-------------------------------------------
The Orville 1x05 Promo "Pria" (HD) ft. Charlize Theron - Duration: 0:31.
This is Captain Pria Lavesque.
I'm in trouble.
Next Thursday, Charlize Theron guest stars.
You meet some pretty wild cultures out there.
Get ready for The Orville's most surprising adventure yet.
She may not be what she seems.
Give me back my ship.
I think everyone's gonna want to see this.
The Orville starring Seth MacFarlane, all new next Thursday on FOX.
-------------------------------------------
SOMETHING HUGE FROM DEEP SPACE IS COMING TO EARTH AND IT WILL BE - Duration: 2:58.
SOMETHING HUGE FROM DEEP SPACE IS COMING TO EARTH AND IT WILL BE CLOSER THAN THE DISTANCE
BETWEEN NEW YORK & TOKYO
And that is only the official estimation!
Many were aware of the potential danger of the asteroid Florence, which barely missed
Earth on September 1st, and fell into a false sense of security.
However, it is time to start paying attention again.
NASA announced that an object they named "2012 TC4" is heading towards the Earth and is expected
to make its approach on October 12th.
New Yorkers will be closer to the object - officially named "2012 TC4" - than to Tokyo.
COMPARE A POSSIBLE IMPACT TO A WATERMELON BEING SHOT WITH A BB GUN Although it is slightly
smaller than Florence, this will not help very much because it is much denser (even
denser than granite!) and it is moving faster.
2012 TC4 is thousands of times heavier than the Chelyabinsk meteorite that devastated
an entire Russian city.
Based on public records, it will make the closest approach to earth of any other asteroid
of its size.
Compare a possible impact to a watermelon being shot with a BB gun.
In this case, Earth is the watermelon, and the BB gun is 2012 TC4.
It would penetrate the crust and get into the magma - causing magma splashes and massive
volcanic eruptions.
Now Imagine 2012 TC4 landing on Texas.
NASA'S PLANETARY DEFENSE SYSTEM WILL BE PUT TO THE TEST ON OCTOBER, 12 Based on the official
numbers from NASA the probability of an impact is 1 in 600.
However, more disturbing information has been uncovered.
In what could not reasonably be a coincidence, NASA is holding doomsday exercises on October
12th, the exact date that the asteroid is supposed to "miss" the Earth.
It is quite possible that these are not exercises at all, but rather preparations.
Although it is likely that few people have any real protection from this event, those
who do have a plan may want to consider it.
The government may simply be keeping this information under wraps to avoid panic.
-------------------------------------------
Lucifer Season 3 "Good To Be Back" Promo (HD) - Duration: 0:31.
Remember me?
FOX Monday...
Murder, suspects, clues.
Gosh, it feels good to be back.
Lucifer returns.
Me detective, you consultant.
Okay.
New time...
I didn't know that they could grow back.
Same devil.
Oh, thank God.
The things dad gets credit for...
Lucifer Season 3 premiere, Monday on FOX.
-------------------------------------------
How To Activate Picture In Picture In Android Oreo(No Root Required) - Duration: 4:40.
Hey what's up guys shark jungle is here in this video I'm gonna show you how to enable
Picture in picture feature if your device running android Oreo
After the latest Oreo update picture in picture feature in no longer available on some devices
like nexus 6P , 5x and Google pixel , you can try that on your device to check if it
is still available or not Press and hold the settings icon in the notification
panel for about 7 seconds , then you will be able to see wrench icon over the settings
icon and that's mean you enabled system UI Tuner
now go to settings , system , then tap system UI tuner , As you see I don't have navigation
bar adjustments feature which is important to enable PIP,and this is a screen shot from
the previous update on android Oreo and Now we don't have this options, In this case you
have to download custom navigation bar App to enable extra button and activate PIP
By using this App you can also customize your Nav bar and I'm gonna talk about that in another
tutorial Now install the App from Google play store
, Open the App and Now you have to grant a permission to let the App to write your device
secure settings , as you see I can not pass this screen unless I gave the App that permission
If your device is Rooted then you can pass this screen using super user but if not you
have to do it via ADB shell Now go to settings , then system , about phone
, hit the build number couple times to enable developer options ,now go to developer options
then turn on usb debugging Now go back to the App
Connect your device to the PC and make sure to install windows drivers for your device
and if you don't know how to do that go ahead and hit the tutorial link in the video description
on your computer download ADB fast boot files and extract it to your PC , you will find
the link in the video description open the folder and hold shift on your keyboard
then right click and hit open command window here on your device hit Allow
Now copy this command and paste it in the command window then hit enter
Now you can pass this screen on your device
select navigation BAR , then on the extra left or right button hit type and choose key
code Hit key code and select manual input then
type 171 hit OK
now choose which Icon you want to use , I'm gonna choose cheveron up as an example
Let's try any App that supports Picture in picture ,
On youtube let's play a video and hit the pip button , as you see I've successfully
activated PIP , you can also do that for Google chrome , Google Maps or any App that supports
this feature , you can search on settings and check which App can do that , you can
also enable or disable PIP for any of them I hope the tutorial was helpful if so plz
don't forget he like and share buttons and subscribe for more videos , thanks you for
watching peace
-------------------------------------------
presentation apprendre a dessiner - Duration: 8:12.
For more infomation >> presentation apprendre a dessiner - Duration: 8:12. -------------------------------------------
CULTURE SHOCK!! Manners in BRAZIL カルチャーショック(マナー編) VIDA no BRASIL[Vlog#18] - Duration: 9:56.
Eating nails..?
Cutting like this..
It's impossible in Japan but it's kinda normal here.
I can't believe it!
Oh well, I don't eat fish.
Culture Shock. MANNERS
Hey, guys. It's Harumi.
Today's topic is a volume 'culture shock'. Well?
I mean, culture shock about manners.
Comparing to Japan there're some shocking
manners.
So I'm gonna pick..well there're actually tons,
but I'll choose 5 and talk.
NAILS
In Brazil even grown ups
bite nails like this.
I often see them.
Even at work
when I'm talking to someone like this.
In Japan biting nails is considered
as a bad manner, isn't it?
Bruno also does that in fact.
So I told him to stop it and now I don't see him
doing that..unless he's doing it behind my back.
It's more like eating it than biting..
No..I don't like it...
SPOON
How to hold spoon, folk and knife.
Normally we hold a spoon
like this, right?
But here
I see people holding it like this
even though NOT everyone
I sometimes see people eating this way.
Bruno as well....
till now...sometimes..
eats like this..
It's horrible, isn't it?
This's the right way, isn't it?
And folks and knives.
In general, for example
having French food,
its table manner is...
(hmmm...)
I'll get an actual folk and a knife!
Normally we hold like this, right?
A folk on the left hand
upside down like this.
If you're cutting a steak
you start cutting from your left side. Then eat it.
You put rice or other things here
even thought I think it's so hard to eat that's the right table manner.
But in Brazil...
people hold them like this.
A folk on the right like we normally do
when we only use a folk if you're right handed.
But Brazilians always hold knives on the left hand.
When they cut steak...
...How do they do that?
(I dropped it..)
Hold a folk like this and...
cut steak from the right side..?
And the like this...
Well it's so hard to explain without a steak!
So I'll show you guys in another video.
But wait..! You put your folk
further from you
and then you start cutting from the side closer to you.
So it's not from the side to side
but something like this.
It's strange. So at first
I was surprised and couldn't get used to.
But now I got this Brazilian way
and actually when you get used to it
it's kinda...
(can't speak properly in Japanese.)
It's kinda practical.
You can cut meat nicely and also when you eat
like rice, you can hold a folk like this normally
and you use a knife
to help putting things on the folk
and eat it.
So personally
comparing to the French table manner
I prefer this Brazilian way.
It's much easier to eat.
All the Brazilians use them like this
Oh! (remembered something)
When I used to eat like this
like the way you eat French food
Bruno or someone asked me
if I was left handed.
"Why are you eating like that?"
So I realised I was really different from everyone
so I trained their way.
And now I'm totally comfortable with it.
So I got kinda made fun of me
so I asked Bruno if Brazilians don't know
that the right table manner is this way.
Then he answered actually they know.
But I think there should be people that don't know.
But it's really practical this way,
I think.
IN A CLASS ROOM
People eat in the class room or stores,
Eating candies or chewing gums
in the class
even pop corns
or meal sometimes...?
well that's a bit too much
but something small
like snacks is so normal here.
Students offer me, too, like "do you want some?"
In Japan you never see that.
And...
yes, in the store
in Japan you definitely can't enter the store
eating ice cream..
coffee or even water,
Ca... can we?
Generally we can't do that but here
it may be a place like that
but I've never seen that.
Maybe like expensive shops..
brand shop..they may say "NO"
maybe...but
normal stores, like fashion store around here
you can enter having whatever with you.
FREE FOOD
This depends on people definitely, of course,
how he grew up, or
it may vary depending on regions..
but through my experience
I've seen quite a few times!
opening a bag of chips
and eat before you pay.
What is he going to do now?
When there's a long line at the cashier
and he finishes eating the whole thing
which I've seen several times,
don't you wanna know what happens next?
"What is he gonna do with that empty bag..
and is he actually gonna pay for it?"
I've seen someone paying for it
but also seen those who didn't pay..many times.
After eating leave the trash there
without paying..
I go like..what do you mean!!?
I got so shocked,
surprised..
And
fruits..here we pay per kilo
so they're not packed
so for example grape fruit..grape fruit?
NO, grapes! sometime I see people tasting them
just like doing a normal thing...
peeling tangerine also happens..
It's not that they're allowed
but it happens
and I see them
sometimes.
LIKES AND DISLIKES
When it comes to food
Brazilians are very...
picky.
Manners..
They don't have...
a very good manner...I feel
sometimes. (actually all the time)
I'm not a picky person
so it may be just my personal opinion..
but..in Japan
dislikes of kids
are normal.
So in general likes and dislikes for food
is children's thing..
That's how we think, isn't it?
Adults saying "I don't like this and this."
is considered as a bad manner, I think.
Don't you think?
You can have one or two things you can't or don't wanna eat,
it's just a preference. But here it goes like
"I DON'T EAT FISH" (denying completely)
She doesn't even try it sometimes.
Well I don't like eating fish here either though, haha
"Well, I don't eat this. I don't eat vegetable."
All the vegetable!?
Well, for example if someone says
"I eat cooked carrot
but don't like raw.."
I can kinda understand.
But here people often say things like "I don't eat vegetable."
"Vegetable"!? That's a big category...
So it's a prejudice.
Brazilians like coffee.
We, Japanese, like it, too.
In Japan iced coffee is popular, too.
Especially in summer.
But in Brazil
iced coffee isn't known at all
so when we talk about this
"WHAAAATTT??? ICED COFFEE!???
NO NO NO NO NO WAY!" (with a horrible face)
They're very prejudiced about food.
And they don't hesitate to express their emotions
so I sometimes get hurt...
cause it's delicious..!
Ok..I think that's it.
I talked about 5 things
about culture shock 'manner' in Brazil.
There're a lot more to talk!
So I'll make more videos.
If you have any comments leave them here.
Don't forget to like the video, subscribe the channel.
Ok then. See you guys! Kisses!!
-------------------------------------------
Top 10 vụ vượt ngục ly kỳ và táo bạo nhất mọi thời đại - Chuyện kinh dị - Duration: 10:38.
For more infomation >> Top 10 vụ vượt ngục ly kỳ và táo bạo nhất mọi thời đại - Chuyện kinh dị - Duration: 10:38. -------------------------------------------
Pain & Culture in Carve the Mark & Parable of the Sower | @fandommattersaf - Duration: 10:38.
Alright, hi. Welcome back to my channel. Today I'm going to be talking about two
books that I've read recently, Carve the Mark by Veronica Roth and Parable of the
Sower and its sequel Parable of the Talents by Octavia Butler. So I'm not
gonna go super into detail about the different plot points of the two novels but I am going to talk about their themes and some
general things that happen in the story, so spoiler warning for either of those.
Both books have a young female protagonist who experiences pain so I
thought it would be fun to discuss them in the same video today. So I finished
reading Carve the Mark just a couple days ago and I really enjoyed it. I held
off on reading it for a while because the general sense that I got from seeing
just posts and tweets about it online was that it was poorly written
racist garbage which I don't think was the case. And I know there's been a ton
of controversy around this book so I just wanted to give my two cents in the
beginning of the video and say that I don't think it was upholding racist or
ablest tropes although I am an able-bodied and white woman so there
might be better people to speak to this than me but I will link somebody's video
down in the description that does speak to this very well: a Youtuber named
Francina Simone did a review of this book and basically says everything I
could say about it in the sense that it is definitely not ablest
or racist. It does depict two different cultures one of which could be seen as
painted in a savage light but it's really just their leader Ryzek who is a
violent monster essentially and the protagonist Cyra (Sigh-ruh) or Cyra (Kigh-ruh) I'm not sure
how to pronounce her name - she is the one who experiences the pain and she is a
really kind and well developed character in my opinion. So I thought the book was
really breaking down a lot of these tropes with really humanizing and well
fleshed out characters. I don't think that the book as a whole depict Shotet
as a savage culture or in a negative way. But basically after reading some reviews
on Goodreads and after watching Francina's video, I've kind of gathered that
the people who are negatively reviewing this book either didn't actually read it
thoroughly or really haven't given it deep thought or are really not
knowledgeable in these areas so I would definitely
watch Francina's video if you're interested in further discussion around
that topic. Now to move on to the discussion of pain in Carve the Mark.
