Postural Orthostatic Tachycardia Syndrome (POTS) is a form of dysautonomia, a group of conditions caused by dysfunction of the autonomic nervous system (ANS).1
The most prominent initial symptoms for people suffering from POTS include fast heart rate upon standing, lightheadedness, fatigue, insomnia, and possibly fainting. However, POTS can evolve over time, ultimately presenting with as many as 100 symptoms in those affected.
POTS and the Autonomic Nervous System
The Autonomic Nervous System (ANS) is a branch of the nervous system that regulates body functions that should occur automatically, such as blood pressure, heart rate, breathing, digestion, tear production, pupil size, and some hormones.2
The ANS can be subdivided into two branches:
- Sympathetic Nervous System
- Parasympathetic Nervous System
The sympathetic nervous system is mostly responsible for the production of hormones which trigger our “fight or flight” response.
The parasympathetic nervous system, on the other hand, is the “rest and digest” system of the body responsible for the regulation of blood pressure, heart rate, breathing rate, tear production, and every aspect of digestion.
POTS & The Parasympathetic Nervous System
POTS is a symptom of dysfunction in the autonomic nervous system and is associated with debilitating issues that severely limit patients’ quality of life.
Often, a POTS patient’s sympathetic nervous system is in overdrive, and the parasympathetic nervous system is underperforming. Patients may become unable to be vertical without experiencing a rush of adrenaline-like chemicals in their bodies.
Even routine activities around the home can be extremely challenging or impossible for people suffering from POTS. The condition is not uncommon, with the number of Americans affected estimated to be 1 to 3 million prior to COVID.3 The number of patients affected is dramatically increasing due to approximately 10-30% of COVID patients developing POTS.4
Is POTS the Only Form of Dysautonomia?
POTS is one of many illnesses that are considered a form of dysautonomia. At current estimates, there are around 15 dysautonomic syndromes.5
Other forms of dysautonomia include:
- Neurological conditions such as Parkinson’s or ALS (amyotrophic lateral sclerosis)
- Certain cancers such as carcinoid cancer and adrenal gland tumors
- Autoimmune issues such as autoimmune autonomic ganglionopathy
Only when these rare conditions are ruled out should one consider the most common form of dysautonomia—Idiopathic POTS.
Is POTS an “Invisible Illness?”
An invisible illness is a condition with symptoms that are not outwardly visible or whose origins are unknown. Because there are often no obvious physical signs to indicate them, invisible illnesses tend to be misunderstood.
Invisible illnesses are not rare. Approximately 157 million Americans were afflicted with a chronic illness in 2020, and the US Census Bureau estimates 96% of chronic illnesses are invisible.6
Invisible illnesses include everything from well-defined autoimmune conditions, heart disease, and diabetes to ill-defined illnesses, including Chronic Fatigue Syndrome (ME/CSF), Ehlers-Danlos syndrome (EDS), and POTS.
Although evidence of illness is not apparent from the outside, these patients often suffer with significant symptoms and even disability. The lack of ability to see the illness does not make it any less real.
“Patients with POTS usually suffer so much, with little or no validation from their doctors. Even the label of POTS does not provide legitimacy for the illness. We must dramatically change how this condition is treated. This mission, for me, is both professional and deeply personal.”
— Dr. Diana Driscoll
Signs and Symptoms of POTS
If you have ever felt lightheaded or dizzy after quickly standing, you have experienced one symptom of POTS, albeit a mild presentation.
The development of symptoms like dizziness when standing is called “Orthostatic Intolerance.” When severe, patients have difficulty completing even the most basic activities of living, such as getting dressed or cooking, due to orthostatic intolerance. Yet this symptom is rarely the worst symptom POTS patients experience, nor does it occur in isolation. Instead, patients experience clusters of symptoms, which is why POTS is considered to be a “syndrome”.
Patients often experience “brain fog,” for example, which is cognitive dysfunction characterized by difficulty with cognition, short-term memory, and focus.
