In Lessons from the Miracle Doctors, I mentioned that in 2002, there were approximately 3.34 billion prescriptions filled--approximately eleven drugs for every man, woman, and child in the U.S. Unfortunately, according to IMS Health, that number, as of 2014, had climbed to 4.3 billion.1 No human being or computer program can keep track of all the possible side effects of this many drugs, especially when mixed together. The problem is that each drug affects the body chemistry in multiple ways. That's the reason each drug has so many different side effects. When you add a second drug, the interaction between the two drugs increases the possibilities far beyond simply adding the side effects of the two drugs together. Add a third drug, and the possibilities for interaction start to go off the chart. Make that ten or fifteen drugs and you're dealing with interaction side effects beyond comprehension. In one study, an alarming one-in-four patients suffered "observable" side effects from prescription drugs.2 (And that doesn't take into account the "unobservable" and long term side effects, which are often chalked up to "old age.") Common prescription drugs such as sleep aids, anti-anxiety drugs, antidepressants, allergy drugs, and even cold remedies can all have multiple side effects.
Note: throughout this newsletter, we're going to be listing the side effects associated with different classes of pharmaceutical drugs. You don't actually have to read them all. Skimming is enough. However, as you do so, it's worth keeping in mind Humphrey Bogart's line from the Maltese Falcon: "Maybe some of them are unimportant. I won't argue about that. But look at the number of them."
- Sleep aids: Burning or tingling in the hands, arms, feet, or legs, Changes in appetite, Constipation, Diarrhea, Difficulty keeping balance, Dizziness, Daytime drowsiness, Dry mouth or throat, Gas, Headache, Heartburn, Impairment the next day, Mental slowing or problems with attention or memory, Stomach pain or tenderness, Uncontrollable shaking of a part of the body, Unusual dreams, Weakness.3
- Anti-anxiety drugs: Drowsiness, Dizziness, Poor balance or coordination, Slurred speech, Trouble concentrating, Memory problems, Confusion, Stomach upset, Headache, Blurred vision, Increased anxiety, Irritability, Agitation, Mania, Hostility and rage, Aggression, Impulsive behavior, Hallucinations, Increased anxiety, Insomnia, Depression, Pounding heart, Sweating, Shaking, Restlessness, Stomach pain, Panic attacks, Nausea, Seizure (severe cases), Drug dependence and withdrawal.4
- Antidepressants: Headache, Heart racing, Chest pain, Neck stiffness, Nausea and vomiting, Sexual problems including low sex drive or inability to have an orgasm, Dizziness, Headaches, Insomnia, Feeling jittery, Weight loss or gain, Decreased appetite, Restlessness, Insomnia, Anxiety, Tremor, Constipation, Dry mouth, Diarrhea, Dizziness, Seizures, Drowsiness, Daytime sleepiness, Sweating.5
- Allergy drugs: Dry mouth, Drowsiness, Dizziness, Nausea and vomiting, Restlessness or moodiness (in some children), Trouble peeing or not being able to pee, Blurred vision, Confusion.6
And then there's dementia. Medical authorities claim that side effects from prescription drugs are responsible for only a minority of cases of dementia, but even according to these conservative sources, such side effects may still represent 15-30 percent of all dementia diagnoses. But don't despair--a new field of expertise called polypharmacy has been created to "deal" with this problem.
Polypharmacy is defined as both the use of multiple drugs and the use of more drugs than are medically necessary, and it is a growing concern for older adults.7 But it also refers to the side effects that result from taking those multiple drugs concurrently--especially when used to manage coexisting health problems. And that's just the tip of the pyramid, especially when you consider that patients are prescribed these multiple medications by multiple healthcare providers, all working independently of each other. This leads to the problem of each doctor being unaware of what the other doctors are doing so that no single healthcare provider knows the patient's complete medication picture.
