PowerPoint Presentation · Pneumonia Pneumo- thorax Anemia Pulmonary Embolus Musculoskeletal Pain...

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The Defense Advanced Research Projects Agency (DARPA) was established in 1958 to prevent strategic surprise from negatively impacting U.S. national security and create strategic surprise for U.S. adversaries by maintaining the technological superiority of the U.S. military. (www.darpa.mil)

http://www.darpa.mil/

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POCT:

The ER Doc’s

Perspective

W. Frank Peacock, MD, FACEP

Professor, Emergency Medicine

The Cleveland Clinic

Time Dependency: It’s Not a Hard Concept

Treat Early or Die

HYPOGLYCEMIA

HYPOXIA

VENTRICULAR TACHYCARDIA

MYOCARDIAL INFARCTION

CEREBRAL INFARCTION

PNEUMONIA

HEART FAILURE

Door to Brain Time

• Prospectively collected Tn TAT data during all ED shifts

• From patient ED arrival until Emergency Physician aware of result

Peacock WF et al. Acad Emerg Med. 2004;11(5):569–570.

Results 25 participating hospitals

N=1,360 patients

Overall

Mean DTBT 115.770.1 minutes Median 100; IQR=73,138

Central lab

Mean DTBT 119.2 70.5 minutes

Median 103; IQR=76,141

Point of Care

Mean DTBT 68.2 40.8 minutes

Median 62.5, IQR=43,83.5

Peacock WF et al. Acad Emerg Med. 2004;11:569–570.

Saves about

1 hour

The Use of a Quantitative POC System Greatly

Reduces the Turn Around Time of Cardiac

Marker Determination

Gaze D, Collinson PO, Haass M, Derhaschnig U, Hirschl MM,

Katus HA, et al for the CARMYT Multicentre Study Group

Gaze D et al. for the CARMYT Multicentre Study Group. Point of Care: The

Journal of Near-Patient Testing & Technology. 2004;3:156–158.

• 5 hospitals

• 4609 Tn POC samples

– 3447 split and sent to lab for CKMB

Locale Hosp

Type

Transp POC

Tn

CL

CKMB

Diff

(mins)

ED Univ Pneumo tube

210.2 (n=1879)

1072.3 (n=1744)

862.3

ED Univ Courier 220.5 (n=855)

721.7 (n=689)

501.5

CCU Rural Nurses 120.5 (n=471)

14764.1 (n=150)

13564.1

ED Muni Pneumo tube

220.8 (n=706)

900.5 (n=185)

681.1

ED Univ Pneumo tube

180.5 (n=698)

521.4 (n=679)

341.4

All 200.2 (n=4609)

851.5 (n=3447)

651.5

Gaze D et al. for the CARMYT Multicentre Study Group. Point of Care:

The Journal of Near-Patient Testing & Technology. 2004;3:156–158.

Delay = Bad Care

• N=42,780

• Long ED stays less often received guideline-recommended

NSTEMI therapies Ann Emerg Med. 2007; 50; 489-96

Delay = Death

N= 13,934,542

• Adverse events increase with the mean LOS in similar patients in

the same ED shift

• OR for Death if LOS ≥6 v <1 hr cohorts

– Hi Acuity 1.79 Low Acuity 1.71 BMJ 2011; 342:d2983

Overcrowding = Long waits

Long waits = Death

• N= 62,495

• Risk ratio for DEATH

– Per hour of ED stay = 1.1 (p < 0.001)

– Per hour of ED wait = 1.2 (p=0.01)

MJA 2006; 184: 208–212

Delay = Bad Care

• N=694 patients Delayed/No antibiotics

– OR 1.05 for each additional WR patient

– OR 1.14 for each additional WR hour

Ann Emerg Med. 2007;50:510-516

Delay = Bad Care

• N=13,758

• Nontreatment of pain associated with

waiting room number

OR = 1.03 for each additional waiting patient

Ann Emerg Med. 2008;51:1-5.]

