Browsing Tag

rheumatoid arthritis

Diseases and Conditions Self-Injection Videos

How to inject Actemra and Kevzara

October 24, 2017
How to inject Actemra and Kevzara

In this week’s edition of RheumDoctor, Dr. Farrell will teach how to inject Actemra and Kevzara in the comfort of your home.  Both of these medications work by blocking interleukin-6, a cytokine involved in inflammation.  Kevzara, also known as sarilumab, recently obtained FDA approval for the treatment of rheumatoid arthritis. Actemra, also known as tocilizumab, is also prescribed for rheumatoid arthritis but also recently obtained FDA approval for the treatment of giant cell arteritis.  Without further adieu…

Preparing for your injection

  • Keep your medication stored in the refrigerator until use
    • Before injecting medication, take the prefilled syringe out of the refrigerator.
    • Allow it to warm up to room temperature.
  • Pick a place in your house that is clean and has room for your materials (such as the kitchen table).
  • Wash your hands thoroughly with either:
    • Soap & water
    • Hand sanitizer
  • Chose an area to inject – Thigh or Stomach.
    • Chose an area that is intact and clear.
    • It should not have any of the following:
      • Cuts
      • Scrapes
      • Bruises
      • Psoriasis patches
      • If you have extensive psoriasis, inject between patches
      • Moles
      • Scars
    • Please rotate area each time you inject (shown in picture below).

Areas to inject subcutaneous medication

  • Cleanse chosen area
    • Cleanse chosen area with either of the following:
      • Alcohol swab
      • Alcohol and a cotton ball
    • Use the chosen alcohol material to “swipe” area
      • Can either use a circular motion or wipe in “strips”
      • Allow the area to dry

Injecting Actemra or Kevzara with a prefilled syringe

  • Pull off the cap and observe the syringe.
  • Pinch the skin around the injection site and enter at a 45-degree angle
  • Press the plunger (slowly) to administer the medication
  • Once the medication is fully administered, the plunger will reach the bottom and a spring will place a cover over the needle

After the injection

  • Properly dispose of the entire prefilled syringe
    • Sharps Container
      • Can be purchased at your local pharmacy
      • Disposal
        • Hospitals may take full sharps containers, ask first.
        • Pharmacies and Doctors’ offices are not allowed to take used syringes or needles
  • Discard remaining materials in the trash (cap, alcohol swabs, etc.)

For more information about Actemra.

For more information about Kevzara.

Credits

Jessica Farrell, PharmD.  Clinical Pharmacist, The Center for Rheumatology/Associate Professor, Albany College of Pharmacy and Health Sciences

With the help of Autumn Koniowka. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences, and Megan Phillips. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences.

A special thanks to Tammy Garren, PhD. Instructional Designer, Center for Innovative Learning, Albany College of Pharmacy and Health Sciences.

Injection site image: By British Columbia Institute of Technology (BCIT). Download this book for free at http://open.bccampus.ca [CC BY 4.0 (http://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

Diseases and Conditions When to see a rheumatologist

What is a positive rheumatoid factor?

October 17, 2017
What is a positive rheumatoid factor?

Introduction

What does it mean to have a positive rheumatoid factor (RF)?  Does this mean that you have rheumatoid arthritis, are you at risk of developing rheumatoid arthritis, is your prognosis worse, or is it completely unrelated to arthritis?

Before answering, what is a positive rheumatoid factor, we need to understand antibodies and how they are made.  We can then better understand autoantibodies, and more specifically rheumatoid factor.

What is an antibody?

The goal of the immune system is to protect yourself from bacteria, viruses, as well as cancers.  The immune system is made up of many different components, however, in broad terms it can be divided into three categories: physical barriers, the innate immune system, as well as the adaptive immune system.  Physical barriers include skin as well as mucous membrane barriers that line your digestive, respiratory, and your reproductive tracts.  The innate immune system is the second line of defense.  This is the part of the immune system that deals with immediate dangers.  For example, the skin reaction you get when you get bitten by a dog or you when you accidently cut your hand with a knife.  The third level of defense is called the adaptive immune system.  This is the part of the immune system responsible for making antibodies.

Antibodies, also called immunoglobulin (Ig), are specialized proteins that defend against specific invaders.  An antigen stimulates your body to make an antibody.  For example, if someone gets the chickenpox (antigen) the body will make antibodies directed against the chickenpox virus.  So the next time that person is exposed to the chickenpox virus, the body will have chickenpox antibodies to prevent the infection.

Antibody structure

Immunoglobulin are made up of light and heavy chains.  They also have two regions, Fab regions and the Fc region.  The Fab region is also called the variable region.  This is the place where specific antigens attach to the antibody.  It is variable, because each antigen has its own antibody.  The Fc region helps the antibody communicate with other parts of the immune system.  The Fc region is also called the constant region.  It’s constant because it doesn’t really vary all that much.[1]

Immunoglobulin structure

 

Are there different types of antibodies?

Yes.  There are 5 different classes of antibodies: IgG (75%), IgA, IgD, IgE, and IgM. Remember how I said the Fc region “doesn’t vary all that much”? The Fc region determines the class of the antibody and in turn, which immune system cells the antibody will interact with.  For example, dust mite particles cause the immune system to make IgE antibodies.  When the body is exposed to dust mites for a second time, IgE antibodies interact with mast cells, which release histamine, which cause an allergic reaction.[2]

Every class of immunoglobulin looks different and as I mentioned interacts with different parts of the immune system. IgM antibodies are made very early on during an infection.  IgG antibodies are made about 2-3 weeks after an infection and you typically find them in blood.  IgA antibodies are made in the gut, nose, lungs, and mammary glands.  IgE antibodies are made to parasites and they trigger allergies.  Currently, we don’t know too much about IgD.

What is a rheumatoid factor?

A rheumatoid factor is created when an IgM antibody binds to the Fc portion of an IgG antibody.  In simple terms, this is a situation where an antibody attacks another antibody.  When you have many antibodies doing this at once, they can form large IgM-IgG antibody complexes, which can stimulate the immune system to make some serious inflammation.

My doctor told me my rheumatoid factor was high.  What does that mean?

