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Diabetic-Neuropathy.png

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Diabetic Neuropathy is a nerve damage complication of Type 1 and Type 2 Diabetes. It is a result of high blood sugar (glucose) which harms nerves typically in feet and legs. Diabetic Neuropathy affects everyone differently, symptoms can range from mild to impairing as it can lead to problems in the digestive system, heart, urinary tract, and blood vessels. Diabetic Neuropathy is a serious health condition that affects about 50% of people who have diabetes. 

There are four main types of diabetic neuropathy which have a variety of symptoms depending on the type and how a persons’ nerves are affected. Due to slow development of symptoms, a person is typically unaware that they have diabetic neuropathy until the nerve has suffered significant damage. 

The four types of diabetic neuropathy:

Peripheral Neuropathy

This is the most common type and it first affects the legs and feet.  It can progress to affect the hands and arms. Symptoms of peripheral neuropathy normally increase at night and include:

  • Numbness to pain or temperature changes
  • Tingling or burning sensation
  • Cramps or sharp pains
  • Muscle fatigue
  • Overly sensitive to touch
  • Foot problems inducing joint damage and infections

Autonomic Neuropathy

This type can affect nerves in the internal organs such as the heart, digestive system, sexual organs, sweat glands, and urinary tract. Signs and symptoms include:

  • Unawareness of hypoglycemia
  • Decrease in blood pressure that causes dizziness or fainting when standing up or sitting down
  • Bladder or bowel issues
  • Gastroparesis which causes nausea, vomiting, or loss of appetite
  • Change in amount of sweating
  • Problems in sexual response (differs in men and women)

Proximal Neuropathy (diabetic polyradiculopathy)

This is the most uncommon type and is seen in about 1% of people with type 2 diabetes. It results in problems with the nerves in legs, buttocks, thighs, or hips. Symptoms typically are on one side of the body but can spread to the other side. Symptoms include:

  • Sharp pains in hip, thigh, or buttocks
  • Weakness in thigh muscles
  • Difficulty sitting upright after sitting
  • Chest or abdominal pain

Mononeuropathy (focal neuropathy)

This type only affects one nerve at a time typically in the face, torso, arm, or leg. Symptoms can differ depending on the nerve being affected however they typically include:

  • Difficulty focusing vision
  • Paralysis on one side of face
  • Tingling sensation or numbness in hands
  • Weakness in hand and inability to hold objects
  • Sharp pain in foot or shin
  • Inability to lift front part of foot
  • Pain in front of thigh

When diabetic neuropathy is diagnosed in early stages there is a higher chance that the medicine will be more effective. In order to diagnose diabetic neuropathy doctors often run tests and examinations such as:

  • Checking muscle strength and reflexes
  • Check muscle response to vibrations, temperature, and touch
  • Ultrasound of urinary tract
  • Electromyography to test muscles response to electrical currents
  • Nerve conduction studies to evaluate flow of electrical current through a nerve
  • Skin biopsy to determine cutaneous nerve innervation
  • Muscle and nerve biopsies for histopathological evaluation

In addition to these tests and examinations, a doctor often tests blood glucose, blood pressure, and cholesterol in order to narrow down the root of the problem.

Treatment for diabetic neuropathy can sometimes be as simple as changes in lifestyle, however more serious stages of neuropathy require medications in order to manage symptoms and pain.

  • In order to prevent further nerve damage a doctor will give you personalized blood sugar goals to decrease blood glucose levels. A few ways to manage glucose levels include developing healthier eating habits which include high amounts of protein and low amounts of carbs. Exercising regularly also manages blood sugar levels and increases insulin sensitivity. 
  • Controlling risk factors such as high blood pressure, high triglycerides, or cholesterol are a must when trying to relieve symptoms. Some ways to control these risk factors are by doing aerobic exercises daily, quitting smoking, and losing weight (if obese or overweight).
  • Managing pain is achieved through different treatments such as medications.

Written by: Sofia H. Davila, Clinical Researcher.


Sources:

Mayo Foundation for Medical Education and Research. (2022, April 29). Diabetic neuropathy. Mayo Clinic. Retrieved February 23, 2023, from https://www.mayoclinic.org/diseases-conditions/diabetic-neuropathy/symptoms-causes/syc-20371580#:~:text=Diabetic%20neuropathy%20is%20a%20type,in%20the%20legs%20and%20feet. 

“Diabetic Neuropathy.” Diabetic Neuropathy | Johns Hopkins Medicine, 18 Aug. 2020, https://www.hopkinsmedicine.org/health/conditions-and-diseases/diabetes/diabetic-neuropathy-nerve-problems. 


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Fats are tasty in food, but not particularly good in the bloodstream. They can also be toxic to the liver and cells in general. We have special cells called adipose cells that store fat in our body. These cells have defenses against dangerous fat components called free fatty acids. Free fatty acids are the high-energy parts of fats, the part that gives you energy. Fatty acids are a great way to store energy and can be turned into power for your body, but the high energy content can also be dangerous in the wrong places. 

The liver transforms free fatty acids into usable energy. From here, the energy is delivered to cells all over the body. The liver is part of the system that makes sure the body’s energy demands match the available energy. Unfortunately, when too many free fatty acids are delivered to the liver, they can start to build up in the liver tissue and cause damage.

Fatty liver is one of the most common ailments in Western countries. One in every three to four people in the US havw a fatty liver. Excessive alcohol consumption can cause a fatty liver, but most sufferers develop non-alcoholic fatty liver disease (NAFLD). Either way, people have steatosis. Steato- means fat, and -osis indicates a condition, especially an abnormal one. Steatosis of 5-10% is problematic and is the earliest indication that the liver is starting to suffer damage. Many people with fatty liver and no other abnormalities can make a full recovery, usually by stopping whatever is causing the steatosis.

We know that alcohol can directly damage the liver, but how does NAFLD start? The causes are complicated, but some similarities exist. Excess fat released from fat cells, excess fat created by the liver, and excess fats from the diet all find their way into the liver. These are normally not an issue, but all are affected when the body isn’t regulating insulin properly. Insulin lets body parts know when you have food or are starving. When insulin isn’t processed correctly the body thinks it’s starving and tries to compensate – even when there is plenty of food present. In the middle of this the liver suffers.

After a prolonged period of fat accumulation, a patient with NAFLD may develop non-alcoholic steatohepatitis, or NASH. Steato- for fat, hepat- indicating the liver, and -itis which means inflammation. This second leg on the terrible journey develops when fat causes inflammation in the liver. The gut changes and gives the wrong signals to the liver. Cells develop insulin resistance and can’t convert sugars into energy or fats correctly. Free fatty acids cause cell problems and elicit an immune response. Stresses on the liver cause a feedback loop, where inflammation disrupts cell function. The body tries to fix the liver but can’t overcome the massive amount of dangerous fats. Cells in the liver die, and the living cells can be damaged trying to compensate. With NASH, the inflammation is long-lasting, also called chronic.

The liver can regenerate from NAFLD and NASH. It can’t sustain forever, however. When the liver is permanently damaged, the tissue can scar and die. This is a permanent reduction in liver function. We call this scarring Cirrhosis. Cirros- is the Greek word for yellow-brown (the color of a dying liver), and -osis refers to a condition, especially an abnormal one. Cirrhosis has multiple stages and can be asymptomatic but cannot be recovered from without intervention. The current treatment for cirrhosis is a liver transplant.

Though we’ve been talking about the dangers of fats in the bloodstream and liver, it should be noted that the body makes a lot of these fats out of carbohydrates – sugars. A healthy diet without too many sugars and with lots of exercise are the best preventative measures for these conditions. Conditions related to insulin resistance, such as type 2 diabetes and metabolic syndrome can both cause and be caused by these conditions. Also, even though we have presented these as a pathway, note that you can progress from NASH to NAFLD or become symptom-free; it’s not a one-way journey! If you have any of these conditions, talk to your primary care physician to look for solutions. Also, keep an eye out for clinical research trials that may alleviate symptoms or the underlying fat buildup.


Sources:

Pierantonelli, I., & Svegliati-Baroni, G. (2019). Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH. Transplantation, 103(1), e1-e13. . https://doi.org/10.1097/TP.0000000000002480

Sanyal, A. J. (2019). Past, present and future perspectives in nonalcoholic fatty liver disease. Nature reviews Gastroenterology & hepatology, 16(6), 377-386.


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March 14, 2023 ENCORE News

Respiratory Syncytial Virus (RSV) is a highly infectious disease which is particularly dangerous for infant and elderly patients. It is one of the major infectious diseases without an approved vaccine, so the effort to develop vaccines has been underway.

To combat this ongoing and widespread disease, companies have been developing vaccines targeting the prefusion F glycoprotein. Prefusion F proteins are RSV surface proteins required for viral fusion into host cells. This is the most promising target for vaccine research. 

GlaxoSmithKline has found preliminary success in its RSVPreF3 OA investigational vaccine in patients over 60 years of age. Their Phase 3, placebo-controlled study is ongoing in nearly 25 thousand participants around the world, including those participants at the Westside Center for Clinical Research, part of ENCORE Research Group.

Recently published results show a significant protective effect of the vaccine, lowering infections by 82% and severe infections by over 94%, all with a favorable safety profile. This will help lower the incidence and hospitalization of RSV in patients and underscores the importance of clinical research and the work of ENCORE Research Group, its sponsors, physicians, staff, and participants in the clinical research process.

 

Sources:

Bergeron, H. C., & Tripp, R. A. (2021). Immunopathology of RSV: an updated review. Viruses, 13(12), 2478. https://doi.org/10.3390/v13122478

Killikelly, A. M., Kanekiyo, M., & Graham, B. S. (2016). Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. Scientific reports, 6(1), 1-7. https://doi.org/10.1038/srep34108

Papi, A., Ison, M. G., Langley, J. M., Lee, D. G., Leroux-Roels, I., Martinon-Torres, F., … & Hulstrøm, V. (2023). Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. New England Journal of Medicine, 388(7), 595-608. https://doi.org/10.1056/NEJMoa2209604


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The liver is an amazing and necessary organ. It can regenerate from a minor injury, break down dangerous chemicals and drugs, and help maintain the proper balance of nutrients, fats, and sugars in the body. It has hundreds of other important roles as well. With all this responsibility, we are in trouble when the liver stops working.

One way the liver stops working is through non-alcoholic steatohepatitis (NASH). Steato- means fat, hepato- indicates the liver, and -itis means inflammation. Steatohepatitis is inflammation of the liver caused by fat accumulation. This is a progressive form of non-alcoholic fatty liver disease – the most common liver disorder in western countries. Progressive means that this disease gets more severe over time. 

NASH is a large problem in America, affecting 3-12% of adults. Furthermore, NASH can lead to cirrhosis, where the liver is permanently damaged, and lead to possible liver transplantation. Over a million adults in America have NASH-related cirrhosis.

How do we get NASH? As the name indicates, this is not caused by alcohol. There are many pathways to developing NASH, but the underlying cause may be excess carbs and fatty acids. This can be due to diet or behavior, underlying genetics, or associated syndromes. Some of the syndromes associated with NASH are:

  • Metabolic syndrome
  • Obesity
  • Type 2 diabetes
  • High blood pressure
  • Dyslipidemia
  • Hypothyroidism
  • Cardiovascular risk
  • Advanced liver problems

The underlying mechanism of NASH can be very complex. A leading precursor to NASH is insulin resistance, where cells fail to respond to insulin. Conditions that cause or are caused by insulin resistance, such as type II diabetes and metabolic syndrome,  may increase your chances of developing NASH. They also may develop or worsen as NASH symptoms get worse. 

Insulin resistance causes different types of fats to accumulate in the liver. This makes it very difficult for the liver to process the fats and they ultimately build up in liver cells. These fats, especially ones called nonesterified fatty acids (NFEAs), are very dangerous. They cause damage to liver cells and can also activate cytokines that start the inflammation process.

Eventually, we get NASH, an inflammation cascade in the liver caused by fats. Cytokines start inflammation in the liver. Cell death attracts the immune system, which enters and causes inflammation while trying to help. Liver cells die and are less able to process fats, which leads to a compounding effect. Eventually, we may transition to cirrhosis, where permanent liver scarring and damage occur.

There are few treatments on the market for NASH. As usual, the primary therapy for NASH is a good diet and regular exercise. Medicinal remedies are all in the experimental phases. Potential targets include increasing insulin sensitivity, decreasing fat creation, decreasing circulating fats, breaking fats down, and anti-inflammation treatments. 

One way to decrease circulating fats is by expelling them through the digestive system. In the liver, moving fats to the gut is regulated by thyroid hormones. Thyroid hormones activate receptors, which exist all over the body and cause many different effects. Thyroid hormone receptor Beta (THR-β) exists almost exclusively in the liver. Scientists are working to create medicines that activate THR-β and help clear fats from the liver in NASH patients. If you are interested in participating in a research study, contact your local ENCORE Research Group site today! 


Sources:

Noureddin, M., & Sanyal, A. J. (2018). Pathogenesis of NASH: the impact of multiple pathways. Current Hepatology Reports, 17, 350-360.

Parthasarathy, G., Revelo, X., & Malhi, H. (2020). Pathogenesis of nonalcoholic steatohepatitis: an overview. Hepatology communications, 4(4), 478-492. https://doi.org/10.1002/hep4.1479

Pierantonelli, I., & Svegliati-Baroni, G. (2019). Nonalcoholic fatty liver disease: basic pathogenetic mechanisms in the progression from NAFLD to NASH. Transplantation, 103(1), e1-e13. . https://doi.org/10.1097/TP.0000000000002480

Pramfalk, C., Pedrelli, M., & Parini, P. (2011). Role of thyroid receptor β in lipid metabolism. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1812(8), 929-937. https://doi.org/10.1016/j.bbadis.2010.12.019


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Eosinophilic asthma is a type of asthma that is characterized by high levels of eosinophils in the airways. Eosinophils are a type of white blood cell that are involved in the body’s immune response to allergens and other triggers. When eosinophils are activated, they release inflammatory chemicals that can cause damage to the airways, leading to asthma symptoms.

Symptoms of eosinophilic asthma include wheezing, coughing, shortness of breath, and chest tightness. These symptoms may be more severe than those of other types of asthma and may not respond as well to traditional asthma treatments like inhaled corticosteroids.

Diagnosis of eosinophilic asthma involves a blood test to measure eosinophil levels and a sputum test to look for eosinophils in mucus from the lungs. Treatment may involve targeted biologic medications that specifically target eosinophils, such as mepolizumab, reslizumab, and benralizumab. These medications work by reducing the number of eosinophils in the airways, which can help to reduce asthma symptoms and improve lung function.

If you or someone you know has severe asthma, clinical trials may be an option for you. Clinical trials are an important way to test new medications and treatments for asthma and other conditions. They allow researchers to gather important data on the safety and effectiveness of new treatments, and they provide patients with access to cutting-edge therapies that may not be available through traditional channels. By participating in a clinical trial, you can play an important role in advancing medical research and helping to improve the lives of people with eosinophilic asthma and other conditions.

Clinical trials for this condition are currently available at ENCORE Research Group’s Jacksonville Center for Clinical Research, University Blvd. location.  To learn more, you can contact us by phone, or sign up on our website. Our knowledgeable staff can guide you through the process and help you determine if a clinical trial is a good option for you.



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Celiac disease is a genetic autoimmune disease that affects the digestive system. It is triggered when a person consumes gluten, which is a protein found in rye, wheat, and barley. When a person with celiac disease eats gluten, their immune system reacts to the protein by attacking the small intestine. The role of the small intestine is to digest food and allow the body to use the nutrients. When the body attacks the small intestine, it damages the lining of the small intestine, resulting in symptoms that include bloating, abdominal pain, and weight loss. Eventually, after the small intestine has suffered damage, it can result in the body’s inability to absorb nutrients, therefore leading to a deficiency of nutrients and health problems. 

It is often difficult to tell if children have celiac disease, as the symptoms in children and adults differ. 

Symptoms in adults include:

  • Fatigue
  • Weight loss
  • Bloating and gas
  • Abdominal cramps/pain
  • Nausea and vomiting
  • Constipation

Adults can also experience a variety of symptoms unrelated to the digestive system, such as: 

  • Anemia
  • Loss of bone density
  • Headaches
  • Cognitive impairment
  • Joint pain

Digestive problems are commonly seen in children with celiac disease, rather than in adults with celiac.

Symptoms in children include:

  • Nausea and vomiting
  • Diarrhea
  • Bloating
  • Constipation
  • Gas
  • Weight loss
  • Anemia
  • Irritability

Symptoms are often not enough to tell if someone has celiac disease. People are more susceptible to celiac disease if they have some of the risk factors listed below:

  • Family history of celiac disease and/or dermatitis herpetiformis (itchy skin rash)
  • Type 1 diabetes 
  • Turner Syndrome or Down Syndrome
  • Autoimmune thyroid disease
  • Microscopic colitis 
  • Addison’s disease

Diagnosis of celiac disease is through blood tests that check for certain antibodies and biomarkers. 

  • A serology test detects elevated antibodies which indicate the body is reacting to the gluten protein. 
  • A genetic test detects human leukocyte antigens in order to eliminate the possibility of celiac disease. 

Often following these blood tests is an endoscopy/biopsy of the small intestine to evaluate the damage caused by the body’s response to the gluten protein.  

Although there is no cure for celiac disease, a change in diet helps to regulate the symptoms of celiac disease. A gluten-free diet often consists of gluten-free foods and vitamin and mineral supplements to regulate the body’s nutrients. Following a gluten-free diet allows the small intestine to heal. Doctors and dietitians can help guide people on their diet and inform them of gluten-free alternatives. This diet is normally life-long in order to prevent symptoms or a flare-up of the small intestine again. Doctors sometimes prescribe steroids as well to help regulate the inflammation of the small intestine. 

It is often difficult for people with celiac disease to eat out at restaurants or buy pre-made food from stores as it is tricky to be one hundred percent certain that a food is truly gluten-free. Stickers on foods say “may contain gluten” as a way to protect the manufacturing companies from lawsuits. However, most of the time the food does not contain gluten itself but has a small chance that it could have been cross-contaminated during the production process. This limits food that people with celiac disease feel safe consuming and buying. The FDA has standards that must be met in order for a food to be labeled as “gluten-free”. The final product must contain, at most, 20 mg/kg (20 parts per million) gluten or less. However, this rule does not apply to alcohol which can contain gluten. This amount of gluten (20 ppm) will not result in any side effects in a person with celiac disease, since it is too small of an amount. Another way people can be sure that they are consuming gluten-free foods is to call a restaurant ahead of time and ask if they have a gluten-free menu or serve alternatives for people with gluten intolerance. 

Written by: Sofia H. Davila, Clinical Researcher


Sources:

Mayo Foundation for Medical Education and Research. (2021, August 10). Celiac disease. Mayo Clinic. Retrieved February 17, 2023, from https://www.mayoclinic.org/diseases-conditions/celiac-disease/diagnosis-treatment/drc-20352225 

NCI Dictionary of Cancer terms. National Cancer Institute. (n.d.). Retrieved February 17, 2023, from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-intestine

U.S. Department of Health and Human Services. (n.d.). Eating, diet, & Nutrition for Celiac Disease. National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved February 20, 2023, from https://www.niddk.nih.gov/health-information/digestive-diseases/celiac-disease/eating-diet-nutrition 


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Atrial fibrillation (AFib) is a heart rhythm disorder characterized by irregular heartbeats in the heart’s upper chambers, called the atria. In AFib, the electrical signals that regulate the heartbeat become abnormal, causing the heart to beat too fast or slow instead of contracting normally. Atrial fibrillation can have detrimental effects such as stroke, heart failure, and blood clots. 


Image Credit: cdc.gov


As a result of the irregular heart beatings, a variety of symptoms can be present such as:

  • Palpitations (fluttering, pounding, or rapid sensation)
  • Shortness of breath
  • Fatigue
  • Weakness
  • Dizziness / lightheaded
  • Chest pain

In some cases, people with AFib may not experience any symptoms, making it difficult for some people to tell whether or not they may have AFib.  

Some broader symptoms can include:

  • Abrupt weight gain
  • Coughing or wheezing
  • Fainting
  • Nausea and appetite loss
  • Depression

Sometimes even these broader symptoms can not help people determine if they have AFib. The only way for people to know if they have AFib without experiencing any symptoms is to get tested and diagnosed by a doctor. It is strongly recommended that if a person has any of the risk factors below, they get checked, just to be safe, by a doctor. 

AFib is often seen in older adults, with risk factors that include:

  • History of heart disease
  • High blood pressure
  • Advancing age
  • Obesity
  • Diabetes
  • Heart failure
  • Hyperthyroidism
  • Chronic kidney disease
  • Smoking or excessive alcohol use

Some treatments are more effective when delivered in the early stages of AFib, which means that a person should not postpone getting checked by a doctor for AFib. However, symptoms and causes of AFib can often differ between men and women. In women, AFib usually is caused by problems with the heart valves. Compared to men, where AFib usually stems from coronary artery disease (CAD). As a result, women with AFib have a greater chance of having a stroke than men with AFib. Women with AFib also are more likely to have heart attacks and congestive heart failure than men with AFib. As a result, treatments for men and women often differ slightly. 

Treatment for AFib is typically a medication to control heart rhythm and prevent blood clots. However, in some cases, procedures such as electrical cardioversion, ablation, or implantation of a pacemaker or defibrillator may be necessary. Men with AFib are often placed on non-drug therapies such as pacemakers and catheter ablation. Women with AFib are more likely to have a cardioversion and be prescribed antiarrhythmic medications such as dofetilide. However, typical treatments for both men and women include blood-thinning medications, surgery, and lifestyle changes to manage AFib risk factors. 

Written by: Sofia H. Davila, Clinical Researcher


Sources:

Miller, K. (2022, December 27). Atrial fibrillation: The difference between men and women. Healthgrades. Retrieved February 17, 2023, from https://www.healthgrades.com/right-care/atrial-fibrillation/atrial-fibrillation-the-difference-between-men-and-women 

Centers for Disease Control and Prevention. (2022, October 14). Atrial fibrillation. Centers for Disease Control and Prevention. Retrieved February 17, 2023, from https://www.cdc.gov/heartdisease/atrial_fibrillation.htm


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February 20, 2023 ENCORE NewsFDA Approved

Two ENCORE Research Group sites, Nature Coast Clinical Research and ENCORE Borland Groover Clinical Research, played a vital role in the clinical trials for “Vibrant,” a new vibrating drug-free capsule designed to treat constipation. In August 2022, the product received clearance from the FDA to be marketed and used for the treatment of constipation. The capsule recently became available for prescriptions as of February 2023.

Vibrant’s unique drug-free treatment works by using gentle vibrations to stimulate the colon mechanically, thus improving its natural motility. The pre-programmed timing of the vibrations is based on the colon’s biological clock, which makes the treatment effective and gentle.

Vibrant’s Phase 3 clinical trial results showed an increased number of complete bowel movements and an improvement in patients’ quality of life. The trial also reported a low incidence of diarrhea at just 1.2%.

It’s important to note that Vibrant is a prescription-only treatment, and it should be recommended by a physician based on the patient’s medical needs and suitability. The treatment’s effectiveness and low incidence of side effects make it a promising option for those struggling with constipation.

Sources:

https://www.vibrantgastro.com/

https://www.medscape.com/


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Our patients are enthusiastic and excited to take part in clinical research.  There are a variety of reasons a patient would want to participate in a clinical trial: they join to benefit future generations, to advance medicine, to get medical help and compensation, and to increase diversity. The most frequent reason for joining a clinical study, however, is to help others. Clinical research is the best framework for ensuring the safety and effectiveness of new medications, devices, and procedures. This includes everyone from participants of phase 1 clinical trials to final consumers after FDA approval. But what does the process actually look like for patients?

People hear about us from a wide variety of sources: advertisements, community outreach programs, the internet, and personal referrals from family and friends. Thousands of our patients are referred to us by friends, family, and their own physicians. People’s great experiences with us make them very likely to recommend us to others. Most of our patients are repeat offenders. In fact, over 99% of our patients return for another study. 

When you are interested in an ENCORE Research Group study, our experienced and compassionate recruiters will talk with you. These experts care about your time more than anything else. They will run through a quick checklist to see if you prequalify for a study. If you prequalify, they will schedule an evaluation. They will find a time that works best for you to come in or receive a call with a research coordinator.

Here the compassionate and attentive nature of ENCORE Research Group excels. You will receive forms to fill out your medical history, medications, and contact information. During your appointment, our attentive and detail-oriented staff will review your documents. They will confirm and expand on any medical conditions that may affect your participation. This step makes sure you are always safe and gives our staff personal knowledge to help you during your study. Patient safety is always our number one priority.

After an evaluation, if you choose to participate, you will start the informed consent process. Here you will review the clinical trial process and the plan for your specific study. Research coordinators will explain and review a highly detailed and regulated consent form. This document informs you about the study, potential side effects, the goals and endpoints of the study, your rights, and what to expect. This is a vital step. We will also remind you that you can end participation in the study at any time for any reason. Your voluntary participation does not oblige you to continue at any point.

What happens from here depends on your specific study, but some things will remain constant. Our doctors and medical staff will talk with you. Other patients describe them as professional, friendly, and compassionate. You may receive medication, a placebo, device, or undergo a procedure. This will have been explained in detail during the informed consent process. One big difference between ENCORE Research Group and a normal doctor’s office is the comprehensiveness and amount of follow-up. Our doctors give you their full, undivided attention when you are in their office. They have plenty of time and want to know the intricacies of your medical history. For most studies, our staff will periodically check up on you after you leave. We are also keenly interested in knowing if you experience any new or changing symptoms. This will continue until your study has concluded. Then, if you wish, we will contact you if you qualify for more studies.

This process results in a streamlined, professional, and personal system. You get to help medicine and society, but also experience top-quality, attentive care for a variety of conditions. Join the clinical trial process with ENCORE Research Group and see why nearly all of our patients come back!

By Benton Lowey-Ball, BS Behavioral Neuroscience



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February 13, 2023 ENCORE News

Heart disease is one of the leading causes of death worldwide, and researchers are constantly searching for new treatments to reduce the risk of cardiovascular events. One area of interest is lipoprotein (a), or Lp(a), a molecule that has been associated with an increased risk of heart disease.

To tackle this issue, Amgen has developed a new investigational drug called Olpasiran, a small interfering RNA designed to lower the body’s production of apolipoprotein(a), a key component of Lp(a). Currently, Olpasiran is being studied in Phase III clinical trials, with Jacksonville Center for Clinical Research (JCCR) and Jacksonville physicians playing a significant role in the clinical research trials.

