By Christopher S. Walter, PT, DPT, PhD
AGEC Geriatric Fellow
Assistant Professor
Department of Physical Therapy
University of Arkansas for Medical Sciences – Fayetteville

Have you ever considered that your current treatment of drug therapies is not working for you? If you have, you aren’t alone. In fact, the top-ten highest grossing drugs in the United States only benefit 4-33% of the people who take them¹.  Unfortunately, research suggests that motor rehabilitation therapies are no different².

Rehabilitation is the action of restoring someone to health or normal life through therapy after an injury, illness, or disease process. Generally speaking, we know that rehab works.  For example, an individual who gets therapy following an injury (e.g., fractured hip, stroke, etc.) is more likely to improve faster, and to a greater extent, than someone who does not get therapy.  This is good news for those getting therapy and those in the rehab field.  However, a closer, individualized look at the process shows that it’s not all sunshine and roses. Some individuals have very good results after rehabilitation, while others show little to no improvement².  This problem is made worse by the fact that the rehab clinician (i.e., physical therapist, occupational therapist, and/or other allied healthcare provider) is unable to predict who might or might not respond to therapy.

The problem is clear; the solution is not.  Science has yet to develop a process that predicts who will respond to therapy and who will not respond.  We do know that age is a factor.  The older the patient, the less they respond to the given therapies^3-5.

There is good news, though. Just because an individual does not respond to one intervention does not mean he/she will not respond to all interventions.   To put this into perspective, consider the following example.  If a medication prescribed by your doctor to lower your cholesterol does not have the desired effect, your doctor could 1) prescribe a larger dose of that medication, or 2) choose a different drug all together.  The goal to lower cholesterol is the same only the method has changed.   Rehabilitation is no different.

There are steps that rehab therapists and professionals can take to ensure that therapy is successful for as many people as possible. First, our treatments should only be selected after thoughtful examination of the patient’s individual characteristics. Further, it is important that our interventions are evidence based with documented effectiveness.  This is where we need your help. You can help by signing up to be a participant in rehab research trials.  Reach out to the local university to see if there is an open study for people like yourself.  Additionally, ARresearch.org is a secure website that allows the community a first-hand look at the research being conducted at UAMS.  Volunteers can provide their information if interested in participating in research. The researchers are then able to contact potential volunteers for their studies.

The goal of rehabilitation is to restore health and quality of life following an injury. To meet this goal, rehab professionals must work to identify characteristics that separate those who will respond to therapy from those who will not.  With passionate professionals and an enthusiastic community willing to volunteer, we can close the gap on rehab success.

1. Schork NJ. Personalized medicine: Time for one-person trials. Nature. 2015;520:609-611.
2. Winstein C. Translating the Science into Neurorehabilitation Practice: Challenges and Opportunities (The Kenneth Viste, Jr. MD Lecture). American Society of Neurorehabilitation Annual Meeting. Washington, DC.2013.
3. Dobkin BH, Nadeau SE, Behrman AL, et al. Prediction of responders for outcome measures of locomotor Experience Applied Post Stroke trial. J Rehabil Res Dev. 2014;51:39-50.
4. Rodeghero JR, Cleland JA, Mintken PE, Cook CE. Risk stratification of patients with shoulder pain seen in physical therapy practice. J Eval Clin Pract. 2017;23:257-263.
5. Walter CS, Hengge CR, Lindauer BE, Schaefer SY. Declines in motor transfer following upper extremity task-specific training in older adults. Exp Gerontol. 2018;116:14-19.

By Katie Cummins, PharmD Candidate 2019 and Lisa Hutchison, PharmD, MPH, BCPS, BCGP, FCCP
Donald W. Reynolds Institute on Aging at UAMS

As our patients age, their bodies undergo physiological changes that alter their responses to many drugs. Kidney and liver function decline so that some drugs stay in the body longer or accumulate to dangerous levels. Body composition changes – muscle decreases while the proportion of fat increases – can lead to the need for smaller doses or longer dosing intervals. In addition, older adults are generally more sensitive to many drugs, especially those that affect the central nervous system. Patients are sensitive to both the effects the drugs are designed for as well as their negative side effects.¹