The answer to this question is varies depending which lab your doctor sent your blood.  Each lab has their own specific cut off points.  Below you will find the cutoff points for Labcorp and Quest Diagnostics.

Labcorp

Methodology: Latex immunoturbidmetry

Negative: < 14.0 IU/mL

Quest Diagnostics

Methodology: Immunoturbidimetric

Negative: ≤ 14 IU/mL

Note: There are many different ways to measure rheumatoid factor and even specific types of rheumatoid factor: IgM, IgG, IgA.  These will all have their own cutoff points.

Now, what does having a positive rheumatoid factor mean?  The answer to this question depends on your symptoms.

Rheumatoid factor and rheumatoid arthritis

About 70% to 80% of people that have rheumatoid arthritis have a positive rheumatoid factor.  Not having a positive rheumatoid factor doesn’t necessarily rule out the disease, but rather, it makes it less likely.  Having rheumatoid arthritis AND having a positive rheumatoid factor is associated with a more severe form of the disease and having non-joint symptoms like nodules or lung involvement (interstitial lung disease).  Unlike lupus, rheumatoid factor doesn’t really go up or down depending how active rheumatoid arthritis, so we don’t follow it if you have an established diagnosis.[3]

What are some other diseases that cause a positive rheumatoid factor?

Rheumatoid factor has an 86% specificity for rheumatoid arthritis.  That being said, if you test positive for rheumatoid factor, there’s a pretty good chance that you have or will have rheumatoid arthritis in the future, but this is by no means set in stone. It’s very important to realize that someone can test positive for rheumatoid factor, AND NOT have rheumatoid arthritis because many diseases can cause the immune system to form antibodies directed towards the Fc portion of an IgG antibody.  However, in most non-autoimmune conditions the rheumatoid factor tends to be lower than in rheumatoid arthritis.  Moreover, when one finds more than one different type of rheumatoid factor particular in the fluid of a joint (e.g., IgM RF and IgA RF), this indicates that we are dealing with rheumatoid arthritis.

Category Disease
Rheumatic diseases
  • Rheumatoid arthritis
  • Systemic lupus erythematosus (SLE)
  • Scleroderma
  • Mixed connective tissue disease
  • Sjogren’s syndrome
Viral infections
  • HIV/AIDS
  • Mononucleosis (Epstein-Barr virus)
  • Hepatitis
  • Influenza
Parasitic infections
  • Malaria
  • Schistosomiasis
  • Trypanosomiasis
  • Kala-azar
  • Filariasisis
Chronic bacterial infections
  • Subacute bacterial endocarditis
  • Tuberculosis
  • Syphilis
  • Salmonellosis
  • Brucellosis
  • Leprosy
  • Yaws
Cancers
  • Lymphoma
  • Leukemia
  • Multiple myeloma
Hyperglobulinemic diseases
  • Sarcoidosis
  • Chronic liver disease
  • Chronic pulmonary disease
  • Cryoglobulinemia
  • Hypergammaglobulinemic purpura[4]

 

It is also important to mention that approximately 5 – 25% of individuals aged 60 years and older have a positive rheumatoid factor without any underlying causative disease.

I have a positive rheumatoid factor, but I have no symptoms

This is where it gets a little tricky.  Here are the following possible scenarios:

  1. You may develop rheumatoid arthritis in the future.
  2. It may be that you actually have another non-rheumatic disease that is causing you to test positive for rheumatoid factor.
  3. The rheumatoid factor is not clinically significant.

When faced with a positive rheumatoid factor, it’s important to rule out other conditions that cause positivity.  If the workup is negative, care monitoring is recommended.  Knowing the symptoms of autoimmune joint disease is of utmost importance as well.

Can you predict who will develop rheumatoid arthritis?

We cannot predict with 100% certainty, who will and who won’t develop rheumatoid arthritis.  There are a few factors that increase the odds like having both a rheumatoid factor AND anti-citrullinated peptide antibodies (anti-CCP)[5].  This is particularly true for people that have high levels of anti-CCP antibodies.[6]

The time between the formation of autoantibodies and rheumatoid arthritis is called preclinical rheumatoid arthritis.  Other terms include: pre-RA, autoantibody-positive arthralgia, probable RA, very early RA, and early undifferentiated arthritis progressing to RA.

Phases of preclinical rheumatoid arthritis

Preclinical RA goes through many phases.  Not everyone progresses so smoothly and some people can even skip steps.

Phase I

People with certain genetic predispositions are exposed to environmental factors that trigger an immune response.  Smoking is a known trigger.

Phase II

The immune system starts making rheumatoid factor and/or anti-CCP antibodies.

Phase III

People start experiencing some joint pain and stiffness, but no swelling or over autoimmune joint pain.

Phase IV

There is some joint swelling, but it’s limited to 1-2 joints.  We can now call this undifferentiated arthritis but it’s not rheumatoid arthritis yet.  If it happens on and off, we sometimes call it palindromic rheumatism.  We think that 30 – 50% of people with undifferentiated arthritis will go into remission, 30-40% will progress to other diseases, and 30 – 40% will evolve into rheumatoid arthritis.

Phase V

It’s spreading!  Now we can call this rheumatoid arthritis.[7]

Is there anything I can do to prevent rheumatoid arthritis?

The following are some modifiable risk factors that can help prevent rheumatoid arthritis.

  • Avoid/quit smoking
  • Maintain good dental hygiene
  • Eat a balanced diet containing fish oil, antioxidants, and vitamin D
  • Avoid excess coffee and foods with high salt content
  • Keep a healthy body weight
  • Prevent infections[8]

Conclusion

If you’ve tested positive for rheumatoid factor and have more questions, I highly urge you to speak with your physician or local rheumatologist.  And remember, doctors treat people not numbers.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

References

[1] L Sompayrac. How the Immune System Works 4th edition

[2] L Sompayrac. How the Immune System Works 4th edition

[3] Rheumatology Secrets 3rd edition

[4] Adapted from Kelley’s Textbook of Rheumatology, 8th edition

[5] Sun J, Zhang Y, Liu L, Liu G. Diagnostic accuracy of combined tests of anti cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis: a meta-analysis. Clin Exp Rheumatol. 2014 Jan-Feb;32(1):11-21.