The development of Olpasiran holds important public health implications for the future of Lp(a) treatment and is a testament to the impact that JCCR and its clinical partners are making in advancing medical progress. By participating in the clinical trials of Olpasiran, JCCR is contributing to the discovery of new treatments that have the potential to improve the lives of millions of people.

Olpasiran development represents a significant step forward in the treatment of Lp(a), and JCCR’s involvement in the clinical research trials underscores the important role that clinical research plays in advancing medical knowledge and improving public health.

Sources:

https://www.pharmaceutical-technology.com/data-insights/olpasiran-what-is-the-likelihood-that-drug-will-be-approved/

https://www.amgen.com/

 


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February 6, 2023 ENCORE News

ENCORE Research Group is proud to announce that it has three highly-skilled and accomplished physicians with the prestigious ACRP Certified Principal Investigator (CPI) credential: Dr. Michael J. Koren, Dr. Kyle Etzkorn, and Dr. Victoria Helow.

This trusted mark of excellence recognizes the expertise and experience of clinical research professionals. To earn the credential, investigators must have 3,000 hours of verifiable work experience as a principal or sub-investigator on multiple studies. They must also pass a standardized certification exam, testing their knowledge and skills in the field.

By having three physicians with the CPI credential on its team, ENCORE Research Group is able to offer sponsors high-level quality clinical research services. These physicians bring a wealth of knowledge, skill, and insight to the company, and they are well-equipped to lead clinical trials and research projects with confidence and competence.

In a field that is constantly evolving and advancing, it is essential to have professionals who are up-to-date on the latest industry developments and who can deliver results that are reliable and trustworthy. The CPI credential is a testament to our physicians’ commitment to excellence in their field, and it is a reflection of the level of care and dedication that they bring to their work.

Click here for Academy of Clinical Research Professionals CPI Certification Information. 


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There are many ways to think of the human body. One of my favorites is that the body is like a donut. The inside of the donut is our entire body and everything that makes us what we are. The outside is our skin. The hole in the middle is made of our mouth, throat (esophagus), stomach, and intestines. The body treats the entirety of the digestive tract as the outside world. The intestines act like the skin; keeping most things out of the body and only letting specific molecules through.

This has some important implications. The whole outside of the donut – including the throat and intestines – is covered in epithelial cells. These are tight cells that interact with the outside world. When these cells determine that they are touching something dangerous they signal to get rid of it immediately. This might feel like burning or itching on the skin, and may be something like diarrhea or vomiting in the digestive tract. These may feel crummy to us, but they are very useful in keeping us safe.

The immune system is in charge of identifying and reacting to chemical and biological dangers. These can be harmful bacteria, worms, and things like splinters or some drugs. The immune system kicks into action, trying to kill or remove the dangerous particles without damaging body cells. This is a tricky dance. Antibodies will identify the dangerous particles or creatures and special B or T cells will widely sprinkle alarm particles, calling for reinforcements.

What the body does next is determined by where the danger is found. In the gut – which the body treats as the dangerous outside world – the defenses are strong. One of the biggest guns we have is a cell called an eosinophil. These are very dangerous cells. They contain highly toxic particles and proteins that aggressively dunk in on invaders. They also signal to the intestines to  contract and eject the contents. They only exist in specific parts of the body and are normally difficult to activate.

Unfortunately, sometimes our body identifies otherwise safe items as dangerous. This is called allergies, and can be very annoying. Many of us suffer from seasonal allergies, but that doesn’t mean we should glaze over the dangers of allergic reactions. One difficult condition is eosinophilic esophagitis. Eosinophilic means it is caused by the dangerous eosinophil cells. Esophagitis refers to the fact that this happens in the esophagus, the throat. Eosinophils do not normally reside in the throat at all. The throat’s main job is to move food into the stomach, so it doesn’t need to detect danger. When eosinophils mistakenly reside in the throat, however, they can misidentify otherwise safe foods before the stomach gets a chance to digest them. This can result in the eosinophils damaging the throat.

Eosinophilic esophagitis affects four in every thousand people, and can affect people of all ages. Most sufferers were diagnosed as children. In fact, it is one of the most common diagnoses for children who have trouble eating. It is chronic, or long lasting,  and symptoms are debilitating. Sufferers experience inflammation of the throat, poor food intake, vomiting, and a poor appetite. Unfortunately there are few treatments available to fix this condition. The most effective has been reducing the diet of patients. This may consist of starting with a very strict diet and reincorporating food slowly to discover triggers. Scientists are actively looking at the underlying causes of why eosinophils are in the throat to begin with. Possible future treatments would likely stop eosinophils in the throat at a cellular or genetic level.  The body may be a donut, but that doesn’t mean everything is tasty and fresh. If you are suffering from eosinophilic esophagitis or other conditions, call ENCORE Research Group and ask about studies you may qualify for.

By Benton Lowey-Ball, BS Behavioral Neuroscience



Furuta, G. T., & Katzka, D. A. (2015). Eosinophilic esophagitis. New England Journal of Medicine, 373(17), 1640-1648. https://doi.org/10.1056%2FNEJMra1502863

Janeway Jr, C. A., Travers, P., Walport, M., & Shlomchik, M. J. (2001). Effector mechanisms in allergic reactions. In Immunobiology: The Immune System in Health and Disease. 5th edition. Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK27112/

Rothenberg, M. E. (2004). Eosinophilic gastrointestinal disorders (EGID). Journal of Allergy and Clinical Immunology, 113(1), 11-28. https://doi.org/10.1016/j.jaci.2003.10.047

Zuo, L., & Rothenberg, M. E. (2007). Gastrointestinal eosinophilia. Immunology and allergy clinics of North America, 27(3), 443-455.https://doi.org/10.1016%2Fj.iac.2007.06.002


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January 31, 2023 ENCORE News

We are proud to announce that Jacksonville Center for Clinical Research, a member of the ENCORE Research Group, is celebrating 26 years of advancing medical research in Florida. Our team of over 100 collaborating physicians have conducted over 2700 studies with 130,000 patients, solidifying our position as the premier clinical research organization in the community.

Our compassionate approach and decades of experience ensure that each patient’s journey through clinical research is safe, beneficial, streamlined and personalized. Our commitment to quality and safety has earned us the trust of our community and we are honored to continue serving them.

When you make the decision to volunteer to participate in a clinical research trial, JCCR and ENCORE Research Group are here to guide you every step of the way. Our team is dedicated to providing a supportive and safe environment, and we are proud to bring you into our community of heroes.

We would like to thank our patients, physicians, and staff for their continued support and trust in our services. Here’s to another 26 years of making a difference in the lives of our community!



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January 31, 2023 ENCORE News

Nature Coast Clinical Research Announces the Remodeling of Its Inverness, Florida Office, Now Offering Phase 1 Clinical Trial Capabilities

Inverness, Florida – Nature Coast Clinical Research is pleased to announce the completion of our remodeled office in Inverness, Florida, across the street from Citrus HCA Hospital. The fully renovated facility, located at 411 West Highland Boulevard, features new, state-of-the-art equipment and trained staff that allows for an expanded selection of clinical trials.

The remodeling project was undertaken to expand and modernize our research capabilities providing the opportunity for members of the community to participate in all phases of clinical trials. Nature Coast Clinical Research now features a dedicated Phase 1 unit, which includes private inpatient rooms for overnight stays, on-site lifesaving medication and equipment, and certified, trained staff in-house 24/7. The office also has multiple newly renovated, cutting-edge outpatient examination rooms for later-phase trials and non-overnight office visits.

Phase 1, or early phase clinical trials, are used to test the safety of new investigational drugs or devices by helping to determine the correct dosage of new investigational treatments. They are a critical step in the clinical trial process and often require that patients complete overnight stays in the unit.

Phase 2-4, or later phase clinical trials, are conducted on investigational medications or devices that have successfully completed earlier phase trials. They further look at safety parameters as well as dosing regimens, and the effectiveness of investigational therapies and devices.

Nature Coast Clinical Research is part of ENCORE Research Group, a full-service clinical research organization with locations throughout the state of Florida specializing in conducting Phase 1-4 clinical trials for Alzheimer’s, digestive issues, fatty liver, cardiovascular diseases, vaccines, and more. We are committed to providing patients in the community access to the latest treatments and therapies through clinical research studies. 

Dr. Rafik Abadier, the medical director of Nature Coast Clinical Research’s Inverness Phase 1 unit, is board-certified and has been practicing cardiology for more than twenty-five years. He has been a Principal Investigator of multiple clinical trials since 2007. 

Dr. Paul Hellstern, the medical director of Nature Coast Clinical Research’s Inverness Outpatient office, is board-certified in internal medicine and gastroenterology. He has been a Principal Investigator of multiple clinical trials since 2000. 

The remodeled office is now open for business and is accepting patients for all phases of clinical trials. Watch this space to learn more about Nature Coast Clinical Research and our new Phase 1 options!

Contact Jill Livingston, Phase 1 Unit Manager, for more information.

(352) 341-2100


Nature Coast Clinical Research – Inverness

411 West Highland Boulevard Inverness, FL 34452

Main Office: (352) 341-2100



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In the 1990’s the philosopher Haddaway posed a critical question: What is love? This Valentine’s Day, many of us will experience love and companionship. We like to think of love as an amorphous, idealistic quality, but there are serious biological underpinnings. What is the biology behind love, and is the heart really where love lies (spoiler: maybe?)

We know that the brain directs our physical actions, but for the brain to come up with an idea, it needs input from the outside world. Interestingly, the brain can’t sense anything directly. If someone were to open up your skull and have a poke around, you would undoubtedly have a weird bit of sensation, but you wouldn’t experience the feeling of touch on the brain. We need special sensors (usually located on the skin) to feel things like touch. Indeed, our brain relies on signals coming in from all over the body to tell us about the outside world. Interestingly, we also rely on signals to tell us about the inside world – what we are experiencing. The brain interprets signals from the body, and we can experience that interpretation as an emotion.

As an example: your heart beats automatically all day, every day, at a hopefully regular interval of around once a second. When you see a scary event, such as a wild lion charging you, your brain and body respond in sync. The heart rhythm changes, beating much faster to provide your muscles, sensory organs, brain, etc., extra oxygen in order to move fast. But this effect isn’t strictly rational. After we escape from the lion, we still feel “amped up.” This effect can last for thirty minutes or so, and the reason for the long-lasting effect is complicated. Our autonomic nervous system – the one in charge of things we don’t consciously control – has kicked into action. This pathway acts like cupid, shooting cortisol through our body and activating special nervous system pathways that take a while to cool down. But our brain also looks at the state of our body to interpret our emotional state. If our palms are sweaty, we’re breathing heavily, and our heart is racing, the brain interprets that as being amped up and decides we’re still pretty excited or scared. The brain is in charge of deciphering which emotion we’re feeling, but the body lets us know how strongly we’re feeling that emotion.

This is why we sometimes still feel the need to continue an argument after the other party has conceded. It’s why telling someone to “calm down” doesn’t work – but taking some deep breaths does. Meditation, stretching, exercise, and sleep all affect our emotional state because the brain looks at the condition of the body and tries to figure out how it’s feeling. In addition, a healthy heart that can respond well to changes may increase a person’s emotional regulation. Does it do this with love as well?

According to neuroendocrinology researcher Robert Sapolsky, it does! The science may not be entirely clear, but the easiest way to be certain of this is by looking at the irrationality of love. Love doesn’t make sense, and it’s so strong that we base enormous portions of our life just on this single emotion. Love is the basis of countless pieces of art, works of literature, grand buildings, and justifications for war. When we experience love – that fluttering of the heart, the excitement and elation, the involuntary smile on our face, and the giddiness so high that our mouths stop working and we say embarrassing, cheesy things – it’s the body to blame. Our heart races when we’re in love and the brain sees this as a huge exciting event – because it is. Just seeing the person we love can change our heart rate. Physical touch from a loving partner can help lower our heart rate in response to stressful situations. And the long-term effects of companionship sometimes include a partial synchronization of our heart rhythms.

We can thank our hearts for at least some of what we call love. This Valentine’s day, get your heart racing with a partner or loved one, and keep that heart beating strong!

By Benton Lowey-Ball, BS Behavioral Neuroscience



Ditzen, B., Neumann, I. D., Bodenmann, G., von Dawans, B., Turner, R. A., Ehlert, U., & Heinrichs, M. (2007). Effects of different kinds of couple interaction on cortisol and heart rate responses to stress in women. Psychoneuroendocrinology, 32(5), 565-574. https://doi.org/10.1016/j.psyneuen.2007.03.011

Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S., Hudspeth, A. J., & Mack, S. (Eds.). (2000). Principles of neural science (Vol. 4, p. 980). New York: McGraw-hill.

Mather, M., & Thayer, J. F. (2018). How heart rate variability affects emotion regulation brain networks. Current opinion in behavioral sciences, 19, 98-104.

Sapolsky, RM. (various works)


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January 24, 2023 ENCORE News

Resmetirom is an investigational oral medication aimed at reducing the symptoms and reversing the effects of Non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease. The medication is delivered to the liver and selectively acts to activate a thyroid hormone receptor, THR-β. This is underexpressed in patients with NASH. Clinical trials for this groundbreaking medication were performed at multiple ENCORE Research Group member sites, including Jacksonville Center for Clinical Research, Nature Coast Clinical Research, and St. Johns Center for Clinical Research. Trials remain ongoing throughout the country and we are excited to see resmetirom continue through the clinical trials process.


Watch a news interview about it here:


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Cardiovascular disease has remained the number one cause of death worldwide.  Multiple clinical trials have revealed that a common and modifiable risk factor for cardiovascular disease is high cholesterol, and if a person lowers their cholesterol, they can lower their risk for heart-related diseases.

Most of us have heard of cholesterol, but what is it? Why is having too much cholesterol a bad thing? How do we get cholesterol in our bodies? What can you do to lower your cholesterol to healthy levels? 

Cholesterols are a broad and useful type of fat found in the body. The body needs them to create hormones, essential vitamins (like vitamin D), and other molecules. They float on the surface of our cells, helping to maintain the structure and function of cell barriers. Cholesterols regulate cell activity and act outside of cells. They insulate the neurons in our brain, allowing us to think.  In fact, cholesterol is so important to daily function, that every cell in the body can make cholesterol from basic materials, except your eyelashes!

There are times when cholesterol is downright bad. LDL cholesterol and Lipoprotein a [Lp(a)] have some particularly sticky portions that can get stuck to the inside of our bloodstream. We call one of these portions ApoB. Sticky cholesterol obstructs blood flow in the form of plaques. Without help, this leads to atherosclerosis, scarring, and hardening of the arteries. Atherosclerosis further cascades into cardiovascular disease, clots, heart attacks, and stroke. This is very bad. Unfortunately, it is also very common; atherosclerosis in the neck is found in ¼ of people worldwide. Lowering excess cholesterol is a global health concern.

Our liver creates enough cholesterol to supply our bodies. We are also able to absorb cholesterol from our diets and make some in other cells. The most effective methods of reducing cholesterol are lifestyle and diet changes. However, for some people, diet and exercise don’t seem to budge their cholesterol numbers at all. For others, the ability to exercise and dietary restrictions may be limited. This is where medications can step in.

To understand how a medication may reduce LDL and/or Lp(a), we need to learn a bit about how the body makes things from DNA. Genes are bits of DNA that contain the blueprint for a protein. Genes provide the blueprint to messenger RNA (mRNA). The mRNA translates genetic code into proteins. The cells then fold proteins into complicated, machine-like shapes. Proteins interact with molecules and other proteins to create all sorts of things for the body – including cholesterol. Clinical research has been expanding which of these steps we can target for medications.

Statins are the first line treatment for reducing cholesterol. They target hydroxymethylglutaryl coenzyme A (HMG-CoA). HMG-CoA is a protein used to construct cholesterol molecules. Reducing HMG-CoA slows the body’s ability to create cholesterol, lowering cholesterol levels. Statins block the production of the “bad” LDL-C cholesterol and lower levels by as much as 60%. The benefits for statins to reduce cardiovascular events have been proven in multiple clinical trials over a diverse patient population.

Other oral medications, including ezetimibe and bempedoic acid, can be taken with statins. Ezetimibe can lower LDL-C levels by approximately 20% by inhibiting cholesterol absorption in the intestines, making it a useful add-on medication when statins alone are insufficient. Bempedoic acid can lower LDL-C by 15-25% by decreasing cholesterol synthesis in the liver.  Because bempedoic acid is converted to an enzyme found only in the liver and not the muscles (like statins), it is often an alternative for patients who have statin-associated muscle myalgias.    

Monoclonal antibodies (MoAbs) are a newer class of medication. MoAbs like alirocumab and evolocumab act like signaling molecules. These two stay outside of cells and tell the liver to produce less of the protein PCSK9. Controlling PCSK9 is a newer method of changing a person’s cholesterol profile. PCSK9 controls how much extra LDL cholesterol is absorbed and recycled by cells. MoAb medications affect this by targeting signaling receptors on the outside of the liver.

Even newer medications target the process by which genes get turned on inside the cells.  They are called gene silencing therapies because they aim to “silence” the gene’s effects.  Antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) stop the liver from producing functional LDL or Lp(a) mRNA molecules. These act at different, very early stages of the cholesterol process. In addition, specialized packaging on the medications deliver them to the liver and not other cells. This can make for very targeted medications that (hopefully) have fewer side effects.

Inclisiran is the first FDA-approved siRNA therapy to lower LDL cholesterol.  It is a subcutaneous injection taken twice a year.  Imagine going to your physician’s office just twice a year to get your “cholesterol vaccine”!

Even more amazing, gene editing tools such as CRISPR could reduce overexpression of PCSK9 or other genes on a long-term basis. These are still in early phase trials, but the future is looking bright.

Lipoprotein a,or “L-P-little-a”,  or Lp(a), is a new target for decreasing the risk of cardiovascular disease. Lp(a) is genetically inherited and increases the risk for both heart disease and stroke because it can promote plaque buildup, blood clots, and inflammation.  New gene silencing therapies are in clinical trials right now using both ASO and siRNA technology.

Diet, lifestyle changes, and statins remain the front-line defense against high cholesterol. New medicines may work with or replace these classical defenses. As technologies move through the clinical research apparatus, we may be able to tailor custom combinations of medications for individual patients. ENCORE Research Group has been involved in every step along this path, helping to study medications in every category. Join our team and help pave the way for new medications to help combat high cholesterol! 



Sources:

Craig, M., Yarrarapu, S. N. S., & Dimri, M. (2018). Biochemistry, cholesterol. https://www.ncbi.nlm.nih.gov/books/NBK513326/

Fernandez-Prado, R., Perez-Gomez, M. V., & Ortiz, A. (2020). Pelacarsen for lowering lipoprotein (a): implications for patients with chronic kidney disease. Clinical Kidney Journal, 13(5), 753-757. https://doi.org/10.1093%2Fckj%2Fsfaa001

Prati, P., Vanuzzo, D., Casaroli, M., Di Chiara, A., De Biasi, F., Feruglio, G. A., & Touboul, P. J. (1992). Prevalence and determinants of carotid atherosclerosis in a general population. Stroke, 23(12), 1705-1711. https://doi.org/10.1161/01.str.23.12.1705

Tokgözoğlu, L., & Libby, P. (2022). The dawn of a new era of targeted lipid-lowering therapies. European Heart Journal. https://doi.org/10.1093/eurheartj/ehab841


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The Role of Apolipoprotein C-III (apoC-III) in Atherosclerosis and Cardiovascular Disease

After we eat a meal, all that energy has to go somewhere. Body cells can use freely floating glucose sugar in the bloodstream, but fats are a bit trickier. Just like oil and water don’t mix, fats have trouble moving through the blood in our veins and arteries. They must be packaged inside special containers called lipoproteins in order to travel where they need to go. For fats that we eat, the fats (called triglycerides) are packaged into ultra-low-density chylomicrons by the digestive system. Our liver also processes and repackages fats. The liver makes very low-density lipoproteins (VLDL) out of triglycerides and ejects them into the bloodstream. VLDLs can then use the bloodstream to travel to fat cells or be converted into other forms of energy storage. The number of triglycerides in the bloodstream at once needs to be well regulated.

For adults, fasting triglyceride levels should be under 150 mg/dL. This number decreases to below 90 mg/dL for people under 19 years of age. Unfortunately, one in ten adults have high levels, called hypertriglyceridemia. When there are too many triglycerides, they can stick to the inside of the bloodstream. They can create and contribute to hard plaques, a condition called atherosclerosis. These put stress on the cardiovascular system and can lead to atherosclerotic cardiovascular disease (ASCVD). Very high triglycerides above 500 mg/dL is called severe hypertriglyceridemia. This can lead to even more problems, including chylomicronemia, pancreatitis, and death.

What contributes to high triglyceride levels? A lot, actually! A diet that is high in sugars and fats, excessive alcohol consumption, being overweight, and a sedentary lifestyle can contribute. Some conditions, such as diabetes, kidney and liver disease, and thyroid problems increase your chances. Anything that affects liver function is likely to change how the body processes fats and may increase triglycerides. This means some life-saving medications, including several cancer, hypertension, and HIV treatments may increase triglycerides. Some people have high or very high triglycerides – usually in the form of chylomicrons – even without these risk factors. This may be because of our genes.

One of the major genetic culprits for increased triglycerides is a gene called APOC-3. This gene codes for a protein of the same name: Apolipoprotein C-III (apoC-III). You can tell these apart because the gene is uppercase, italicized, and uses a (3), while the protein is mostly lowercase and uses roman numerals (III). The protein apoC-III can lead to some detrimental effects. Normal triglycerides bind to a different protein, apoC-II. This helps them get broken down in the bloodstream. ApoC-III binds to triglycerides in the same place as apoC-II but makes them less able to be processed. These triglycerides build up in the bloodstream and can cause atherosclerosis and ASCVD. Scientists also have evidence that apoC-III makes triglyceride-rich molecules stickier to the arteries. ApoC-III binds to chylomicrons very well, making these fats especially resistant to breaking down.

So why do we have apoC-III anyway? It turns out, not all of us do! Different people have different variations of the APOC-3 gene. Some people have a gene that produces excessive apoC-III protein, and a few have genes that produce none! People with defective APOC-3 genes seem to be just as healthy as everyone else. Maybe healthier, as their levels of triglycerides are very low, even after a fatty meal! Researchers consider a defective APOC-3 gene to be cardioprotective, meaning that it lowers the chances of heart disease.

Are there methods for us to lower the production of apoC-III and our triglyceride-rich chylomicrons? It looks possible. The liver produces more apoC-III in response to high levels of blood sugar and most fats, so lowering these may help. It decreases production of apoC-III when it encounters high levels of insulin or polyunsaturated fats (such as Omega-3 fatty acids). This may be helpful, but is bad news for those with type 2 diabetes. In these patients the bloodstream has extra glucose and lacks insulin.

Treating high triglycerides can be complicated. A diet low in alcohol, carbs, and fats but high in omega-3 fatty acids can help. Exercise and weight loss are often helpful. Doctors may also prescribe fibrates, nicotinic acid (niacin), or statins. Unfortunately, these medications may not work if you have excessive levels of apoC-III and high chylomicrons. A diet that is very low in fats – under 20 grams a day – has been the only option for some patients. New classes of medication may be helpful as well. Antisense oligonucleotides, gene therapy, and custom antibodies can be used to target the production of specific proteins. Antisense oligonucleotides, for instance, bind to APOC-3 mRNA in the cell, preventing it from creating apoC-III proteins. They do this with extreme specificity, targeting only the gene in question. They can also do this only in liver cells by being packaged in a special way. Drugs that target apoC-III production may be able to bring down otherwise stubbornly high triglycerides without too many side effects. A side effect of being on this ENCORE Research Group mailing list is learning about these new medicines and when they may be available for you in a trial!



Sources:

Alves-Bezerra, M., & Cohen, D. E. (2017). Triglyceride metabolism in the liver. Comprehensive Physiology, 8(1), 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376873/

Goldberg, R. B., & Chait, A. (2020). A comprehensive update on the chylomicronemia syndrome. Frontiers in endocrinology, 11, 593931. https://doi.org/10.3389/fendo.2020.593931

National Institute of Health, National Heart, Lung, and Blood Institute. (April 7, 2022). High blood triglycerides. U.S. Department of Health and Human Services. https://www.nhlbi.nih.gov/health/high-blood-triglycerides

Rahmany, S., & Jialal, I. (July 18, 2022). Biochemistry, Chylomicron. https://www.ncbi.nlm.nih.gov/books/NBK545157/

Taskinen, M. R., Packard, C. J., & Borén, J. (2019). Emerging evidence that ApoC-III inhibitors provide novel options to reduce the residual CVD. Current atherosclerosis reports, 21(8), 1-10. https://doi.org/10.1007/s11883-019-0791-9


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January 11, 2023 BlogDiabetesMedEvidence

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In fifth grade, I learned that mitochondria are the powerhouses of the cell. But what’s the fuel? The answer is carbohydrates. Big carbohydrates are broken down by digestion and converted into a couple of simple sugars. The most abundant of these simple sugars in our bodies is glucose. 

Glucose is small, simple, and packed with energy. We transport it through our bloodstream to cells in our body. Glucose levels are regulated by the liver and pancreas. Unfortunately, conditions like diabetes can result in the dysregulation of blood glucose levels. Having too much sugar in the blood is very bad over time. It can result in damage to the eyes, kidneys, nerves, and heart. On the flip side, having low blood sugar can get dangerous right away. Glucose is the fuel that powers our cells, without it the brain and other organs can’t function.

We know that glucose is critical to body function. We also know that glucose levels can get out of control. What can we do to make sure glucose levels stay safe? The most important piece of the puzzle is information. Good information on what our blood glucose levels are is critical to know what to do. We get this information by testing our blood glucose levels. There are three major ways of testing blood glucose; chemical redox reactions, color change, and enzyme-based reactions.

  • Chemical redox reaction testing works because glucose reacts with metals. By measuring how the metals react to blood, we can indirectly measure the amount of glucose. Unfortunately, other chemicals in the blood react to metal as well and can complicate the results. This method is rarely used these days.
  • The second method is through color change. This method combines blood and a special chemical called o-Toluidine. The o-Toluidine reacts to a specific part of the glucose molecule and changes it to be bright green (normally it is white or colorless). We can measure the color change visually, using test strips or with a digital glucose meter. Color change is cheap and effective, but the o-Toluidine can react to other sugars and give distorted results.
  • The industry standard for the last few decades has been enzyme-based reactions. A special enzyme, usually glucose oxidase or glucose dehydrogenase reacts with blood. This enzyme is very specific and only reacts to glucose. A result of this reaction is the production of H2O2, hydrogen peroxide. This is easily measured by digital devices. This method is inexpensive and specific, giving good results.

Now we know the chemical methods of measuring glucose, but how do we actually test our glucose level? Three broad testing types exist: oral, self-test, and continuous glucose monitors. These are differentiated mainly by the frequency and invasiveness of the test. 

