classwork: Precision Medicine

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2/10/18, 12:34 - Dr. Rakesh Sir Iq City changed the subject from "ATGCu" to "Precision medicine group"
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2/10/18, 15:33 - vivek poddar esa: Thanks for making this group.
2/10/18, 15:38 - vivek poddar esa: This is valuable input Avinash for our current write up on precision Medicine. Should we make a separate whatsapp group for those who may like to contribute to the write up? It may not be a review article only though and authorship for participants will depend on the quality and quantity of inputs (judged by the primary invited authors). Inputs can be in the form of problem statements that show and illustrate the current imprecision medicine that exists through published or unpublished common but complex case scenarios followed by our own work and imaginings to address the problem statement
2/10/18, 16:20 - ‪+91 98482 69227‬: What should we include in the write-up? A brief summary or a flow chart regarding the requirements would help..
2/10/18, 16:26 - Srija Katta: Solutions that are possible or expecting would be near possible or even far behind our imagination but can be true one day for the queries that we face daily in our patients !! Ultimately aiming the precision of the medical practice that we do !!
2/10/18, 16:27 - Srija Katta: This message was deleted
2/10/18, 16:28 - Srija Katta: Contribution can also come from. Raising the problem statements that are encountered every day with the Practice
2/10/18, 17:23 - Dr. Rakesh Sir Iq City: Let me share the invitation letter as that may provide some leads
2/10/18, 17:25 - Dr. Rakesh Sir Iq City: Dear Dr. Biswas,

We are arranging a Special Issue "Precision Public Health and Genomic
Medicine" in the journal /Healthcare/, edited by Dr. Alanna Kulchak
Rahm, Dr. Amy Curry Sturm and Dr. Susan T. Vadaparampil:

Special Issue "Precision Public Health and Genomic Medicine"
Submit Deadline: 30 May 2018
Website:
http://www.mdpi.com/journal/healthcare/special_issues/genomic_medicine

We think you could make an excellent contribution based on
your expertise and the following paper:

comparative effectiveness research collaboration and precision medicine. ANNALS OF NEUROSCIENCES 2015, 22, 127-129.

On behalf of Dr. Rahm, Dr. Sturm and Dr.Vadaparampil, we would like to
invite you to submit a paper to the Special Issue. You can ask some of
your staff/post-docs to write the paper in case you don't have time
yourselves.

-----------------------------
Now seven authors agreed to contribute papers to this special issue and
three authors are interested in this project. Please see the seven
agreed authors: Dr. Tolstikov, Dr. Ping, Dr. Birkeland, Prof. Miceli,
Dr. Graves, Dr. de Mendoza, Dr. Scherr.
-----------------------------

Please submit your manuscript at https://susy.mdpi.com/ when it is
ready. We will arrange fast peer review process. Submitted papers should
not be under consideration for publication elsewhere. We also encourage
authors to send a short abstract and tentative title in advance.

The instructions to prepare and submit the paper can be accessed at the
link: http://www.mdpi.com/journal/healthcare/instructions

/Healthcare/ (ISSN 2227-9032) is an international, scientific, open
access journal on health care systems, industry, technology, policy,
and regulation, and is published quarterly online by MDPI. Because it
is an open access journal, papers published will receive high
publicity. Rapid publication: manuscripts are peer-reviewed and a first
decision provided to authors approximately 33 days after submission;
acceptance to publication is undertaken in 7 days (median values for
papers published in this journal in 2016). Now /Healthcare/ is indexed
by ESCI, PubMed and PMC. Please see the indexing information at
http://www.mdpi.com/journal/healthcare/indexing

We appreciate your consideration and sincerely hope you will accept our
invitation to contribute to this Special Issue.

Look forward to hearing from you.

Sincerely,

On behalf of

Guest Editors
Alanna Kulchak Rahm, PhD, MS, CGC
Amy Curry Sturm, MS, CGC
Susan T. Vadaparampil, PhD, MPH

Zhenfang Zhao
Managing Editor

Healthcare (http://www.mdpi.com/journal/healthcare)
Indexed by ESCI / PubMed/PMC

--
Healthcare Editorial Office
MDPI AG
St. Alban-Anlage 66, 4052 Basel, Switzerland
Tel. +41 61 683 77 34 (office)
Fax: +41 61 302 89 18
E-mail: healthcare@mdpi.com
http://www.mdpi.com/journal/healthcare
2/10/18, 17:58 - Dr. Rakesh Sir Iq City: Can each of this writing team's members google "comparative effectiveness research, precision medicine, case experiences reasoning, decision making and after you share the review of literature here we could discuss the evolving framework for this write up?

Let's first discuss precision Medicine beginning with the most popular definition?
2/10/18, 18:03 - Dr. Rakesh Sir Iq City: Here's https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587042/

a link to a past write up that was also a similar invited article. Again our current write up will be based primarily on what "medicine" we are currently working on especially illustrating the imprecision in current workflows and how we may overcome these utilizing available and evolving solutions to usher in the era of "precision Medicine."
2/10/18, 18:11 - vivek poddar esa: Precision medicine (PM) is a medical model that proposes the customization of healthcare, with medical decisions, treatments, practices, or products being tailored to the individual patient.

the National Research Council explains: Precision Medicine refers to the tailoring of medical treatment to the individual characteristics of each patient.
2/10/18, 18:12 - ‪+91 98482 69227‬: Will we be including cases in this write-up?
2/10/18, 18:15 - ‪+91 98482 69227‬: In the above article the main issue which was discussed was on how to improve the quality of the care to the patient and how we can achieve by improving the standard of the MBBS education. This is what I could make out of the above article in few sentences.
2/10/18, 18:18 - ‪+91 98482 69227‬: This write-up would be focusing on the various obstacles faced by the medicine fraternity while treating the patients and how imprecise we are when we get to treat the patients.
2/10/18, 18:18 - ‪+91 98482 69227‬: Am I correct in what I have understood of the main motive behind this write-up?
2/10/18, 18:20 - Dr. Rakesh Sir Iq City: Yes obstacles in terms of individual patient decision making (and we need not think about fraternities, just patient problems and solutions)
2/10/18, 18:36 - vivek poddar esa: Like if a patient is admitted in the hospital and undergoing different diagnostic evaluations and despite all the available diagnostic modalities in a given hospital, if we are uncertain about any particular diagnosis and then we are trying to resolve that uncertainty for that patient through precision medicine!!
2/10/18, 18:37 - vivek poddar esa: so that we can tailor and modify our approach toward solving the problem even in a low resource setting.
2/10/18, 18:37 - Dr. Rakesh Sir Iq City: Yes but how
2/10/18, 18:38 - Dr. Rakesh Sir Iq City: Can you share any example where you saw this happen?
2/10/18, 18:52 - Dr. Rakesh Sir Iq City added Dr. akshay anand PGI
2/10/18, 18:52 - Dr. Rakesh Sir Iq City added Amy price maam
2/10/18, 18:53 - Dr. Rakesh Sir Iq City added Abhishek sir IBM
2/10/18, 18:53 - Dr. Rakesh Sir Iq City: As medicine is essentially diagnosis and treatment can we have the group's inputs on what would they consider to be "precision diagnosis" and "precision treatment?"
2/10/18, 18:56 - vivek poddar esa: In one of our patient who admitted to us with COPD and Pneumonia. We did CT of lung which showed pneumonia in this patient. We wanted to take sample from the lung and had a dilemma between "Sheath vs non-shealth bronchoscopy". After searching on literature we found that shealth bronchoscopy is most preferred as chances of contamination is less but we also found that ET Tube suctioning is as good as sheath bronchoscopy. Hence, we went for ET suctioning for C/S.

As sheath broncoscopy was not available at that hospital and we needed to collect the sample, so we did the ET suctioning which was available in that hospital and helped us to get sample.

Is it really an example of precision medicine practice sir? .To be able to answer your question can more clearly with more examples will clear the whole picture of precision medicine.
2/10/18, 18:56 - Deepak Bhadani BMJ: Sir even if we come to know about any patient? How to individualise this thing to every patient. I mean to say that as every disease is different & so does the each patient. I mean to say how to know patient's thinking on individual basis. This would be more helpful i think.

Another thing to ponder upon is why in rural India patients are hiding their disease making them worse cases?
2/10/18, 18:57 - Deepak Bhadani BMJ: That is what i conclude after reading that article you shared earlier.
2/10/18, 19:00 - Dr. Rakesh Sir Iq City: Could be an example for good clinical practice perhaps but perhaps not "precision Medicine?"
2/10/18, 19:01 - Dr. Rakesh Sir Iq City: Which brings me back to this previous query, "Can we have the group's inputs on what would they consider to be "precision diagnosis" and "precision treatment?"
2/10/18, 19:03 - vivek poddar esa: Many patients are prescribed or self-prescribed antibiotics when it doesn't require. If a patient presented to us and has history of recurrent fevers and previously patient had been prescribed with antibiotics. Now, if we advise the patient to do fever charting and send us the fever chart, we can guide the patient if any actions need to be taken further and should wait.

Patient is not able to do the charting manually and can not communicate to us properly.

So, this is a problem that the patient is facing.
2/10/18, 19:03 - Dr. Rakesh Sir Iq City: Good questions. More food for thought. Yes one way we can do that currently which will be our ultimate proposed solution in the article has been discussed by us before. Can you review the literature further and share or even more ideas are welcome
2/10/18, 19:03 - ashwini usa: This is pretty cool. Would love to contribute
2/10/18, 19:03 - ashwini usa: Give me a day. I'll think of something as well
2/10/18, 19:05 - Dr. Rakesh Sir Iq City: This illustrates our current imprecise medicine that is our daily bread and what we tried to highlight in Cuttack as making do with a workflow where we see an incomplete or blurred picture most of the time.
2/10/18, 19:07 - Deepak Bhadani BMJ: But sir it is not only about over the counter (OTC) drugs that patients are getting. Other drugs which are not supposed to available without prescription are easily available without any prescription. That is making patient's way easy to not to consult physician at appropriate time.
2/10/18, 19:11 - vivek poddar esa: Precision treatment could be reaching inside at the genomic level of the patient condition and finding a treatment that can target the genomic defect of that specific patient?
2/10/18, 19:17 - vivek poddar esa: A patient presenting to us recurrently with a particular disease and to prevent recurrence we may try to make a clinical prediction tool for that patient that will help us to predict future recurrence of the same disease and help early intervention for that patient.

I am making out whatever in my mind coming. But, it forces thinking from different angles.
2/10/18, 19:57 - Dr. Rakesh Sir Iq City added Aadipta Iq City
2/10/18, 19:57 - Dr. Rakesh Sir Iq City added pratya bhowal
2/10/18, 19:57 - Dr. Rakesh Sir Iq City changed the subject from "Precision medicine group" to "Precision medicine FGD"
2/10/18, 19:59 - Dr. Rakesh Sir Iq City: FGD stands for focused group discussion and for those of you who are research methodology enthusiasts here can you review the literature on this qualitative research tool and discuss how we may utilize it to write our current paper?
2/10/18, 20:01 - Dr. Rakesh Sir Iq City: This is the current popular thought about precision Medicine but can we share why should diagnosing and treating illness with precision be limited to genomics when we are aware that it is a product of gene and environmental drivers?
2/10/18, 22:22 - Dr. Rakesh Sir Iq City added ‪+91 77097 62525‬
2/10/18, 23:13 - Sreyash Chwathey Bmj: Therapeutic Drug Monitoring (TDM) and checking for specifics like CYP polymorphism; possible adverse effects of drugs and avoidance of drugs based on patient profile maybe also included? Any suggestions??
2/10/18, 23:50 - Dr. Rakesh Sir Iq City: Alright these are different ways to reach precision for a given patient but can anyone share what it would look like in terms of reaching precision toward diagnosis and treatment?
2/10/18, 23:51 - Dr. Rakesh Sir Iq City: In other words what image or picture comes in our mind when we think of an ideal diagnosis or treatment outcome?
2/10/18, 23:59 - Sreyash Chwathey Bmj: A particular protocol to tackle various aspects of physician patient contact from first contact to reaching diagnosis using set guidelines and methods as per evidence based literature and reaching a management strategy
2/11/18, 00:02 - Dr. Rakesh Sir Iq City: These are alright as far as an average requirement is concerned but can it make us cater to the individual patient's requirement with precision?
2/11/18, 00:02 - Sreyash Chwathey Bmj: Thanks RB
Ok now I understand more clearly
2/11/18, 00:04 - Sreyash Chwathey Bmj: We need to tailor all medical investigations, treatment and methods to monitor and follow up as per patient profile and needs
2/11/18, 00:07 - Sreyash Chwathey Bmj: https://labiotech.eu/ardigen-ai-precision-medicine/
2/11/18, 00:08 - Sreyash Chwathey Bmj: This lab uses AI to develop precision medicine
2/11/18, 00:09 - Sreyash Chwathey Bmj: What’s the difference between Precision medicine and personalised medicine? @919617604831 @918096688887 @8801752868045 @19544716143
2/11/18, 00:10 - Dr. Rakesh Sir Iq City: Problem with non precision current generation population based medicine is well summarized here,

"Facing a rapidly growing body of medical knowledge, physicians rely on high-level aggregate-based knowledge resources, such as online knowledge bases, meta-analyses and clinical practice guidelines. However, this results, by default, in clinicians treating individual patients as if they were members of a homogeneous group."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289871/
2/11/18, 00:10 - Srija Katta: Comparison between normal and the pathological conditions of the Patient gives us diagnosis then pathological conditions and normal gives us therapeutic action
This can give us precision
2/11/18, 00:12 - Sreyash Chwathey Bmj: Is it right to think that we need precision medicine mainly for patients whose characteristics fall on either side of the distribution curve beyond the 95% confidence intervals?
2/11/18, 00:13 - Sreyash Chwathey Bmj: Or is it applicable to personalised medicine?
2/11/18, 00:16 - Sreyash Chwathey Bmj: https://ghr.nlm.nih.gov/primer/precisionmedicine/precisionvspersonalized
2/11/18, 00:16 - Sreyash Chwathey Bmj: There is a lot of overlap between the terms "precision medicine" and "personalized medicine." According to the National Research Council, "personalized medicine" is an older term with a meaning similar to "precision medicine." However, there was concern that the word "personalized" could be misinterpreted to imply that treatments and preventions are being developed uniquely for each individual; in precision medicine, the focus is on identifying which approaches will be effective for which patients based on genetic, environmental, and lifestyle factors. The Council therefore preferred the term "precision medicine" to "personalized medicine." However, some people still use the two terms interchangeably.
2/11/18, 00:16 - Dr. Rakesh Sir Iq City: Both are same
2/11/18, 00:17 - Sreyash Chwathey Bmj: Thanks RB
2/11/18, 13:27 - Dr. Rakesh Sir Iq City: Yes Shreyas although currently the terms are used nearly interchangeably there is a lot of difference in their literal meanings.
2/11/18, 13:29 - Sreyash Chwathey Bmj: Thanks RB
2/11/18, 13:31 - Dr. Rakesh Sir Iq City: And I guess in that context I need to reframe my initial question when I asked the group's thoughts on what do we mean by "precise" diagnosis and treatment and perhaps I should ask what comes to our minds when we hear "ideal" way to diagnosis and treatment and I shall try to illustrate my own answer to this with a case (not my own)
2/11/18, 13:34 - Sreyash Chwathey Bmj: We are waiting 😊
2/11/18, 14:27 - Dr. Rakesh Sir Iq City added ‪+91 81260 21556‬
2/11/18, 13:46 - Dr. Rakesh Sir Iq City: Actually the answer will be anywhere but precise and perhaps the nature of Medical practice is to think diffusely with a wider net of differentials and once a large amount of data (both from the patient as well as general knowledge) is gathered we settle down into weaving a story of the where and why of the problem till we reach a stable decision point when we begin to think about what can be done about it. Again this is just system 2 thinking that would not be done in critical care emergencies when one would read whatever data is visible on the surface of the body and jump to action for example intubating a person who is gasping and collapsed with hypotension. I too am waiting to describe the other chronic case scenario which is where system 2 needs an ideal vision that can come from precision thinking and mind you often the critical ill collapsed person will recover and then you will need to deliver care for the chronic problem that made him collapse in the first place
2/11/18, 14:54 - Deepak Bhadani BMJ: https://youtu.be/AIjU6VtpVO4
2/11/18, 15:37 - Dr. Rakesh Sir Iq City: Thanks for sharing this. As soon as we get into the introduction of his lecture we are shown that the medicine that is prescribed is currently not precise. What is not well highlighted to the public including scientists at large is that the process of Medicine is not often about the active principles in our medicine but more often about time and ill understood cellular events in the body that lead to healing (aka the target of precision Medicine). This point will find important mention in our paper
2/11/18, 17:04 - Deepak Bhadani BMJ: <Media omitted>
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2/11/18, 17:08 - Dr. Rakesh Sir Iq City: Share your own thoughts and insights that you had after reading the book
2/11/18, 17:09 - Deepak Bhadani BMJ: Sure Sir
2/11/18, 17:14 - Dr. Rakesh Sir Iq City: I'm also going through what you shared and it is written very lucidly I must say
2/11/18, 17:22 - Deepak Bhadani BMJ: Precision medicine as per book is defined as to reaching as much as closer to a specific symptom or in better words looking for root cause of a symptom.

☆ As earlier we used to treat diseases purely based upon the symptoms but now there is much need to know about how a particular sign & symptom is arising because not only every human but every cell (out of all 50-75 trillion) are different & functioning differently and there is need to understand mechanism of symptoms.

e.g. Prescribing antipyretics just because patient have a fever will not solve our motto if we think from *precision medicine* point of view.

And definitely no doubt in this: "Precision medicine is the reinvention of human disease", as author kept title of chapter one. There is need to understand symptoms from very starting & using all our knowledge to get good results in the end. Because i am very satisfied here that every disease develops in so called *sequential process.* There is a need to understand all those steps which is responsible for occurence of a disease to effectively use available treatment in a precise manner.
2/11/18, 17:24 - Deepak Bhadani BMJ: And Sir to kept all the pages in a very summarised manner seems difficult as i read more i found every line is written very much appropriately & differently here.