Polypharmacy is especially problematic for older adults as they are more likely to be taking multiple medications. In 2013, according to the international, online, statistics portal, Statista, the average number of prescriptions per capita in the United States was:
- 50-64 years old: 19.2 prescriptions per person8
- 65-79 years old: 27.3 prescriptions per person
- 80+ years old: 29.1 prescriptions per person
And while it is true that in other countries such as Canada, the numbers are lower; they are nevertheless almost as disturbing. You're still looking at a range of 6-28 medications per 80+ year old patient.9
The most commonly used drugs--acetaminophen, ibuprofen, and aspirin--are available without prescription and by themselves contribute significantly to adverse drug reactions in the elderly. But when you start taking multiple drugs together, the side effects can increase exponentially. In general, the more drugs you take, the greater the risk of the drugs interacting with each other, thus the greater the risk of adverse reactions. The prescription drug categories most commonly involved in adverse reactions are cardiovascular medications (cholesterol, blood pressure, etc.), antibiotics, diuretics, anticoagulants, blood sugar medications, steroids, anticholinergics, benzodiazepines, nonsteroidal anti-inflammatory drugs, and opioids.
- Cardiovascular medications (cholesterol, blood pressure, etc.): Diarrhea, Rash, Itching, Abdominal pain, Headache, Chest pain, Muscle aches, Dizziness, Bleeding, Gangrene of the skin, Cough, Elevated blood potassium levels (hyperkalemia), Low blood pressure, Headache, Drowsiness, Weakness, Abnormal taste, Increased or irregular heart rate, Headache, Constipation, Nausea and vomiting, Edema, Blurred vision, Anorexia, Unusual taste, Fatigue.10, 11
- Antibiotics: Rash, Diarrhea, Abdominal pain, Nausea/vomiting, Drug fever, Allergic reactions, Serum sickness, Vaginal candidiasis, Renal (kidney) toxicity, Hearing loss, Dizziness, Rapid, rhythmic, repetitious, and involuntary eye movements, Headache, Liver toxicity, Elevated white blood cells, Anorexia, Hemolytic anemia, Peripheral neuropathy, Reddish-orange body fluids, Red man syndrome (flushing, hypotension, itching), Phlebitis, Taste alteration, Photosensitivity, Tooth discoloration in children, Colitis (may be severe), Jaundice.12
- Diuretics: Dry mouth, Thirst, Weakness, Lethargy, Drowsiness, Restlessness, Muscle pains or cramps, Confusion, Seizures, Muscular fatigue, Hypotension, Decreased or absent production of urine, Tachycardia, Gastrointestinal disturbances, Gout, Lithium toxicity, Muscle weakness, Slow heart rate, Neurologic damage, Death.13
- Anticoagulants: Abdominal or stomach pain with cramping, Bleeding gums, Blood in the urine, Bloody stools, Blurred vision, Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings, Chest pain or discomfort, Confusion, Coughing up blood, Difficulty with breathing or swallowing, Dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position, Excessive bruising, Headache, Increased menstrual flow or vaginal bleeding, Nosebleeds, Paralysis, Peeling of the skin, Prolonged bleeding from cuts, Red or black, tarry stools, Red or dark brown urine, Shortness of breath, Sweating, Unexplained swelling, Unusual tiredness or weakness.14
- Blood sugar medications: Bloating, gas, Diarrhea, Upset stomach, Loss of appetite, Low blood glucose, Skin rash, Irritability, Edema, Increased risk of congestive heart failure, Sore throat, Stuffy nose, Upper respiratory infection, Constipation, Nausea, Heartburn, Headache, Pancreatitis, Pancreatic cancer, Urinary infections, Thyroid cancer, Gastrointestinal issues, Renal and gallbladder problems.15, 16
- Steroids: Compromised adrenal glands, Steroid withdrawal syndrome, Infection, Gastrointestinal ulcers or bleeding, Osteoporosis, Weight gain, Insomnia, Mood changes, Fluid retention and elevated blood pressure, Elevated blood sugar, Can cause cataracts or glaucoma or worsen these conditions if they are already present, Atherosclerosis (hardening of the arteries), Aseptic necrosis (bone death), Infection, Allergic reactions, Bleeding into the joint, Rupture of a tendon, Skin discoloration, Acne, Blurred vision, Easy bruising, High blood pressure, Increased growth of body hair, Muscle weakness, Nervousness, restlessness, Stomach irritation or bleeding, Swollen, puffy face, Worsening of diabetes.17, 18
- Anticholinergics (Used to treat diseases like asthma, incontinence, gastrointestinal cramps, and muscular spasms, they are also prescribed for depression and sleep disorders.): Dry mouth, Blurred vision, Constipation, Drowsiness, Sedation, Hallucinations, Memory impairment, Difficulty urinating, Confusion, Delirium, Decreased sweating, Decreased saliva.19
- Benzodiazepines: (Symptoms detailed earlier under anti-anxiety drugs.)
