Annexure

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Scientific rational

A) Anecdotal reports of brain death reversal

Despite the label of irreversibility associated with the 1968 Harvard Ad Hoc Committee definition, there are several documented cases in the literature of potential brain death reversal, primarily associated with younger subjects

10-month-old boy who was found submerged in a bathtub and 42 hours after the incident, fulfilled all criteria for brain death according to Canadian Neurological Determination of Death Forum recommendations. He was given cardio-pulmonary resuscitation for 37 minutes and began breathing 15 hours later. This finding was done over six years ago and questioned the assumption that brain death was irreversible

Very recent Jahi McMath and Bobbi Kristina

Arion Sharon former prime minister Israel, Michael Schumacher etc

1.Jahi macath https://en.wikipedia.org/wiki/Jahi_McMath_case
2.Bobbi Kristina Brown is ‘not brain dead’. – Oldenburg, Ann – USA Today. –
http://www.usatoday.com/story/life/people/2015/02/05/bobbi-kristina-brown-not-braindead/22928581/

3.A 10-month-old infant with reversible findings of brain death – Joffe AR, Kolski H, Duff J,deCaen AR. – Pediatr Neurol. 2009 Nov;41(5):378-82. doi:
10.1016/j.pediatrneurol.2009.05.007.

4.Spontaneous in utero recovery of a fetus in a brain death-like state – Ueda K, Ikeda T,
Katsuragi S, Parer JT. – J Obstet Gynaecol Res. 2010 Apr;36(2):393-6. doi: 10.1111/j.1447- 0756.2009.01141.x.

5.Return of EEG activity after electrocerebral silence: two case reports – Joseph B. Green,Andre Lauber – J Neurol Neurosurg Psychiatry 1972;35:103-107 doi:10.1136/jnnp.35.1.103

6.Return of spontaneous respiration in an infant who fulfilled current criteria to determine brain death – Okamoto K, Sugimoto T. – Pediatrics. 1995 Sep; 96 (3 Pt 1):518-20

7.http://www.ncbi.nlm.nih.gov/pubmed/19818943

8.http://www.ncbi.nlm.nih.gov/pubmed/20492393

9.http://jnnp.bmj.com/content/35/1/103.abstract

10. http://www.ncbi.nlm.nih.gov/pubmed/7651788

B) Presentation in American academy of neurology

http://www.neurology.org/content/82/10_Supplement/P4.285

C)Approach being safe:

Autologous Stem cells are being used in various neurological indications in living subjects

D) Definition of brain death is very old dated 1968

Brain Death: A Reappraisal – Springer 2007th Edition – C. Machado – ISBN-10: 038738975X– ISBN-13: 978-0387389752

When ‘life support’ is really ‘death support’. – Landau, Elizabeth – CNN. –
http://www.cnn.com/2013/12/28/health/life-support-ethics/

How much of the brain must die in brain death? – Bernat JL. – J Clin Ethics. 1992Spring;3(1):21-6; discussion 27-8.

Are Brain Dead Patients Really Dead? – John D Banja – Department of RehabilitationMedicine, Emory University, and the Center for Ethics, Atlanta, Georgia 30322, USA. – TheJournal of head trauma rehabilitation – 03/2009; 24(2):141-4. DOI:10.1097/HTR.0b013e3181a2858d

E) Need of Animal studies

However, when you come to the topic of brain death, good animal models are few and far between, using all sorts of exotic methods to poison pigs with carbon monoxide gas etc. and they would provide us with quite limited answers.

With respect to brain death no standard criteria exist defining brain death in lower animal (what exact observation period needed in animals) so any study even successful will not provide clear answers.

Biological studies on lower animal have a great limitation as intrinsic regenerative power of lower animal is huge. In one of the study on spinal cord injury 40 percent of control group animals were able to walk despite removal of 3 cm of cord.

Japan has come out with special legislation and removed the compulsory need of animal studies. Even Indian CDSCO has given go ahead for phase 2/3 trial to few cell based therapy without need of animal studies

F) lack of strong scientic data

Till date there has never been a systematic study to determine validity of brain death definition

Reversal of brain death has not yet appeared in peer review journal and probably we would be first one to report

Need to do in India

It is not because of lack of law in India The law and regulations are same and as stringent as in USA or developed world

US FDA guidelines

USFDA: FDA does not require investigators to comply with the IND or IDE regulations for studies of FDA-regulated products in the recently deceased, provided that tissues or organs for use in humans will not be recovered from the individual after, or during, the research activity. Lorrie H. McNeill ,Director,Center for Biologics Evaluation and Research.Food and Drug Administration USA

There has already been Studies on BD subjects for other outcomes in USA. it has legitimately (and quietly) gone on for many years now (primarily for using the “human model” in toxicology, pharmacokinetic, and pharmacodynamic studies), at locations including University of Chicago, M.D. Anderson Cancer Center in Houston, and University of Pittsburgh Medical Center,
http://articles.baltimoresun.com/2003-02-02/news/0302020371_1_research-living-dead-university-of-pittsburgh

3. It is primarily Indian study, our concept. We don’t want it tour credit for this study being diluted by doing it elsewhere. It may sound funny but we wish to prove the world that India can lead in medicine too and probably world will follow Indian guidelines for defining BD

(We also developed interlocking nailing option from this small city)

4. Of course it is cheap

Ethical

Over 60 million people globally suffer each year. And at any given point . Many centres extend the ventilator support and trying pharmacologic ways at the request of relatives .We all encounter numerous situations when parents /relatives want Drs to give due chance before weaning of ventilator

As per existing guidelines 6 hrs of observation is needed .our study can either confirm or suggest more hours of observation. Since 6 hrs criteria was based on modalities available in1965 and we believe it’s time to review.

Our study is just an attempt to EXTEND THE VENTILATORY SUPPORT AND observe the BD subject for few more days and additionally use autologous stem cells ( just an extension of stem cell application as being used to treat many neurological situations)

No money being charged. Subjects are insuraed for the cost of treatment if any one comes out of BD status

Results of study will end debate or controversies surrounding with BD

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