According to Dysautonomia International, 80-90% of POTS patients have brain fog.7
Additional POTS Symptoms
POTS is a complex syndrome that manifests differently and varies in severity, depending on the patient, the length of illness, and additional health challenges. Some commonalities, however, include some of the following signs and symptoms:
- Extreme fatigue
- Mood disorders
- Sound sensitivity
- Heat or cold intolerance
- Light sensitivity
- Body pain
- Surges of anxiety
- Waves of depression
The sheer number of symptoms with no clear explanation has led many physicians to interpret POTS as a psychological issue — anxiety or hypervigilance, for example. Since the beginning of social media, patients have formed online communities to justifiably rebel against what they believe to be an unfair and misinformed interpretation of their symptoms.
POTS Care® Clinic is the only treatment center rejecting the belief that POTS is due to low blood volume, deconditioning, or psychological conditions. Instead, attention turns to locating and treating the underlying medical causes of the illness. Psychiatric symptoms are seen as secondary issues to the medical condition and treated as such.
“It is a rare patient who can come up with a symptom that I cannot relate to personally! In fact, at some point in my long illness, I had almost 200 symptoms. No one was interested in looking for patterns in my case to help figure out what the underlying problem was. Even more frustrating was that my symptoms were changing almost daily.”
— Dr. Diana Driscoll
How Is POTS Diagnosed?
The simplest, most effective way to diagnose Postural Orthostatic Tachycardia Syndrome (POTS) is the use of a tilt table, with the caveat that the criteria for diagnosis on a tilt-table test are purely arbitrary. Patients can, instead, perform an “at-home tilt table test” to watch for an abnormal heart rate response to standing.
What Is a Tilt Table Test?
In a tilt table test, the patient is asked to lie on their back on a flat table. The physician takes a reading of the patient’s resting heart rate in this horizontal position.
The table is slowly tilted to a vertical position. Patients with POTS will experience tachycardia—a rapid and abnormal increase in heart rate.
A patient is considered to have POTS if their heart rate on the tilt-table:
- Increases by 30 beats per minute; or
- Exceeds 120 beats per minute after being tilted for up to 10 minutes.
With young children, the diagnosis is made when the heart rate increases by 40 beats per minute.
With the “at-home tilt-table test,” the patient’s heart rate response is less dramatic. Rather than diagnosing POTS based on the arbitrary criteria used in a tilt-table test, suspicions of POTS occur in an at-home test when the heart rate increases over 8-10 beats per minute.
What Are The Causes of POTS?
The onset of POTS often follows viral illness and other infections, hinting that POTS is not a psychological illness but could involve the immune system. Traumatic events, surgeries, and pregnancy can also trigger the onset of POTS.8
Every case of POTS is different and complex, making each case analysis difficult. Some potential commonalities in patients include abnormal intracranial pressure, vagus nerve dysfunction, connective tissue disorders, and vascular problems and are discussed in Dr. Driscoll’s newly-revised ebook, The Driscoll Theory.®
“It is critical to understand that a patient’s trigger for POTS is not the cause of their POTS! It is, instead, their body’s abnormal response to the trigger that causes POTS. This abnormality must be identified for resolution of POTS.”
— Dr. Diana Driscoll
Who Is At Risk For POTS?
The number one risk factor for the development of POTS is a combination of family history and a bacterial or viral infection. There are many patients, however, who are not able to recognize a trigger of any kind. Instead, a general feeling of being unwell increases over time until they become significantly ill.
Though there is still much to learn about POTS, we do know that women are more likely to have POTS (80-85% of cases), particularly women between the ages of 15 and 50.9
A family history of orthostatic intolerance can be indicative that a person is more likely to develop POTS. Locating the genetics contributing to this tendency is complex — there is no “POTS gene.” Instead, genetics involving the underlying medical causes of POTS must be explored.
What is Idiopathic POTS?
Confusion over the signs, symptoms, and causes of POTS has left the majority of POTS Syndrome patients without clear answers and appropriate treatment. When no clear cause of an illness is identified, the condition is considered “idiopathic.”
When labeled with Idiopathic Postural Orthostatic Tachycardia Syndrome, patients are treated traditionally in an attempt to mask the symptoms. This traditional treatment of Idiopathic POTS can be damaging to the patient in the long term because it does nothing to address the true medical issues of illness.
Traditional POTS Treatment
In traditional treatment, “symptom management” is axiomatic. Traditional treatment focuses on living with and managing symptoms of POTS because the syndrome is considered incurable according to practitioners approaching POTS in this way.