Medications that are “potentially inappropriate” for older adults are detailed in the Beers’ Criteria. The Beers’ list is a tool for providers to help identify medications that could be problematic for older patients. It can also be used as a guide for future drug selection. Some of the concerns outlined in the 2015 Beers’ criteria include adverse events like: dizziness, drowsiness, constipation, confusion, bleeding risk, orthostatic hypotension, and delirium.²

However, these side effects are not limited to prescription drugs; the over-the counter (OTC) section of the pharmacy contains medications that may be inappropriate or even dangerous to older adults. Though they may appear to be safer options since they are widely available, they are not without risk for harm. Some of these potentially inappropriate OTC medications are:

1. Diphenhydramine: also known as Benadryl³
   1. Commonly found in products branded as PM or Nighttime – Tylenol PM, Advil PM, Unisom, ZzzQuil, Delsym Cough+Cold Nighttime, Theraflu Nighttime Severe Cold and Cough
   2. Used as sleep aid or anti-histamine for allergies
   3. Side effects: confusion, drowsiness, dizziness, delirium, dry mouth, constipation
2. Oxybutynin: also known as Oxytrol for Women⁴
   1. Topical patch marketed for overactive bladder
   2. Side effects: drowsiness, delirium, dizziness, dry mouth, constipation
3. Meclizine: also known as Dramamine Less Drowsy, Bonine⁵
   1. Commonly found in products marketed for motion sickness or vertigo
   2. Side effects: dizziness, drowsiness, dry mouth, constipation, can worsen dementia symptoms
4. NSAIDs (non-steroidal anti-inflammatory drugs): ibuprofen, naproxen,
   1. Common brand names: Motrin, Advil, Aleve
   2. May increase risk of GI bleeding, cardiac events²
      1. Take extra caution if taking daily aspirin or prescription blood thinners or anti-platelets like warfarin, clopidogrel (Plavix), prasugrel (Effient), apixaban (Eliquis), dabigatran (Pradaxa)
5. PPIs (proton pump inhibitors): such as omeprazole, lansoprazole
   1. Common brand names: Prilosec, Prevacid
   2. May contribute to bone loss with long-term use which increases fracture risk with a fall
   3. Can increase risk of bacterial C. difficile infections – symptoms include severe diarrhea²

This is not to say that older adults should avoid all OTC products in the community but rather to show that it is important to for providers to ask if they are taking these products. Documenting this information can prevent the need for additional prescriptions to treat side effects that may be caused by an OTC product – halting a prescribing cascade in its tracks.

References

1. Hajjar ER, Gray SL, Slattum Jr PW, Hersh LR, Naples JG, Hanlon JT. Geriatrics. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e New York, NY: McGraw-Hill; http://accesspharmacy.mhmedical.com/content.aspx bookid=1861&sectionid=146077984. Accessed July 26, 2018.
2. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of the American Geriatrics Society. 2015;63(11):2227-2246. doi:10.1111/jgs.13702.
3. Diphenhydramine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed July 26, 2018.
4. Oxybutynin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed July 26, 2018.
5. Meclizine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed July 26, 2018.

UAMS logo

By Hope Quattlebaum, PharmD candidate and Lisa C Hutchison, PharmD, MPH
Donald W. Reynolds Institute on Aging at UAMS

Blood thinners, such as novel oral anticoagulant agents (NOACs), reduce the risk of developing an emboli (clot) in conditions such as atrial fibrillation (afib), deep venous thrombosis (DVT), and other cardiovascular conditions. The NOACs include apixaban (Eliquis), rivaroxaban (Xarelto), dabigatran (Pradaxa), and edoxaban (Savaysa).  Using blood thinners prevent clots of all kinds, even ‘good’ clots. When ‘good’ clots are inhibited serious bleeding can occur, such as intracranial hemorrhage (ICH).

Clinicians sometimes mitigate risk by choosing to use aspirin in place of a NOAC since it is thought to have a lower risk of ICH. However, studies show that apixaban 5 mg twice daily did not increase ICH compared to aspirin therapy in afib patients⁶. Based on this, apixaban is a better choice than aspirin since it poses no additional risk and is more effective. However, it was not known if this conclusion could be applied to other disease states.  A meta-analysis published in 2018 attempted to answer this question.