Delay = Bad Care

• N=162 “boarded” patients (waiting for room)

• Undesirable event • Missed meds, lab results, arrhythmias, or other adverse

events

• 27.8% had an undesirable event

Ann Emerg Med. 2009;54:381-385.]

What business would

intentionally kill its customers?

• If you had a way of getting data quickly,

why wouldn’t you do it?

I Got Three Jobs

Diagnosis

Treatment

Disposition

It would be convenient if patients

had the diagnosis tattooed

on their forehead

Erectile

Dysfunction COPD

The Shortness of Breath Pie

http://www.mrs-o-kitchen.com/blueberrypielarge1.gif

Heart Failure

Pneumonia

Pneumo-

thorax

Anemia

Pulmonary Embolus

Musculoskeletal Pain

MetHgb

Mondor’s

Syndrome Tietze’s

disease

COPD

exacerbation

Pneumomediastinum

Breast

Cancer

Cyanide poisoning

FB

Aspiration

Metabolic

acidosis

Anaphylaxis

Chemical

Exposure

Mediastinitis

Lung

Cancer

Anxiety

Panic Attack

DKA

Subdiaphrag

Abcess

Empyema

Amniotic Fluid

Embolus

IVDA Pulm Infarction

Asthma

http://www.mrs-o-kitchen.com/blueberrypielarge1.gif

Prehospital Effects

• 8,315 EMS runs

• 499 HF

• Overall Mortality = 10.9%

• Excluded BP < 100

• Tx= ntg, ms, lasix

• Linear rln btwn high BP & Tx

• Treated n=241

• Untx’d n=252

• If EMS Tx: 36 min sooner

• Scene time: 1.9 mins longer

Wuerz R et al. Ann Emerg Med. 1992;21:669-74.

If treated,

OR of survival 2.51 (1.37-4.55) p<0.01

Early treatment works

The Scary Part

• 106 non-HF final dx…..BUT tx’d for HF by EMS

– Asthma, COPD, pneumonia, bronchitis

– Represented 15% of dyspneic patients

Mortality (p<0.05)

Non-HF pt. treated for HF 13.6%

No treatment 8.2%

Treated with bronchodilators 3.8%

Prehospital Effects

Wuerz R et al. Ann Emerg Med. 1992;21:669-74.

Impact of BNP Assay on Accuracy

Maisel AS, NEJM, 347(3), 161-7, 2002.

26 %

wrong

Mortality vs. Quartiles of Diuretic Time & BNP Level

0

2

4

6

8

<1.05 1.05-2.22 2.23-4.98 >4.98

<449

450-864

865-1738

>1738

BNP

pg/mL

Mo

rtali

ty

Time to Diuretic/BNP

46,599

ED ADHF

4.3

10.9

4

20

4.5

7

23.1

19

27

0

5

10

15

20

25

30

Mortality % ICU Hospital ICU LOS % Invasive Rate (%) Transfer LOS (days) (days) Procedures

4,096 in ED 1.1 hr

3,499 inpatient 22 hr

*P = 0.0001

*

*

*

*

*

253% 500% 150% 155% 142%

Vasoactive

by location

Peacock WF et al. Ann Emerg Med. 2003;42(4):S26.

Liability Perspective

Guidelines on the Treatment of NSTEMI

Biomarker data be available to the

physician within 30–60 minutes

following the patient’s arrival in the ED

Braunwald E, Antman EM, Beasely JW, et al. Circulation. 2002;106:1893–1900.

American College of Cardiology

American Heart Association

9 Cardiologists and

3 Emergency Physicians

4 month Internet writing

• Followed by a consensus

panel meeting

• Further refinements and

publication ready

• Topical

• 153 references

Silver MA et al. Congest Heart Fail. 2004;10(5 suppl 3):1–30.

• The laboratory should perform BNP

testing on a continuous 24-hour basis

with a turn-around-time (TAT) of

60 minutes or less

• The TAT is defined as the time from

blood collection to notification of

test result to physician or caregiver

• Either central laboratory instrumentation or

point-of-care testing systems are acceptable

Consensus Statement 1.1

Silver MA et al. Congest Heart Fail. 2004;10(5 suppl 3):1–30.