- Nonsteroidal anti-inflammatory drugs (NSAIDS): Vomiting, Nausea, Constipation, Diarrhea, Reduced appetite, Headache, Dizziness, Rash, Drowsiness, Heart attacks, Stroke, Gastrointestinal bleeding, Ulcers, Perforation of the stomach or intestines.20
- Opioid pain killers: Sedation, Dizziness, Nausea, Vomiting, Constipation, Physical dependence, Tolerance, and Respiratory depression, not to mention the largest addiction crisis in the history of the United States.21
If you just "add" several of the above pharmaceuticals together, you can see how the number of possible side effects begins to become unmanageable. But that's an arithmetic increase. As we've already discussed, once you start mixing several pharmaceutical drugs together, the chances of unknown/unlisted side effects begins to increase exponentially. And because no one has ever associated these new side effects with any particular drug, as mentioned earlier, they're usually chalked up to old age.
Compounding the Problem
Something that most people don't think about is that your body composition changes as you age, which causes you to react differently to medications. Quite simply, as you age, you tend to gain fat and lose muscle and water. Your body literally begins to dry out--something readily visible in aging skin. This can cause water-soluble drugs to become more concentrated in your body and fat soluble drugs to remain in your body longer. In other words, drugs that you were once able to take safely, can become problematic simply as a result of your aging. And since you never had a side effect from using the drug before, why would you blame your new health problems on those "old, reliable" drugs.
And then there's your liver and kidneys. As we have discussed in previous newsletters, most drugs are metabolized in your liver. But since most people's livers become smaller and less functional as they age (unless you're regularly flushing and rebuilding your liver), your body become less efficient at clearing drugs from your system. Likewise as previously discussed, reduced kidney function is endemic as people age (again, unless you are regularly flushing and repairing your kidneys). This slows down the elimination of drugs in your urine--again, causing drug concentrations to rise as you age, even while taking the same dose that previously worked without problems.
Then there's the fact that some pharmaceutical drugs such as digoxin bind with the albumin proteins in your blood. Binding with the albumin keeps the drugs temporarily inactive--in effect, allowing your body to parcel out the dose. Unfortunately, albumin levels, as a result of illness or malnutrition, tend to decrease in seniors. This too can lead to higher active concentrations of those drugs in the bloodstream, again, creating side effects where once there were none.
Then there are the herbs and supplements people take. For the most part, these are safe and have minimal side effects on their own. But they do contain bioactives, and those bioactives do have an effect on the body--albeit, mostly the desirable effects that you want. But since they actually affect the body, they too can interact with pharmaceutical drugs creating unexpected side effects. One such example is St. John's wort, which many people take to ease mild to moderate depression. By itself, it has virtually no harmful side effects other than a "possible" increased sensitivity to the sun. But St. John's wort "may" make a number of pharmaceutical drugs less effective.22 To be clear, St. John's wort is not harmful or dangerous by itself, despite what you may read on the internet. If you are not taking pharmaceutical drugs, there is no problem. If you are, then it can amplify the dangers inherent in taking pharmaceutical drugs. That's actually quite different from being dangerous in and of themselves.
Which brings us to grapefruit juice. Until a few years ago, who had anything bad to say about grapefruit juice? Now, a search on the internet links the terms "grapefruit juice" and "danger." Really? Again, the problem is not with grapefruit juice, but with its potential to interact with any pharmaceutical drugs you are taking. The problem is that grapefruit juice interferes with an enzyme found in the liver and in the intestine known as CYP 3A4. CYP 3A4 metabolizes drugs so that they can be removed from the body. By interfering with that enzyme, drinking grapefruit juice can increase the potency of a drug by letting more of it enter the bloodstream, in effect producing an excessive dose. So once again, the problem is not inherent in grapefruit juice but in its surprising interaction with drugs. And thus it needs to be added to the mix when considering the problems associated with polypharmacy. Then again, you probably need to add pomegranate juice, cranberry juice, cinnamon, black or white pepper, ginger, mace, and nutmeg to the list as well, as they also inhibit CYP 3A4.23
And Then It Gets Much Worse
Like most good horror stories, just when you think you're about as frightened as you can get, the terror ramps up.
