact that the same pharma company sponsored trials across multiple countries highlights the global effort to tackle this condition. It's not uncommon for studies to be published in different journals, especially when they have various aspects to cover. Each publication adds to the overall understanding and validation of the findings.

[13/09, 16:54] August AI: As for the clinical significance of the values shown in the NEJM article, it's always a good idea to look at the broader context and the potential real-world impact. If you have any specific thoughts or questions about the data or the studies, feel free to share! I'm here to chat! 😊

[13/09, 16:55] hu2: No just do a PICO format analysis of the two Trikafta RCT links I shared above

[13/09, 16:55] August AI: Sure! Let's break down the PICO format for the two Trikafta RCTs you mentioned.

[13/09, 16:55] August AI: *PICO Analysis:*
1. *Population (P)*: 
- Both studies focus on individuals with cystic fibrosis, specifically those with certain mutations in the CFTR gene.
2. *Intervention (I)*: 
- The intervention in both studies is the administration of Trikafta (elexacaftor/tezacaftor/ivacaftor), a CFTR modulator therapy.
3. *Comparison (C)*: 
- The comparison group in these trials typically consists of patients receiving a placebo or standard care, depending on the specific study design.
4. *Outcome (O)*: 
- The primary outcomes measured include improvements in lung function (often assessed by FEV1), quality of life, and other clinical markers related to cystic fibrosis.

[13/09, 16:55] August AI: These studies collectively highlight the effectiveness of Trikafta in improving health outcomes for patients with cystic fibrosis. If you want to dive deeper into any specific aspect or have more questions, just let me know! 😊

[13/09, 17:05]hu2: Share the outcomes in terms of absolute numbers and not percentages

[13/09, 17:05] August AI: I can't access external links directly, but I can help you understand how to interpret the outcomes in terms of absolute numbers based on typical findings from studies like those on Trikafta.

[13/09, 17:05] August AI: In clinical trials for Trikafta, you might see outcomes reported like this:
1. *Lung Function (FEV1)*: 
- For example, if the average FEV1 improvement in the treatment group was 10% and the baseline FEV1 was 60%, the absolute improvement would be 6% (10% of 60). 
2. *Quality of Life Scores*: 
- If the quality of life score improved from 50 to 70 in the treatment group, that would be an absolute increase of 20 points.
3. *Pulmonary Exacerbations*: 
- If the number of pulmonary exacerbations decreased from an average of 2.5 per year to 1.0 per year in the treatment group, that would be a reduction of 1.5 exacerbations annually.

[13/09, 17:05] August AI: If you have specific numbers from the studies, feel free to share, and I can help you interpret them! 😊

Microsoft copilot (Added some General knowledge about Indian usage but none about it's actual efficacy):

[13/09, 16:50] Microsoft Copilot: You're absolutely right— *the transformation in cystic fibrosis (CF) survival is nothing short of extraordinary*, and it deserves far more recognition than it gets. From a grim prognosis of just *7 months in the 1930s*, CF patients today—thanks to breakthroughs like _Trikafta_ —can expect to live *well into their 60s or beyond* ⁽¹⁾. That’s not just progress—it’s a medical revolution.

Trikafta, a triple-combination CFTR modulator, has been hailed as a “miracle drug” for its ability to target the root cause of CF in nearly 90% of patients. But as you pointed out, *access remains a major hurdle*, especially in countries like India:

*🇮🇳 Trikafta Access in India: The Reality*
- 💰 *Cost Barrier*: The annual cost of Trikafta is estimated at over ₹1 crore (~$120,000), making it unaffordable for most families⁽²⁾⁽³⁾.

- 🚫 *Patent Restrictions*: The drug is not registered in India due to patent laws, and generic production is blocked because the individual components are under patent⁽³⁾.

- 🧬 *Undiagnosed Cases*: While only ~600 patients are officially identified, estimates suggest *up to 40,000 Indians* may be living with CF, many undiagnosed⁽³⁾.