☆ Explaination of DSM
☆ Explaination of disease step process and many more are nicely explained.
2/11/18, 17:30 - Deepak Bhadani BMJ: And Sir in chapter 9 of the same book, chapter named, "The Alternative Futures of Precision Medicine", there is a subheading "Do it yourself Medicine." Will provide summary about those pages too.
2/11/18, 17:52 - Sreyash Chwathey Bmj: That’s very interesting “DIY Med”
2/11/18, 18:47 - Dr. Rakesh Sir Iq City: https://www.personalizedmedicinebulletin.com/2016/02/29/capitalizing-on-collaboration-the-presidents-precision-medicine-initiative/
2/11/18, 19:27 - Deepak Bhadani BMJ: https://youtu.be/MKiw7yAqqsU
Sir this is the video link for same. I saw it before that TED talk which i shared earlier.
2/11/18, 20:47 - Dr. Rakesh Sir Iq City: <Media omitted>
2/11/18, 20:54 - ashwini usa: Hi so I just went through the entire discussion here. Have a couple of doubts:
The invitation speaks of integration of precised public health and genomics.
What is precise public health- if precision medicine is tailoring it down to individual patients ? Isn't it a little misleading !
2/11/18, 20:55 - ashwini usa: And are we just limited to discussing genomics and molecular level say drug designing or something like that to the individual level ?
2/11/18, 20:55 - ashwini usa: Also based on what we are discussing I think we are just discussing evidence based medicine like seeing the literature and deciding appropriate treatment
2/11/18, 20:56 - Abhishek sir IBM: Very interesting thread. Hopefully it remain on by the time I am back full time on WhatsApp👍
2/11/18, 20:56 - ashwini usa: So precision medicine will be different than that right ?
2/11/18, 20:56 - Dr. Rakesh Sir Iq City: I shall clarify by using a specific case based example.
2/11/18, 20:57 - Dr. Rakesh Sir Iq City: Look at the case discussion in the global learning group
2/11/18, 20:58 - ashwini usa: Oh I haven't seen that group yet. Will do so
2/11/18, 20:59 - Dr. Rakesh Sir Iq City: No this would be traditional approach to medicine that we also engage in but what we do differently is use case based reasoning. See the details in the links and PDF shared on this
2/11/18, 21:24 - Madhava Sai Bmj: @919140654820 @8801752868045 @8801515269048 Could someone please mail me the chat of this conversation I lost my phone and now I am backed up so that I could be on track
2/11/18, 21:24 - Madhava Sai Bmj: Please this would help me a lot
2/11/18, 21:26 - Avinash Kumar: sent
2/11/18, 21:26 - Madhava Sai Bmj: Thank you bro
2/11/18, 21:27 - Avinash Kumar: wc!
2/11/18, 22:07 - ashwini usa: Yes sir
2/11/18, 22:49 - Avinash Kumar: @917409548443 bro, plz share book pdf/epub here, we will also read.
2/11/18, 22:50 - Deepak Bhadani BMJ: I am reading it from google book itself.

https://books.google.co.in/books?id=2UE7DwAAQBAJ&pg=PA56&lpg=PA56&dq=cellular+events+in+precision+medicine&source=bl&ots=52ai4Blj5J&sig=PYN_pHM7Mpf5GeTbDzwkuG8uYEI&hl=en&sa=X&ved=2ahUKEwi7iO-r153ZAhUMLY8KHYFmCiMQ6AEwBHoECAwQAQ#v=onepage&q=cellular%20events%20in%20precision%20medicine&f=false
2/11/18, 22:51 - Avinash Kumar: thanks a lot..will find in libgen
2/11/18, 22:51 - Deepak Bhadani BMJ: Welcome 😇
2/11/18, 22:57 - ashwini usa: Thank you ! This seems like an interesting book
2/11/18, 23:04 - Deepak Bhadani BMJ: Welcome!
2/12/18, 14:51 - Madhava Sai Bmj: <Media omitted>
2/12/18, 14:53 - Madhava Sai Bmj: <Media omitted>
2/12/18, 14:53 - Madhava Sai Bmj: <Media omitted>
2/12/18, 14:54 - Madhava Sai Bmj: Shared by Amy mam
2/12/18, 15:09 - vivek poddar esa: Thanks Madhava for sharing it here.
2/13/18, 09:17 - vivek poddar esa: Mayo Clinic researcher Dr. DeLisa Fairweather is taking a new approach to heart disease – she’s exploring how heart disease develops in men versus women, with the goal of finding new diagnostic tests and individualized therapies based on these sex differences.

https://individualizedmedicineblog.mayoclinic.org/2018/02/06/a-new-approach-to-heart-disease-individualized-therapies-for-men-and-women/?utm_source=linkedin&utm_medium=sm&utm_content=post&utm_campaign=mayoclinic&mc_id=us&geo=national&placementsite=enterprise&cauid=105028&linkId=47844066
2/13/18, 09:29 - Abhishek sir IBM: Yeah... Pretty nice line of work
2/13/18, 09:48 - Deepak Bhadani BMJ: https://youtu.be/795u8zl82GI

Can we link this concept with concept of David Barker: Barker's Hypothesis?
2/13/18, 09:49 - Dr. Rakesh Sir Iq City added madhumita iq city
2/13/18, 09:50 - Dr. Rakesh Sir Iq City: Elaborate how would you propose to link it
2/13/18, 09:55 - Deepak Bhadani BMJ: Sir with proper nutrition very early from reproductive age itself to maintain it in prenatal, antenatal & postnatal life. And then focussing or continuing our approach in the way as mentioned in above article (Heart disease more common in males). Although it seems much costly to study this thing throughout this period.
2/13/18, 09:57 - Deepak Bhadani BMJ: Applying RMNCH+A concept not only in preventive way what we read in books but in real sense to tackle non communicable disease from starting. Understanding reproductive physiology & providing proper nutrition to pregnant females.
2/13/18, 09:58 - Dr. Rakesh Sir Iq City: As "precision Medicine" currently appears to be elucidation of the biomic pathways to disease we would first need to be able to observe these inside a biological system first and prove Barker's hypothesis?
2/13/18, 09:59 - Dr. Rakesh Sir Iq City: It is logical that undernutrition at any stage of life can be harmful and there is no reason to support any program that tries to eradicate it?
2/13/18, 10:00 - Dr. Rakesh Sir Iq City: No reason not to
2/13/18, 10:00 - Deepak Bhadani BMJ: And Sir rather than providing pure folic acid or iron tablets we can provide them plant sources of folic acid & iron. i.e millet diet during period of pregnancy. How it will affect prognosis?
2/13/18, 10:03 - Dr. Rakesh Sir Iq City: Pure sources lack the precision offered by a mg dosage that is quantifiable and hence thought to be better evaluable?
2/13/18, 10:06 - Deepak Bhadani BMJ: <Media omitted>
2/13/18, 10:10 - Deepak Bhadani BMJ: Yes sir agreed.
2/13/18, 10:35 - Dr. Rakesh Sir Iq City: May turn out to be expensive unless we propagate the concept of growing one's own food
2/13/18, 10:39 - Deepak Bhadani BMJ: Yes this is major problem to apply it for general population.
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2/13/18, 13:06 - ‪+880 1725-266274‬: Can all of us give some more case example for precision medicine? So that whenever I look for precision medicine, I can pinpoint "yes this what precision do". I was a bit backdated if it all discussed clearly. Suppose I am a patient and have been admitted to a hospital with some sort of clinical problems e.g. pneumonia. Now apart from giving me traditional ways of diagnosis and treatment, how precision can improve my requirements which would otherwise be absent?
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2/13/18, 13:24 - Dr. Rakesh Sir Iq City: Yes digging deeper into a case is a very good way to understand the learning requirements in any area of healthcare as a 'case' is the basic unit of any healthcare activity around which our research universe is built
2/13/18, 17:23 - Dr. Rakesh Sir Iq City added arunan sir
2/13/18, 17:23 - niharika cg 1st joined using this group's invite link
2/14/18, 16:41 - Dr. Rakesh Sir Iq City: One of the problems with current medical innovation ecosystems (both drugs and devices) is that they create solutions that are like straitjackets forcing a one size fits all? Again that is understandably linked to market forces but is there any chance of being close to creating an ecosystem that may allow answering individual requirements in a precise personalized manner?
2/14/18, 16:58 - Dr. Rakesh Sir Iq City: We need to submit the title and abstract of the final product of this group work by coming week and one of the title that I suggest is

"Developing a case based blended learning multidisciplinary ecosystem toward precision Medicine."

This way we can build on our previous work here

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587042/

and update others about the recent additions shared yesterday by Avinash along with the crux of the article that will systematically review case reports which represent work that tried elucidating molecular pathways for various aspects of disease, namely infection, autoimmune and neoplasm.

Hunch is we may find that current mechanisms of elucidating pathways are grossly inadequate and will require a different approach that we shall try to elaborate.

I will share a first case report asap. This case report already has nearly 2000 citations!
2/14/18, 17:02 - ‪+880 1725-266274‬: Okay sir
2/14/18, 17:04 - Madhava Sai Bmj: 👍🏽
2/14/18, 17:05 - Deepak Bhadani BMJ: 👍🏻
2/15/18, 17:58 - vivek poddar esa: sir can u share the case report?
2/15/18, 18:00 - Dr. Rakesh Sir Iq City: Am having final mbbs exams so not getting day time but will try at night. It's very tedious. I'm having to go through it and understand and will have to share it in a way that will illuminate our way forward.
2/15/18, 18:01 - Dr. Rakesh Sir Iq City: And not just one. One infection and another immune dysfunction followed by similat cases and insights shared by this group once everyone gets the idea
2/15/18, 20:26 - Dr. Rakesh Sir Iq City: Getting into Doctor’s Mind

Doctors may not be the brainiest in society; yet the fascinating ways in which they think and make decisions has been the subject of interesting research. A book by Dr Jerome Groopman attempts to analyse it.

There are some parts of the brain that a doctor uses preferentially over others, memory being the most important to start with. It begins from the time a youngster thinks of taking the entrance exam to medical school – he is required to read, retain and reproduce a large number of factual information and names of body parts and functions.

Unlike the engineering, management, or law students, medical aspirants are hardly required to use mathematical problem solving, creative thinking, logic or thinking out of the box. But ask them names and profiles of thousands of organs, tissues, cells and drugs, and they will have it on their fingertips!

As they progress to the next phase of clinical work, doctors learn to recognise “patterns” of symptoms and signs in patients, and try to fit these into the puzzle board of diagnosis. Chest pain accompanied by sweating would suggest a heart attack, or jaundice with loss of appetite would fit the pattern of “hepatitis”, for instance.

When the doctor starts maturing as a clinician, he starts to pick up a feature called “probabilistic” thinking, wherein the patient’s profile starts becoming a key factor rather than the symptoms alone. To take the example of chest pain again, he starts recognising that the same symptom in a young 20-year-old girl is almost always of neuro-muscular origin and hardly ever from the heart, while in a 50-year-old overweight smoker with high BP, it is very likely to be a heart attack, requiring immediate referral to a cardiac ICU.

With further development in his career, he starts factoring in several aspects of his patient in the process of decision-making. In other words, it is at this stage that he starts incorporating the “art” of decision making to the text-bookish science that he has crammed. Does the vegetable vendor who has come down with cough and fever for 2 days after getting wet in the rain require to be subjected to a CT scan of the chest or would an antibiotic suffice? Does the 16-year-old schoolgirl with recent onset vomiting prior to the board exams require an endoscopic examination right away? What if she had had these symptoms last year too when she was stressed before her final exams?

The mature doctor then is not just a repository of facts, information and knowledge. It is the unconscious assimilation of years of experience, marinated with a sensitive understanding of his patient’s concerns and constraints, and with an iota of intuition thrown in, that make him take decisions that posterity usually seems to approve.

In present times, things get pretty amusing. I often get patients demanding investigations to find out what the reports say and that would explain their symptoms. And then the doctor has to explain why the reports don’t give a clear diagnosis!

Good clinical decision making, like good wine, matures over time. Knowledge alone does not make a good doctor; the flavor matters!
2/15/18, 22:03 - ‪+91 81260 21556‬: agreed.. .. one thing about the systematic reviews based evidences i am confused is ,”whether the flavour is neglected in decision making..is clinical experience overlooked ?”
2/16/18, 17:02 - ankita cg 1 joined using this group's invite link
2/16/18, 17:02 - Dr. Rakesh Sir Iq City added ‪+91 94419 02421‬
2/17/18, 11:18 - vivek poddar esa: we need to submit our short abstract and tentative title asap
2/17/18, 12:34 - Avinash Kumar: sending in an hour.
2/17/18, 12:36 - Srija Katta: I shared a link it can help I guess Check u r mail
2/17/18, 12:38 - Madhava Sai Bmj: Please send it to me too
2/17/18, 12:41 - Srija Katta: I shared to all you guys dint u get??
2/17/18, 12:41 - Madhava Sai Bmj: No
2/17/18, 12:41 - Sreyash Chwathey Bmj: Is this the WHRC thing? Or this Precision Med??
2/17/18, 12:42 - Srija Katta: Ok I shall resend the signal is very bad here
2/17/18, 12:42 - Madhava Sai Bmj: Precision Medicine
2/17/18, 12:46 - ‪+91 98482 69227‬: Which one?
2/17/18, 12:47 - Sreyash Chwathey Bmj: Okay
2/17/18, 12:47 - Sreyash Chwathey Bmj: Even i didn’t get the mail
2/17/18, 13:01 - Dr. Rakesh Sir Iq City: I shall confirm the title and abstract. Don't send without my confirmation. Have it in my head but not finding time to write it
2/17/18, 13:01 - Avinash Kumar: will share here only sir
2/17/18, 13:02 - Avinash Kumar: writing need.
2/17/18, 13:03 - ‪+880 1725-266274‬: Thanks Avinash and Srija. I was worried as deadline for the tentative title submission was approaching soon.
2/17/18, 13:05 - Madhava Sai Bmj: Thanks avinash and srija
2/17/18, 13:22 - ‪+880 1725-266274‬: Yes sir
2/17/18, 15:43 - Srija Katta: “Crowdsourcing Medical Evidences in a / Developing a case based blended learning multidisciplinary ecosystem toward precision Medicine."
Final Abstract:-
Current imprecise medical system has replaced eminence-based medicine to evidence-based system coming from the application of analytics, called the imperfect science of statistics on a very small subset of care seeking or healthy individuals with a placebo and drug for the treatment which is accelerated by high tech. Labs and various case reports of diseases and other evidences to match patterns for diagnosis, where again labs have been very useful. Dealing with the imprecise becomes the art of experienced practitioner, to become as accurate as possible. This process of healthcare have design fault of one size fits all and always brings some know/unknown harm along with desired benefits. Our Idea of precision medicine is based on taking every patient journey mapped as source of evidence in form of various media like text, image, graphs, videos, etc. which shared in HIPAA compliant online record in our blended learning ecosystem where multidisciplinary community deals with creating questions in PICO format and exploring answers, trying to explore from medical, engineers and social perspectives to find answers for patient-centered challenge in an individual performing shared decision making. Our efforts generate well recorded patient journey/history along with possible questions where some we find answers and some become topics of research interest and blended learning exercise generates data for creating and Artificial intelligence based system to learn from various patient journey recorded and learn all the patterns as well as questions and answers from various disciplines understanding anatomical anomalies visible by a naked eye to genomics & metabolomics and various pathies. This AI system works as a clinical decision system and helps in precision public health by its uses/ access monitoring. The way we making our medicine practice more precise is by having interdisciplinary team engaged in decision-making process based on pieces of evidence, while we are generating a novel way of precision diagnostic and treatment to revolutionize health care of future on our foundation of blended learning process and our paper details the above mentioned creterias with a case based illustrations and showcase the challenges.

(by Srija & Avinash)
2/17/18, 15:52 - Avinash Kumar: Abstract. please review. need to Topic name also.
2/17/18, 15:59 - Dr. Rakesh Sir Iq City: Well done Avinash and Srija. Share your current abstract with Amy on email as it will need to be edited. I shall add from my end soon. Please check if they mentioned a word limit for the abstract. I shall meanwhile share more thoughts when I find time. We have exams continuously even on Sundays
2/17/18, 16:00 - Avinash Kumar: thanks sir. we will share ma'am in separate thread because in main thread journal ppl are there, to whom it may not be best to show raw version.
2/17/18, 16:00 - Avinash Kumar: thanks sir.
2/17/18, 16:02 - Dr. Rakesh Sir Iq City: My title: shortened

Developing a Case based blended learning ecosystem toward precision Medicine: current limitations and way forward
2/17/18, 16:06 - Dr. Rakesh Sir Iq City: Off course definitely not the journal editors as currently only Amy and Myself are a part of that thread. When I shared that thread with you all I didn't include the journal editors. Share only with Amy with a Cc to me, Vivek et al
2/17/18, 16:06 - Avinash Kumar: yes sir. thanks.
2/17/18, 16:06 - Avinash Kumar: updated.
2/18/18, 08:29 - Dr. Rakesh Sir Iq City: <Media omitted>
2/18/18, 15:50 - Dr. Rakesh Sir Iq City: What do you feel would be the role of precision Medicine in addressing the issue represented in the quote below?

"Atul Gawande, the surgeon-researcher-public health activist in his recent essay describes the current medical practice so succinctly : "Millions of people are receiving drugs that aren’t helping them, operations that aren’t going to make them better, and scans and tests that do nothing beneficial for them, and often cause harm."

Once a test or a procedure or an operation becomes popular, it is difficult to dislodge them. And the hospitals offer hundreds of such interventions, based on rituals and anecdotes. They have no proven value. Indeed many of them are harmful. Time that the medical community decides to treat patients on solid scientific evidence, and not on tradition."
2/18/18, 16:21 - ‪+880 1725-266274‬: N of 1 trial?
2/18/18, 16:56 - Dr. Rakesh Sir Iq City: What are the limitations of n=1 trials?
2/18/18, 17:10 - ‪+880 1725-266274‬: " N-of-1 trials are applicable to chronic, stable, or slowly progressive conditions that are either symptomatic or for which a valid biomarker has been identified.
*Acute conditions offer no opportunity for multiple crossovers*
*Rapidly progressive conditions (or those prone to sudden, catastrophic outcomes such as stroke or death) are not amenable to the deliberate experimentation of n-of-1 trials*.
*Asymptomatic conditions make outcomes assessment difficult*, unless a valid biomarker exists"

Treatments to be assessed in n-of-1 trials should have relatively rapid onset and washout (i.e., few lasting carryover effects).
*Treatments with a very slow onset of action (e.g., methotrexate in rheumatoid arthritis) could outlast the patience of the average patient and clinician*
*treatments with prolonged carryover effects would require a substantial washout period to distinguish between the effects of the current treatment and the previous treatment*
*regimens requiring complex dose titration (e.g., loop diuretics in patients with comorbid congestive heart failure and chronic kidney disease) are not well suited for n-of-1 trials*
" https://effectivehealthcare.ahrq.gov/topics/n-1-trials/research-2014-4
2/18/18, 17:13 - ‪+880 1725-266274‬: <Media omitted>
2/18/18, 17:13 - ‪+880 1725-266274‬: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972259/
2/18/18, 17:14 - ‪+880 1725-266274‬: The success of an n-of-1 trial largely depends on the collaboration and commitment of both clinician and patient. So, the factors from both the patient and clinicians will determien in many cases the success of these trials.
2/18/18, 17:15 - ‪+880 1725-266274‬: "N-of-1 trials are a specific form of randomized or balanced designs characterized by periodic switching from active treatment to placebo or between active treatments (*withdrawal-reversal" designs*). "
2/18/18, 17:18 - ‪+880 1725-266274‬: Historical background of N of 1 trials for all- " N-of-1 trials were introduced to clinicians by Hogben and Sim as early as 1953, but it took 30 years for the movement to find an effective evangelist in the person of Gordon Guyatt at McMaster University."
2/18/18, 20:50 - ‪+880 1725-266274‬: Precision medicine can play a role on building personalized evidence?'
2/18/18, 20:54 - Avinash Kumar: evidence based practice takes us towards precision medicine and every patient treated generates evidence hence helping us be more precise.

evidences *are used to* personalise treatment. and on treatment data / evidence generated are personalised evidences as well as evidence for population too..
2/18/18, 20:58 - ‪+880 1725-266274‬: We are need to generating evidence after every patient treated and if that would happen then the practice would be more precise
2/18/18, 20:58 - ‪+880 1725-266274‬: We are not**
2/18/18, 21:03 - Sreyash Chwathey Bmj: Lack of evidence (due to a number of reasons) and “eminence based” medicine —> unnecessary investigations/procedures—> “defensive” medicine
2/18/18, 21:15 - ‪+880 1725-266274‬: Systematic reviews of case reports can be a good personalized evidence?
2/18/18, 23:08 - Dr. Rakesh Sir Iq City: How?
2/18/18, 23:21 - ‪+880 1725-266274‬: When we encounter patients, we look for case reports that match with the admitted case and how they approached and in this we see if those patients presented with similar clinical features. If we can systematically review case reports with matching characteristics then, probably the next new case may get more benefit?
2/18/18, 23:36 - Srija Katta: Role : Targeted promisable or seems to be effective precision treatment/diagnosis can be economic and increase quality of life( in all the way round)
2/18/18, 23:39 - ‪+880 1725-266274‬: how precision medicine can target the individual patients problem such as the story shared by sir? Any ways?
2/19/18, 10:19 - ashwini usa: I apologise about the non involvement in the discussions since the last few weeks. Once I am back to India I'll be back in action.
Thank you
Ashwini Ronghe
2/19/18, 14:49 - Dr. akshay anand PGI: Can use it there to argue

http://www.tribuneindia.com/mobi/news/in-focus/the-healing-code/545905.html
2/19/18, 16:04 - Dr. Rakesh Sir Iq City: This is interesting. There appears to be considerable overlap of ideas. Is it because these authors may be connected to some of us (are they your students Akshay?) or is it that many people are thinking on a similar direction in the present phase of our scientific evolution that appears poised for transformation?
2/19/18, 16:04 - Dr. akshay anand PGI: Completely unrelated to our group
2/19/18, 16:05 - Dr. akshay anand PGI: Presumably, they seem to have read our previous article as there are references to NMC published in the same newspaper

You must contact them
2/19/18, 16:05 - Dr. Rakesh Sir Iq City: How do we contact them?
2/19/18, 16:06 - Dr. akshay anand PGI: Write to editorinchief@tribuneindia.com
2/19/18, 16:07 - Dr. akshay anand PGI: And also high time that you communicate your ideas as a separate article
In the same mail you could explore this with editor
2/19/18, 16:12 - Dr. Rakesh Sir Iq City: Well we are working on a paper here in this group to communicate our ideas but yes a newspaper may have better impact. 😊
2/19/18, 16:12 - Deepak Bhadani BMJ: Sir how complementary medicine is separate from precision medicine as per this article?