At POTS Care®, most traditional treatment is discouraged and is often found to worsen the patient’s illness in the long run.
Add Salt to Your Diet
Patients are often told to drastically increase their sodium intake. The typically recommended increase is to about 10,000 mg of salt, compared to the recommended intake of 2,300 or less for healthy adults not suffering from POTS.
Should orthostatic tolerance be due to short-term dehydration, this treatment approach makes sense.10 But for those suffering with a chronic illness, the dangers of high-dose salt outweigh the short-term benefits for the patient and are discouraged by POTS Care®.
Some of the dangers of high-dose salt include kidney disease, heart disease, and vascular disease11, yet most POTS practitioners continue to recommend high salt to their patients.
Increase Fluid Intake
Like salt, an increase in fluid intake can help decrease heart rate if it is high due to dehydration. Becoming dehydrated worsens POTS symptoms. Doctors often recommend those with POTS increase their fluid intake to two liters per day.12 Rarely, if ever, however, is POTS due to chronic dehydration, putting too much emphasis on fluid intake, or worse—putting the blame for the illness on the patient.
Dietary Changes Also Lessen Symptoms
Some POTS patients have seen improvement by eating many small meals over the course of the day instead of a few big ones. This is suspected to be helpful because of blood pooling in the abdomen that can occur when the stomach is full, but other causes are possible. A balanced diet with few restrictions may be helpful in reducing POTS symptoms. Limiting simple carbohydrates and processed foods can also be helpful.
Many patients who develop POTS have a good, balanced diet, and instructions for those suffering should not be reduced to “just improve your diet and you’ll be fine.” POTS is not due to a poor diet, but a poor diet can worsen some symptoms.
Exercise & Activities
Exercise is often difficult for patients with POTS. Doctors recommend activities that allow a patient to stay seated or to lie down to avoid an onset of tachycardia if they are unable to be vertical. One point of exercise is to avoid deconditioning that can worsen POTS.
A few options for mild exercise include:
- Recumbent Biking
Over-exertion is known to exacerbate POTS symptoms, especially with POTS patients who experience Chronic Fatigue Syndrome (ME/CFS). Most traditional POTS practitioners recommend physical reconditioning as a part of recovery, and if the patient has become deconditioned, this is important.13
This does not mean, however, that lack of exercise is the cause of the illness. The recommendation for reconditioning also falsely assumes that POTS patients are deconditioned. Most patients do not develop POTS from deconditioning. Many POTS patients are in great physical health (many are true athletes) when they fall ill. Their illness must not be minimized to mere deconditioning.
Beta-blockers are a class of prescription medication designed to reduce heart rate as well as blood pressure. Doctors prescribe beta-blockers to manage tachycardia in POTS patients. Studies indicate that beta-blockers can help to manage symptoms in children with POTS.14
But slowing heart rate is merely covering up one symptom of POTS, and beta-blockers often contribute to side-effects such as depression, fatigue, and the inability to exercise. One reason traditional treatment includes beta-blockers is that a fast heart rate is often the only objective finding doctors locate.
Leading Organizations in Traditional Treatment of POTS
Although POTS is not well understood and much research is being done, some organizations are working to better understand this condition.
Dysautonomia International is a volunteer-run non-profit organization that raises awareness of POTS (along with other conditions that fall under the umbrella of dysautonomia) and advocates on behalf of its patients.
The Dysautonomia Project is another organization that provides patients with resources and helps them find medical care.
Genetic Disease Investigators, LLC has been exploring the genes that can make patients susceptible to POTS.
Because POTS is a complex illness, other organizations not directly devoted to dysautonomia study POTS, such as the International Society of Neurovascular Disease.
What is the POTS Care® Clinic?
POTS Care® Clinic does not treat POTS traditionally.
Instead, POTS Care® is the only clinic dedicated to addressing the underlying medical causes of POTS, not just the symptoms.
- There is no “one size fits all” treatment for POTS
- Each case of POTS is unique to the patient
- POTS Care® Clinic’s treatment focuses on an individual’s systemic cause of POTS
Following the research of Dr. Diana Driscoll, a former POTS patient, patient evaluation and treatment is a total departure from traditional POTS treatment—coined “The Driscoll Approach™.” So, how does it all work? Here’s a summary of the treatment approach for patients with POTS.