Can’t figure out the liability

perspective

Sunday in the ER

Operational

Perspective

Cleveland Clinic ED 32 beds

– 18 critical care – Most get marker testing

– 14 fast track – Rare marker testing

Average LOS ~4 hours = can handle 152 pts/day

If decrease LOS ~3 hours = can handle 228 pts/day

An additional 76 pts/day

– @ mean billing of $250/pt = in gross billables $19,000/day

– If only get an extra 30 pts/day (40% of 76) = $7,500/day

– If only 30% (n=10) of these get marker testing = $2,500/day

– If only 50% (n=5) of these get out 1 hour early = $1,250/day

– If collection rate is 30% = $375/ day………. $136,875/yr

Lets talk about

reality…

Time, Risk & Money

They dont’ really matter

if its your family

Got a daughter?

Put your money

where your mouth is

2006 Press-Ganey

• 1.5 million ER patients, >1,500 US hospitals

• Mean ED LOS = 4h • 18 mins vs 2005

• LOS for all states, except Hawaii.

• ED LOS increases 30 minutes for each 10,000 vol

• State ED LOS: 158 to 381 mins (> 6 hours)

• Patient satisfaction

– Lowest 3:00-11:00 p.m.

– Highest 7:00 AM – 3:00 p.m. (busiest ED time)

• Patient satisfaction a direct function of ED LOS • 89.3 if < 1 hour

• 77.7 if > 4 hours.

http://www.pressganey.com/ER-report.pdf




Mount Sinai

Saint Alexis Hospital

Guess who is driving away???

There goes a

Citroen…………..

2006 Press-Ganey Highest levels of patient satisfaction

“These cities

represent some of the

most competitive

health care markets in

the country and their

exemplary focus on

the patient’s

experience is setting

a new standard for

excellence,”

1. Milwaukee

2. Indianapolis

3. Columbus

4. Oklahoma City

5. New Orleans

6. Detroit

7. Nashville

8. Cleveland

9. Kansas City

10. Chicago





We are the BORG

My Ulcer

Admit them all

and let the

insurance

company sort

them out…

Discharge them all

and let God

sort them out…

ADHERE CART: Predictors of

Mortality

SYS BP 115 n=24,933

SYS BP 115 n=7,150

6.41%

n=5,102

15.28%

N=2,048

21.94%

n=620 12.42%

n=1,425

5.49%

n=4,099

2.14%

n=20,834

BUN 43 N=33,324

Greater than Less than

2.68%

n=25,122

8.98%

n=7,202

Cr 2.75 2,045

Highest to Lowest Risk Cohort

OR 12.9 (95% CI 10.4-15.9)

Fonarow JAMA 2004; 293:572-80.

Mortality According to Time in Hospital and Troponin Status at Presentation

Troponin-positive

Troponin-negative

Days in Hospital

Cu

mu

lati

ve

Mo

rta

lity

(%

) 25

20

15

10

5

0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

P <0.001*

*Dashed lines show 95% CI

Peacock WF et al. N Engl J Med. 2008;358:2117-26.

In-Hospital Mortality Risk by Initial BNP and

Troponin Levels

48,629 (63%) out of 77,467 pt episodes had BNP assessment at initial evaluation

42,636 (87.6%) with troponin I or T along with BNP levels

Q2 2003 to Q4 2004

2.2

4.44.8

10.2

0

2

4

6

8

10

12

InH

osp

ital

Mo

rtali

ty

BNP < 840,

Tn Neg

(n=20439)

BNP > 840,

Tn Neg

(n=19827)

BNP < 840,

Tn Pos

(n=734)

BNP > 840,

Tn Pos

(n=1626)

P<0.0001

Business You can have any two

Faster

Better

Cheaper

Fini’

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w w w . b a n y a n b i o . c o m

Name and Title

Here

Banyan Biomarkers, Inc. Traumatic Brain Injury Diagnostic Test

“Bench to Bedside”

The Banyan Biomarker assays are for investigational and research use only and are not intended for clinical diagnostic purposes.