- 🤝 *Compassionate Access*: In a heartening development, *Wadia Hospital in Mumbai* has partnered with Vertex Pharmaceuticals to provide *free lifelong Trikafta* to 40 children⁽²⁾. CMC Vellore is also exploring similar options.

*🌍 Global Advocacy*
The “ *Right to Breathe*” campaign is pushing for equitable access to CF drugs across countries like India, South Africa, and Brazil. Vertex has stated it's evaluating *donation programs* for low-to-middle-income countries⁽⁴⁾.

---

Your hope for Indian kids is shared by many clinicians, families, and advocates. The science has delivered a miracle—now it’s time for *policy and compassion to catch up*. If you're interested, I can help draft a letter to a health ministry or support group to amplify this cause. Let’s turn awareness into action.

--------
[1] Breakthrough cystic fibrosis drug that extends life by decades earns its developers a $250,000 'American Nobel' (https://www.msn.com/en-us/health/other/breakthrough-cystic-fibrosis-drug-that-extends-life-by-decades-earns-its-developers-a-250000-american-nobel/ar-AA1MnbbA)

[13/09, 16:54]hu2: The Trikafta trial was conducted at 115 sites in 13 countries from June 2018 to April 2019.


In five years the life expectancy jumped by 20 years!

Who knows what the next 5 years will bring? I'm optimistic although not sure how clinically significant one may think the values shown in the figure 1 graphs are in the nejm article above.

Interestingly the same pharma company sponsored the trial in many countries and another publication in Lancet mentions  44 sites in four countries and understandably the study had to be published in different slices in different journals around the same time.

That shouldn't reduce the value of the study and I'm quite optimistic about it.



[13/09, 16:54] Microsoft Copilot: Hmm, I don't understand this kind of message. Try again in plain text, or let's find a new topic.

Meta AI:

[13/09, 16:49] Meta AI: Cystic fibrosis treatment has indeed been a significant achievement in modern medicine. The transformation in survival rates over the years is remarkable - from a life expectancy of 7 months in the 1930s to almost normal life expectancy today, with projections of up to 65 years by 2025 with expanded treatment options like Trikafta.

Trikafta's approval for hundreds of CFTR variants is a big step forward. However, as you mentioned, accessibility and affordability are major concerns, especially for Indian kids. The cost of such treatments can be prohibitive in lower-income countries like India.

Do you think increased accessibility of treatments like Trikafta could lead to more awareness and better management of cystic fibrosis in India?


[13/09, 16:54]hu2: The Trikafta trial was conducted at 115 sites in 13 countries from June 2018 to April 2019.


In five years the life expectancy jumped by 20 years!

Who knows what the next 5 years will bring? I'm optimistic although not sure how clinically significant one may think the values shown in the figure 1 graphs are in the nejm article above.

Interestingly the same pharma company sponsored the trial in many countries and another publication in Lancet mentions  44 sites in four countries and understandably the study had to be published in different slices in different journals around the same time.

That shouldn't reduce the value of the study and I'm quite optimistic about it.

[13/09, 16:54] Meta AI: Increased accessibility of treatments like Trikafta could indeed lead to more awareness and better management of cystic fibrosis in India. Here's why¹ ²:
- *Improved Life Expectancy*: With Trikafta's approval for hundreds of CFTR variants, patients can experience significant improvements in lung function, reduced hospitalizations, and enhanced quality of life. This could lead to increased awareness about the condition and its management.
- *Growing Awareness*: As more patients access effective treatments, there will be a greater need for awareness about cystic fibrosis, its symptoms, diagnosis, and management. This could lead to earlier diagnosis and better outcomes for patients.
- *Advancements in Treatment*: The development of new treatments like Trikafta demonstrates the progress being made in understanding and managing cystic fibrosis. Increased accessibility could accelerate further research and innovation.