As there mentioned use of Chinese medicine + Ayurveda + Patient's detailed history including not only 24 recall apart from calculating digestive ability and sleeping hours & pattern. It is very good article.

Second question is it possible to take history in that much detail by a practicing physician or surgeon in setup like in India?
2/19/18, 16:15 - Dr. Rakesh Sir Iq City: There is no complementary medicine or allopathic medicine only there is medicine with or without evidence. All medicine can and should be integrated into evidence based medicine (if there is sufficient evidence to integrate them).

We train our PICMs to take these histories and they will hopefully train machines to do that
2/19/18, 16:18 - Dr. akshay anand PGI: Yes I also want to know Rakesh, is it practical to do this?
2/19/18, 16:19 - Dr. akshay anand PGI: I almost lost track:(
2/19/18, 16:19 - Deepak Bhadani BMJ: Yes Sir keen to know. 😊
2/19/18, 16:23 - Dr. Rakesh Sir Iq City: Practical to do whatever is evidence based
2/19/18, 16:24 - Dr. akshay anand PGI: I mean will this not take a lot of time ?
2/19/18, 16:29 - ‪+91 81260 21556‬: my sister studying in an ayurveda college wanted to research on a drug that has been traditionally used in ayurveda for hypertension , there is not much documentation but the practitioner have been using them.. its a good approach to give the best to our patients irrespective of the system we use..
2/19/18, 16:29 - ‪+91 81260 21556‬: linking to evidence base will make good care available to our patients in a scientific way
2/19/18, 16:50 - Dr. Rakesh Sir Iq City: With n of 1 trial perhaps not
2/19/18, 20:49 - ‪+880 1725-266274‬: *Salient features for guiding the paper* (Shared by Amy ma’am)

Precision Medicine needs a portfolio beyond genetics to revolutionize healthcare

A topic sentence that will grab attention and describe your population.

# For example- Precision medicine has a missing ingredient and that is the life, values and preferences of the patients they aspire to help

# Full precision requires a full person

*Structure*:

# Population

# Purpose and objectives

# Methods(briefly)

# Outcomes (one it is built what will it produce that you can measure?

# Time How long will all this take?

Questions that need to be answered

What are the current case based blended learning and approach; and how precision medicine can do more precision to the current approach?

We need to define our target population and what is the need for the target population?

What are the purposes of this Case-based blended learning ecosystem and what are the objectives to fulfill this target.?

How do we think that a case based blended learning will fulfill the target? Why is it the need of the hour? Why precision medicine matters and to what extent it can change the practice of current medicine?

What outcomes are we expecting and how are we going to measure the outcome?

How long will this take and how we are planning to take it ahead?
2/19/18, 20:50 - ‪+880 1725-266274‬: *Articles*:
1. Precision medicine--delivering the goods?

https://www.ncbi.nlm.nih.gov/pubmed/24769075

2. Precision medicine: beyond genomics to targeted therapies

https://www.futuremedicine.com/doi/abs/10.2217/pme.15.48

3. From genomic medicine to precision medicine: highlights of 2015

https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0265-4

4. New approaches beyond genetics: towards precision medicine in diabetes

https://search.proquest.com/openview/e4a1481041effa7d01f5600c4b2f09ff/1?pq-origsite=gscholar&cbl=48469

5. Beyond Genes and Molecules — A Precision Delivery Initiative for Precision Medicine

http://www.nejm.org/doi/full/10.1056/NEJMp1613224

6. Will the President's Plan Move Precision Medicine Beyond the Hype?

https://www.genomeweb.com/policy-legislation/will-presidents-plan-move-precision-medicine-beyond-hype

7. Brutalist medicine: a reflection on the architecture of healthcare

http://www.bmj.com/content/359/bmj.j5676

8. Data, data everywhere: the challenges of personalized medicine

http://www.bmj.com/content/359/bmj.j4546

9. Medicine is the ultimate personalised technology

http://www.bmj.com/content/357/bmj.j1750

10. Personalized Proteomics: The Future of Precision Medicine

http://www.mdpi.com/2227-7382/4/4/29?utm_source=TrendMD&utm_medium=cpc&utm_campaign=Proteomes_TrendMD_1

11. Personomics: The Missing Link in the Evolution from Precision Medicine to Personalized Medicine

http://www.mdpi.com/2075-4426/7/4/11?utm_source=TrendMD&utm_medium=cpc&utm_campaign=J_Pers_Med_TrendMD_0

12. Advances in Precision Medicine: Tailoring Individualized Therapies

http://www.mdpi.com/2072-6694/9/11/146?utm_source=TrendMD&utm_medium=cpc&utm_campaign=Cancers_(Basel)_TrendMD_0

13. What is precision medicine?

http://erj.ersjournals.com/content/50/4/1700391?utm_source=TrendMD&utm_medium=cpc&utm_campaign=_European_Respiratory_Journal_TrendMD_1

14. The promise of precision medicine for health systems

http://www.ajhp.org/content/73/23/1907?utm_source=TrendMD&utm_medium=cpc&utm_campaign=American_Journal_of_Health-System_Pharmacy_TrendMD_1&sso-checked=true
2/20/18, 08:07 - Dr. Rakesh Sir Iq City: Thanks Vivek for this extensive review of the introduction to precision Medicine. Can we now begin searching for specific case reports illustrating the success or failure of precision Medicine? I too shall contribute soon. The final mbbs is finishing today but still have 160 theory papers to correct.
2/20/18, 08:19 - ‪+91 81260 21556‬: thanks .. very useful for those who missed discussions..
2/20/18, 08:34 - ‪+880 1725-266274‬: Thanks sir. We will search
2/20/18, 08:34 - ashwini usa: Hi I am sorry I haven't been following the discussion. Vivek can you please let me know what is to be done ?
2/20/18, 08:34 - ‪+880 1725-266274‬: Thank you
2/20/18, 08:36 - ‪+880 1725-266274‬: We need to search for the specific case reports as sir advised.
2/20/18, 08:37 - ‪+880 1725-266274‬: And also we are preparing for abstract and Srija and avinasj wonderfully wrote abstract. We need to add and modify and improve further before 1 march.
2/20/18, 08:37 - ‪+880 1725-266274‬: This will parallaly go with writing the paper
2/20/18, 08:39 - ‪+880 1725-266274‬: Avinash**
2/20/18, 09:10 - ashwini usa: Can you resend the abstract please ? Sorry I have really been out of the whole thing thanks to electives. Will be back on track soon
2/20/18, 09:12 - ‪+880 1725-266274‬: Abstract :
“Developing a Case based blended learning ecosystem toward precision Medicine: current limitations and way forward”
Final Abstract:-
Current imprecise medical system has replaced eminence-based medicine to evidence-based system coming from the application of analytics, called the imperfect science of statistics on a very small subset of care seeking or healthy individuals with a placebo and drug for the treatment which is accelerated by high tech. Labs and various case reports of diseases and other evidences to match patterns for diagnosis, where again labs have been very useful. Dealing with the imprecise becomes the art of experienced practitioner, to become as accurate as possible. This process of healthcare have design fault of one size fits all and always brings some know/unknown harm along with desired benefits. Our Idea of precision medicine is based on taking every patient journey mapped as source of evidence in form of various media like text, image, graphs, videos, etc. which shared in HIPAA compliant online record in our blended learning ecosystem where multidisciplinary community deals with creating questions in PICO format and exploring answers, trying to explore from medical, engineers and social perspectives to find answers for patient-centered challenge in an individual performing shared decision making. Our efforts generate well recorded patient journey/history along with possible questions where some we find answers and some become topics of research interest and blended learning exercise generates data for creating an Artificial intelligence based system to learn from various patient journey recorded and learn all the patterns as well as questions and answers from various disciplines understanding anatomical anomalies visible by a naked eye to genomics & metabolomics and various pathies. This AI system works as a clinical decision system and helps in precision public health by its uses/ access monitoring. The way we making our medicine practice more precise is by having interdisciplinary team engaged in decision-making process based on pieces of evidence, while we are generating a novel way of precision diagnostic and treatment to revolutionize health care of future on our foundation of blended learning process and our paper details the above mentioned criterias with a case based illustrations and showcase the challenges.

(by Srija & Avinash)
2/20/18, 09:13 - ‪+880 1725-266274‬: This is what we will use for further structuring and modification
2/20/18, 09:17 - ashwini usa: Okay thank you
2/20/18, 09:33 - Sreyash Chwathey Bmj: Can I edit a bit of the abstract for sentence structure?
2/20/18, 09:33 - Sreyash Chwathey Bmj: It’s a very good one
2/20/18, 09:35 - Avinash Kumar: 18. From Dyadic Ties to Information Infrastructures: Care-Coordination between
Patients, Providers, Students and Researchers Contribution of the Health Informatics
Education Working Group
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587042/
19. Capitalizing on Collaboration – The President’s Precision Medicine Initiative
Antoinette F. Konski
https://www.personalizedmedicinebulletin.com/2016/02/29/capitalizing-on-collaborati
on-the-presidents-precision-medicine-initiative/

20. Improving precision medicine using individual patient data from trials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289871/
21. Reconciling evidence-based medicine and precision medicine in the era of big
data: challenges and opportunities
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165712/
2/20/18, 09:38 - ‪+880 1725-266274‬: These articles are great
2/20/18, 09:39 - ‪+880 1725-266274‬: That's we are here
2/20/18, 09:39 - ‪+880 1725-266274‬: That's why
2/20/18, 09:39 - ‪+880 1725-266274‬: We all can work
2/20/18, 09:41 - Madhava Sai Bmj: Bro is it 1st week of March or 1st of March??

Just a clarification so that we can work accordingly
2/20/18, 09:41 - ‪+880 1725-266274‬: 1st march I guess
2/20/18, 09:41 - Madhava Sai Bmj: Okay, no problem
2/20/18, 09:43 - Sreyash Chwathey Bmj: Yes 😊
2/20/18, 10:07 - Dr. Rakesh Sir Iq City: Let's begin by searching for cases that begin with the whole patient description along with life events reflecting environmental pathways that also delves deeper into elucidating the molecular pathways in the same patient
2/20/18, 10:08 - Sreyash Chwathey Bmj: Conducting Precision Medicine Research with African Americans
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154850

A new initiative on precision medicine
http://www.nejm.org/doi/full/10.1056/nejmp1500523

A precision medicine approach to a patient with unresolved pain following orthopedic surgery: a case report.
https://www.ncbi.nlm.nih.gov/m/pubmed/28231802

Medical case reports in the age of genomic medicine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673439/

Arriving at the Right Diagnosis in an Era of Precision Medicine
https://www.karger.com/Article/Pdf/447351

Uncovering Medical Insights from Vast Amounts of Biomedical Data in Clinical Case Reports
https://www.biorxiv.org/content/biorxiv/early/2017/08/04/172460.1.full.pdf

Model-based optimization approaches for precision medicine: A case study in presynaptic dopamine overactivity
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179575
2/20/18, 10:10 - Dr. Rakesh Sir Iq City: This case report below has 2000 citations

"A 59-year-old male patient who was originally from India but who had lived in Sweden for many years and who often returned to India had type 2 diabetes mellitus and had had multiple strokes. In November 2007, he traveled to India and on 5 December was hospitalized in Ludhiana, Punjab, with a large gluteal abscess. In December 2007, he was admitted to a hospital in New Dehli, where he was again operated on and where he developed a decubital ulcer. On 8 January 2008 he was referred to Örebro, Sweden. During his stay in New Dehli he received amoxicillin (amoxicilline)-clavulanic acid, metronidazole, amikacin, and gatifloxacin (all of them parenterally).

Clinical isolate K. pneumoniae 05-506 was derived from a urinary culture on 9 January 2008. He had no clear symptoms of urinary tract infection at that time. The amount of bacteria found in a culture of his urine was only 1,000 CFU/ml. Both ESBL-positive Escherichia coli and a carbapenem-susceptibleAcinetobacter sp. were isolated from his deep wounds. An ESBL-positive E. coli strain was also found in a culture of fluid resulting from external otitis.

http://www.nejm.org/doi/full/10.1056/nejmp1500523

Biomarker development in the precision medicine era: lung cancer as a case study

https://www.nature.com/articles/nrc.2016.56
2/20/18, 10:18 - Sreyash Chwathey Bmj: http://care.diabetesjournals.org/content/39/11/1889
2/20/18, 10:19 - ‪+880 1725-266274‬: We need to search such reports now.
2/20/18, 10:22 - Sreyash Chwathey Bmj: http://m.molecularcasestudies.cshlp.org/content/4/1/a002303.full.pdf
2/20/18, 10:22 - Dr. Rakesh Sir Iq City: There are a few above already shared by Shreyas, Madhava and me above
2/20/18, 10:22 - Sreyash Chwathey Bmj: A de novo Ser111Thr variant in aquaporin-4 in a patient with intellectual disability, transient signs of brain ischemia, transient cardiac hypertrophy, and progressive gait disturbance
2/20/18, 10:22 - Sreyash Chwathey Bmj: This is for the article
2/20/18, 10:26 - Sreyash Chwathey Bmj: A novel PRRT2 pathogenic variant in a family with paroxysmal kinesigenic dyskinesia and benign familial infantile seizures
http://m.molecularcasestudies.cshlp.org/content/4/1/a002287.full.pdf
2/20/18, 10:27 - Dr. Rakesh Sir Iq City: While we are currently sharing case reports to get a hang of what we are aiming at (to begin a discussion), in the main article we shall try to only share original cases shared online by our students here. For example here

http://bmjcaselogvivek.blogspot.in/2017/02/?m=1
2/20/18, 10:29 - Dr. Rakesh Sir Iq City: Vivek do you remember what happened to this case that you had first shared with us? Do you have her follow up? If not that can still contribute to our limitation data
2/20/18, 10:29 - Sreyash Chwathey Bmj: Thanks RB
2/20/18, 10:34 - Dr. Rakesh Sir Iq City: CCMB working to make personalised medicine a reality
http://www.indiansciencejournal.in/drugs-medicines/ccmb-working-to-make-personalised-medicine-a-reality-459316
2/20/18, 10:37 - Dr. Rakesh Sir Iq City: Current work on precision Medicine in Hyderabad summarized in lay terms
2/20/18, 11:20 - ‪+880 1725-266274‬: I don't have follow up but her son is connected to me on fb.
2/20/18, 11:21 - ‪+880 1725-266274‬: I will try to connect for current condition
2/20/18, 14:31 - Dr. Rakesh Sir Iq City: Will be looking forward to it. Let's start exploring every case report from other teams shared here to find out the patient utility of the precision Medicine approach particularly in terms of how precision Medicine influenced patient outcomes. My hunch is that we will find that the molecular elucidation of disease pathways using molecular precision Medicine doesn't till now influence patient outcomes but the clinical pathway elucidation does and this is what we may try to establish through the cases shared online by our students (how many Avinash in total)?
2/20/18, 17:37 - Dr. Rakesh Sir Iq City: Sharing a simpler infectious disease case report that used molecular diagnostics, not to precise in terms of pathway elucidation but just take a look and discuss if it was useful in the four cases?

https://www.sciencedirect.com/science/article/pii/S2405579417300347
2/20/18, 17:37 - Dr. Rakesh Sir Iq City: Not too precise
2/20/18, 20:05 - ‪+880 1725-266274‬: "ase 1 was a 14 year old girl who was on ATT for 2 months without any improvement and sputum CBNAAT test detected MDR Tuberculosis. CB-NAAT test detected Mycobacterium Tuberculosis with Rifampicin resistance. That was later confirmed by Line probe assay through RNTCP. Child was treated as per RNTCP & IAP guidelines for MDR Tuberculosis. *So, diagnosis the child in first child as MDR TB led to the change in the drugs, although they didn't report if that improved the childs condition*
2/20/18, 20:10 - ‪+880 1725-266274‬: Sir, do we want to say in these kind of cases where molecular diagnostics may not be required and could be treated based on clinical diagnostics?
2/20/18, 20:14 - ‪+880 1725-266274‬: I.e. rather than looking for molecular diagnostics, could the clinical elucidation of this patient could have been more better for this patient? Should this be asked ourselves when thinking about this first case?
2/20/18, 20:28 - ‪+880 1725-266274‬: Case 2: A 9yr old boy was admitted with features of meningitis. No induration noted in the Mantoux test. CSF analysis. showed cells count of 140 cells, predominately lymphocytes, protein of 138mg/dl, sugar of 99 mg/dl and *CSF culture showed no growth* but CSF *CB - NAAT was positive for MTB.and it was sensitive to Rifampicin. Child was started on Anti Tubercular Therapy (ATT) and steroids as per guidelines. The child has improved. So, here, this was helpful in terms of diagnosis of TB
2/20/18, 22:38 - Dr. Rakesh Sir Iq City: Not clinical but cellular diagnostics such as culture which was also done for this child and revealed similar findings. However we need not be anti CBNAAT and just need to find out if elucidation of clinical pathways alone is efficacious enough although again one may think more data is always better to decision making
2/20/18, 22:40 - Dr. Rakesh Sir Iq City: Well in this case the child would have been treated for TB even with just that CSF report but again as I said above, having more precise data at all clinical, cellular, molecular levels is always welcome
2/20/18, 22:47 - Sreyash Chwathey Bmj: How do we learn about molecular data in India ? @919617604831 it’s difficult
2/20/18, 22:54 - Dr. Rakesh Sir Iq City: Search for cases that have been published
2/20/18, 22:57 - ‪+880 1725-266274‬: "My hunch is that we will find that the molecular elucidation of disease pathways using molecular precision Medicine doesn't till now influence patient outcomes but the clinical pathway elucidation does and this is what we may try to establish through the cases shared online" Sir, in our paper, we want to demonstrate through our true cases that *clinical pathway elucidation may better influence than molecular precision medicine* . Although we welcome molecular data too. *Now by clinical pathways what else are we excluding?* Sorry if I still didn't understand.
2/20/18, 23:09 - Dr. Rakesh Sir Iq City: Let's look at the pathways this way:

