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The Power of Continuous Core Temperature to Change the Future of Health A Company’s Vision to Improve and Save Lives - A PUBLICATION OF PRIMA-TEMP - TABLE OF CONTENTS Introduction 1 The Relationship of Temperature & Circadian Rhythm 3 The Story of Prima-Temp 2 What Prima-Temp Can Accomplish 4 Introducing Priya Conclusion Introduction Prima-Temp Redefines Thermometry for Better Health One patient dies every 2 hours from complications due to neutropenia (low white blood cell count), a side effect from chemotherapy. Donna Deegan, a three time breast cancer survivor and an established TV News Anchor, was nearly part of this statistic. Actively undergoing chemotherapy, she was at dinner with a friend when she suddenly started to feel unwell. Deegan’s doctor had advised her to call immediately with any sign of a fever. She didn’t think having a slight fever was a big deal, but followed protocol and called her doctor. The doctor told Deegan to come in right away. She told him that she would come in as soon as the 11pm broadcast was complete. Her doctor said no way, this is an emergency, come right now. Every second counts for cancer patients with a fever since their body doesn’t have the white blood cells to help fight the infection. The sooner the patient gets treatment the more likely antibiotics and other medications to help increase white blood cells will work to save the patient's life. Introduction There is a possibility that by simply measuring continuous core temperature, doctors can see patterns that predict conditions such as an impending infection. The pattern that continuous core temperature reveals is an individual's circadian rhythm. This pattern can reveal a problem before one even has physical symptoms. Had Deegan’s doctor been able to capture Deegan’s continuous core temperature, she may have been able to see the patterns that indicate an infection was ensuing, and got to the hospital sooner. She fought for her life for over a week which caused a potentially deadly delay in her chemotherapy treatment. Infection is not the only thing measuring continuous core temperature can predict. Capturing circadian rhythms via continuous core temperature can also improve areas such as weight loss programs and fertility. By creating products that capture circadian rhythm, doctor’s and individuals will be able to make better decisions about their health. Prima-Temp is a company on a mission to use temperature patterns to redefine thermometry to make this possible. Introduction The first product Prima-Temp created will be on the market early 2017 and will help women to effortlessly pinpoint their ovulation, allowing them to more-easily conceive and potentially save them thousands of dollars by avoiding IVF and other fertility treatments. CHAPTER ONE The Relationship of Temperature & Circadian Rhythm The Relationship of Temperature & Circadian Rhythm The Power of Circadian Rhythm There is a signal called circadian rhythm in your body that tells what time each day your hair will grow, when you will get sleepy and when you will get hungry. Circadian rhythm is a powerful signal that changes gene expressions to produce hormones, and even creates your sleep patterns. You may be familiar with what happens when this signal is “off” if you have traveled and experienced jet-lag: it can take days for your circadian rhythm to catch up to the new time-zone, and can make you feel like you are fighting the flu until it resets. An amazing discovery is that your brain regulates the circadian rhythm clocks by using changes in body temperature. Using temperature, your brain helps coordinate nearly 3.5 trillion clocks in your body that affect you physically, mentally and behaviorally. The Relationship of Temperature & Circadian Rhythm If you took your core temperature throughout the day, you would see that your temperature rises and falls with a distinct pattern unique to your own body. This rise and fall of temperature is a signal that is used to turn on and off gene expressions. These 3.5 trillion clocks in our bodies function on an imperfect cycle (1). The Relationship of Temperature & Circadian Rhythm Each of these 3.5 trillion clocks needs to be slightly reset every day to match the 24-hour day. Every day, the brain pushes the body’s clocks back into place with a temperature change. So profound is this effect that you can track your circadian rhythm using temperature. Continuously measuring your body’s core temperature allows you to see the signals that help coordinate body function throughout each hour of the day. As you would imagine, each of us have a different set of clocks. Some of us rise early in the morning and some of us prefer to stay up late at night. Your circadian rhythm patterns are as unique as your fingerprint. Since temperature helps regulate these clocks, core temperature is the most reliable biomarker for circadian rhythm, meaning that if you can measure core temperature, then you can see patterns in your circadian rhythms and assess how your clocks are working (2). By measuring temperature and therefore circadian rhythm patterns, ovulation can be predicted, sleep disorders can be diagnosed, cancer treatments can be more effective, and lives can be saved. Circadian rhythms are essential for our well-being: when the clocks are off, they have been linked to weight gain, sleep deprivation, and diseases. 