  • Oral tests are a lengthy and (frankly) pretty gross affair. You fast for several hours, then drink an offensively sweet beverage and wait another hour. Blood is drawn and tested to determine how well your body can break down and clear the glucose from the bloodstream.
  • Self-tests involve drawing blood and putting it on a strip or in a digital detector. This is quick and can be done many times a day if needed. Unfortunately, repeated pricks can be annoying and you can’t test overnight unless you wake up. 
  • Continuous glucose monitors (CGMs) are worn like a patch and have a tiny sensor that goes just under the skin into the interstitial space and sends results to an external monitor. This tests blood glucose constantly, typically reporting every 1-5 minutes. CGMs can let people know their glucose via a phone app or external device. 

As the old saying goes, knowledge is power! With the help of the latest CGM technology, we are able to see information in real-time such as how food, exercise, and stress impact glucose levels. This helps us take immediate action to manage our glucose levels. So, take action to keep your blood glucose in the healthy range with your new knowledge, a good diet, and consistent exercise. Make sure it stays there by monitoring your blood glucose levels regularly. Keep your eyes open to look for new studies looking at ways to monitor your blood glucose and keep your cells powered up!



Sources:

American Diabetes Association (n.d.). Understanding A1C diagnosis. American Diabetes Association. https://diabetes.org/diabetes/a1c/diagnosis

McMILLIN, J. M. (1990). Blood glucose. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Chapter 141. https://www.ncbi.nlm.nih.gov/books/NBK248/

Wang, H. C., & Lee, A. R. (2015). Recent developments in blood glucose sensors. Journal of food and drug analysis, 23(2), 191-200. https://doi.org/10.1016/j.jfda.2014.12.001


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Cardiovascular disease (CVD) is the leading cause of death in the United States. There are several risk factors for cardiovascular disease. This can include things you can’t change, such as sex, age, and genetics. They can also include things you can change. The WHO identifies four big behaviors that can change your risk of developing CVD:

  • Poor diet
  • Low exercise
  • Excessive alcohol consumption
  • Smoking

These behaviors generally lead to other undesirable indicators of health, including obesity, hypertension, high blood sugar, and increased cholesterol. Clearly, ceasing the behavioral risks is a high priority. Unfortunately, this is often easier said than done.

One of the most difficult habits to quit is smoking. Studies show that those attempting to quit without assistance have an over 90% relapse rate. Several medications exist to help quit smoking, including Bupropion SR (aka Wellbutrin) and Varenicline (aka Chantix). There are also nicotine-based alternatives, including gum, inhalers, lozenges, nasal sprays, and patches.  Nicotine rewires the brain as it’s consumed. It releases dopamine, the brain’s reward drug, and rewards us for smoking. Researchers think the frequency of smoking may be partially to blame for the intensity of the addiction. The amount of dopamine released is not particularly high compared with other drugs, but nicotine also causes changes to the striatum. The striatum is part of the reward circuit in the brain. Through a complicated mechanism, nicotine increases the amount of a protein called FosB, which changes the striatum’s sensitivity to dopamine. This is a change at the genetic level which makes the brain more susceptible to further reward signals. Nicotine seems to make normal activities more pleasurable. Unfortunately, as nicotine adjusts the brain’s mechanisms, the brain relies on it to get to a baseline of reward. Upon quitting smoking, the brain finds normal activities less enjoyable.

On its own, nicotine may have negative effects, and in heavy doses it has been shown to be dangerous. The biggest dangers of smoking, however, are likely in the myriad of other chemicals in tobacco and cigarettes. Though nicotine causes changes in the brain, cigarettes cause changes to the fats in your body, further increasing CVD risk. Along with this, cigarettes cause cancer, COPD, diabetes, erectile dysfunction, and immune system changes. Clearly, quitting smoking is critical to health. With the addictive nature of nicotine and the low success rate of quitting cold turkey, assistance may be needed. 

The brain gets addicted to nicotine, but we can fight back using behavior. You can actually help yourself “break the cycle” of nicotine addiction by changing your daily routines. For example if the first thing you do in the morning is reach for a cigarette, change your routine to going to the bathroom and brushing your teeth first instead. Behavioral interventions can make a significant difference. Combining behavior changes and counseling with a nicotine replacement or medication can help quit rates approach 30%. Indeed, nicotine replacements are most effective when used with behavioral interventions. 

Changing your behavior or routine can have positive impacts on your health. So next time you want to reach for a cigarette, grab your phone instead! Give us a call and discover what clinical trials you can take part in!



Sources:

Bancej, C., O’Loughlin, J., Platt, R. W., Paradis, G., & Gervais, A. (2007). Smoking cessation attempts among adolescent smokers: a systematic review of prevalence studies. Tobacco control, 16(6), e8-e8. https://doi.org/10.1136%2Ftc.2006.018853

Fiore, M. (2008). Treating tobacco use and dependence; 2008 guideline. https://stacks.cdc.gov/view/cdc/6964/cdc_6964_DS1.pdf

Garbin, U., Fratta Pasini, A., Stranieri, C., Cominacini, M., Pasini, A., Manfro, S., … & Cominacini, L. (2009). Cigarette smoking blocks the protective expression of Nrf2/ARE pathway in peripheral mononuclear cells of young heavy smokers favouring inflammation. PloS one, 4(12), e8225. https://doi.org/10.1371/journal.pone.0008225

Koren, M. (Host). (2022, May 22). Nicotine replacement therapies to help stop smoking  [Audio podcast episode]. In Medevidence! Truth behind the data. ENCORE Research Group. https://www.buzzsprout.com/1926091/10484183-nicotine-replacement-therapies-to-help-stop-smoking

Messner, B., & Bernhard, D. (2014). Smoking and cardiovascular disease: mechanisms of endothelial dysfunction and early atherogenesis. Arteriosclerosis, thrombosis, and vascular biology, 34(3), 509-515. https://doi.org/10.1161/ATVBAHA.113.300156

NIDA. (2018, September 28). Recent Research Sheds New Light on Why Nicotine is So Addictive. https://nida.nih.gov/about-nida/noras-blog/2018/09/recent-research-sheds-new-light-why-nicotine-so-addictive

US Department of Health and Human Services. (2014). The health consequences of smoking—50 years of progress: a report of the Surgeon General. https://www.ncbi.nlm.nih.gov/books/NBK294320/


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We humans seem to like making a fresh start. Whether it’s the beginning of a semester, a month, or a week, we like having a “clean slate” to make changes. The most widely used of these fresh start times are at the beginning of the year, with a New Year’s Resolution. Over 40% of all Americans make New Year’s resolutions, but much like a firework, we make a bright claim with a loud noise, only for it to burn out quickly as the year goes on. How can we make good resolutions that we are likely to follow, and are there strategies we can use to help us follow through?

Probably the most important piece of a New Year’s Resolution is coming up with a good resolution in the first place! Surveys show that around two-thirds of all resolutions are health-oriented, including eating healthier, exercising, getting in shape, etc. Psychological studies have shown that the wording of your resolution matters. Most resolutions can be broadly lumped into either activation or avoidance goals. Activation goals are those that encourage you to do something: exercise more, eat more greens, etc. Avoidance goals are those that encourage you to not do something: watch less TV, eat less pizza, etc. Several studies have shown that activation goals are significantly more likely to be successful than avoidance goals

Sometimes our end goal is to decrease something: to lose weight, stop smoking, or eat slightly fewer cookies. In order to increase chances of success, it can be helpful to reimagine these goals as activation goals. Instead of losing weight, we can aim to exercise four days a week. Instead of stopping smoking, we can try to chew gum daily. Instead of eating fewer cookies, we can try to do some push-ups instead. When trying to avoid negative things, it can be hard to find rewards and easy to identify failures. By trying to do positive things, we can enjoy the reward of achieving our goal incrementally. Even small changes can help. Instead of “I resolve to eat no cookies this year” we can set the goal as “I resolve to do a push-up instead of eating a cookie every day.” Eventually, we will focus more on the positive action, the push-up, than the negative one, the cookie. This way our brain will spend more time focusing on the things we resolve to do!

When we follow through on a resolution, we are making a behavioral change. These changes are governed by our brain, and mimic changes within it. Some of our most popular resolutions correspond to changes in our reward pathway, called the mesocorticolimbic circuit. This contains several brain structures and is a part of the brain that is hijacked by addictive drugs. Two structures in particular, the nucleus accumbens and striatum, seem to be affected by things like resolutions. Addictive things including sugar decrease these areas’ sensitivity to naturally occurring dopamine. This makes the brain need more and more of those items to find the same level of reward. Lowering sugar, drugs, and alcohol can help restore the dopamine receptors and give your brain a fighting chance. Studies have also shown that exercise increases dopamine sensitivity of the mesocorticolimbic circuit, giving some protection against addictive undesirable behaviors. Other behaviors that we do frequently and repetitively will also make changes to the brain’s pathways, reinforcing the behaviors.

So now we know how to structure our resolutions, and how our brain responds to changes, but what can we do to make sure we don’t give up on our resolutions? The most important change is a lifestyle change. This is true with resolutions, but also with weight loss medications, smoking cessation, etc. Changing the triggers for what you want to avoid makes it easier to do the activities you desire. Even small changes – like sitting in a different chair than your preferred cookie-binge recliner – can make the process easier. Along with this, we want to make sure we have strategies to deal with tempting situations. If work has cookies on Fridays, drinking a lot of water can fill your stomach and help alleviate the temptation. Unexpected situations can also arise. If your mother invites you for afternoon tea and biscuits – only for you to learn that “biscuit” is British for “cookie”- having a plan to politely decline can be very handy. Finally, realize that resolutions aren’t all-or-nothing. If I succumb to chocolatey chip temptation and eat a cookie today, it doesn’t mean I’ve failed at my resolution and should give up. Instead of looking at hiccups as failures, look at them as learning opportunities. These are great opportunities to learn what triggered your lapse and practice a strategy to act positively and avoid this trigger in the future.

Taken together we have solid starting points for our resolutions. Resolve to do positive actions that you want to accomplish. Structure resolutions to be activation based and give yourself opportunities to celebrate success instead of regretting failure. Give yourself the advantage of changing your lifestyle to accommodate and incentivize your resolution. Give yourself a break when you miss a day and learn how to move forward better tomorrow. When we resolve to do things we want to do, we only have to countdown the days until we celebrate another New Year and a successful resolution!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Larimer, M. E., Palmer, R. S., & Marlatt, G. A. (1999). Relapse prevention. An overview of Marlatt’s cognitive-behavioral model. Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism, 23(2), 151–160. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760427/

Oscarsson, M., Carlbring, P., Andersson, G., & Rozental, A. (2020). A large-scale experiment on New Year’s resolutions: Approach-oriented goals are more successful than avoidance-oriented goals. PLoS One, 15(12), e0234097. https://doi.org/10.1371/journal.pone.0234097

Trifilieff, P., & Martinez, D. (2014). Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity. Neuropharmacology, 76 Pt B(0 0), 498–509. https://doi.org/10.1016/j.neuropharm.2013.06.031

Wimmer, S., Lackner, H. K., Papousek, I., & Paechter, M. (2018). Goal orientations and activation of approach versus avoidance motivation while awaiting an achievement situation in the laboratory. Frontiers in psychology, 9, 1552. https://doi.org/10.3389/fpsyg.2018.01552


Does-Chocolate-Really-Have-Health-Benefits.jpg

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Most of us have heard by now that chocolate is healthy, or that a small amount is healthy, or that you can eat an infinite amount of chocolate and it will be healthy forever. Where do these claims come from, and do they add up? 

There is evidence of people consuming chocolate up to 1600 years ago. It is native to the Americas and was said to be the “food of the gods” in mesoamerica. Today we think of chocolate as sweet and delicious and the perfect food, but this was not always the case. Chocolate is thought to have originally been mixed with water and drunk as a bitter, spiced beverage. During the 1500’s chocolate was brought to Europe, where it was considered as exotic as Mars. Healers claimed chocolate healed diseases of the liver and stomach, and that it could help with fever.

By 1631, chocolate had changed. Adding sugar was now typical, and the prescriptions for chocolate had changed as well. Chocolate in this era was used to help gain weight (likely due to sugar), stimulate the brain (likely due to caffeine), and aid in digestion.

Ironically, the same benefits chocolate seemingly presented to chronically underweight pre-industrial people has become a bit of a problem for us. By the mid to late 1800’s there were investigations into the health problems associated with chocolate’s additives – milk and sugar. They found that regularly eating fatty, sugary foods might not be healthy. By the 1900’s chocolate began to be associated with obesity, tooth decay, gum disease, etc. The “dark” chocolate age had begun.

By the early 2000’s, the opinion pendulum on chocolate had begun to swing back. Individual components of chocolate, such as flavanols, methylxanthines (Methyl-zan-theens) and polyphenols were shown to be beneficial to heart function in a lab. Since then there have been claims that chocolate helps everything from cardiovascular problems to metabolic ones and even cancer. It looked like chocolate was on a holiday high in medical opinion.

Unfortunately, these results may have been candy-coated. Research trials haven’t shown as much benefit as in the lab. One sweet spot picked up by newspapers was an observational meta-study which looked at over 300,000 participants. This study looked for an association between chocolate consumption and coronary artery disease (CAD). They found that people who ate chocolate more than once a week (or more than 3½ times a month) had a significantly lower incidence of CAD, heart attack, heart failure, and acute coronary syndrome. It is important to note that this was not an interventional study, and only looked at associations. Additionally, this didn’t take into account the type of chocolate eaten. Finally, this study found that some negative indicators actually rose, likely due to the extra calories from fats and sugars added to chocolates.

The best way to look for health benefits or drawbacks of any medicine is to do an interventional experiment – a clinical trial. This is where you compare groups randomly assigned to take chocolate or a placebo. An examination of 15 such studies where chocolate was the medicine sadly found few benefits. These studies looked for changes in:

  • Skin condition
  • Weight / BMI
  • Blood glucose
  • Blood pressure
  • Cholesterol
  • Cognitive function

When looking at all 15 studies, there was no significant change in any of these indicators. The only significant change across studies was a decrease in triglycerides. This can be helpful, as high triglycerides can be a risk factor for CAD, stroke, and pancreatitis. Overall, however, chocolate doesn’t appear to be the miracle drug it’s been touted as for the last millennium and a half. As we have learned countless times, using randomized clinical (interventional) trials is the best and often only way to discover if medicines have the effects people claim!

Interventional trials are conducted at clinical research organizations such as ours, ENCORE Research Group. We are a premier clinical research organization that has conducted more than 2,500 clinical trials over 25 years and has worldwide recognition for providing patients access to cutting edge medical research.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Krittanawong, C., Narasimhan, B., Wang, Z., Hahn, J., Virk, H. U. H., Farrell, A. M., … & Tang, W. W. (2021). Association between chocolate consumption and risk of coronary artery disease: a systematic review and meta-analysis. European journal of preventive cardiology, 28(12), e33-e35.https://doi.org/10.1177/2047487320936787

Lippi, D. (2015). Sin and pleasure: the history of chocolate in medicine. Journal of agricultural and food chemistry, 63(45), 9936-9941.

Montagna, M. T., Diella, G., Triggiano, F., Caponio, G. R., Giglio, O. D., Caggiano, G., … & Portincasa, P. (2019). Chocolate,“food of the gods”: History, science, and human health. International Journal of Environmental Research and Public Health, 16(24), 4960. https://doi.org/10.3390/ijerph16244960

Tan, T. Y. C., Lim, X. Y., Yeo, J. H. H., Lee, S. W. H., & Lai, N. M. (2021). The health effects of chocolate and cocoa: A systematic review. Nutrients, 13(9), 2909. https://doi.org/10.3390/nu13092909


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December 12, 2022 BlogMedEvidence

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With the onset of frosty weather and short days, we can all use a boost. Luckily, giving gifts can produce a “warm glow” to help out. This isn’t just decorative talk, giving gifts has been shown to increase well-being in people across the globe. In study after study, psychologists have found that acts of kindness, such as giving gifts, have positive results on both the receiver and the giver.

In one study, scientists gave children treats while measuring happiness. The children were then asked to give treats to a puppet. These could be their own treats or ones from a researcher’s supply. The data showed the children were happier to give a treat to the puppet than to receive one for themselves and were happiest when they gave their own treat to the puppet. Overall, the cheer of giving seemed maximized when giving away more important gifts.

Why could this be, though? Why would gift giving be beneficial for the person losing something? Could it be that giving a gift clears your already extremely crowded gingerbread house and increases your Feng shui? The real answer is that gift giving is a prosocial behavior. This means that it promotes social acceptance and friendship. This is a positive behavior in social contexts. Prosocial behaviors are seen in several social animals, including apes and dogs.

Scientists have shown that giving gifts can increase synchronization between friends. In two studies, scientists hooked pairs of friends up to brain scanning devices. The friends performed cognitive tasks, then one would give the other a gift (at a random time), and they would perform the task again. The scientists found that accuracy on the tasks increased. In addition, activity increased in the dorsolateral prefrontal cortex (DLPFC). This is part of the brain located beneath the hairline (assuming you have hair). It is associated with decision making and memory, and is also implicated in suppressing selfishness and building relationships. This helps with cognitive tasks, but also with forming and maintaining friendships. Even more interesting, they found that the brain waves of friends were synchronizing! The brainwaves measured in the DLPFC would “sync up” and produce similar patterns after gift giving! Giving a gift doesn’t just increase friendship, it helps you think like your friends too!

The DLPFC isn’t the only section of the brain that’s active when giving. When giving to charity, people’s mesolimbic reward system and subgenual areas activate. The mesolimbic reward system is a general reinforcement pathway in the brain, and also rewards for things like food, sex, and drugs.  The subgenual area releases important hormones such as oxytocin (the love hormone) and vasopressin. These make us feel good and increase our social happiness.

So this winter, give gifts to keep yourself warm inside and out. By giving gifts you can increase your own happiness, strengthen bonds with friends, and release dessert-like chemicals in the brain. Also, consider giving the gift of health to others by volunteering for a clinical trial at one of our ENCORE Research Group locations. 

By Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Aknin, L. B., Barrington-Leigh, C. P., Dunn, E. W., Helliwell, J. F., Burns, J., Biswas-Diener, R., … & Norton, M. I. Prosocial Spending and Well-Being: Cross-Cultural Evidence for a Psychological Universal.https://doi.org/10.1037/a0031578

Aknin, L. B., Hamlin, J. K., & Dunn, E. W. (2012). Giving leads to happiness in young children. PLoS one, 7(6), e39211. https://doi.org/10.1371/journal.pone.0039211

Balconi, M., Fronda, G., & Vanutelli, M. E. (2019). A gift for gratitude and cooperative behavior: brain and cognitive effects. Social cognitive and affective neuroscience, 14(12), 1317-1327. https://doi.org/10.1093/scan/nsaa003

Balconi, M., Fronda, G., & Vanutelli, M. E. (2020). When gratitude and cooperation between friends affect inter-brain connectivity for EEG. BMC neuroscience, 21(1), 1-12.

Curry, O. S., Rowland, L. A., Van Lissa, C. J., Zlotowitz, S., McAlaney, J., & Whitehouse, H. (2018). Happy to help? A systematic review and meta-analysis of the effects of performing acts of kindness on the well-being of the actor. Journal of Experimental Social Psychology, 76, 320-329. https://doi.org/10.1016/j.jesp.2018.02.014

Moll, J., Krueger, F., Zahn, R., Pardini, M., de Oliveira-Souza, R., & Grafman, J. (2006). Human fronto–mesolimbic networks guide decisions about charitable donation. Proceedings of the National Academy of Sciences, 103(42), 15623-15628. https://doi.org/10.1073/pnas.0604475103


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The familiar wub-dub of the heart accompanies us throughout our lives, providing a gentle beat that keeps us alive. But for some of us, the beat might not be so steady. For 33 million people worldwide, the heartbeat lacks a rhythm at all. It sounds like shoes in a clothes dryer and gets progressively worse. This is called Atrial Fibrillation, or AFib for short. The risks of AFib increase with age, and there is a genetic component as well. Other risk factors include:

  • Heart failure
  • Ischemic (low blood flow) heart disease
  • High blood pressure
  • Diabetes
  • Obesity
  • Sleep Apnea

In order for AFib to occur, doctors believe there needs to be a trigger and a substrate. A trigger, or driver, is the electric signal that travels to the heart and initiates an arrhythmic event. This can be from several areas, but is frequently from one of the big pulmonary veins that carry oxygen to the heart. A substrate is the underlying condition that makes a sustained event possible and could be structural or electrical. Common substrates include the electrical system of the heart, dilation (or stretching) of the atrium, cellular-molecular changes, and/or an increase in disruptive cells called fibroblasts. In general, many or all of these changes would occur, leading to constant AFib.

AFib is very dangerous. Other than a wonky pulse, there are three major complications: heart failure, stroke, and myocardial infarction (a heart attack). Heart failure is when the heart can’t pump enough blood, while stroke and myocardial infarction can be caused by stray blood clots. Heart failure is both a risk and a symptom, which illustrates one way in which AFib is a progressive disease. Through complicated electric and biocellular mechanisms, long term AFib seems to cause more AFib.

Treating AFib has proven difficult. It is effective to treat the underlying risk factors, such as obesity and diabetes, but this is difficult and the actual cause of AFib isn’t always clear. Controlling the rhythm of the heart is also tough and risky, as messing with heart rhythm can easily lead to big problems. Atrial fibrillation ablation is an effective treatment. It is an intensive surgical procedure where doctors scar problem areas to reduce electrical activity. Even with this method, the risk of resurgence is over 30% after 5 years.

Two of the biggest complications of AFib are related to blood clots. Because of this – and the difficulty of other treatments – major pharmaceuticals often target thromboembolisms, or clots. The clotting system itself is very complicated. A simple version is that platelets activate and produce several enzymes. These enzymes make thrombin, which makes a big mesh-like protein called fibrin. This would be a slow process, except that thrombin also activates amplifier enzymes, which makes this process very fast. The fibrin then catches red blood cells and blocks wounds – or blood vessels. When these clots travel to the brain they can cause a stroke. When they restrict blood flow to the heart they can cause a myocardial infarction – a heart attack.

Classic anticoagulants, such as Warfarin (also called Jantoven and Coumadin) work by stopping the clots before they start. These are Vitamin K dependent anticoagulants and can be effective at reducing clots. Unfortunately, they are occasionally too effective. The biggest side effect of Vitamin K dependent anticoagulants is increased bleeding. This can be a serious problem for several patients, including high-risk older patients. 

Doctors are investigating new classes of medications which do not depend on vitamin K. These are called Non-vitamin K oral anticoagulants (NOACs) and some target the amplification pathway of clotting instead. There are  currently four FDA-approved NOAC drugs on the market; dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa). Thrombin and fibrin still get produced and some clotting can occur, but the rapid amplification is shut down. The hope is that this can allow the body to repair trauma and stop external bleeds without building internal clots from AFib. With your help and participation in clinical trials, we can push science without pushing clots.

By Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Iwasaki, Y. K., Nishida, K., Kato, T., & Nattel, S. (2011). Atrial fibrillation pathophysiology: implications for management. Circulation, 124(20), 2264-2274. https://doi.org/10.1161/CIRCULATIONAHA.111.019893

Wijesurendra, R. S., & Casadei, B. (2019). Mechanisms of atrial fibrillation. Heart, 105(24), 1860-1867. http://dx.doi.org/10.1136/heartjnl-2018-314267

Vann, M. R. (May 10, 2013) The Sound of an Afib Heartbeat. Everyday Health. https://www.everydayhealth.com/heart-health/sound-of-afib-heartbeat.aspx


C.-diff-stomach-pain.jpg

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Clostridioides difficile, C. difficile, or just C. diff is a particularly nasty bacteria that can make us very sick. The bacteria itself has the name difficile because it was difficult to isolate and study when it was first discovered. Forms of the problem bacteria are found all over the environment, but most can’t make us sick. The organism itself doesn’t kill cells like a virus; instead, it can produce toxins that can kill cells in the gut. C. diff has over 800 different strains, but only a few produce dangerous toxins. Overall, C. diff causes dangerous infections in hundreds of thousands of patients each year.

Several people have C. diff inside their gut already, but it doesn’t cause them problems. Other bacteria in our gut can outcompete C. diff and keep it from causing damage. Unfortunately, one of the biggest medical breakthroughs, antibiotics, can destroy these helpful bacteria and allow C. diff to start running amok. In fact, any kind of immunosuppression can increase your risk of developing C. diff, including HIV/AIDS medications and those used after organ transplants. Being above 65 years old is another large risk factor. Close contact with some animals, like pigs, can also pose a risk. The most dangerous forms of C. diff are spread from person to person. This occurs with our most vulnerable populations: those in hospitals and those in elderly care. Due to the innate nature of care, people in hospitals and care homes can be exposed to C. diff unknowingly.

How does C. diff survive in the notoriously clean hospital environment? The bacteria has a special trick up its sleeve; it can become dormant – and almost invincible. C. diff has two life cycle stages, the spore and vegetative stage. While in the spore stage, C. diff is inactive. It doesn’t need to eat or breathe. While in this stage it can survive in the environment, the stomach, through most antibiotics, and through alcohol washes. When a C. diff spore makes it into our gut, however, trouble can begin. It germinates in the duodenum – the part of the intestine connected to the stomach. Here it transforms into the vegetative stage. In the vegetative stage, C. diff is active. It can’t survive the stomach or in oxygen, but thrives in the intestines. Here it grows and reproduces. This is also where some strains produce dangerous toxins.

The toxins of C. diff can produce a host of issues. The toxins can degrade and kill intestinal cells and cause inflammation of the intestines. Major symptoms are diarrhea, inflammation of the gut, and tissue necrosis (cell death). Other symptoms can include:

  • Fever
  • Tenderness and pain in the stomach
  • Loss of appetite and nausea
  • A severely dilated colon (toxic megacolon)
  • Sepsis (severe infection response)
  • Death

So what can be done to fight C. diff? The first line of defense is the simplest: wash your hands! Prevention is the strongest barrier: avoid close contact with people who have an active infection and wash clothes and linens regularly. A medical professional (who should be wearing gloves!) can monitor any antibiotics an infected person is currently taking and might suggest probiotics. Some specific antibiotics target C. diff, including Metronidazole, Vancomycin, and Fidaxomicin. These may have unpleasant side effects, but can be effective. Treatments available include fecal microbiota transplantation (FMT), antitoxins, new antibiotics, and injectable antibodies. Additionally, prophylactics that can help protect the gut and vaccines against the dangerous toxins are in development. Keep an eye out, and with your participation in clinical trials, we can help protect those at the highest risk from  C. diff!

By Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Dayananda, P., & Wilcox, M. H. (2019). A review of mixed strain Clostridium difficile colonization and infection. Frontiers in microbiology, 10, 692.https://doi.org/10.3389/fmicb.2019.00692

Smits, W. K., Lyras, D., Lacy, D. B., Wilcox, M. H., & Kuijper, E. J. (2016). Clostridium difficile infection. Nature reviews Disease primers, 2(1), 1-20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453186/

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (September 7, 2022). What is C. diff  https://www.cdc.gov/cdiff/what-is.html


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When EMTs arrive on the scene of an emergency, they have to remember their ABCs. These are Airway, Breathing, and Circulation. The absolute top priority for any patient is to ensure they have an open airway to breathe, that air is entering the lungs, and that the heart is pumping blood to the brain and other organs. This is also the most important thing our body does in daily life as well. We can go weeks without food, days without water, hours without ice cream, and minutes without oxygen.

In order to get oxygen from the lungs to our brain and organs, we rely on one of the most remarkable organs in our body: the heart. The heart pumps automatically, nonstop, 24/7, from womb to grave. It consists of four chambers, two on top, and two on the bottom. Each heartbeat pulls blood into the top two chambers and pumps it out of the bottom two. The bottom two are more muscular and do the heavy lifting. Unfortunately, the heart can deteriorate and lead to heart failure. 

Heart failure is a condition where the heart can’t pump well enough to deliver oxygen to the organs effectively. The heart is still pumping, but organs are not receiving enough oxygen to function. This is not good. Heart failure affects over six million Americans and ten times as many people worldwide. Risk factors for heart failure include:

  • Heart disease, including Coronary Artery Disease
  • High Blood pressure
  • Tobacco
  • Excessive alcohol
  • Poor diet
  • Lack of exercise
  • Obesity
  • Diabetes

Heart failure has several signs and symptoms. Some of the most consistent are edema and shortness of breath. Edema is fluid trapped in the body’s tissues and most often pools in the lower extremities and the abdomen. Shortness of breath is due to the heart failing to deliver enough oxygen. This is particularly prevalent when trying to do activities or when lying down. Shortness of breath can keep patients from exercising or sleeping, which only exacerbates problems. Patients who have limited exercise in their routine may not be aware of progressive difficulty, masking this important symptom.

Other symptoms can be broad and nonspecific. They include:

  • Sudden weight gain
  • Persistent coughing or wheezing
  • Lightheadedness and fainting
  • Depression
  • Nausea and loss of appetite
  • Irregular heartbeat, high pulse, and palpitations
  • Fatigue

If you have heart failure and find yourself experiencing several of these conditions simultaneously, especially with edema and shortness of breath, we urge you to contact your physician immediately. Additionally, you may want to keep track of your level of fatigue because this symptom increases as the heart failure progresses. The excellent news is that new and exciting monitoring devices are currently being developed to help patients manage their heart failure and determine if their condition is deteriorating.

Check out clinical research options available to you with ENCORE Research Group on our enrolling studies page. 

By Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Albert, N., Trochelman, K., Li, J., & Lin, S. (2010). Signs and symptoms of heart failure: are you asking the right questions?. American Journal of Critical Care, 19(5), 443-452. https://doi.org/ajcc2009314

Groenewegen, A., Rutten, F. H., Mosterd, A., & Hoes, A. W. (2020). Epidemiology of heart failure. European journal of heart failure, 22(8), 1342-1356. https://doi.org/10.1002/ejhf.1858

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (October 14, 2022). Heart failure  https://www.cdc.gov/heartdisease/heart_failure.htm


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November 16, 2022 BlogMedEvidence

We all know how Thanksgiving works. A giant meal with a giant turkey followed by tasty desserts. Then, after the meal, sleepiness sets in. But why? We usually blame the turkey and the tryptophan in the protein. But I’m a vegetarian, and I still get the post-thanksgiving snoozies. So, what is tryptophan, and does it make us tired, or is there something else to blame? This article contains a cornucopia of information to help answer these questions.

Tryptophan is an essential amino acid. Amino acids are the building blocks of proteins and are baked into many of the body’s needs. Being an “essential” amino acid means that we can’t create our own tryptophan and must instead gather it from the foods we gobble up. We need some tryptophan in our diet because it is used to create some critical molecules our body uses.

Two of these important molecules are the neurotransmitter serotonin and the hormone melatonin. These are critical little molecules derived from tryptophan and – interestingly, both interact with our sleep cycle. Serotonin acts on parts of the brain involved with learning, pain, social behavior, and sleep, among many others. Melatonin is like turkey dressing; it’s harvested further from serotonin and can increase sleepiness. Neither of these gets produced in large quantities after eating turkey, however. The large amount of other amino acids found in turkey protein keep tryptophan from making a pilgrimage to the brain after a meal because the amino acids compete for rides on the path to our brain.

So then, why do we feel tired after a big Thanksgiving meal? Well, one reason might be linking carbs (sugars) to tryptophan. Some carbohydrates can increase the ability of tryptophan to cross into the brain and get serotonin and melatonin cooking. Additionally, heavy carbohydrate intake has been associated with higher levels of tiredness and lower levels of alertness. This can be attributed to the rise in blood sugar from the heavy carbohydrates which is followed by release of insulin to lower the blood sugar.  The lower blood sugar causes you to feel tired.  So too much dessert might be resulting in a blood sugar crash after the meal.

In fact, too much of everything may be making you tired. When we eat large meals, the body activates the parasympathetic nervous system. This is also known as the “rest and digest” pathway, and does exactly what it sounds like. After a large meal, the body focuses on relaxation and digestion. This can cause extra blood flow into the stomach and can make you less alert and awake.

Turkey may get too much blame for our tiredness. As my sweet tooth will attest, the desserts may be a bigger culprit. So, this Thanksgiving, feel free to gather the family to feast (and nap) as you please, but squash the blame on the turkey!

Written by: Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Ballantyne, C. (2007). Does Turkey Make You Sleepy? Scientific American. https://www.scientificamerican.com/article/fact-or-fiction-does-turkey-make-you-sleepy/

Høst, U., Kelbaek, H., Rasmusen, H., Court-Payen, M., Christensen, N. J., Pedersen-Bjergaard, U., & Lorenzen, T. (1996). Haemodynamic effects of eating: the role of meal composition. Clinical Science, 90(4), 269-276.

Mantantzis, K., Schlaghecken, F., Sünram-Lea, S. I., & Maylor, E. A. (2019). Sugar rush or sugar crash? A meta-analysis of carbohydrate effects on mood. Neuroscience & Biobehavioral Reviews, 101, 45-67.

Vreeman, R. C., & Carroll, A. E. (2007). Medical myths. Bmj, 335(7633), 1288-1289.


Hawthorne-Effect-Lightbulb.jpg

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Several of my friends hate flossing their teeth. They go months without flossing, which I think is pretty gross. But then an odd thing happens. About a week before their dental appointment, these same friends will start flossing. By the time they reach their appointment, they have unusually clean gums (though dentists can see through this fairly well, I’m told). On a different tone, some family members have a condition called White Coat Syndrome. When they go to the doctor’s office, their nervousness causes a spike in blood pressure or heart rate, giving deceptively high readings. What’s going on? Can psychological effects like these be used to our advantage?


The Hawthorne Effect is a term used to describe a very beneficial effect seen in clinical trials. This is named after a productivity study in Hawthorne Works, a Western Electric factory in the 1920s and 30s. The study was attempting to discover a link between the amount of light and productivity of workers. When increasing the amount of light, productivity increased. Strangely, when lowering the amount of light, productivity also increased! Researchers attributed the increase in productivity to the workers simply being observed. In research, we tend to see increased positive results for patients simply because we are observing them in a study.


Hawthorne Works


Let’s analyze a 2014 sleep study. Researchers measured 195 patients’ amount and quality of sleep at night. 81 days later, before any medical intervention, researchers measured the patients again. They found that patients slept an average of 30 minutes longer per night and had an increased quality of sleep. This was before any medication or intervention! The change was attributed to the Hawthorne Effect.

Patients at ENCORE Research Group comment on the excellent quality of care they receive during clinical trials. Instead of seeing a doctor for a few minutes once a year, patients see doctors and medical staff for much longer and are encouraged or required to call and report changes in health. Quality of care is increased and makes for a pleasant and healthful patient experience. Patients in clinical trials may also experience more observation time from medical professionals due to the attention to detail that clinical trials require for data integrity in studies.

Finally, patients are found to have better adherence to medication requirements while undergoing clinical trials. The increased emphasis on accuracy and adherence results in better patient outcomes, even when they are part of a placebo or standard-of-care group.

In clinical trials, we see these benefits and must account for them. Randomization of patients helps spread the effect. Everyone sees increased baseline results on average; we are interested to find out if those receiving investigational treatment do even better. Join a clinical trial today and experience the Hawthorne Effect for yourself… and floss your teeth!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Benedetti, F., Carlino, E., & Piedimonte, A. (2016). Increasing uncertainty in CNS clinical trials: the role of placebo, nocebo, and Hawthorne effects. Lancet Neurol, 15, 736-47. http://dx.doi.org/10.1016/S1474-4422(16)00066-1

Cizza, G., Piaggi, P., Rother, K. I., Csako, G., & Sleep Extension Study Group. (2014). Hawthorne effect with transient behavioral and biochemical changes in a randomized controlled sleep extension trial of chronically short-sleeping obese adults: implications for the design and interpretation of clinical studies. PLoS One, 9(8), e104176. https://doi.org/10.1371/journal.pone.0104176

ENCORE Research Group. (2020, October 14). Hawthorne effect.[Video]. Youtube. https://www.youtube.com/watch?v=1DH7jwqFlyw

Mayo, E. (1993). The human problems of an industrial civilization. The Macmillan Company. 

McCarney, R., Warner, J., Iliffe, S., Van Haselen, R., Griffin, M., & Fisher, P. (2007). The Hawthorne Effect: a randomised, controlled trial. BMC medical research methodology, 7(1), 1-8. https://doi.org/10.1186/1471-2288-7-30


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The liver is critical to maintain body function. Unfortunately, millions of Americans suffer from liver disease. When the liver suffers prolonged damage, scarring can form. This scarring, called cirrhosis, is debilitating and reduces liver function. Cirrhosis is sometimes called end stage liver disease, and is irreversible. On its own, cirrhosis can be painful and cause suffering, but is frequently made worse through complications. One of these is encephalopathy.

Encephalopathy is a broad term used to describe several diseases and disorders. The unifying concept is that these diseases change the brain’s structure or function. When the cause of this change is through cirrhosis, the condition is called hepatic encephalopathy. This is the condition caused by cirrhosis of the liver, and can be horrible. It comes with a high mortality rate, over 25%, and affects over 30% of people with cirrhosis.

The full mechanism of how hepatic encephalopathy works isn’t fully known. The most likely candidate for hepatic encephalopathy is a buildup of ammonia in the bloodstream. Ammonia is a common waste product for many cells. A damaged liver has trouble filtering ammonia from the blood. The ammonia accumulates in the blood where it can travel to the brain and cause confusion and disorientation at first. Additionally, liver damage can result in reduced muscle mass and immunosuppression. Muscles can remove excess ammonia from the blood, but may become damaged without a functional liver and be unable to help. A reduced immune system can lead to a buildup of harmful bacteria that produce excess ammonia. These combine to create excess toxic levels of ammonia in the bloodstream that make their way to the brain.

The brain is normally protected from toxins in the blood through the blood brain barrier. Astrocytes are special cells in the brain that surround blood vessels and help filter the blood, letting only specific nutrients and particles through. Excess ammonia in the blood appears to damage astrocytes, with wide ranging effects on the brain. When the blood-brain barrier is reduced, toxins can enter the brain. This can lead to damage in neurotransmission, meaning the brain cannot function effectively. There is also an increased chance of infection in the brain and alterations to brain metabolism.

This is a devastating compilation which can drastically reduce quality of life. In the early stages of hepatic encephalopathy, people may experience a general slowing of the brain. This is noticeable in attention, some motor response, and other vague areas. As the encephalopathy progresses, people experience more severe symptoms. Changes in personality have been reported, such as irritability and impulsivity. They may angrily buy m&ms in the checkout line. It also slows the brain and reduces its ability to function. People may become disoriented, experience distortions of time and space, become excessively sleepy, and descend into a coma. Clearly this condition needs medical attention!

Luckily, hepatic encephalopathy can be reversible in many patients! The most important short-term treatment is to get rid of excess blood ammonia. The current standard of care is lactulose, a chemical that binds to ammonia and expels it rectally. This helps in the short term, and can also be recommended to help reduce recurrence. Though effective, lactulose is a laxative and can cause bloating, cramping, and other undesirable side effects. Because of this, many patients don’t like using this drug long term. Since the immune system is suppressed with cirrhosis, antibiotics may help as well. In fact, antibiotics may be helpful in preventing hepatic encephalopathy in the first place by eliminating harmful, ammonia producing bacteria before they can produce too much ammonia. Used with or without probiotics and drugs that help restore normal brain chemistry, we may be able to lower the burden of hepatic encephalopathy for those who suffer.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Bustamante, J., Rimola, A., Ventura, P. J., Navasa, M., Cirera, I., Reggiardo, V., & Rodés, J. (1999). Prognostic significance of hepatic encephalopathy in patients with cirrhosis. Journal of hepatology, 30(5), 890-895. https://doi.org/10.1016/s0168-8278(99)80144-5

Ferenci, P. (2017). Hepatic encephalopathy. Gastroenterology report, 5(2), 138-147. https://doi.org/10.1093/gastro/gox013


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In science and medicine we measure if and how well things work using measurements. This idea may sound simple, but it’s often a challenge to find out exactly what to measure – and how. We typically measure things that can change – things that can vary. We call these things variables. Variables can be broadly split into two major categories: dependent and independent. Either type of variable can change, the difference is what changes them.

Independent variables are changed by researchers, particularly in clinical (patient) research. This variable in a medical research study is what we are testing. The changes to an independent variable may include dose, length, and method of drug delivery. We evaluate independent variables that may change outcomes of the people in a study – but sometimes they do not. In order to understand the effect of medicines, researchers test the medicine against a control. The control could be a placebo (something that has no effect) or a standard of care (the current normal medicine).

Dependent variables are what we expect to change during a trial. In a clinical research, we may expect changes in blood pressure, cholesterol levels, disease symptoms, mortality, and other categories. In a well designed study, we assess changes in the dependent variables related to changes in the independent variables. There is always the chance that the dependent variables are changed by other things, however. A patient might take a new blood pressure medicine but retire from their job. The reduced stress could decrease their blood pressure even if the medicine did not. 

Because of individual changes in people’s circumstances, researchers use statistics to find trends. If your blood pressure medicine was only studied on the one person above, you might have erroneous results. Instead clinical trials have dozens, hundreds, or even thousands of participants. With large populations these little differences get figured out. One person might retire, but another might get fired, having an opposite effect. Altogether, statistical analysis can help discover if any changes in the dependent variable are due to the effects of the independent ones.

Chart 1. Each amount of Rosuvastatin on the left corresponds to an amount of LDL on the right. The dependent variable (LDL levels) change in proportion to the amount of independent variable (rosuvastatin) taken by the patient.


Other variables exist in a study. The most concerning of these variables is known as a confounding variable. This is a variable that can undermine the study at a fundamental level. A confounding variable can be introduced by researchers and might include things like placing all overweight patients in the 10 mg group and all underweight people in the placebo group. ENCORE Research Group (and any legitimate clinical research group) avoids confounding variables and bias by randomizing patients. Patients are randomized through an impartial method (usually a computer program) which will randomly place patients into any of the test groups. By randomizing patients, we can avoid the most concerning confounding variables and make sure we are studying what we intend to!

To learn more about the clinical trial process, call our Recruitment Team at (904) 730-0166.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Schweiger, C. (2003). Clinical trials with rosuvastatin: efficacy and safety of its use. Italian Heart Journal: Official Journal of the Italian Federation of Cardiology, 4, 33S-46S. https://pubmed.ncbi.nlm.nih.gov/14983745/

Stewart, P. A. (1978). Independent and dependent variables of acid-base control. Respiration physiology, 33(1), 9-26. https://www.nlm.nih.gov/nichsr/stats_tutorial/section2/mod4_variables.html


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A pandemic spread around the planet in the first quarter of the century. Not this century, however, but the last. The 1918 Flu Pandemic was the largest and deadliest outbreak of disease since the bubonic plague in the 1300s. The first official reported case was in Kansas in 1918. This gives the disease its proper name, the 1918 Influenza Pandemic. A much more common name, however, is the Spanish Flu.           

The name Spanish Flu is an unfair name. Spain lost around a quarter million people to the 1918 Influenza. This is less than half as many as the USA, and fewer than Afghanistan, Mexico, Russia, Italy, and Japan. On top of that, India lost somewhere above 18 million people, and China between four and nine million. The big difference in losses was due to Spain being neutral during World War I. Because of this, they weren’t shy about publishing accurate data. Spain was the first country to publicly disclose that the pandemic was real, and other countries underreported or lied about numbers for years. This may strike some as familiar; during the COVID-19 pandemic, several national and local governments around the world tried to downplay the severity of COVID for political gain.           

But what is influenza? Influenza, known as the flu, is very similar to COVID-19 in many ways. It is a viral infection, and its primary symptoms are cough, fever, joint pain, headache, body aches, and others. However, more serious complications such as pneumonia, liver damage, or brain problems can be triggered by influenza. It spreads through the air and can survive in water. Soap, changes in pH, and heat can destroy the influenza virus. The most dangerous part of influenza is how variable it is.  

The influenza virus has several subtypes, and each of these mutates constantly.  This makes it hard for the immune system to detect and fight new forms of the virus. It also means the specific symptoms of infections can change. In the 1918 influenza pandemic, the strain of influenza was particularly deadly for young, healthy people. This resulted in a lot of excess deaths compared to other strains. 

The 1918 Influenza Pandemic was made much worse because of World War I. The war resulted in overcrowded barracks, troops stuffed in ships, and people crowding in shelters. Additionally, it spread wide and far as governments deployed troops around the world. A lack of accurate reporting and proactive measures certainly didn’t help. The biggest difference between then and now was medicine. 

1918 was over a hundred years ago, but in the realm of medicine, it may as well have been much longer. Viruses were only discovered around 20 years prior, and there were no effective ways to fight them. There were no antiviral medications. For patients that developed pneumonia, there were no ventilators and no antibiotics. On top of this, there was no influenza vaccine. 

The “Spanish flu” of 1918 helped refocus medical attention around pandemics – particularly influenza. In the early 1930s new vaccines were being developed from chicken eggs, and less than ten years later, the first experimental influenza vaccines were developed. Today, our yearly flu shots come from a direct line of response from the 1918 influenza pandemic. A century later, we have come a long way with medical advances, and since we know the influenza virus mutates regularly, the best way to help continue the fight against it is to participate in a clinical trial for the latest flu vaccines.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Hayden, F. G., & Palese, P. (2009). Influenza virus. Clinical virology, 943-976.

Jester, B., Uyeki, T. M., Jernigan, D. B., & Tumpey, T. M. (2019). Historical and clinical aspects of the 1918 H1N1 pandemic in the United States. Virology, 527, 32-37.

Johnson, N. P., & Mueller, J. (2002). Updating the accounts: global mortality of the 1918-1920″ Spanish” influenza pandemic. Bulletin of the History of Medicine, 105-115.

Knobler, S. L., Mack, A., Mahmoud, A., & Lemon, S. M. (2005). The threat of pandemic influenza: are we ready? workshop summary.

Mayer, J. (29 January 2019). “The Origin Of The Name ‘Spanish Flu’”. Science Friday. Retrieved 30 July 2021. https://www.sciencefriday.com/articles/the-origin-of-the-spanish-flu/

CDC, National Center for Immunization and Respiratory Diseases. (September 28, 2022). Similarities and Differences between Flu and COVID-19​. https://www.cdc.gov/flu/symptoms/flu-vs-covid19.htm


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September 27, 2022 BlogDiabetesMedEvidence

How does the body use energy? After we eat, most food is broken down into parts that cells can use for energy. The bloodstream carries these pieces through the bloodstream to our cells, which let them in and convert food to energy. In some cases, the cells don’t let food particles in. In these cases, the problem may be diabetes.

Cells need to separate their insides from the environment around them. Cells only let in specific molecules at specific times. Insulin is the molecule that tells cells to let in sugars in the form of glucose. It is produced by the pancreas and is released when the pancreas detects high levels of sugars in the blood. In some cases, such as with obesity, fatty acids can disrupt how cells absorb and use sugar in the blood. When this happens, cells are less sensitive to insulin and absorb less blood sugar per unit of insulin in the blood. Since blood sugar stays high, the pancreas produces more and more insulin, which has less and less effect. Cells can’t respond to all the excess insulin and are increasingly resistant to its effects.

Insulin is also the hormone the pancreas uses to communicate with the liver about blood sugar. When the liver detects insulin it converts blood glucose into glycogen, a short term storage molecule. When high levels of insulin persist, the liver sends extra energy to fat cells.

After long periods of insulin resistance, the pancreas itself stops working properly. Pancreatic cells become damaged and unable to produce insulin. This is called Type 2 Diabetes (T2D). With T2Ds, blood sugar stays high, insulin stops being produced, any produced insulin is less effective, and cells stop metabolizing properly. On top of this, the body gains excess weight which can stress the pancreas further. Other symptoms include cardiovascular disease, nerve dysfunction in the extremities (called neuropathy), and increased chance of death.

Diabetes is very common in the United States. Tens of millions of Americans have T2D. Type 1 diabetes is an autoimmune disorder which results in pancreatic damage. Type 2 diabetes is an insulin resistance disorder and can have a slow onset.  Major risk factors are obesity and lack of exercise. These should be the first steps to managing T2D as well.

When a healthy diet and exercise aren’t enough to manage healthy blood sugars, or aren’t an option, several key medications exist to help with type 2 diabetes:

  • Insulin: By injecting insulin with meals, the effects of a compromised pancreas can be reduced. Synthetic insulin, such as glargine, is in wide use.
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RA): These stimulate the pancreas and coerce it into properly releasing the correct amounts of insulin. It slows some pancreatic cells and helps restore the pancreas-liver communication lines. One generic name for GLP-1 RA drugs is semaglutide, often branded as Ozempic and Rybelsus. A benefit of these drugs is that a common side effect is weight loss, one of the drivers of type 2 diabetes.
  • Metformin: Originally inspired by the French Lilac plant, metformin lowers blood sugar levels by acting on the liver, bloodstream, intestinal tract, and even the gut microbiome! The complex action on different areas of the body results in overall lower blood sugar levels.
  • SGLT2 Inhibitors: These act on the kidneys, changing the threshold of reabsorption of sugar so they excrete more than usual removing blood sugar through the urine. 

Altogether, there are several medications which may be helpful for controlling type 2 diabetes. Discovering how these medications interact, lowering side effects,  and finding treatments that are easy and straightforward is key. If you have type 2 diabetes, look for enrolling studies soon and improve your diet and exercise if possible!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Berg, J. M., Tymoczko, J. L., & Stryer, L. (2012). Biochemistry (7th Ed., pp 798-803). New York: W. H. Freeman and Company

DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., … & Weiss, R. (2015). Type 2 diabetes mellitus. Nature reviews Disease primers, 1(1), 1-22. https://www.nature.com/articles/nrdp201519

Olokoba, A. B., Obateru, O. A., & Olokoba, L. B. (2012). Type 2 diabetes mellitus: a review of current trends. Oman medical journal, 27(4), 269. http://doi.org/10.5001/omj.2012.68

Rena, G., Hardie, D. G., & Pearson, E. R. (2017). The mechanisms of action of metformin. Diabetologia, 60(9), 1577-1585. https://doi.org/10.1007%2Fs00125-017-4342-z

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (August 10, 2021). Insulin Resistance and Diabetes https://www.cdc.gov/diabetes/basics/insulin-resistance.html

U.S. Department of Health & Human Services/Centers for Disease Control and Prevention (December 16, 2021). Type 2 Diabetes https://www.cdc.gov/diabetes/basics/type2.html

Witters, L. A. (2001). The blooming of the French lilac. The Journal of clinical investigation, 108(8), 1105-1107.https://doi.org/10.1172%2FJCI14178


Alzheimers-disease-Pathological-Tau-protein.jpg

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Methods used to diagnose Alzheimer’s disease are changing. In the past, the only definitive way to diagnose Alzheimer’s disease was after death, by an autopsy, which is not exactly helpful for treatment. The autopsy would reveal both amyloid plaques and tau tangles in the brain; these are hallmarks that characterize Alzheimer’s disease. Thankfully, science has drastically improved over the years. We currently have spinal fluid tests that look for these two key biomarkers and imaging tests that show changes in the brain.

A recent example of other evolving diagnosis methods is COVID-19. Early in the pandemic, when there were no COVID-19 tests, the only way to know if someone might have the virus was to check for a fever. Nowadays, we look for biomarkers – such as with a rapid antigen test – which can detect antigens to the virus even in asymptomatic people. 

We now understand that a person can be suffering from the progressive nature of Alzheimer’s even if they do not yet show signs of cognitive impairment. Without biomarker testing, most patients’ first symptoms are memory loss, including long and short-term. Alzheimer’s is usually associated with increased age because the biological underpinnings of the disease accumulate over time. Diagnosis can be made by using something called the ATN framework. This framework describes the two major proteins involved, amyloid plaques and tau tangles, and the associated neurodegeneration – changes in the brain structure.


Let’s discuss the AT part of ATN: the two protein accumulations called amyloid plaques and tau tangles. It is no coincidence that these are also the biomarkers sought by scientists and doctors when diagnosing Alzheimer’s. Amyloid plaques are bundles of protein that build up outside of cells in the brain. They disrupt how cells connect and communicate with each other. Tau tangles are proteins found inside the neurons. In a healthy neuron, tau proteins help stabilize the microtubule that transfers nutrients. In Alzheimer’s patients, the tau proteins become corrupted and tangled, blocking the neuron’s transport system. This leads to cell death. As more cells die and neural network connections break down, areas in the brain begin to shrink.  In the late stages of Alzheimer’s disease, there is widespread loss of brain volume.


The N of ATN is neurodegeneration which is the deterioration of neurons causing specific structural changes to the brain. A structural MRI and a radioactive PET scan are two classic methods of determining neurodegeneration. These are effective as staging tools, discovering how far along the disease has progressed. They are effective but can be expensive and time-consuming.

The good news is that researchers are currently working on blood tests that will hopefully be able to detect tau biomarkers quickly and easily. A blood test should be easy, cheap, and relatively simple. With luck, these early biomarker findings will also help drive the effectiveness of clinical therapies, paving the way for better Alzheimer’s treatments in the years to come.

By Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S., Hudspeth, A. J., & Mack, S. (Eds.). (2000). Principles of neural science (Vol. 4, pp. 1149-1159). New York: McGraw-hill.

Largent, E. A., Wexler, A., & Karlawish, J. (2021). The Future Is P-Tau—Anticipating Direct-to-Consumer Alzheimer Disease Blood Tests. JAMA neurology, 78(4), 379-380. https://doi.org/10.1001/jamaneurol.2020.4835

Ossenkoppele, R., Reimand, J., Smith, R., Leuzy, A., Strandberg, O., Palmqvist, S., … & Hansson, O. (2021). Tau PET correlates with different Alzheimer’s disease‐related features compared to CSF and plasma p‐tau biomarkers. EMBO molecular medicine, 13(8), e14398. https://doi.org/10.15252/emmm.202114398

Peterson, R. C. [UCI MIND] (2019, April 3).  Diagnosis of Alzheimer’s disease in the era of biomarkers – Ronald C. Petersen, MD, PhD [Video]. Youtube. https://www.youtube.com/watch?v=KtS5xynes2M

What Happens to the Brain in Alzheimer’s Disease? (2017, May 16) National Institute on Aging. https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease


Kidney-Impariment.jpg

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Imagine if your plumbing stopped up. Not your toilets, but your sink and shower. How would you get rid of the dirt and junk off your skin? How would you make sure you stay clean? Our kidneys ask this question every day. The blood in our body travels around and around, including the critical filtration stage of the kidneys. The kidneys act as a big two-way filter. Impurities and excess minerals or water are extracted from the blood, and necessary minerals or water are added as needed. The kidneys keep the ingredients of blood at healthy levels. Finally, kidneys get rid of waste products and extra water by producing urine. When this goes wrong, your blood can’t function properly and waste products can build up.

When dealing with the kidneys, you may see three terms thrown about. The origin of “kidney” is unknown, but likely English. “Renal” is the Latin word for kidneys, and the prefix “nephro-” is Greek in origin. If you see any of these terms you can bet we’re dealing with the kidneys. With this in mind, when the kidneys fail to perform their job, we call it renal insufficiency.

There are two major divisions in how the kidneys fail, based on the amount of time. 

  • Acute kidney injury (AKI) has a sudden onset. It may affect 100,000 people a year in the United States, with a higher proportion of sufferers being Black or African American than White.
  • Chronic kidney disease (CKD) is the long term degradation of the kidneys.  It is harder to measure, as the kidneys do a pretty good job compensating: until they don’t. It is estimated that around 2 million Americans may be suffering from CKD, with the majority being men.

There are several possible causes of renal impairment. The vast majority of causes are “upstream,” meaning something affects the blood before it gets to the kidneys.

In acute cases, this can be hypotension – not enough fluid, some drugs, such as NSAIDs, or organ failure. When there isn’t enough fluid in the bloodstream, the kidneys compensate by releasing more water, which can deplete the kidney’s reserves and cause failure.

In chronic kidney disease, the most frequent cause is diabetes, especially type 2. Prolonged hypertension, and vascular diseases can also be the culprit. With chronic cases, the kidneys will do their best to compensate – constantly filtering out excess blood sugar, for instance. Over time, the excess sugar damages the blood vessels in the kidneys.  Some parts of the kidneys may fail and the remaining portions get stressed and eventually decompensate. This is when the kidney fails as an organ.

Other possible causes of renal impairment are contained in the kidneys and “downstream” blockages. The kidneys themselve can be the victim of disease or injury, possibly due to long term upstream stress. The ability of the kidney to release urine can also -in rare cases – be disrupted.

Regardless of the cause, renal impairment is very dangerous. The kidneys are responsible for keeping blood healthy. A failure of the renal system can result in a need for dialysis or transplant. Dialysis is when external technology filters blood and maintains levels. This is uncomfortable, cumbersome, and expensive.

Fixing renal impairment can be a tall order. The most important step is usually treating the underlying cause. Since the kidneys filter several drugs out of the bloodstream, stopping or replacing them may be key. Fluids may need to be replaced in acute cases, and lifestyle changes may be needed in chronic ones. Maintaining healthy blood sugar levels can be key if the root cause is diabetes. For heavily progressed chronic renal impairment, dialysis or transplant may be the only options.

Transplant and dialysis are not fun, so we should try to avoid renal impairment before it starts. Many of the tactics to keep your kidneys healthy are the same to keep the rest of your body healthy. Exercise, not overindulging on sugar, and keeping your diet under control can help. Additionally, maintaining a healthy blood pressure is vital. Finally, lowering or cutting out tobacco and alcohol can help keep your kidneys healthy.  When it comes to filtering your blood, give your kidneys every advantage you can!

By Benton Lowey-Ball, BS Behavioral Neuroscience



Adapted from:

Bindroo, S., & Rodriguez, Q. BS; Challa, HJ Renal Failure. (February 24, 2022). StatPearls; StatPearls Publishing: Treasure Island, FL, USA. https://www.ncbi.nlm.nih.gov/books/NBK519012/


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Heart failure is quite frankly, a terrifying sounding condition. It is severe, but not as immediately drastic as it sounds. Put simply, heart failure is when the heart fails to pump as much blood as the body will need long-term. The heart works like a balloon, filling with blood and contracting to pump it out. Ejection fraction is a term used to describe the amount of blood pumped out compared with the total the heart can hold. In a normal heart, 50-70% of blood is ejected with each heartbeat. When this amount falls below 40%, a person has a reduced Ejection Fraction (the rEF of HFrEF). This is a serious condition.

The heart pumps blood to every cell in the body. This is how cells receive oxygen and nutrients, and how they get rid of waste products. Without enough blood, cells suffocate. Oxygen isn’t reaching cells and the brain interprets this as being short of breath. Common symptoms of HFrEF include:

  • Fatigue
  • Difficulty breathing, especially when lying down or sleeping
  • Inability to exercise
  • Ankle swelling

Inside the body, doctors can also look for diagnostic markers. These may include structural changes to the heart and increased natriuretic peptides. Natriuretic peptides are hormones that regulate the amount of salt and water in the blood. They act as vasodilators, opening blood vessels which can be helpful in compensating for heart failure. The body attempts to compensate for the loss of oxygen and nutrients in the blood in many ways, but long term the body has trouble sustaining with heart failure.

Who is at risk of developing HFrEF? Unfortunately, it is more prevalent in the United States than almost anywhere else, affecting 6.5 million Americans each year. Risk factors include age, being male, obesity, and smoking. Additionally, other medical conditions increase your risk of developing Heart Failure with reduced Ejection Fraction. Previous heart attacks, coronary heart disease, diabetes, and hypertension are some associated conditions. All told, HFrEF leads to around a million hospitalizations every year, and being hospitalized for HFrEF comes with a low 5-year survival rate.

What can be done? There are several methods of dealing with a reduced ejection fraction. Some methods treat symptoms, such as diuretics, and others can help reduce mortality, such as beta-blockers. There are several other medications and even some implantable devices that can help with HFrEF. These can help improve your ejection fraction or health outcomes but are not yet a silver bullet. New medications with increased outcomes and fewer side effects are entering clinical trials and may help with the underlying condition. To learn more about current heart failure research options, call our office today.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Bloom, M. W., Greenberg, B., Jaarsma, T., Januzzi, J. L., Lam, C. S., Maggioni, A. P., … & Butler, J. (2017). Heart failure with reduced ejection fraction. Nature reviews Disease primers, 3(1), 1-19. https://www.nature.com/articles/nrdp201758

Martinez-Rumayor, A., Richards, A. M., Burnett, J. C., & Januzzi Jr, J. L. (2008). Biology of the natriuretic peptides. The American journal of cardiology, 101(3), S3-S8. https://doi.org/10.1016/j.amjcard.2007.11.012

Murphy, S. P., Ibrahim, N. E., & Januzzi, J. L. (2020). Heart failure with reduced ejection fraction: a review. Jama, 324(5), 488-504. https://doi.org/10.1001/jama.2020.10262


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If someone in your family had a heart attack or stroke before the age of 60, you could be at risk and might want to have your blood tested for this little-known hereditary risk factor, Lp(a). Cardiovascular disease remains the leading cause of death in the United States, even during the COVID-19 pandemic. Determining and reducing the risk factors for cardiovascular disease is critical. 

Lipoprotein(a), also called Lp(a), pronounced “LP Little a” is a particularly dangerous culprit.  Its levels are controlled by a single gene, and a single genetic variation in this gene is enough to drastically change Lp(a) levels. Unfortunately, since it is genetically determined, diet, exercise, and lifestyle have little or no effect on Lp(a) levels. High Lp(a) can contribute to several cardiovascular conditions. These include a two to three times increase in the risk of developing:

  • Coronary heart disease
  • Peripheral heart disease
  • Aortic valve stenosis
  • Ischemic stroke

Lp(a) has been referred to as the evil twin of the more familiar LDL (bad) cholesterol and is a triple threat because it is:

  1. Pro-atherogenic:  higher risk fatty deposits in the walls of arteries
  2. Pro-thrombotic:  promotes blood clots
  3. Pro-inflammatory:  inflammation is an important risk of cardiovascular disease

There are two methods of measuring Lp(a).  The most common method of measuring Lp(a) is by mass, in mg/dL. Measuring how many individual particles, regardless of size, is another method and is measured in nmol/L. It is important to know which method was used when understanding your numbers. If you have never had your Lp(a) level checked, we offer Lp(a) testing to our ENCORE community for those who pre-qualify (call for details). 

Currently, there are no approved therapies to lower Lp(a) levels and reduce one’s risk.  However, three exciting therapies are currently being studied in clinical trials at ENCORE Research Group sites across Florida. The good news is that because of clinical research and your involvement, we have new treatments for elevated Lp(a) on the horizon!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Sources:

Kamstrup, P. R. (2021). Lipoprotein (a) and cardiovascular disease. Clinical chemistry, 67(1), 154-166. https://doi.org/10.1093/clinchem/hvaa247

Miksenas, H., Januzzi, J. L., & Natarajan, P. (2021). Lipoprotein (a) and cardiovascular diseases. JAMA, 326(4), 352-353. doi:10.1001/jama.2021.3632

Health.harvard.edu

Amgenscience.com


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Fatty liver disease is incredibly prevalent in the United States. Some estimates place the number of Americans with non-alcoholic fatty liver at over 30%, that’s around 100 million people in this country! Liver diseases are deadly serious; the liver is a critical organ and without it we cannot survive. The biggest problem with all liver diseases is that they frequently progress without symptoms. Because of this, the disease may progress to a dangerous or irreversible stage before it is even detected. Clearly, early, and routine testing for people at risk is critical.

We can’t see the liver from the outside, so the only way to learn about how it is doing is by looking at it. We can look through the skin using technology or under a microscope using a biopsy.

A biopsy – looking at a section of the liver under the microscope – is the “gold standard” of liver diagnostic techniques. This has drawbacks, however. Patients typically need to dedicate half a day to the procedure, and there can be rare complications. A biopsy is an invasive procedure requiring a piece of the liver be taken and examined. It is a critical piece of the liver diagnosis pie but is not a routine procedure to be done without cause.

Imagining techniques can be very effective in diagnosing a fatty liver. Some techniques, such as a CAT scan and ultrasound, can’t diagnose the amount of scarring on the liver but can give an indication that there is fat present. CAT scans use x-rays, but imaging is otherwise safe. An ultrasound is fast and non-invasive. It is an excellent first step that many doctors use when they suspect a fatty liver. Magnetic Resonance Imaging (MRI) is the next best diagnostic procedure to a liver biopsy. With an MRI, doctors can clearly see the state of the liver. They are expensive, however. This again means they are an excellent tool for those who are known to have fatty liver but may not be an option for all patients to use regularly.

Ultrasonic elastography is a different technique. It is commonly called Fibroscan, after the manufacturer of the diagnostic tool. Fibroscan uses sound waves to gently shake the liver and measure how it responds. The liver will stretch slightly. In a healthy liver, the tissue stretches more, but hard scar tissue is less elastic. The fibroscan can interpret the difference and determine how much fat and scar tissue is present. The test is very similar to an ultrasound; it is painless, fast, and safe. The fibroscan does not replace other imaging techniques but is cheap and effective at determining the stage of fatty liver present. Unlike other techniques, a Fibroscan can be done routinely for anyone who is at risk of having fatty liver.

Fibroscans are very popular around the world, including in Europe, Asia, South America, and Canada. It is a cheap procedure with little reimbursement for practitioners, which unfortunately prevents widespread use in the USA. Risk factors for non-alcoholic fatty liver include being overweight or obese, being prediabetic or having diabetes, and eating a high-fat diet. If you are concerned about fatty liver, talk to your primary care physician and/or contact ENCORE Research Group for a complimentary Fibroscan.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Afdhal, N. H. (2012). Fibroscan (transient elastography) for the measurement of liver fibrosis. Gastroenterology & hepatology, 8(9), 605.

Koren, M. (Host). (2022, July 20). Common fibroscan technology questions [Audio podcast episode]. In Medevidence! Truth behind the data. ENCORE Research Group. https://encoredocs.com/medevidence/

Koren, M. (Host). (2022, July 13). You cannot live without your liver [Audio podcast episode]. In Medevidence! Truth behind the data. ENCORE Research Group. https://encoredocs.com/medevidence


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Metabolic syndrome is a cluster of conditions which have been slowly rising in people in the United States. It is also known as insulin resistance syndrome.

It is currently defined as three of the following conditions:

  • Excess fat around the waist
  • High plasma glucose concentration
  • High blood pressure
  • High triglycerides
  • Low levels of good cholesterol or HDL 

Having one of these conditions does not mean that you have metabolic syndrome. Having three or more of these conditions will result in a diagnosis of metabolic syndrome and will increase your risk of health complications.  If left untreated, metabolic syndrome can lead to heart disease, Type 2 diabetes, and stroke. 

Metabolic syndrome is incredibly prevalent – affecting over one-third of Americans. Hispanic adults are at the highest risk. Among non-Hispanic adults, white men and black women are at higher risk than other groups. Other risk factors include lifestyle, age, family history, and use of some medications. Similar conditions may increase the chances of getting metabolic syndrome. These include being overweight or obese, immune system and sleep problems, and PCOS. Unfortunately, these risk factors overlap with the symptoms. This implies that metabolic syndrome may spiral and get worse over time.

The exact mechanism of metabolic syndrome is unknown, but scientists have an idea of what is to blame. It may be insulin resistance, dysfunctional fat cells, inflammation, and oxidative stress. Insulin resistance causes the cells to store sugars instead of using them. This makes cells (and people) tired and increases fat. Fat cells may become overactive and grow so large that they die, prompting an immune response. The immune system may cause inflammation and plaque build ups in the bloodstream. Inflammation can further cause skin problems and long-term damage.

While it sounds like this is all the fault of insulin resistance, it is not that clear cut. There may be many pathways into metabolic syndrome. Inflammation can be caused directly through a dysfunctional molecule responsible for fighting tumors. The liver has an important role in guiding the insulin response of the body. Obesity can cause oxidative stress that damages fat cells. Several other processes can interrupt these systems. Additionally, each symptom can increase the risk of developing others.

So what can we do about metabolic syndrome? There are no approved medications to cure the underlying condition. For medical solutions, doctors may prescribe symptomatic treatments. These treat the parts of metabolic syndrome that we can diagnose: high triglycerides, cholesterol, and hypertension. 

Currently, our best way to fight metabolic syndrome is through diet and exercise. This may seem overwhelming to some people and making solid changes takes time. Instead of exercise, many need to think of movement.  Movement can look like walking in the neighborhood, gardening, housecleaning, or anything that gets you moving, gets your heart rate up and is something you enjoy. 

Changes in other lifestyle choices may include consuming less sugar and sugary drinks, cutting out smoking and drinking, and getting regular sleep! Lack of appropriate sleep can increase your appetite for high-calorie foods due to hormonal changes.  There are two hormones that make you hungry or full.  Ghrelin is the hormone that increases your appetite and makes you crave food.  Leptin is the hormone that makes you feel full with little appetite.  These hormones can become unbalanced with lack of sleep, leading to negative changes in appetite.

There is no silver bullet for everyone, but it’s a good start to take steps towards healthier lifestyle changes.

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



References:

McCracken, E., Monaghan, M., & Sreenivasan, S. (2018). Pathophysiology of the metabolic syndrome. Clinics in dermatology, 36(1), 14-20. https://doi.org/10.1016/j.clindermatol.2017.09.004

Moore, J. X., Chaudhary, N., & Akinyemiju, T. (2017). Peer reviewed: Metabolic syndrome prevalence by race/ethnicity and sex in the United States, National Health and Nutrition Examination Survey, 1988–2012. Preventing chronic disease, 14.

Zimmet, P., Alberti, K. G. M. M., Stern, N., Bilu, C., El‐Osta, A., Einat, H., & Kronfeld‐Schor, N. (2019). The Circadian Syndrome: is the Metabolic Syndrome and much more!. Journal of internal medicine, 286(2), 181-191. https://onlinelibrary.wiley.com/doi/full/10.1111/joim.12924


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With flu season on the horizon, reviewing the vaccine pathway and how we got to where is worthwhile. We have an amazing and complex immune system. It has several specialized cells, but detection is the first line of an immune response. Detecting a harmful organism that has invaded the body can be surprisingly tricky. This is because cells have to chemically discover specific proteins or sugars on the outside of pathogens. These proteins or sugars can (and do) mutate in quickly-replicating pathogens. Luckily, our immune system can learn the danger of closely-related pathogens. 

Vaccines have a long and storied history. From the first records of vaccines in China hundreds of years ago to the first inoculation against smallpox (using cowpox) to today’s cutting-edge mRNA vaccines, the technology is constantly improving. Here are some of the major ways vaccines are made:

Use a weak virus

The cowpox-smallpox vaccine was an example of a live, whole-pathogen vaccine. This is a type of vaccine where doctors inject small amounts of live viruses into the body. The body responds and becomes inoculated against large doses of the virus in the wild. In the 1950’s live-attenuated vaccines became available. In these, the virus is weakened in a lab so it does not cause serious disease in people. This type of vaccine provides a strong and long-lasting response. Examples of live attenuated vaccines include measles, mumps, and rubella vaccine (MMR), smallpox, chickenpox, and yellow fever. 

Use a dead pathogen

There are other methods to mitigate the problems of live viruses. An inactivated vaccine uses dead virus or bacteria. This makes the vaccine much safer and comes with fewer side effects, but is less effective. The current yearly flu vaccines are inactivated vaccines. Some manufacturers use hen’s eggs to grow the vaccine before inactivation. The resulting vaccine can contain very small amounts of egg protein as a result. The CDC still recommends those with egg allergies get the flu vaccine.

Use part of a virus or bacteria

Subunit vaccines are pieces of a pathogen – generally protein or sugar pieces. These aren’t whole viruses and have fewer side effects as a result. Additionally, these subunits may be able to grant protection against many forms of a pathogen. The Hepatitis B vaccine is an example of a protein subunit vaccine.

Target a dangerous product

Toxoid vaccines such as DPT can help lessen the damage of infection because some bacteria do their damage by releasing dangerous toxins instead of attacking cells. Toxoid vaccines train the body to recognize these toxins as dangerous. Diphtheria and tetanus vaccines are examples of toxoid vaccines. 

Get the body to do the work

Nucleic acid vaccines are a new and different approach that has many benefits. Instead of using a weakened or inactivated pathogen to trigger our immune system, nucleic acid vaccines employ the body to make the vaccines in house. DNA, mRNA, and vector virus vaccines use genetic code created in a laboratory; there is no virus needed to develop the vaccine. Messenger RNA (mRNA) vaccines are the best known and use mRNA, a blueprint for creating specific proteins. When injected into the body, they provide the instructions for our body to produce antigens (proteins) that trigger an immune response. The T-cell and antibody response that follows can fight the disease. This can provide long-lasting, stable, relatively low symptom responses. The real benefit, however, is the time it takes to develop a new vaccine is drastically reduced. This was evident with COVID-19, when researchers created a brand-new vaccine in less than a year. Equally important was distributing it to hundreds of millions of people one year after. A typical vaccine takes 10-15 years to develop – and even longer to scale production.

New studies are coming to compare the effectiveness of mRNA-based vaccines to inactivated vaccines for viruses and diseases beyond covid. Keep a lookout to join this new and developing vaccine research. 

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



References:

NIH, National Institute of Allergy and Infectious Diseases. (2021). Flu vaccine and people with egg allergies. https://www.cdc.gov/flu/prevent/egg-allergies.htm

NIH, National Institute of Allergy and Infectious Diseases. (2019). Vaccine types. https://www.niaid.nih.gov/research/vaccine-types

Greenwood, B. (2014). The contribution of vaccination to global health: past, present and future. Philosophical Transactions of the Royal Society B: Biological Sciences, 369(1645), 20130433.

Boylston, A. (2012). The origins of inoculation. Journal of the Royal Society of Medicine, 105(7), 309-313.


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Earlier this year, a bipartisan bill was introduced in the US congress to increase diversity in clinical research trials. The DEPICT act, as it’s called, has many major changes to how clinical trials would be conducted. These changes would affect sponsors, the government, and clinical research sites. Sponsors are the companies which develop new drugs and devices in clinical trials.

The bill would require new demographic analyses for drug and device trials by sponsors. Demographic data includes age, sex, race, and ethnicity. Sponsors would investigate the rates of a disease among demographic groups before starting a trial. They would then devise a diversity action plan. This ensures the clinical trial includes a representative sample of the affected population. Let’s say a drug targeted lung cancer, for example. The sponsor would have to find out who has increased chances of getting lung cancer. If they found that Black Americans were at higher risk, they would make a plan to ensure this group was included in any research trials. Plans could include community outreach, specific site selection, and diversity training.

A key aspect of the bill is discovering how to best reach diverse communities. Research sponsors would need to submit annual reports. These would outline how successful their studies were at reaching the demographic goals. If they failed to meet goals, they would give possible reasons they did not. The Food and Drug Administration (FDA) would compile and analyze the reports. The FDA would issue public reports on diversity and enrollment targets. They would also publish justifications for failure to meet targets and recommendations to solve this. Additionally, the National Institute of Health (NIH) would provide outreach. For sponsors, they would issue best practices for increasing diversity. They would engage with minorities to bring awareness of clinical research trials. They would also help local organizations inform their community about research trials.

The final piece of the bill is increasing access. The bill would enhance clinical research infrastructure in underserved communities. The bill provides grants to expand clinical research facilities. These would be in rural areas, on Indian tribal lands, and in federally recognized underserved communities. The grants would help facilities conduct research trials in these areas.

Altogether, this bill addresses the shortcomings of clinical trials in diverse communities. It closes the gap between who suffers from medical conditions and who participates in clinical research trials. It helps find out which methods increase clinical trial diversity. It also helps expand access to clinical trials in underserved communities. There is still a long way to go before this bill makes it to the voting floor, but it’s a good step.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Source:

Text – H.R.6584 – 117th Congress (2021-2022): DEPICT Act. (2022, February 3). https://www.congress.gov/bill/117th-congress/house-bill/6584/text


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Hypertension is one of the most prevalent conditions on the planet. Scientists estimate that it affects 30-45% of adults, somewhere over a billion people! Hypertension is the chronic elevation of blood pressure. The CDC defines it as above 130 mmHg systolic or above 80 mmHg diastolic. For short periods of time, elevated blood pressure can be useful – for exercise, say. People can have high blood pressure for years without symptoms. For long periods of time, however, hypertension is deadly serious. Unfortunately, living with high blood pressure can lead to a host of problems. Hypertension can lead to heart attack and stroke, and damage to the heart, brain, kidneys, and even eyes!       

Everyone is at risk of high blood pressure. In America, men have a higher likelihood of hypertension. There are also differences in ethnicity and race, non-Hispanic Black or African American adults are at the highest risk. Unfortunately, even the lowest risk categories still have around a 40% prevalence of high blood pressure. Clearly this is a large issue in America and around the world.           

The big culprit behind hypertension is the Renin–angiotensin–aldosterone system (RAAS). RAAS is a critical system for maintaining blood pressure. It regulates two primary factors: the amount of blood and how constricted blood vessels are. It does this through the kidney, liver, and adrenal gland (just above the kidneys). In response to body signals, the kidneys release an enzyme to the liver. In response, the liver produces the hormone angiotensin I. Another enzyme, angiotensin-converting enzyme (ACE) converts this to angiotensin II, which goes to work.  

Angiotensin II has wide-ranging effects to increase sodium and water retention. It also causes blood vessels to constrict. Angiotensin II is very short-lived, only lasting 1-2 minutes. One of its many effects is to get the adrenal gland to produce aldosterone. Aldosterone has similar effects as angiotensin II, but instead of a few minutes, it takes hours or days to take effect. The end result is that two major hormones – one fast-acting and one slow-acting – cause high blood pressure.          

There are many medications available to fight hypertension. Most of these, such as diuretics or beta-blockers, have wide-ranging side effects. This is because they are system-wide, indiscriminate actors on the body. Beta-blockers, for instance, slow the heart. This is helpful in lowering blood pressure but obviously leads to other effects on the body. RAAS-acting specific medications may be more helpful in combating hypertension with minimal side effects. ACE inhibitors, for instance, stop the fast-acting angiotensin II from having its effect on the body. This targeted approach to hypertension can lead to fewer side effects in some patients. Unfortunately, by acting on only the fast-acting portion of RAAS, they must be taken daily. Even worse, a few missed doses can have longer-term effects on blood pressure. Luckily, researchers are investigating other targeted methods of reducing the effect of RAAS, and blood pressure! Keep an eye out for a clinical research study to help investigate this exciting part of the fight against hypertension.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Sources

Fountain, J. H., & Lappin, S. L. (2017). Physiology, renin angiotensin system.

National Center for Chronic Disease Prevention and Health Promotion, Division for Heart Disease and Stroke Prevention. (September 27, 2027). Facts about hypertension. U.S. Department of Health and Human Services. https://www.cdc.gov/bloodpressure/facts.htm


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Celiac disease is one of the major health issues on our planet, affecting around 1% of the population (that’s about 80 million people!). Celiac disease is more likely to occur in females. Though onset can occur at any age, it is most likely to be discovered around age two or during young adulthood.

Celiac disease is commonly known as gluten intolerance and is classically characterized by its gastrointestinal symptoms including diarrhea, loss of appetite, weight loss, and other digestive issues. Additionally, there are other symptoms that are unrelated to the digestive system. These include anemia, bone density issues, neurological symptoms, skin rash, and more. Together these make for a severe detriment in the quality of life of most celiac sufferers.