The Driscoll Approach™
The Driscoll Approach™ does not include traditional treatment for POTS. No salt or beta-blockers are used at POTS Care® Clinic.
Instead, the first step is to understand the patient’s medical cause of POTS through a detailed medical history and unique testing.
The second step is to apply understanding of the patient’s medical history to create an intelligent combination of medications, supplements, diet, exercise, mental management, and education. This approach treats the underlying medical causes of the illness and allows the patient to take charge of their health once again.
Review of Medical History
Intelligent treatment starts with a review of the patient’s medical history.
POTS can co-present or be confused with other medical conditions. That’s why POTS Care® cross-references the patient’s medical history with a list of over 200 potential signs and symptoms.
- MRI Review – A review of brain MRIs looks beyond the radiology report for more subtle clues to illness. The doctors review past brain MRIs and prescribe MRIs if necessary.
- Blood Work – Collect data from past blood work and order new blood work, customized for the patient’s presentation and history.
- Autonomic Testing – Autonomic testing consists of a series of short, non-invasive procedures that evaluate whether a patient’s autonomic nervous system functions normally or shows signs of dysfunction.
- Tilt Table Test or an At-Home Tilt Table Test – This autonomic test evaluates blood pressure and oxygen saturation when a patient is placed in a vertical position. Clues to the cause of POTS can be found based on whether the blood pressure goes up or down when vertical, for example.
- Heart Rate Variability Tests – A test evaluating the variability in heartbeats from beat to beat. When low, it is a sign of poor autonomic balance.
- Ocular Testing & Exams – Ocular tests provide an unparalleled window to clues of the underlying causes of POTS.
- Unique Physical Exam – Patients have usually had extensive testing with their physicians, including cardiac testing. When evaluating patients, POTS Care® looks for clues to the underlying causes of POTS by closely examining signs of connective tissue abnormalities, vascular problems, and additional systemic disorders that can be easy for others to miss.
Exercise, Diet, and Sleep
Depending on the underlying problems causing POTS, recommendations can be made concerning diet, exercise, and sleep. The key is to provide recommendations that fit the patient and that address the medical problems causing POTS.
Biofeedback & Mental Management
For many POTS patients, dramatic surges of adrenaline and other chemicals lead to intense feelings of anxiety. These surges also increase the intensity of POTS and worsen the condition and patient’s quality of life.
POTS Care® treats these surges by treating the medical cause first, then addressing the mental management that can be used to help control them until recovery has occurred. To the uninformed, these surges can look like a panic attack when, in actuality, they are a sign of something else that must be identified for resolution.
A Complete POTS Treatment Plan
Effective POTS treatment requires time. Most patients have struggled for a long time, and all dominoes that have fallen as a result of the illness need to be identified.
As part of a comprehensive two-month treatment program, patients are given an individualized roadmap to recovery that may include prescription medications. No medications are prescribed, however, to try to mask symptoms. Everything recommended is to address specific underlying medical issues that can allow the body to recover.
“Traditional treatment for many invisible illnesses focuses on managing symptoms, but this has nothing to do with treating the underlying medical problems causing the illnesses. We must dig deeper. The future of these patients’ lives depends on it.”
— Dr. Diana Driscoll
What is Inflammatory POTS?
Approximately 80% of the patients seen at POTS Care® have some form (or more than one form) of chronic inflammation as a cause or contributor to POTS. It is critical to locate these inflammatory conditions and treat these appropriately for optimal patient recovery.
Dr. Diana Driscoll, Clinical Director, coined the term “Inflammatory POTS” to describe this presentation.
Inflammatory Conditions Related to POTS
Many inflammatory conditions can contribute to POTS including, but not limited to the following:
- Autoimmune conditions
- Adrenal gland disorders
- Addison’s disease
- Nonclassical Congenital Adrenal Hyperplasia
- Mast cell disorders
- Eosinophil disorders
- Genetic disorders of inflammation
- Autoinflammatory conditions
These conditions must be identified and managed for the proper resolution of POTS.
Learn more about Inflammatory POTS.
The Vagus Nerve & POTS: Is There A Connection?
