Presents: CareTaker™

CareTaker™

24/7 Beat by beat blood pressure Heart rate: accurate as ECG VAST APPLICATIONS (EXAMPLES) REPLACEMENT OF ARTERIAL CATHETERS HOME DIALYSIS REQUIRED Heart rate: accurate as ECG NO ELECTRODES OR ADHESIVES NO WIRES NO DERMATITUS Respiration rate NO CHEST BANDS NO ELECTRODES INSPIRATORY EFFORT NO IRRITATION

CareTaker Physiological Monitor Extracts pulse signal from finger Analyzes (decomposes) pulse wave form into the five characteristic constituent pulses Tracks beat by beat blood pressure Systolic, Diastolic, Mean, Pulse pressure Heart rate as accurately as ECG Respiration rate Detects hemorrhaging before shock sets in

How does this pulse sensor work? What is the magic?

PULSE Actual raw data If the arteries are flexible, all five constituent pulses can often be observed

PULSE 44 year old male With flexible arteries Actual Raw data

Pulse Pressure Wave Form P2P1 is the ratio between the amplitude of the second systolic peak,P2 ( the first reflection), and P1, the primary systolic peak. P2P1 tracks systolic pressure. T13 P1 P2 T13 is the time that elapses between the primary (first systolic peak) and the diastolic peak second reflection). T13 tracks the pulse pressure. The first reflection (~17% of the pulse energy) occurs near the renal artery at the aorta and the second occurs near the iliac artery bifurcation (~40%). Example of actual raw data of pulse shape obtained by CareTaker at the finger.

What Can CareTaker Do?

CARETAKER FOLLOWS ECG ALMOST PERFECTLY 21 year old R = 0.998

65 year old man with right side bundle branch block NOTE POOR QUALITY OF ECG FOR HEART RATE DETERMINATION NOTE GOOD QUALITY OF CARETAKER SIGNALN (RED TRACE)

HRV Differences in inter-beat interval (heart rate variability, HRV) Large HRV is a sign of good health Low HRV is associated with illness (deteriorates before symptoms) HRV Each point is a heart beat

cNIBP CONTINUOUS NONINVASIVE BLOOD PRESSURE (cNIBP) Necessary and required for home dialysis systems Overall correlation of SYSTOLIC PRESSURES from 43 dialysis runs. Overall correlation of PULSE PRESSURES from 43 dialysis runs. NHLBI SBIR Phase I, Continuous BP Monitor for dialysis applications, 1R43HL087476-01A1

cNIBP Trends in brachial cuff systolic pressure (red squares) and P2P1 over a 2.25 hr dialysis session (patient 24). Detail inset displays inspiratory-based modulations. Trends in brachial cuff pulse pressure (red squares) and T13 over a 2.25 hr dialysis session (patient 24). Detail inset displays inspiratory-based modulations. NHLBI SBIR Phase I, Continuous BP Monitor for dialysis applications, 1R43HL087476-01A1

CARETAKER TRACKS CENTRAL BLOOD PRESSURE 65 year old man Overlap between CareTaker (red) and central catheter (black) for 90 second observation

All Results of Central Catheter Comparison with CareTaker 3,417 Heart Beats

Bland-Altman Analysis Central Line Study

Lower Body Negative Pressure Chamber to Simulate Hemorrhage

CareTaker Tracks Hemorrhaging World’s First Hemorrhage monitor 16 tests in lower body negative pressure chamber All showed strong dependence on T13 as a function of simulated hemorrhaging. 15 of 16 showed no relationship of conventional cuff measured BP to hemorrhaging. T13 changes from a normal value of about 300 msec to about 200 msec for loss of one liter of blood. 500 1000 1500 2000 200 220 240 260 280 300 0 mmHg -60 mmHg -45 mmHg -30 mmHg -15 mmHg T13 (milliseconds) Time (Seconds) PDA - T13 Statistical comparison between 15 cuff measurements taken simultaneously with T13. Statistically, pulse pressure can measure hemorrhaging, but not in an individual measurement. ONR SBIR Phase II with options, N0001404C0204, Anti-Terrorism-Consequence Management and Recovery

