Just want to stand and he does too soon.

Just in the slightest.

As easy to there is.

Obvious world in years which is.

This year's I mean good riddance
a great pleasure to do good news

twenty seventeen seasons and
look for that my home life will

tell you this sure as it is
say to the Muslim woman or

to the sure that it will be the one that.

Needed readers why is the science.

News it's.

Just one of the rare originals
were significant news.

Understanding to be all.

But also on groups and here.

Is for the editors of medicine places for
research to hear what was the all those

reports that shortly afterwards was also
one of the you will hear its citizens.

Graduated magna model from our
own received and then moved to

Stanford Medical School where you
see through this was the Masters.

And later master called Powell
from Johns Hopkins hope.

This is his moment.

Internet reading this is
just as long a reason for

all this and this is all over the phone or
the answer is the same.

As the hiring decision off
of the sickle cell from.

President Bush.

Into law I told him or.

So I'm going to skip over some
of these are the reasons.

Our.

Lives words just two.

Hours what would keep going as.

Our stuff like.

This and.

Men's lives you.

Know on my i am it's a coup.

Thank you.

That introduction was so
good I start to apply for myself.

So this is a real honor
to be here quite frankly.

A had some degree of trepidation
wirework School of Engineering ask

a physician to come and talk to people who
know more about differential equations and

I forgot ever and but

it's a real privilege after meeting
Bob nearly and really just sitting for

a moment in this atrium and
understanding how

this building was built the inspiration
and the sense of community.

Put together to have really a sense of
scholarly activity as well as community.

Spirit about discovery and
I really think that quite frankly

he gets the an A for the applause so
I wouldn't want to do that.

So yeah I mean I mean or
quite frankly I saw

I'm a what should I talk about well you
know traditionally when I give talks it's

almost always data driven and
I am compelled to tell you how I.

You know started just the project to
give you some data about the middle of

the project and give you the end but
I want to try to shift your paradigm for

a minute and and
have a think about this concept that

if we are going to support others in
scholarly activity that our strategy

should be a one in which we
are missionary workers we go to a place

we do something in that location we
leave and quite frankly that model for

my opinion doesn't work very well and
really what we should be thinking about

is an intersection in knowledge
between not only providing support but

also advancing the care in them something
that I didn't mention in the slides but

I will mention here this perception that
knowledge is one way that you go from

a higher income country to a low income
country and that it can be the other way

that we can learn from people who
are in low resource environments

I think is is a is a misperception of
how knowledge should be transferred so

I just have a few slides discuss the basis
of sickle cell disease are touchy about

the original patient they get me
interested in this challenge problem

to try to solve the one thousand nine
hundred one when I was a human fellow.

And then I'll talk a little bit about.

My road trip to northern Nigeria.

The trial that came out of their road trip

the more definitive Phase three
trial is still in progress and

then a new problem that I hope
the engineers here in Georgia can solve or

at least help the south there will
hopefully save lives so this is a very.

Traditional.

Slide that you would see in
medical school it's a picture of.

Sickle cells and their blood cells
are seen under the microscope and

the typical red blood cell is round and
discords shape and

you can see these cells are look
like circles they're fragile.

They have a decrease of
Vive all of fifteen or

twenty days versus one hundred twenty
days or rigid and inflexible and

they cause are chronic Amala says with
laboratory of the mallards as a result of

some pioneering work has been done over
thirty plus years newborn screening is

now mandatory United States every state in
the union provides newborn screening for

children with circles for every
newborn and as a result of this effort

there's a significant reduction in death
and illness in infants with super cells

so this is actually one of my favorites
lies to show it turns out that

if you are interested in public health you
will spin a disproportionate amount of

your resources on the most common diseases
in the in the country identified in

the board screen turns out the sickle cell
disease occurs one in twenty four hundred

newborns regardless of race after
it actually in African-Americans is

one in four hundred now you compare that
to congeal hypothyroidism which is one in

three thousand cystic fibrosis
which is one in three thousand and

in variance of P.K.U.
which is one in thirteen thousand so

despite the common prevalence of this

rare disease when compared to the other
disease resource allocation is actually

nowhere near reflective of the patients
born with this disease in United States so

this is a quote taken from William also it
describes the concept of laboratories and

clinics in selected states
clinical laboratories

laboratories of the highest order.

So I want to flashback to nine hundred
ninety one someone who may not even been

born in one thousand nine hundred one but
I was definitely alive and working.

Hard and then I got a phone call.

I won't draw this drama out
it was actually my mother.

Was a human talent young fellow and
she was a Montessori teacher for

the only Montessori school in
a public school in in Missouri and

she had a trainer older was a student.

And she was concerned that this student
was a man unable to remember skills that

she had mastered three months ago and I
remember dramatic still remember today and

so Mom Tell me a little bit more about the
student you know in so she would go on and

it's described that she completely lost
her skill set so well as she walked in

a gym you know because at that time
a third grade teachers would go out for

gym class and go after recess she's
fine she's having a good time

you know she's not having any
challenges walking up steps.