Jackson Streeter MD Chief Executive Officer

[email protected]


Banyan Biomarkers Overview

Located in Alachua, FL and Carlsbad, CA

Major Discoveries at McKnight Brain Institute at University of Florida

Intellectual Property: 9 patents issued

61

Sid Martin Biotechnology Incubator, Alachua, FL

w w w . b a n y a n b i o . c o m 62

Henry L. Nordhoff, Executive Chairman

Gen-Probe, Pfizer, TargeTech

Ronald L. Hayes PhD, Founder, President

Professor McKnight Brain Institute Univ. of Florida

Jackson Streeter MD, Chief Executive Officer

PhotoThera, American Veterinary Laser, United States Navy

Steven P. Richieri, Sr. VP Operations and Clinical / Regulatory

PhotoThera, Egea Biosciences, NuVista, Immune Response

Luis DeTaboada MSEE, VP Engineering

PhotoThera, Laser Mechanisms

Larry Hayes, VP Sales and Business Development

W.L. Gore & Associates, Endologix

Management Team

63 w w w . b a n y a n b i o . c o m

Banyan Biomarkers is developing the first Point of Care test for the diagnoses of mild, moderate, and severe Traumatic Brain Injury


Diagnostic Test for Traumatic Brain Injury

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Hand-held battlefield

ready and EMT use Point-of-Care

First of its kind test to accurately detect

and quantify mild and moderate TBI

‘I think this will revolutionize brain-injury care,’ says

Col. Dallas Hack, a medical doctor in charge of the

US Army’s combat casualty treatment. He says

the Army’s goal is to one day have a portable

blood-test device that a medic could carry into the

battlefield.

“…the discovery could be a milestone in

brain-injury care, says Gregory O'Shanick,

national medical director for the Brain Injury

Association of America.

‘We will find people who are under the radar

and then treat them appropriately,' he says.

The Army collaborated on the biomarker

program with Florida-based Banyan

Biomarkers, company created by former

faculty member of the University of Florida.”

“Led by Banyan Biomarkers…the blood tests

showed the presence of certain proteins --

biomarkers -- that do not normally show up in the

blood of uninjured people. The theory is that the

concussive jolt to the brain unleashes these

proteins in the bloodstream.”

Good Morning America reports on Banyan

Biomarkers technology on 10/16/2010

New Test for Brain Injury on Horizon July 20, 2010

Blood Test to Flag Concussions? Army

Says Yes Oct 15, 2010

Diane Sawyer, World News Tonight, reports on Banyan

Biomarkers technology


Name and Title

Here


ABOUT TRAUMATIC BRAIN INJURY

A critical unmet medical need



Current problem with TBI management

“The challenge to the emergency physician is identifying which

patients with a head injury have an acute traumatic intracranial

injury, and which patients can be safely sent home.”

ACEP TBI guidelines

67

Neurological Examination (eg GCS)

Imaging Study

(eg Head CT)

Admit or

Discharge


CT scan has many challenges for TBI diagnosis

1http://abcnews.go.com/Health/CancerPreventionAndTreatment/story?id=4136914&page=1 2http://www.nejm.org/doi/full/10.1056/NEJMra072149 3Journal of Neurotrauma. November 2002, 19(11): 1405-1409

68

1. Detection Capabilities

• Can detect hematoma and

swelling but not mild and

some moderate TBI

2. Overuse

• 1/3 of all CT scans are

unjustified1

• Over 20 million head CT

scans each year in US2

3. Radiation Risks

• CT of head = 100x more

radiation than chest x-ray

4. High Cost

• Head CT: $700-$1,000

Is this a normal CT or does

this patient have a TBI?