[6] Heidari B, Firouzjahi A, Heidari P, Hajian K. The prevalence and diagnostic performance of anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: the predictive and discriminative ability of serum antibody level in recognizing rheumatoid arthritis. Ann Saudi Med. 2009 Nov-Dec;29(6):467-70.

[7] Paul BJ, Kandy HI, Krishnan V. Pre-rheumatoid arthritis and its prevention. Eur J Rheumatol. 2017 Jun; 4(2): 161–165.

[8] Paul BJ, Kandy HI, Krishnan V. Pre-rheumatoid arthritis and its prevention. Eur J Rheumatol. 2017 Jun; 4(2): 161–165.

Immunoglobulin image By Fvasconcellos 19:03, 6 May 2007 (UTC) [Public domain], via Wikimedia Commons

Self-Injection Videos

How to inject methotrexate

September 12, 2017
How to inject methotrexate

Methotrexate is commonly prescribed to treat rheumatoid arthritis, psoriatic arthritis, psoriasis, as well as many other autoimmune diseases. It comes as a pill but in certain situations the medication may be more effective if it’s injected.  That being said, injectable methotrexate comes as a auto-injector pen but due to cost, often times we need to rely on the good old-fashioned method: needle, syringe, and a vial of methotrexate.  First, Dr. Farrell is going to teach us how to inject a vial of methotrexate.  In the second video, she will teach us how to inject with an auto-injector pen.

Preparing for your injection

  • Keep your medication stored in the refrigerator until use
    • Before injecting medication, take the vial out of the refrigerator.
    • Allow it to warm up to room temperature.
  • Pick a place in your house that is clean and has room for your materials (such as the kitchen table).
  • Wash your hands thoroughly with either:
    • Soap & water
    • Hand sanitizer
  • Chose an area to inject – Thigh or Stomach.
    • Chose an area that is intact and clear.
    • It should not have any of the following:
      • Cuts
      • Scrapes
      • Bruises
      • Psoriasis patches
      • If you have extensive psoriasis, inject between patches
      • Moles
      • Scars
    • Please rotate area each time you inject (shown in picture below).

Areas to inject subcutaneous medication

  • Cleanse chosen area
    • Cleanse chosen area with either of the following:
      • Alcohol swab
      • Alcohol and a cotton ball
    • Use the chosen alcohol material to “swipe” area
      • Can either use a circular motion or wipe in “strips”
      • Allow the area to dry

Injecting a methotrexate vial

Drawing the medication

  • If it is your first time using the vial, you will have to remove the plastic cap from the vial
  • Clean the top of the vial with an alcohol swab
  • Open syringe packaging and take syringe out
    • Be careful while doing this – the needle may come apart, so make sure the needle is securely on the syringe before moving on
  • Double check the dosage on your prescription.  Does your doctor want you to inject 0.5 mL? 0.6 mL?
  • Pull plunger to get air into the syringe
    • The amount of air should be half the amount of the dose that you are going to draw up (Example: if you need a dose that is 1 mL of methotrexate, draw up 0.5 mL of air)
  • Press the needle into the vial
    • Should be right into the center of the top of the vial at a 90-degree angle
  • Push the plunger to transfer the air into the vial
  • Flip the vial upside down with the needle still in
  • Pull back on the plunger to draw liquid into the syringe
    • If an air bubble appears into the syringe, push the plunger back up and try pulling out again
    • This may take a few tries before you get only medication into the syringe
  • Once you have withdrawn the dose of the medication that you need, flip the vial and take the needle out

Injecting the medicine

  • Pinch cleansed skin
  • Insert needle into the chosen area at a 45-degree angle
    • You may keep the skin pinched or let go of the skin
  • Push the plunger slowly to inject the medication
  • Once you have injected all of the medication, take the needle out of your skin

After the injection

  • Properly dispose of the entire syringe
    • NEVER recap the needle
    • Sharps Container
      • Can be purchased at your local pharmacy
      • Disposal
        • Hospitals may take full sharps containers, ask first.
        • Pharmacies and Doctors’ offices are not allowed to take used syringes or needles
  • Discard remaining materials in the trash (cap, alcohol swabs, etc.)

Injecting methotrexate with an auto-injector pen

Injecting Otrexup®

  • There will be a number “1” labeled on the auto-injector
    • Twist cap off
  • There will be a number “2” labeled on the auto-injector
    • Press with thumb to flip cap off
  • Place tip of the auto-injector on the skin at a 90-degree angle
  • Press button to release medication
    • Hold for 10 seconds
    • May feel a slight pinch and tingling as the medication goes in

Injecting Rasuvo®

  • There will be a yellow cap at the end that you will pull straight off
  • Place tip of the auto-injector on the skin at a 90-degree angle
  • Press button to release medication
    • Hold for 10 seconds
    • May feel a slight pinch and tingling as the medication goes in

After the injection

  • Properly dispose of the auto-injector.
    • Sharps Container
      • May be provided by the drug company (depending on the medication)
      • Can be purchased at your local pharmacy
      • You may use a coffee can if you are unable to attain a sharps container
      • Disposal
        • Hospitals may take sharps
        • Pharmacies and Doctors’ offices are not allowed to take used syringes or needles
  • Discard remaining materials in the trash (cap, alcohol swabs, etc.)

Credits

Jessica Farrell, PharmD.  Clinical Pharmacist, The Center for Rheumatology/Associate Professor, Albany College of Pharmacy and Health Sciences

With the help of Autumn Koniowka. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences, and Megan Phillips. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences.

A special thanks to Tammy Garren, PhD. Instructional Designer, Center for Innovative Learning, Albany College of Pharmacy and Health Sciences.

Methotrexate vial image: By Li Wa/Shutterstock

Injection site image: By British Columbia Institute of Technology (BCIT). Download this book for free at http://open.bccampus.ca [CC BY 4.0 (http://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

Diseases and Conditions Patient Advocacy

Guide to living with rheumatoid arthritis: part 3

August 30, 2017
the prior authorization process: how medication get covered by your insurance company

If you’re reading this post, there’s a good chance you’ve just been diagnosed with rheumatoid arthritis (RA).  In Part 1 of the Guide to Living with Rheumatoid Arthritis, we went over the symptoms, diagnosis, and treatment of rheumatoid arthritis.  In Part 2 of the Guide to Living with Rheumatoid Arthritis, we went over expectations, how to break the news to your loved ones and your boss, as well as important topics like food, exercise, and lifestyle.