So well I'm not really sure so
I was my mother's son so

she asked me these questions and
these were the questions that have

essentially been a cornerstone
of what I have focused on

since one nine hundred ninety one the
first one was what's wrong with the show.

And then the next was what
can you do to treat or.

And then for teacher it was all
about what can I do help her learn.

And so for tourists Lee for me.

It turns out that she was
the patient the student was in

a natural history study
sponsored by the Unite and

in one nine hundred eighty nine the M.R.I.
or is seen here on the left in.

And then subsequently she had an M.R.I.
again as part of this natural history.

Study and it was and what you see is on
the Right now the official report was no

change but
clearly I had the benefit of my mother

asking me questions at every family get
together what's wrong with my student.

So we have learned often I'm sure this is
the case in engineering where you check

the impaired data yourself and so despite
the radiology reports say no change.

It doesn't take a new radiologist to see
that they're fat with a white arrows

are or new lesions and
this is about the time that new create

new technology had been introduced and
so there was a skepticism

among our new radiology colleagues almost
all of which were adult radiologists.

And they really weren't any
pediatric radiologists who were

board certified at the time and
Lee said our institution and

they basically called this
artifact in if you go bat

through these in our eyes there were done
in the early ninety's the description is

actually an identifiable bright objects
that's actually a term that they use or.

Requires clinical correlation
of unclear significance.

But because of this.

Patient and

belief that she did have something there
was cognitively in despair a cognitively.

Disruptive I pursued a series of studies
that are just briefly go over now.

One of them is this
concept of how prevalent

is a sound stroke in children and
adults with simple celled anemia and

what you hear here is
the mean age on the X.

axis in the province of silence we were
in a farce on the what Wired says and

have these various studies
there were done across the.

Globe where they are.

Children and adults into an M.R.I.
scanner where no prior symptoms or

knowledge of having a focal neurological
deficit indicating a stroke and

getting an M.R.I. to determine if
they've actually had an infant and

is every point represents
actually different studies and

this was you know plotted out quite nicely
this and I didn't make this plot up

the last circle in fact is from our center
of Vanderbilt when I moved from Washington

versity to Vanderbilt in two thousand and
ten the adult humor tonnages was.

Who's a friend and
I mentioned him in a circle was

less than interested in getting
surveillance in our eyes but.

As we pointed out if you look at by
eighteen years of age thirty nine

percent of the children adolescence
before they finish high school have

the presence of a cell a stroke very few
conditions in medicine where the pretest

probability is almost forty percent so why
would you not want to know if the adult

you're taking care of has had a silent
enfant in so with the data that we

had previously published we were able to
go ahead and continue to do surveillance

from our eyes in the adults in this was
the result of the publication showing that

over half of the dolls by thirty five
years a person from from Italy two years

of age will have sounds we will in four
hours so this is a complicated slide but

I want to spin a few minutes
describing the impact here so what.

You know so when you find these lesions
in the brain it took me about a decade of

meticulous clinical research of first
describing where the location of the and

forge were whether the infortunate
associated with specific neurocognitive

domains whether the influx were associated
with academic difficulty because at

the end of the day if I tell a parent your
child has lost five I.Q. points that isn't

necessarily translate into anything for
the average parent but what it does.

TO is translated to children
who have sound strokes

actually have a higher
rate of great failure so

we went through our that to eventually
get to a point where over a course of.

Multiple years from ninety six to two
thousand and eleven there were roughly ten

studies that looked at the impact of the
presence of a solitary will in fart on for

scale are killed compared to the impact
of full scale arc of the M.R.I.

when there is no in fart on your
full scale or kill an essentially

in this forest plot here you
see you see it is words.

You mean this is.

A mushroom I'm sure in this here or
here we don't so

in this forest cloud this is for
the students who don't normally see forest

plots I can just give you the bottom line
typically you want to look at the diamond

at the end which isn't there which is
a summary of that and is based on which

assumptions you use to model the pooled
analysis whether you use the.

Random or fixed of fat but we got a list
you can see that on average you lose about

five I.Q. points for children who've
had the presence of a salad in far so

I would be willing to bet that there's
not a single parent is wrong there were

are you to say that that's not
a consequential loss in their child's four

skill I.Q. typically for lead poisoning or
something their pediatrician screened for

particular in urban settings screening for
a.

Screening for a effective lead poisoning
of two or three I.Q. points maybe four or

five I.Q. points is a dramatic shift
in the curve of this population.

So I was part of a larger group
cooperative study sponsored by the and

I agent in this study we were able to do
surveillance from our eyes the young.

Student And I mention before was
part of this larger than I study

which was actually which was nine have
parties driven out wanted to characterize

the Natural History the disease and
thank goodness for nine had part

of his driven work to characterize a rare
disease because you can see here on the X.

axis is the follow up time in two
hundred forty eight patients on the Y.

axis is the curator of stroke risk and

you can see that other patients who had
a silent strokes during the first M.R.I.

they had a ongoing progressive risk
of new lesions in their brain or

strokes when compared to patients
who are normal in morons so

I just summarized him basically
a decade worth of work in seven slides.