The meta-analysis included five major randomized controlled trials (RCTs) with the purpose to assess the risk of ICH with NOACS versus aspirin in all indications⁵. The researchers looked for RCTs that compared apixaban and rivaroxaban to aspirin for 3 or more months. The primary endpoint was rates of ICH in NOACs versus aspirin. The table provides information on the age, disease state and comparison groups in each of the five studies.

After pooling evidence, the researchers determined that the risk of ICH with rivaroxaban 10-20mg daily is 3.31 times higher than aspirin. Lower doses, 10 mg daily or 5 mg twice daily, were not associated with higher risk of ICH. Apixaban did not show an increased risk. Researchers calculated that 15-20 mg rivaroxaban can cause an additional 3 hemorrhages per 1000 patients compared to aspirin or apixaban. Evaluation of the secondary endpoint showed that rivaroxaban 15-20 mg increased the rate of fatal bleeding by 2.37 times compared to aspirin and apixaban 5mg twice daily. Also, the same dose is associated with 2.64 times higher risk for major bleeding compared to aspirin, while apixaban showed no increase in risk.

This meta-analysis provides substantial evidence that rivaroxaban at higher doses (15-20 mg daily) increases risk of ICH and fatal bleeding in many patients needing anti-thrombotic therapy. These doses are equivalent to those recommended in afib, DVT treatment, but higher than the recommended dose for DVT prevention, 10 mg daily.  Apixaban 5 mg twice daily and rivaroxaban 10mg were not associated with these increased risks. Unfortunately, no direct comparisons could be made between aspirin and dabigatran or edoxaban.

References

¹ Hart RG, Sharma M, Mundl H, et al; NAVIGATE ESUS Investigators. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378(23):2191-2201. doi: 10.1056/NEJMoa1802686
² Eikelboom JW, Connolly SJ, Bosch J, et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377(14):1319-1330. doi:10.1056/NEJMoa1709118
³ Anand SS, Bosch J, Eikelboom JW, et al; COMPASS Investigators. Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial. Lancet. 2017;S0140-6736(17)32409-1.
⁴ Weitz JI, Lensing AWA, Prins MH, et al; EINSTEIN CHOICE Investigators. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017;376(13): 1211-1222. doi:10.1056/NEJMoa1700518
⁵ Huang W, Singer DE, Wu Y, et al. Association of Intracranial Hemorrhage Risk With Non–Vitamin K Antagonist Oral Anticoagulant Use vs Aspirin Use: A Systematic Review and Meta-Analysis. JAMA Neurol. Published online August 13, 2018. doi:10.1001/jamaneurol.2018.2215
⁶ Connolly, S. J., Eikelboom, J., Joyner, C, et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011; 364(9), 806-817.

Theresa Horton, MNSc, CNP, GNP-BC, CADDCT, CFRDT
Director of Education
South Central Center on Aging

Anti-Bullying Month is observed in October.   Bullying is typically associated with a younger population. However, bullying among adults occurs in multiple settings and older adults are not immune from being victims.     Bullying is defined as “unwanted aggressive behavior; observed or perceived power imbalance; and repetition of behaviors or high likelihood of repetition.”

It is estimated that 20% of older adults experience some form of bullying.   Healthcare professionals, staff and families should be aware of what bullying behavior looks like and its potential effects.   It can be subtle or aggressive.  Bullying can include behaviors such as teasing, insulting, gossiping, criticizing, ignoring, whispering, name calling, laughing at or taunting someone, sarcasm, rude comments, use of threats, arguing, lying about the victim, destruction of property, stealing, pushing, hitting, barring from entering or exiting a room, physical or verbal sexual harassment, shunning, ostracizing, spreading rumors, enforcing non-existent seating assignments, using negative body language (offensive gestures or facial expressions, mimicking physical disability, turning away when victim speaks, etc.), and cyber bullying.

Traits that cause a person to bully someone vary and can include increased stress, the need for power or control, low self-esteem, passive-aggressive behavior, verbal or physical aggressiveness and a superiority complex.   Some older adults have a history of bullying that has continued throughout life.  An older adult may bully because of prejudices or because of a sense of loss of control in their life.   They may be dealing with loneliness or boredom or suffer from health conditions, such as dementia, that may contribute to bullying behaviors.