Now that you’re acquainted with RA, you may have realized that some of these medications are very expensive.  In Part 3 of Guide to Living with Rheumatoid Arthritis I’ll be covering the way doctors prescribe medications, how health insurance pays for the cost of medications, and finally how they end up in your possession.

The Process

As we’ve discussed previously, to treat rheumatoid arthritis you need to fight fire with fire.  In the case of RA, fire = a disease modifying anti-rheumatic drug or DMARD.  This is a medication that puts the immune system back in-check and calms it down.

They’re are two kinds of DMARDs: conventional DMARDs and biologics.  Conventional DMARDs like methotrexate are less complex and do not target a particular cytokine (type of inflammation).  They tend to cost less and typically don’t need pre-approval from your insurance company. Fortunately, methotrexate is the gold standard for the treatment of rheumatoid arthritis.

Biologics are the second type of DMARDs. These medications are a lot more complex and they do target a specific cytokine.  Biologics are typically used if there’s a good reason you can’t take a conventional DMARD or if they haven’t worked in the past.  Sometimes a rheumatologist may use a biologic and a conventional DMARD at the same time because they work better together.  Biologics come as self-injectable pens, prefilled syringes, and infusions (i.e., via an IV going into your veins).

Unlike conventional DMARDs, biologics are VERY expensive and do need pre-approval or prior authorization from your insurance company before starting the medication.  This means your doctor needs to justify this medication to the insurance company.

Prior Authorization

You may have heard your doctor say, “I’m going to need to get a prior authorization”.  A prior authorization is the process by which your doctor and his or her team will justify the use of the medication to your insurance company.  It typically involves A LOT of paperwork and phone calls.  Sometimes the process takes weeks to days, but sometimes it can take months.  If this is your first biologic, it typically takes 2 – 3 weeks from the moment your doctor prescribes the medication to the moment you receive it.  But again, every situation is different.  This is just an average.

First, every single medical office does prior authorizations slightly differently.  Let’s go through an example.

Getting started

  • Your doctor talks to you about the risks and benefits of a certain medication. If you consent to treatment, he or she will ask his assistant to start a prior authorization.
  • The assistant then gathers all your medical insurance information and starts filling out forms. There’s a different form for every medication and for every different insurance company.  The assistant then sends your doctor’s last progress note stating why you should receive this medication.  The package is then sent to your health insurance plan.
  • At this point, your health insurance plan will go over your case and decide whether they will approve the medication. The medical reviewers follow a strict set of guidelines set forth by the insurance plan.
  • Let’s say they don’t approve the medication. In some cases, your doctor could appeal their decision by speaking to a medical director at the insurance company.  At times, they want more information or a written letter with supporting scientific papers.  Sometimes this works and sometimes it doesn’t.  If it does great!  If it doesn’t your doctor may try to look into patient assistance programs if one is available or they may alter your treatment plan.

You’re approved!

Now let’s say the medication gets approved! The insurance company will contact your doctor’s office and let them know.  Because these medications are so expensive, your local pharmacy will not carry them.  They may need to go to a specialty pharmacy who will mail them to your house.

  • The assistant will alert your doctor and he/she will send the prescription to your pharmacy.
  • The specialty pharmacy then prepares the script and sets a delivery date with you.
  • The medication is then mailed to your house.
  • The process is a little different when it comes to infusible biologics. In this case, the medication will NOT be mailed to your house.  Instead, once your doctor’s office obtains the prior authorization, the infusion team at your doctor’s office will call to set up an appointment.  Sometimes, you may need to go to an infusion clinic or a hospital for treatment.

Now you see why prior authorizations take a long time!

Biologic medications

There are many types of biologic medications that work in all sorts of different ways, however, they are given in either of these forms:

  1. Infusions
  2. Self-injectables
  3. Pills

If prescribed an infusion you will get the medicine at your doctor’s office, an infusion center, or a hospital.  Treatment can range between 1-5 hours.  The doctor’s office will give you the medication and bill your insurance.

If you’re prescribed a medication that is self-injected, the medication will be mailed directly to you.  This may seem very daunting, however, many clinics have a team in place to help you through this process.  In my clinic, we have a dedicated team that will help you inject the medication for the first time in a supervised setting.  During that visit you can ask questions that you may have about the medication: how to store it, how to dispose of the syringes and/or pens, what to do when traveling with biologics, side effect, etc.

If you’re prescribed an oral biologic medication, then the medication will be mailed directly to your house and you would take it just like you would take any other pill, i.e., follow your doctor’s written instructions.

What if your insurance company does not want to cover the full cost of your medication or if you have a high deductible plan?

You should rest assured that there are several financial assistance options available if your insurance will not cover the full cost of the medication or if you have a high deductible plan.  Mind you, this does not guarantee that you will qualify but you won’t know unless you try.

For Commercial Insurance Plans (Group, Individual, Exchange) not Medicare

Some commercial insurance companies let their customers use a copay assistance card issued by the pharmaceutical company to help with the cost of the drug.  Call me old-fashioned, but in my experience, talking to an actual human being is much faster and effective than email or using a contact form.  For more information call the appropriate phone number listed below. If your plan allows the use of a copay card, the drug can often be obtained at a much smaller charge.

For Medicare Plans

The same medication options and medication administration options are available if you have Medicare or a Medicare Supplemental Plan, except you CANNOT use a copay assistance card.

Depending on the type of Medicare/supplemental plan that you have, the coverage of in-office infusions or self-administered shots widely vary.  They may cover the entire cost or only a portion of the medication.  For example, if your doctor prescribed you rituximab, your insurance company may cover 80% of the cost of the medication, leaving you with 20% of the total bill.  When a medication costs about $22,000, 20% is a lot!