But nevertheless we were able to show
that solid strokes are prevalent

they are associated with a five I.Q. point
drop and there progressive in nature so

when you have these Castor lation
of findings coming associated

with a morbidity and progressive in nature
then the next obvious step is to go back

to the question the My mom had asked me
which was what can I do to to prevent this

from a car so there's a two step process
as is typical years in clinical.

A patient oriented research with
clinical research The first is you have

a feasibility trial so I was funded by the
doors to charitable foundation in ninety

nine and we set up of feasibility trial
to see if a families would be willing to

accept transfusions for children less
strokes and B how long they would be

followed in here into monthly transfusion
as the results were supportive and

we used their data to ultimately get
a more definitive trial funded by the US.

From two thousand and three to do thousand
and thirteen the primary had part

of the sis was there prophylactic
blood transfusion therapy and children

with sounds feeble and far to result in an
least an eighty six percent well the risk

reduction in a poor portion of patients
who are clinically evident strokes or

no progressive strokes there were twenty
nine sidestep participated included sites

in Canada U.K. and France we had
a statistical data coordinating center

imaging center we actually have about
a positive or a where we have more allies.

So lines for ongoing supply of D.N.A.
in the trial actually

take took ten years to complete so
this is the second ten years of my life.

And it was published in
August of two thousand and

fourteen with in medicine I won't
bore you with all of the details but

I do want to take a moment to
tell you about the patients.

Participating in this trial.

These.

When you look at the majority of the
patients from the United States the yearly

income per capita was eighty eighty
five hundred dollars so that means for

family of three they were getting by.

On less than twenty six
thousand dollars a year.

This what we asked their families to do.

They had to come in for
three years for monthly transfusions.

They had to have three in our eyes of the
brain I don't know if anybody's ever had

in their lives their lives Marx's many
adults can go through them but in

order to complete this trial you have to
have three M.R.I.'s letter for Neurology

evaluation spire pediatric neurologist yet
have three cognitive tests.

SESSIONS You have to have two
quality of life sessions.

So with all of that.

We had the eighty six
percent completely destroyed

so this you know so I'll always marveled
you know with the misinformation about

what black patients will do or won't do
in terms of persuading clinical trials

you could not have asked for more onerous.

Trial.

For a population who is more economically

disadvantaged and yet
you had eighty six percent complete all.

So and then the rest we had
some had partial completion and

and some we had no exit data.

So what about the result I'm going
to summarize it into slices.

So first the risk of
an enforced recurrence so

you've had a sound a stroke and
a question is what happens again

do you have another son a stroke or an
overt stroke so that in fact recurrence.

And so the risk of in fart recurrence or
T.I.A. which is probably in this setting

evidence of skimming injury to the brain
was five point six events one hundred

patients years when we use
blood transfusion Monthly and

the risk of infight recurrence when
treated with regular blood transfusion

therapy for sounds we were in Farquhar
two events per hundred patients years.

Now there's a there's a new one for
the hematology soon and

I just want to mention we had
randomized roughly ninety nine in.

Patients in each group roughly and
it turns out that all of the ninety

patients to ninety nine patients
who were supposed to be transfused

nine did not receive any transfusions
at all beyond six months so

we were obligated to still used intention
to treat which is a much more conservative

strategy than saying OK we're going to
count those nine patients who never

received transfusions as a non transfer
as a trance nine transfuse group

even though they were randomly allocated
to the transfusion on but nevertheless we

stuck by the book and because we knew this
trial would come under much scrutiny and

despite all of that we still found
favorable results showing evidence

to support our partners so
the second challenge that we have is

blurred it monthly as an onerous
very difficult challenge for

families they typically come in the day
before to get the type in cross and

they may spend three to four hours to
be transfused the following day so.

Often it's two visits a year
a month sometimes even more and

so some of my colleagues will say in in
I understand their hesitation Well why

would we want to transfuse a child give
them this burden to protect their brain.

And so I struggled with this discussion
because I know it was my child's brain

we would be there every week not long
every other month earlier than four weeks

every four weeks we would be there
often as often as they requested and so

what I ended up doing was trying to
identify an anchor that would allow for

judgment to be commensurate with what
society has says is the appropriate

prevention for stroke and
so you may not know but

it turns out if you have this condition
car atrial fibrillation standard care in

the world is to give a or
at a coagulant And

what we're trying to do is prevent those
patients from having a stroke and so

for those patients the event rate is four
point four events praja patient news.

So often grassed beat louder than words
and so I just wanted to reemphasize this

point if you had a hypothetical
quarter of a thousand

children with sickle cell anemia sounds
sort of Linfox follows for five years.