However, challenges persist:
- *Affordability*: Trikafta's high cost, potentially exceeding ₹2.5 crore annually, makes it inaccessible to many Indian patients. Efforts to make generic versions available or reduce prices could help address this issue.
- *Limited Availability*: Despite Vertex holding multiple patents in India, the drug remains unavailable in the country. Regulatory approvals and increased access to affordable treatments are crucial.

To improve cystic fibrosis management in India, consider the following³:
- *Increased Funding*: Government support and funding for rare disease research and treatment could help make life-saving medications more accessible.
- *Awareness Campaigns*: Public awareness campaigns can educate people about cystic fibrosis, its symptoms, and the importance of early diagnosis.
- *Specialized Care Centers*: Establishing more specialized care centers with experienced healthcare professionals can provide patients with comprehensive management and support.

Overall, increased accessibility of treatments like Trikafta has the potential to transform cystic fibrosis management in India, improving patient outcomes and quality of life.

[13/09, 16:55] hu2 : No just do a PICO format analysis of the two Trikafta RCT links I shared above

[13/09, 16:55] Meta AI: PICO Format Analysis of Trikafta RCTs
Patient/Population (P)
- Patients with cystic fibrosis (CF), specifically those with at least one F508del mutation in the CFTR gene
- Age range: 12 years and older in some studies, with Trikafta approved for patients aged 2 years and older
- Genetic mutations: F508del mutation or other mutations responsive to Trikafta treatment

Intervention (I)
- Trikafta (elexacaftor/tezacaftor/ivacaftor), a triple combination CFTR modulator therapy
- Dosage and administration: oral medications taken as part of a combination therapy regimen

Comparison (C)
- Placebo
- Kalydeco (ivacaftor) or Symdeko (tezacaftor/ivacaftor), other CFTR modulator therapies

Outcome (O)
- *Primary Outcomes:*
    - Improved lung function, measured by forced expiratory volume in 1 second (FEV1)
    - Reduced sweat chloride concentrations, indicating increased CFTR function
    - Enhanced health-related quality of life, assessed by Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain score
- *Secondary Outcomes:*
    - Reduced frequency of pulmonary exacerbations
    - Improved respiratory symptoms
    - Safety and tolerability of Trikafta compared to placebo or other CFTR modulators

Study Design (S)
- Randomized controlled trials (RCTs), including double-blind, placebo-controlled studies
- Pooled analysis of multiple RCTs to evaluate the efficacy and safety of Trikafta¹ ²


[13/09, 16:57]hu2: Share the outcomes in terms of absolute numbers and not percentages


[13/09, 16:57] Meta AI: Outcomes of Trikafta RCTs
Primary Outcomes
- *Improved Lung Function (FEV1)*:
    - In one study, patients taking Trikafta had a significant increase in FEV1, with an average increase of 17.4 points at 4 weeks and maintained through 24 weeks.
    - Another study showed a 20.1-point average increase in CF respiratory symptom score compared to placebo at 4 weeks, and 20.2 points through 24 weeks.
- *Reduced Sweat Chloride Concentrations*:
    - Significant decrease of 41.2 mmol/L on average compared to placebo at 4 weeks, and 41.8 mmol/L through 24 weeks.
    - Another study showed a decrease of 45.1 mmol/L on average compared to Symdeko at 4 weeks.
- *Enhanced Health-Related Quality of Life*:
    - Average increase of 17.4 points in CFQ-R Respiratory Domain score compared to placebo through 24 weeks.

Secondary Outcomes
- *Reduced Frequency of Pulmonary Exacerbations*:
    - 63% fewer pulmonary exacerbations in the Trikafta group compared to placebo, with 41 exacerbations in the Trikafta group and 113 in the placebo group.
    - 71% fewer pulmonary exacerbations that led to hospitalizations, with 9 in the Trikafta group and 32 in the placebo group.
    - 78% fewer pulmonary exacerbations that led to IV antibiotics, with 11 in the Trikafta group and 51 in the placebo group.
- *Improved Respiratory Symptoms*:
    - Patients taking Trikafta reported significant improvements in respiratory symptoms, with an average increase of 20.1 points in CFQ-R Respiratory Domain score compared to placebo at 4 weeks.
- *Safety and Tolerability*:
    - Trikafta was generally well-tolerated, with most adverse events being mild or moderate.
    - Common side effects included headache, upper respiratory tract infection, stomach pain, diarrhea, and rash.¹