External: life events

Internal: cellular and molecular events

Instead of discriminating between clinical and molecular. Aren't glucose, creatinine, albumin also molecules that we regularly depend on?
2/20/18, 23:10 - Sreyash Chwathey Bmj: Thanks RB
2/20/18, 23:33 - Madhava Sai Bmj: Sir, so how do we identify such potential cases or shall we have to look at every case both externally and internally.
2/20/18, 23:37 - ‪+880 1725-266274‬: Thanks sir. You are right.
2/21/18, 09:44 - Dr. Rakesh Sir Iq City: Yes every case, till we reach a breakthrough. See this example shared by Aadipta here

https://mobile.nytimes.com/2018/02/14/magazine/her-various-symptoms-seemed-unrelated-then-one-doctor-put-it-all-together.html?referer=http://m.facebook.com/
2/21/18, 10:41 - Dr. Rakesh Sir Iq City: Although this example is relatively simpler as it involves elucidation of life event pathways (external and internal) to match a rare disease (provided you have all the documented patient information), what our elective students are (need to be) engaged with are elucidation of external and internal pathways in common diseases and this is more difficult
2/21/18, 10:44 - Dr. Rakesh Sir Iq City: One of our past students who had been publishing with us since his 3rd year mbbs (fever uncertainty, case based experiences)is currently at the cutting edge of elucidating internal pathways to precision Medicine as he is now a professor of hemat-onc in Milwaukee, Wisconsin. Have asked him to join this writing team and he too is keen.
2/21/18, 10:48 - ‪+880 1725-266274‬: Wowww. This is a great news sir
2/21/18, 10:49 - Sreyash Chwathey Bmj: Wow that’s amazing RB
2/21/18, 10:53 - Madhava Sai Bmj: Awesome news, sir
2/21/18, 11:18 - Abhishek sir IBM: Wow!
2/21/18, 21:06 - ‪+91 97043 21828‬: 👍🏻.
2/22/18, 16:50 - Dr. Rakesh Sir Iq City: Yes Vivek some more thinking around this question: logically external life event pathways are likely to apparently influence patient related outcomes because of the very meaning of "patient related outcomes" which are distinguished from "disease related outcomes" that are often represented by "internal pathway representatives such as hba1c, cholesterol or even PFT values.

Better elucidation of both external life event pathways and internal cellular and molecular event pathways through precision medicine approaches may help to predict something even better than the currently pedestalled "patient related outcome?"
2/22/18, 17:48 - Dr. Rakesh Sir Iq City: " In the colloquial sense, “precision” also implies a high degree of certainty of an outcome, as in “precision-guided missile” or “at what precise time will you arrive?” So will precision medicine usher in an age of diagnostic and prognostic certainty?

In fact, the opposite will probably result. The new tools for tailoring treatment will demand a greater tolerance of uncertainty and greater facility for calculating and interpreting probabilities than we have been used to as physicians and patients."

http://www.nejm.org/doi/full/10.1056/NEJMp1608282
2/22/18, 18:21 - Dr. Rakesh Sir Iq City: Some fresh thoughts on the abstract that I thought I would share here for you all to see how you may fit it in with the current aggregore.

"Abstract :

The term Precision medicine appears to promise diagnostic and therapeutic certainty and yet involves the elucidation of hitherto unknown myriad pathways to illness and recovery that involve an interplay of multicellular organisms such as humans, their individual cells and the building blocks of those cells in the form of molecules.

Every academic healthcare institution globally aspires to derive the best diagnostic and therapeutic precision possible for their patients and we describe a population of students and patients that form part of a multidisciplinary case based blended learning ecosystem whose workflow involves case based inputs through patient and student (mobile user) driven raw patient data processed further through online global groups with an aim to attain diagnostic and therapeutic precision for each and every patient.

Current strengths, weaknesses and the way forward blending conventional telemedicine tools with evolving artificial intelligence in medicine tools will be discussed through original case based illustrations prepared by students and patients collaborating together."

Would be great to have your inputs
2/22/18, 18:22 - Dr. Rakesh Sir Iq City: The current title appears to be here, ""Developing a Case based blended learning ecosystem toward precision Medicine: current limitations and way forward"
2/24/18, 12:09 - ‪+880 1725-266274‬: Yes sir. Will work on it. Had exam actually.
2/24/18, 12:14 - Dr. Rakesh Sir Iq City: Good is it over? Madhava what about your exams?
2/24/18, 12:16 - ‪+880 1725-266274‬: Not over but was a bit stressed for this exam. I don't understand what's the fun asking definitions and all without testing for understanding.
2/24/18, 12:20 - Sreyash Chwathey Bmj: Rat race 🐒
2/24/18, 12:28 - Dr. Rakesh Sir Iq City: Slavery to those who have defined our lives? 🙂
2/24/18, 12:29 - Dr. Rakesh Sir Iq City: But then I am not sure what's the fun in slavery. Security? Assured food, shelter? Maybe
2/24/18, 12:29 - Sreyash Chwathey Bmj: No RB the system 1
This is colonial hangover
2/24/18, 12:31 - Dr. Rakesh Sir Iq City: Are we addicted to it then? The other Awsar group is not here to field this question? 🙂
2/24/18, 12:59 - Sreyash Chwathey Bmj: Well it seems like we have conveniently accepted this
Hardly anyone wants change
To change systems require lot of administrative will
2/24/18, 13:02 - Deepak Bhadani BMJ: https://youtu.be/qH1HCYy1NTc

Although it is off topic i know. Sorry sir for this. 🙂
2/24/18, 13:05 - Sreyash Chwathey Bmj: System !!!
2/24/18, 13:05 - Sreyash Chwathey Bmj: And hence Students!!!!!
2/24/18, 13:20 - Dr. Rakesh Sir Iq City: Perhaps if we bring it into the topic here from a precision Medicine perspective let's think of the learning system as one human body and the students as individuals? So what kind of inflammation may happen if (as Shreyas mentioned earlier), the will to change is homogeneous? More inflammation or less? Let me illustrate this with a story of glomerular inflammation written a few decades ago (although the Harrison cartoons used to illustrate may not have changed drastically)
2/24/18, 13:21 - Dr. Rakesh Sir Iq City: https://consciousnotebooksequel.blogspot.in/2015/12/the-story-of-glomerular-injury.html?m=1
2/24/18, 13:22 - Dr. Rakesh Sir Iq City: The story above elucidates how external life events can be correlated to internal disease pathways
2/24/18, 15:10 - Dr. Rakesh Sir Iq City added Anamika Mehta maam (abhi sir's sis)
2/24/18, 14:54 - Anamika Mehta maam (abhi sir's sis): Hi Everyone
2/24/18, 14:55 - Anamika Mehta maam (abhi sir's sis): @919617604831 thank you
2/24/18, 14:55 - Anamika Mehta maam (abhi sir's sis): Happy to share by inputs where ever applicable
2/24/18, 15:02 - Dr. Rakesh Sir Iq City: Thanks Anamika. Would you like to comment on the abstract or even add to it or modify it?
2/24/18, 15:17 - Anamika Mehta maam (abhi sir's sis): Well I would say focus on precision wellness.
2/24/18, 15:27 - Madhava Sai Bmj: There is an exam on 25th and 28th sir , after that it is done
2/24/18, 15:48 - Madhava Sai Bmj: Beautiful story sir.

Off topic but If we talk about educational system as a one human body, some organs has been mutated initially (the school system) which had immediate good results (good marks and scores in exams) but later in the near future it lead to very adverse reactions.

The cells in the school system are so mutated and their progression is rapid that if a new cell develops and shows a characteristics of unmutated cell the external pressure and forces by the other cells in the system forced the new cells to change their internal pathway and convert into one of them.

Finally with the gradual development of cells, when the actual function is required (when they reach college and graduate) they cannot function individually to the challenges as they lost their function so they uses drugs or other cells in the body which are not mutated (they bring specialists from the other countries with humungous amount of money as they lack skills) who uses their skills (may be in their country they were successful with this).

Finally they may resolve it or give a temporary or sometimes permanent solution can also be expressed.
2/24/18, 15:50 - Madhava Sai Bmj: Hello anamika mam @971507375157 , How are you??

Here is the abstract that we are discussing about.

Some fresh thoughts on the abstract that I thought I would share here for you all to see how you may fit it in with the current aggregore.

"Abstract :

Would be great to have your inputs
2/24/18, 15:57 - Anamika Mehta maam (abhi sir's sis): Sure gradually as I said before my focus has been precision wellness by looking into multiomics and integrating ancient knowledge like ayurveda with molecular biology and in near future it will be quantum biology and we are going to need AI and quantum computing to achieve wellbeing for all. It will all lead to not only curing all lifestyle related diseases but also slowing of ageing and may be reversing it to some extend eventually.
2/24/18, 17:37 - Dr. Rakesh Sir Iq City: Excellent idea. So I am assuming there may be separate pathways that can be elucidated for precision wellness as opposed to precise illness pathways that we in the illness industry are mostly engaged in. So we would need case studies to illustrate how these wellness pathways may have been elucidated. Anamika please share a few
2/24/18, 19:32 - Anamika Mehta maam (abhi sir's sis): It's interlinked all metabolic pathways
2/24/18, 20:13 - Dr. Rakesh Sir Iq City: Thanks Anamika we are also considering the link between external macro world pathways (life events) and internal metabolic pathways and trying to find case studies to illustrate them. So due to your inputs we need to also find case studies that elucidate wellness pathways (such as the story of a person who leads a normal healthy existence for most period of his her life...is there any such person or is it very common? If so what is the life path for such people?). For beginning to illustrate abnormal macro pathways and their links to internal molecular pathways we had shared an illustrative scenario just before you joined us and will share the link again here https://consciousnotebooksequel.blogspot.in/2015/12/the-story-of-glomerular-injury.html?m=1
2/24/18, 21:12 - Anamika Mehta maam (abhi sir's sis): https://www.cellsignal.com/contents/science-cst-pathways-pi3k-akt-signaling-resources/mtor-signaling-interactive-pathway/pathways-mtor-signaling
2/24/18, 21:17 - Dr. Rakesh Sir Iq City: Excellent I shall try to provide an interpretation of this micro internal pathway from a macro multicellular organism perspective. 🙂
2/24/18, 21:17 - Anamika Mehta maam (abhi sir's sis): Thank you
2/24/18, 21:19 - Anamika Mehta maam (abhi sir's sis): mtor pathway is influenced by nutritional, environmental, stress, hormones clues
2/24/18, 21:21 - Anamika Mehta maam (abhi sir's sis): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687363/
2/24/18, 21:21 - Anamika Mehta maam (abhi sir's sis): Link to show how mTOR is involved in ageing and age related diseases
2/24/18, 21:23 - Anamika Mehta maam (abhi sir's sis): Metformin also influences this pathway. You know there are reports to show metformin may be the anti cancer and anti ageing drug. ( saying on basis of show articles I've read)
2/24/18, 21:24 - Dr. Rakesh Sir Iq City: Yes so from a macro multicellular organism perspective, when we talk about such "atypical serine/threonine kinase" proteins governing the lives of these single cells as their regulators or perhaps decision makers as to which path to choose when confronted with decision nodes such as challenges in the external cellular mileu, we automatically need to study those "diverse nutritional and environmental cues, including growth factors, energy levels, cellular stress, and amino acids" that make up the immediate external mileu around each of the more than trillion cells we harbor?
2/24/18, 21:24 - Anamika Mehta maam (abhi sir's sis): The other gene of interest is SIRT 1 (why fasting is good for health)
2/24/18, 21:29 - Dr. Rakesh Sir Iq City: What I am driving at is that currently precision Medicine is happy to dig out one small factor (protein or nucleic acid) and immediately try to link it with an environmental factor that may have some marketable role in influencing it artificially. Perhaps precision Medicine needs more pathway elucidation to the point of linking macro world pathways with microworld pathways before we can see if artificial chemicals can influence these pathways?
2/24/18, 21:29 - Anamika Mehta maam (abhi sir's sis): That's a part of lot of things happening at the same time.
2/24/18, 21:32 - Anamika Mehta maam (abhi sir's sis): Yes going back to mtor the balance of mtor complex 1 and 2 are important to maintain the pathways and that is influenced by UCHL1. So, could we using antisense UCHL1 influence the metabolic pathways?
2/24/18, 21:33 - Anamika Mehta maam (abhi sir's sis): Will follow with papers I basing it on.
2/24/18, 21:34 - Anamika Mehta maam (abhi sir's sis): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482593/
2/24/18, 21:35 - Anamika Mehta maam (abhi sir's sis): <Media omitted>
2/24/18, 21:36 - Dr. Rakesh Sir Iq City: While the antisense may appear to make sense it's based on miniscule data on a fraction of what may be required to see the big picture. So while research will continue to fund antisense interventions and demonstrating minimal efficacy over placebo we could even start looking at the natural course of such pathways when the cell is left alone to its own devices similar to observational studies that document natural history of human illnesses without any major interventions
2/24/18, 21:38 - Anamika Mehta maam (abhi sir's sis): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3592026/
2/24/18, 21:38 - Dr. Rakesh Sir Iq City: As mentioned earlier these tools are based on very miniscule data and in our enthusiasm to target we may be missing the possibly more intelligent mechanisms evolutionary biology has equipped our multicellular systems with?
2/24/18, 21:38 - Anamika Mehta maam (abhi sir's sis): Yes
2/24/18, 21:39 - Anamika Mehta maam (abhi sir's sis): Agree
2/24/18, 21:41 - Dr. Rakesh Sir Iq City: From a multicellular macro perspective I would love to see this article as the story of another actor that creates conflict and tries to disrupt one pathway (hitherto discovered by a species of multicellular organisms aka humans) and I am sure the article could be made to represent an action thriller.
2/24/18, 21:46 - Anamika Mehta maam (abhi sir's sis): Very important what you mentioned here. What has evolution conserved from so gel cell to humans? It can give us a lot of clues.
2/24/18, 21:47 - Dr. Rakesh Sir Iq City: Do we, should we artificially target any pathway toward wellness except perhaps put things on the right path?
2/24/18, 21:47 - Anamika Mehta maam (abhi sir's sis): In this case tandem repeats in our DNA could be playing an imp role.
2/24/18, 21:48 - Anamika Mehta maam (abhi sir's sis): I would say to put things on right path
2/24/18, 21:50 - Anamika Mehta maam (abhi sir's sis): Single cell to humans
2/24/18, 21:52 - Dr. Rakesh Sir Iq City: Let's write this article to define the right path (between single atoms, simple molecules, complex quaternary molecules aka proteins and the cells they constitute and the multicellular universe constituted by those cells? Perhaps not just one path but describe in detail it's myriad branchings so that the world is able to appreciate the entire tree?
2/24/18, 21:54 - Anamika Mehta maam (abhi sir's sis): Yes
2/24/18, 21:54 - Dr. Rakesh Sir Iq City: And let's utilize original data gathered by us to write it?
2/24/18, 22:20 - ‪+880 1725-266274‬: I missed reading this article before and they nicely mixed external and molecular events. In our paper, when we will utilize the original data, whereever we have external pathyways aka life events, but if we don't have known precise molecular pathways of a patient, shall we then present the known generalized mechanisms as examplified in the link?
2/24/18, 22:36 - Dr. Rakesh Sir Iq City: Yes that as well as even just demonstrate how not knowing the exact pathways (other than from similar past published data) still creates a picture of an external patient pathway that seems complete (especially with follow up data)? Can we dig into the similarities and dissimilarities between the macro clinical approach to understanding multicellular organism pathways and micro molecular approach toward elucidating micro cellular and genomic pathways?
2/24/18, 22:46 - Dr. Rakesh Sir Iq City: But let's continue reviewing the literature. Till date Vivek you have shared a few links but not discussed any of them in detail. Let's discuss one borrowed case study review in the context of precision Medicine and one original case study documented online by our elective students
2/24/18, 22:47 - Dr. Rakesh Sir Iq City: Let me again share that 2009 case report paper that was cited 2000 times
2/24/18, 22:50 - Dr. Rakesh Sir Iq City: External pathway elucidation :

Internal pathway elucidation:

On 6 March 2008, the patient was discharged to a nursing home. On 1 April a new urine sample for culture was taken, and an ESBL-producing K. pneumoniae isolate was found. The original carbapenem-resistant K. pneumoniae isolate has never been found in any other cultures of samples from the patient. As K. pneumoniae 05-506 was carbapenem resistant and positive by the MBL Etest (AB bioMerieux), it was investigated further. Moreover, fecal samples were collected from the patient during his stay at the nursing home to identify the source of 05-506; however, while 05-506 could not be recovered, an MBL-positive E. coliisolate was recovered and was designated E. coli NF-NDM-1."
2/24/18, 22:52 - Dr. Rakesh Sir Iq City: Can we try to dissect and identify the pivotal nodes in the above elucidated pathways (pivotal in changing the course)?
2/24/18, 23:52 - ‪+880 1725-266274‬: multiple strokes in his life started changing course of life and he was doing well until he travelled to India and developed gluteal abscess requiring hospital admission.
2/24/18, 23:53 - ‪+880 1725-266274‬: Though he used to travel India very often, but in 2007 he got that abscess
2/24/18, 23:58 - ‪+880 1725-266274‬: after the operation for abscess he developed the decubital ulcer and turned him into a subject of elucidating internal pathway of different strains of microbeson various samples.
2/25/18, 01:27 - ‪+880 1725-266274‬: "During his stay in New Dehli, he received amoxicillin (amoxicillin)-clavulanic acid, metronidazole, amikacin, and gatifloxacin"- Any relation of this to the clinical isolations of microbes in urine, stool, deep wound, fluid resulting from otitis externa?
2/25/18, 14:35 - Anamika Mehta maam (abhi sir's sis): uae-health/dubai-to-map-genome-of-all-its-residents
2/25/18, 14:37 - Anamika Mehta maam (abhi sir's sis): https://m.khaleejtimes.com/news/uae-health/dubai-to-map-genome-of-all-its-residents
2/25/18, 21:02 - ‪+880 1725-266274‬: Need ur lead further sir to take it further.
2/25/18, 21:12 - Dr. Rakesh Sir Iq City: Thanks Vivek you have very well dissected the external pathway of the 2009 block-buster case that focused more around the agent cell (bacteria) rather than the internal molecular interactions between agent and host. Not sure if we can do better in terms of finding a better picture here than what you did given the limited data we have. See if you can gather more from the full text here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786356/ but I believe we need a better representative case that would illustrate the host agent cellular and molecular interactions better. Once we let go of this we shall next dig into two of our own cases of malignancy that revealed dramatic external pathways
2/25/18, 21:30 - ‪+880 1725-266274‬: The article has too much of microbial genetics sir 😟
2/25/18, 21:39 - Dr. Rakesh Sir Iq City: Ask for help from Anamika or Akshay here if there is any area that you need genetic opinion.
2/25/18, 21:43 - ‪+880 1725-266274‬: Okay sir.
2/25/18, 23:32 - Dr. Rakesh Sir Iq City: Vivek meanwhile would you like to share the two ovarian tumor case studies with dramatic external pathways and see if we can elucidate a connection between their external and internal?
2/26/18, 00:01 - ‪+880 1725-266274‬: An interesting case presented to us two months ago in the month of August with Shortness of breath, abdominal distension. A CT scan showed mass in the ovary. An laparotomy was done to perform Total Abdominal Hysterectomy with Bilateral Salpingo-oophorectomy. The patient developed hypotension on the table and the surgeons were forced to stop the surgery after excision of the mass. The mass measured 6,600 grams and the specimen was sent to histopathological examination. The report came out to be clear cell carcinoma of the ovary. https://saratuppaluri.blogspot.in/2017/10/case-of-ovarian-mass-with-chronic.html?m=1
2/26/18, 00:01 - ‪+880 1725-266274‬: http://bmjcaselogvivek.blogspot.in/2017/11/55f-with-post-op-hypotension-following.html
2/26/18, 07:59 - Dr. Rakesh Sir Iq City: Share the PPT presentation as it contains the sequence of external pathways well delineated there
2/26/18, 11:38 - Dr. Rakesh Sir Iq City: This is the picture of the pathways that affect a human being that every doctor believing in precision Medicine strives to achieve

https://qph.ec.quoracdn.net/main-qimg-1b1bd275db02d8432557047b33c97335
2/26/18, 11:41 - Dr. Rakesh Sir Iq City: The image was shared by Mark Roseman in response to this question

https://www.quora.com/Is-a-doctor-more-intelligent-than-an-engineer
2/26/18, 16:57 - Dr. Rakesh Sir Iq City: <Media omitted>
2/26/18, 16:58 - Dr. Rakesh Sir Iq City: Vivek above is the presented version of the external pathway data of the first patient.
2/26/18, 17:03 - Dr. Rakesh Sir Iq City: <Media omitted>
2/26/18, 17:04 - Dr. Rakesh Sir Iq City: Vivek above is a presentation of the elucidated internal pathway for the same patient
2/26/18, 17:05 - Dr. Rakesh Sir Iq City: Can you summarize the pathways from the information above?
2/26/18, 18:10 - ‪+880 1725-266274‬: Yes. Thank you sir.
2/28/18, 23:26 - Dr. Rakesh Sir Iq City: Just chanced upon this case https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1630706/#!po=0.746269