With transfusions on your trunk no
transfusions which you would expect in

the transfusion group is that out of
these a thousand patients ninety five

over the course of five years who are have
had progressive injury to the brain and

of the children who were not transfuse

two hundred fourteen would have
had new lesions in their brain

if you compare that to adults who
are not with atrial fibrillation

who are not treated which all of us
would consider below standard of care.

Approximate two hundred will had a stroke.

So let's go to this to.

Sort of questions that my mom
peppered me with an hour so

what can I do to help teach Michelle.

So this is a long line
of investigation and

I'm just going to give you some high
rise former mentee a minute Dr King.

Board certified pediatric Metallica's and
powers has gone on to get a Ph D.

in education is this is her major focus
now is how to improve the lives of

students with sickle cell
disease who've had in Fox So

we set up a Palo randomize education
rehab trial and demonstrated that

it is feasible in children with
sickle cell and strokes we show that.

The concept of of having a disease and
isolation of the home

environment is is misnomer there poverty.

In as I mentioned earlier disproportionate
number of the children that we take care

of are poor but
the parent education as indicated by.

Graduation was associated with a six I.Q.
difference

where the presence of a sound three we're
in for it was five I.Q. difference.

In the household income had a greater
influence on grade failure than

the presence of a sound and from so so

that takes me to like two thousand and

nine OK And so looking ahead to
the babies that I've been telling

grew up in are becoming dogs and
I have to go through this uncomfortable

transition of taking care of a of
an adolescent for twenty years and then

handing them over to an adult provider
who may see things differently than I do.

And so I was actually in Atlanta
at the C.D.C. on sabbatical and.

I received the email from one
of my patients who wanted to

contact me because I was
an insane lords and and this is.

A story that I'll tell in a set in
a Before I tell a story I want to give you

the background of this picture
this is a picture written by

a drawn by individual who has circle so
busy and

is called Ten redefine and
the story that he gave

a national meeting about how he came
back this picture was that the common.

Language in a hospital when you're in
pain is described to me how bad your pain

is and then based on how bad you say
your pain is I will give you your pain

medication you can see that this could be
quite an abcess or you know action where.

Health care provider may not
believe you are in pain and

so in his description that he was.

Ten.

Health care provider say well I
don't believe you until now so

I'm not going to give you your pain.

And so he appropriately
drew a picture to defer to

the finest moment in called this
ten redefine hour for you know for

those who think that this
is an isolated incident.

It's not.

Currently in many major medical centers
adults with sickle cell disease who are in

excruciating pain.

Sitting emergency room for
six eight hours.

So it's a problem that has
not been met with much.

Acceptance within our system.

So this is the email they're my
now twenty two year old semi.

So.

I know it's been a long overdue
since we've last talked but

I'm hoping to break the silence today

I wanted to ask you if you knew of any
A Don't hematology who provides good care.

So as I've been here despite doing
everything that I've been told to do

take in how drugs are me and folic acid or

why we're even taking out in cotton
an oxy cold down around the part these

are paid very powerful pain medications
are still being encouraged to pay my

hemoglobin when I stay up past three point
seven sometimes law for more than a week

at a time despite receiving constant blood
transfusions and a Caesar shutter release

I feel as though all the longer I stay
here the worse my health becomes.

So I ended up having to come to
grips with it is good to be.

In I did investigate it's good to lead
a little national trial get a life

Adelaide for that but at the end of
the day when I go back to see my

patients they don't really care about that
I mean quite frankly it doesn't matter to

them at all in fact when I went to
Washington Vanderbilt one of the first

patients I saw the mother say you came lay
a hand on my child to you tell me what you

know about services so really from them
from a very practical point of view.

Is nice to get these accolades but
when I'm in the womb with a family

they just want me to take the child and
the young and them and

the older adult wants me to take
care of their young adult child.

So I kind of chucked it all in.

A washer and
said I want to try something different.

I wanted to create a medical home for
children and

adults who could receive medical care
crosses the life spectrum with the same

philosophy of care because a life
spectrum I thought it was unfair for

the pediatric in metalliferous to
have one style of care and then for

them to immediately go to another provider
a completely different style of care

something is different as what
would your pain medication be or

something is different as how I would
want to manage your home versus how we're

going to manage you in the hospital so
Vanderbilt was.

Willing to take a gamble on and an addict
have some very simple requests but

one was that we would take the medical
care out of the academics are these

monstrosities which you know
eighth flight eight on parking.

Garages surrounded by the hospital

is very difficult to navigate a cup of
coffee because you know three hours.

Much past ten dollars for two in and

go into the neighborhood in which
many of our families were located.

So we wanted to so we created this
mission to provide an American home

serving in the best available medical
care educational support and research for

all the children and adults in their
families whose lives were affected by

sickle cell disease so what does this
mean we have even clinic weekly because

as I've already told you many of my
mothers are working poor and fathers and

they have to get off work to four
five a car so I need to have.

Clinic that was available and
even I knew their planet on Saturdays and

listed it initially as twice a month
we reduced it to once a month again for

the same reasons I wanted a primary
function lab in the clinic because twenty

five percent of my children that
I take care of have asthma and

I wanted a psychologist who was going
to be available now when I came in

made new they gave me a blast to
create a program the way I wanted to.