Each character when they are in their puberty years develops an ability and
that ability seems to stem from something they're experiencing at the
time, or thinking or dealing with. So for example the protagonist's brother
Ryzek who is the villain of the book, he develops the ability to give his
memories to other people and you could say that that is from him having a lot
of negative experiences, his father showing him a lot of pain and violence
and then as a sort of defense mechanism to that it seems as if he developed a
way to get rid of those memories although he doesn't use it in a
particularly kind way. So Cyra (Kigh-ruh) or Cyra (Sigh-ruh), I'm gonna call her Cyra (Kigh-ruh) because that's
how I read it in my head - so she develops this ability where she experiences pain
all the time. This pain kind of flows through her veins. It's described as
these shadows that flow over her body and so she's in chronic pain at all
moments of every day but she's also able to give that pain to someone else
through touch so if she touches anybody they feel this horrible pain that she
feels so her brother uses her as a torturing device. She has to push her pain
on to these individuals who are Ryzek's enemy. So basically, she lives with
chronic pain and must be physically distant from others until the male lead
Akos comes along, where his ability is to stop all of these current abilities
so if he touches her than her pain stops for the time being.
Throughout the novel Cyra grapples with being used as a torturing device for her
brother. She really hates that he uses her and she hates him and what he does
and what he stands for as the leader of their entire nation but
she also has a lot of guilt because she accidentally killed her mother
using this pain. She freaked out and kind of channeled all of her pain into her
mother and it caused her to die so she's dealing with a lot of different issues
surrounding this topic of her gift or her pain and so it's not really
depicted as a good thing. We see that it's a problem for her throughout
the book. We see that when Akos touches her she experiences immense
relief and is able to have a few breaks from the pain but it also doesn't stop
her from being totally badass so that's really cool to see as well. So
we see her struggling with it. We see the negatives of what she's experiencing but
we also see her training and being a fighter and a dancer. She's very physical.
She's very talented at different forms of fighting in her culture and she has a
lot of interests she reads a lot of books and so what she's experiencing
doesn't stop her from being a well-rounded and interesting human.
In that regard I think pain is shown in a pretty realistic light where yes it's an
issue and a constant issue for her but she's also very strong from it and she -
since she deals with it all the time she's able to try her best to live her
life when she can. Let me know if you thought differently from that or if you
found parts of it problematic. Now to move on to the second book that I'm
talking about in this video, Parable of the Sower and its sequel Parable of the
Talents. These books cover so many topics in fascinating ways from the collapse of
America to environmental catastrophe, politics, religion, empathy, slavery, and
indentured servitude. And family and friendship and love. It's such a complex
book. It has a lot of the same themes as Harry Potter which is my favorite book
series so I enjoyed seeing so much depth in this two-part series as well. Through
these two books you follow the life of a woman named Lauren Oya Olamina from
age 17 to age 81 at her death so you follow her throughout her entire adult
life and you become or at least I became very attached to her and interested in
her and I didn't like her a ton when I first started reading Parable of the
Sower but as you go with her on her journey and you learn what motivates
her and her thoughts and what she's focusing on in life, at least I became
really vested in her goals and her work toward achieving those goals. And so the
protagonist Lauren has something called hyperempathy syndrome which she was born with
because her mother was addicted to a specific fictional drug in this series
so she experiences others pain when she sees it so if she sees somebody who's
stabbed she feels that stab wound in her own body and she's completely stopped by
it in a lot of cases. So, she has to protect herself sometimes from seeing
these instances of pain and she also says at one point that she can often not
afford to only injure someone when they're attacking her; that she has to
have great aim and kill them because she can't afford to injure and then feel
their pain and then be stopped herself and then probably killed. That's a pretty
harsh look of her hyperempathy or sharing as she calls it, but she's also
able to read her companions' pain. She's very perceptive and able to react
accordingly when people around her are suffering. So in general, her sharing is
more of an obstacle than it is a benefit just as it is for Cyra in Carve the Mark.
And I just want to talk about Parable of the Sower and Parable of the Talents a
little bit more broadly. So the character Lauren essentially writes a religion: a
set of beliefs and values and also a destiny for the human race that she sees
as true and she wants to spread it and develop communities. So this religion is
called Earthseed and she writes a book called Earthseed: The Books of the Living
which has the general philosophy that God is changed and therefore
adaptability is essential. The Earthseed destiny is that Earthseed, or people,
must take root among the stars. I think that's a really beautiful goal.
It's obviously very aspirational but the rest of her set of beliefs, her book, is a
lot of practical and useful information. She writes that God is change and
so you therefore need to learn how to shape or adapt to that change to reach
your goals and in the first Earthseed community that she builds called Acorn,
they build their own huts and they build a school and they teach children. They
farm and plant and live off of their own land and they're all very capable of
doing that because they're all working toward common goals and a common
community. They travel from Los Angeles County up to I guess Northern California
where they build this community. So much of the country collapses. Hardly anyone
has jobs. Most people live as squatters. It's very hard for people to acquire
work and money. There's a lot of stealing. There's a lot of violence which is where
her sharing comes into play a lot when they're attacked along the road.
It's a very intense book. In the second one, Parable of the Talents, there is a
political leader named Jared and he wants to... keep in mind this was written
in the 90s I believe... so this political leader Jared wants to make America
great again - is this slogan, gross. And he has these religious fanatics that
are all about like conservativism and some of them go as far as to enslave
people in re-education work camps and it's horrific and reading it is so
uncomfortable and awful. They put these slave collars on the characters in
the Acorn community. It's just horrible and it's scary to me. I'm afraid that the
world will turn out in any of these possibilities in the desperate and
extreme poverty or even in this intense religious conservativism, people being
put into slavery for having different beliefs. That's horrifying and it is one
of my greatest fears. The book was interesting to see all of this fleshed out
and to see someone fighting it and working toward her own beliefs, her own
goals and never giving up on that. That was really inspiring. Thank you for
watching this video. I hope you enjoyed this discussion of culture and religion
and pain and politics and I hope to see you in my next video. Also as a reminder
I have a Patreon and you can get some cool perks like a button that says
fandom matters or being able to choose a video topic and I will link that in the
description as I always do. Bye!
-------------------------------------------
Simone Milasas Invites You To A Book Club Done Different - Duration: 1:08.
Hey everyone, here is an invitation to you to come to the Joy Of Business bookclub
This is the Joy Business book, have you read it yet?
It's in 11 languages soon to be 14 as well but there's lots of good stuff!
See there you go that's all the good stuff that's in this book.
But what we'd like to invite you to is the Joy of Business bookclub
which is totally and utterly free and we have joy business facilitators from all over the world
who are going to be coming on talking about each chapter and giving you some more
tools and more processes and some extra information on about all of this so that
you can actually learn to have a joy in business or you can even acknowledge
that you already have a joy in business that's one of the things I see so many
people who are not willing to acknowledge that they actually like what
they're doing and what if you could even increase that more.
What if you could ask for more money to show up what if business was easy?
What if life was easy? So come join us at the Joy of Business bookclub.
Details in the link below. Talk to you soon bye!
-------------------------------------------
Breaking: NFL Ticket Sales Numbers Are in… Absolutely Brutal News for Anthem Haters | Top Stories - Duration: 3:03.
The NFL and its flag-disrespecting players just got the worst news possible, which is
topping off a week of nothing but bad news.
First, one of the biggest broadcasters of football games announced that it would break
its own policy and allow outraged fans to cancel their sports packages.
We thought that was great.
Little did we know what as to come.
Today recent ticket sales for the troubled league have been revealed — and they show
that fans have declared all-out war on the NFL, hitting them right in the wallet.
The Washington Examiner has just reported that professional football ticket sales have
plummeted nearly 20 percent this week compared to last week.
That information was based on data from TickPick, a major online ticket reseller.
Specifically, the retail site reported a drop of 17.9 in the last week.
"We have seen a massive decrease in NFL ticket purchases this past week in comparison
to years past.
Week 3 seems to usually have less ticket orders than week 2, but this year ticket purchases
are down more than 7 percent from this time last year," TickPick representative Jack
Slingland explained.
For a league that takes in a huge amount of revenue annually, a 17.9 percent drop in ticket
sales could mean a loss of billions of dollars.
The football ticket sales expert stopped short of specifically blaming the NFL's anti-anthem
antics for the drop, but strongly hinted that this was the cause.
"[T]he conversation around the NFL this week has focused on the president's comments
as well as the players' and owners' reaction," Slingland told The Washington Examiner.
"As viewers continue to abandon their NFL Sunday habits, both the number of ticket sales
and the purchase price of tickets will drop."
Given that the American people are squarely arrayed against the NFL, Slingland probably
could have curried some goodwill from fans if he had just embraced the truth wholeheartedly
— the American people are furious that multimillionaires think their lot in life is worse than the
average American's.
Showing just how out of touch the Trump-deranged liberals are, they actually didn't see a
problem with such an insane claim (I guess the derangement explains that, huh?).
They actually thought the American people would sit there to be lectured by people who
make more money, saying that everyday Americans are the real problem.
And just as they did before the last presidential election, left-leaning groups dramatically
under-estimated the number of patriotic Americans who are fed up with being ignored and insulted.
Red-blooded Americans have had enough.
If we haven't reached the tipping point where they lose millions of fans over this,
we're almost there.
Let's keep the heat on them!
Please press "Share on Facebook" if you think the arrogant NFL is getting exactly
what it deserves.
Is the NFL getting what it deserves?
what do you think about this?
Please Share this news and Scroll down to comment below and don't forget to subscribe
top stories today.
-------------------------------------------
PACCARB 7th Public Meeting Day 2, Pt 1: Welcome and Presentations: Agency Updates and Goals 2 – 5 - Duration: 1:27:30.
>> Martin Blaser: Welcome to day two of PACCARB seventh public
meeting.
I'm Martin Blaser, chair of the council.
It's my pleasure to welcome everybody to this event.
Today, we'll continue with updates from federal agencies on the year two activities and their
work on the milestones of the National Action Plan.
We'll also hear from our working group co-chairs and council on the work they're been doing
over the past year about incentives.
Then there will be a council discussion and a vote on the report.
And, now I'd like to hand over the microphone to Jomana Musmar the acting designated federal
official to open today's meeting.
Jomana --
>> Jomana Musmar: Thank you, Dr. Blaser.
Good morning everyone, and welcome back to the second day of our public meeting.
The Presidential Advisory Council and Combating Antibiotic Resistant Bacteria, my name is
Jomana Musmar, I am the designated federal officer of the Advisory Council.
Thanks to everyone that sent in public comments or signed up to provide a comment, in person
today.
As a reminder, this meeting is conducted via teleconference, is being streamed live and
is open to the public.
There will be time for public comments at the end of this meeting today.
The majority of the work of this advisory committee, including information gathering,
drafting of reports and the development of recommendations is performed by designated
working groups, who in turn report to the full council for deliberation of final vote,
as you all see this afternoon.
I will now go through role call for all council members, followed by ex-officios.
Please let us know if you are present by sitting here.
Alternates, please identify yourself and provide the name of the principal that you are representing
today.
I'll start to my left with our chair.
Dr. Martin Blaser?
>> Martin Blaser: Here.
>> Jomana Musmar: Michael Apley?
>> Jomana Musmar: Helen Boucher?
>> Helen Boucher: Here.
>> Jomana Musmar: Angela Caliendo?
>> Angela Caliendo: Here.
>> Jomana Musmar: Alicia Cole are you with us by phone?
Sara Cosgrove?
Peter Davies?
>> Peter Davies: Here.
>> Jomana Musmar: Lonnie King?
>> Lonnie King: Here.
>> Jomana Musmar: Kent Kester?
>> Kent Kester: Here.
>> Jomana Musmar: Ramanan Laxminarayan?
>> Ramanan Laxminarayan: Here.
>> Jomana Musmar: Aileen Marty?
>> Aileen Marty: Here.
>> Jomana Musmar: John Rex?
>> John Rex: Here.
>> Jomana Musmar: Tom Shryock?
>> Thomas Shryock: Here.