Statistical Results of 15 LBNP Tests Tests at University of British Columbia

LBNP Comparison Finometer and CareTaker Hemorrhaging (simulated) LBNP Comparison Finometer and CareTaker The Finometer Pro at $40,000 a copy Note digital noise Note higher resolution of CareTaker Test at USAISR, San Antonio

T13 - THE HEMORRHAGE PARAMETER T13 as tracked by CareTaker tracks T13 (red) and as by central catheter (black)

Detection of Occult Hemorrhage T13 is a parameter that tracks pulse pressure Pulse pressure correlates with hemorrhaging T13 values for adults are about 200 - 300 msec T13 changes during hemorrhaging and can be used as a monitor of hemorrhaging.

Applications to Combat Casualty Care Real time vital sign for casualties on ground Detects and monitors hemorrhaging Warns caregivers, via radio, of out of range vital signs (example: tachycardia)- Triage Could serve as continuous noninvasive blood pressure (cNIBP) input to algorithmic resuscitation systems in development by both the Army and Navy

Nocturnal Dip A potentially explosive health issue The next slides show Daytime hypertension may not be much of a problem even if untreated Nocturnal hypertension may be a big problem and needs to be treated immediately Why is nocturnal BP dipping greater than 20% also a problem? Because kidneys, heart, and brain need higher blood pressure for perfusion to work

– Syst-Eur Placebo Cohort Conventional, 24-h, Daytime and Night-time SBP as Predictors of Cardiovascular Endpoints – Syst-Eur Placebo Cohort Systolic blood pressure (mmHg) 2-year incidence of cardiovascular endpoints 0.20 0.16 0.12 0.08 0.04 0.00 90 110 130 150 170 190 210 230 Night-time 24-h Daytime Conventional Very Dangerous Staessen JA et al. JAMA 1999;282:539–46

Dolan et al. Hypertension 2005;46:1-6 5-YEAR RISK OF CARDIOVASCULAR DEATH Relation to Clinic and Ambulatory BP - The Dublin Outcome Study Night time 24-hour Daytime Clinic Adjusted for other covariates N = 5292 Dolan et al. Hypertension 2005;46:1-6

IDACO - Characteristics by categories of the night:day ratio of SBP (n = 7458) Nocturnal hypertension is not treated in US Dipping class Limits Number of patients Women, % Age, y AH treatment , % Diabetes mellitus , % CV disorder , % extreme <0.80 1513 44.2 59 22 7 9 normal ≥0.80 to <0.90 3754 46.0 55 19 7 decreased ≥0.90 to <1.00 1754 47.4 57 25 8 9 reverse ≥1.00 437 42.6 63 37 12 14 6% ! Across the 4 groups, all characteristics were significantly different with the exception of the proportion of women. Reverse dippers were older, more patients with a history of DM or previous CVD. And importantly reverse dipperes were more often on AHT.

Tabs show parameter history Tab for continuous observation of T13 Tab for observation of continuous blood pressure

Display for CareTaker Raw data of pulse Beat by beat blood pressure Individual pulse parameters Reconstructed pulse Vertical lines show P1, P2, and P3

LIKELY measurements available with CareTaker multi-parameter physiological system: Augmentation Index for arthrosclerosis Sleep apnea monitor, screening/diagnosis device Obstructive sleep apnea Central sleep apnea CPAP efficacy monitor Hemorrhagic shock monitor/predictor Aortic aneurism detector Fatigue or stress indicator Cardiac output measurement Circadian clock tracker Advanced warning for nocturnal hypoglycemia Predictor of disease state before symptoms

Other Uses for CareTaker Safer Dialysis sessions, home dialysis machines Replaces most arterial catheters (80 – 90%) Home uses for elderly and worried well Remote monitoring, observation, dosage adjustment, self medication, arrhythmia detection and classification Home use for recovery from surgery Can send data to doctor rather than go to ER CareTaker has detected and located aortic aneurisms Under evaluation (predicted & located 5 of 5 in tests) Leg amputees are vulnerable to abdominal aneurysms