Identifying factors that can increase the risk of an older adult being bullied is important for intervention and prevention. Some of these include being new to a community, having little or no support network, being heavily dependent on others for daily needs, or having a passive demeanor.   Others may be at risk for bullying if they annoy or irritate others or are quick-tempered. Health conditions or physical disabilities can increase the risk as well.

Bullying can have cognitive, physical, psychological or emotional consequences and can affect not only the victim, but also those who witness it.   Policies should be in place to develop clear rules and expectations, including appropriate assessments and interventions. It is important that any complaints be taken seriously and that staff be educated to recognize and report bullying immediately.

Sources:

Bullying Among Seniors (and Not the High School Kind). National Center for Assisted Living.   2017

http://www.mybetternursinghome.com/senior-bullying-guest-post-by-robin-bonifas-phd-msw-and-marsha-frankel-licsw/

By Robin McAtee, PhD, RN, FACHE, Director, Arkansas Geriatric Education Collaborative (AGEC), a Geriatric Workforce Enhancement Program (GWEP) at the University of Arkansas for Medical Sciences (UAMS) Donald W. Reynolds Institute on Aging (DWR IOA)

Fall greetings from the Arkansas Geriatric Education Collaborative (AGEC), the Geriatric Workforce Enhancement Program for Arkansas. As we enter into the final few months of 2018, we are very busy with programs.  We have conducted many community programs for older adults and those that care for older adults including family caregiver workshops, Alzheimer’s experience events, continuing education activities, and more.

In August, academic classes that support and focus on geriatric topics and content were started once again at UCA and ASU. We are excited about continuing our partnerships with them and training bright young people who are entering the healthcare field in the critical area of geriatrics. In October, we had our first fall webinar.  Ashley Stepps, JD, Arkansas Elder Law & Special Needs Trusts Attorney from The Raymon B. Harvey Law Firm provided a 2018 Healthcare Law Update regarding: Living Wills, Advanced Care Planning, Powers of Attorney, AR Lay Caregiver Act, and More Topics.  Ashley fielded many questions both live and on-line.

On December 5^th, we will host our second fall Webinar that will feature Dr. Rhonda Mattox who will speak on Insomnia: A Golden Opportunity to Address Psychiatric Disorders. In addition, we are also hosting a 4 day train-the-trainer program on Stanford’s Chronic Pain Self-Management program. Many of our partners such as Carelink, the Arkansas Federal Prison System, the Northwest AAA, UAMS programs, and others have registered for this program that filled up after only a few days.  We are excited that so many want to learn how to teach these classes and participant in this effort to attack the opioid crisis.  Plans are to offer this training again in the spring.

In November, we are excited to partner with Circle of Life Hospice to provide a 3 day FREE CE Event (up to 22 CE hours). The Community Hospice and Palliative Care Symposium can be attended in person in Northwest AR or attended via live streaming.  Please visit our website for more information on our upcoming programs.

As winter approaches, we will continue to seek ways to engage healthcare providers and community members in learning more about the care of older adults. We continue to seek new ways to reach and teach these audiences and if you have any suggestions, please let us know. Have a safe and happy fall!

By Robin McAtee, PhD, RN, FACHE, Director, Arkansas Geriatric Education Collaborative (AGEC), a Geriatric Workforce Ehancement Program (GWEP) at the University of Arkansas for Medical Sciences (UAMS) Donald W. Reynolds Institute on Aging (DWR IOA)

Hello from the Arkansas Geriatric Education Collaborative (AGEC), the Geriatric Workforce Enhancement Program for Arkansas. Spring time was very busy for the AGEC with a lot of programs happening all across the state.  We had a webinar in April about the latest Shingles Vaccine and other needed adult vaccines by Dr. Bob Hopkins and Kara Jones one in March “Improving the Quality of Life of Senior Cancer Survivors” by Lisa VanHoose, PhD, one of our AGEC Geriatric Fellows from last year.  Our academic partners, ASU and UCA, were also busy reaching thousands of students with geriatric content during the spring semester!  We were also busy with Family Caregiver Workshops, Dementia Experiences, and Dementia Practitioner and First Responder Dementia trainings.  We had wonderful audiences at these events and look forward to expanding these programs in year four.