>> Jomana Musmar: Randy Singer?
>> Randall Singer: Here.
>> Jomana Musmar: Bob Weinstein?
>> Robert Weinstein: Here.
>> Jomana Musmar: Rich Carnevale, are you with us by phone?
>> Richard Carnevale: Yes, I am, Jomana.
>> Jomana Musmar: Thank you, Rich.
Jay Butler?
>> Jay Butler: Here.
>> Jomana Musmar: Sherrie Dornberger, are you with us by phone?
Liz Wagstrom?
>> Elizabeth Wagstrom: Here.
>> Jomana Musmar: And Elizabeth Jungman?
>> Elizabeth Jungman: Here.
>> Jomana Musmar: Thank you.
>> Martin Blaser: And Sara Cosgrove's just a few minutes late.
>> Jomana Musmar: Okay.
All right, ex-officios.
Of CDC, Michael Craig?
>> Michael Craig: Here.
>> Jomana Musmar: Dennis Dixon?
>> Jane Knisley: Jane Knisley for Dennis Dixon.
>> Jomana Musmar: Thank you, Jane.
Joe Larson?
Shari Ling?
>> Shari Ling: Here.
>> Jomana Musmar: Daniel Sigelman?
>> Daniel Sigelman: Here.
>> Jomana Musmar: Larry Kerr?
>> Lynn Filbi: Lynn Filbi for Larry Kerr.
>> Jomana Musmar: Paige Waterman?
>> Paige Waterman: Here.
>> Jomana Musmar: Brian McCluskey?
>> Brian McCluskey: Here.
>> Jomana Musmar: Jeffrey Silverstein?
>> Neena Anandaraman: Neena Anandaraman for Jeff Silverstein.
>> Jomana Musmar: Thank you, Nina.
David Goldman?
All right, thank you so much and thank you all for attending this important meeting.
Just a few more housekeeping items to remember.
I ask that all members, please identify yourselves when speaking into the microphone, so that
those listening via webcast or reading the transcript after the meeting will know who
made which comment.
Especially during discussion of the report this afternoon.
Please make sure that your microphone is turned off after your comment is made.
And, I will now turn it over to our co-chair, Dr. Lonnie King.
>> Lonnie King: Thanks very much, Jomana.
And, let me add my welcome to all of you and thanks for being with us today.
So, this morning we are going to continue listening to our federal agencies and partners.
Yesterday, they updated us on stewardship and today we'll have them update us, update
what they've done for the last two years in terms of infection -- infection prevention
and the goals two through five.
So, we'll do that for the morning, we'll take a mid-morning break, have lunch, and then
come back and devote our time to our report.
So, to get us started, Michael Craig, do you want to start please?
>> Michael Craig: Sounds good.
So, good morning, I'm Michael Craig.
I'm Senior Advisor for AR coordination and strategy at the Center for Disease Control.
Yesterday, you heard from Dr. Srinivasan about CDC's portfolio for antibiotic stewardship.
Today, I'm going to be talking essentially about the rest of CDC's portfolio for the
prevention of AR infections.
And a couple highlights just to start off -- nope.
So, CDC's work on antibiotic resistance really is going to fall into especially our prevention
portfolio is going to fall into three main buckets.
Detection and response, prevention and containment, and innovation.
And some of the themes that you're going to hear today are really going to be about improved
detection, how that leads to faster response, and how that faster response ultimately means
fewer infections and fewer people getting sick of drug resistant infections, which is
our ultimate goal.
On the laboratory and diagnostic side, I'm going to be highlighting some of the important
work and important investments that are going into improving laboratory detection specifically.
Across our country, at the state level, at the regional level, with the new AR lab network.
How that work is ultimately going to support improved detection, which is, then -- that
detection is then going to the boots on the ground.
The first responders at state public health departments and CDC, so that when new forms
of resistance are identified, they are responded to expeditiously and effectively in a way
that prevents infections from occurring, contains transmission of resistance and hopefully with
the ultimate goal of saving lives.
We'll also touch on some of the other activities that CDC has, our communications and guidance.
Some of this was covered yesterday by Dr. Srinivasan.
We try to out the best science and try to talk about the best science and talk about
how resistance is evolving.
What we're seeing, what are some new things that health care providers or other folks
who are working on resistance need to be aware of, how patients can protect themselves, how
the community can protect themselves.
Arjun a lot on improved antibiotic use, it's in some of the materials we've put out there.
Here you see some of the core elements, which as Dr. Srinivasan noted yesterday, have really
become the basis for a lot of the work that's going on at CMS and the joint commission,
in terms of improving antibiotic use and really standardizing practices across health care.
On our innovation side, we're also going to be touching on what are the gaps in science?
What are the things that need to be improved upon?
And, how can we do better?
How can we look at what's happening in prevention, what's not being prevented and then ultimately
make improvements?
And, then last, but certainly not least, we're going to take all of what we develop in public
health and see how we can contribute to research and development of new diagnostics and ultimately
new drugs and new therapeutics as well.
So, to start off, I'm going to start on the health care side and this chart really talks
about the traditional approach to preventing health care associated infections.
And, as you can see here, there has been tremendous success at preventing health care associated
infections.
Specifically, central line associated blood stream infections, surgical site infections,
catheter associated urinary tract infections, in our country.
This work has really been a combined effort, by CDC, CMS, ARC and OASH.
And, we continue to work toward those goals, to prevent these types of infections.
What I would note though, is that the challenge is that when we introduce antibiotic resistance
and when we address CDIF and we deal with drug resistance, that creates new complexities.
And the traditional approach of improving the practices is in a single health care facility
and in a single hospital, really aren't sufficient.
We have to approach things from a public health perspective.
We have to look at a community, because effectively patients are moving from one health care facility
to another.
They're moving from a nursing home, they're moving from their own home to a long term
acute care, to a hospital and back.
And when they're moving and they're either colonized or infected with the drug resistant
organism, they are taking those pathogens with them and they are potentially spreading
them across the community.
So, we need approach that's a regional approach and we need an approach that looks at this
movement, that looks at the risks across the communities, and that has an infrastructure
in place, both a laboratory, a detection infrastructure.
As well as an infrastructure in the state public health department to be able to respond
to those threats, when they emerge.
And to this end, CDC has been investing in with new resources, capacity in 27 states
and four cities to really aggressively expand this regional approach to antibiotic resistance,
especially at the health care level.
And this has been really critical to making advances and to be standing up an infrastructure
that is going to have long lasting results for our country.
To support this, we have established an AR lab network.
The AR lab network, as you can see here, is comprised of supports for both individual
state health department labs, as well as regional labs that do more sophisticated testing on
par with what CDC does.
We also, this year, are rolling out the first national TB molecular surveillance center.
That new center, which is actually going to be based out of Minnesota -- oh sorry, Michigan,
is going to be sequencing every TB case in the United States.
And, through whole genome sequencing, we actually expect to learn a lot more about the dynamics
of transmission and what we're seeing for TB in this country, with the goal of ultimately
coming up with new ways of preventing its transmission in the U.S.
The rest of the lab network is doing things similar for a variety of other pathogens.
Ultimately, we're trying to improve the detection of new forms of resistance so that the capacity
I described at states to be able to respond to these things, can effectively respond.
I'll go into that in more detail.
So, part of what we're doing here is trying to contain new forms of resistance.
And, we're really approaching over the past two years, coming up with a containment strategy.
And, this slide is really showing you why this is important.
So, Klebsiella pneumoniae carbapenemase KPC is a type of resistance found in CRE and CRE
is the nightmare bacteria.
The one that is resistant to most of our antibiotics, including the most powerful ones, the carbapenems.
What you see here is this form of resistance was very rare in 2001.
And we didn't have infrastructure in place, we didn't have the ability to detect it, we
didn't have the ability to respond to it, and as you see here, because we lack that
infrastructure in the U.S., it marched across our country.
So, it went from something that was terrible and rare to something that was terrible and
endemic.
And this is ultimately what we don't want to happen and this is what we ultimately want
to change, with the investments that we're making in prevention at CDC.
So, the strategy of containment is really looking at what are the rare threats, what
are the new threats that are emerging?
New forms of CRE, MCR1, pan resistant organisms, Candida auris -- which, if folks aren't aware
is a new form of Candida that is extremely resistant and has been spreading across the
globe and we definitely want to avoid it becoming endemic in this country.
And, we really look at the settings, where we have historically seen lots of transmission
and amplification of drug resistance.
Long-term care settings, long term acute care settings, skill nursing facilities.
And we really want to focus on when we identify one of those threats, that we act aggressively
to stop it and contain it and try to make sure the transmission is stopped.
And so, these are maps of what we see today.
So, OXA-48, VIM, IMP; these are all very technical forms of CRE and right now they are rare and
we do not want these maps to become fully blue, like we saw with KPC.
We want to stop them and contain them, where they're at.
C, auris is the same way.
This is something as I noted, we definitely want to avoid it becoming endemic in our health
care facilities, because it will have grave consequences for patients.
And this is where we're at right now and what we really are trying to do with the containment
strategy, is that when one of these cases is identified in the lab network, there is
a robust response by the state health department to be able to stop it, contain it and make
sure that we don't see additional cases.
And, to date, we've had success.
We have seen that, starting in January of this year, we have identified 2000 CRE cases.
About 15 percent of those are new forms of resistance and when we've seen those, we have
triggered a comprehensive response by the state health department.
This year alone, there have been over 40 investigations just since January of this year, there have
been over 40 investigations for drug resistant infections in health care that CDC has helped
consult on.
We have worked to contain very specific outbreaks and have had success for things like C. auris,
where, you know, for example the state of Oklahoma we had an imported case come in that
was identified very quickly, it triggered a very robust response, and we had no onward
transmission in that facility or in the state, whatsoever.
And, that's really what we're going for.
We want these things to be contained, we want to stop the movement of them across the country.
We do not want them to become endemic in the United States.
So, moving on from containment, touching on something that is also an added benefit of
our expansion of laboratory resources, the CDC and FDA AR Isolate Bank.
So, this is taking the isolates that we have identified, either through containment efforts
or from prevention efforts and being able to support industry, diagnostic industry,
therapeutic industry, as well as reference labs to have the best available strains to
be able to make sure that they are testing either new innovations or their existing diagnostics
against what is being seen in our country, in terms of resistance.
This has been in place since July of 2015, and it has been extremely popular and extremely
successful.
It's curated from over 450,000 islets in CDC's collection and today, we've had over 571 unique
customers and 637 orders processed.
And what this ultimately looks like, in terms of this, you can actually see the quote here
from a diagnostic developer.
Part of the reason we did this in partnership with FDA, as that the FDA noted that when
a diagnostic company, especially comes to them with a new diagnostic, they often test
them against a variety of resistant pathogens that they find from private companies and
everyone tests them against different pathogens.
We're trying to provide, and we are providing, a single curated set of islets that the FDA
can direct diagnostic manufacturers to test against the same panel, so that we can actually
better compare diagnostic performance because they're being compared apples to apples, in
terms of their performance.
So, that's one of the added benefits of it, but as you can see here, a lot of other companies
we've worked with, some drug companies and therapeutic companies, as well, and they're
testing new compounds against the emerging forms of resistance, to see if there are opportunities
to create new drugs or therapeutics.
So, other aspects of our innovation here, that I just want to highlight, is that we
do a lot in terms of trying to fill the gaps in knowledge.
That prevention is not stagnant.
We always have to be coming up with new ways of filling our tool kit with new tools to
prevent resistance, because, quite frankly, resistance is evolving and we have to evolve
our prevention portfolio with it.
So, we do a lot of innovation work with academic researchers, with health care providers, and
with other investigators in the area of health care, in the area of agriculture and food,
in the area of the environment, and in the area of community infections, as well.
Really trying to understand how transmission is happening, how it can better be detected
and how it can better be prevented, and, what are the new ways of preventing them.
So, turning more specifically to some of the community aspects of our portfolio.
Really, this is following a lot of the same themes of improving detection, so that we
have faster response, so that fewer people ultimately get sick of various infections.
On the food side, we've talked about this previously that CDC is investing in whole
genome sequencing in every state.
To be able to detect salmonella and other food borne disease outbreaks.
And what this ultimately means is that whole genome sequencing will give us more granular
data, more specific data about resistance and the transmission dynamics.
And this is also happening in concert with expansion of whole genome sequencing that's
happening at FDA for food and whole genome sequencing that's happening at USDA on the
animal side.
Ultimately, we have the goal of trying to work across those agencies to better, to more
rapidly identify food borne disease outbreaks and to stop them.
And as you can see here, we have made tremendous progress over the past couple years in expanding
whole genome sequencing capacity at the state level, with the goal that the salmonella in
our country by 2019, 90-plus percent of it, hopefully even more than that, hopefully 100
percent of it will be tested via whole genome sequencing.