With their six months the prior
sickle cell team left.

And which was always low down
to to lead a team in and

you'd be the only member on the team.

So a social worker left
the other he Metallica's left

in the in the nurse case manager laugh but

that was OK because I was able to
hire people who I could handpick

who willingly give up their Saturdays to
come see these families and to put their

needs second to the needs of our family so
we were providing medical care for.

So it's it's worked out quite well but
I want to drill down on how

we handle this academic challenge for
our students will circle cell disease so

you know I guess I am probably more like a
principal than I am like a doctor because

when I see my students in the office I
will ask them how they are doing and

automatically now after seven years they
know I'm not talking about the sickle

cell disease but I'm talking
about their academic performance.

And saw a vision move on to
the sickle cell disease but

I would be willing to bet that someone's
quality of life is heavily related

to their ability to be independently.

Supportive and in our in this
era that's highly correlated

with the ability of finish high school and
to get some type of occasional training or

college education and so this is
a story of a young boy that take care.

And he was nine years old at the time.

We do surveillance of our eyes of all of
our children with sickle cell disease for

the reasons I've already stated his
grades range from Ace to D.S. and

you know I'm pretty direct and
so I said So tell me why you.

Why are you getting these and he he just
basically started to cry as I'm too slow.

So at that time there were no academic
accommodations there were made for

this child Mom was unfamiliar
with how the navigator system

we had the benefit of a psychologist
on the team we perform these

standard evaluations I want to
point out that the full scale I.Q.

was one hundred which is
exactly what you would expect.

And yet despite this child's I.Q.
being one hundred processing speed was

five percent and one of the tests
that we asked him to address

was his ability copy figures and it
really doesn't take you know his creation

specialist to see that he has some
challenges in me copying these figures so

what happened after shortly
after that we provided a written

report to the family and the school our
social worker attended a meeting for

the individual educational plan and he was
doing a five as having a written language

disability those classroom accommodations
in two thousand and fourteen mostly

A's and B.'s is scored in a professional
range all standardized tests in math and

language skills and much more
confident young man now that I see him

in two thousand and sixteen and actually
has aspirations to go on to college so

this is hard to capture
in a manuscript but

it makes all the difference to this
plan and all the difference to me so.

When I was a Vanderbilt
after being there for

about nine months at a toll it was
a friend close friend of mine.

A lawyer when a friend at the time and
said says.

He you think you are so
good at what you do

how can you be good at what you do and
I have any presence in Nigeria.

And you've completely ignored the problem
of sickle cell disease and I do.

So what it added Tola know that I had
a passing not even a passing knowledge I

just knew there was a lot of sickle
cell in Subsaharan Africa but

I didn't know where I was so this is
a quarter gram of the estimated number of

newborns with sickle cell anemia
based on demographics metallic and

interventions and what you see here is
the obvious large darker space is Nigeria.

And it turns out that.

Nigeria has one hundred fifty thousand
children born with service all of

these years.

Ghana has fourteen thousand in the US
has around twenty four hundred

so you know how this academic
thing you see in this dog and

pony show you get invited to to
come places and you give talks so

I have Buddy still have by name Baba and
he said look I want to bring you

to Nigeria as a strange situation as will
become an idea somebody does challenge me

and I have been trying to get there for
some time so barber had me on this.

Role show.

On a road trip from we
flew into a bugger and

then we had to go all the way up to
Siena just right below the Niger and

and so what that Bob and tell me and
I wasn't worldly enough to know was there

he was going to have me start like
every three hours and give a talk.

So.

So I did and what he also didn't
tell me was collective asses for

the identies or so
before you know before so.

Was we had to have an escorted driver and
and we were we were.

We were guests of the governor and
his private.

Security Force was actually my daughter
with me and so I had said to him

Well I'll go on this trip and you can
do with me as you will I'll talk as

long as you want me to but at the end of
the trip I want to have a retreat for

girls or a camp for girls with sickle cell
disease because I know that we want to and

I will remember it will be that something
they were may remember and my wife or

my daughter will enjoy it and they have
been doing this I wouldn't say Lourdes for

about nine years so

my wife daughter his wife and
daughter went on this road trip with us.

And so since I was working the whole time.

This weekend was their time and we're And
so they put together this camp score and

you can see introduction breakfast
games relaxed pain scale crafts

they had a skit practice because they
had a skit at the end of this innit.

Interaction at some other point I can
tell you about the skid is actually very

fascinating taught me a lot even
today that I still use in my care for

this part of patients and in this
region lunch we had a dress rehearsal

they had a dress rehearsal for the skit
certificates presentation in a diner and

on Nowhere do you see that there
is any environment of an indie

is all about the girls and the women
that are supporting this activity.

So this is a picture of a little girls or
participate in the activity but

what I didn't know you didn't is a play
was that the parents are travel.