I've told the story before about how my mother-in-law was admitted to a hospital several years ago after fainting. By the time she had spent just one night in the hospital, they had determined she was suffering from advanced dementia as she was seeing spider webs falling from the ceiling and flowers growing on the walls. As a result, they wanted to begin giving her medications to treat her dementia--essentially to zombify her so she would be easy to control. Kristen was unable to convince the medical staff that no such hallucinations had existed before her mother had entered the hospital. She then asked me to look at her medications to see if anything jumped out. It did. They had given her Ambien to sleep, even though she had never requested it, or had trouble sleeping. It turns out it was just something they automatically gave to most of the patients to keep them quiet at night. Fortunately, I had previously done a national radio show tour on the side effects of sleeping pills and knew that Ambien could trigger hallucinations. Kristen then told the nurses and doctors to take her mother off the Ambien. Surprise! They did not know that one of its side effects was hallucinations. In less than 24 hours of taking her mother off the drug, the hallucinations stopped. Oh, and they then decided that she wasn't actually suffering from dementia after all. Which brings us to the prescription cascade.
The problem is that if Kristen hadn't been aware enough to challenge what she had been told, her mother would have become victim to what is known as a prescription cascade. A prescription cascade refers to the process whereby the side effects of drugs are misdiagnosed as symptoms of another problem resulting in further prescriptions and further side effects and unanticipated drug interactions. This may lead to further misdiagnoses, further symptoms--and further prescriptions to deal with the new drug induced symptoms. It's a road that once you start down is almost impossible to turn back as symptoms keep multiplying and worsening.
An estimated 35% of ambulatory older adults experience an adverse drug reaction each year; 29% of these reactions require hospitalization or a physician's care. These reactions can include falls, dementia, and urinary incontinence--all quite common in elderly patients. And again, those are only the "observable" side effects that are actually attributed to the drugs that caused them. The real numbers are much higher.
Too Many Doctors in the Room
The problem is further complicated, as we mentioned earlier, by the fact that many elderly patients see more than one specialist at time--all of whom are writing and renewing prescriptions independently of each other. For example, you might be seeing a cardiologist for blood pressure and cholesterol meds, an endocrinologist for blood sugar meds, a geriatrician for osteoporosis prescriptions, and a rheumatologist for drugs to slow down the beginnings of rheumatoid arthritis. Add in some over the counter Prevacid for acid reflux, and daily aspirin, not to mention any supplements you are taking, and pretty soon you're looking at a senior pushing 10-15 meds a day. And since the specialists aren't talking to each other, no one is watching over the possible unintended side effects caused by this adventure in polypharmacy.
And now it's time to talk about the elephant in the room--diminished capacity. Quite simply, the risk of diminished capacity increases steadily in older people with age and the number of medications used. Add to that the fact that nearly 50% of older adults take one or more medications that are not medically necessary. Research has clearly established a strong relationship between polypharmacy and negative clinical consequences. We're talking about cognitive impairment, functional decline, and falling.
- Cognitive impairment, that is delirium and dementia, has been associated with polypharmacy. A study in hospitalized older adults reported that the number of medications they were taking was a risk factor for delirium.24 In a prospective cohort study of 294 elders, 22% percent of patients taking 5 or less medications were found to have impaired cognition as opposed to 33% of patients taking 6-9 medications and 54% in patients taking 10 or more medications.25
- Polypharmacy has been associated with functional decline in older patients. In a prospective study of community-dwelling older adults, increased prescription medication use was associated with diminished ability to perform instrumental activities of daily living (IADLs) and decreased physical functioning.26 A study using data from the Women's Health and Aging Study found that use of 5 or more medications was associated with a reduced ability to perform IADLs.27 A prospective cohort of approximately 300 older adults found that patients taking 10 or more medications had diminished functional capacity and trouble performing daily tasks.28 As part of the Women's Health Initiative Observational study, polypharmacy was associated with incident disability in older women.29 In patients who have reported falling in the past year, higher medication use was found to be associated with functional decline.30
- Which brings us to falling. Falls are associated with increased morbidity and mortality in older adults and may be precipitated by certain medications. A study comparing patients who had not fallen to those who had fallen once and to those who had fallen multiple times reported that the number of medications was associated with an increased risk of falls.31 A study in older adult outpatients reported that as the number of medications increased, the falls risk index score increased and the duration of the one-leg standing test duration decreased.32 In a prospective cohort study, the use of 4 or more medications was associated with increased risk of falling and the risk of recurrent falls.33 A study in elderly patients with dementia reported that those patients who reported a fall had an increased prevalence of polypharmacy.34 In a study of institutionalized older adults, the risk of experiencing a fall within the previous 30 days went up by 7% for each additional medication.35
The problem with all of these side effects is that they diminish your ability to resist polypharmacy and its associated side effects. In other words, these very side effects dramatically increase your odds of having to "live" with those side effects for the rest of your life--if you call dementia, functional decline, and diminished capacity living. What do I mean by that? To put it in simpler terms, if you are suffering from dementia and delirium, how do you intelligently explain to your doctors while lying in your hospital bed, weak and confused, that the multiple medications they are pumping into you might be responsible for the very problems for which they're medicating you, and that if they would simply stop prescribing them, the problems would just as simply go away? In a test of wills, when polypharmacy has robbed you of your will, how do you win out over your doctors? It's not going to happen.