And, again, this is lab capacity for gonorrhea and our ability to not only detect the resistance
that we're seeing, but respond to it.
You can see here, in terms of the yellow states are regional labs that are testing for germ
resistant gonorrhea and our blue states are our rapid response sites that are, when germ
resistant gonorrhea is being identified, they're responding to it and acting very aggressively
to make sure it doesn't spread.
And as you can see, between the then and now, there has been a tremendous increase in our
capacity nationally to test for germ resistant gonorrhea and to be able to identify emerging
trends and we are seeing emerging trends and one thing of note for germ resistant gonorrhea,
specifically is that CDC actually develops the treatment guidelines for germ resistant
gonorrhea.
And so, this data is actually being directly used and analyzed by our CDC subject matter
experts in the GC program, so that they can put out the best possible guidance to clinicians
about the best courses of treatment for what people are seeing in the United States.
Continuing, we also have a variety of things that we're working on actively, on the tuberculosis
side, domestically.
In addition to some things that we're doing on the international side, which I'll touch
on in a minute.
One, very critical piece is that we're looking at the TB medical exam.
Right now, immigrants that come to the U.S. are screened for TB and have to have effectively
a clean bill of health on the TB side before they can come to the U.S.
However, other types of visas, specifically students, skilled workers, long term visitors,
those aren't screened at all for TB before they come to the U.S. Countries, such as Great
Britain, Australia, New Zealand, have all instituted a program to expand their visa
categories that are screened for TB overseas.
It has the benefit of actually identifying TB in those individuals and helping them.
It also has the added benefit of reducing the spread and transmission and importation
of TB into the host country.
And so, we're actually looking at how we can expand that with the state department.
We're also looking at innovations in TB treatment both, right now domestically, but we think
they have global applications.
Trying to see how directly observe therapy, which is the gold standard for TB treatment
right now, can be done via smart phone or through new technologies, to make it less
burdensome on patients and potentially more effective.
We've also established in the U.S. a stockpile of TB drugs.
Over the past few years, we have seen that there have been some interruptions in the
drug supply for TB drugs in the U.S. that have affected treatment and have potentially
prolonged outbreaks or made state public health responses more challenging.
And we've established the TB stockpile to try and mitigate any of that.
I also want to just touch on here, example of some of our global work to combat AR.
Most of the portfolio that we have at CDC is focused domestically, but we know and,
as we have talked about yesterday, that resistance knows no borders and that we have tremendous
amount of work that needs to be done globally, we saw that and heard that at the U.N. General
Assembly.
And we want to be supportive and we want to lead in the U.S. and CDC wants to support
as many countries as possible, to improve their detection of antibiotic resistance and
to prevent those infections, within their countries, to improve their stewardship in
those countries, with the ultimate goal of not only helping those countries, bur of protecting
Americans.
Because we know that these pathogens can and will move globally.
So, here's some examples of some of our work that we're investing in right now.
The first national TB program in China has been set up in the past two years, and we
think has a lot of potential to really address some significant challenges with TB that that
country faces.
We do all of this in partnership with the ministries of health with those countries,
because we know that our expertise is important, but it's even more important that that expertise
be shared with those countries and that those countries be invested in so that they can
do a lot of this work themselves.
We've also done a lot in terms of strengthening and trying to establish programs related to
health care and associated infections than AR surveillance in Vietnam and India and trying
to really get a handle on what resistance is being seen in health care settings there
and what infection control can be put in place, so that we can either mitigate the transmission,
prevent the transmission, contain some of those forms of resistance that we're seeing
there.
And then last, I just want to sort of note, in terms of pre and post, you know that's
been sort of a theme that I'm touching on here.
You know, prior to CARB, prior to the investments that the Congress made in antibiotic resistance
-- it's a dramatic change and this slide is really trying to be instructive of the then
and what the now was.
Ultimately, this goes back to is resistance going to move across our country and is no
one going to act to stop it?
And right now, we are establishing and as I've described, we are putting in place an
infrastructure that will be able to detect new forms of resistance, will be able to respond
and we think, will be able to contain some of these threats.
It's not perfect right now and there's a lot of improvements that can be made.
You know, this is really work that has happened over the past two years and really its work
that's really only happened over the past year, in terms of getting state health departments
invested in and where they need to be.
But it's work that we need to be vigilant about, that we need to continue investing
in, and that we think will have, ultimately, incredibly long-term importance for the future
of our nation's ability to prevent and respond to antibiotic resistant infections.
Thank you.
>> Lonnie King: Michael, thanks very much.
So, we'll continue and by the way, we have a 30-minute question and answer discussion
period after all of our presenters.
So, we'll wait until then, so hold your questions until the end.
So, we're pleased to have colleagues from the FDA.
Bill Flynn who, back from yesterday, and Steven Gitterman.
So, welcome and the floor is yours.
>> William Flynn: Good morning.
Thank you again for the opportunity to update the council.
I'm just going to provide a very few brief updates related to the activities on the veterinary
sector and then I will turn over to Dr. Gitterman.
We certainly have quite a number of activities going on with regard to objectives and goals
two and five and in the interest of time, we'd just like to focus on goal two.
Seems like this isn't advancing.
Here we go.
Two key objectives, that I just want to spend a little -- provide some updates on, which
are important.
First objective, related to expanding capacity of veterinary food safety laboratories, to
provide the capability to anti-microbial susceptibility testing.
And then second, enhancing monitoring both on resistance, sales use, and management practices.
Next slide, please.
So, with regard to expanding laboratory capacity and sampling, FDA does coordinate with Vet-LIRN,
which is the Veterinary Laboratory Investigation and Response Network and there were objectives
within the national plan to expand that program.
Unfortunately, with limited resources, we had difficulty in doing that, but despite
that, we have made some advances, which I just want to highlight here.
So, in 2016 and 2017, we were able to provide sequencing equipment to two of those laboratories,
so there's now a total of four network laboratories that have the capability for whole genome
sequencing and are participating in the whole genome sequencing initiative.
We now have a total of 20 of these Vet-LIRN laboratories that are collaborating to conduct
anti-microbial susceptibility testing on veterinary clinical islets, and as of July 2017, over
850 samples have been tested.
So, while we're not hitting necessarily the goals that we necessarily set out in the action
plan, we are making some progress in this arena.
Just looking at, reflecting on several comments, or recommendations that were in the March
2016 initial assessment by the PACCARB, certainly funding has been an important issue for us
and two recommendations related to objective 2.4, which relates to modern and resistant
sales uses and management practices.
It is the point about making sure that FDA and USDA have sufficient funding for surveillance.
Again, for FDA, we did receive some additional funding in 2015, which has helped us make
some expansion to the NARMS program, which I'll briefly speak to.
But, there's been no additional funding since that time, and, as Dr. McCluskey referenced
yesterday, I think there's some positive movement forward on the USDA side, in terms of on farm
data collection, in terms of surveys moving forward, under the NOMS program.
Next slide, please.
So, certainly, as resources continue to be something that slows progress a bit, we are
continuing to look for opportunities to leverage what resources we currently have and look
for opportunities to collaborate with other agencies, as well as working to take advantage
of public private partnerships.
Next slide, please.
So, I'm going to talk briefly about sort of three areas.
Work that we're doing as far as monitoring resistance trends, second being monitoring
drug sales, and then third, drug usage.
So, as far as monitoring resistance, as I mentioned, we did receive some additional
funding in 2015, the NARMS program, or National Antimicrobial Resistance Monitoring System,
as you know, is a joint effort between FDA, CDC, and USDA.
FDA, CVMs, the key element FDA focuses on, in terms of contributing data to that system
is the retail meat arm of the program.
So, based on the increased funding, we were able to expand, not only the number of samples
collected, but also number of sites in various states that have been enrolled in that program.
So, we have increased the number of retail meat samples collected from 6700 in 2015 up
to over 17,000 in 2017.
We've also increased the number of sites that has been conducting testing on enterococcus
from four to 11 sites and for E.coli from four to nine.
It was mentioned early by Michael Craig, the importance of whole genome sequencing and
the significance of that.
At this time, all salmonella and campylobacter, as well as select enterococci and multi-drug
resistance E.coli are now being subjected to whole genome sequencing, under the NARMS
program and that data is being published in NCEI.
We've also made some enhancements is just how data is being reported out through the
NARMS program.
Really starting with the 2014 reporting year, we have a much enhanced integrative report
that also includes some very exciting interactive data dashboards.
And if you visited that site, I recommend that you do that.
We are working on the 2015 reporting year integrative report and hope to have that out
soon.
Next slide, please.
With regard to monitoring sales data, I briefly mentioned this to the council yesterday, I
think two updates in terms of progress moving forward in this arena.
One is we did finalize a rule in 2016 regarding sort of processes for submitting the process
for drug companies to submit sales data to FDA.
And in doing that, made some enhancements, including the new requirement that when that
data be submitted, that companies report out estimates of the quantity of product sold
based on the major food species that's on the label.
Prior to that, data was provided in a lumped data, essentially, for all species on the
label.
Many products that are marketed or market for multiple species.
So, while these are estimates, we do feel they provide us some assistance in helping
to interpret the overall sales data that's being reported.
Somewhat related to that, more recently, just this past August, we did also publish essentially
a white paper for public comment by seeking input on a possible approach for using what
we're calling a "bio-mast denominator" sort of adjustor and that enables us to look at,
at least what we're proposing here is to use this adjustor as a way to try to take into
account animal populations, when we're looking at overall sales data.
That is now open for public comment, and, you know, we'll consider those comments and
kind of move from there.
But we think that does provide us some help in terms of, again, interpreting sales data
as one element of information that's important to assessing antibiotic use practices.
Next slide, please.
And then, lastly, on monitoring usage, again, sales data has its limitations in that it
doesn't necessarily represent what's actually happening at the farm level.
We do believe that it's very important that we have additional data to augment that, and
we are making some progress in this -- in this arena.
We did fund, utilizing some existing funds in August 2016, cooperative agreements.
Two projects were awarded.
The intent is to pilot methodologies for collecting information on on-farm antibiotic use in cattle,
swine, chickens, and turkeys.
So, there are two projects ongoing now, one focusing on cattle, the other focusing on
swine, chickens, and turkeys.
We're continuing to fund that work, and it's looking very promising, and we're hopeful
as to having some very useful information coming out of those ongoing studies.
And then, secondly, as I also mentioned yesterday, we continue to work very closely with our
colleagues at USDA Center for Epidemiology and Animal Health in terms of sharing information
in terms of what we're doing and the work that's going on through these cooperative
agreements, working with USDA on the survey work that they're doing, and also working
to better understand how best not only to collect this type of information, but also
how to -- how to report it in a way that provides the appropriate context.
So, that's the updates I have, and I will now turn it over to Dr. Gitterman.
Thank you.
>> Steven Gitterman: Thank you.
>> Female Speaker: Are you able to get it to work?
Or is it -- okay, just say, "Next slide."
>> Steven Gitterman: Next slide.
[laughs] Hi.
Thank you, again, for the opportunity to update the committee.
I'll try and move a little quicker.
Next slide.
There's been tremendous progress at the agency, and rather than taking the strategy that Dr.
Flynn took, many of our -- many of the progress crosses a number of objectives, so I'm just
going to approach it as a list.
But within CDRH and antimicrobial drug development, there's been a tremendous amount of progress.
There's been a number of guidance documents for both standard and unmet needs that have
been published.
There's been a series of public meetings.
I know several people around the table have participated in them.
Excuse me.
FDA's working very closely and more active than ever with both the EMA and the PMDA -- that's
the Japanese equivalent of the USFDA -- on recommended trial designs.
People have heard the messages that things need to be more standardized to permit international
development.
There's quite a number of qualified infection disease -- qualified infectious disease products
that have been designated at this point, over, you know, 136 total designations for 71 different
products.
And as everyone's aware, a number of the products that have had -- that have been given designation
are now approved.
There's eight recently approved antimicrobial, antifungal products that have the designation,
and there's been many efforts to revise clinical trial designs to allow more rapid progress
and more streamlined approaches to addressing unmet medical -- unmet medical needs.
Next slide.
Right now, there's a tremendous amount of resources implemented in the 21st Century
Cures Act.
We'll talk about that again, but the section 3044, susceptibility testing criteria, a tremendous
advance, which I'll show a slide later, which I think will substantially reduce the amount
of time to getting updated MIC information to clinicians, and the limited pathway for
antimicrobial, antifungal development.
Again, this was passed late last year, and there's a lot of work in implementing that.
And again, there's work, a lot of work, which I'll talk about very quickly later, on CDRH
and coordinated development of antimicrobial drugs in diagnostic tests.
Next slide.
On device development, we're -- again, it's very, very active.