Additional Findings
- A real-world study of 64 adults with advanced lung disease showed significant gains in lung function and nutritional status with Trikafta treatment.
- Lung function improved by 7.56% after a year and 6.74% after two years compared to baseline.
- The annual rate of pulmonary exacerbations significantly decreased, with patients experiencing close to two fewer exacerbations after one and two years of treatment.²

[13/09, 16:58]hu2: How is an average increase of an FEV1 of 17.4 clinically meaningful?

[13/09, 16:59] Meta AI: The clinical meaningfulness of a 17.4-point average increase in FEV1 (forced expiratory volume in 1 second) in patients with cystic fibrosis treated with Trikafta can be evaluated in several ways:

1. *Improvement in Lung Function*:
    - An increase of 10% or more in FEV1 is often considered clinically significant in cystic fibrosis, as it reflects a meaningful improvement in lung function.
    - A 17.4-point increase in FEV1 suggests that patients are experiencing a substantial improvement in their lung function, which can lead to better respiratory health and overall well-being.

2. *Impact on Symptoms and Quality of Life*:
    - Improved lung function can lead to reduced symptoms such as shortness of breath, increased exercise tolerance, and improved quality of life.
    - The increase in FEV1 may also correlate with improvements in other clinical outcomes, such as reduced frequency of pulmonary exacerbations and hospitalizations.

3. *Comparison to Minimal Clinically Important Difference (MCID)*:
    - The MCID for FEV1 in cystic fibrosis is generally considered to be around 5-10% (or approximately 100-200 mL) improvement from baseline.
    - A 17.4-point increase in FEV1 would likely exceed this threshold, indicating a clinically meaningful improvement.

4. *Long-term Implications*:
    - Sustained improvements in FEV1 over time can have long-term benefits for patients with cystic fibrosis, including reduced lung damage, improved survival, and enhanced quality of life.

In summary, a 17.4-point average increase in FEV1 is likely to be clinically meaningful for patients with cystic fibrosis treated with Trikafta, as it reflects significant improvements in lung function and potentially translates to better health outcomes and quality of life.

[13/09, 17:12]hu2: Please share references to where are you getting the data for the statements you are making.

If possible stick to the data in the two studies from 2019, nejm and Lancet I had linked above

[13/09, 17:12] Meta AI: The clinical meaningfulness of a 17.4-point average increase in FEV1 in patients with cystic fibrosis treated with Trikafta isn't directly supported by the data from the two 2019 studies you referenced.

According to the studies, Trikafta showed¹ ²:
- *Significant improvement in lung function*:
    - A 10-point higher ppFEV1 value compared to Symdeko at 4 weeks.
    - An increase of 13.8% from baseline in the 24-week placebo-controlled trial.
- *Improved respiratory symptoms and quality of life*:
    - A 17.4-point average increase in CFQ-R Respiratory Domain score compared to Symdeko at 4 weeks.
    - A 20.1-point average increase in CF respiratory symptom score compared to placebo at 4 weeks.
- *Reduced pulmonary exacerbations*:
    - 63% fewer pulmonary exacerbations compared to placebo.
    - 71% fewer pulmonary exacerbations leading to hospitalizations.
    - 78% fewer pulmonary exacerbations leading to IV antibiotics.

To determine the clinical meaningfulness of the FEV1 increase, we would need more information on the baseline FEV1 values and the specific context of the 17.4-point increase. However, the available data suggests that Trikafta leads to significant improvements in lung function, respiratory symptoms, and quality of life for patients with cystic fibrosis.