As we currently swelter in the middle of an Arkansas summer, we are continuing to have great programs and activities throughout the state and are planning for year four activities.   We have just received notice about a small GWEP supplemental grant revolving around the opioid crisis.  This was developed, submitted and approved!  We have also received our HRSA funding for year four of the AGEC and are very active getting the associated programs started. We continue to seek new ways to reach and teach all audiences and if you have any suggestions, please let us know.

By Karah Bogoslavsky, PharmD candidate and Lisa C Hutchison, PharmD, MPH
Donald W. Reynolds Institute on Aging at UAMS

Bleeding is a serious complication of treatment with oral anticoagulants or blood thinners. Andexanet alfa (AndexXa) has recently been approved for the reversal of life-threatening or uncontrolled bleeding in patients treated with apixaban (Eliquis) and rivaroxaban (Xarelto).¹ It joins idarucizumab (Praxbind) which is marketed for bleeding with dabigatran (Pradaxa).  Similar to idarucizumab, andexanet alfa binds free rivaroxaban or apixaban in the blood so they are no longer able to work. There were two major trials that were used to test the efficacy of andexanet alfa, the ANNEXA-A/ANNEXA-R trial and the ANNEXA-4 trial.^2,3

The ANNEXA-A/ANNEXA-R study tested andexanet alfa bleeding reversal activity in healthy volunteers 50 to 75 years old, with an average age of 58 years old.² Bleeding activity was rapidly reduced within 2 to 5 minutes as compared to placebo. After administration of andexanet alfa was completed, the reversal of bleeding activity persisted for 2 hours. This finding is consistent with the half-life of the drug, which is approximately 1 hour.

The ANNEXA-4 study is an ongoing open label study of patients with acute major bleeding from apixaban or rivaroxaban.³ The average age was 77 years old, and two thirds of patients had atrial fibrillation.  Effectiveness was rated as “excellent” if the bleeding stopped within 1 hour after the infusion and “good” if it stopped within 4 hours.  Of the 77 enrolled patients, 20 were not included in final analysis due to low or missing anti-factor Xa activity.  Of the 47 patients in the effective population, 31 patients had “excellent” hemostasis and 6 had “good” hemostasis, 12 hours after the andexanet alfa infusion.  Effective normalization between the bleeding and blood clotting activity was achieved 12 hours after infusion of andexanet alfa in 79% of the patients studied.

However, treatment with andexanet alfa has been associated a high rate of thrombosis including heart attacks, stroke, cardiac arrest, and sudden death. In the ANNEXA-4 study, events that involved dislodged blood clots occurred in 18% of the patients in the safety population, and 15% of the patients died during the 30-day follow-up.³ It is unknown whether andexanet alfa has a prothrombotic effect of its own, or if the absence of an anticoagulant in a high risk patient is the cause of this high rate of thrombosis and follow-up was limited to 30 days.

Andexanet alfa comes in a 100 mg vial and requires storage under refrigeration until reconstitution with sterile water for injection. A specific reconstitution technique is described in the package insert.¹ Dosage is 400 mg infusion for lower doses of apixaban or rivaroxaban, and 800 mg infusion for higher doses.

The availability of a reversal agent for apixiban and rivaroxaban levels the playing field between them and dabigatran; however, much is still unknown regarding the risk of newer oral anticoagulants and reversal agents in older adults.⁴ Since the rate of serious bleeding is lower in the newer anticoagulants, and their effects wear off quickly, in most cases stopping the drug will be sufficient treatment for bleeding and no antidote will be required.  Limiting use of andexanet alfa to individuals with life-threatening hemorrhage is most prudent, given the risk of thrombosis and unknown long-term outcomes in older adults.

References

1. Andexxa (andexanet alfa) . South San Francisco, CA: Portola Pharmaceuticals, Inc; May 2018.
2. Connolly SJ, Milling TJ Jr, Eikelboom JW, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med 2016; 375:1131.
3. Siegal DM1, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. 2015 Dec 17;373(25):2413-24. doi: 10.1056/NEJMoa1510991. Epub 2015 Nov 11.
4. Hunt BJ, Levi M. Engineering reversal—finding an antidote for direct oral anticoagulants. N Engl J Med 2016; 375:1185-6.