As people are aware, because we keep mentioning it at different meetings, is the first clearance
of a biomarker test to aid clinicians in antibiotic stewardship and both the initiation and discontinuation
of antibiotic -- of antibiotics.
And people go to scientific meetings or read the press, that's a very, very exciting area
right now.
A lot of development.
There's been new technologies for rapid phenotypic susceptibilities, something I personally didn't
think was going to occur.
And it's very, very encouraging to see that people are working on technologies for phenotypic
susceptibility, some of which are very exciting.
As Dr. Craig mentioned earlier, there's continued support for the FDA/CDC Antimicrobial Resistance
Bank.
One thing Dr. Craig didn't mention is that a big part of the original, I guess, initiation
of the bank, was the fact that a lot of device companies couldn't get these isolates.
They would -- they would have to search everywhere, and we'd say, "You have to have the isolates,"
and they'd have to be beating the bushes.
Through a lot of CDC's efforts and some very excellent cooperation, these panels are now
available which substantially accelerates device development.
And there's been continued development of FDA-ARGOS of having standardized genomic material
that device companies could use.
Next slide.
We have cleared, last year, but late last year, the CRE molecular device for detecting
CREs in stool.
I'm told that's very exciting.
There's support -- and this is particularly exciting -- I've used that word a little too
much -- but for new semantic interoperability standards, and there actually is a contract
with Regenstrief to produce a manual and outreach to doing semantic interoperability.
This is the -- basically, the very straightforward concept that all antimicrobial resistance
tests, all, basically, antimicrobial diagnostics, are coded the same way and reported the same
way such that every laboratory, basically, becomes an active means of communicating information.
And we're very excited about this.
We think this could enable decision support.
Can do real-time epidemiology.
Everybody who's doing -- you know, basically, doing these tests can contribute to an ongoing
database for identification.
And this is also an effort that's been very -- which we're very encouraged -- it's been
very active participation from CDC, NLM, ONC, and other partners, especially industry.
But we do have, actually, a published standard on how device manufacturers can communicate
to laboratories how to code these efforts automatically.
Because we have been very keen on the idea that we're actually reducing work for laboratories,
not making new challenges.
And as people are aware, there's a new breakthrough pathway for devices.
Next slide, please.
There's an FDA draft guidance, you know, addressing delays in making susceptibility tests that
was published last year.
There's final guidance expected shortly, and currently, in coordinated development -- I
forgot the title of the slide -- we have nine current pre-submissions.
We're seeing this as a very, very prominent success.
I don't want to push it too much, but the recent approval of delafloxacin, if I have
this correct, had three AST devices available within a month of the drug approval.
And we're really hoping -- we have a draft guidance out.
We're going to revise it to make it, you know, based on comments we've received, and we really
hope this is going to be a very successful model.
Next slide, please.
Next slide, please.
Ah, thank you.
Just one quick illustration of the -- of the impact of the 21st Century Cures Act.
I'm not going to talk through, but this is the old way.
And the blue boxes are just blocking out some confidential information, although I see one
may not have worked that well.
But basically, the old process where the CLSI changed the break point, then a company had
to come in with a labeling supplement for drugs.
That had to be approved.
Then you first -- device companies could first start considering it.
This is a real example, and this was about a three-year process.
The 21st Century Cures has lopped off basically everything between -- parts of the 21st Century
Cures and Coordinated Development have lopped off the first four arrows.
So we've easily cut, on average, probably a year and a half, if not more, from this
process.
Then we ask questions about the details.
People have to fill them in later, but it's a tremendous advance.
Next slide, please.
And just to -- not to waste -- not to go into too much detail, but this is the example of
the coordinated pathway.
And again, we really hope that we're addressing a lot of what have been concerns expressed
at these meetings and others that companies can actually submit an application, a 510(k),
for a device approval, even before the drug is approved.
And that is going to require good coordination between the drug manufacturer, the device
manufacturer, and FDA.
But we do have in place a process that can actually get these devices out very, very
rapidly.
We do not -- we're tired of hearing that the regulatory process is a burden.
And that should not be the case moving forward.
Thank you very much for the opportunity.
And if there's any questions, I'll be glad to address them subsequently.
>> Lonnie King: Thanks very much, Dr. Flynn, Dr. Gitterman.
So, now I'll turn to CMS.
So, Shari, we're working you pretty hard.
So, thanks for being backup.
>> Shari Ling: [laughs] It's my honor to represent the agency
and report out on CMS activities.
This will be a relatively brief presentation, and I'll try to use this opportunity to also
meet the council's request to talk about the evolution of the implementation -- evolution
and implementation of the quality measurement into payment programs.
Next slide, please.
So, yesterday, I touched briefly on the policy and program levers to set the minimum safety
standards for facilities and the surveillance to -- compliance with those expectations.
I also talked a little bit about quality improvement.
And today, I will present on CMS work that supports goal two, specifically objective
2.2, which is expand and strengthen the national infrastructure for public health surveillance,
data reporting, and providing incentives for timely reporting of antibiotic resistance
and antibiotic use in all healthcare settings.
Today, we'll actually focus using the hospital as an -- as an example, both for the evolution
of a quality measure.
But also please know that our work in adopting quality measures that utilize NHSN as a vehicle
of information reporting spans and expands to other care settings beyond the hospital
in a very consistent way to meet the needs that Michael so eloquently illustrated, the
systems approach.
So if we actually go to the next slide, please.
So -- sorry.
Before we get there, I want to also mention that when we talk about payment for quality,
we have to distinguish pay for reporting, which is paying for a facility to participate
by contributing information or quality measure data into the system, where there is a payment
adjustment in the downward direction, also known as a ding, if quality data are not provided.
So, that is pay for reporting.
In addition, though, the next step would be paying for either attainment or achievement
of specific metrics, and that would be paying for outcomes or value.
So, that is pay for performance, which is the next step beyond pay for reporting.
So, there are several -- there's the Hospital Inpatient Quality Reporting System that appears
on Hospital Compare, all of the -- for public purposes to inform consumers for their care
decisions.
There is also, then, Hospital Value-Based Purchasing.
So, Hospital Value-Based Purchasing, the goals and the intent of the program is to promote
the attainment and improvement towards better clinical outcomes for hospital patients and
also improve the patient experience of care during the hospitalizations and providing
the encouragement to improve and go beyond the minimum safety standards -- that is, beyond
the floor that's set by the COPs.
So, this is about quality and value.
Value-based payment incentives are made based on a hospital's performance -- that is, attainment
of a certain score -- but also that they improve from their baseline.
So, there are two constructs there about what is actually being paid for.
The details of Hospital Compare and also the Hospital Value-Based Purchasing Program are
available on the CMS website, and the Hospital Compare site is provided here.
I will also emphasize that in order for quality measures to be implemented in a value-based
purchasing program, in a hospital VBP, they must appear on Hospital Compare for a full
year or longer.
So, next slide, please.
So, this slide just provides for you a couple of points, illustrates a couple of points.
One is that this is the finalized construct for the fiscal year 2018 Hospital VBP Program.
I called your attention to the safety domain that includes C. diff infections -- that is
facility-wide C. diff infection -- in addition to which, we have two healthcare-associated
infections: catheter-associated urinary tract infections, and central line-associated bloodstream
infections, as well as MRSA.
All of these are actually reported into the National Health Safety Network, so again,
in close collaboration with our CDC colleagues.
These have been proposed and finalized through rulemaking for the fiscal year 2018 payment
year.
I will also call your attention to the domains.
So the domains here, safety is worth one-fourth of the total scoring for this fiscal year's
payment adjustments, equal to clinical care measures that are depicted in blue, efficiency
and cost reduction, as well as person and community engagement, so the patient's experience
of care.
So these are equally weighted.
Again, these quality measures in the safety domain have actually been included on Hospital
Compare since 2015.
So, illustrating that, you know, they were implemented for public reporting purposes,
pay for reporting purposes, first, and then subsequently proposed and adopted through
rulemaking in the Hospital Value-Based Purchasing Program.
So, the measures that you see here have all been NQF indoors.
That means opined upon by a multi-stakeholder entity thought to be -- these concepts were
important to measure, actionable, met test characteristics.
And these are all measures that CDC is a measured steward for.
In addition, the process that is required is that those measures have to be included
in the measures under consideration list, and that list -- the doors open each December.
That list is, then, opined upon by the measure application partnership, which is also implemented
and hosted by the National Quality Forum.
But it goes the next step of the consideration.
Not only are these -- do these measure meet endorsement criteria, but also have accountability
assessed, have been demonstrated that they are useful and feasible to measure.
These all take into account how the measures are used, so not that -- just the measure
construct, but that they are used for payment, with payment implications, is also deliberated.
So, that is part of the process, and this is a reflection -- the display of the final
outcome of that process.
Those measures that are supported for implementation are then proposed through rulemaking and finalized.
That finalization includes consideration of public comment.
And again, CMS has to respond to each and every comment, whether or not just to consider,
or often, those comments provide us -- provide CMS with the opportunity for logical outgrowth.
So, without that opportunity, there's risk and need to often finalize as proposed.
So, the public has an important role to play in the consideration and shaping of all of
these programs, whether IQR or value-based purchasing for hospitals, or the use of quality
measures across all care settings.
Next slide, please.
So you may recall, also, that there is -- so this is a good example of the anatomy of a
quality measure.
This quality measure is a measure that was stewarded by our colleagues at CDC, measure
NQF number 2720, and that is a measure on antibiotic used based on medication administration
data collected by hospitals and reported electronically to the CDC's NHSN.
It was endorsed and met endorsement criteria in 2015 and was then submitted to the Measure
Application Partnership for consideration in 2016.
So, the -- it includes a numerator statement, a denominator statement, and if outcome measures
also will include any risk adjustment that was determined necessary.
The Measure Applications Partnership, in 2016, provided conditional support pending CDC's
recommendation that the measure's ready for use in public reporting and pending resubmission
to the MAP for review of implementation data.
So, that is another update for you.
So, not only are we providing the update of the measures included in VBP for this fiscal
year, but also a status report of where this specific measure is in the process.
Next slide, please.
So, many of you may wonder what happens in this -- in the circumstance of a disaster.
We have seen several in the recent history.
So, in September, CMS actually released a memo granting exemptions to the reporting
under the quality reporting and value-based purchasing programs.
This applies -- these exemptions apply to locations designated by FEMA as major disaster
counties or parishes.
And this actually -- the intent of this is to permit facilities, encourage facilities,
to do the right thing, which is take care of the patients first, focus on disaster recovery,
and also on the -- focusing on the restoration of services.
So, we're continuing to monitor the situation and will provide updates on the exemptions
as time unfolds.
And I will stop there and thank you.
>> Lonnie King: Dr. Ling, thank you very much.
So now we're pleased to have Dr. James Cleeman from AHRQ, and so we're looking forward to
your report.
Thank you.
>> James Cleeman: Thank you very much, Dr. King.
I'm Jim Cleeman.
I'm the Director of the Division of Healthcare-Associated Infections at AHRQ, and I'm delighted to have
this opportunity to provide an update to the council on AHRQ's activities preventing healthcare-associated
infections.
In the area of HAI prevention, AHRQ's activities span the spectrum from research through implementation.
AHRQ supports research to develop improved methods of preventing HAIs and improve the
safety of healthcare -- these studies tell us what to do -- supports research to develop
effective implementation strategies for HAI prevention, a branch of implementation science
-- studies that tell us how to do it -- then translates the research findings into tools
for implementing HAI prevention, and finally, promotes implementation of HAI prevention
with effective methods, strategies, and tools from the first three steps.
Next slide, please.
With respect to HAI prevention research, AHRQ renewed its funding opportunity announcements
in September of 2016.
There was an announcement for large research projects, R01, and large demonstration and
dissemination projects, R18.
And these announcements highlight the intimate connection between HAI prevention and CARB.
We're fond of saying that every HAI prevented is an episode of antibiotic use avoided, a
clear contribution to stewardship.
And in addition, every HAI prevented slows the development of resistance.
The announcements cover applications in all settings: acute care, long-term care, and
ambulatory care.
And they identify broad areas of research interests that include the efficacy and effectiveness
of preventive interventions and relevant epidemiological aspects including the assessment of risk factors
for HAIs and sources of antibiotic-resistant HAIs.
Next slide, please.
Thought I'd give you a couple of examples of currently-funded research in HAI prevention.
You see the first is in nursing homes and the second in households, and this is intended
to signal that AHRQ is certainly funding research in the hospital arena, but beyond the hospitals
in long-term care and in ambulatory care, including even the household.
Project Protect is examining universal decolonization to reduce infections with multi-drug resistant
organisms in nursing homes.
Decolonization is with chlorhexidine body wash and nasal ionophore.
And this is a very interesting study, because the PI of this effort is also the PI of a
suite of four decolonization studies.