It’s always advisable to contact the doctor’s office or Medicare to find the out-of-pocket costs before receiving any treatment to fully understand the potential costs.

Regardless if you have a Medicare, commercial health insurance plan or if you do not have any health insurance at all, you may still qualify for financial assistance if you cannot afford treatment.  Pharmaceutical companies and other non-profit organizations have many options that can even cover the full cost of treatment.

If you have concerns or questions about the costs of your treatment, please speak to your doctor or the patient advocate in your doctor’s office.

Conclusion

I hope this guide to living with rheumatoid arthritis has been informative and that you learned some valuable information about your diagnosis.  Here are a few final thoughts:

  • Please follow your rheumatologist’s management plan. If you have any concerns, about your symptoms or your medications, it’s always important to keep an open line of communication.
  • It’s important to tell all your different doctors about your new diagnosis and any new medications that you are taking.
  • Always carry an updated list of you medications in your wallet. You never know when someone may ask for it.  The doctor in the emergency room may not have access to your doctor’s records at 2 AM.
  • Make sure that you regularly follow-up with your rheumatologist in clinic. Your doctor may need to adjust your medications and watch for any side effects or complications.
  • If you cannot make a follow-up appointment, please contact your doctor’s office at least 48 hours in advance and re-schedule.
  • Learn as much as you can about your condition.
  • Talk to your friends and your family about your condition. You’re not alone.
  • Stay positive, keep active, and keep smiling!

Please leave your comments or questions below.

 

Co-written by Jessica Chapman, MD and Ilene Leveston, Patient advocate

Edited by Jessica Farrell, PharmD

Patient assistance programs for non-Medicare patients

Cimzia

1 (866) 952 – 7968

https://cimplicityonline.com/

Enbrel

1 (888) 4ENBREL or 1 (888) 436 – 2735

https://www.enbrel.com/support/financial-assistance/

Humira

1 (800) 4HUMIRA or 1 (800) 448 – 6472

http://www.abbviepaf.org/

https://www.humira.com/humira-complete/cost-and-copay

Simponi

1 (877) MYSIMPONI or 1 (877) 697 – 4676

http://www.janssenprescriptionassistance.com/simponi-cost-assistance

Remicade

http://www.janssenprescriptionassistance.com/remicade-cost-assistance

Xeljanz

1 (855) 493 – 5526

http://ra.xeljanz.com/rheumatoid-arthritis-support-resources/financial-help

Orencia

1 (800) ORENCIA or 1 (800) 673 – 6242

https://www.orencia.bmscustomerconnect.com/orencia-patient-assistance

Actemra

1 (800)-ACTEMRA or 1 (800) 228-3672

https://www.genentech-access.com/hcp/brands/actemra/find-patient-assistance.html

Kevzara

1 (844) 538 – 9272

https://www.kevzarahcp.com/kevzara-connect

https://www.kevzara.com/kevzara-copay-card

Rituxan

https://www.genentech-access.com/hcp/brands/rituxan/rituxan-ra/find-patient-assistance.html

Note: Rules, regulations, and contact information are subject to change.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

Diseases and Conditions Self-Injection Videos

How to inject Humira, Enbrel, Simponi, and Cimzia

August 28, 2017
Video demonstrations on how to how to inject Humira, Enbrel, Simponi, and Cimzia

Humira®, Enbrel®, Simponi®, and Cimzia® are medications commonly prescribed for rheumatoid arthritis, psoriatic arthritis, psoriasis, and ankylosing spondylitis.  All of these come in self-injectable pens or pre-filled syringes.  You will be asked to inject these yourself or by a love one, in the comfort of your home.  Today, we’re going to go over how to inject these self-injectable medications.

Preparing for your injection

  • Keep your medication stored in the refrigerator until use
    • Before injecting medication, take the autoinjector out of the refrigerator.
    • Allow it to warm up to room temperature.
  • Pick a place in your house that is clean and has room for your materials (such as the kitchen table).
  • Wash your hands thoroughly with either:
    • Soap & water
    • Hand sanitizer
  • Chose an area to inject – Thigh or Stomach.
    • Chose an area that is intact and clear.
    • It should not have any of the following:
      • Cuts
      • Scrapes
      • Bruises
      • Psoriasis patches
      • If you have extensive psoriasis, inject between patches
      • Moles
      • Scars
    •  
    • Please rotate area each time you inject (shown in picture below).
Areas to inject subcutaneous medication

By British Columbia Institute of Technology (BCIT). Download this book for free at http://open.bccampus.ca [CC BY 4.0 (http://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons

  • Cleanse chosen area
    • Cleanse chosen area with either of the following:
      • Alcohol swab
      • Alcohol and a cotton ball
    • Use the chosen alcohol material to “swipe” area
      • Can either use a circular motion or wipe in “strips”
      • Allow the area to dry

The injection

  • Take off the white cap, observe the medication in the window to be sure that it is clear (no cloudiness or crystals.)
    • You will see a small air bubble within the window, this is normal and will not cause harm when injecting
  • Press down firmly on the clean area of skin, so that the pen is flush with the skin (90-degree angle).
    • The pen needle will not eject unless pressed firmly to skin

For Cimzia® and other medications that come in prefilled syringes

  • Pinch the skin around the injection site and insert the needle at a 45-degree angle
  • Press in the plunger slowly

You may notice the plunger is hard to press this is due to the size of the medication, be sure to continue to inject slowly to administer all medication

  • Press button to inject the medication.
    • You may feel a slight pinch as the needle enters your skin, and tingling as the medication is administered
    • If you have trouble pressing the button try lifting the pen off your skin, and repressing the pen firmly to the area
  • Hold for 15 seconds.
    • Window will become colored (yellow) but continue to hold dose for at least 15 seconds to ensure that all medication is administered

What to do after the injection

  • Lift the pen up from skin and place the whole pen into the sharps container.
    • If you do not have a sharps container available, contact your pharmacy/doctor’s office about obtaining one
      • In the meantime, you may use an old coffee container with a lid
    • Some hospitals take full Sharps Containers for disposal. Here at the office we do not. Contact your pharmacy for more information about the disposing of your Sharps Container.
  • Discard remaining materials in the trash (cap, alcohol swabs, etc.)