Up to 1/3 of TBI patients

are misdiagnosed3

The Impact of TBI in the Emergency Room

Centers for Disease Control and Prevention and http://www.brainandspinalcord.org/brain-injury/statistics.html

69

• 1.7 million ER visits

• 275,000 hospitalization

• 52,000 deaths

• Actual number of TBIs not seen by medical professional is unknown

• Economic cost of TBI is >$60 billion



Sports Concussions

70

• >1.6 million sports related concussions occur each year

• NFL found that dementia-related diseases much higher in former players than national population

• Chronic Traumatic Encephalopathy (CTE)

• Lawsuits (high school, college, and pro)

http://educationalissues.suite101.com/article.cfm/tbi_statistics

http://www.cdc.gov/NCIPC/tbi/FactSheets/Concussion_in_Sports_factsheet.pdf



Grey Team - Afghanistan

71

En route to Kandahar, Afghanistan January 2011 aboard C-130


IED explosion

>50,000 troops injured

Severe TBI are medevac

immediately Many others - Mild

Concussions

Definitive Care Hospitals Combat Surgical Hospital


Bethesda

Landstuhl

Military Need for POC Test


TBI in the US Military

73

>30,000 diagnosed specifically with TBI1

1. DVBIC (http://www.dvbic.org/Totals-at-a-Glance.aspx) accessed 4/7/2012 2. U.S. Ground Force Capabilities through 2020, Center for Strategic and International Studies, Oct 2011 3. http://siadapp.dmdc.osd.mil/personnel/MILITARY/rg1109.pdf 4. Sergeant Major of the Army’s Luncheon 10/5/09 http://www.ausa.org/meetings/Documents/TranscriptRemarksby20GenPeterChiarelli_061009v2.pdf

780,000 active ground forces2

1.4 million total active military personnel (mandatory screening at physical examination) 2

“This issue is real, and must be addressed. And I need each of you to be part of the

solution. Contrary to what some believe, PTSD and TBI are not phantom conditions

exhibited by weak soldiers trying to get out of a deployment.”4

-General Peter Chiarelli, Vice Chief of Staff of the Army

speaking at the Sergeant Major of the Army’s Luncheon

http://www.dvbic.org/Totals-at-a-Glance.aspx







http://www.ausa.org/meetings/Documents/TranscriptRemarksby20GenPeterChiarelli_061009v2.pdf


Name and Title

Here


Biomarkers


Biomarkers are already used in hospitals

Biomarker - term often used to refer to a protein measured in blood whose

concentration reflects the severity or presence of some disease state.

75

Troponin is a biomarker used to diagnose acute myocardial

infarction (AMI) in Emergency Rooms

>15.5 million tests each year in the US

Dominated by 5 major companies

*Triage® MeterPro™ Meter


Biomarkers for TBI will improve patient care

76

Improve Patient Care

Ability to properly diagnose will improve patient outcomes

Cost Effective Releases patients without TBI from ER quickly and allows better

monitoring of those with mild or moderate TBI

Complementary Can be used with existing imaging and clinical TBI assessment methods

(e.g. Glasgow Coma Scale)

Safe Reduces reliance on imaging techniques and radiation exposure,

especially for children


Banyan Portfolio of Candidate TBI Biomarkers Panel

Axonal injury

Synaptic Injury Markers

(Sypt-1)

Microgliosis-

Neuroinflammation

Markers

(EAMP-II)

Vascular injury

Markers (N-

CAM)

UCH-L1 SBDP150 SBDP120 GFAP(Banyan) MBP/ frag. MAP2

Acute markers Subacute markers

BA-0293

Chronic markers

Demyelination Cell body damage Dendritic injury Gliosis / Glial Injury

Necrotic Apoptotic

77


Banyan Biomarker Panel for TBI

78

Glial Fibrillary Acidic Protein Ubiquitin Carboxyl-Terminal Esterase L1

• Structural protein of the intermediate

filament of Astroglia 50 kDa

• Highly enriched in the nervous

system.