Inflammation is controlled by the vagus nerve in a normal, healthy patient. When this nerve is not functioning well, management of inflammation is difficult. The vagus nerve is one of twelve cranial nerves in the body, linking the brain to areas like the neck and torso. It’s also the longest cranial nerve, running from the brainstem to the colon. Patients with POTS may experience vagus nerve dysfunction, and this needs to be identified and properly treated.
Symptoms of Vagus Nerve Dysfunction
The following list is a collection of signs and symptoms associated with vagus nerve dysfunction:
- Chronic constipation
- IBS (irritable bowel syndrome)
- Delayed gastric emptying
- Low pancreatic enzymes
- Difficulty breathing
- Abnormal heart rate
- Dry eye
- Orthostatic Hypotension
- Fast Heart Rate (Tachycardia)
- “Brain Fog” and Poor Short-Term Memory
- Fatigue, Especially Fatigue That Worsens With Exertion
- Emotional Instability
- Chronic Inflammation
What is Idiopathic Intracranial Hypertension (IIH)?
First released in The Driscoll Theory®, many (but not all) patients with POTS have a propensity for abnormal intracranial pressure. Intracranial pressure refers to the fluid pressure around the brain, spinal cord, and optic nerve. The brain is suspended in cerebrospinal fluid (CSF). Our bodies drain and produce fluid to maintain a consistent level of pressure.
Sometimes the pressure becomes too high, causing a range of symptoms to occur, including increased heart rate, anxiety, and feeling overheated. These often occur at night, in bed, when the patient is lying down. If not treated correctly, the patient is at risk of developing a secondary spinal leak, which can be disabling in and of itself.
Is IIH a Headache or Migraine?
Some IIH patients are misdiagnosed with chronic migraines. Because both migraine headaches and headaches due to high intracranial pressure (IIH) can both occur with nausea, the diagnosis can be missed.
Headaches due to IIH can also be misdiagnosed as craniocervical instability, tension headaches, and cervicogenic headaches. Complicating the presentation, some patients have multiple reasons for headaches, and each one must be identified for resolution. Interestingly, IIH can occur in the absence of headaches, making this condition a confusing one for many practitioners.
IIH can occur in conditions unrelated to POTS yet can contribute to significant symptoms.
Learn more about IIH and high intracranial pressure.
Long COVID & POTS
COVID-19 is an ongoing global tragedy that will affect public health for at least the next half-century, if not longer.
Between 10-30% of post-COVID patients develop POTS4, much like the development of POTS from other viral triggers. POTS is often triggered by extreme stress or illness, including some bacterial infections and respiratory viruses. If the infection has passed and symptoms persist with the development of new symptoms, POTS should be suspected.
“Long COVID” patients may begin to experience a fast heart rate upon standing, brain fog, fatigue, dizziness, headaches, and sweats, among other symptoms when POTS begins.15
Post-COVID POTS is present, real, and legitimate, just like other virally-triggered POTS16—yet misdiagnosis and misunderstanding continue.
POTS Care® has been treating post-viral POTS for more than six years and has significant experience treating post-COVID POTS. Patients who are experiencing new symptoms weeks or months after contracting the virus should be evaluated for POTS.
I Think I Have POTS. What Comes Next?
Your physician and/or cardiologist can check your heart rate and heart structure to look for Idiopathic POTS. When your heart is structurally unaffected, yet your heart rate jumps up when you are vertical, POTS should be suspected.
- Bring HR Data To Your Physician: If your insurance requires a referral from a primary care physician, use your heart rate data to make a case for a referral.
- Enlist Help & Gather Medical Records: Patients with POTS/dysautonomia are often misdiagnosed as suffering from anxiety, hypervigilance, or other psychological conditions. Ask a spouse, relative, or friend to advocate for you.
- Call a Dedicated Clinic: It’s crucial to find a private practice, clinic, or organization familiar with POTS and the immediate needs of patients like you.
Is There A Cure For POTS?
POTS is not a disease. Diseases can be cured or treated. POTS is a presentation — a sign of something else. When this “something else” is identified and treated, POTS can go away.
“Drink water, eat salt, rely on pain medication and antidepressants—we now know that these treatments can damage the patient and should not be relied upon for POTS treatment. We must work harder for these patients.”
— Dr. Diana Driscoll
What is POTS Care® Clinic?