Very similar case was presented by our department of Dermatology and pathology last Thursday where we managed to even discuss desmoglein
3/1/18, 17:23 - ‪+880 1725-266274‬: This message was deleted
3/1/18, 17:24 - ‪+880 1725-266274‬: She was born 50 years back and was divorced one year after marriage. She was apparently healthy after this incidence until after 15 years of doing Job when she was diagnosed with Schizophrenia. She presented to casualty 5 years after being menopaused and diagnosed diabetes at the age of 50 years with abdominal distension, Pain.
3/1/18, 17:31 - ‪+880 1725-266274‬: In the USG abdomen, a right ovarian mass sied 20*20 cm, but her left ovary and other organs were normal. Biochemically, her CA-125 marker was elevated (196.5 IU). She was taken for right oophorectomy.
3/2/18, 20:36 - Deepak Bhadani BMJ: http://www.bbc.com/news/health-43246261?ocid=socialflow_facebook&ns_mchannel=social&ns_campaign=bbcnews&ns_source=facebook

*The results, published in The Lancet Diabetes and Endocrinology, showed the patients could be separated into five distinct clusters.*

Prof Leif Groop, one of the researchers, told the BBC: "This is extremely important, we're taking a real step towards precision medicine.
"In the ideal scenario, this is applied at diagnosis and we target treatment better."
3/2/18, 20:41 - Deepak Bhadani BMJ: http://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587(18)30051-2.pdf

Original article.
3/2/18, 23:53 - ‪+880 1725-266274‬: Interesting article.
3/3/18, 07:09 - Dr. Rakesh Sir Iq City: Elaborate on how you can use it for the write up
3/3/18, 07:51 - ‪+880 1725-266274‬: We can write this to illustrate the internal pathways based on this existing data and that I think can help our illustration of our own cases?
3/3/18, 07:54 - ‪+880 1725-266274‬: Will try to think more about its utilization
3/3/18, 08:51 - Dr. Rakesh Sir Iq City: Good. Would it help to illustrate better with theory the problems that you may write about your current patient of dm 1?
3/3/18, 12:27 - Dr. Rakesh Sir Iq City: http://www.theprecisionmedicinesummit.com/washington-dc/2018/overview
3/3/18, 12:29 - Sreyash Chwathey Bmj: I would be glad if I could attend this precision medicine Conference
3/3/18, 12:29 - Sreyash Chwathey Bmj: Can we create something to submit them also ?
3/3/18, 12:38 - ‪+880 1725-266274‬: dm 1 patient will be better sir.
3/3/18, 12:43 - Dr. Rakesh Sir Iq City: Yes why not? Good idea
3/3/18, 12:43 - Dr. Rakesh Sir Iq City: Let's summarize where we have reached till now?
3/3/18, 12:44 - Sreyash Chwathey Bmj: I am thinking about “Challenges in precision medicine in resource poor settings: An Indian Perspective”
3/3/18, 12:44 - Sreyash Chwathey Bmj: This message was deleted
3/3/18, 12:45 - Dr. Rakesh Sir Iq City: Very good. It's also the theme of what we are working on here although we have titled it with a focus on our own work
3/3/18, 12:46 - Dr. Rakesh Sir Iq City: The whole idea of BMJ global health case reports is essentially that
3/3/18, 12:48 - Sreyash Chwathey Bmj: Thanks RB. We can review our work for something we can present there as well then
3/3/18, 12:49 - Sreyash Chwathey Bmj: I am thinking if we can write a comprehensive review on this by going through all the current Indian precimed literature
3/3/18, 12:53 - Dr. Rakesh Sir Iq City: Yes why not? Please lead this part of the write up
3/3/18, 12:53 - Sreyash Chwathey Bmj: Thanks RB
3/3/18, 13:03 - Dr. Rakesh Sir Iq City: Vivek can you share a completely deidentified version of the bronchial adenocarcinoma patient who had been planned for precision Medicine treatment based on precision bio markers from Tata memorial center?
3/3/18, 13:05 - Sreyash Chwathey Bmj: RB I had a query: should prophylactic cranial irradiation be performed in bronchial adenocarcinoma/NSCLC as is advocated for SCLC?
3/3/18, 13:05 - Sreyash Chwathey Bmj: Because this patient had a brain met
3/3/18, 13:32 - ‪+880 1725-266274‬: http://bmjcaselogvivek.blogspot.com/2018/03/62-years-old-man-with-non-small-cell.html
3/3/18, 13:38 - ‪+880 1725-266274‬: It has metastasized to right para saggital occipital lobe
3/3/18, 13:51 - ‪+880 1725-266274‬: Initially in the CxR, radiologists observed emphysematous changes in both lung, lobulated parenchymal lesion in left upper lobe (3*2.8 cm) and small nodule in the right lower lobe and enlarged mediastinal lymph nodes and they aked further investigation into ruling out bronchogenic Ca.
3/3/18, 13:52 - Dr. Rakesh Sir Iq City: Yes "traditionally, whole-brain radiation therapy (WBRT) has been the standard treatment for brain metastases with multiple intracranial lesions although studies have shown no overall survival benefit and no improvement in quality of life.
It's one of the reasons why oncologists currently have shifted to what are termed as precision Medicine approaches and one sees case reports where "small-molecule inhibitor of EGFR-TKI is used in lung adenocarcinoma with brain metastases showing EGFR mutation-positive with reasonable quality of life outcomes. This is perhaps what has also been planned for our patient in Tata memorial. Shreyas do you have his current update?
3/3/18, 13:57 - ‪+880 1725-266274‬: in the HRCT
3/3/18, 14:02 - Sreyash Chwathey Bmj: I have his relatives number
Will ask about it
3/3/18, 14:03 - ‪+880 1725-266274‬: He had a history of chronic cough
3/4/18, 20:52 - Dr. Rakesh Sir Iq City: *HISTORY TODAY IN MEDICINE*
March 4
*DR.Thomas Stephen Cullen*
(Nov 20, 1868 - March 4, 1953)

🔹Canadian Gynecologist

His contributions...
▪Pioneer in the development of _Gynecologic Pathological Laboratory_ in Johns Hopkins University, Baltimore
▪He was the first in America to examine tissues removed in the operating room, using the microscope 🔬to make diagnoses
▪His research focussed on carcinoma uterus, endometrial hyperplasia, fibroid uterus and extrauterine pregnancy
▪He had published four Monographs📚
* Cancer of the uterus (1900)
*Adenomyoma of the uterus (1908)
*Myomata of the uterus (1909)
*Disease of the umbilicus (1916)
▪His publications were extensively illustrated with drawings and photographs
▪In 1918, he described *CULLENS SIGN* - Superficial edema and discoloration around the peri-umbilical region in the ruptured ectopic pregnancy

A day to commemorate

_*Dr.Thomas Cullen*_ 🙏🏼

......................................
🔹Dr.M.Gowri sankar.MD
GMC &ESIC Hospital
Coimbatore
3/4/18, 20:52 - Dr. Rakesh Sir Iq City: Cullen, Virchow lived in a golden period where they were clinicians also using the microscope and laboratory with equal ease. With precision medicine shall we be able to reenter that golden era again?
3/4/18, 20:52 - Dr. Rakesh Sir Iq City: <Media omitted>
3/4/18, 20:53 - Dr. Rakesh Sir Iq City: Any updates?
3/5/18, 22:26 - Sreyash Chwathey Bmj changed from +91 97303 42200 to +1 (313) 312-6160
3/6/18, 13:04 - ‪+880 1725-266274‬: My 2.5 months long exams just finished today. Now I am relaxed. 😇😇😇😇
3/6/18, 13:11 - Dr. Rakesh Sir Iq City: 👌👌
3/6/18, 13:21 - ‪+880 1725-266274‬: Sir how would you like to illustrate our original cases? Any set of basic questions that we will try to answerwith every illustration?
3/6/18, 13:25 - Dr. Rakesh Sir Iq City: What are the external life event pathways elucidated for that case? What are the internal macro-micro-molecular event pathways elucidated (or planned as in your current bronchogenic carcinoma) for that case? What is the precise diagnosis and therapy that can be arrived at given whatever data we have on hand?
3/6/18, 13:34 - ‪+880 1725-266274‬: Vitiligo case report
3/6/18, 13:34 - ‪+880 1725-266274‬: IκK-16 decreases miRNA-155 expression and attenuates the human monocyte inflammatory response

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598939/
3/6/18, 14:00 - Dr. Rakesh Sir Iq City: Case Report ase Report
A 23-year-old woman was admitted
to the University Hospital Center, due to prominent, generalized depig-
mented patches.
The disease began acutely, »over night« (in patients`
own words), and progressed in the following order: dorsal
aspects of hands, upper extremities, trunk, face and lower
extremities. Within a few weeks 60% of her body was af-
fected.
On admission to the hospital her height was 175 centi-
meters and weight was 60 kilograms, and the body mass
index was normal (19.6)
3/6/18, 14:02 - Dr. Rakesh Sir Iq City: The affected area had no associated scaling. There was
a lack of cutaneous induration or sclerosis. Skin lesions
were asymptomatic and lacked clinical sings of infl amma-
tion. During dermatological examination leukotrichia of
the occipital area was found. There was no mucosal in-
volvement. She was without any subjective diffi culties (e.g.
pain, fever, weight loss).
There was a family history for this disorder; patient’s
12-year-old brother has acrofacial vitiligo. The disease ap-
peared almost simultaneously in both siblings. The onset
of disease was attributed to emotional stress; after their
mother had died in a car accident 6 months earlier, patient
noticed the fi rst lesions of vitiligo. She also noticed new
depigmented lesions in sites of physical injury (Koebner
phenomena).
The history of chronic sun exposure was negative. She
was a non-smoker.
Illumination with Wood`s lamp showed no fl uorescence
of affected depigmented skin.
3/6/18, 14:03 - Dr. Rakesh Sir Iq City: On ad-
mission, excisional biopsy of depigmented and non-lesion-
al skin was performed.
Histopathological analysis of lesional skin has shown
characteristic histologic features of vitiligo, such as total
loss of melanocytes of the basal layer of the epidermis.
Collagen fi bers were not affected. There was no epidermal
alteration or cellular infi ltrate. Immunohistochemical ana-
lysis revealed the absence of melanocytes, without DOPA-
positive melanocytes, which appear to be replaced by
Langerhans` and dermal dendritic cells.
3/6/18, 14:04 - Dr. Rakesh Sir Iq City: HLA typing was positive for HLA A2, B51,
B62, DR11, DR13, DR52, DQ1 and 3. In addition, our patient
had autoimmune endocrinopathies; type I, insulin-depen-
dent diabetes was diagnosed when she was 10 years old.
A serum thyroid-stimulating hormone (TSH) level and
antithyroperoxidase antibodies were elevated, while T4
level was low. Additional laboratory fi ndings include anti-
thyroglobulin antibodies were within normal range. Ul-
trasound imaging of the thyroid gland revealed diffuse
enlargement of the thyroid gland
3/6/18, 14:06 - Dr. Rakesh Sir Iq City: Topical class III corticosteroids were used for depig-
mented patches on her arms twice daily for two months,
resulting in several perifollicular repigmentations. She
had developed several side-effects such as atrophy and
telangiectasiae. Topical 0,1% tacrolimus ointment was
used for face and intertriginous areas twice daily for two
months, but with no apparent success.
Narrow-band UVB was applied for six months with the
total of 48 exposures. The starting dose was 250 mJ/cm2,
with 10% increments at each subsequent exposure. Treat-
ment was administered two times per week but never on
two consecutive days. Following the aforementioned ther-
apeutic scheme, neither perifollicular repigmentation nor
repigmentation from the periphery was detected.
3/6/18, 14:10 - Dr. Rakesh Sir Iq City: After the particular knowledge about the patient below is some general knowledge about this condition
3/6/18, 14:11 - Dr. Rakesh Sir Iq City: Vitiligo is a multifactorial disorder, therefore, several
hypotheses regarding the etiopathogenesis of vitiligo ex-
ist. The importance of genetic background is supported by
studies demonstrating signifi cantly higher (7–10 times)
incidence of vitiligo among fi rst degree relatives. Familial
occurrence of vitiligo is present in approximately 20% of
cases and is characterized by polygenic, non-Mendelian
inheritance with incomplete penetrance and multiple sus-
ceptibility loci. Notably, studies suggest earlier onset of
disease in familial vitiligo as opposed to non-familial, so
our case report refl ects those from the literature12. Certain
HLA types have been frequently associated with vitiligo
worldwide, primarily HLA A2 also found in our case, DR4,
DR7 and Cw61,14.
Emotional stress, such as death of a close relative or
other psychological trauma of similar intensity is a well-
documented trigger of vitiligo in susceptible patients, just
as described in our patient whose parent’s death had been
followed by appearance of vitiligo in her and her brother15.
Numerous studies demonstrate that mental stress can
directly and/or indirectly infl uence the survival and struc-
tural integrity of melanocytes15,16. Neurogenic factors in-
fl uenced by mental stress, such as neuropeptide Y (NPY),
calcitonin gene-related peptide (CGRP), catecholamines,
and nerve growth factor (NGF), lead to melanocyte de-
struction15.
3/6/18, 14:12 - Aadipta Iq City: Great
3/6/18, 14:17 - Dr. Rakesh Sir Iq City: Above description was mostly about the external pathways and although there was a passing mention of cellular pathogenesis we shall now move into meeting what are currently poster boys of precision medicine and heavily represent what we know of micro molecular pathways till date. Meet micro RNA
3/6/18, 14:20 - Dr. Rakesh Sir Iq City: MicroRNAs are a class of short, non-coding, evolutionary
conserved RNA molecules that can modulate the tran-
scription of other genes
3/6/18, 14:20 - Dr. Rakesh Sir Iq City: In silico studies and gene mapping
suggest that miRNAs regulate 30 % genes of human gen-
ome. miRNAs are highly specific for every cell type and
developmental stage [3]. They control the basic biological
functions, such as apoptosis, organogenesis, proliferation,
embryogenesis, antiviral response and the stress
3/6/18, 14:21 - Dr. Rakesh Sir Iq City: Generally, miRNA-155 together with miR-146 is
induced by proinflammatory stimuli like tumour necrosis
factor a (TNFa), Toll-like receptors (TLRs), LPS,
pam3CSK4 and interleukin 1 by the activation of tran-
scription factors like MAP kinases such as JNK and
NF-kB. miRNA-155 is also known to regulate the Th1 cells
and positively regulate the TNFa mRNA
3/6/18, 14:23 - Dr. Rakesh Sir Iq City: miRNA-155 has a key role in autoimmunity. In the hae-
matopoietic compartment, it promotes the development of
inflammatory T cells. It has also been shown to be involved in
the cytokine production (IL-6, IL-17 and IL-22) and local
bone destruction [21]. Experiments with knockout mice
demonstrate the absence of miRNA-155 results in the
impaired memory response, which is the indication that it
might regulate generation of memory B-cells [22].
miRNA-155 regulates several immune responses. Acti-
vated B and T cells and activated macrophages showed its
higher expression.
3/6/18, 14:25 - Dr. Rakesh Sir Iq City: Aberrant expression of several
miRNAs in the skin and serum of patients with vitiligo
has been demonstrated by microarray analysis (12, 13).
Using quantitative reverse transcription-PCR (qRT-
PCR), dysregulation of miR-224-3p, miR-4712-3p
and miR-3940-5p has been shown in peripheral blood
mononuclear cells of patients with vitiligo (14). A single
nucleotide polymorphism, rs11614913 in miR-196-a-2,
has been found to be associated with vitiligo (15). How-
ever, little is known about the role of miRNAs in the
pathogenesis of vitiligo.
3/6/18, 14:27 - Dr. Rakesh Sir Iq City: "To investigate the potential role of miRNAs in vitiligo,
we selected 12 miRNAs with known functions in the
regulation of cell proliferation and differentiation
(miR-10a, miR-99b, miR-125a, miR-125b and miR-
199a-3p), immune responses (miR-146a, miR-146b,
miR-155, miR-223 and miR-511), skin homeostasis
(miR-203) and melanogenesis (miR-145)"
3/6/18, 14:40 - Dr. Rakesh Sir Iq City: Of 12 studied miRNAs with proven
functions in cell proliferation, differentiation, immune
responses and melanogenesis, miR-99b, miR-125b,
miR-155 and miR-199a-3p were found to be increased
and miR-145 was found to be decreased in the skin of
patients with vitiligo. Combined pathway and target
analysis revealed melanogenesis-associated targets for
miR-99b, miR-125b, miR-155 and miR-199a-3p. In situ
hybridization analysis demonstrated increased expres-
sion of miR-155 in the epidermis of patients with viti-
ligo. Correspondingly, miR-155 was induced by vitiligo-
associated cytokines in human primary melanocytes and
keratinocytes. When overexpressed, miR-155 inhibited
the expression of melanogenesis-associated genes and al-
tered interferon-regulated genes in melanocytes and ke-
ratinocytes.
3/6/18, 14:40 - Dr. Rakesh Sir Iq City: <Media omitted>
3/6/18, 14:41 - Dr. Rakesh Sir Iq City: IκK-16 decreases miRNA-155 expression and attenuates the human monocyte inflammatory response