If you have any concerns about your medication (e.g., excessive pain, swelling, redness bruising, bleeding, fever, breathing problems), please contact your rheumatologist.

For more information

Humira® – Abbvie

Enbrel® – Amgen

Simponi® – Janssen

Cimzia® – UCB

Jessica Farrell, PharmD.  Clinical Pharmacist, The Center for Rheumatology/Associate Professor, Albany College of Pharmacy and Health Sciences

With the help of Autumn Koniowka. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences, and Megan Phillips. Doctor of Pharmacy Candidate Class of 2018, Albany College of Pharmacy and Health Sciences.

A special thanks to Tammy Garren, PhD. Instructional Designer, Center for Innovative Learning, Albany College of Pharmacy and Health Sciences.

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

Diseases and Conditions Featured

Guide to living with rheumatoid arthritis: Part 2

August 2, 2017
People that suffer from rheumatoid arthritis need to exercise on a daily basis, eat healthy, and find ways to reduce stress in their lives

If you missed Part 1 of Guide to living with rheumatoid arthritis please follow the link.  In part 1 we covered the basics: what is rheumatoid arthritis, the cause, symptoms, diagnosis, and treatment.  In part 2, I’ll be covering how rheumatoid arthritis (RA) can affect your day-to-day living, habits that worsen RA, exercise, food, and stress reduction techniques.  Without further adieu, here is Part 2 of the Guide to living with rheumatoid arthritis.  I hope you enjoy!

How will rheumatoid arthritis affect my life?

Rheumatoid arthritis changes your life. Depression, anxiety, feeling overwhelmed, these are all emotions that are perfectly natural when you get diagnosed with rheumatoid arthritis or any chronic illness. These should improve with time as you learn more about the illness and with the help of family and friends.

The Arthritis Foundation is a national non-profit organization who’s mission is to help, “conquer everyday battles through life-changing information and resources, access to optimal care, advancements in science and community connections. Our goal is to chart a winning course, guiding families in developing personalized plans for living a full life – and making each day another stride towards a cure. We also publish Arthritis Today, the award-winning magazine that reaches 4.2 million readers”.

They definitely are a good group to check out and they have chapters across the country.

The physical aspect

Other than, psychological and emotional impact of the illness, there is also the physical part. There will be good days and bad days. It’s very important to work closely with your rheumatologist when you suffer from RA. It is of utmost importance to go into remission as quickly and safely as possible. There are many medications used to treat RA. Some may work for you and some may not. By working together, you can help your rheumatologist tailor the best possible treatment plan for you.

The goal is to get you back doing what you used to do with the least amount of limitations as possible.

Be aware, even in the best of situations, expect flares. Stress, infections, the weather, and hormonal changes can precipitate a flare. Another goal is to make flares a rare event. Not the norm.

The financial aspect

Finally, although no one likes to talk about it, another important impact that rheumatoid arthritis has on your life is its impact on your wallet. Rheumatoid arthritis is expensive.  Frequent doctor’s appointments. Not only do you need to see your rheumatologist on a regular basis, but you may also need to see other specialists such as an ophthalmologist, nephrologist, pulmonologist, etc. So many co-pays.

Medication costs can get very expensive. Even with health insurance the out-of-pocket costs can be enormous. In my clinic, this is a daily problem. In fact, I’m lucky to work in a practice that has a dedicated patient advocate that helps my patients find solutions to get access to care without breaking the bank. I call her my “health insurance whisperer”.  She kindly agreed to impart some of her knowledge in Part 3 of Guide to Living with Rheumatoid Arthritis.  It’s going to be a real treat!

Other costs

These medications tend to have a long list of potential side effects. These require routine bloodwork. Yet another co-pay.

Lost work days. The less you work, the less you make.

Time. One of the most, and arguably THE most important financial costs.

I do realize that I seem to be painting a very bleak picture, but I want to make it very clear that YOU are in control. Your experience with RA will depend on how much you let it affect you. It will change you for sure but not conquer you.

Will I be able to work?  How do I tell my boss?

I won’t lie.  Rheumatoid arthritis can lead to work disability, abseeteeism, and presenteeism (at-work productivity loss) at a high cost to you but also to your employer.  You’ve had the conversation with your family and friends but now it’s time to tell your boss.

First, you’re not legally required to disclose your RA to your employer.  However, as an employer myself, I would appreciate it if my employee would disclose this information.  What if your job requires heavy lifting or standing around for a very long time?  Maybe I can help you and re-arrange your work duties to better accommodate you?  Maybe you need a better chair or a better mouse?  Every situation is different.  Not everyone with RA has horrible disease but on the flip side not everyone’s employer is accommodating.

There’s also the situation with doctor’s appointments.  Most people with RA see their rheumatologist every 3 to 6 months for regular checkups.  Some people may need medications that only come as infusions.  These infusions are given in clinic and last between 1.5 hours to half a day.  That’s more time off work.

By informing your employer, you are entitled to certain legal rights, as outlined in the Americans with Disabilities Act and the Family and Medical Leave Act.  For more information, please click on the following link[1].

Ultimately, the choice to tell your boss or not is yours.  You are in control.

What habits worsen rheumatoid arthritis?

Smoking

At this point, I hope everyone understands that smoking is a terrible habit associated with a multitude of negative health outcomes.  But did you know that smoking can also predispose people to develop antibody positive rheumatoid arthritis (seropositive)?

Costenbader et al. prospectively studied 103 818 women from 1976 to 2002.  Of those women 680 developed rheumatoid arthritis.  The researchers found that both past and current cigarette smoking was associated with a 40% increased risk of developing seropositive rheumatoid arthritis.  Here are some of the other findings:

  • Increasing duration and intensity of cigarette smoking increases the risk of RA.
  • Greater than 10 pack years of smoking increases the risk of RA in a dose-dependent way.
  • It takes about 20 years of smoking cessation for the risk to return to the “never smoker” category.[2]

What if you already have rheumatoid arthritis?

Does smoking have any impact on active rheumatoid arthritis?  Anecdotally, it’s a lot more difficult to control rheumatoid arthritis when someone smokes cigarettes.  We end up having to cycle through more medications and use more medications at high doses.  However, when you think about it, it makes logical sense.