All over the state to come in his activity
and they were leaving so on Saturday they

were like stop to the girls and you could
imagine that there was no free discussion

with the girls there was no fun because
the parents were in their space so

my wife decided the one day that I
thought I was off I need to come in and

entertain a pass so
I had the parents of these forty two girls

on one room while the girls were in
another room and in the pores of

mirrors told me impromptu What do you do
with you know forty two sets of pairs.

All day so so
I ended up teaching the parents like.

I would teach any parent
that was in my class and so

we started to go over little things and
here I am teaching the nurses and

the parents how to feel for the spleen so
in a splint on the same side of the heart.

Is in their right and if there is a real
cage or point out the real cage and

you want to feel for the spleen in this
is a very standard approach to all of us

undertake to educate our families
about complication of this disease and

then in the course of this
six hour educational session.

One of the parents described
their daughter and

they describe specifically that
their daughter can no longer why.

What a normal gay she couldn't
hold a pencil with her hand and

shoes to a poorly in
the classroom Saturday and so

I said Well unfortunately I believe
your daughter has had a stroke and

so don't no one in the room knew
what a stroke what they never

knew their child could have struck so
this was kind of them moment of clarity.

And so you know my whole thing for the day
was this is all about the girls not about

the parents the parents were kind of a tug
of war we want to see what a stroke looks

like go get this girl and I'm pretty
stubborn I was pretty adamant no this

is not the reason I'm here I'm not here to
be a doctor I'm here to educate you and

you can see a doctor about the stroke but
they would take no for

an answer and obviously she ended
up in the wrong with the pairs.

So this is Barbara interviewing the mother
and the little girl and she had.

Him passes on the right side and the
mother stopped her from going to school

because she felt that she was carted to
really impaired and therefore was unworthy

of attending school so
we had some discussions about that and

you know I was pretty adamant that
she should have the privilege

to go to school and that she would
have skills as they could be learned.

Now when you look at the.

Challenge six of the forty two girls
in that retreat Camp had a stroke

because once we had deep defy their
logo or stroke there were five others

who had a camp US role so of course
every mother see him this daughter.

Has.

To be upon the children are.

Struggling.

And so when you when you go back and you
look at the public health that are about

ten percent of the children before
screening for stroke in treating.

A blood transfusion
United States develops.

A stroke and so if you take a birth
cohort of one hundred fifty

thousand children then that
will mean in the country.

And the jury will be fifteen thousand
children if they live to fifteen

they would have a stroke and

if you look at children with Salar
strokes it's three times that is so

I have to tell you that that dinner
was sour because we we were we were.

We just.

We knew we were sad and you know we
came here to do something fun and

we found a problem there seem
to be challenges and overwhelm.

So.

We can do work we've learned to
do as physicians scientists and

all this training that Bob described.

And we said and we tried to come up with
a strategy to address this problem and

it wasn't easy right as you say well you
have these children who've had a stroke

do you go after a secondary stroke or
eventually you have children who

have risk for stroke or
at the time the only treatment for

preventing a stroke was transfusions and
I'll give you a few slides about this.

Is there a way that we can predict who is
going to have a stroke an ear says yes and

this is but done by a guy named Bob Adams
at the Medical College of Georgia.

Really insightful and
transformative in a careless population so

Bob showed that if you
use a probe you could

look at the velocity of the blood flow
to the middle so we will ordering and.

You could measure that the velocity above
a certain level would be predictive

of having a stroke and
I just want to go over the briefly so

typically as you can see here
the probe is put up to them in CA and

you get a velocity which is highlighted
in red and really the vessel is pay.

And the velocity is typically
low as the vessel becomes

slightly Eastern Arctic the velocity
will go up a bit and when the vessel is

morse tonight it will actually
have levels that are very high and

this is what it typically looks like for
an imaging T.C.D.

again the main to see in this particular
case is one hundred one which is low but

he was able to show quite nicely
that if you stratified the velocity.

Of the patient according to three groups
less than one seventy one seventy to one

ninety nine and greater than two hundred
that the individuals who are most

likely to have a stroke were those who had
the last is greater than two hundred and

what you see here is a capital
Meyer plot where time is on the X.

axis and a probability remaining
stroke free is on the Y.

axis and you actually don't need a
statistician to see that if you're to see

the velocity is over two hundred
you have a problem so so

as a result of that really
transformative effort of research.

We now have a primary
prevention of stroke for

children with sickle cell anemia which is
drop the rate of stroke a major academic

centers are able to apply this technology
to their patients in a routine basis

is dropped the prevalence
by a lot of hope and

now it can be as low as one percent
as opposed to ten percent so

the typical paradigm you have
a screen to see the typically.

Annually you measure the transplant
velocity in the middle sleeve or

ordering the terminal portion and internal
carotid you stratify the patients above

two hundred or below two hundred if
they're above two hundred you typically

get transfusions up until recently it was
monthly for an indefinite period of time.

However at the time
that we were in Nigeria

transfusions would just not
instill is not an option

there's an adequate blood supply
there's a cost of monthly transfusions.