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598939/
3/6/18, 14:42 - Dr. Rakesh Sir Iq City: Above we have an individual patient with a problem and the current state of the art in terms of molecular internal pathway possibilities. Please add more to it if possible
3/8/18, 23:28 - Dr. Rakesh Sir Iq City: Anyone would like to summarize the above case study in terms of it's external and internal pathways and their relevance toward the end goal of precision Medicine?
3/9/18, 00:27 - Anamika Mehta maam (abhi sir's sis): I would need some to do that. Have to read through it but do that in few days time.
3/9/18, 00:28 - Dr. Rakesh Sir Iq City: Will be looking forward to it
3/9/18, 01:04 - vivek poddar esa: https://www.kevinmd.com/blog/2018/03/patient-becomes-medical-student.html My journey from being sick to helping the sick....... a story of those medical students who had been a patient.
3/9/18, 03:58 - ‪+880 1515-269048‬ left
3/9/18, 17:14 - ‪+880 1725-266274‬: Yes
3/9/18, 18:21 - ‪+880 1725-266274‬: This young women developed overnight and acutely prominent generalized depigmented patches and the skin lesions were asymptomatic and lack any signs of inflammation and without any fever, weight loss or pain). She has a family history for the disorder in her brother. *The same disease appeared in the siblings almost at the same time* after the emotional stress following the death of their mother in car accident. This patient also noticed the lesions in sites of physical injury. Histopathological findings were consistent with vitiligo (total loss of melanocytes). HLA typing was positive for HLA A2, B51, B62, DR11, DR13, DR52, DQ1 and 3 and autoimmune endocrinopathies. Two months of Topical corticosteroids use did perifolicular repigmentation, but caused atrophy and telangiectasiae. Topical 0,1% tacrolimus ointment and Narrow-band UVB use could not give any benefits. Vitiligo is a multifactorial disorder- genetic predisposition (first degree relatives), *HLA association* *emotional stress* and all these factors were present in this patient.
3/9/18, 18:25 - ‪+880 1725-266274‬: Now Micro RNAs
3/9/18, 18:52 - ‪+880 1725-266274‬: There are so many good information on microRNAs and target therapies. Reading this and will try to explain here tonight
3/9/18, 18:54 - Dr. Rakesh Sir Iq City: 👍👍
3/9/18, 18:54 - Anamika Mehta maam (abhi sir's sis): 👍🏼
3/9/18, 18:55 - Anamika Mehta maam (abhi sir's sis): Will read it later.
3/9/18, 18:56 - Anamika Mehta maam (abhi sir's sis): There is a relationship to emotional stress and molecular changes
3/9/18, 18:57 - Anamika Mehta maam (abhi sir's sis): Will post the papers later.
3/9/18, 18:57 - Anamika Mehta maam (abhi sir's sis): Emotional stress works at epigenetic level by changing the expression of the genes. In some cases switching off or on certain genes
3/9/18, 18:58 - ‪+880 1725-266274‬: Something happen with microRNA in stress?
3/9/18, 18:59 - Anamika Mehta maam (abhi sir's sis): Will share the papers later. I have been reading more on long non coding RNA but micro RNAs are also involved.
3/9/18, 18:59 - ‪+880 1725-266274‬: Okay ma'am.
3/9/18, 19:00 - Anamika Mehta maam (abhi sir's sis): Anamika......
3/9/18, 19:02 - ‪+880 1725-266274‬: Couldn't get you!!
3/9/18, 19:03 - Anamika Mehta maam (abhi sir's sis): I prefer being called by name
3/9/18, 19:04 - ‪+880 1725-266274‬: Oh okay. But I am very younger
3/9/18, 19:05 - Anamika Mehta maam (abhi sir's sis): 😀ok up to you.
3/9/18, 22:00 - pratya bhowal: *Treating my cancer through bone marrow transplant.*

I am a 21 year old medical student currently from India, studying in Burdwan Medical College, West Bengal. I suffer from a rare form of blood cancer of the type Early T Precursor Acute Lymphoblastic Leukemia (ETP ALL). I have been in treatment since February 2015. I'm proud to say that I've passed both my medical board exams on my first attempt despite the gruelling chemotherapy schedule, and I was hopeful that I would be able to f...

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3/9/18, 22:00 - pratya bhowal: Subham Mukherjee, student of 3rd prof.part 1 MBBS from Burdwan Medical College, has been suffering from Early T-cell Precursor Acute Lymphoblastic Leukaemia(a rare and severe form of blood cancer) since 2015. He was undergoing routine chemotherapy. Unfortunately a few days ago, a relapse occured and he now has to undergo bone marrow transplant which although life saving is very costly. So I request everyone to help as much as they can by donating and sharing this to other people. Any kind of help would be greatly appreciated.
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3/9/18, 22:00 - pratya bhowal: https://www.ketto.org/fundraiser/Subhamsfight
3/9/18, 22:00 - pratya bhowal: Last one is the link to donate money...
3/10/18, 16:48 - ‪+880 1725-266274‬: MicroRNAs are non-coding molecules that *regulate 30% human gene expression* and control apoptosis, embryogenesis, organogenesis, proliferation, antiviral response, stress. miRNA has a key role in *autoimmunity*. Aberrant expression of miRNAs in skin and serum is seen in vitiligo patients such that miR-99B et al are increased and miR-145 decreased in the skin and *miR-155 expression increases om the epidermis* and this miR-155 over-expression inhibits *the expression of melanogenesis-associated genes and altered interferon-regulated genes in melanocytes and keratinocytes*
3/10/18, 16:49 - ‪+880 1725-266274‬: Now IκK-16 *decreases miRNA-155 expression* and attenuates the human monocyte inflammatory response. Now the question is how attenuating human monocyte inflammatory response will help?
3/10/18, 17:09 - ‪+880 1725-266274‬: This message was deleted
3/10/18, 17:09 - ‪+880 1725-266274‬: miR-155 has the capacity to impact melanogenesis and inflammatory responses in vitiligo directly through its effect in melanocytes and keratinocytes.
3/10/18, 17:13 - ‪+880 1725-266274‬: Consistent with its overexpression in the epidermis, miR-155 was induced in response to TNF-α, IFN-α, IFN-γ and IL-1β, the proinflammatory cytokines that have been previously reported to be associated with vitiligo pathogenesis. When overexpressed, miR-155 inhibited the expression of genes known to affect melanocyte differentiation and melanogenesis. (miR-155 is known as a proinflammatory miRNA)
3/10/18, 17:16 - ‪+880 1725-266274‬: IκK-16 is a selective blocker of inhibitor of kappa-B kinase (IκK), on miRNA expression and the monocyte inflammatory response.
3/10/18, 17:17 - ‪+880 1725-266274‬: IκK-16 is a new therapy recently studied in animal models of sepsis and shock [9, 10] that reduces nuclear factor-κB (NFκB) activation by selectively blocking inhibitor of kappa-B kinase (IκK), and thus decrease the magnitude of the pro-inflammatory response.
3/10/18, 17:19 - ‪+880 1725-266274‬: This paragraph explain how reducing nuclear factor-κB (NFκB) activation helps.
3/16/18, 03:06 - Ashwini ai msai left
3/22/18, 21:34 - Dr. Rakesh Sir Iq City: Some food for thought on the introduction to our write up

"Today, the three classical biological explanations of the individual self––the immune system, the brain, the genome––are being challenged by the new field of microbiome research. Evidence shows that our resident microbes orchestrate the adaptive immune system, influence the brain, and contribute more gene functions than our own genome. The realization that humans are not individual, discrete entities but rather the outcome of ever-changing interactions with microorganisms has consequences beyond the biological disciplines. In particular, it calls into question the assumption that distinctive human traits set us apart from all other animals––and therefore also the traditional disciplinary divisions between the arts and the sciences."

http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2005358
3/22/18, 22:03 - ‪+1 (313) 312-6160‬: So what does this imply?
We are what our microbes make us?
3/23/18, 02:08 - ‪+880 1725-266274‬: This is really energy yielding food for beginning. Will start working on this paper.
3/23/18, 07:21 - Dr. Rakesh Sir Iq City added ‪+91 95855 15234‬
3/23/18, 07:21 - Dr. Rakesh Sir Iq City: Thanks Vivek let's rewrite the abstract in the imrad format and let's all begin sharing our case based experiences to weave together the write up using a case-study design. More here to enable you to write the methods section. Please share your first draft using your experiences of macro life events that you have encountered in diverse patients ranging from infective, immune mediated and neoplastic some of which already discussed using others published experiences above. Currently we need to weave this thread using our own unpublished similar experiences. The diversity of the experiences shared by this group here may help to weave a perfect cover
3/23/18, 07:22 - Dr. Rakesh Sir Iq City: More here to enable you to write the methods section
https://explorable.com/case-study-research-design
3/24/18, 13:43 - Anamika Mehta maam (abhi sir's sis): https://youtu.be/H3eSwkSSNAU (cancer needs to be tackles from multiple angles) Cancer X prize to be launched or is already launched? Not sure
3/24/18, 13:44 - Anamika Mehta maam (abhi sir's sis): https://www.xprize.org/cancer
3/24/18, 13:54 - Dr. Rakesh Sir Iq City added ‪+1 (868) 492-3694‬
3/24/18, 13:54 - Anamika Mehta maam (abhi sir's sis): I wish to start a team for Cancer Xprize
3/24/18, 13:55 - Dr. Rakesh Sir Iq City: Yes we can form one right here
3/24/18, 13:56 - Anamika Mehta maam (abhi sir's sis): Yet to be launched the Prize. But let's start exploring how to overcome cancer.
3/24/18, 13:57 - Anamika Mehta maam (abhi sir's sis): https://youtu.be/0uaquGZKx_0
3/24/18, 13:57 - Anamika Mehta maam (abhi sir's sis): We would need Moonshot thinking for it.
3/24/18, 13:59 - Dr. Rakesh Sir Iq City: Can you share your past experiences here around genomics and how you have been able to relate it (or not) with pathways that could result in cancer which in turn could be explored further toward finding solutions?
3/24/18, 14:05 - Anamika Mehta maam (abhi sir's sis): Yes I will.
3/24/18, 14:09 - Dr. Rakesh Sir Iq City: This message was deleted
3/24/18, 14:11 - Dr. Rakesh Sir Iq City: I guess we have already covered some parts of the 6 step moonshot plan?

Identify the problem — think huge ideas rather than bitesized.

Along with your big idea there needs to be the potential to overcome the problem (this part is mission impossible rather than mission tricky)

Form a team of committed, motivated, collaborative experts.

Work out what the most difficult aspect of the project is and set to work.

Foster a growth mindset. Learn from and celebrate failure.

Get buy in to the project at every level of your business.

Get to work and reach for the stars.
3/24/18, 14:11 - Dr. Rakesh Sir Iq City: https://www.google.co.in/amp/s/journal.thriveglobal.com/amp/p/ffffdae2de74
3/24/18, 14:12 - Anamika Mehta maam (abhi sir's sis): 👍🏼
3/24/18, 14:22 - Anamika Mehta maam (abhi sir's sis): I'm been associated with cancer from various aspects. Genomics was a part of it. Will share a presentation by next Friday to give you an idea how I wish to build it but yet too early. Shared my interest here if anyone is also interest in it to find out about that. I've been working for almost 5 years now with functional medicine doctors and looking to prevention of cancer and all chronic diseases.
3/24/18, 14:25 - Anamika Mehta maam (abhi sir's sis): We known there are genetic changes in cancer cells. And cancer cells metabolism is rewired but It's the environmental (stress and nutrition included) triggers that lead to it.
3/24/18, 14:29 - Anamika Mehta maam (abhi sir's sis): https://www.sciencedirect.com/science/article/pii/S0092867408010660
3/24/18, 14:34 - Dr. Rakesh Sir Iq City: Very interesting Anamika so we did talk about external and internal pathways to disease here before as exemplified by the tree image contributed by Dr Modali and you suggest that external macro life pathways may have an influence on internal micro genomic life events. While we shall be sharing a case study of two patients recorded by our students (online record shared earlier), one of them is still currently admitted it would be great if you could share similar case based experiences from your end
3/24/18, 14:52 - Anamika Mehta maam (abhi sir's sis): Yes
3/24/18, 14:53 - Anamika Mehta maam (abhi sir's sis): External factor influences the gene expression mainly.
3/24/18, 14:53 - Anamika Mehta maam (abhi sir's sis): But genetic instability in cancer could be result of Warburg effect
3/24/18, 14:55 - Anamika Mehta maam (abhi sir's sis): Will try. But we worked with healthy people. Idea was to keep them health.
3/24/18, 15:19 - Dr. Rakesh Sir Iq City: Will be looking forward to hearing what you found in healthy people
3/24/18, 15:40 - Anamika Mehta maam (abhi sir's sis): We were working on it focusing on prevention
3/24/18, 15:40 - Anamika Mehta maam (abhi sir's sis): No finding as such because it need lots of data
3/24/18, 15:50 - Dr. Rakesh Sir Iq City: So while we elucidate molecular internal micro pathway data from normal humans can we discuss what are the macro external event pathways in normal humans that help to classify their lived lives as normal?
3/24/18, 15:51 - Anamika Mehta maam (abhi sir's sis): Yes
3/24/18, 15:55 - Dr. Rakesh Sir Iq City: Sharing two patients with internal cancer where their external lives also appear to be abnormally lived here

http://bmjcaselogvivek.blogspot.com/2018/02/51-year-old-women-with-psychosis.html

https://saratuppaluri.blogspot.in/2017/10/case-of-ovarian-mass-with-chronic.html?m=1
3/24/18, 16:02 - Dr. Rakesh Sir Iq City: Now as a moonshot I would like to suggest that there is a Warburg effect that one may discern in current human society that is proliferating using seemingly inefficient drivers (like in malignant cells that use glucose instead of oxidative phosphorylation for their energy needs) and accumulating excesses that appears to be pushing them into a vicious cycle
3/24/18, 16:06 - Anamika Mehta maam (abhi sir's sis): Don't have case study. Will share our wellness presentation later. Can't find it right now in my mobile.
3/24/18, 16:07 - Anamika Mehta maam (abhi sir's sis): That'll give you an idea of how we were going to work with customers
3/24/18, 16:50 - Dr. Rakesh Sir Iq City added ‪+91 91778 01726‬
3/24/18, 17:24 - ‪+91 91778 01726‬: Thank you for adding me Dr Bishwas!
3/24/18, 19:31 - Avinash Kumar: in prevention or treatment ?
3/24/18, 19:36 - Anamika Mehta maam (abhi sir's sis): Both
3/24/18, 19:37 - Anamika Mehta maam (abhi sir's sis): Early detection mainly for all cancer. Simple and cost friendly for all countries
3/24/18, 19:39 - ‪+1 (868) 492-3694‬: We could actually apply the new strategy called seek-test-treat which has been tried in HIV program for end AIDS by 2030
3/24/18, 19:39 - Anamika Mehta maam (abhi sir's sis): Yes
3/24/18, 19:41 - Avinash Kumar: wow
3/24/18, 19:41 - Avinash Kumar: i wish to be in team, will share docs with ideas i can think of.
3/24/18, 19:41 - ‪+1 (868) 492-3694‬: I also have some experience on these early detection and screening from IARC during my fellowship in cancer prevention. Also applied that for a pilot study on breast cancer in Oman
3/24/18, 20:02 - Avinash Kumar: wow
3/24/18, 20:05 - ‪+1 (868) 492-3694‬: Let’s come together as a formal group to contribute our parts
3/24/18, 20:06 - ‪+1 (868) 492-3694‬: And Dr Rakesh can look at it after our contributions and then he will take forward
3/24/18, 21:35 - Dr. Rakesh Sir Iq City: 👍👍
3/24/18, 21:39 - Dr. Rakesh Sir Iq City: Yes we need every potential author to start contributing asap and finally authorship can be decided depending on whose input- contributions are utilized maximally. Shall share a brief detail of our tentative abstract here again to provide an idea of how we have already planned the write up and we are open to modifications
3/24/18, 21:59 - ashwini usa: Dr Anamika can you please share your work so far around cancer prevention and which areas you are interested in exploring further ?
3/24/18, 21:59 - ashwini usa: Oh sorry just saw the message about the presentation
3/25/18, 10:38 - Dr. Rakesh Sir Iq City: <Media omitted>
3/25/18, 10:39 - Dr. Rakesh Sir Iq City: (Illustration: Those conditioned to believe Pavlov more than the dog cannot be trusted to know the truth.)
3/25/18, 11:00 - Anamika Mehta maam (abhi sir's sis): Hi it has been on commercial side. Do not have paper to share. But the long coding RNA I have worked on during research days is where the genomics work is involved. I'll later share the wellness package we were to launch here that would lead to prevention. And for the Xprize It's too early. But I will only venture on that once I find some basic funding for that (if at all) so we can in small way compensate people contributing their knowledge and time. There has to be an internal legal understanding too to it. That legal framework will come from the funding body. But they would have their own interest in it. So It's to early for any talks right now on this only that I intend to.
3/25/18, 11:19 - Dr. Rakesh Sir Iq City: Thanks I guess you can still share your research experiences in detail (without sharing those that may be copyright protected) so that we can see how to fit it into our article?
3/25/18, 11:26 - Dr. Rakesh Sir Iq City: Some previous thoughts on the abstract that I thought I would share here for you all to see (especially for those joining in late) how you may fit it in with the current aggregore.