Like most autoimmune disorders, the leading symptoms come from the body’s immune system overreacting and causing damage. Celiac disease is unusual in that the reason for the immune response is gluten, which we eat. Gluten is a structural protein found in wheat, rye, barley, spelt, and kamut. Gluten isn’t fully digestible, and some intact protein pieces make it through the stomach into the intestines. In celiac patients, the protein pieces cross the intestinal lining and are mistaken for dangerous particles or microorganisms. This can trick the immune system into action, causing inflammation and damage.

The number of people with celiac disease has been growing significantly. Five times as many people had the condition in 2000, compared with 1975. Scientists are still unsure why the disease has been growing worldwide. Better clinical testing, a spread of high gluten Mediterranean diets, and new varieties of grain are leading theories. Scientists have been able to discover much of the underlying mechanism of how celiac disease occurs, thankfully. It is genetic, and the key player appears to be HLA-DQ2 or HLA-DQ8 antigens which mistake gluten for danger. The presence of HLA-DQ2/DQ8 isn’t enough to guarantee celiac disease, but it is required. Additional contributors are thought to be other genes, environmental factors, and gut microbiota. Regardless, 95% of celiac patients have one of these dangerous antigens.

Currently, the only treatment for celiac is a strict gluten-free diet. This can be difficult to maintain, and even with a gluten-free diet, some patients continue to have symptoms. Additionally, contaminants can be unknowingly present in food and even low amounts of gluten can cause a resurgence of symptoms. Scientists are looking for new ways to combat this disease and participating in clinical trials is the best way that you can help move celiac disease medicine forward.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Source:

Caio, G., Volta, U., Sapone, A., Leffler, D. A., De Giorgio, R., Catassi, C., & Fasano, A. (2019). Celiac disease: a comprehensive current review. BMC medicine, 17(1), 1-20.


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Listen to the article here:


My buddy recently bought an e-bike on the internet. It has an enormous battery, goes pretty fast, and is salt air resistant – an important feature at the beach. It’s the perfect bike. Or at least it would be, except it is still on a dock in China, waiting for a cargo ship to deliver it. The bike is no good if it can’t get to where it needs to be. The same is true of drugs: a drug is only as good as its delivery system.

Usually, the “buyer” of a drug is a cell somewhere in the body. Sometimes they are in specific areas, and sometimes they’re all over the place. Regardless, getting the drug to the target cells has always been a challenge. Our main delivery routes currently are swallowing, inhalation, skin absorption, and injection. Each has different uses, benefits, and drawbacks, but the route isn’t enough. Ingested medicines, for example, need to survive the harsh stomach acid but still be absorbable by the intestines. Injected medications are cleared by the liver at high speeds, reducing the effectiveness of a drug. Effective drug delivery means getting medicine to the right place at the right time, intact.

One of the best-known developments in medications has been the use of mRNA in COVID vaccines. Actually getting the delicate molecules inside cells for an immune response was one of the unsung heroes of this vaccine. Scientists implemented lipid nanoparticles to get the job done. This was no easy challenge. Lipid nanoparticles are teeny packages of fat that protect the mRNA vaccine until it can get into target cells. They are small and strong to enter cells without disintegrating in the bloodstream. The development of lipid nanoparticles was just in time for the COVID pandemic and has shown to be very effective. The drawbacks are that they must be produced perfectly every time for billions of doses and must be kept extremely cold, at least currently.

A much less widespread development has been the creation of microneedles. These are already in use for cosmeceutical applications. Microneedles are generally smaller than one or two millimeters and don’t puncture the skin all the way to the blood layer. This allows for simpler delivery and at-home administration of some medicines. Microneedles can also be coated with a dry version of medicines, allowing for shelf-stable drug delivery. This could be particularly helpful in areas with inadequate infrastructure and a lack of medical personnel.

Researchers are developing many other new and exciting delivery methods. Targeted organ delivery is the practice of delivering medicine to specific organs. One example is coating a medicine in a urine-resistant coating for injection into the bladder. Cellular delivery uses living cells to carry medication to the target site. These living cells may be red blood cells or beneficial cyanobacteria.  Attaching medicine to red blood cells can help drugs resist the powerful cleanup mechanism of the liver. This may allow for lower doses to have bigger effects. Attaching to beneficial spirulina platensis cyanobacteria may help medicines cross the stomach intact and deliver medicine straight to the intestines. This can allow for targeted organ delivery or for longer release of medicines. Finally, some scientists are experimenting with physically squeezing cells. This opens temporary pores for direct drug delivery. Such a system could enable scientists to deliver medicine to billions of cells per minute.

All these exciting new delivery systems will have a big impact. Medicines of the future may be delivered in lower doses and with fewer side effects. We can also expect new uses for old medicines, as they will be able to be used in new ways and able to target new organs. Several of our clinical trials at Encore Research Group use these new methods. It’s an exciting time to help be on the cutting edge of what new medicine delivery will look like in the future. With luck, these new delivery methods will open new doors for medicines to help save lives and heal conditions. With even more luck, my buddy might get his bike by the end of the year.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Sources:

May, M. (2022). Why drug delivery is the key to new medicines. Nature Medicine, 28(6), 1100-1102.

National Institute of Health, National Institute of Biomedical Imaging and Bioengineering. (October, 2016). Drug delivery systems. U.S. Department of Health and Human Services. https://www.nibib.nih.gov/science-education/science-topics/drug-delivery-systems-getting-drugs-their-targets-controlled-manner


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Heart disease is the leading cause of death in the United States. Though there are several types of heart disease, one of the main ways the heart actually dies is through congestive heart failure, when the heart fails to pump effectively. Ineffective pumping causes blood and other fluids to build up throughout the body. Eventually, the fluid buildup may keep the heart from functioning at all, a condition called acute decompensated heart failure. This is an emergency condition, and without rapid medical treatment quickly leads to death. Fortunately, with early intervention, several patients can recover – at least temporarily. Clearly, one of the keys to saving people is early intervention.

The vocal cords and lungs may be affected by congestive heart failure. As these fill with fluid, there are changes in how the voice sounds. These changes are difficult for people to hear, but technology might be able to help out. One type of technology looking to tackle the topic is a deep neural network called HearO.

Deep neural networks are a subset of artificial intelligence. These systems learn how to make predictions from examples. The HearO system, made by the company Cardio Medical, analyzed the voices of people with congestive heart failure. The system learned by comparing people’s voices while they were “wet” (fluid-filled while in the hospital) and “dry” (after hospital treatment and discharge). Using this, the system learned to detect voice differences in the severity of the condition.

The HearO system has now been packaged as a smartphone app. Patients talk into the app every day and it compares their voice to itself. It scans for changes that indicate a fluid build-up (and danger!). The hope is that HearO will help detect changes in the voice before acute decompensated heart failure occurs. Clinical trials are currently underway to test the HearO’s effectiveness and some of our ENCORE Research Group sites are enrolling for this. 

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Sources:

Amir, O., Abraham, W. T., Azzam, Z. S., Berger, G., Anker, S. D., Pinney, S. P., … & Edelman, E. R. (2022). Remote speech analysis in the evaluation of hospitalized patients with acute decompensated heart failure. Heart Failure, 10(1), 41-49.

Brooks, M. (2015, December 15). Smartphone app could give voice to congestion in heart failure. Medscape. https://www.cordio-med.com/wp-content/uploads/2021/12/smartphone-app-could-give-voice-to-congestionin-heart-failure.pdf

Tomov, N. S., & Tomov, S. (2018). On deep neural networks for detecting heart disease. arXiv preprint arXiv:1808.07168.


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We’ve all heard enough about COVID-19, but it’s worth remembering that other viruses still try to get cozy in our respiratory system. One virus that is very prevalent in the United States is Respiratory Syncytial (“sin-sish-ul”) Virus, or RSV for short. It’s so widespread that the CDC states that nearly all children will get RSV before their second birthday. The oldest (above 65) and youngest (under 5) populations are most at risk of complications. Those most in danger are premature children, those with compromised immune systems, and those with underlying heart or lung diseases. All told, RSV accounts for around 177,000 hospitalizations of seniors (65+) and 58,000 children (under 5) each year.

RSV is easily transmissible. It passes from person to person through coughs, sneezes, or indirect means, like touching a doorknob and then your face. Most patients experience mild, cold-like symptoms. These include runny nose, fever, cough, sneezing, etc. Symptoms usually come in stages over a couple of weeks. Very young children and those at higher risk may experience more severe symptoms. In children under six, RSV might present as irritation, decreased activity, and breathing difficulty, which can be severe – and very scary! In adults over 65, severe symptoms can include a worsening of asthma or COPD, pneumonia, and the development of Congestive Heart Failure – a fluid buildup in the heart that prevents it from pumping effectively.

Much like the flu, RSV is seasonal. In most of the United States, the season is from September to February. The Florida Department of Health notes that Florida has a longer season than the rest of the nation. Here, the season for RSV is from August through April. The CDC has found that all across the south the year-round RSV cases increased. 2021 saw an unexpected surge of RSV over the summer. This is in part because the same tactics used to stem COVID-19 also protect against RSV. These protective measures include wearing masks, washing hands and surfaces, and social distancing. As these restrictions were lessened, cases of RSV rose to unprecedented summer levels. 

Unfortunately, there is no cure for RSV. As it’s a virus, antibiotics are ineffective. Most patients will recover naturally. For others, best practices are treating symptoms by managing fever, pain, fluid intake, and any complications. For children and infants at severe risk, monthly Palivizumab injections may be available. Unfortunately, there are no publicly available vaccines for adults at increased risk. There are vaccines currently being researched that are going through clinical trials. With your help, we can find an effective RSV vaccine and help protect those at risk.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Sources:

Centers for Disease Control and Prevention. (2019). Respiratory Syncytial Virus Infection (RSV). Atlanta, USA.

Centers for Disease Control and Prevention. (2021). Increased interseasonal Respiratory Syncytial Virus (RSV) activity in parts of the southern United States. Atlanta, USA.

Florida Department of Health. (2022). Respiratory Syncytial Virus (RSV) in Florida. Tallahassee, USA


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June 12, 2022 BlogPresbyopia

Vision is our main way of interacting with the world, and it can be debilitating when our vision deteriorates. Unfortunately, presbyopia – the gradual loss of ability to focus on nearby objects – is basically inevitable. Presbyopia affects nearly 25% of the world population; almost 2 billion people. People usually see symptoms in their 40s, but the path starts in childhood.

The exact cause of presbyopia is unknown, but the effects are well documented. The eye’s lens is the bit that changes shape, allowing us to focus at different distances. During childhood, the lens gradually becomes less flexible. Since it can’t change shape as easily, we stop being able to focus as rapidly and accurately. It gets more difficult to focus at close or mid-lengths. There are four broad methods suggested for increasing focal range, each with its own trade-off.

Changing focus over time is the first method. Think of it like having several pairs of glasses. When focusing on close things you might use readers. Different glasses may be used for mid-length, or distance viewing. This is what our eyes do naturally (when we’re young at least!). So far there are no pharmaceutical or implantable devices that can accomplish this. Using several glasses is a good – if bulky – approximation for millions of people, however.

Changing focus depending on where you look is the second method. Bifocals are the classic example. This solution is quick and convenient. There are downsides, however. Changing from near to mid-focus can be jarring, vision can be blurry, and eye strain occurs sometimes. One often overlooked issue is that bifocals can introduce other dangers, such as falls due to unfocused areas near the feet when walking.

Changing focus between eyes is an interesting method. With this approach, one eye is corrected for close vision, and the other stays focused at a distance. Each eye only focuses narrowly, but together you can see across a wide range. Even though this is easy to try by putting in only one contact lens, it can be hard to get used to and lead to a loss of binocular vision. Judging distances of objects may be more difficult with this method, and it can be uncomfortable for some people.

The final method is to increase the focal range across distances. This is an innovative method where the eyes are changed to have more in-focus at the same time. If you’ve ever had an eye exam where they dilate your pupils, this is the opposite. The pupils are artificially constricted. This extends your depth of field, making it easier to focus on things near and far at the same time! Some side effects may include a loss in quality and contrast, and a loss of low-light sensitivity. One of the big hurdles researchers have is the precision required to pull this off successfully. Methods to induce increasing focal range can be permanent, such as with implanted lenses; but mitigation of side effects may be easiest with special eye drops. Some of these eye drops are being tested currently in clinical trials.

With so many different angles to attack presbyopia, and volunteers helping with clinical trials, we may be looking at a universal treatment soon! 

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Source:

Chang, D. H., & Waring, G. O. (2021). Presbyopia Treatments by Mechanism of Action: A New Classification System Based on a Review of the Literature. Clinical Ophthalmology (Auckland, NZ), 15, 3733.


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Have you ever had a headache that you couldn’t shake, even for hours or days? One that may make you nauseous or unable to function? Then you may have had a migraine. And you’re not alone. A survey from 1990 to 2010 found that about 15% of the world’s population have migraines each year. That makes migraines the third-highest source of long-term injury! Women are around twice as likely to get migraines than men.

Migraines can be broadly lumped into two categories based on frequency, episodic and chronic. People with episodic migraines experience between 0 and 14 days with migraines a month. More than that and the condition is called chronic migraine. The difference between these two categories isn’t set, and a small percentage of those with either condition may evolve or degrade into the other. Either way, migraines are debilitating. They last hours to days and may be accompanied by an aura: a visual indication of an impending bad day.

The exact underlying causes of migraines are unknown, but there are some areas where intervention is possible. The pain and debilitating effects of migraines are caused, at least in part, by something called vasodilation. This is just a fancy term for when blood vessels expand, allowing more fluid to pass through. Vasodilation can occur for many reasons, but one of the main suspects in migraines is a protein called CGRP (calcitonin gene-related peptide, for the curious). This protein acts on the coverings of the brain, causing vasodilation that inflames this area. It is unclear exactly what happens after this, but the end result is debilitating pain. It has even been shown that injecting CGRP can cause a migraine to start.

Interventions against this vasodilation are possible through a couple of different routes. One of the classic ways of tackling a migraine is through a medication called Dihydroergotamine, or DHE for short. This medication causes some arteries in the brain to constrict, counteracting the vasodilation from CGRP. This can “interrupt” the migraine and provide relief. This relief often effectively ends the migraine. DHE has been available for injection in the US for some time, though in other countries it is available as a nasal spray. Researchers are working to get approval for this method in the US as well.

Another intervention being researched is stopping the vasodilation at the source. There is ongoing research in stopping CGRP from acting on the brain coverings at all. This is a new avenue that may help provide migraine relief with fewer side effects. Research in this field is also ongoing, ask us about the different ways you can help provide research insight into relief for this real headache of a condition.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Sources:

De Matteis, E., Guglielmetti, M., Ornello, R., Spuntarelli, V., Martelletti, P., & Sacco, S. (2020). Targeting CGRP for migraine treatment: mechanisms, antibodies, small molecules, perspectives. Expert review of neurotherapeutics, 20(6), 627-641.

Marmura, M. J. (2018). Triggers, protectors, and predictors in episodic migraine. Current pain and headache reports, 22(12), 1-9.

Shafqat, R., Flores-Montanez, Y., Delbono, V., & Nahas, S. J. (2020). Updated evaluation of IV dihydroergotamine (DHE) for refractory migraine: patient selection and special considerations. Journal of Pain Research, 13, 859.

Vos, T., Flaxman, A. D., Naghavi, M., Lozano, R., Michaud, C., Ezzati, M., … & Harrison, J. E. (2012). Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet, 380(9859), 2163-2196.


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Ulcerative colitis (UC) is a chronic and progressive autoimmune disorder that causes inflammation and ulcers to develop in the intestines, which can be very uncomfortable or debilitating. Ulcers are breaks or holes in the protective lining that can cause bloody diarrhea, with or without mucus. One of the significant symptoms of UC  is a high urgency of bowel movements. Other symptoms include abdominal pain, bowel inflammation, and constipation. UC is not a fun condition to experience, to say the least! It is usually experienced in cycles of remission and relapse with periods of terrible high and thankfully low (or no) symptoms. The high periods can even lead to hospitalization. 

UC can develop at any age but is more likely to develop in people 15 to 30 years old. Interestingly, there seems to be a lower chance of developing UC if your appendix has been removed or if you are a smoker. This disease doesn’t play favorites, so there is no difference between men and women developing UC. Racial differences may be minimal compared to differences in diet and lifestyle. For example, a diet that includes eating refined sugars and processed grains may increase the likelihood of developing the disease.

As mentioned above, diet can be a risk factor; this may be because of an immune response to the food. Research continues to show that the food you eat can affect all parts of the body. People with genetic factors have an immune system that attacks non-harmful gut bacteria, and low gut microbiota diversity may also be a risk factor.

Ulcerative colitis often presents with other diseases. Data suggests that there is a relationship between UC and rheumatoid arthritis. Some experts think joint pain and swelling may be part of the same immune response responsible for ulcerative colitis. Other comorbidities include acute hepatitis (liver inflammation) and occasional skin conditions.

Treatments for UC aim at inducing a period of remission. All of them come with side effects, so your doctors, specialist and primary care, should all be informed about the medications that you are taking. A particularly unpleasant and severe treatment is a colectomy or bowel resection, which removes part of the affected colon. 20-30% of people with UC  may have to undergo this procedure. 

The good news is that researchers continue to look for better ways to treat UC. With your help, we can make a difference!  Visit our enrolling studies page to get involved in the latest clinical research.

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Sources:

Gajendran, M., Loganathan, P., Jimenez, G., Catinella, A. P., Ng, N., Umapathy, C., … & Hashash, J. G. (2019). A comprehensive review and update on ulcerative colitis. Disease-a-month, 65(12), 100851.

Lee, S. H., eun Kwon, J., & Cho, M. L. (2018). Immunological pathogenesis of inflammatory bowel disease. Intestinal research, 16(1), 26.

Attalla MG, Singh SB, Khalid R, Umair M, Epenge E. Relationship between Ulcerative Colitis and Rheumatoid Arthritis: A Review. Cureus. 2019;11(9):e5695. Published 2019 Sep 18. doi:10.7759/cureus.5695


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May 22, 2022 BlogNASH

The liver is a critical organ that has many functions. It balances the body’s energy budget, filters blood, and metabolizes drugs, for a start. Since the liver is so imperative, it goes without saying that when the liver starts to fail, a lot can go wrong. It is widely known that excessive alcohol consumption can damage the liver, but there are also other pathways to liver damage.  One particularly dangerous pathway for liver disease is Non-Alcoholic Steatohepatitis or NASH which is the most severe form of non-alcoholic fatty liver disease. The exact cause of NASH is unknown.  

NASH is a disease characterized by an accumulation of fat in the liver coupled with liver enlargement due to chronic inflammation and cell death. It is difficult to diagnose NASH. The symptoms, tiredness and/or pain in the upper right side of the abdomen, are not very specific to NASH or helpful in diagnosis. Most often, patients do not have symptoms at all until the later stages of the disease. 

NASH is widespread, affecting between 3-5% percent of the worldwide population. It has been referred to as a modern lifestyle disease, with things like overeating and sedentariness contributing to it.

There are several risk factors for developing NASH:

  • Female
  • Aged 50+
  • Heart disease
  • High lipid levels (ie: cholesterol/triglycerides)
  • High blood pressure
  • Metabolic syndrome
  • Overweight or obesity
  • Type 2 diabetes
  • Insulin resistance
  • Genetic and environmental factors

NASH is a progressive liver disease, meaning it gets worse over time without treatment or lifestyle changes. The first step of NASH is fibrosis, where repeated scarring occurs. This scarring forms when the liver is repeatedly damaged and healed.  NASH patients develop more severe forms of fibrosis about twice as fast as those with alcohol-induced liver damage. In NASH, unlike with alcoholic liver disease, the cause of damage is not always known. Fibrosis is scarring that is reversible with treatment. 

If NASH progresses further, cirrhosis may occur. This is scarring and liver failure that is permanent, though people can live with it for years. In cirrhosis, the cells of the liver themselves suffer damage. The final two stages of NASH are hepatocellular carcinoma, a type of liver cancer, and death. Tackling NASH early on is vital to those suffering from this disease!

Unfortunately NASH is an understudied disease with few routes to recovery. Currently, the most effective treatment appears to be weight loss, accompanied by dietary and lifestyle changes. In scientific studies, this has been only achievable by about 50% of those with NASH. With this in mind, and only the early fibrosis stage of NASH being reversible, the search for medications that can treat NASH has been described as the “Quest for the Holy Grail.” There are currently no FDA-approved drugs to treat NASH. Several clinical trials exist and will continue to enroll and may lead to a treatment soon. If you have NASH, it’s important to consider participating in clinical trials to help find effective treatments. Find out which clinical trials are enrolling near you by visiting our enrolling studies page. 

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience



Sources:

Povsic, M., Wong, O. Y., Perry, R., & Bottomley, J. (2019). A structured literature review of the epidemiology and disease burden of non-alcoholic steatohepatitis (NASH). Advances in therapy, 36(7), 1574-1594.

Sharma, M., Premkumar, M., Kulkarni, A. V., Kumar, P., Reddy, D. N., & Rao, N. P. (2021). Drugs for non-alcoholic steatohepatitis (NASH): quest for the holy grail. Journal of Clinical and Translational Hepatology, 9(1), 40.


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Ahoy ye mateys! Have you ever wondered which enemy was the most dangerous to sailors during the 1700’s? James Lind, a Royal Navy surgeon, described a foe which “proved a more destructive enemy, and cut off more valuable lives, than the united efforts of the French and Spanish arms.” In order to conquer this threat, Lind employed a brand new weapon. This weapon was previously unknown to science, and has now been used to defeat countless foes. The enemy was scurvy, and the weapon was a clinical trial.

May 20, 2022  marks the 275th anniversary of that first clinical trial. Scurvy could lead to muscle pain, gum disease, fatigue, jaundice, and death. Remedies at the time varied widely and only anecdotal, word-of-mouth evidence for them was available. Every sailor who was afflicted with scurvy sought a cure, but the overall disease was caught in the doldrums without a solution for 150 years. Lind had bigger ambitions. His big insight wasn’t trying to treat just a few individuals for scurvy, but instead trying to solve the problem of scurvy on the scale of public health. Though he only had 12 participants in that first trial, how Lind compared different remedies showed his big-picture thinking. He sought not to give relief to just those 12 patients, but to quantify and share his results to cure the whole of the Royal Navy.

In this effort Lind laid the groundwork of the modern clinical research study. He started with a set of 12 patients with conditions “as similar as I could have them.” He controlled extraneous variables, giving all patients the same diet during the study and keeping them on the same boat. He split them into 6 random conditions:

  • A quart of cider per day
  • Elixir vitriol (sulfuric acid and alcohol), 3x daily 
  • 2 spoonfuls of vinegar, 3x daily
  • ½ pint of seawater per day
  • 2 oranges and 1 lemon per day
  • Bigness of nutmeg (a medicinal paste made of herbs and spices)

The results were clear; citrus gave quick and significant relief.  Importantly, Lind didn’t leave his findings high and dry. He recorded and reported what he saw. Probably the most important aspect of Lind’s clinical trial was that he looked at the results in an unbiased way. He wrote extensively on the need to remove personal and societal bias:

“it is no easy matter to root out old prejudices, or to overturn opinions which have acquired an establishment of time, custom, and great authorities; it became therefore requisite for this purpose, to exhibit a full and impartial view of what has hitherto been published on scurvy.”

Today the same core ideas guide clinical trials, but there are many more safeguards for participants. A good clinical trial today is grounded in science, provides benefits to patients that should outweigh any risks, and treats patients with respect. Critically, clinical trials have informed consent; all participants join voluntarily and must have full knowledge of any risks before signing up. Trials also have oversight from Institutional Review Boards and have medical staff on site to help with any adverse reactions. Following Lind’s example, clinical trials also target specific conditions, have randomized patients, control conditions (as much as possible), and dutifully record and report their findings.

Though his aim was to blow scurvy out of the water, Lind ended up making waves in how scientists solve medical problems in general. His quantitative, balanced approach gave the world a system to tackle medical problems. On this International Clinical Trials Day we can help keep up the bounty of Lind’s legacy by volunteering as a clinical research trial participant and send some diseases to Davy Jones’ Locker!

Written by Benton Lowey-Ball, BS Behavioral Neuroscience



Lind, J. (1753). A treatise of the scurvy: in three parts, containing an inquiry into the nature, causes, and cure, of that disease, together with a critical and chronological view of what has been published on the subject. Bulletin of the World Health Organization: the International Journal of Public Health 2004; 82 (10): 793-796.From https://www.jameslindlibrary.org/lind-j-1753/


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Attention-deficit hyperactivity disorder (ADHD) is a disorder that is often diagnosed in childhood. When most people think of ADHD, they envision young children with an overabundance of hyperactivity and impulsiveness. However, there are three kinds of ADHD: hyperactive, inattentive, and combined presentation (inattentive and hyperactive). Researchers feel that inattentive ADHD is underdiagnosed because the symptoms present quite differently and are less noticeable. It is a chronic condition that causes attention difficulties, hyperactivity, mood swings, and impulsiveness.

In more recent years, it has come to light that ADHD might be associated with some memory loss. Other common reasons for memory loss include brain injuries, illnesses like Alzheimer’s or depression, effects of drugs and alcohol, and nutritional deficiencies. Other examples that can cause memory loss are age, stress, or lack of sleep.

Many people with ADHD go undiagnosed, especially if they have inattentive ADHD. Adults with ADHD do report memory loss, especially long-term memory. More recent studies have focused on why adults with ADHD have memory loss.

An article under the National Library of Medicine states that “it is well documented that adults with ADHD perform poorly on long-term memory tests. ”Their study concluded that adult ADHD reflects “a learning deficit induced at the stage of encoding.”

Researchers aren’t clear about ADHD and memory loss or whether having ADHD as an adult puts you at higher risk for developing dementia. Another study done in 2017 discussed the overlapping symptoms of ADHD and a type of dementia called mild cognitive impairment.

Continued research is essential to increase understanding of ADHD and the link between memory loss. ENCORE Research Group sites do not currently have any research studies for ADHD, but you can find some by searching clinicaltrials.gov. If you are experiencing memory loss, it’s vital to speak with your doctor about your symptoms. If you are over 50 and have memory loss, Jacksonville Center for Clinical Research offers a free memory screening assessment. You can contact us at (904)-730-0166.


Sources:

Skodzik T, Holling H, Pedersen A. Long-Term Memory Performance in Adult ADHD. J Atten Disord. 2017 Feb;21(4):267-283. doi: 10.1177/1087054713510561. Epub 2016 Jul 28. PMID: 24232170.