2 CHAPTER TWO The Story of Prima-Temp The Story of Prima-Temp Patterns of Temperature have Predictive Powers Dr. Wade Webster, one of the founders of Prima-Temp, believes that one’s legacy is the impact one can make on the lives of others, and to make life better. As an Emergency Room Physician, relieving pain and providing empathy was a profound and humbling answer. His experience in the ER lead him to understand that the patterns of temperature have predictive powers, and with continuous body temperature regulation, there is incredible potential to improve and save lives. He could leave a legacy and relieve suffering for millions of people through a better understanding of temperature regulation. The Story of Prima-Temp Dr. Webster grew frustrated when he saw patients developing severe infections unnecessarily. The opportunity to help humans, however, did not present itself right away: “My father knew about my interest in temperature and so he called to tell me that someone had devised a way of measuring a dairy cow’s internal body temperature precisely and accurately throughout her lifetime. With some research, it was apparent that larger dairies were having difficulty with increasing disease rates. This was an opportunity staring me in the face. Together with a team of engineers, I co-founded a company built on the idea that we could preserve milk production and use less antibiotics if a dairy farmer could identify an infection early rather that later. I was amazed by what you could learn as you move forward with an idea. While assembling a ‘cow-temperature monitoring company’, I was introduced to the team of talented engineers that were originally assembled by Goodyear to measure temperature and pressure inside a car tire. It was a talented group that could develop a better human thermometer. And that is how Prima-Temp was born.” The Story of Prima-Temp Prima-Temp was born out of a mission to create the most advanced continuous temperature sensors that utilize algorithms to find patterns in circadian rhythm to transform healthcare. Dr. Webster brought on the talented and experienced executive, Dr. Lauren Costantini, to be the CEO of Prima-Temp and bring to life the vision of measuring continuous core temperature to help with precision medicine, weight loss, diabetes, sleep and fertility. 3 CHAPTER THREE What we Can Accomplish by Measuring Core Temperature Predictive Healthcare in Your Hands Prima-Temp Technology to Transform Healthcare Challenges FERTILITY DETECTION In the United States alone, 11 million women are trying to conceive at any one time and 50% of those women use products to help them achieve that goal. Continuous core temperature monitoring identifies the subtle changes in body temperature, providing a convenient and precise means of determining the fertile window more accurately than any other method on the market. By tracking continuous core temperature in women, patterns in their temperature can predict when they are about to ovulate and if they have ovulated. This type of monitoring would be an immediate improvement on the arduous and inaccurate methods currently available, and help couples achieve their dream of having a baby. “My children were born due to temperature. We couldn’t get pregnant with both of our busy work schedules. My wife was a head nurse at an infertility clinic and she learned how to find the temperature pattern which we used to conceive all our children,” says Dr. Webster. EARLY DISEASE DETECTION Sepsis kills an estimated 200,000 Americans every year – more than most cancers, strokes and heart attacks. Sepsis is the most expensive cause of hospitalization in the United States, with an annual cost of more than $24 billion, according to the U.S. Agency for Healthcare Research and Quality. For every hour delay in treatment of sepsis, there is a 7.6% increase in mortality. Surprisingly, hospitals still have a nurse coming into your room every few hours to take your temperature orally or rectally. This provides only a snapshot of your temperature, and does not allow the full circadian rhythm to be seen. Nurses can only see when a fever has already developed, which is too late for septic patients. Continuous core temperature monitoring provides critical data that can predict hospital-acquired sepsis several hours before a diagnosis. Continuous core temperature sensing can identify patterns in circadian rhythm that predict when a person is going to get a fever, 1-2 days PRIOR to the fever happening. Measuring temperature accurately has the power to pick up a mild infection days prior and prevent a patient becoming fatally septic. In this way, treatment can be started earlier, saving lives in the process. There are even signatures of temperature patterns unique to different infections. For example, there are 5 different kinds of malaria that can be sub-typed based on the pattern of temperature spikes. Looking at these signals, doctors can prescribe the right medication for these specific infections sooner. PRECISION MEDICINE/CANCER CHEMOTHERAPY TREATMENT Did you know that when chemotherapy is administered based on your specific circadian rhythm, the outcomes are significantly improved, and side effects are significantly reduced? Doctor’s have always know this, but they have never had a way to measure circadian rhythm before. By measuring continuous core temperature, we could help create precision medicine that is tailored for each individual person including chemotherapy. The disruption of the temperature circadian rhythm has been associated with cancer progression. Yet if you time the medication with the patient's circadian rhythms, its amplification results in cancer inhibition in experimental tumor models. Circadian timing of anticancer medications improves treatment tolerability up to fivefold and doubles efficacy. Also, as mentioned with the Donna Deegan story, capturing core temperature can also alert patients that they have a fever before they may even have symptoms. This will allow them ample time to get the help they need to potentially save their lives. SLEEP DISORDERS Recent studies suggest that poor sleep can affect metabolism and weight gain and contribute to mental health conditions such as depression. In addition, the studies infer that poor sleep can impact memory, cognition, day-to-day performance, and even increase the risk of cancer. A study from Harvard Medical School estimates the costs of undiagnosed sleep apnea to be $65 billion to $165 billion a year, taking into account medical costs, lost productivity, and traffic accidents. Continuous core temperature monitoring