The transfusions are unsafe and there's a
high probability of blood borne sanctions

so the only alternative is how
drugs the rear of the F.D.A.

approved for sickle cell disease in United
States increases the total hemoglobin

which would now decreases the velocity
goes through the vessel significantly

decreases A T C D in children with
sickle cell disease and in a normal

city values there's some effort to see
in a set of a straw prevention and

it's very cost effective and practical so
we put together a trial I'm.

I'm a dreamer and so we made this
logo Well before we got funded.

And then we got funded so
this was a feasibility trial for

primary stroke privilege and
children with sickle cell anemia.

Colonel Nigeria.

We had three measures of acceptability.

The first was of the families
that we approach how many would

agree to the screen to be honest trial
because we had to do a transfer and

you dump the second was all
the families who are eligible

how many agreed to participate in
the trial in ninety two percent.

Now we asked these families
to come back monthly.

There were no missed visits.

For over two and
a half years this is rural urban Nigeria.

In terms of laboratory values we saw
a toxicity we saw no leverage or

evidence of severe miles oppression are as
a low white count or toxicity in the group

using a fixed dose of had reaction wheel
of twenty milligrams we kilogram Pradelle.

And then in terms of adverse events namely
death we were very concerned about death

which was the main reason that we started
this trial children five years of age or

older because the mortality rate in
children with sickle cell anemia look

less than five years is very high
estimated in some environments to be as

high as seventy percent so
we started for the woods.

Golden above five in there were two
deaths in the treatment group and

ten deaths in a comparison group and when
you looked at the significance between

the two there was no difference so from
that point of view very appealing to move

forward although this was an intermediate
outcome the definitive outcome is whether

Now we prevented children have a stroke
These are children we started on drugs we

had fixed dose of twenty milligrams per
kilogram per day and there was eighty

five percent reduction in T.C.D.
velocity after starting one direction.

Again very supportive so
we were able to leverage this batter.

And our main support for
our planet data was that

first this is a this literally was
the first randomized control trial for

sickle cell disease in all of
Africa sponsored by the and I and

so we felt that we had strong evidence for
its success based on the acceptability of

potential safety of a moderate dose of our
drugs really and that the initial pilot

data was supportive of using her drugs
three or four primary stroke of venture.

And so this is our new logo or
stroke prevention in Nigeria.

Is a mentee of mine it's Vanderbilt and

it's now a full fledged leader of this
trial and we are is actually a colleague

social Professor Vanderbilt who is
from this city town in Nigeria and

our primary had part of his was that
there will be a sixty six percent.

Reduction of primary straw prevention was
sickle cell anemia with elevated T C D So

a very large trial with screening over two
thousand children two hundred twenty will

be randomly allocated in the fifty
dollars to twenty makes for

kid versus ten my colleagues and
women say well why are you using twenty

versus ten as opposed to twenty
versus Max will tolerate adults.

A C.B.C. in this region costs five
dollars and most families can't.

Ford And so if the if the effect
of decreasing the T.C.T.

can be seen in a lower dose that doesn't
cause any toxicity then we may be able to

have a bigger impact and have to dose
a tweet treats twice as many children for

the same cost so
we design a hypothesis solve a goddess

of the result will get an outcome that
will help that would change the field.

And in time will tell will finish
in two thousand and twenty one.

July.

So I just have my last two slides and
I want to end with this so what

is Sickle Cell look like in a country that
has one hundred fifty thousand children.

So this is a picture of
Mohammed hospital this is

the hospital that is one of
the participating sites in Canada

they see over one hundred children
with sickle cell disease a day

five days a week they max out at two
hundred and two hundred they tell

a families they have to go home because we
can't service our tumor children to the.

Majority of children a perfectly
valid medical care by nurses and

community health workers on
Wednesdays only Wednesdays.

The patient is seeing the child
is seen by a physician and

usually that's when the diagnosis.

They have over ten
thousand children managed.

And so when we expanded
the feasibility trial to this setting

we saw something said
we had not seen before.

And so.

Specifically we saw that

we had five percent of the children
had hemoglobin is less than.

Six grams per deciliter So

in a super cell population in the United
States we have the data from this last

trial less than point one percent of
all children in high income countries.

Had hemoglobin levels less than six
percent there was an important turns out

that he McGovern levels less than
six your normal human go on for

most of us is between twelve and fourteen.

Is a risk factor for
the early death and their work flow for

how they decided to let a family know
what the hemoglobin was last and

six was not time sensitive lab
will be drawn on Monday with

the family back on West in town come back
in and because this is a formal trial.

Child died in the interim.

So as many of my colleagues know point
of care testing has become the new

wave in medical engineer and
so we looked for

our machines that would advertise that
they could measure the hemoglobin at

the point of contact with the challenges
the companies who develop these machines

were going where the money was and
that you have to have a normal hemoglobin.