The first was the landmark REDUCE MRSA study that showed the effectiveness of universal
decolonization for preventing MRSA transmission in ICUs, hospital intensive care units.
The second was in hospital non-ICUs, wards.
The third, in decolonizing patients upon their discharge from hospital.
And now this one, universal decolonization in nursing homes.
And the study has collected baseline data on the prevalence of MDRO colonization.
These data will be released at ID Week.
So, stay tuned.
They're very interesting, and they are beginning the decolonization protocol in the intervention
arm.
The second study is looking at the integration of personal and household environmental hygiene
measures to prevent MRSA.
The personal decolonization is with chlorhexidine and nasal mupirocin, and the household approach
is to clean the environmental surfaces.
And in addition, AHRQ is funding studies to prevent C. diff transmission and infection
as well.
Next slide, please.
Some examples of the implementation research for preventing HAIs.
The first is a study that's looking at the implementation of chlorhexidine bathing to
reduce HAIs in non-ICUs.
This is using a systems engineering approach that focuses on how various aspects of systems
interact to influence patient safety.
This study is going to produce a toolkit to help other institutions succeed in their efforts
to implement chlorhexidine bathing in their patients.
And the second example is Project SMART, which is looking at the implementation of management
strategies to reduce HAIs.
The PI previously identified several management strategies that enhance HAI prevention.
These include explicit goal setting, inter-professional collaboration, and meaningful use of data.
And this study will culminate in the development of a management practices toolkit for HAI
reduction.
So, you see, in a sense, toolkits from HAI research studies exemplify AHRQ's commitment
to translate the knowledge from research into tools for broad use as has been recommended
by PACCARB.
Next slide, please.
In the air of promoting -- in the area of promoting implementation of HAI prevention,
AHRQ's strong suit is the Comprehensive Unit-based Safety Program, or CUSP.
CUSP is a proven method for preventing HAIs.
It was developed at Johns Hopkins with AHRQ's support, and Dr. Cosgrove has been significantly
involved in the CUSP activities at Hopkins.
CUSP combines improvement in safety culture, teamwork, and communication together with
a checklist of proven practices for preventing the HAI in question.
This combination of behavioral elements in the first set -- safety culture, teamwork,
and communication -- with the clinical elements in the second -- checklist of proven practices
-- creates a powerful tool for accelerating the adoption of evidence-based practices to
prevent HAIs.
Next slide, please.
AHRQ has mounted a set of CUSP implementation projects over the last few years.
Their first was CUSP for central line-associated bloodstream infections, or CLABSI, and then
after that, for catheter-associated urinary tract infections in hospitals, CAUTI, and
then for safe surgery, both in in-patient and ambulatory settings for mechanically-ventilated
patients, for CAUTI in long-term care, for persistently elevated CLABSI and CAUTI rates
in ICUs, and for improving surgical care and recovery.
And I'll say a little more about the last three of these.
Next slide, please.
The CUSP for CAUTI in long-term care project was completed in September 2016, a nationwide
project that achieved a 54 percent reduction -- a highly significant reduction -- in CAUTI
rates in over 400 nursing homes around the country.
And the project produced a toolkit to reduce CAUTI in long-term care facilities that was
released in March 2017, and this toolkit assists other nursing homes to achieve the success
that was seen in this project.
Next slide, please.
With respect to PACCARB's recommendations, this project exemplifies several of them,
coordination with other agencies.
CDC and CMS staff served on the technical expert panel that guided implementation of
the project, and CMS and CDC staff are involved in dissemination of the toolkit as well.
And this project had significant partnerships.
The American Hospital Association's HRET, or Health Research and Educational Trust,
led the conduct of the study together with APIC, the Association of Professionals in
Infection Control and Epidemiology; the Baylor College of Medicine; the Society of Hospital
Medicine; the University of Michigan; and state nursing home associations.
And these partnerships greatly strengthened the expertise and effectiveness of the project.
Next slide, please.
Another project is the CUSP for persistently elevated CLABSI and CAUTI rates in ICUs.
This is a follow-up to nationwide CLABSI and CAUTI projects that AHRQ has previously mounted.
The nationwide CLABSI project produced a 41 percent reduction in the rate of CLABSI, but
not all of the ICUs that participated achieved the same success.
And the nationwide CAUTI project produced a 30 percent reduction in over 700 non-ICUs,
but the ICUs did not reduce their CAUTI rates significantly.
And so, AHRQ felt duty-bound to go back and help ICUs do better in their -- with their
persistently elevated CLABSI and CAUTI rates.
The study has -- the project has completed recruitment of over 300 ICUs across four HHS
regions, has tailored the CUSP interventions to ICUs with persistently elevated rates -- this
begins with an assessment of the ICU's gaps and needs, and then tailors tools and training
to meet those gaps -- has established a project infrastructure using state hospital associations
as coordinating entities, and implementation of CUSP interventions are currently ongoing.
And we are now poised to expand the reach of this project from four regions to nationwide
coverage, and this will happen in the next several weeks.
Next slide, please.
Exemplifying several PACCARB recommendations, coordination with other agencies, this project
has relied on CDC and CMS.
They've been instrumental in identifying ICUs eligible for recruitment into the project.
NHSN data are bound by confidentiality requirements, so they cannot be shared on the level of individual
ICUs, shared with AHRQ, and so CDC has identified ICUs that have elevated CLABSI and CAUTI rates,
and CMS has identified those that are participating in their quality improvement projects.
CDC and CMS staff serve on the technical expert panel that guides implementation of the project.
And significant partnerships have included HRET conducting the lead, the American Nurses
Association, APIC, the Michigan Health and Hospitals Association, the Society for Critical
Care Medicine, the Society of Hospital Medicine, University of Michigan, and state hospital
associations.
And again, this strengthens the expertise and effectiveness of the project.
Next slide, please.
And a third project currently underway is the CUSP for improving surgical care and recovery.
This is a five-year project launched in September of 2016.
It is promoting the implementation of evidence-based practices to enhance recovery, improve outcomes,
and reduce complications including the reduction of surgical site infections and catheter-associated
urinary tract infections.
And some examples of evidence-based practices that are being promoted include state-of-the-art
analgesia with reduced use of opioids, avoidance of prolonged periods of fasting, and early
mobility.
The project is currently recruiting for the first cohort on colorectal surgery.
Recruited 150 hospitals thus far, which is pretty good, considering that 100 hospitals
was our target.
There's a lot of enthusiasm for this kind of approach, and many more hospitals are waiting
to sign up.
Future cohorts are planned for other forms of surgery, including orthopedic, gynecologic,
emergency general, and bariatric surgery.
Next slide, please.
Exemplifying PACCARB recommendations in this project, coordination with other agencies,
CDC and CMS staff again serve on the technical expert panel that guides implementation of
the project.
And the significant partnerships here are with Johns Hopkins University that is leading
the project with its expertise in CUSP and in enhanced recovery.
The American College of Surgeons, that knows a bit -- something or other about surgical
practices and about enhanced recovery, and Westat, that has significant data capabilities.
And finally -- next slide, please -- AHRQ has released new CUSP implementation toolkits:
a toolkit to improve safety in ambulatory surgery centers, that has tailored the implementation
of practices to improve safety in ambulatory surgery centers including the surgical safety
checklist, so that these approaches, these practices, are not simply borrowed from the
hospital setting, but are adapted to be useful specifically in ASCs; a toolkit to improve
safety for mechanically-ventilated patients that incorporates the project's bundle of
evidence-based interventions.
These interventions include low tidal volume ventilation, trials of reduced sedation and
weaning from the ventilator, and early mobility.
And finally, the toolkit for safe surgery in the inpatient setting, which is the product
of a project that reduced surgical site infections by 25 to 40 percent, and the release of this
is planned for later this year.
Next slide, please.
So, we return to the core slide which shows AHRQ's HAI prevention program spanning the
spectrum from research through implementation.
AHRQ is committed to helping the field generate new knowledge for preventing HAIs and translating
that knowledge into action, into the adoption of more effective practices for preventing
HAIs and improving the safety of healthcare.
Thank you for the opportunity to address the council.
>> Lonnie King: Dr. Cleeman, thank you very much.
Appreciate it.
So, we have one final presentation this morning before break, and we're going to turn to Dr.
Jane Knisely from NIH.
Dr. Knisely.
>> Jane Knisely: Good morning.
Thank you for the opportunity to present NIH's work on the CARB National Action Plan.
We play roles in goals two through five, and I've kind of broken those out as I go through
the talk.
Next slide, please.
So, just to orient everyone of who NIH is and who NIAID is, our mission statements are
here on the slide.
You can read them for yourself.
NIAID is part of NIH, and we are one of 27 institutes and centers.
We are the second largest.
And the focus of the division that I work in is on microbiology and infectious diseases.
We're responsible for all infectious diseases other than HIV/AIDS, so it's a big mandate.
And the budget of the NIH is divided -- it's about 10 percent is spent on research intramurally,
so we have scientists working on the NIH campus as well as through other facilities throughout
the country.
And the rest of the budget, most of it goes out the door to grants and contracts to fund
work throughout the country and around the world.
Next slide, please.
So, on the left, you see a photo of one of our guiding documents here, the National Action
Plan, which you're all very familiar with.
On the right, you see the cover of a document that NIAID put together in 2014 that outlines
our antibacterial resistance research strategy.
And what this document emphasizes is that we take a comprehensive approach to addressing
this topic by focusing on basic research, translational research and product development,
and clinical research.
And we do always have an eye towards the development of better ways to diagnose, prevent, and treat
antibacterial-resistant infections through all the work that we do.
In this document, you will also find some areas for enhanced emphasis that we identified.
So this is a few years old now, but we have, I think, made good on putting money where
our mouth is and stimulating work in those areas.
And so, that includes things like non-traditional therapeutics -- so trying to move a little
bit away from small molecule therapeutics, although they're still very important, but
to explore some other new types of therapeutic approaches that are coming on the horizon
-- and an enhanced emphasis on diagnostic technologies, because we view it as really
a critical component to addressing many aspects of this problem, as well as enhanced studies
to optimize how to use the drugs that we have.
So, the existing arsenal of drugs that we have, we need to make the best of them, because
we won't have them forever.
And so we have a number of studies to address that, which I'll talk about a little bit more
on future slides.
Next slide, please.
So, we do have just a little piece of goal two.
Surveillance is not really our area, but I think in objective 2.1, we are playing a collaborative
role here and bringing some of the technologies that we support and some of the infrastructure
that we have to enhance some of the collaborations that are going on.
So, the CDC and FDA Isolate Bank was already mentioned, and NIH is also a partner in that
effort and has provided sequencing services for some of the isolates that have been identified.
This is just part of NIAID's genomic sequencing program which has sequenced over 3,000 bacterial
genomes since 2012.
And all of our genomic data is rapidly released to the public through deposition and NCBI
databases, which is housed at the National Library of Medicine, which is another of NIH's
institutes and centers.
Also housed at NLM is the NIH National Database of Resistant Pathogens, which includes data
on over 130,000 pathogen isolates and includes genome sequencing data and drug susceptibility
phenotypic data when it's available.
And also on this slide, a couple of other technology services that we provide.
We have bioinformatic services.
One is referred to as PATRIC.
That's the bacterial one that we house.
And that group is responsible for developing bioinformatic tools, and they can also assist
researchers with analyzing all of the data that are coming out of these new technologies.
So, that is a resource for the community, along with genomic sequencing.
We have the capacity to sequence collections of isolates kind of in an on-demand fashion
for people in the community, free of charge.
And we also have structure determinations.
So these are things that aren't captured on other slides, so I thought I would mention
them here.
Next slide, please.
So moving on to objective three, which is the -- or, the goal focused on diagnostics.
We've done a lot of -- we have many programs where investigator-initiated projects for
diagnostic development can come in.
So, our small business grant programs, investigator-initiated R01s, things of that nature.
But we've also issued a lot of targeted funding opportunities, and I've just listed a few
here that have come out in the past few years that are really focused on the goals laid
out in the CARB National Action Plan.
So, the one from FY 15 -- and there's more information about all of these available online
-- partnerships for diagnostics to address antimicrobial resistance of select bacterial
pathogens.
This was really focused on diagnosis of infections in healthcare-associated settings, and it
brought in some really interesting technologies that are progressing really well, and it's
exciting to see.
The one for FY 18 is actually currently on the street.
So you know, for any investigators out there, feel free to check it out, submit an application.
Partnerships for the development of clinically-useful diagnostics for antimicrobial-resistant bacteria.
And the focus of this one is phenotypic susceptibility testing.
And so, we've heard that that is -- that is a gap, and so we're trying to address that
gap through a targeted funding opportunity.
And then also on this slide, a line -- just a single line devoted to what is actually
a pretty big commitment.
This is a collaboration with BARDA, an antibacterial resistance diagnostics challenge competition.