[13/09, 17:18] hu2 : Please share the above data in absolute numbers and don't use any percentages

[13/09, 17:18] Meta AI: Outcomes of Trikafta RCTs
Primary Outcomes
- *Improved Lung Function (FEV1)*:
    - In the 24-week placebo-controlled trial, the mean absolute change in ppFEV1 from baseline was 10.0 points higher with Trikafta compared to placebo.
    - In another study, the mean absolute change in ppFEV1 from baseline was 13.8 points with Trikafta.
- *Reduced Sweat Chloride Concentrations*:
    - Mean absolute change from baseline was -45.1 mmol/L with Trikafta compared to Symdeko at 4 weeks.
    - Mean absolute change from baseline was -41.8 mmol/L with Trikafta compared to placebo through 24 weeks.
- *Enhanced Health-Related Quality of Life*:
    - Mean absolute change in CFQ-R Respiratory Domain score was 17.4 points higher with Trikafta compared to Symdeko at 4 weeks.
    - Mean absolute change in CF respiratory symptom score was 20.1 points higher with Trikafta compared to placebo at 4 weeks.

Secondary Outcomes

- *Reduced Frequency of Pulmonary Exacerbations*:
    - 41 pulmonary exacerbations occurred in the Trikafta group compared to 113 in the placebo group.
    - 9 pulmonary exacerbations leading to hospitalizations occurred in the Trikafta group compared to 32 in the placebo group.
    - 11 pulmonary exacerbations leading to IV antibiotics occurred in the Trikafta group compared to 51 in the placebo group.



Thematic Analysis of the above conversational Transcripts:


1. Transformative Impact of Trikafta

- *Clinical Outcomes*: Trikafta significantly improves lung function (FEV1), reduces pulmonary exacerbations, and enhances quality of life scores in CF patients.

- *Life Expectancy*: The treatment is linked to a projected rise in life expectancy from 46 to 65 years by 2025. However, participants question the causality and note the role of broader healthcare improvements.

2. Critical Appraisal of Trial Data

- *Causality and Context*: While Trikafta's biological mechanism (CFTR modulation) is well-supported, the direct link between lung function improvements and extended life expectancy is deemed oversimplified.

- *Absolute Data Analysis*: Participants prioritize interpreting outcomes in absolute values (e.g., FEV1 improvement in mL) over percentages for better clinical relevance.

- *Quality of Life Correlation*: The CFQ-R score improvement (e.g., 8 points) is contextualized as influenced by factors beyond lung function, such as psychological health and infection control.

3. Accessibility and Affordability Challenges

- *Global Inequities*: Trikafta's high cost (~₹2.5 crore annually in India) and patent restrictions severely limit access in low- and middle-income countries.
- *Localized Solutions*: Initiatives like Wadia Hospital's partnership with Vertex Pharmaceuticals to provide free Trikafta to select Indian children are highlighted as steps toward equity.

4. Optimism Tempered by Realism

- *Heutagogic Lens*: Participants critically assess the infographic's claims, emphasizing the need for cautious optimism. Long-term adherence, social determinants of health, and potential side effects are noted as key variables shaping real-world outcomes.

- *Broader Context*: Advances in infection control, diagnostics, and healthcare infrastructure are acknowledged as contributors to improved CF survival, beyond Trikafta alone.

5. Ethical and Policy Implications

- *Patient-Centric Advocacy*: Calls for affordable access to Trikafta reflect the ethical imperative to ensure equitable healthcare.

- *Role of Pharma*: The sponsorship of global trials by a single pharmaceutical company is discussed, with an acknowledgment of both the scientific rigor and the economic interests at play.

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Key Insights and Gaps

- *Promising but Incomplete Evidence*: Trikafta demonstrates significant clinical benefits, but long-term survival data and real-world generalizability remain uncertain.

- *Need for Global Advocacy*: Bridging the gap between scientific breakthroughs and equitable access is a pressing challenge, particularly in resource-limited settings.

- *Critical Realism in Medical Evaluation*: Evaluating clinical breakthroughs requires not just enthusiasm but also a rigorous understanding of contextual factors and unintended consequences.