POTS Care® is the only clinic dedicated to addressing the underlying medical causes of POTS, not just the symptoms. POTS Care® offers a dramatic departure from traditional POTS treatment in numerous ways.
Unique Treatment Plans
POTS Care® provides individualized care that moves beyond symptom management. There is no “one size fits all” approach. Each patient is unique and requires a unique treatment plan.
Proven Science, Compassionate Care
Dr. Diana Driscoll, the founder of POTS Care®, suffered from POTS for over a decade and understands POTS and invisible illnesses on both a rigorously scientific and deeply personal level. Compassion and empathy are central to the treatment processes at POTS Care®.
Have Questions? Contact POTS Care®.
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2. Low P. Overview of the Autonomic Nervous System – Brain, Spinal Cord, and Nerve Disorders. Merck Manuals Consumer Version. https://www.merckmanuals.com/home/brain,-spinal-cord,-and-nerve-disorders/autonomic-nervous-system-disorders/overview-of-the-autonomic-nervous-system.
3. Postural Orthostatic Tachycardia Syndrome (POTS). Johns Hopkins Medicine. https://www.hopkinsmedicine.org/health/conditions-and-diseases/postural-orthostatic-tachycardia-syndrome-pots.
4. Parums DV. Editorial: Long COVID, or Post-COVID Syndrome, and the Global Impact on Health Care. Med Sci Monit. 2021 Jun 7;27:e933446. doi: 10.12659/MSM.933446. PMID: 34092779; PMCID: PMC8194290. https://pubmed.ncbi.nlm.nih.gov/34092779/
5. Dysautonomia: Symptoms, Causes, Types, & How to Live With. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/6004-dysautonomia.
6. Driscoll D. Invisible Illnesses: Underlying Medical Problems. Disabled World. https://www.disabled-world.com/disability/types/invisible/dr-diana-driscoll.php. Published February 23, 2021.
7. Arnold A. The Dysautonomia Dispatch. https://www.dysautonomiainternational.org/blog/wordpress/cognitive-dysfunction-and-brain-fog-in-pots/. Published February 3, 2016.
8. Postural orthostatic tachycardia syndrome. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/9597/postural-orthostatic-tachycardia-syndrome.
9. Raj SR, Levine BD. Postural Tachycardia Syndrome (POTS) Diagnosis and Treatment: Basics and New Developments. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2016/01/25/14/01/postural-tachycardia-syndrome-pots-diagnosis-and-treatment-basics-and-new-developments. Published February 7, 2013.
10. Garland EM, Gamboa A, Nwazue VC, et al. Effect of High Dietary Sodium Intake in Patients With Postural Tachycardia Syndrome. Journal of the American College of Cardiology. https://pubmed.ncbi.nlm.nih.gov/33926653/.
11. Farquhar WB, Edwards DG, Jurkovitz CT, Weintraub WS. Dietary sodium and health: more than just blood pressure. J Am Coll Cardiol. 2015 Mar 17;65(10):1042-50. doi: 10.1016/j.jacc.2014.12.039. PMID: 25766952; PMCID: PMC5098396. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098396/
12. Nicholson L. Diet and Fluids. POTS UK. https://www.potsuk.org/diet_and_fluids. Published August 22, 2020.
13. Fu Q, Levine BD. Exercise and non-pharmacological treatment of POTS. Autonomic neuroscience: basic & clinical. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289756/. Published December 2018.
14. Deng X, Zhang Y, Liao Y, Du J. Efficacy of β-Blockers on Postural Tachycardia Syndrome in Children and Adolescents: A Systematic Review and Meta-Analysis. Frontiers in pediatrics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854016/. Published November 7, 2019.
15. Post-COVID Conditions. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects.html
16. Blitshteyn S, Whitelaw S. Postural orthostatic tachycardia syndrome (POTS) and other autonomic disorders after COVID-19 infection: a case series of 20 patients. Immunol Res. 2021 Apr;69(2):205-211. doi: 10.1007/s12026-021-09185-5. Epub 2021 Mar 30. Erratum in: Immunol Res. 2021 Apr 13;: PMID: 33786700; PMCID: PMC8009458. https://pubmed.ncbi.nlm.nih.gov/33786700/