It's a new way of doing things that NIH hasn't really done before.
And so this is a phased challenge competition.
Total $20 million pot, some smaller amounts dispersed at different steps along the way
and then a bigger pot at the end.
So earlier this year, 10 semifinalists received $50,000 each for prototype development.
The focus of the projects is either on rapid determination of -- or rapid discrimination
between viral and bacterial infections or rapid determination of antibiotic susceptibility
tests.
And the focus is also on point of care tests, so things that are going to be maximally useful
in the clinical setting.
The semifinalists are a mix of academic and companies, and there's a diversity of approaches,
and three of those 10 received previous NIAID support for their technologies.
The next step is that they will submit prototypes and analytical data in September of next year,
and then up to 10 finalists will be selected, also next year.
And then, the third phase is the evaluation of those prototypes in two independent CLIA-certified
laboratories.
And then, the finalists will be -- or the winners will be announced in 2020.
So that's the prize competition.
Next slide, please.
The Antibacterial Resistance Leadership Group is a program that we have that spans -- it's
a clinical focused program, but it spans both diagnostics and drug development and drug
optimization studies.
So, I'll mention it again later.
This is some of their diagnostics work.
They've really hit diagnostics very hard, and I think it's promising to see some of
the work that they're doing.
They have a project that is focused on host-based signatures to distinguish viral from bacterial
respiratory infections.
They have some resources for the community, including a virtual viral repository where
different members from this group of clinician investigators have clinical isolates with
associated metadata.
They're stored in their labs in their freezers.
They have an online catalog where people can go and request those isolates for studies
on drugs, on diagnostics, whatever.
So, it's a complement to the isolate bank that's been mentioned a few times.
They also have the capability to collect clinical specimens to aid diagnostics development.
So, this is something they've been able to do a number of times now for a couple of companies.
And they are working on a really novel idea of a master protocol for validation of multiple
diagnostics simultaneously.
So, for the same clinical syndrome, can you use the same patients to validate multiple
tests at the same time?
And it was logistically very challenging to set the first one of these studies up, but
it is up and running and rolling and actually going very smoothly.
So that's a very exciting development.
And they are about to launch a clinical trial that's sort of meant to be a definitive trial
for the United States on using procalcitonin levels to identify community-acquired pneumonia
patients who will not benefit from antibiotics -- randomized, controlled placebo trial.
Next slide, please.
So these are all of our responsibilities in Goal 4.
They get a little tangled from here on out, so these are the objectives.
And next slide, I'll just kind of tell you broadly about the things that we are doing.
So, again, for CARB goal four, this is the development of antibacterial and vaccines.
And we have, once again, issued quite a few different funding opportunities for antibacterial
therapeutics since 2015.
And that includes things that are a little bit more basic, like our new systems biology
centers, things that are a little bit more translational, like our partnerships programs
on non-traditional therapeutics and host-targeted therapeutics, and also clinical research.
So, some of the work that ARLG is doing, some of the things going on in some of our other
centers that I'll mention.
We've also had three targeted funding opportunities for antimicrobial-resistant vaccines since
2015.
One is focused specifically on gram-negative bacteria.
One is focused on TB, and then one is part of a bigger initiative, but includes vaccines
on resistant pathogens on the CDC threat list.
All of this is supported by preclinical services and clinical trials networks, which I'll talk
a little more about.
And we also conduct workshops on targeted topics to help bring groups together to discuss
challenges and gaps in the field and to really help guide us when we're trying to put together
kind of where to target our funding next.
Next slide, please.
I did just want to give one example, because it's a lot of, you know, we did an RFA here,
we did an RFA there.
But here's an example of kind of how our different funding mechanisms can work in concert to
produce something pretty cool.
So we have funded, for many years, an investigator called Andrew Myers who's at Harvard University.
He was working on -- he's a chemist.
He was working on synthesis of novel tetracyclines, so complete synthesis of tetracyclines.
And you know, he was going on, he was synthesizing these things and doing really well, and ended
up founding a company that's called Tetraphase Pharmaceuticals.
And then, at a certain point in time, his grant came in for renewal, and the study section
said, "Well, tetracyclines.
These are really old drugs.
This is not innovative, you know.
We're not going to support this."
We actually were able to sort of rescue that one from the dust bin and say, "No, actually,
this is really valuable," and were able to fund it through a selective pay to keep that
-- to keep that work going.
We have very few slots, but we can do it every now and then.
So, the sort of more basic work was funded through grant support.
He then -- that company then went on to receive grant and contract support for preclinical
development of some of their candidates, and then some of their candidates have moved on
to BARDA and have actually completed phase three clinical trials.
So, it's a really cool example of how support throughout the development enterprise can
work in concert.
Next slide, please.
This is just a depiction of our preclinical services.
This is a suite of services that we have available to researchers, free of charge.
We will provide data and tools and technologies.
We can do things like in vitro assessments of antimicrobial activity, MICs, MIC90s, things
like that.
We have interventional agents contracts that can do pharmacokinetics and toxicology studies.
Can also do chemistry manufacturing and control.
We can do GMP manufacturing.
We can do testing of -- for both drugs and vaccines.
And we also have animal model capabilities so we can establish new animal models on demand
to help provide data that companies need to move forward.
Next, please.
In terms of our clinical programs, so the different types of programs are listed on
the left, and then the -- sort of the buckets of studies that they conduct are on the right.
The targeted clinical trials is a program that started about a decade ago and was initially
a series of solicitations focused on addressing questions like dose, duration, and how to
administer the drugs that we currently have to optimize them and reduce the risk of antimicrobial
resistance.
And this came up a little bit yesterday.
So, a couple of them have finished now, and, well, yes, most of the studies -- most of
the clinical trials that have been done looking at short versus long course have shown that
the short course is equally good.
Actually, in our acute otitis media trial, they found that it's -- that the short course
is not quite as good, clinically.
And so, this is -- this is why we need to do the experiments.
So, there are some areas where it's absolutely fine, and then there are others where the
data say, not so fast.
The Antibacterial Resistance Leadership Group is picking up on some of those studies.
They're doing one in pediatric CAP.
They're doing, also, optimization and PK/PD studies, and we also have a couple of other
things where we can support companies who come in and need a phase one trial or other
types of studies, as well as the STICTG, which can do gonorrhea trials.
Next slide, please.
I'm going to skip this one, because I think BARDA will cover it.
Next.
And just the last is our international activities.
Primarily, what we do here is about communication and collaboration with our counterparts in
other countries.
And much of it is driven by our investigators at the scientific level, and that's the way
we like to have it.
But what has been very useful to us is the Transatlantic Task Force on Antimicrobial
Resistance, where we have gotten to know our counterparts in the European Union and have
been able to align some clinical trials to help make them the most informative that they
can be.
And we've also done some workshops and presentations with them as well.
And that's all.
Thank you very much.
>> Lonnie King: Dr. Knisely, thank you very much.
So I want to thank all of our presenters this morning.
Great information.
You're very succinct and very impressive, so thank you for what you're doing.
So we're going to take a 10-minute break right now.
Get coffee in hand, and we have a lot more to hear.
So we'll welcome you back about 10:40.
Thank you.
>> Martin Blaser: Panel members, write down your questions so
we don't forget.
Thank you.
-------------------------------------------
PACCARB 7th Public Meeting Day 1, Pt 6: Council Q&A - Duration: 22:25.
>> Sara Cosgrove: We now have time for some discussion, and
we're going to do the official thing where we do this, just to indicate that we have
a question, rather than what we usually do, which is hands flying all over the place.
And I know Dr. Blaser would like to start with the first question.
>> Martin Blaser: Thank you, Sara.
Thank you, panelists, for really education.
I want to address Dr. Szymczak and Dr. Mangione-Smith; it's the same question but you may have different
approaches.
We saw from the CMS data that there's a big geographic differences in prescribing patterns,
and we've seen that in many different studies.
Dr. Hicks has produced a lot of work that the geographic distance -- differences are
regardless of age, in young and old.
So, there's a real geography, and, therefore, there must be a sociology, or a culture, because
it doesn't -- the real rates of serious bacterial infection don't coincide with those maps.
So, what's underneath this, and how do we fix it?
>> Julia Szymczak: I'll go ahead.
So -- well, first I will say that I am aware of those data, and, actually, when I first
saw the map of -- that indicated that it -- it really lit all of my sociological light bulbs
went off, in that this is a fascinating problem that is exactly the way you interpreted it.
This is a problem of culture and social beliefs and norms.
So, I am not aware of anything as of yet that has actually investigated the reason why,
but it is a problem that I think we need to do some observations of, you know, what's
happening in these clinical encounters.
We need to talk to prescribers, and patients, and family members in those areas to understand
how they think about antibiotics and what they believe about health, illness, and disease.
And what prescribers think about their patients and their capacity, you know, to come back
if they have, if they get worse.
So, I think that question is a sociologic one that deserves further in-depth inquiry.
>> Rita Mangione-Smith: So, in our current trial, we're all over the
country in practices, and I will be fascinated to see if there are geographic differences
in our ability to affect change.
We did some of our initial work down in Los Angeles and had no problem finding over-prescribing
and inappropriate prescribing, but when we did a second study after I moved up to Seattle
-- it was, like, wow -- all I had to do was move to fix the problem.
[laughs] So I'm excited to find out whether this kind of intervention -- I think it is
going to have variable effect because of context.
And I think that's a ripe area to study and understand why we see the geographic differences
we do, because there is clearly a different culture and context.
>> Martin Blaser: And the differences are big --
>> Julia Szymczak: Huge.
Yeah.
>> Martin Blaser: -- large.
Large differences.
>> Sara Cosgrove: Lori, have you done any work with that, that
you want to add, since we always talk about your graph -- your chart, your map, I guess?
>> Lori Hicks: So we have actually looked at some of the
reasons for the geographic variability, and I think I've mentioned this previously.
But when we look at conditions for which antibiotics are not warranted, so, bronchitis, non-specific
upper respiratory infections -- we certainly see -- oh, thank you -- we certainly see that
there is a difference in the frequency of prescribing for those conditions.
So, in the Southeast, in the Appalachian region, prescribing for uncomplicated acute bronchitis,
as well as non-specific URI, is higher, so those are conditions that don't warrant antibiotics.
And that's compared to the Pacific Northwest, Hawaii -- I just did an interview, and they
asked, "Why is Hawaii so much lower?"
Well -- and I also do think that there some population-level differences in terms of health
that are also driving some of the differences that we're seeing.
So, I think, to answer the question, we'd have to look both at the sociological issues
that are driving it, as well as the population-level health factors.
And I don't know how to combine those two into one study but I think Julia and I need
to talk about that.
>> Sara Cosgrove: Thank you.
Dr. Caliendo.
>> Angela Caliendo: Thanks.
So, my question is for Drs. Szymczak and Safran.
You've both referred to fear, getting providers over the fear factor.
So -- any insights into, one, what they're afraid of, and two, what to do about it?
Because I could see that people would be afraid of being sued, or their patient really having
a bad outcome, or being afraid of, "You're just adding work to me, you're -- I'm going
to be here longer."
I mean, those are really different fears, and, so, do you have any insights into that?
>> Julia Szymczak: Sure.
So I think, you know, as I said, again this is the emotional dimension of prescribing
I don't think has received the attention that it needs, but I can hypothesize, based on
my many interviews with prescribers, that there are diverse types of fears, many of
which you discussed.
And I think a lot of this is about, you know, changing perception.
So, the disaster -- the prevention of disaster -- is a sticky motivation.
It sticks to the front of your brain, it's very, you know, it's just there.
It's more there than the sort of vague epidemiologic ether that we all live in.
And so, I think part of this is both identifying what people are afraid of, and then addressing
each of those domains of fear with -- either it's an education to help to reveal to people,
"Look, people actually aren't getting sued," if that's the case, for antibiotic -- you
know, sort of like pulling back on antibiotics.
So, trying to counter the things that people are afraid of.
And getting antibiotic ambassadors or advocates from different disciplines.
So, for example, like neonatal ICU.
Neonatology is a very interesting area that I spent a lot of time investigating, and they're
very resistant to stewardship in a lot of cases and I think trying to find change agents
from within to address the fears of their professional colleagues might go a longer
way.
But there isn't an answer to that just yet.
I still think we need to do more exploration of what those fears are so we can address
them systematically.
>> Elana Safran: Yeah, I think my answer, in some ways, is
quite similar.
I don't know the context very well for stewardship, but I would think, first, where are there
information asymmetries, where a provider or patient might know something different
and not be sharing it.
Or they have expectations about the other, where it might be possible to have literature,
or something, hanging on the wall in the exam room to help equalize what everyone knows
and what everyone is committing to.