CareTaker for MRI and fMRI Presently used in Six Countries 33 feet of Teflon tubing separate the CareTaker unit from the finger cuff Brachial artery better than finger because of signal losses in tubing CARETAKER IS THE ONLY cNIBP SYSTEM THAT WORKS IN AN MRI

Modified Early Warning System (MEWS now NEWS) Display windows show trends over hours or days of: Heart rate, breathing rate, blood pressure, SPO2, Core Temperature and possibly other parameters All parameters transmitted via radio to server Nurses never have to touch the patient Patients need not be waked up during the night Near immediate results of drug/treatment efficacy Allows dosage adjustment over short times Continuous record of patient’s vital signs Provides triage plan for disasters using limited staff

MEWS The MEWS, specifically five selected parameters, may be used as a rapid, simple triage method to identify medical patients in need of hospital admission and those at increased risk of inhospital death. Modified early warning score predicts the need for hospital admission and inhospital mortality (VC Burch, G Tarr, C Morroni, Emerg Med J 2008;25:674-678 oi:10.1136/emj.2007.057661)

Why CareTaker is Necessary Exponential decrease in per capita number of physicians over next 10 to 15 years Exponential increase in per capita need for physicians over next 10 to 15 years System breaks down at 2020-2025 without telemedicine World’s largest economies will transition to remote diagnosis, treatment, and monitoring

Telemedicine funding at VA - a huge opportunity for CareTaker Ischemia: 1 in 3 Viet Nam Vets (200K) due to Agent Orange Sleep apnea: High incidence Diabetes: High incidence Many vets live in rural areas not near hospitals 5.5 M Vets already enrolled 1400 points of service 18,000 doctors

Sleep Studies and Long Surgeries Detroit Sleep Studies in Progress – continuous blood pressure of spinal cord injured patients Cooperative data sharing agreement with VA Cooper University – 8 exploratory surgeries for five to seven hours - 30 in study Comparison with arterial catheters, instruments New method to determine arterial stiffness discovered – patent in preparation Manuscript in preparation

Aortic Aneurysms and Sudden Cardiac Arrest Detected and located five of five aortic aneurysms – monitored before/ after surgery Characteristic signals disappeared after surgery Blind study – University of Virginia All signals obtained from the hand Tested CareTaker to determine Pulselessness at Cleveland Clinic – Published Applications to sudden cardiac arrest warning system built into wrist watch

Rheoencephalography Neuro ICU for detection of vasospasms, now nearly undetectable, but often fatal Trials at NMRC (Walter Reed) for monitoring traumatic brain injury (TBI) Trials in neuro ICU of University of Virginia Requires CareTaker and conventional EEG and trans cranial impedance (TCI)

MRI Use of CareTaker Installed in about 40 MRIs and fMRIs around the world as the only available beat by beat blood pressure monitor. Primarily used to study psychological effects. Manuscripts being prepared. Use in Japan to study antihypertensive medicines and use during dialysis.

New Relationships Forming China: clinical trials at Beijing Union Hospital (highest rated hospital, #1) planned for June 2013 Relations with Suning of China are progressing for remote home health care monitor ONR: current funding $850K. Option to start 2012 for $990K, resuscitation, HRWatch development Animal and human resuscitation trial at UTMB, algorithmic fluid resuscitation, waiting on contract

More New Relationships BioPac Systems: worldwide distributor of CareTaker for MRI use (not Japan). 35 sold Upcoming presentation to Telstra (Australia), possible 3700 beds Trials in Tanzania for Dr. Ellegala for remote hospital care. Planned for 2012 Medica Teknika: Japanese distributor of CareTaker about 30 units

FDA Trials for CareTaker University of Virginia in progress. Trial design approved by FDA. 60 cohorts. Actual arterial line comparisons for four hours each. Progress: 25% of data analyzed. All patients completed. FDA: approvals for 510k are normally completed within 90 days Predicted approval – summer 2013

First US Market Penetration of CareTaker into Markets 7 million arterial catheters used annually About 0.2% cause blood borne infections or blood clots Average cost of treating blood born infection is $35,000 to $65,000 CareTaker could eliminate about 85+% of invasive catheter use Cost of CareTaker is about the cost of one catheter and the surgical insertion