That are abnormal in low and he and
I was sleep children with sickle cell

anemia have known him a globalist So
despite talking to the scientific rep for

the company guaranteeing me that they
could still pick up in a global test.

We went out and bought these machines and
they didn't work so

my challenge to the Georgia Tech
community is help me figure out a way

to get a machine that will give me
is detainees hemoglobin readouts for

children with hemoglobin S S It won't just
help these children Nigeria they have

the same group of children in India where
forty thousand children a year are born

and as well as children the United States
live in rural America so.

The team back home.

With a few of the people from our team
member some got a Nigerian is picture

that you very much you.

Are you and.

A.

Yes R S a great question so I just want to
this is a great question particularly for

the engineering students so
when we started this in ninety one and

I worked with in a radiologist for
since early system in ninety so

we in this large trial we had over
a thousand images at a have a cow it

still McCully then agreed to map
out the region of the brain for

every one of these lesions so that we can
have a density map of where they occurred

and so you know we've both been busy
solar power for years three years ago

I asked him to I say hey I'm ready to
analyze this data that you painstakingly

like mapped out on all of these images and
he said my I don't have the time but

I have something better for you so it
turns out that the folks at Mallinckrodt

have created a workflow to do a heat
to city mapping of all the lesions

if I have time I show you but it's it's in
the border zone region between the A.C.M.

CA in CA in B.C.
so in a maps are beautifully and

what we want to do is publish this so

that it will help the clinician say
this is the zone that we expect for

silence we will in fact to occur if you
see these white lesions outside of this

Joe Zone think of an alternative diagnosis
obviously we're not going to make

a diagnosis but we want to give them
a probability of where the losers

are based on this location but
probably a leisure and

a salad for so stay tuned we're working
on a product image is a beautiful.

This.

Was Yes So.

You know every culture
has its subcultures and

there within every subculture there
are fractions of those cultures and

what I can say is that if I just look
at the data none of those patients

none of the parents missed a single
appointment for their child to come in.

Who is receiving this medication.

And I am of the belief that I know and
what is just one of these

family's lives three hours away and
had to go through unbelievable.

Driving situations to get
to the clinic monthly.

And that's what the roadblocks and

security blocks a risk of kidnapping
in the risk of the light and

so I would call it all
objective evidence I have is

they care about their children just as
much as my parents care about the and

just as much as I care about mine so
I don't I think there when you are able

to explain always been an inordinate
amount of time I mean we spent a boatload

of time explaining what the drug is we
have gave him a hamburger in house and

a handbook in English we made a video
what a stroke is only the people who

will go on the people who they know
are the ones that we educate it for

four years so is there people
telling them what the problem is

I'm just I get all the credit but I have
a stinker of a single patient in Nigeria.

So I would say all
the objective evidence is

there the significance of a stroke
in the lives of a child in Nigeria

is a significance of a stroke in
the lives of our own children.

He.

Was.

Yes.

Is.

Is.

Is so so this true real quick you have
says in the first in the situation

I was in clear voice enough to ask for

the age of the transfusion it's because
we had ninety patients transfuse for

thirty six months so
that's a lot of transfusions but

I just wasn't a cipher enough to know to
say age of the unit may have an impact or

who we've heard who didn't and
the second is that I think uniformly and

most centers are I'm aware of we would
prefer to get the young cells and

we preferentially receive the young cells
in St Louis where we set up a direct donor

program average age of cells were
usually seventy nine days seven to nine

days in the obvious reason is if you
infusion say the horse then they last one.

And I was mostly concerned about well if
I can take every four week in of all for

mother and a child to have a six week
interval the Nats save the Nash family

an extra couple trips per year and
many trips over

the course of a decade because many of
the children were transfused indefinite.

Removes.

Us.

Years.

Yeah so
I would be remiss if I didn't say that.

That my wife is my best friend.

Been with me since my days or Howard and

saw really I get all the credible she's
a silent partner and I do a lot of work at

home and and she is drops or maybe not
eased up but here's a conversation.

You know we get to discuss in
a discussion about unsolicited advice but

her unsolicited advice has
been more valuable to me than

any of the solicited advice that I've
gotten from United study session.

And because she comes from a totally
different point of view and

I'll just give you one and
then we can close honors So

the biggest challenge in our
capacity building in Nigeria for

our primary stroke prevention is
the machine cost fifteen grand but

we have a grant to take care of that and
we have capacity building in the grant but

then I didn't have anyone radiologist
who knew how to do the T.C.D. and

so originally I was talking about Adams
and I was trying to set up workshops and

bringing them to Georgia for years to see
the workshops are going in London but that

was costing an arm and a leg and so I was
the mole in the fact that I didn't have

any way to do that and she says why don't
you just teach Nigerians how to do it and

so that became an obvious solution and
now we have

a radiologist who probably
astray more individuals

who do want to see than anyone other than
Bob Adams and so we have built our own

system in a house that is now expanding
to other I toured in this region.

And in all I would say keep an open mind.

And solicit vice from people who are your
best friends they'll be the most honest.

People.