And then, the other thing that I would look at, also, is, kind of, time inconsistencies
or asymmetries, where if you're afraid of something happening way in the future versus
right now -- how do you bring, kind of, the future to the now moment and vice-a-versa,
so the benefits of what you do now toward the future.
>> Jeffrey Linder: Sorry for jumping the gun on my talk, but
this is -- actually it's not in my slides -- but I sort of want to make the point that
there's an interesting paper that came out a couple months ago about the dominant gists
that doctors have when they're confronted with -- and this is an out-patient, overwhelmingly
about upper respiratory infections -- what's the balance they're trying to strike, and
what mental construct are they using?
And the dominant one was, "Antibiotics aren't that dangerous.
What's the harm?"
Or -- that was one of them, and the other one was, "Something bad could happen to my
patients, and I'm really protecting them by giving them an antibiotic."
And my solution -- untested, but I talked to residents -- it's to try to replace the
squishy stewardship.
Because we're really talking about an instance where antibiotics have no chance of helping,
and a real chance of hurting, if we're talking about colds and acute bronchitis -- replace
the squishy balancing the benefit of my patient with societal harm with righteousness.
So, not in a paternalistic way, but you're there to do the right thing by your patient
and protect them from harm.
And so, like, how do we replace that gist?
And I think we have a lot of work to do on that.
But that's one strategy I've used.
>> Sara Cosgrove: Thanks.
Alicia Cole is on the phone.
>> Alicia Cole: Yes.
You know, I loved the presentations this afternoon.
They've been so informative and so well done.
The consistency theme that I'm seeing is the need for better communication and better interpersonal
skills at the -- at the point of care.
And so, I'm wondering, because when you have a parent who feels like they're not getting
answers -- or a patient, in general -- who gets, like you said, that negative response
with no follow-up.
It may not be that you're necessarily seeking antibiotics, you're seeking answers, or help,
or suggestions.
So, my question is, how are we -- and what -- can you tell us what you're doing bring
this to medical schools and training, and taking this research and using it at the point
of, you know, training doctors and care providers before they go out into the community and
they're actually dealing with patients -- teaching some of these techniques?
And are you working with schools currently, and do you have a program in place that you
will be sharing this information, and incorporating this in some of the training?
Thank you.
>> Rita Mangione Smith: So, one of our full intentions, once we're
done with the trial and we really feel whether -- first, we want to show proof of concept.
We want to really show that doing -- we think, based on our observational work that we will
see the prescribing needle move, and we will have been able to change the way people are
communicating during visits.
Once we're able to show that, it is our full intention to take the suite of tools that
belong to this intervention and make them quite publicly available.
So, we're already working with American Board of Pediatrics to try to make this a Maintenance
of Certification Part 4 program.
So, that if you measure your prescribing at three different time points and, you know,
go through the program, you can get your MOC4 credit for people already out in practice.
I have a very strong interest in medical education and using this as an educational tool during
-- probably, right now, pediatric residency training is where I would put it in -- but
I could see it going down even further that that.
So, I have a strong desire to disseminate it and we'll look for partners in that wherever
I can.
>> Michael Craig: And I would just add to that.
CDC is working with CMS on the MIPS program, specifically looking at outpatient stewardship
and how we can take some of these tools and provide them as part of the CMS-required training,
so that when physicians have to do their training as a part of the MIPS program that this is
a component that they could choose to do and have the most up-to-date research and the
most up-to-date understanding of best practices in this area
>> Alicia Cole: Thank you.
>> Sara Cosgrove: Dr. Apley.
>> Michael Apley: Thank you.
Dr. Szymczak, finally, it's good to meet you.
So I -- this sounds like the start of a joke.
I'm a veterinarian, and I'm standing in line at the airport with a pediatrician and an
internist -- walk into a bar.
[laughter]
>> Robert Weinstein: Usually there's a rabbi.
>> Michael Apley: There's a rabbi -- no rabbi in this one, thank
you.
[laughter]
But we were standing there, and I'm newly invigorated with my knowledge from serving
on this great council, and we were talking about bronchitis.
And he said, "Well, where are you going now?"
And I said, "The PACCARB."
And he said, "What's that?"
So we talked about that and I said, "You know, one in five -- some of the data shows that
only one in five would actually ever need an antibiotic, truly need it."
And the answer was, "As soon as you can tell me which is the one, and which is the four,
I'll stop giving it to the five."
Which gets back to the component of avoiding that rare, but catastrophic, worst case -- and
Angie asked, along this line, with the fear, et cetera -- but I really think we may -- and
you probably don't -- but I have underestimated the concern for avoiding even that one in
a 100 rare occurrence where you're caught having not used the antibiotic.
And then, the other thing, I think, I see among multiple types of health care professionals
is how far they view the issue of antimicrobial resistance, even to the point of really questioning
what a resistant isolate actually means to clinical outcome.
It sounds like that's a fairly consistent finding from what you all are finding?
>> Julia Szymczak: Yeah, that the risk perception is sort of
very far removed from the bedside at the moment in which the decision is to be made.
And again, my argument is that person sitting in front of you -- that mother, that sick
person, whatever -- that's what's really overriding your -- these kind of bigger picture concerns.
>> Jeffrey Linder: Others have looked at this.
Again, sorry for jumping into my own talk, but I have a whole slide that says, like,
diagnostics are not the answer for ambulatory.
Because even if you take people who have acute bronchitis, and I'm going to show you data
from an intervention we did, but part of the trial we looked at adverse outcomes when we
reduced the inappropriate antibiotic prescribing rate.
And the return rate for something bad was less than 0.05 percent.
And so, our perception -- you know, we all remember the bad thing that happened -- but
it really is a one in 10,000 thing.
And you're going to run into it in your career, but it's really, really rare.
And there's plenty of good evidence that even the one in five with acute -- 40 years of
clinical trials say that, you know, antibiotics don't help for acute bronchitis.
So, some of them are bacterial -- antibiotics still don't help.
>> Rita Mangione Smith: One of the things we've done with the DART
intervention is, it's not just the communication piece.
We're trying to take a very multi-faceted approach, so I've got my ID colleagues -- actually,
Julia works with one of them -- is Matt Gerber, where they are doing an equal amount of education
around how rare things like mastoiditis are, or that you're going to cause meningitis in
a young kid who you don't treat for a bacterial otitis.
So, we're trying to address that sort of fear factor also with data, basically showing that
this is so rare -- however, look how often Stevens-Johnson syndrome happens, and that's
devastating.
And that happens more often than these things that you're worried about, theoretically.
So --
>> Sara Cosgrove: Go ahead.
Helen's cutting in line.
>> Helen Boucher: Sarah's allowing me to cut in line.
I think that that gets at an even bigger social issue, which is the issue of what we're willing
to -- the risk we're willing to accept for the patient before us, versus the societal
issue.
And this notion -- the thing I was going to ask about was this notion that we encounter
in stewardship sometimes from our colleagues who say, "You don't understand how sick my
patients are, because I'm doing X crazy procedure that you don't know anything about."
[laughter]
And it's true -- I don't know anything about that particular cardiac procedure, what have
you.
And so overcoming that fear is difficult.
But this other issue, I think, the issue of having one child getting mastoiditis -- you
know, in the U.K. they look at this differently, and I lived there twice.
And when my daughter was in kindergarten a little boy in kindergarten got a facial nerve
palsy from mastoiditis from untreated otitis media.
And the lesion was that the child was not told to follow up after being seen the first
time, and so that's how it was missed.
But societally, they're very comfortable with that, that, you know, we're going to protect
the population, we're going to spend less on health care -- it's a very different conversation
in society.
And I think here that's kind of been one of the elephants in the room is, we discuss these
issues and will we ever even get to prioritization of what comes first.
It's out there.
>> Female Speaker: That's cultural.
>> Helen Boucher: Yeah.
Yeah.
>> Jeffrey Linder: This idea that, you know -- another dominant,
sort of, mental construct we have as the doctor is, "I do everything for my patients."
But it's not even in the back of a lot of doctors' minds that they could be doing too
much and hurting their patients.
>> Martin Blaser: I just want to jump in on this one because
every study shows that this enormous variation between practitioners.
There's some practitioners that prescribe antibiotics all the time, some who prescribe
it almost never, and a lot in the middle.
And in every study, whether it's regional, or country, or state, or group practice that
variation exists.
So, we have to come to grips with that one, too.
But there are some doctors who can seem to withstand all those pressures, so what makes
them different?
>> Jeffrey Linder: Well, if you look on a national basis -- so,
Dr. Hicks' data from a while ago that totally lines up with the Blue Cross Blue Shield report
that came out three weeks ago -- that the antibiotic prescriber rate in the United States
is about 820 or 830 prescriptions per thousand people per year.
And in Sweden it's like 350, and they want to get it to 250, and the Swedes are not dropping
dead from, you know -- not getting facial nerve palsy.
So we're clearly over-medicating and we could do similar studies here.
>> Sara Cosgrove: So we'll do one more question from Jay, and
then we can keep the same line of questioning going after the next set of presentations
because they're going to be similar.
So, don't be upset.
>> Jay Butler: Thank you, Dr. Cosgrove, and I appreciate
the re-ordering because Dr. Apley is a very tough act to follow.
I don't have a joke.
Thank you for all of the presentations.
I think this has really been a great overview.
And my question is for Dr. Szymczak.
You were talking about defining new social norms which I think is our goal, and is very
possible.
And if you don't believe that, just imagine we were having this meeting 55 years ago.
We would not have come into the room to a bottle of water, we would have come in and
had an ashtray in front of each one of us.
Whereas, if I lit up a cigarette right now, you'd be calling security.
So social norms do change.
And we've heard from earlier presentations how human factors engineering, and some of
what I would interpret as making the right choice the easy choice, is how we begin to
make those changes.
This group has just spent a year thinking very long and hard about various types of
incentives, and there are positive incentives, or incentives for behavior that we'd like
to see, and incentives for negative behavior.
And there was a reference earlier to the HCAHPS survey, so it brought to mind question number
14 about, "Has your provider done everything they could to control your pain?" which I
know a number of people have raised questions about whether that creates a incentive for
negative behavior as it relates to prescription of analgesics.
So, my specific question -- I am getting to one -- is, are there incentives for inappropriate
antimicrobial prescribing, or antimicrobial use, that we should be focusing on, or that
you would want to call our attention to?
Thank you.
>> Julia Szymczak: I think that's a real interesting question.
I have been thinking about that a little bit.
I think that, you know -- again, my disciplinary perspective is to think about social incentives.
So, there's a lot of literature on the impact of financial incentives, and I tend to err
on the side of how can we make doing the right thing the popular thing.
And so, if that is -- and, you know, and I think we really have to go to the individual
clinical communities to try to leverage thought leaders or people who can sort of lead the
cause, and be the ambassador, and be the advocate to set the positive intention.
But it's very hard, and I think, you know, there are certainly other examples of social
movements -- and tobacco is a great example of -- it takes regulatory pressure, it takes,
you know, group norms, it takes people seeing bad outcomes being made very clear.
So, again, I would say it's a social -- it should be a social incentive.
That should be something that we should be thinking about -- how do we engage individual
groups to reframe the issue, alongside your financial and, you know, your carrots and
your sticks?
I think it's a combination of all.
There's not going to be a one size fits all.
>> Sara Cosgrove: So we're going to take our short break, as
it says.
It's 10 minutes this afternoon, as opposed to five.
So if everyone could come back at 2:40 we'll reconvene this discussion.
-------------------------------------------
SIX GUILTY PLEASURES about ME - Duration: 1:42.
I'm very hesitant to even tell you.
A lot of people lose respect for me when I tell them this.
Hey folks!
This is six guilty pleasures about me.
So this will be embarrassing.
Number one. I like Legally Blonde okay.
That movie is good.
It's got a great plot line.
I love how she proves everybody wrong by going to law school.
Number two is that I like listening to the Joe Rogan podcast.
I just really love how he interviews such interesting people.
Number three you might already know.
I have an unhealthy obsession with quesadillas.
I do like the taste of a quesadilla, but I mainly just love to film myself making them.
Mostly because I think it's funny.
Number four is that I like a lot of weird foods such as:
black licorice, hot cheetos, pickles, garlic stuffed green olives.
Guilty pleasure.
Number 5 is I love to trim my fingernails.
I love a good pair of nail clippers. Yeah I love to get the hang nails off.
Number six is by far the most embarrassing.
I'm very hesitant to even tell you.
A lot of people lose respect for me when I tell them this.
I like listening to Owl City sometimes okay.
Just that one album with the boat on the front of it.
I just think that it's very happy and uplifting.
It puts me in a good mood.
I just, I understand if you're not watching this video anymore.
Not something I'm proud of.
A bonus guilty pleasure is that I enjoy a good dab.
So yeah. Welcome to me.
Không có nhận xét nào:
Đăng nhận xét