"Abstract :

What is the current understanding of precision medicine and why precision medicine should not be limited to genetics and to what extent we should extend beyond the genetics? Can this revolutionize the healthcare? If yes, how this can be revolutionized?What are the current case based blended learning and approach; and how precision medicine can do more precision to the current approach?We need to define our target population and what is the need for the target population?What are the purposes of this Case-based blended learning ecosystem and what are the objectives to fulfill this target.?How do we think that a case based blended learning will fulfill the target? Why is it the need of the hour? Why precision medicine matters and to what extent it can change the practice of current medicine?What outcomes are we expecting and how are we going to measure the outcome?How long will this take and how we are planning to take it ahead"
3/25/18, 18:59 - Aadipta Iq City: The most important question is how epigenetics affect the cancer pathways which is individualized for every single human being?
3/25/18, 20:30 - Dr. Rakesh Sir Iq City: I'm forgetting who had asked these previous questions. Was it Avinash, Srija, Vivek or Madhava?
3/25/18, 20:30 - ‪+91 91778 01726‬: 👌🏾👌🏾👌🏾
3/25/18, 20:33 - Dr. Rakesh Sir Iq City: This can be better illustrated with just one single case? Vivek would you like to take up the patient shared by Abhishek where you and Shreyas looked at the internal molecular pathways from a therapeutic precision perspective and we were trying to include it here as it's closer home so that all of us could relate to it. Vivek did you make his online record eventually and do we have any updates on his molecular markers?
3/25/18, 20:36 - ‪+91 95855 15234‬: Sir... I might be able to share my case... (it's in a rough draft form)... but it's not an oncology case
3/25/18, 20:51 - Dr. Rakesh Sir Iq City: Thanks Kaushik. Good to hear your voice here. We are looking to cover all pathophysiologies in our article and perhaps find the common internal micro pathways that binds their roots. Please share your experiences and as more and more of us share our case based experiences we shall all be amazed to discover their common roots/routes. 🙂
3/25/18, 20:57 - Dr. Rakesh Sir Iq City: Introducing Kaushik Sundar DM neurology, currently working as an interventional neurologist but still a passionate learner who used to ask me questions that I enjoyed learning from when I had the good fortune to teach him in his mbbs days. His daily interventions in addressing macropathways in his stroke patients that needs stenting hasn't dimmed his enthusiasm to learn about the micropathways that may influence the macro accretions that he addresses. I am looking forward to again learn a lot from his experiences shared here. 🙂
3/25/18, 21:04 - ‪+91 95855 15234‬: Thanks a lot for the intro sir... Will send my case right away
3/26/18, 08:01 - ‪+880 1725-266274‬: Actually I asked these questions
3/26/18, 08:19 - ‪+880 1725-266274‬: https://docs.google.com/document/d/147z2MA0WKVwhhdNDxsQU1KXq9AGVkzkkgyVYzLzkNzA/edit We will use this google doc for the draft. Please make sure to turn on option "suggesting" on the top right corner.
3/26/18, 08:27 - ‪+91 95855 15234‬: <Media omitted>
3/26/18, 08:31 - ‪+91 95855 15234‬: This is a rough draft... Will be happy to share any other details if required..
3/26/18, 08:33 - Dr. Rakesh Sir Iq City: Looking forward to reading it and having a good discussion to merge and unify all our pathways. 🙂
3/26/18, 08:40 - ‪+1 (868) 492-3694‬: Just a quick question... are we including the discussion on Problem
Based Learning which is common in many medical schools in Canada, West Indies, Middle East as well when we addressing the target audience?
3/26/18, 08:46 - Dr. Rakesh Sir Iq City: Very good question Vijay. Yes our form of case based blended learning is a form of problem based learning where the problem based questions on the primary case is often discussed online in a conversational manner. The questions raised around the case (for example in the JBCR review group, the case could be the paper under review) are raised online once the primary data collectors (those who upload the data containing the problem to be discussed) upload their data online.
3/26/18, 08:49 - ‪+1 (868) 492-3694‬: Got it 👍
3/26/18, 08:53 - Dr. Rakesh Sir Iq City: Vijay you can see the excellent case based problem shared here by Kaushik that will now be reviewed by this audience who shall raise Socratic questions followed by a dialogue that can bring around novel insights into this area which will enable us to unify hitherto untouched theories around this area and share it with the world moving the global thought process a few steps if we are successful in raising the appropriate questions and finding the right direction. The rightness or goodness of fit would be decided by our global audience if when we are published and perhaps measured if when our paper receives citations
3/26/18, 08:57 - ‪+1 (868) 492-3694‬: Dr Rakesh, I have a thought which comes to my mind when we are talking about precision medicine. I haven’t read anywhere but a random idea - since precision medicine ultimately leads to quality care which again leads to improved quality of life and life expectancy. So here we have 3 different types of care for patient when we talk - patient centered, person centered and patient directed types. My hypothesis is to include this angle of any of these types of care to add the value to Precision medicine.. may be it a cancer or a chronic scenario. Does it make sense?
3/26/18, 08:57 - Dr. Rakesh Sir Iq City: Thanks Vivek for collating some of the previous discussion here in the form of a draft. Please share it also with Amy so that she can begin editing it as we move forward in terms of collecting original primary data in the form of case based experiences shared already by yourself and Kaushik. Avinash and Madhava please share your case based experiences too that can be woven together to cover all organ systems toward a grand unifying theory. 🙂
3/26/18, 08:58 - Dr. Rakesh Sir Iq City: Vivek, Avinash can you blog all that has transpired in this group till now and share the link?
3/26/18, 08:59 - Dr. Rakesh Sir Iq City: Vivek share your bronchogenic carcinoma patient update after getting the information from Abhishek?
3/26/18, 09:21 - Madhava Sai Bmj: http://sivapuramsai.blogspot.in/2017/10/pregnancy-that-changed-her-life.html?m=1

This is one of the most challenging case whom we suspected to be of ANA negative APLA syndrome.

This can also be kept from a prespective of different phases of lives.

Sir instead of taking only multiple organ dysfunction why dont we add different phases of life to it.

From childhood to adulthood with different systems involving.

To add to it, life style diseases of our diabetes case which we are working on

This shows that the external pathways can always be linked to internal pathways in all phases of lifes and diseases.
3/26/18, 09:24 - ‪+1 (868) 492-3694‬: I like this innovative thought 👍
3/26/18, 09:27 - Dr. Rakesh Sir Iq City: Yes let's see the critical mass of different cases building up here to finally weave our grand unifying theory (a qualitative meta analysis) toward our aim of demonstrating how we may leapfrog solutions to current precision Medicine internal pathway roadblocks using external pathway indicators
3/26/18, 09:27 - ‪+1 (868) 492-3694‬: Madhava... I feel I should also give a flavor of Humanistic Health approach... treating the person as a whole with human values and not treating just the infection or damaged organ
3/26/18, 09:31 - Madhava Sai Bmj: Thank you sir, but we actually formulated it for a Art of imperfect brain symposium which we had presented in the Indian academy of neuro sciences conference which was led by sir, where I, avinash and vivek were also part of it.
3/26/18, 09:32 - ‪+1 (868) 492-3694‬: That’s good... just sharing the concept to give you an idea. We can use or omit based on the scope of our work and objectives. Feel free to decide
3/26/18, 09:33 - Dr. Rakesh Sir Iq City: Yes this is a very interesting dilemma that we have to deal with. When we adopt a precision approach we are trying to focus on to the internal disease pathways with razor sharp precision that can often make us ignore the external life events, a patient's journey, pre and post morbidity may otherwise help to illustrate. So in a way it appears to be a choice between the forest and the trees? The question is how do we reconcile both effortlessly in to our workflow? 🙂
3/26/18, 09:37 - Madhava Sai Bmj: Yes sir i feel that humanstic health should be needed to the current work flow which could enable the over all wellness of the patient
3/26/18, 09:40 - ‪+1 (868) 492-3694‬: You will see my editorial coming next month on Journal of Family Medicine and Primary Care where I have clearly discussed the 3 types of care and the humanistic approach. I can share the article once it’s available online in a week’s time. It’s a summary and description piece
3/26/18, 09:42 - Dr. Rakesh Sir Iq City: Even Anamika is trying to build on that from the opposite direction ie by addressing the micro internal genomic pathways that could possibly influence macro external life events? Anamika correct me if I'm wrong.
3/26/18, 09:46 - Dr. Rakesh Sir Iq City: Will be looking forward to it.

We need to find a way to integrate a humanist macro life bedside approach with the cold calculative scientific addressing of micro event approach at the bench?

Currently our schooling is such that most of us just feel comfortable with one of these worlds?

We need our blended learning forum to fast track diffusion of our comfort zones into both these worlds?
3/26/18, 10:03 - ‪+1 (868) 492-3694‬: Well.. you are raising another different concept when we talk about current schooling. I feel this is the main crux of the issue. How many medical schools follow the holistic approach of community health e.g sevagram model, CMC vellore and few more. I am not talking small about any school, with due respect I want to say that when a school takes the students to community right from their day one to villages and make them understand the wider environmental, community, society, culture and norms, then they get sensitized to these humanistic values. It can’t be taught in a course during a semester. No college takes that pain unless it’s in their institutional mission and vision. I am
Lucky to be from one of them where each student adopts 4 families for whole MBBS duration and we learn all the non medical issues in health care, health seeking, health etiology and finally we audit where things went wrong. This is just for a reading for interested ones.
3/26/18, 10:08 - Madhava Sai Bmj: Will be looking forward to redung your next editorial journal sir.

It is nice to know the concept of adopting families and understanding their lives but now a days we dont see such opportunities, even if we get them the management is not willing to take such things forward instead they keep us more busy with more and more exams, less and less exposure
3/26/18, 10:10 - Dr. Rakesh Sir Iq City: You are absolutely right about this issue. Our current elective program tries to promote a macro understanding of human life event related values into the current curriculum and the challenges with it that you pointed out are quite disconcerting to say the least but instead of again just focusing on macro life events and values (when it becomes labeled as soft), we also need to integrate micro internal pathways (aka and perhaps misunderstood to be the crux of precision) into current medical cognition driven by our learning ecosystem?
3/26/18, 10:14 - ‪+1 (868) 492-3694‬: Well the answer to that would be we need to create this young vibrant group to revamp and relook at the loopholes for future generation.. they need proper dedicated mentors. Am sure you are already doing that since years now 👍
3/26/18, 10:24 - Dr. Rakesh Sir Iq City: Yes so what we are trying to do is create a global group of life long learners to integrate patient macro event requirements with micro event pathways and this is an attempt to disrupt the traditional dyadic doctor patient relationship into a collective learning ecosystem with multiple actors. More here

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4587042/
3/26/18, 10:29 - ‪+1 (868) 492-3694‬: Excellent ! Commendable 👌
3/26/18, 10:32 - Dr. Rakesh Sir Iq City: While the above paper was based on how we are doing it at the warm bedside this paper will be not only about how to go about it with a deeper understanding of the cold bench but also how to use our insights from macro events to guide understanding of micro molecular events (aka targets in the language fostered by the bench). 🙂
3/26/18, 21:43 - ‪+880 1725-266274‬: Thank you Sir for sharing this case. I was interested about the MTHFR gene mentioned in your case. So, sharing some basic workflow of this gene. MTHFR gene provides instructions for making an enzyme ( important for a chemical reaction involving forms of the vitamin folate) called methylenetetrahydrofolate reductase (MTHFR). It sets up a stage through series of reactions for breaking down homocystine and converting into methionine.
3/26/18, 21:43 - ‪+880 1725-266274‬: Now:
3/26/18, 22:08 - ‪+880 1725-266274‬: Studies have also found that men and women with two C677T gene variants and elevated homocysteine levels may be at a mild increased risk for blood clots (venous thromboembolism).[4]
3/26/18, 22:10 - ‪+880 1725-266274‬: But, in this person, homocystiene levels were normal
3/26/18, 22:12 - ‪+1 (313) 312-6160‬: Can we add Ethical considerations of our method of precision medicine to the paper?
3/26/18, 22:14 - ‪+880 1725-266274‬: Can you elaborate more on this?
3/26/18, 22:15 - ‪+1 (313) 312-6160‬: Can I add to the document some relevant papers?
3/26/18, 22:18 - ‪+1 (313) 312-6160‬: Yes: Many times precision medicine uses molecular methods and data is stashed away in inventories which may later be utilised, But the patients may not be aware of this?

Can a particular gene be associated with stigmatisation?
3/26/18, 22:30 - ‪+880 1725-266274‬: MTHFR plays an important role in folate metabolism, which catalyzes the reduction of 5,10-methylenetetrahydrofolate to produce 5-methyltetrahydrofolate. The product is the dominant form of circulating folate, and provides a methyl group for the remethylation of homocysteine (Hcy) back to methionine. A common MTHFR polymorphism, 677C-T transition results in decreased enzyme activity and elevated plasma Hcy levels.7,8 The latter is known to cause vascular endothelial damage.
3/26/18, 22:42 - ‪+880 1725-266274‬: https://www.sciencedirect.com/science/article/pii/S1059131114000314 The objective of this study is to evaluate the precise association between MTHFR C677T polymorphism and epilepsy.
3/27/18, 00:19 - ‪+880 1725-266274‬: In subgroup analysis stratified by ethnicity, the results revealed that the MTHFR C677T polymorphism was associated with significantly increased epilepsy susceptibility in Asian populations in all genetic models. this association cannot be detected in white populations in any genetic model. Hence, some potential factors may contribute to the results that the same gene polymorphism affects different ethnic populations. Firstly, the differences in genetic backgrounds may play a role. Secondly, epilepsy is a multi-factorial chronic disease with socioeconomic status, access to health care and environmental exposure such as neurocysticercosis involved in its pathophysiology.44
3/27/18, 02:02 - ‪+880 1725-266274‬: will try to integrate more centered toward this case
3/28/18, 17:59 - Dr. Rakesh Sir Iq City: Below is another share for this article by one of our past students Binod who currently teaches hemato oncology in Wisconsin :

In a frigid Wisconsin morning last December, I received a phone call from my friend. As it turned out, my friend’s brother was in battle for his life against Multiple Myeloma. Patient’s disease had progressed after multiple lines of chemotherapy including two stem cell transplants in a mere span of 4 years. He seemed desperate for a ray of hope. With ample caution, I routed them towards relevant myeloma clinical trials in their area. Fast forward a few months, my friend called me again, but this time excitement was palpable through the phone. His brother was able to get enrolled in to a clinical trial using bcl2- inhibitor (venetoclax) – a drug active against a particular sub-type of multiple myeloma with t (11:14) (ref). This result, also shared by many others would open a new era of precision medicine in the therapeutic armamentarium of multiple myeloma.

In 1927, a brilliant physicist from Germany, Werner Heisenberg, introduced a principle, well known as “The Heisenberg Uncertainty Principle” that would become pivotal for the development of quantum mechanics. The principle asserts the fundamental limit to our precision with which certain pairs of physical properties of a particle can be known. The modern medicine, particularly the field of oncology, on the other hand, is rapidly moving towards a precision approach, as the molecular underpinnings of the disease evolution are made possible. One of the major goals of cancer research has been to gain a better understanding of the genetic changes responsible for the establishment of the “cancer clone” and the “key pathways” that could be targeted therapeutically. New insights into human cancers are emerging from basic research, and this has potential to revolutionize disease diagnostics, therapeutics and clinical decision-making.

“Precision Medicine”—an abundant term in medical literature, refers to the tailoring of medical treatment guided by genomic or molecular features of the disease and not by the clinicopathological features (ref). Since cancer is the disease of genome, the field has been the perfect choice to enhance the impact of precision medicine (ref). Because every single cancer patient exhibits a different genetic profile and the profile can change over time, “tailored” treatment rather than “one-size-fits-all” approach is likely to benefit patients and hence is an attractive concept. Whether it is a mere concept or realistically assures a better future in oncology continues to remain a debate. The precision medicine approach has transformed the outlook of some of the deadly cancers. One of the most notable examples is the discovery of bcr-abl gene fusion and development of imatinib for Chronic Myelogenous Leukemia (CML). CML has been hailed as a poster child of success in precision medicine as imatinib resulted in the unprecedented results with a 5-year survival of 90% and some patients even inching towards cure (ref). The other example includes the human epidermal growth factor receptor-2 (HER-2) and development of agents like trastuzumab. Compared to conventional chemotherapy, addition of this agent has resulted in significant improvement in progression free survival and reduction of death by 20% (ref). These examples illustrate how identification of key molecular pathways that could be targeted therapeutically could alter the disease course and result in the desired outcomes. What about the other cancers? Has precision medicine delivered its promise in other cancers as well and is it a time to celebrate? Or has our approach for more “precision” resulted in more “uncertainty” as described by Heisenberg?

In the context, the design and the results of SHIVA trial are worth a discussion. It is a phase 2, randomized multicenter trial, which assessed the efficacy of several molecularly targeted therapies based on molecular profiling compared to conventional therapies in patients with advanced cancers (ref). The results showed no improvement in progression free survival (the primary end-point) with the use of molecularly targeted agents compared to physician’s choice of chemotherapy. However, it is important to realize that majority of the patients in the trial received hormone modulator or mTOR inhibitor and thus the justification of the failure of the precision approach based on this limited data is not reasonable. The other was that the study was powered to determine whether the use of an algorithm-based approach to treatment allocation can improve patient outcomes — regardless of the nature of such allocated treatments(ref). In the trial each patient served as his or her own control in terms of primary end-point assessment. This calls for novel methods of designing the trials with clinically meaningful end points using the precision medicine. One of the other concerns has been the possible lack of valid biomarkers. We are experiencing another revolution in personalized treatment with the introduction of various immune-based approaches. Currently immune-based approaches represent the most exciting area for diseases like melanoma, non-small lung cell cancer, and hematological cancers including multiple myeloma. One of the reasons for the variability in patient response with immunotherapy is the lack of predictive biomarkers. Identifying predictive biomarkers is a challenge in immunotherapy and the other challenges include cost, toxicity and the tumor heterogeneity that impedes the efficacy of immune-based therapy. For checkpoint inhibition, PDL1 has been proposed as a putative bio-marker as pembrolizumab (anti-PD1) is approved in NSCLC only in patients whose tumor PD-L1 levels are ≥50%. Unfortunately, with the different temporal, spatial and methodological heterogeneity, it remains an unreliable biomarker (refs). The other unreliable biomarker includes the ERCC1 for NSCLC to platinum therapy (ref).

Despite the challenges, precision medicine holds a lot of potential in cancer therapy. While we need to conduct a well-designed randomized trials to assess the broader efficacy of the personalized medicine, and validate the bio-makers; we can also enjoy the tremendous success of KIT mutations in GIST, BRAF V600E in melanoma, EGFR, ALK, and ROS1 alterations in NSCLC. In a study that my friend’s brother participated, venetoclax monotherapy resulted in unprecedented response rates of 40% in heavily pre-treated patients with multiple myeloma (ref). Biomarker analysis confirmed that response to venetoclax correlated with higher BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios which are predominantly seen in patients with t (11:14). These results, for the first time, pave the way for precision medicine in multiple myeloma with a significant potential to change practice in a certain sub-group of patients.

Several clinical trials are constantly evolving to overtake tumor heterogeneity from patient to patient in their design. The Molecular Analysis for Therapy Choice (NCI-MATCH) is a clinical trial selecting treatments based on genetic features of patients, not traditional tumor histology. Thus far, 2,500 patients in the USA have been enrolled in one of the 24 arms of this trial, representing one-half of the recruitment goals (ref). The Molecular Profiling-based Assignment of Cancer Therapy (NCI-MPACT) is another innovative clinical trial to test the hypothesis that targeting an oncogenic driver mutation is more efficacious than not targeting it. NCI-MPACT will recruit advanced cancer patients who have been unresponsive to standard therapeutic options and possess mutations in one of three genetic pathways that include DNA repair, PI3-K/mTOR (phosphoinositide-3 kinase/mammalian target of rapamycin), and Ras/Raf/MEK (mitogen-activated protein kinase). The efficacy of diagnosis and therapies using with precision medicine could be significantly enhanced with the results of these trials.