The current paradigm of RA pathogenesis is that people with certain genetic risk factors first are exposed to environmental triggers that cause local inflammation.  These people then produce autoantibodies and with time some of these people go on to develop full-blown rheumatoid arthritis.  Cigarette smoking is thought to be one of these triggers by causing local inflammation in the lungs[3].

If someone already has RA and continues smoking, well that’s like trying to put out a fire with gasoline.  You’re trying to put out the fire with DMARDs but you’re also adding to the fire by smoking cigarettes.

Another great reason to stop smoking when diagnosed with RA, is the fact that rheumatoid arthritis is well-known to increase the risk of cardiovascular disease.[4]  Other traditional cardiovascular risk factors include high blood pressure, high cholesterol, diabetes, obesity, and physical inactivity. This brings me to my next point, “not moving”.

Not moving

Sedentary behavior is defined as any waking behavior characterized by an energy expenditure of ≤ 1.5 METs and a sitting or reclining posture.  It is associated with poor health outcomes in rheumatoid arthritis.  Although adopting a sedentary lifestyle won’t necessarily directly cause increased disease activity, this lifestyle can worsen muscle density, functional disability, bone mass, and cardiovascular risk.[5]

Everyone knows that life can get really busy sometimes, and going out to the gym sometimes is the last thing on your “to-do” list.  Believe me, I don’t have a gym membership because getting into my car, driving to the gym, changing into workout gear, hopping on a boring treadmill, changing back into my regular clothing, and driving back home is the last thing I want to do after a long day at work.

But being active doesn’t necessarily mean going to the gym.  A 30 minute walk around your neighborhood 5 days week is enough.  Does walking sound boring?  How about catching up on your reading while strolling about.  Amazon has a ton of audiobooks via Audible.  This is NOT affiliate marketing.  I simply use this service on regularly during my daily walks.  I walk at least 30 minutes a day AND read about a book a week.  Win-win!

Now if you tend to forget to get active and need a little nudge to get you going, check out these free IFTTT recipes I made to help you stay active 30 minutes a day.  You need to have a Fitbit, cell phone, and an IFTTT account (which is free) for it to work.

Periodontal disease

In recent years researchers have found a correlation between rheumatoid arthritis and periodontal disease more specifically Porhyromonas gingivalis.[6] Now the question is whether treatment of periodontal disease have any effect on rheumatoid arthritis?  The answer is yes.  A recent systematic review meta-analysis showed that there was a reduction in DAS 28 (this is a scale that we use to measure RA activity) in patients with rheumatoid arthritis after periodontal treatment.[7]  Interestingly, treatment with DMARDs does not improve periodontal disease in people with rheumatoid arthritis.[8]

To keep up with good oral health, the American Dental Association (ADA) recommends brushing your teeth twice a day for two minutes and flossing once a day.  They also recommend eating a healthy diet, limiting snacks, and of course, regular dental check-ups.[9]

Which exercises are safe with rheumatoid arthritis?

This is a very frequent question.  What exercises are “good” and which exercises are “bad”.  Personally, I don’t think that there are any good or bad exercises for rheumatoid arthritis.  What really matters is whether you are you moving.  You should try being active for about 30 minutes a day.  Choose an activity that you enjoy and stick with it.  If someone tells you swimming is excellent for RA but you really don’t like swimming, chances are you won’t stick with the program.  Be active in a way that brings you joy.  Here are some examples.

  • Walking
  • Swimming
  • Yoga
  • Tai chi
  • Jogging
  • Rowing
  • Etc

Have fun!

What types of food should I eat with rheumatoid arthritis?

This is a very common question yet there is very little quality evidence-based research about this topic. Most studies with robust quality controls focus on cardiovascular disease as opposed to rheumatoid arthritis. There is very little quality evidence to support a specific diet for RA.

What is Epigenetics?

Everyone is born with genes. Some of these genes are active and some remain dormant. Your genotype is the entire makeup of your genes. Your phenotype is the result of how your genetic material is expressed. For example, you may have the genes for blue eyes and brown eyes. If the genetic material for brown eyes is dominant, you’ll have brown eyes.

This is where it gets really interesting. Over the course of your lifetime, some of your genes are turned on and off. This is influenced by factors like aging, the environment, and lifestyle. Epigenetics is the study of how genes are turned on and off based on external influences.

Epigenetic changes can be good but can also cause harm. We think that some of these changes can result in autoimmune diseases. It’s important to remember that epigenetics is in its infancy. Researchers still are not 100% sure how this happens, let alone, how to specifically manipulate the environment to cause favorable epigenetic change.

What types of foods are good for people with rheumatoid arthritis?

First, listen to your body. If you find that your arthritis worsens when you eat nightshades, then stop eating nightshades. Look for patterns.  Journaling is helpful in finding these patterns.

Since there isn’t great data supporting a specific diet for RA, I typically recommend a diet that is good for overall health. For this I recommend adhering to the principles of the Blue Zone Project, more specifically the Power 9. The Blue Zones Project initially began as a research project funded by the National Geographic. They sought to find regions in the world where people tend to live to 100 years of age and be healthy.  They identified 5 zones:

  • Ikaria, Greece
  • Okinawa, Japan
  • Ogliastra region, Sardinia
  • Loma Linda, California
  • Nicoya Peninsula, Costa Rica

All these regions have very different cultures and geography, yet they all live by these 9 common attributes. They called them the Power 9.

Move Naturally

People that live to 100 years don’t necessarily run marathons or go the gym. They are always on the go and they move naturally. For example, they tend a garden, they walk to the market, and they use stairs instead of the elevator.

Purpose

People that live in the Blue Zones live with purpose. They wake up every morning, and they know “why I wake up in the morning”. Having a clear purpose in life can add an extra 7 years of life expectancy.

Down Shift

We all know that stress can cause inflammation. I often see people in my clinic who’s rheumatoid arthritis was in perfect control until something really bad happened, like a divorce, job loss, or a death in the family. Chronic stress leads to chronic inflammation. People in the Blue Zones develop daily habits to help reduce stress.