provides a much-improved picture of sleep via circadian rhythm, when compared with other sleep tracking systems. Interventions can be tested and determined for efficacy in real time by using sensors that track continuous core temperature. OBESITY AND WEIGHT LOSS Obesity is a global epidemic and in spite of health organization and government efforts, population obesity continues to increase. Calories burned during any activity vary from individual to individual and depend on the metabolic rate. A small rise in core temperature can substantially alter metabolic rate. Core body temperature provides personalized, real-time data for more effective weight loss. HEAT EXHAUSTION An estimated 5 to 10 million people in the United States work in industries where heat stress is a potential health and safety hazard, including firefighters and military personnel. Each year, more than 1,000 people die from heat stroke in the United States. Continuous core temperature monitoring can better detect heat exhaustion and provide early alerts to take action, well before heat exhaustion progresses to heat stroke. 4 CHAPTER FOUR Introducing Priya Timing is the Key to Conception “ Trying to get pregnant does not need to be difficult or tedious. Sometimes its just a matter of timing and knowing when to have intercourse. Don Aptekar, MD FACOG Introducing Priya Timing is the Key to Conception Perhaps you are aware that when women ovulate, their temperature rises. Well that’s not all that is happening. Right before ovulation, there is a change in pattern coinciding with a subtle change in temperature. If measured accurately, this change acts as a crucial element for predicting ovulation and can allow for women to know when it is time to ‘get busy’ with their partner. After all, intercourse during this time significantly increases the chances of creating a baby (3). Since the egg only lives for 12-24 hours, timing is vital for conception. Sixteen years ago, researcher Mary Coyne and her team confirmed that women’s menstrual and fertility cycles can be reliably tracked by continuous core body temperature (4). By measuring continuous core temperature, they found a distinct circadian rhythm that can detect the phases of a woman’s menstrual cycle and predict impending ovulation. They noticed that about 2 days before ovulation, there is a subtle dip in temperature. What this means is that if women can measure their core temperature continuously, they can predict impending ovulation and detect whether or not they ovulated with 99% accuracy. If you or someone close to you has ever had difficulty trying to conceive, you can imagine how life changing this could be! Introduction Priya Statistically, the percent chances in a woman’s cycle that she can get pregnant granted that the sperm lives 5 days are: The graph above shows the probability of getting pregnant during certain days of your cycle. Clearly the 2 days leading up to ovulation show the highest probability of getting pregnant, but this probability drops off steeply as soon as ovulation occurs. Priya notifies you know 2 days PRIOR to ovulation, giving you the optimal opportunity to conceive. Introducing Priya Introducing Priya Current methods of ovulation detection tell you when you’ve already ovulated – and this is too late! Only core (ie internal) temperature is the most reliable way to measure circadian rhythms. Oral temperature can be affected by external cues. While there are sensors on the market that measure temperature from the ear, mouth, underarm or wrist, internal core body temperature is far and away the most accurate. In fact, literature shows that using peripheral thermometers do not provide accurate readings and should not be used to influence clinical decisions (5). x Introducing Priya Priya is the only sensor on the market that allows for a woman to go about life as usual and requires no daily effort. When she is most fertile, the wearable sensor sends a message to her phone. Women using Priya will be able to view their circadian rhythm data to see precisely when they are most fertile, and also a rise in temperature to indicate that they have ovulated. Since the Priya Ring is internal and measures core temperature all day and night, it eliminates the possibility for human error and is the most accurate reading possible. Priya Ring will even work for women with regular and irregular cycles, as well as for women with PCOS. Conclusion Prima-Temp has revolutionized wireless, continuous temperature sensing. The platform technologies will transform many of today’s healthcare challenges, and empower you to engage in your own health and well-being. Our simple and effortless digital technologies will transform many of healthcare’s challenges with the most accurate, continuous, core temperature sensors and machine learning algorithms. Disease Detection Heat Exhaustion Precision Medicine Sleep Disorders Weight Loss Fertility Detection Why Guess when You can Know? Priya harness the power of wearable sensors with machine learning algorithms to provide you with the most effortless and accurate fertility detection possible. LEARN MORE HERE Interested in Partnering with Prima-Temp? Contact Lauren Costantini, CEO at [email protected] References 1. Goa, S. Biological clocks, circadian rhythm and weight control. Aminoz. May, 2014. 2. Buhr ED, Yoo SH, Takahashi JS. Temperature as a universal resetting cue for mammalian circadian oscillators. Science 330(6002):379-85. Oct, 2010. 3. Wilcox et al. Timing of Sexual Intercourse in Relation to Ovulation — Effects on the Probability of Conception, Survival of the Pregnancy, and Sex of the Baby. N Engl J Med 1995; 333:1517-1521. Dec, 1995 4. Coyne et al. Circadian Rhythm Changes in Core Temperature over the Menstrual Cycle: Method for Noninvasive Monitoring Physiol Regulatory Integrative Com Physiol. AM J 279:1316-132. Oct, 2000. 5. Niven et al. Accuracy of Peripheral Thermometers for Estimating Temperature: A Systematic Review and Meta-analysis. Annals of Internal Medicine. Nov, 2015.