With the development of novel technologies, we will be able to obtain deeper understanding of tumor complexity and the immune system. These will be critical in designing tailored combination therapy in future. The recent development of sequencing technologies has enhanced our ability to sequence cancers at both population and a single cell level. Diverse mechanisms that lead to disease evolution, disease response, and refractoriness are slowly being understood. These advancements, we hope, will translate to more targeted therapies with better outcomes in patients with cancers in future. With the recent approval of several targeted therapies in cancers by FDA, “precision medicine” may be in the offing in the oncology world! While it may be premature to celebrate the success of precision medicine yet, it is also a time to remain hopeful of the potential it has in the care of our cancer patients in future."
3/28/18, 18:00 - Dr. Rakesh Sir Iq City: Vivek let's connect with Amy on email to collate what we have received so far?
3/28/18, 18:01 - ‪+880 1725-266274‬: I am going to make an email to send Amy ma'am.
3/28/18, 20:40 - Srija Katta: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306023/
3/28/18, 20:40 - Srija Katta: The phenotypes of an organism are determined by the complex interactions between genetic factors (GFs) and environmental factors (EFs). The interactions between GFs and EFs link them together to form complex networks and thus work together on the network level to influence phenotypes and diseases, especially complex ones such as cancer and cardiovascular diseases. Recently, the theories and methods of network medicine have shed light on the network-level study of GF–EF interactions1. The computational analysis and modeling of the GF–EF interactions greatly improved the understanding of the mechanisms of EFs and explored new GF–EF interactions. For example, the analysis and modeling of one class of important environmental factors, drugs, and their interactions with their targets (GFs) has revealed a number of important insights2 and identified new drug-target interactions3. Moreover, the analysis of the interactions between drugs and genetic factors has successfully identified new indications for approved drugs that not only generate revenues for pharmaceutical companies but also benefit patients, which is the real incentive4.

microRNAs (miRNAs) are a class of newly identified GFs, which mainly repress the expression of target mRNAs at the post-transcriptional level5. Studies have reported that miRNAs are critical in various important biological processes, such as cell growth, proliferation, differentiation, development, and apoptosis6. In terms of their importance, a miRNA dysfunction is thus associated with a broad range of diseases7. More recently, increasing studies have shown that miRNAs can functionally interact with a wide spectrum of EFs, such as drugs8, virus9, alcohol10, cigarette11, stress12, diet13, and radiation14. *Moreover, miRNA–EF interactions critically affect and determine phenotypes. Hence, the dysfunction of miRNA–EF interactions is associated with abnormal phenotypes and even diseases15*
3/28/18, 20:40 - Srija Katta: In summary, we analyzed and modeled the interactions between miRNAs and EFs and their relationship to human diseases. We found that miRNA–EF interactions are significantly correlated to miRNAs characteristics, including the miRNA expression level, tissue specificity, conservation, and DSW. *This result indicates that the interactions between miRNAs and EFs are not random but have significant regular patterns* The uncovered patterns suggest new ways of identifying new miRNA-EF interactions. In addition, we constructed an EF–EF interaction network using miRNA signatures of EFs. We found that the module structure of the network is coupled with miRNAs of specific functions. More importantly, we discovered that the miRNA signatures of cancer treatment drugs and radiation could predict the results of cancer treatment. This finding suggests that the miRNA signatures of drugs are potential indicators for the evaluation of disease therapy results and propose a possible way of improving disease therapy at the miRNA level. The outcome of cancer therapy can be evaluated by monitoring the differentially expressed miRNAs of the patients after the drug or radiation treatment. Finally, we presented a computational model to predict potential associations between EFs and human diseases by combining the miRNA signatures of the EFs and human disease
3/28/18, 20:40 - Srija Katta: More importantly, we quantitatively showed that the miRNA signatures of drug/radiation could be used as indicators for evaluating the results of cancer treatments. Finally, we developed a computational model that could efficiently identify the possible relationship between EF and human diseases. Meanwhile, we provided a website (http://cmbi.hsc.pku.edu.cn/miren) for the main results of this study.
3/28/18, 20:50 - Srija Katta: This article shows the correlation and the change in expression of MiRNA with environmental factor
so in this we need to know the what are the possible environmental factors that the Patient has exposed and that caused the early expression of MiRNA then it can lead to finding out a *precise diagnosis* contributing to have precisions treatment to my knowledge though there are no available treatment In specifc to regulation of MiRNA? we can prevent the exposure to participular environment factors!! @971507375157 is there any available compounds which can regulate the expression of MiRNA?
3/28/18, 21:02 - Srija Katta: @971507375157 @919617604831 please comment on this!!
3/28/18, 21:51 - Anamika Mehta maam (abhi sir's sis): Will look up.
3/28/18, 21:52 - Anamika Mehta maam (abhi sir's sis): But will answer within 24hrs
3/28/18, 21:52 - Srija Katta: Thank you 😊
3/28/18, 22:03 - Dr. Rakesh Sir Iq City: [3/10, 4:34 PM] Vivek Poddar 2: Now IκK-16 *decreases miRNA-155 expression* and attenuates the human monocyte inflammatory response. Now the question is how attenuating human monocyte inflammatory response will help?
[3/10, 4:54 PM] Vivek Poddar 2: miR-155 has the capacity to impact melanogenesis and inflammatory responses in vitiligo directly through its effect in melanocytes and keratinocytes.
3/29/18, 20:42 - Anamika Mehta maam (abhi sir's sis): Hi I have to do more research before I can provide any meaningful answer to question asked.
3/30/18, 10:53 - Aadipta Iq City: https://www.google.co.in/url?sa=t&source=web&rct=j&url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333888/&ved=2ahUKEwjs5ce-o5PaAhXJQY8KHaYcCicQFjAEegQICRAB&usg=AOvVaw0FRcQhJ8152IODnUMI2sG7
3/30/18, 10:54 - Aadipta Iq City: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795376/
3/30/18, 10:55 - Aadipta Iq City: https://academic.oup.com/ndt/article/24/4/1088/1894805
3/30/18, 10:55 - Aadipta Iq City: The above links provide an insight into the interrelation between miRNAs and epigenetics
4/1/18, 10:57 - ‪+880 1725-266274‬: Deadline for our paper to submit is 30 May 2018
4/1/18, 10:59 - Madhava Sai Bmj: Yes we
should start writing the articles the google docs.
4/1/18, 20:24 - Dr. Rakesh Sir Iq City: Would both of you be able to come to KIMS post presentation in Delhi? We may be able to write it up faster if you guys are around as we may be able to discuss faster face to face. Also you can write up the many pending case studies generated here every week?
4/1/18, 22:04 - Madhava Sai Bmj: Thank you for the opportunity sirr, please give us some time to discuss about it
4/1/18, 22:05 - ‪+880 1725-266274‬: Yes sir.
4/2/18, 20:02 - ashwini usa: Hi I am back
Vivek I'll call you. Please let me know what is to be done
4/2/18, 20:29 - Dr. Rakesh Sir Iq City: Can one of you connect to Ron (see details below) and learn more from him about his work to see if there can be a potential collaboration
4/2/18, 20:33 - Dr. Rakesh Sir Iq City: Ron Martin

Yesterday

I'm actively involved with identifying the evidence base in the literature (PubMed) for the connection between genetics/epigenetics, health/mental health and our environment, including but not limited to nutrition. -- Ron Martin (Nutrigenetics Unlimited, Inc.)

11:39 PM

Hello Prof. Biswas, Thank you for accepting my invitation to connect on LinkedIn. If you're not already familiar with the online database at Nutrigenetics.net, it's a subset of PubMed.gov articles relevant to genetics/epigenetics and health/mental health, but further indexed with standardized terminology (controlled vocabulary), including for genes and gene variants, as further described at:www.nutrigenetics.net/FAQs.aspx It allows creation of an index of subtopics for any given topic, or for any given combination of topics, thereby enabling discovery of otherwise hidden relationships. Related article titles serve as links to the corresponding PubMed records. The "Description" column of our indexes shows the common synonyms for many topics. By scrolling down below the first A-Z listing, you'll see a second A-Z listing of genes and gene variants. Knowing the synonyms for the gene variants is especially useful, since the terminology differs considerably between authors. Beyond health conditions alone, it's also useful for illuminating gene-environment interactions generally, including but not limited to nutrition -- which can also be of interest to students (e.g., sports, social environment, stress, lifestyle, well-being, etc.), including high-school STEM students. Access is free for everyone on weekends (Pacific U.S. time) when logging in with Free as the username, and Weekends as the password, as also shown on the login page at:https://Nutrigenetics.net/Login.aspx You're welcome to explore it on a complimentary basis anytime (24/7) from now through April with the following login, which you're also welcome to share with others as desired: Website: Nutrigenetics.net Username: April Password: Free835 [note that passwords are case-sensitive] Complimentary round-the-clock access to the database is also provided to members of the International Society of Nutrigenetics/Nutrigenomics (ISNN):www.NutritionAndGenetics.org ISNN's 12th Congress will be held on September 30 - October 3, 2018 in Winnipeg, Manitoba, Canada:www.ISNN2018.org After logging into our database, you can return to one of our homepage links likehttp://nutrigenetics.net/Home/ThePublic.aspx to browse hundreds of interesting article titles. Healthcare professionals can find value in our page athttp://nutrigenetics.net/Home/Professionals.aspx for more on health conditions. Because we use standardized terminology for indexing the articles, we're constantly adding new topics, or enhancing the indexing for existing ones, including deeper searches and cross-referencing of variations in terminology. Please let me know if you see an opportunity for how our database can be further enhanced to more perfectly suit your own needs, or the needs of those you serve. While making our database more useful and valuable to you, we're simultaneously helping all other users as well. If at any point you or any of your colleagues would like to see a live demo of our database, I can provide this via Skype or via Google Hangouts by sharing my screen while we talk. If interested, just let me know (I'm located in the Los Angeles time zone). There's more to the story which is easier to explain while chatting. Finally, I invite you to read my open-access article entitled, "Gene-Environment Interactions: Emergence of Knowledge, and Its Successful Translation into Practical Applications" at:https://www.ecronicon.com/ecnu/pdf/ECNU-01-000S1.pdf Comments always welcome. Kind regards, --- Ron Ron L Martin, MS Nutrigenetics Unlimited, Inc. 1742 Peacock Lane Fullerton, CA 92833 USA Office: +1-714-656-3956 Skype: nutrigenetics Nutrigenetics.net
4/2/18, 20:51 - ‪+1 (313) 312-6160‬: I can try
4/2/18, 20:51 - Dr. Rakesh Sir Iq City: Please do and share what you learn
4/2/18, 21:03 - ‪+1 (313) 312-6160‬: Thanks RB
4/2/18, 23:01 - ‪+880 1725-266274‬: sure. go through this doc https://docs.google.com/document/d/147z2MA0WKVwhhdNDxsQU1KXq9AGVkzkkgyVYzLzkNzA/edit?usp=sharing and start contributing. Amy ma'am given some useful inputs. you can review and answer those. And also there are several questions pending answer in the document.
4/2/18, 23:01 - ‪+880 1725-266274‬: Shreyas, please talk with him and update feedback once you get.
4/2/18, 23:23 - ‪+1 (313) 312-6160‬: Okay
4/3/18, 00:05 - ashwini usa: Thanks a lot. I'll do that
4/3/18, 12:35 - ‪+880 1725-266274‬: " Hippocrates, the father of modern and ancient medicine, said it is more important to know what sort of
person has a disease than to know what sort of a disease a person has. That's another way of saying that it's important to understand the patient and then you'll understand the disease."
4/3/18, 12:38 - ‪+880 1725-266274‬: "Variability is the law of life and as no two faces are the same, so no two bodies are the alike, and no two individuals react alike and behave under the alike conditions which we know as disease".
4/3/18, 23:10 - Dr. Rakesh Sir Iq City added ‪+1 (501) 246-1208‬
4/3/18, 23:10 - Dr. Rakesh Sir Iq City: Added Dr Swaminathan who is a nephrologist and a physician scientist at university of Virginia. Welcome to the group Swami. 🙂
4/3/18, 23:11 - ‪+1 (313) 312-6160‬: Welcome to our group Dr Swaminathan
4/3/18, 23:11 - ‪+880 1725-266274‬: Warm welcome Dr. Swami sir. I am Vivek. Very happy to have you with us.
4/3/18, 23:12 - Madhava Sai Bmj: Welcome to the group Dr. Swaminathan sir, this is Madhava Sai
4/3/18, 23:12 - Srija Katta: Hearty welcome to the group Dr. Swaminathan 😊
4/3/18, 23:13 - ‪+1 (501) 246-1208‬: Hi All, thanks Rakesh.
4/3/18, 23:13 - ashwini usa: Hello ! Nice to meet you
4/3/18, 23:18 - Dr. Rakesh Sir Iq City: Swami would you like to elaborate on your recent post which I quote again here, "Immunity, Metabolism and Cell-to-Cell communication govern not only cellular but also organismal fate!
At the cellular level, cellular intelligence/metabolism is "tejas" and cellular immunity is "ojas", and the flow of intelligence and communication at the cellular level is "prana" and these processes govern systemic health. We now have established these to be relevant using modern tools."
4/3/18, 23:27 - ‪+1 (501) 246-1208‬: I will get back to you on this soon.
4/3/18, 23:30 - Srija Katta: Wow seems interesting 😀
4/3/18, 23:31 - Avinash Kumar: Welcome Dr. Swaminathan sir!😊
4/4/18, 07:06 - ‪+91 91778 01726‬: Good morning folks! Interesting. Just wondering whether this is just semantics?
4/4/18, 07:32 - Dr. Rakesh Sir Iq City: Thanks Prof David yes semantic meanings are evocative and can drive the human mind to think in directions it may otherwise shy of. 🙂 Most of us who are Western trained would be scared of the identifiable Eastern semantics in the statement and some of us may assume a knowledge of its meaning as a birthright but the truth as usual perhaps lurks somewhere in between? 🙂 Vivek can we share again the image of the tree and it's roots offered by Dr Ravi and proceed to add the external macro life events from one of our currently discussed and presented online records to its branches and internal micro life events to its roots to create a collage (a graphic record that can go as illustrative figures in the article) of the external and internal pathways that is an essential prerequisite to achieving precision Medicine in each of our individual patients? I shall try to elucidate further the nature of past and present changes in precision Medicine thinking with yesterday's patient experience in our casualty of a person who came with abnormal behavior and a history of monkey bite 2 months back and having completed post exposure antirabies vaccine.
4/4/18, 08:40 - Dr. Rakesh Sir Iq City: Yesterday I got a call from my PG student who needed cognitive help with the patient's diagnosis and treatment plan and even before I had seen the patient I was sure with my 30 years of experience seeing (a few) rabies patients I would easily resolve the issue but this patient was anything unlike I had encountered before as what I could call a 'black and white' rabies.
He didn't fit the diagnostic prototype that I had grown used to by just noticing aerophobia (rarely having to test for hydrophobia) and yet there was some circumstantial suggestion to the diagnosis as mentioned before.
In the past by noticing those few clinical features that I learned from my seniors as being diagnostic I could precisely prognosticate and seal his fate sending him to the dungeon of our government infectious disease hospital where most such patients would be allocated to die and the last such patient's family I remember few years back gave in after I told them that 'yes we may be even able to save the patient after a protracted battle with ventilatory support perhaps necessitating a few years of ventilation as was being increasingly described in case reports but would they be able to afford it?'
That was the closest I had come to prognostic and therapeutic imprecision in rabies where in most other cases I could precisely guide them to the dungeon with clinical impunity.
Yesterday's case floored me with its diagnostic imprecision where I began wondering if I was dealing with an evolving form of the virus where the disease was changing it's clinical characteristics or was it a just a patient of psychosis with a background of rabies providing an opportunity for diagnostic imprecision? Either way it appears that over the ages (as we age in our clinical careers) all of us may gain these opportunities to experience imprecision in situations that we used to take for granted in the past?
4/4/18, 09:28 - Avinash Kumar: <Media omitted>
4/4/18, 09:28 - Avinash Kumar: <Media omitted>
4/4/18, 09:29 - ‪+880 1725-266274‬: Thanks avinash for sharing this. I was not able to trace it.
4/4/18, 09:29 - ‪+880 1725-266274‬: Can you share the full version here
4/4/18, 09:30 - Avinash Kumar: yes dada, pdf have full version
4/4/18, 09:30 - Avinash Kumar: shared above
4/4/18, 09:30 - ‪+880 1725-266274‬: Oh got it.
4/4/18, 09:32 - Avinash Kumar: sir, is this situation is common in young physicians like when i saw damaged ear and expected it may be related to genetic cause but i haven't read/know/remember.

what a physician should do when they know that they don't know situation at hand?

i mean what is to be done when puzzle pieces are so less, than while we are searching for a Face painting of monalisa, we not even getting even its a human or land or what in these few pieces of puzzles.

(some content is from our art of medicine project done previously)
4/4/18, 09:37 - Dr. Rakesh Sir Iq City: Thanks Avinash I had nearly forgotten this image and we shall need to find an image of a. Similar tree minus the labels on the branches and roots as we plan to structure it conceptually in a different manner by incorporating external macro life events to the external tree and internal micro life events to the internal tree (roots). I shall share again the data from one of our recent patients that you can help incorporate into the tree. Avinash how different would it be from your VR online record and can we use this as an opening page for each of your VR online records?
4/4/18, 09:39 - Dr. Rakesh Sir Iq City: Will get back asap
4/4/18, 10:00 - Dr. Rakesh Sir Iq City: This may be common in physicians who are not averse to repeatedly putting themselves in imprecise situations as that may drive their learning highs and as they may be addicted to learning they keep getting into these situations where many of their peers would choose to avoid it. So it's an interesting area of "medical cognition" that you raked up Avinash. I am sure there are many other view points here that we could further learn from. Currently interviewing a family of potential osler rendu Weber syndrome in the OPD with one of our PG students and anticipating more precision as we try to collect more and more artifacts to build our case and actually enjoying these moments of imprecision in anticipation of that complete picture (of Mona Lisa) revealed moment. We know that in most clinical encounters we would just have to live with the partial picture and as long as the patient feels guided and supported in their journeys precision takes a backseat?
4/4/18, 10:01 - Dr. Rakesh Sir Iq City: Avinash can you put all the past content here into a blog and share the link?
4/4/18, 10:12 - Avinash Kumar: yes sir we can.. and while a DTI show's everything going inside consciousness (cognitive record book, may be mostly conscious), a tree make us stand outside of cognitive record and brings in real *life* real events happening (conscious and subconscious) since the moment of zygote formation till death.

AI was expected to have 5 senses and BCI is working on cognition, combining together we go ahead of DTI and nurture a tree of life.
4/4/18, 10:14 - Avinash Kumar: yes sir. doing it, will take some time.
4/4/18, 10:15 - Avinash Kumar: (currently AI have got 5 senses and working on creativity. also any human task that can be broken into 1 second units can be done by AI now, as said by prof. Andrew NG).
4/4/18, 10:25 - Dr. Rakesh Sir Iq City: <Media omitted>
4/4/18, 10:26 - Dr. Rakesh Sir Iq City: <Media omitted>
4/4/18, 10:26 - ‪+880 1725-266274‬: <Media omitted>
4/4/18, 10:27 - Avinash Kumar: image from google? checked copyright?
4/4/18, 10:28 - Avinash Kumar: to use in VR project we need to avoid copyright infringement.
4/4/18, 10:28 - ‪+880 1725-266274‬: Same image in the pdf
4/4/18, 10:28 - Dr. Rakesh Sir Iq City: Avinash and Vivek can we put the external and internal pathway data from the patient information shared above into your tree?
4/4/18, 10:29 - Dr. Rakesh Sir Iq City: Yes let's just click an image of the tree outside your house
4/4/18, 10:29 - Avinash Kumar: mago tree👌🏼
4/4/18, 10:29 - Dr. Rakesh Sir Iq City: And add roots to it
4/4/18, 10:30 - Avinash Kumar: so that cube can give us many pics to use for VR
4/4/18, 10:30 - Avinash Kumar: making each case unique. (if interested).
4/4/18, 10:30 - Avinash Kumar: will use any tree outside for now.
4/4/18, 15:12 - Dr. Rakesh Sir Iq City: Very good idea Avinash. You managed to merge it with our original health record botanical identifier strategy. 🙂
4/4/18, 15:25 - Avinash Kumar: thanks sir. will discuss with arunan sir.

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Wednesday, 4 April 2018

Precision Medicine

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