80% Rule

The Japanese have a saying “Hara hachi bu”. This is a mantra that Okinawans say before every meal, reminding them to stop eating when they feel about 80% full. There is a delay between feeling full and actually being full. When you feel 80% full, you are actually full. So if you stop eating when you feel full, you are overeating. People living in the Blue Zones tend to eat their largest meal at breakfast and their smallest meal at dinner.

Plant Slant

Although not all regions of the Blue Zones eat meat, their diets all mainly consist of fresh veg and beans. Lot’s of beans: fava, soy, lentils, etc. They eat meat very sparingly and servings are small, “about the size of a deck of cards”.

Wine @ 5

Thank goodness for this one! People in the Blue Zones, except for Adventists, drink alcohol moderately and regularly. Typically, they drink 1-2 glasses of wine per day with friends and family at the end of the work day. They found that people who drink regularly and moderately tend to live longer than those who don’t.

Belong

Almost all people who live until 100 tend to belong to some sort of faith-based community. They found that attending a service 4 times a month can add up to 4 – 14 years of life expectancy.

Loved Ones First

People living in Blue Zones tend to live close to their families. It’s common to have children, parents, and grandparents living under the same roof. They also tend to commit to a life partner.

Right Tribe

People in the Blue Zones keep strong social networks. Not only are these social strong, but they also foster healthy behaviors. Women in Okinawa create “moais” early on in life. These are groups of 5 friends that are completely committed to each other for life.

Does stress affect rheumatoid arthritis?

Psychological stress can trigger RA flares.  A recent study looked at 274 people with RA.  They found that the most frequent reasons for joint symptoms were psychological stress/mood disorder (86.1%) followed by infection.[10] Other studies have also shown similar [11] findings and I do regularly see this in clinic.

Techniques to reduce stress

Everyone experiences stress in a different way and everyone has different stress thresholds.  When it comes to the best way to reduce stress in people with rheumatoid arthritis, well the data is very poor.  There are a many studies that look at different methods but they have poor quality standards.

The Mayo clinic has a page on their website dedicated to stress management and techniques[12].  It’s quite good.  Some techniques include:

  • Autogenic relaxation
  • Progressive muscle relaxation
  • Visualization
  • Deep breathing
  • Massage
  • Meditation
  • Tai chi
  • Yoga
  • Biofeedback therapy
  • Music and art therapy
  • Aromatherapy
  • Hydrotherapy

Try a few and see what works for you.  Remember, consistency is key.

Conclusion

Thus concludes Part 2 of a Guide to living with rheumatoid arthritis.  In part 3 I’ll be covering the financial aspect of rheumatoid arthritis with some help from my “health insurance whisperer”.  Since you are reading this article, there’s a good chance you just were diagnosed with rheumatoid arthritis.  Now the question that I know must be on your mind, “How am I going to pay for these expensive medications?”

Medical Disclaimer

This information is offered to educate the general public. The information posted on this website does not replace professional medical advice, but for general information purposes only. There is no Doctor – Patient relationship established. We strongly advised you to speak with your medical professional if you have questions concerning your symptoms, diagnosis and treatment.

References

[1] https://www.dol.gov/general/topic/benefits-leave/fmla

[2] Costenbader KH, Feskanich D, Mandl LA, Karlson EW. Smoking intensity, duration, and cessation, and the risk of rheumatoid arthritis in women. Am J Med. 2006 Jun;119(6):503.e1-9.

[3] Sparks JA, Karlson EW. The roles of cigarette smoking and the lung in the transitions between phases of preclinical rheumatoid arthritis. Curr Rheumatol Rep. 2016 Mar;18(3):15. doi: 10.1007/s11926-016-0563-2.

[4] Balsa A, et al. Prevalence of comorbidities in rheumatoid arthritis and evaluation of their monitoring in clinical practice: the Spanish cohort of the COMORA study. Reumatol Clin. 2017 Jul 12. pii: S1699-258X(17)30134-1. doi: 10.1016/j.reuma.2017.06.002. [Epub ahead of print].

[5] Fenton SA, Veldhuijzen van Zanten JJ, Duda JL, Metsios GS, Kitas GD. Sedentary behaviour in rheumatoid arthritis: definition, measurement and implications for health. Rheumatology (Oxford). 2017 Apr 7. doi: 10.1093/rheumatology/kex053. [Epub ahead of print]

[6] Azzi L, et al. Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas gingivalis. J Biol Regul Homeost Agents. 2017 Apr-Jun;31(2 Suppl 1):97-103.

[7] Calderaro DC, Correa JD, Ferreira GA, Barbosa IG, Martins CC, Silva TA, Teixeira AL. Influence of periodontal treatment on rheumatoid arthritis: a systematic review and meta-analysis. Rev Bras Reumatol Engl Ed. 2017 May – Jun;57(3):238-244. doi: 10.1016/j.rbre.2016.11.011. Epub 2017 Jan 4.

[8] Ayravainen L, Leirisalo-Repo M, Kuuliala A, Ahola K, Koivuniemi R. Meurman JH, Heikkinen AM. Periodontitis in early and chronic rheumatoid arthritis: a prospective follow-up study in Finnish population. BMJ Open. 2017 Jan 31;7(1):e011916. doi: 10.1136/bmjopen-2016-011916.

[9] http://www.ada.org/en/science-research/science-in-the-news/periodontal-disease-affects-nearly-half-us-population

[10] Yilmaz V, Umay E, Gundogdu I, Karaahmet ZO, Ozturk AE. Rheumatoid arthritis: are psychological factors effective in disease flare. Eur J Rheumatol. 2017 Jun;4(2):127-132. doi: 10.5152/eurjrheum.2017.16100. Epub 2017 Jun 1.

[11] Nagano J, Sudo N, Nagaoka S. Yukioka M, Kondo M. Life events, emotional responsiveness, and the functional prognosis of patients with rheumatoid arthritis. Biopsychosoc Med. 2015 Jun 23;9:15. doi: 10.1186/s13030-015-0043-3. eCollection 2015.

[12] http://www.mayoclinic.org/healthy-lifestyle/stress-management/basics/stress-basics/hlv-20049495