Callahan, B. L., Bierstone, D., Stuss, D. T., & Black, S. E. (2017). Adult ADHD: Risk Factor for Dementia or Phenotypic Mimic?. Frontiers in aging neuroscience, 9, 260. https://doi.org/10.3389/fnagi.2017.00260


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Could our guts affect how smart we are? A new study of over 14,000 women provides evidence. The study followed middle aged, 50-60 year old women over seven years from 2014 to 2018. It found that the longer a person used antibiotics, the greater the mental decline. At the high end, two months of antibiotic use was correlated with a mental decline equal to aging an extra 3-4 years.

This study does not imply causation. All participants self-reported their data, meaning they answered questionnaires. This does not allow scientists to see a direct cause-effect relationship. Other confounding effects may have been in play. One is that participants who used more antibiotics were more likely to have been sick. The scientists in charge of this study attempted to account for these differences. Study scientists adjusted for:

  • Age and socioeconomic factors (education level, spousal education level)
  • Lifestyle  (smoking, alcohol use)
  • General health (weight, physical activity, eating habits, multivitamin use)
  • Mental health (depression, antidepressant use)
  • Cardiovascular health (heart medication, blood pressure, cholesterol, history of heart attack)
  • Other big health issues (stroke, diabetes, emphysema)

After this they still found that antibiotic use was the leading indicator of mental decline.

The link between the gut and the brain is an area of intense and active investigation. Information can travel back and forth between the gut and the brain along a special route called the gut-brain-axis. This takes advantage of a large nerve, the vagus nerve. The vagus nerve directly links the digestive tract and the brain. Animal studies show that altering the gut bacteria can alter a host of mental processes. In developing animals, reducing gut bacteria alters how their brains develop. Animal stress hormone levels also vary in response to changes in gut bacteria levels. Several of these changes reverse or decline when normal bacterial levels are restored. More experimental information could help solidify the link between the gut and the brain.

Mehta, R. S., Lochhead, P., Wang, Y., Ma, W., Nguyen, L. H., Kochar, B., … & Chan, A. T. (2022). Association of midlife antibiotic use with subsequent cognitive function in women. Plos one, 17(3), e0264649.


Sources:

Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology, 28(2), 203.

Heijtz, R. D., Wang, S., Anuar, F., Qian, Y., Björkholm, B., Samuelsson, A., … & Pettersson, S. (2011). Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences, 108(7), 3047-3052.


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May 1, 2022 BlogGlaucoma

The eye is a fragile and carefully balanced organ. At the very front of the eye is a fluid-filled chamber called the anterior chamber. This is located between the clear cornea at the front and the pupil, where light enters the rest of the eye. The fluid that fills this area is called the aqueous humor. The aqueous humor is critically important for cleaning and bringing nutrients to the lens. It is like a clear version of blood. Another key job the aqueous humor performs is maintaining eye pressure.

The pressure in the eye needs to be maintained within a very specific range (12-22 mm Hg). Aqueous humor continuously flows through the front of the eye at a very slow rate (like blood, but slower). When the flow rate out of the eye gets disrupted, eye pressure increases.

Doctors call high eye pressure ocular hypertension. The major characteristic is increased eye pressure without other symptoms. When eye pressure causes damage to the optic nerve, we call it glaucoma. Glaucoma can occur in two ways, closed angle or open angle. Closed angle is sudden and a medical emergency. Open angle makes up almost all cases of glaucoma and is gradual in onset. Typical symptoms of open angle glaucoma are vision problems in the middle of sight. These can include trouble with reading, seeing faces, walking, and driving. Both types will cause permanent blindness if untreated.

Open angle glaucoma can happen to anyone, but is much more common with adults over 60 years old. Most cases are females, and black and Asian populations experience higher rates of the condition. There are several underlying reasons for open-angle glaucoma: vascular, anatomical, genetic, or immune. Because of this wide spread of causes, there are several risk factors:

  • Genetics / Family history
  • Diabetes
  • Extreme nearsightedness
  • Hypertension
  • Eye injury
  • Eye abnormalities
  • Steroid use
  • Smoking

Several treatments are available for glaucoma. These include surgical and medication-based treatments, and surgically implanted medications. The goal of all treatments is to increase the flow of fluid out, decrease the amount of fluid coming in, or to decrease the volume of the anterior chamber. Medications are quite effective when taken properly. Unfortunately, fewer than one third of patients adhere to doctor recommendations for glaucoma eye drops after a year. This is in spite of the condition being progressive in nature and leading to blindness. Effective implanted medication delivery systems may provide better outcomes for patients.

To get involved in the latest glaucoma research, contact our Nature Coast Crystal River office.


Sources:

Allison, K., Patel, D., & Alabi, O. (2020). Epidemiology of glaucoma: the past, present, and predictions for the future. Cureus, 12(11).

Li, F., Huang, W., & Zhang, X. (2018). Efficacy and safety of different regimens for primary open‐angle glaucoma or ocular hypertension: A systematic review and network meta‐analysis. Acta ophthalmologica, 96(3), e277-e284.

Robin, A. L., & Muir, K. W. (2019). Medication adherence in patients with ocular hypertension or glaucoma. Expert Review of Ophthalmology, 14(4-5), 199-210.


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Listen to the article here:

Chronic heartburn and acid reflux are symptoms of gastroesophageal reflux disease (GERD). This disease can result in the wearing away of the tube between the stomach and throat. When wearing away does not occur, a specific type of GERD occurs. This type is non-erosive reflux disease (NERD). 

The rates of GERD in the US are very large, affecting 1 in 5 people. Most of those cases are actually the NERD type. This works out to 14% of Americans experiencing NERD. It affects men and women at equal rates, and in the USA rates are constant across racial lines. 

Several factors can increase the chances of getting NERD. Your chances are increased with:

  • Age, peaking around 70 years old
  • Smoking
  • Drinking excessive coffee
  • Drinking excessive alcohol
  • Obesity
  • Eating large amounts of food
  • Eating fatty foods
  • Eating at night

NERD does not destroy the esophagus, but comes with its own host of issues. Heartburn and irritation of the food tube define NERD, and are uncomfortable on their own. It can also cause chest pain, vomiting, asthma, coughs, and sleeping problems. Furthermore, a major class of GERD-targeting drugs are less effective on the non-erosive form, NERD. These drugs are called proton-pump-inhibitors.

Proton pump inhibitors are the most effective medications for treating GERD. Major name-brand proton-pump-inhibitors include Prilosec, Protonix, Nexium, Prevacid, and several others. The generic names are omeprazole, pantoprazole, esomeprazole, and others. All of these work by reducing the stomach’s ability to make stomach acid, lowering its ability to burn. As a result, GERD is both less painful and less destructive to the esophagus.

Several people experiencing NERD are resistant to proton-pump-inhibitors. There are several possible reasons. In some patients, high concentrations of stomach acid isn’t the cause of their issues. In fact, only around half of NERD patients have abnormal acid levels, so lowering stomach acid may not be helpful as a treatment. These patients may have acid reflux even when acid levels are normal. They may also have a particularly sensitive esophagus. This could result in the feeling of heartburn even with lower acid levels. These patients need new treatments to help manage NERD. With luck, a clinical trial will pave the way to widespread adoption of an effective treatment soon!


Sources:

Ang, D., How, C. H., & Ang, T. L. (2016). Persistent gastro-oesophageal reflux symptoms despite proton pump inhibitor therapy. Singapore medical journal, 57(10), 546.

Dent, J., El-Serag, H. B., Wallander, M., & Johansson, S. (2005). Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut, 54(5), 710-717.

Hershcovici, T., & Fass, R. (2010). Nonerosive reflux disease (NERD)-an update. Journal of neurogastroenterology and motility, 16(1), 8.

ICRMD (2021, August 27). What is non-erosive reflux disease? ICRMD. Retrieved March 24, 2022, from https://icrmd.com/2021/08/27/what-is-non-erosive-reflux-disease/ 

Ribolsi, M., Cicala, M., Zentilin, P., Neri, M., Mauro, A., Efthymakis, K., … & Penagini, R. (2018). Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non‐erosive reflux disease. Alimentary Pharmacology & Therapeutics, 48(10), 1074-1081.

Yamasaki, T., & Fass, R. (2017). Reflux hypersensitivity: a new functional esophageal disorder. Journal of Neurogastroenterology and Motility, 23(4), 495.


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Crohn’s disease is one of two types of irritable bowel disease. Unlike the more narrowly located Ulcerative Colitis, Crohn’s disease can be very widespread. Crohn’s disease is caused by inflammation of the bowel walls which can occur anywhere between the mouth and anus. This inflammation is frequently interspersed with healthy tissue. It affects the entire thickness of the bowel walls. Crohn’s is usually diagnosed by age 35 and affects 1.5 million people in the USA alone.

Crohn’s disease is an autoimmune disorder. That means your body’s immune system is mistakenly attacking healthy cells. It is also a multifactorial disease. This means there are several possible underlying causes for it. Scientists know that the causes include genetic and environmental factors. Some risk factors are a low fiber diet, high carb diet, altered microbiome, and the use of NSAID medication. Lifestyle factors that influence Crohn’s include sleep, stress, exercise, and smoking. Unlike ulcerative colitis, smoking doubles a person’s chance of developing Crohn’s disease.

Having such a large amount of possible causes makes Crohn’s disease very difficult to cure. So far researchers have only found ways to intermittently fix the symptoms of Crohn’s disease. Surgery has the best chance of providing long-term help however surgery comes with massive side effects. There are two classic drug-based solutions corticosteroids and immunomodulators. Corticosteroids reduce the body’s inflammatory response. Immunomodulators change how the immune system acts. The newest type of Crohn’s medication to market is biologics, which targets only specific parts of the immune system to keep effectiveness high and side effects low. Several of these are still in the research phase along with some brand new classes of oral drugs. To learn more about getting involved in Crohn’s disease research studies, visit our enrolling studies page or call your local ENCORE office today. 

Written by: Benton Lowey-Ball, B.S. Behavioral Neuroscience


Source

Gajendran, M., Loganathan, P., Catinella, A. P., & Hashash, J. G. (2018). A comprehensive review and update on Crohn’s disease. Disease-a-month, 64(2), 20-57.


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Parkinson’s disease is a brain disease known for producing problems with muscle movement. These problems can include shaking tremors, muscle stiffness, and difficulty with balance and walking. The direct cause of these problems is a decrease in dopamine production. Dopamine is a chemical in the brain used to communicate information between nerves. It is also used to direct motor function. The motor coordination part of the brain, the basal ganglia, requires dopamine to function. Without dopamine, the basal ganglia cannot coordinate your muscles well. This means you cannot coordinate smooth, balanced, and nuanced movements. The stereotypical shaking in Parkinson’s patients is the result. It is akin to what would happen if the traffic lights in a city were not receiving enough power. Cars would still get through town, but traffic would be slow, backed up, jerky, and would only get worse.

Parkinson’s is a progressive disease, meaning that it gets worse over time. It affects about 1% of those 65 and older and 3% of adults over 80. Additionally, it is expected that the number of people with Parkinson’s disease may increase by up to 30% by 2030. Though it can affect any older individual, it is more common in men. Genetic and environmental factors can increase the chance of getting Parkinson’s. These include being of European or South American descent, smoking, and exposure to pesticides. Surprisingly, there is also a link between Parkinson’s and your gut!

Your gut has a direct link to the brain through the gut-brain axis via a special nerve called the vagus nerve. The vagus nerve travels from the brain and some important parts of the digestive system (stomach, large, and small intestine). This nerve communicates a lot of information. It is partially responsible for mood, hunger, energy, and helps coordinate immune responses. Though the brain is the thinking center of the body, it needs input from the body to make decisions. Interestingly, 90% of vagus nerve information flows from the gut to the brain! Therefore, disruptions in the gut can have massive effects on how your brain functions.  This appears to be true with Parkinson’s disease. Research shows that misfolded proteins called alpha-synuclein may be able to travel through the vagus nerve. This may damage the part of the brain responsible for muscle control, called the basal ganglia.

Research has found that disruptions of the gut can affect every system the vagus nerve touches. This might be one of the causes for some of Parkinson’s other effects, including non-motor disruptions.  These can include rapid eye movement behavior disorder (RBD), mood disorders, cognitive problems like attention and learning, and even hallucinations.

So far, there are no therapies that can reverse the effects of Parkinson’s Disease. Doctors prescribe l-DOPA to replicate dopamine production in the brain. This helps the basal ganglia coordinate movement to reduce the symptoms of Parkinson’s. Unfortunately, we cannot yet reverse the progressive nature of the disease. Fortunately, clinical trials are aiming to discover disease-modifying treatments!

Sources:

Breit, S., Kupferberg, A., Rogler, G., & Hasler, G. (2018). Vagus nerve as modulator of the brain–gut axis in psychiatric and inflammatory disorders. Frontiers in psychiatry, 44.

Kandel, E. R., Schwartz, J. H., Jessell, T. M., Siegelbaum, S., Hudspeth, A. J., & Mack, S. (Eds.). (2000). Principles of neural science (Vol. 4, pp. 1227-1246). New York: McGraw-hill.

Kouli, A., Torsney, K. M., & Kuan, W. L. (2018). Parkinson’s disease: etiology, neuropathology, and pathogenesis. Exon Publications, 3-26.

Lanciego, J. L., Luquin, N., & Obeso, J. A. (2012). Functional neuroanatomy of the basal ganglia. Cold Spring Harbor perspectives in medicine, 2(12), a009621.

NIH, National Institute on Aging. (2017). Parkinson’s Disease. https://www.nia.nih.gov/health/parkinsons-disease

Schwarz, P. B., & Peever, J. H. (2011).Dopamine triggers skeletal muscle tone by activating D1-like receptors on somatic motoneurons. Journal of neurophysiology, 106(3), 1299-1309.

Shaik, L., Kashyap, R., Thotamgari, S. R., Singh, R., & Khanna, S. (2020). Gut-brain axis and its neuro-psychiatric effects: A narrative review. Cureus, 12(10).


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April 3, 2022 BlogExercise

There are many good things about April.  Spring is sprung, Easter egg hunts, and Earth Day. You may not have known, but April is also “Move More Month!” This April challenge is a great way to get into a good routine of getting up and moving! Exercise is such an excellent benefit for your health. Exercise has proven to help people sleep better, increase serotonin levels (happy hormone), and overall be healthier.

Some simple ways to get moving are going on walks, stretching, lifting small weights, riding a bike, and many more! It’s all about making small changes to get into a routine. Our ENCORE Research staff challenged themselves for April to get moving, even while at the office. Every hour we get up and move, doing a quick exercise. We find that setting a reminder alarm helps to keep us on track. We hope that you can follow along and get inspired to move more!

Here are some ideas to help get you started:


Easy:

  • Walk in place
  • Chair sits
  • Countertop plank
  • Countertop push-ups
  • Step-ups
  • Go for a walk

Medium:

  • Chair squats (not fully sitting)
  • Knees down Plank
  • Knees down push-ups
  • Hand slap step-up
  • Go for a walk/run (alternating)
  • Speed Clean (set a 5-minute timer)

Hard:

  • Squats
  • Planks
  • Push-ups
  • Stair (or bench) step-up
  • Go for a run



MedEvidence! Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings and Dr. Michael Koren. This month’s MedEvidence Radio discusses the Silent Killer, Lipoprotein(a), Diabetes, and Clinical Research Technologies.

We will dive into the following:
🩺 Clinical Research
💙 Lipoprotein(a)
🍬 Diabetes
❤️ Cardiovascular Health
🔬 Clinical Research Trials

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals.  Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.  On a personal note, Dr. Koren has a lifelong interest in history, technology, Public Health, and music. He has written two musical plays.


Listen to the full episode here:




MedEvidence! Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings and Dr. Michael Koren. This month’s MedEvidence Radio discusses Damar Hamlin’s cardiac event during a football game on January 2, 2023.

We will dive into the following:
🩺 Commotio cordis
🩺 Hypertrophic Cardiomyopathy
🩺 Atrial Fibrillation
❤️ Cardiovascular Health
🔬 Clinical Research Trials

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals.  Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.  On a personal note, Dr. Koren has a lifelong interest in history, technology, Public Health, and music. He has written two musical plays.


Listen to the full episode here:




MedEvidence! Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings and Dr. Michael Koren from St. Augustine, Florida. This month’s MedEvidence Radio discusses the diabetic epidemic in the US.

We will dive into:
💉GLP-1 Drug Class
💉SGLT2i Drug Class
💉Newer Class of Diabetic Drugs
❤️Cardiovascular Safety
🔬 Past and New Clinical Research Trials

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals.  Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.  On a personal note, Dr. Koren has a lifelong interest in history, technology, Public Health, and music. He has written two musical plays.


Listen to the full episode here:




On this month’s MedEvidence radio episode, Doctors Michael Koren, MD, Matthew Todd Braddock, DO, Jackson Downey, MD, Albert Lopez, DO and WSOS Radio Host Kevin Geddings discuss NASH, Fatty Liver, and Fibroscans.

This month’s MedEvidence! Radio will answer:

  • What is NASH?
  • What are the stages of NASH?
  • How do you treat NASH?
  • Is NASH reversible?
  • Is NASH related to cholesterol problems?

MedEvidence! Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings from St. Augustine, Florida. Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals.  Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.  On a personal note, Dr. Koren has a lifelong interest in history, technology, Public Health, and music. He has written two musical plays.


Listen to the full episode here:




Clinical Trials Day is celebrated around the world in May to recognize the day that James Lind started what is often considered the first clinical trial aboard a ship on May 20, 1747.

Here’s the story…

Also included in this month’s MedEvidence! Radio

  • Why we do Clinical Trials
  • Phases of Clinical Trials
  • Why you may want to participate in clinical trials

MedEvidence! Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings from St. Augustine, Florida. Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals.  Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.  On a personal note, Dr. Koren has a life-long interest in history, technology, Public Health, and music. He has written two musical plays.


Listen to the full episode here:


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Healthy eating and exercise can help with not only your waistline but also cardiometabolic health. Carrying around extra fat can negatively affect your whole body; some areas of concern include the liver, heart, and joints. Although many people can maintain a healthy diet and exercise routine to keep the weight off, some folks need extra help with medication.

The liver is the largest organ inside your body and is integral in filtering harmful substances from your blood. When too much fat builds up in your liver, this is called fatty liver disease. This can progress to damaging and scarring of the liver. The scaring can ultimately lead to liver failure. Lifestyle changes, like healthy eating and exercise, are currently the only treatments for fatty liver disease, although many clinical trials are currently looking for a safe and effective therapy.

Heart disease remains the world’s leading killer. While extra fat itself does not directly cause heart attacks, it leads to other causes that can. High cholesterol, high blood pressure, and diabetes are among those that build up plaque in the arteries leading to heart attacks. ENCORE Research Group offices have many clinical trials in these areas!

Being overweight can affect your joints by raising your risk of developing osteoarthritis. The extra weight puts additional stress on your weight-bearing joints, such as your knees, which can cause additional wear and tear. Additionally, inflammation associated with weight gain might contribute to problems in other joints such as the hands.

For the folks who need more than just a healthy diet and exercise to help with medical conditions, the good news is that many new cutting-edge treatments are being studied and are available to you. Call your local ENCORE Research Group office today to get involved in our research trials.

Sources:
heathline.com
health.clevelandclinic.org
health.harvard.edu


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Diabetic peripheral neuropathy is a type of nerve damage associated with diabetes that most commonly affects the peripheries of the body (toes, feet, legs, hands, and arms).  Symptoms can range from mild to severe and can be painful, debilitating, or even fatal. The most common neuropathy symptom people seek medical attention for is pain. Since diabetic neuropathy currently does not have a cure, the best thing people can do is treat the pain and make sure their blood sugar levels are well controlled.

Diabetic neuropathy symptoms are often worse at night.  Symptoms include:

  • Lack of sensation to pain or temperature in those areas
  • A tingling, burning or needle pricking feeling
  • Sharp pain or cramps
  • Extreme sensitivity to touch
  • Problems with balance and coordination

People who have had diabetes for at least 25 years have the highest rates of nerve damage.  Neuropathies are also more common in people who cannot keep their blood sugar under control, have high blood pressure, or are obese.

Current treatment options for pain are limited by poor effectiveness and high rates of side effects, leaving many patients without adequate pain control. With chronic use, nonsteroidal anti-inflammatory drugs (NSAIDs) pose a potentially serious gastrointestinal and liver toxicity risk. Opioids are commonly prescribed for moderate-to-severe pain but are limited by safety and tolerability issues and have high abuse rates. Opioid-associated death rates have also increased over the past two decades.

Given the limited treatment options, combined with the risks and ineffectiveness of currently available treatments, developing new treatments is vital for better pain management and health outcomes. We are involved in many cutting-edge research trials at ENCORE Research Group, and some of our locations currently have research studies for painful diabetic peripheral neuropathy. To learn more about participating in our cutting-edge clinical trials, call our main office today! (904)-730-0166


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What is EoE?
Eosinophilic esophagitis (EoE) is a chronic disease of the esophagus. Your esophagus is a muscular tube that carries food from your mouth to your stomach. EoE is when white blood cells (called eosinophils) build up in your esophagus.

What are the symptoms?
Some of the most common symptoms of EoE are:

  • Trouble swallowing
  • Chest pain or heartburn
  • Abdominal pain
  • Vomiting
  • Food getting stuck in your throat due to narrowing (this is a medical emergency)
  • Stunted growth or poor weight gain in children

How to get diagnosed.
Your doctor will most likely want you to have an endoscopy to diagnose EoE. An endoscopy is a procedure where an endoscope (a tube with a light and camera attached at the end) is inserted into the body to let your doctor look inside an organ. For an esophageal endoscopy, the endoscope is put in your mouth and down your throat to examine the esophagus. But don’t worry, you’re not awake for that part! Other ways you can be diagnosed are biopsies, blood tests, and an esophageal sponge.

Current research on EoE.
Science continues to move forward for new treatments of eosinophilic esophagitis, and we are delighted to be involved in these cutting-edge research trials at some of our ENCORE Research Group locations. To learn more about participating in our cutting-edge clinical trials, call our main office today! (904)-730-0166


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Alzheimer’s is a devastating disease that affects 5.5 million people of all ages in the United States. Along with the diagnosis and reality of living with this disease, the families of these patients are now left with the question, “how will we take care of our loved one?” For many families, the option is having a designated person take care of the patient on their own. A caregiver is someone that assists with the daily needs of another person. There can be a “formal” caregiver, considered a paid person along with training, and an “informal” caregiver is a family or friend who provides care without pay. It can be a challenge for informal caregivers, especially with no training. Around 65.7 million people in the United States are informal caregivers. With that large of a statistic affecting a specific population, there are always great tips that can be provided.

 

Asking For Help

Taking care of someone with Alzheimer’s can be challenging. If it becomes too difficult for a caregiver, sometimes they feel guilty in asking for help. If taking care of someone becomes too emotionally and physically draining, there’s no shame in asking for help or even hiring someone to come in and help. The most important thing is making sure that your loved ones can get the best care they can get.

 

Staying Connected

Studies show that caregivers who stay in touch with their families and friends have better emotional health than those who feel isolated. Reaching out to express your feelings about being a caregiver and the challenges that come with it can help relieve stress. Staying in contact with other family members and keeping them updated on their loved ones allows them to step in and support when needed.

 

Making Your Health A Priority

Caregivers, along with the patient, must make sure their health is a priority. Without the caregiver in good health, they wouldn’t be able to provide the optimum care the patient needs. Along with regular check-ups, making sure you get yearly Flu shots, testing, and staying active is important. Being a caregiver can be physically demanding, and your health is just as important as the Alzheimer’s patient’s health.

 

Participate in Research for Alzheimer’s

There is currently no cure for Alzheimer’s, but there are clinical studies that the patient and caregiver can participate in. Since the caregiver needs to assist the patient with all that comes with being in a study, both the caregiver and the patient would receive a stipend. The more participants in Alzheimer’s studies, the more research is done, getting us closer to a cure! For more information on our currently enrolling Alzheimer’s disease studies, give our office a call.


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February 20, 2022 BlogCardiovascular

How Do You Know If You Have High Blood Pressure?

The truth is, you don’t. The only way to really know if you have high blood pressure is by getting your blood pressure checked regularly. High blood pressure or hypertension (HTN) is known as the “silent killer” because it causes sudden heart attacks or strokes resulting in serious injury or possibly death with no warning.

The Effects of Hypertension 

HTN causes more than just heart attacks and strokes. Prolonged HTN can cause serious illnesses such as:

  • Kidney Disease — HTN may cause damage to the arteries surrounding the kidney. The damage can affect the kidney’s ability to filter blood efficiently. 
  • Heart failure — Heart failure occurs when the heart has to work harder to supply blood to the body, and HTN can cause extra work for the heart. 
  • Loss of Vision HTN can strain or damage blood vessels in the eyes.
  • Sexual Dysfunction — HTN can lead to erectile dysfunction in men or lower libido in women. 
  • Angina — Over time, HTN can lead to heart disease or microvascular disease (MVD). Angina, or chest pain, is a common symptom.
  • Peripheral artery disease (PAD) — Atherosclerosis caused by high blood pressure can cause a narrowing of arteries in the legs, arms, stomach, and head, causing pain or fatigue.

How to Prevent a Visit from the “Silent Killer.”

One way to decrease your risk of heart disease from HTN is to know your numbers. Below is a chart from the American Heart Association that accurately details healthy vs. unhealthy blood pressure numbers.

The second way is to be aware of your risk. 

There are many risk factors for HTN and being aware of them can give you the knowledge to make healthy changes. 

  • Diet — Diet plays a considerable role in elevated blood pressure levels. Diets high in salty, fatty, and processed food increase your blood pressure, causing HTN. A good diet would be one that is high in vegetables, fruits, and lean meats.
  • Physical Activity — Regular physical activity improves blood circulation and decreases your risk for HTN. 
  • Alcohol and tobacco use — Excessive alcohol and tobacco use can cause HTN and increase your risk of heart attack, stroke, and heart disease.

Other risk factors that you need to be aware of but are out of your control are:

  • Family history 
  • Age
  • Gender 
  • Race 

Overcome Hypertension 

How can you overcome hypertension? One way is to talk with your doctor about any medications or specific lifestyle changes you can make to reduce your risk. Another way is to participate in clinical trials. Clinical trials are a great tool to get to know your health more, receive one-on-one quality attention from a medical professional, and access to the latest therapies that are not currently on the market. ENCORE Research Group is currently enrolling in studies for hypertension.  If you or someone you know would like to participate, please call 904-730-0166 or visit encoredocs.com.





In this episode of MedEvidence, we delve into the critical issue of healthcare burnout during the pandemic. Dr. Michael Koren and Dr. Lisa Kirvin-Dawes, bring their expertise and insights as healthcare professionals to discuss the challenges and impacts of the pandemic on the mental and emotional well-being of healthcare workers. They share their experiences and offer practical advice for navigating burnout, managing stress, and finding support. Join us for a thought-provoking conversation on an important issue affecting the healthcare industry today.