• 1% of total brain protein

• Small compact 24 kDa protein

• Expressed at a high level in neurons

• 5% of total brain protein

GFAP UCH-L1

GFAP dimer


Name and Title

Here


Clinical Research


200 Patient Study severe TBI

(Completed)

ALERT

Severe Study

Publications

1,650 Patient Pivotal Phase III Clinical

Trial (Current)

6 Published Animal

Studies

53 Publications

17 Abstracts

Clinical Development Program

Preclinical

Studies

Mild studies 295 Patient Study mild TBI (Completed)

300 Pt study (Analysis Ongoing)

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Severe TBI study

81

Acad Emerg Med. May 2008

Levels of Serum GFAP Are Associated With Severity Of Injury In Patients With Mild And

Moderate Traumatic Brain Injury

SUMMARY:

GFAP was systematically assessed in human

serum following mild and moderate TBI. GFAP

levels were significantly elevated in this

population using ELISA analysis, including

those with mild TBI. Furthermore, GFAP was

able to discriminate TBI patients from

uninjured controls and serum levels were able

to distinguish orthopedic and motor vehicle

controls form TBI patients


Mild and moderate TBI study (GFAP)

82

Annals of Emergency Medicine

May 29, 2011

Elevated Levels of Serum Glial Fibrillary Acidic Protein Breakdown Products in Mild

and Moderate Traumatic Brain Injury Are Associated With Intracranial Lesions and

Neurosurgical Intervention

SUMMARY:

GFAP-BDP is detectable in serum within an

hour of injury and is associated with measures

of injury severity, including the GCS score, CT

lesions, and neurosurgical intervention. Further

study is required to validate these findings

before clinical application.


Human Mild & Moderate TBI – Feasibility Study

Study Objectives:

Biomarkers elevated in serum

Association to acute traumatic lesions on CT scan

Principal Investigator:

Linda Papa MD Orlando Regional Medical Center

Study Groups:

Controls: Uninjured (normal), trauma controls without TBI

TBI: mild and moderate TBI within 4 hours of injury

83


Human Mild & Moderate TBI Study Results

Serum

UCH-L1 are elevated in mild & moderate TBI


Human Mild & Moderate TBI Study Results

When CT Scan was

Positive for Brain Lesions

When CT Scan was

Negative for Brain Lesions

UCH-L1 ≥0.09 ng/ml 28 blood samples 61 blood samples

UCH-L1 <0.09 ng/ml 0 blood samples 16 blood samples

UCH-L1 was able to detect

100% of mild TBIs that had a

positive CT Scan

Potential to eliminate

unnecessary CT scans in

this group of patients

61 CT scans did not detect

mild TBI

85


Mild and moderate TBI Study (UCHL-1)

86

Journal of Trauma

May, 2012

SUMMARY:

UCHL-1 was detected in the serum of mild

and moderate TBI (MMTBI) patients and

able to identify CT positive patients


Name and Title

Here


Clinical Studies



ALERT Study Timeline (Pivotal Study)

Subject enrollment Pre-IDE 28 July filing

Pending final FDA protocol review

Expected FDA Approval

2014

88


“GATOR” Study: Mild TBI in Sports

UF Athletic Association:

Men’s Football

Women’s Lacrosse and

Soccer

Enrollment on-going

n=300



September 26, 2009 Florida vs Kentucky, Tim Tebow

from Univ. of Florida suffered a mild concussion

89




Sub-acute and Chronic Markers of TBI Post Combat

90

Pilot Landstuhl Project

Samples collected in

Landstuhl, Germany

Samples and data

transferred to Banyan

Biomarkers, Inc.

Development of biorepository

of blood samples


Upcoming Milestones

ALERT Study

PMA Application

2015 2013 2012 2011 2014

US Market Launch

Clincial Trial FDA Process Commercialization

EU Market Launch

FDA Approval

CE Marking

91


Strong Intellectual Property Position (13 Issued Patents)

92

• 41 pending international applications for 12 different inventions • 16 pending US non-provisional applications for 16 different inventions • 5 PCT applications awaiting entry into the national phase • 4 provisional applications based on 4 inventions

Japan (2) Issued

Australia (4) Issued

United States (5) Issued

Canada (1) Issued

Europe (1) EPO Issued/ 9 Regional


Name and Title

Here

Thank You

Jackson Streeter MD Chief Executive Officer

[email protected]

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PowerPoint Presentation · Pneumonia Pneumo- thorax Anemia Pulmonary Embolus Musculoskeletal Pain...

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