Lisa Kirven-Dawes, MD, is a practicing physician in Jamacia focusing on infectious control, diseases, and care & the former Chair of Medicine and graduate of Harvard Medical School. Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.

He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.

Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials, including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been published in the most prestigious medical journals. Dr. Koren has also designed a research training course for physicians, now in its 20th year.


Prefer to listen to the podcast without video? You can do that below!








Dr.’s Michael Koren and Dennis Leahy wrap up the MedEvidence Lipoprotein A series by exploring Lp(a) clinical trial treatments. Dr. Leahy shares his personal clinical research experience and platform for encouraging everyone to have their LP(a) blood work drawn. Tune in to learn more about this lesser-known condition, possible treatment options, and the future of Lp(a).

Dr. Dennis Leahy is a retired interventional cardiologist living in San Diego. He received his education from Princeton University and Columbia University and his residency at the University of California. In addition to enjoying the opportunity to surf and golf, he has maintained a personal and professional interest in Lipoprotein A research and treatment.

Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.

He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.

Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials, including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been published in the most prestigious medical journals. Dr. Koren has also designed a research training course for physicians, now in its 20th year.


Prefer to listen to the podcast without video? You can do that below!








Continuing with Part 3 of Dr.’s Michael Koren and Dennis Leahy discussion on MedEvidence exploring Lipoprotein A treatments. Dr. Leahy shares his personal experience with Lp(a), and the duo delves into cutting-edge treatments and research. Tune in to learn more about this lesser known condition and possible treatment options.

Dr. Dennis Leahy is a retired interventional cardiologist living in San Diego. He received his education from Princeton University and Columbia University and his residency at the University of California. In addition to enjoying the opportunity to surf and golf, he has maintained a personal and professional interest in Lipoprotein A research and treatment.

Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.

He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.

Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials, including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been published in the most prestigious medical journals. Dr. Koren has also designed a research training course for physicians, now in its 20th year.


Prefer to listen to the podcast without video? You can do that below!








Dr.’s Michael Koren and Dennis Leahy, cardiovascular specialists, continue with part 2 in a 4 part series of MedEvidence exploring Lipoprotein A, also know as Lp(a). Dr. Leahy shares his personal experience with Lp(a), and the duo delves into cutting-edge strategies for managing this risk factor for cardiovascular disease. So, tune in to learn more about this lesser known condition and possible treatment options.

Dr. Dennis Leahy is a retired interventional cardiologist living in San Diego. He received his education from Princeton University and Columbia University and his residency at the University of California. In addition to enjoying the opportunity to surf and golf, he has maintained a personal and professional interest in Lipoprotein A research and treatment.

Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.

He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.

Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials, including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been published in the most prestigious medical journals. Dr. Koren has also designed a research training course for physicians, now in its 20th year.


Prefer to listen to the podcast without video? You can do that below!








Join Dr.’s Michael Koren and Dennis Leahy, cardiovascular specialists, in a 4 part series of MedEvidence exploring Lipoprotein a, also known as Lp(a). Dr. Leahy shares his personal experience with LP(a), and the duo delves into cutting-edge strategies for managing this risk factor for cardiovascular disease. So, tune in to learn more about this lesser-known condition and possible treatment options.

Dr. Dennis Leahy is a retired interventional cardiologist living in San Diego. He received his education from Princeton University and Columbia University and his residency at the University of California. In addition to enjoying the opportunity to surf and golf, he has maintained a personal and professional interest in Lipoprotein A research and treatment.

Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.

He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.

Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials, including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been published in the most prestigious medical journals. Dr. Koren has also designed a research training course for physicians, now in its 20th year.


Prefer to listen to the podcast without video? You can do that below!







In honor of American Heart Month,  Dr. Michael Koren was on the SCRS Talks podcast to share his top tips for heart health. Dr. Koren also explores how cardiovascular research and treatment have progressed over the past several years and some exciting new learnings for this vital therapeutic area.

Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.

He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.

Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials, including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been published in the most prestigious medical journals. Dr. Koren has also designed a research training course for physicians, now in its 20th year.

On a personal note, Dr. Koren developed a lifelong interest in technology and Public Health during his time at The Massachusetts Institute of Technology and The Harvard School of Public Health. He also loves music. He has written two musical plays.






Join us on the MedEvidence podcast as we reunite Staten Island middle school friends Dr. Michael Koren and Mick LaSalle. As experts in their respective fields, their discussion explores the intersection of clinical research, film criticism, and humor. Don’t miss this unique and entertaining episode of the MedEvidence podcast!

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Mick LaSalle, film critic for The San Francisco Chronicle and former on-air film critic for the ABC-TV affiliate in San Francisco, KGO. He is the author of Complicated Women: Sex and Power in Pre-Code Hollywood (2000), Dangerous Men: Pre-Code Hollywood and the Birth of the Modern Man (2002); The Beauty of the Real: What Hollywood Can Learn from Contemporary French Actresses (2012); and Dream State: California in the Movies (2021).  With Leba Hertz, he hosted the Mick LaSalle podcast between 2005 and 2010. He wrote and co-produced the Complicated Women documentary for Turner Classic Movies, which Jane Fonda narrated. He has also written introductions to several books, including The Enduring Star, Peter Cowie’s biography of Joan Crawford (Rizzoli, 2009). He met Dr. Michael Koren in Middle School during the 1970s.


Prefer to listen to the podcast without video? You can do that below!








Dr. Michael Koren sits down with his middle school buddy, Mick LaSalle, a well-known film critic, to discuss changes in the direction of medicine & media. Their “Staten Island humor” is evident as they talk about how the media markets medicine from aspirin to covid, what the media says vs. what the medical data proves.

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Mick LaSalle, film critic for The San Francisco Chronicle and former on-air film critic for the ABC-TV affiliate in San Francisco, KGO. He is the author of Complicated Women: Sex and Power in Pre-Code Hollywood (2000), Dangerous Men: Pre-Code Hollywood and the Birth of the Modern Man (2002); The Beauty of the Real: What Hollywood Can Learn from Contemporary French Actresses (2012); and Dream State: California in the Movies (2021).  With Leba Hertz, he hosted the Mick LaSalle podcast between 2005 and 2010. He wrote and co-produced the Complicated Women documentary for Turner Classic Movies, which Jane Fonda narrated. He has also written introductions to several books, including The Enduring Star, Peter Cowie’s biography of Joan Crawford (Rizzoli, 2009). He met Dr. Michael Koren in Middle School during the 1970s.


Prefer to listen to the podcast without video? You can do that below!








Brad Hightower, the founder of Hightower Clinical, clinical research professional, and host of the Note to File podcast, sits down with Dr. Michael Koren to discuss clinical research as a care option, decentralized clinical trials, and clinical research technology and data collection using EMRs and CTMS such as Clinasyst.

Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine and fellowship in cardiology at New York Hospital/Memorial Sloan-Kettering Cancer Center/Cornell Medical Center.

He is a fellow of the American College of Cardiology, fellow and two-time president of the Academy of Physicians in Clinical Research, and the regional chapter of the American Heart Association.

Dr. Koren has served as an Investigator in over 2,000 trials and as the international lead investigator for many multi-centered trials, including ALLIANCE, ROLE, TREAT to TARGET, OSLER, and MENDEL studies. He has written and co-authored over 100 peer-reviewed articles and been published in the most prestigious medical journals. Dr. Koren has also designed a research training course for physicians, now in its 20th year.

On a personal note, Dr. Koren developed a lifelong interest in technology and Public Health during his time at The Massachusetts Institute of Technology and The Harvard School of Public Health. He also loves music. He has written two musical plays.

Brad Hightower, founder of Hightower Clinical, clinical research professional, and host of the Note to File podcast. Brad lives, works, and podcasts from Oklahoma City, OK.  He has worked at the site level in clinical research for ten years and is the former Executive Director of the Oklahoma Heart Hospital Research Foundation.  Brad has since started his own integrated site network, Hightower Clinical.
To learn more about Hightower Clinical, please visit hightowerclinical.com.
To connect with Brad, please reach out on LinkedIn.





The Next Generation of Clinical Researchers series concludes with a discussion of research outreach, research ambassadors, and the value of educating the community about clinical research to help advance medicine and healthcare for all.

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Adrian Rowda, a second-generation clinical researcher, graduated from Jacksonville University in 2008 with a BSN. Followed by working as a nurse in Mayo Clinic’s Surgical Intensive Care Unit and ED for 6 years.  In 2014 she graduated from Jacksonville University with her MSN as a Family Nurse Practitioner and began working at UF Health in their Trauma/Surgical Intensive Care Unit for 3 years.  Since 2017 she has been with Baptist Medical Center in their Neuro Intensive Care Unit.


Prefer to listen to the podcast without video? You can do that below!







Episode three in the MedEvidence series, The Next Generation of Clinical Researchers discusses patients’ value propositions for the next generation as spoken by a second-generation researcher.

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Adrian Rowda, a second-generation clinical researcher, graduated from Jacksonville University in 2008 with a BSN. Followed by working as a nurse in Mayo Clinic’s Surgical Intensive Care Unit and ED for 6 years.  In 2014 she graduated from Jacksonville University with her MSN as a Family Nurse Practitioner and began working at UF Health in their Trauma/Surgical Intensive Care Unit for 3 years.  Since 2017 she has been with Baptist Medical Center in their Neuro Intensive Care Unit.


Prefer to listen to the podcast without video? You can do that below!







What characteristics, quality & attributes are needed for the Next Generation of Clinical Researchers? Listen in as the current, future & second-generation of researchers discuss this topic and share personal stories.

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Adrian Rowda, a second-generation clinical researcher, graduated from Jacksonville University in 2008 with a BSN. Followed by working as a nurse in Mayo Clinic’s Surgical Intensive Care Unit and ED for 6 years.  In 2014 she graduated from Jacksonville University with her MSN as a Family Nurse Practitioner and began working at UF Health in their Trauma/Surgical Intensive Care Unit for 3 years.  Since 2017 she has been with Baptist Medical Center in their Neuro Intensive Care Unit.


Prefer to listen to the podcast without video? You can do that below!







Listen in on the new MedEvidence series, The Next Generation of Clinical Researchers, to learn how research transfers knowledge from generation to generation as spoken by a second-generation researcher.

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Adrian Rowda, a second-generation clinical researcher, graduated from Jacksonville University in 2008 with a BSN. Followed by working as a nurse in Mayo Clinic’s Surgical Intensive Care Unit and ED for 6 years.  In 2014 she graduated from Jacksonville University with her MSN as a Family Nurse Practitioner and began working at UF Health in their Trauma/Surgical Intensive Care Unit for 3 years.  Since 2017 she has been with Baptist Medical Center in their Neuro Intensive Care Unit.


Prefer to listen to the podcast without video? You can do that below!







The MedEvidence Diabetes series concludes with managing individual patients’ diabetic needs with anecdotes and stories by Dr. Koren and Sharon Smith.

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Sharon Smith, RN, CDCES, is the VP of Recruitment at ENCORE Research Group and a Diabetic Educational Nurse with a passion for educating patients as well as staff on healthy lifestyle options without giving up on special treats.


Prefer to listen to the podcast without video? You can do that below!







In part 3 of the MedEvidence Diabetes series Dr. Koren and Sharon Smith discuss choosing drug classes for diabetes, weight loss and cardiovascular health.

💉GLP-1 Drug Class
💉SGLT2i Drug Class
🔬 Past and New Clinical Research Trials

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Sharon Smith, RN, CDCES, is the VP of Recruitment at ENCORE Research Group and a Diabetic Educational Nurse with a passion for educating patients as well as staff on healthy lifestyle options without giving up on special treats.


Prefer to listen to the podcast without video? You can do that below!







What does a diabetic educational nurse want you to know about blood sugars, and what is a cardiovascular doctor doing in the diabetes space? Let’s find out! In part 2 of the MedEvidence diabetes series, Dr. Michael Koren and Sharon Smith will discuss:

🩺  4 Main Components of Type 2 Diabetes Care
💉  Newer Classes of Diabetic Drugs
❤️  Cardiovascular Safety
🔬  New and Past Clinical Research Trials

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Sharon Smith, RN, CDCES, is the VP of Recruitment at ENCORE Research Group and a Diabetic Educational Nurse with a passion for educating patients as well as staff on healthy lifestyle options without giving up on special treats.


Prefer to listen to the podcast without video? You can do that below!







In honor of American Diabetes Month, we are releasing the MedEvidence! Diabetes series. In this episode, Dr. Michael Koren and Diabetic Nurse Educator, Sharon Smith explain the basics of diabetes and the history of diabetic drugs.

In this issue, you will learn:
🩺Type 1 vs Type 2

💉History of Diabetic Drugs

❤️Cardiovascular Safety

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.


Prefer to listen to the podcast without video? You can do that below!






MedEvidence Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings and Dr. Michael Koren from St. Augustine, Florida. This month’s MedEvidence Radio discusses all the various viruses coming our way this season.

We will dive into:

  • RSV – Respiratory Syncytial Virus
  • COVID
  • Flu
  • Developing a virus strategy plan
  • Vaccine effects
  • Antibody levels

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.


Prefer to listen to the podcast without video? You can do that below!





MedEvidence! Radio is a monthly live broadcast from WSOS 103.9 FM / 1170 AM with Kevin Geddings and Dr. Michael Koren from St. Augustine, Florida. This month, Dr. Erich Schramm joins the conversation in discussing whether patients benefit from clinical research and, if so how?

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Erich Schramm, MD, is a board-certified family physician in Ponte Vedra, Florida, with 22 years of experience. He is currently a principal investigator with ENCORE Research Group.


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This week’s MedEvidence podcast concludes with episode 4 of our series about MedEvidence. Dr. Koren explains the passion, goals, and need for MedEvidence a trusted resource at a time when the world is filled with misinformation.  Meet the team behind MedEvidence, where we learn how medical truths are found. What hypothesis testing is, the history of finding truth through research, and Dr. Koren’s founding of  Jacksonville Center for Clinical Research.

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.




This week’s MedEvidence podcast continues with episode 3, where we learn how medical truths are found. What hypothesis testing is, the history of finding truth through research, and Dr. Koren’s founding of  Jacksonville Center for Clinical Research.

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.




This week’s MedEvidence podcast continues with episode 2, where we learn a little personal history about our founder, Dr. Michael Koren. From the gas attendant’s son to Harvard Medical School to ENCORE Research Group, who is the man behind the white coat?

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.




This MedEvidence podcast is a four-part series. MedEvidence, What Is It and Why Does the World Need It?  Michelle McCormick asked Dr. Michael Koren why he created MedEvidence and why it’s so important in a world filled with misinformation.

You will learn how MedEvidence will:

  • MedEvidence is a truth-based interface to help people make medical decisions
  • How MedEvidence will help you understand confusing claims in medical news
  • Help you decipher medical scenarios that are difficult to sort through
  • Learn more about Clinical Research

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.




This week’s MedEvidence podcast is on Medical Marijuana. Meet Dr. Charlie Booras, former Principal Investigator at Jacksonville Center of Clinical Research, and Baptist Primary Care physician who grew his practice into Booras MD as a tribute to his father after treating his ALS with medical cannabis as a medication. Dr. Michael Koren and Dr. Booras dive into the scientific basis for the efficacy of medical cannabis.

You will learn:

        • Florida Medical Marijuana Law and Process
        • THC vs. CBD
        • Health Benefits for Medical Marijuana
        • History of Marijuana
        • Learn more about Clinical Research
        • Learn more about BoorasMD

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.


Prefer to listen to the podcast without video? You can do that below!






This week’s MedEvidence podcast is the second episode in a two-part series on Liquid Biopsy.

In this 24-minute episode Doctors, Michael Koren and Bharat Misra discuss liquid biopsy usage now & in the future of medical evaluations.

You will learn:

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Bharat Misra is the Medical Director of ENCORE Borland Groover Clinical Research and has been a Principal Investigator of numerous clinical trials. He also serves on the board of directors at Memorial Hospital and Jacksonville Center for Clinical Research in Jacksonville, Florida. He completed his residency in internal medicine and fellowship in gastroenterology at the Nassau University Medical Center, State University of New York, and his Bachelor of Medicine and Bachelor of Surgery from Gandhi Medical College in India.


Prefer to listen to the podcast without video? You can do that below!





This week’s MedEvidence podcast is a two-part series on Liquid Biopsy: What is it & Do I Need One?

In this 22-minute episode Doctors, Michael Koren and Bharat Misra explain liquid biopsies and conditions that are subject to evaluations with liquid biopsies.

You will learn

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Bharat Misra is the Medical Director of ENCORE Borland Groover Clinical Research and has been a Principal Investigator of numerous clinical trials. He also serves on the board of directors at Memorial Hospital and Jacksonville Center for Clinical Research in Jacksonville, Florida. He completed his residency in internal medicine and fellowship in gastroenterology at the Nassau University Medical Center, State University of New York, and his Bachelor of Medicine and Bachelor of Surgery from Gandhi Medical College in India.


Prefer to listen to the podcast without video? You can do that below!





“What’s New with the Flu?”  Dr. Michael Koren, Dr. Victoria Helow, and Michelle McCormick discuss Flu and COVID.

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Victoria Helow, is a well-respected pediatrician, clinical research investigator at ENCORE Research Group, and practicing emergency room physician.


Prefer to listen to the podcast without video? You can do that below!





Wrapping up this month’s MedEvidence! podcast series on “What to do after a Heart Attack or Stroke?”  Doctors, Michael Koren and Albert Lopez, DO discuss treatments, medications, and clinical research you need to know as a post-heart event patient.

You will learn:

  • Treatment therapies to use after a heart attack or stroke
  • What is Lp(a)
  • Male vs Female Symptoms
  • Cardiovascular Disease Research

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Albert Lopez, DO practices Internal Medicine with Millennium Physician Group in Jacksonville, Florida. He is also a Principal Investigator with ENCORE Research Group specializing in lipid clinical trials. Dr. Lopez, DO completed his residency at the University of Pennsylvania and his Doctor of Osteopathic Medicine at Nova Southeastern University in Miami, Florida. He is known as one of the earliest evidence-based physicians in Jacksonville utilizing nutrition and lifestyle for disease prevention.
I believe in “N” of one” because “N of one” is about the patient. If it is not about the patient, then it is about nothing. – Dr. Albert Lopez, DO


Prefer to listen to the podcast without video? You can do that below!





This month’s MedEvidence! podcast is a three-part series on “What to do after a Heart Attack or Stroke?” In the first MedEvidence segment we established that people who have had either a heart attack or stroke have a high risk for a repeat procedure or event. We also discussed knowing who’s on your Heart Health Team, PCP, specialist, and family. What’s abnormal, normal, and what to do when symptoms last greater than 20 minutes? In this 15-minute episode, Doctors, Michael Koren and Albert Lopez DO discuss the Risk Factors You Need to know for your heart health.

You will learn:

      • What modifiable risk factors are
      • What non-modifiable risk factors are
      •  What you can do to help your risk factors
      • How clinical trials and research find other drug benefits
      • How to be involved in a clinical trial

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Albert Lopez, DO practices Internal Medicine with Millennium Physician Group in Jacksonville, Florida. He is also a Principal Investigator with ENCORE Research Group specializing in lipid clinical trials. Dr. Lopez, DO completed his residency at the University of Pennsylvania and his Doctor of Osteopathic Medicine at Nova Southeastern University in Miami, Florida. He is known as one of the earliest evidence-based physicians in Jacksonville utilizing nutrition and lifestyle for disease prevention.
I believe in “N” of one” because “N of one” is about the patient. If it is not about the patient, then it is about nothing. – Dr. Albert Lopez, DO


Prefer to listen to the podcast without video? You can do that below!





This MedEvidence! podcast is a three-part series on “What to do after a Heart Attack or Stroke?” In this episode, Doctors, Michael Koren and Albert Lopez, DO help you identify your heart health team.

You will learn:

    • Who do I call if I think I’m having a heart attack?
    • What are my risks for another event?
    • How can my family help?
    • How to find a clinical trial

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Albert Lopez, DO practices Internal Medicine with Millennium Physician Group in Jacksonville, Florida. He is also a Principal Investigator with ENCORE Research Group specializing in lipid clinical trials. Dr. Lopez, DO completed his residency at the University of Pennsylvania and his Doctor of Osteopathic Medicine at Nova Southeastern University in Miami, Florida. He is known as one of the earliest evidence-based physicians in Jacksonville utilizing nutrition and lifestyle for disease prevention.
I believe in “N” of one” because “N of one” is about the patient. If it is not about the patient, then it is about nothing. – Dr. Albert Lopez, DO


Prefer to listen to the podcast without video? You can do that below!





In this final 30-minute episode Doctors, Michael Koren and Bharat Misra dive into new treatments in clinical trials for Fatty Liver Disease and NASH.

You will learn

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Bharat Misra is the Medical Director of ENCORE Borland Groover Clinical Research and has been a Principal Investigator of numerous clinical trials. He also serves on the board of directors at Memorial Hospital and Jacksonville Center for Clinical Research in Jacksonville, Florida. He completed his residency in internal medicine and fellowship in gastroenterology at the Nassau University Medical Center, State University of New York, and his Bachelor of Medicine and Bachelor of Surgery from Gandhi Medical College in India.


Prefer to listen to the podcast without video? You can do that below!





This month’s MedEvidence! Hour is a three-part series on You Cannot Live without Your Liver.   In this 14-minute Part 2 episode Doctors, Michael Koren and Bharat Misra answer your questions on Fibroscans.

  • Who should receive a Fibroscan
  • How often should I get a Fibroscan
  • Should I ask my primary doctor for a Fibroscan
  • Liver Biopsy vs. Fibroscan
  • Insurance and Fibroscan
  • What should I do after my Fibroscan
  • How to find a free Fibroscan

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Bharat Misra is the Medical Director of ENCORE Borland Groover Clinical Research and has been a Principal Investigator of numerous clinical trials. He also serves on the board of directors at Memorial Hospital and Jacksonville Center for Clinical Research in Jacksonville, Florida. He completed his residency in internal medicine and fellowship in gastroenterology at the Nassau University Medical Center, State University of New York, and his Bachelor of Medicine and Bachelor of Surgery from Gandhi Medical College in India.


Prefer to listen to the podcast without video? You can do that below!





This month’s MedEvidence is a three-part series on the liver.   In this 12-minute episode Doctors, Michael Koren and Bharat Misra discuss technologies to diagnose dysfunctions of the liver.

You will learn:

  • Technologies in clinical research
  • What a fibroscan is
  • Why your doctor may not be offering you a fibroscan
  • Liver biopsy vs. MRI vs. fibroscan

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.

Dr. Bharat Misra is the Medical Director of ENCORE Borland Groover Clinical Research and has been a Principal Investigator of numerous clinical trials. He also serves on the board of directors at Memorial Hospital and Jacksonville Center for Clinical Research in Jacksonville, Florida. He completed his residency in internal medicine and fellowship in gastroenterology at the Nassau University Medical Center, State University of New York, and his Bachelor of Medicine and Bachelor of Surgery from Gandhi Medical College in India.


Prefer to listen to the podcast without video? You can do that below!





In this episode, Dr. Michael Koren and Michelle McCormick wrap up their discussion on how clinical trials find the truth as well as truth vs. faith and the conclusion of lady tasting tea. Could she actually tell whether the milk or tea was put in first?

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.


Prefer to listen to the podcast without video? You can do that below!





In this episode, Dr. Michael Koren and Michelle McCormick walk through the history of Clinical Trials. From Biblical stories of Daniel through the smallpox pandemic to our present COVID pandemic. How far have we come and where do we go from here?

Some of what you will learn:

  • History of Clinical Research
    • Daniel and King Nebuchadnezzar
    • Newgate Prison
    • Cotton Mather & Onesimus
  • Current Vaccine Trials
    • Chickenpox
    • Shingles
    • Covid
    • Flu
    • RSV
  • Future of COVID

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.


Prefer to listen to the podcast without video? You can do that below!





In this second episode, Dr. Michael Koren, New York Central High School alumni, and Michelle McCormick take us back to high school minus having that awkward conversation about asking your date to prom.  Listen to find out what your high school classes have to do with clinical trials.

Some of what you will learn:

  • What makes a good hypothesis
  • Statistical concepts
  • Statistical methods involved in carrying out a study
  • The vocabulary of clinical research
  • History of clinical research
    • Newgate Prison
    • Daniel and King Nebuchadnezzar
    • Pepsi vs. Coke

Dr. Michael Koren is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.


Prefer to listen to the podcast without video? You can do that below!





In a four-part series on What are Clinical Trials & Why are they important, in this first episode Dr. Michael Koren and Michelle McCormick talk about The Science of Clinical Trials, What makes a good Clinical Trial, good?

What do these things have in common?

  • R.A. Fisher
  • Lady Tasting Tea
  • Truth vs Faith
  • Experiments
  • Clinical Trials

Dr. Michael Koren, is a practicing cardiologist and CEO at ENCORE Research Group. He has been the principal investigator of 2000+ clinical trials while being published in the most prestigious medical journals. Dr. Koren received his medical degree cum laude at Harvard Medical School and completed his residency in internal medicine with a fellowship in cardiology at New York Hospital / Memorial Sloan-Kettering Cancer Center/ Cornell Medical Center.


Prefer to listen to the podcast without video? You can do that below!





In the final episode of Kicking the Nicotine Habit, It’s a Brain Thing. The MedEvidence! doctors roll out the clinical trials on Cytisinicline, an approved therapy in central and Eastern West Europe for the past 20 years.

This month Dr. Michael Koren and Michelle McCormick talk with Dr. Mitchell Rothstein, a clinical Pulmonary and Sleep Medicine physician for 30 years in the Jacksonville, Florida area.  Dr. Rothstein is the Medical Director of the Phase 1 unit at Jacksonville Center for Clinical Research.

Inside this episode:

  • Cytisinicline
  • Alpha4beta2 Nicotine Receptor
  • Clinical Trials to help quit smoking

Prefer to listen to the podcast without video? You can do that below!





Part 3 in a 4 part series on Kicking the Nicotine Habit, It’s a Brain Thing. The MedEvidence doctors continue their discussion on smoking while diving into nicotine replacement therapies.

This month Dr. Michael Koren and Michelle McCormick talk with Dr. Mitchell Rothstein, a clinical Pulmonary and Sleep Medicine physician for 30 years in the Jacksonville, Florida area.  Dr. Rothstein is the Medical Director of the Phase 1 unit at Jacksonville Center for Clinical Research.

Inside this episode:

  • Nicotine Replacement Therapies
  • Quit smoking medications
  • E-cigarettes & Vaping
  • IQOS – heated tobacco products

Prefer to listen to the podcast without video? You can do that below!