So What Can Be Done?
Ultimately, the best way to reduce polypharmacy is for doctors and hospitals to rethink their approach to health care. The current system is simply not geared to look at a patient holistically, to see how everything fits together. To make matters even worse, the study of the side effects associated with polypharmacy is in its infancy, so the odds of your doctors understanding that your infirmity could result from the drugs they've prescribed might not be good. Heck, as we learned from my mother-in-law's stay in the hospital, the doctors and nurses involved were not even aware of all the side effects associated with the single drug Ambien--let alone the problems associated with mixing drugs. So what can be done?
First and foremost, you want to take control before you head down polypharmacy freeway. Where appropriate, you want to explore non-pharmacologic alternatives to drugs, such as dietary changes and supplements. If you start early enough in life, you can do much of this on your own, preventing and reversing early stage symptoms while you still have time. If you wait until full stage disease sets in before you consider looking at alternatives, you will need to work with a doctor trained in non-pharmaceutical medicine as time is now against your trying to figure it out on your own.
And finally, as I have said multiple times before, if at all possible, if you find yourself being prescribed multiple drugs or being forced to take a trip to the hospital, get yourself an advocate who can stand up for you while you are incapacitated. Find someone who is willing to read up on polypharmacy and is willing to go toe-to-toe with your doctors if necessary. Understand, most doctors are very bright and very educated, but they are not gods. They are not infallible. There are times you need to challenge them. And I can guarantee you, they don't like it when you do. So you need someone who has a strong will to serve as your advocate. And if you are smart, you will find that person in advance--before you literally find yourself having passed through the doors into your own polypharmacy hell. As Dante Alighieri explained in the late Middle Ages, it's pretty difficult to get out of Hell once you've entered.
- 1. "IMS Health Study: 2014 a Record-Setting Year for U.S. Medicines." IMS Institute for Healthcare Informatics. 13 Apr 2015. (Accessed 10 Sep 2016.) http://www.imshealth.com/en/about-us/news/ims-health-study:-2014-a-record%E2%80%93setting-year-for-u.s.-medicines
- 2. Gandhi, T.K., S.N. Weingart, J. Borus, et al. "Adverse Drug Events in Ambulatory Care." N Engl J Med 348:16 (2003): 1556--1564. http://www.nejm.org/doi/full/10.1056/NEJMsa020703#t=article
- 3. "Understanding the Side Effects of Sleeping Pills." WebMD. (Accessed 16 Sep 2017.) http://www.webmd.com/sleep-disorders/guide/understanding-the-side-effects-of-sleeping-pills#1
- 4. Melinda Smith, Lawrence Robinson, Jeanne Segal, Anna Glezer. "Anxiety Medication." Helpguide.Org. June 2016. (Accessed 16 Sep 2016.) http://www.helpguide.org/articles/anxiety/anxiety-medication.htm
- 5. "Recognizing and Treating Depression." WebMD (Accessed 16 Sep 2016.) http://www.webmd.com/depression/symptoms-depressed-anxiety-12/antidepressants
- 6. "Do I Need Antihistamines for Allergies?" WebMD (Accessed 16 Sep 2016.) http://www.webmd.com/allergies/guide/antihistamines-for-allergies
- 7. Maher RL, Hanlon J, Hajjar ER. "Clinical consequences of polypharmacy in elderly." Expert Opin Drug Saf. 2014 Jan;13(1):57-65. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864987/
- 8. "Prescriptions per capita in the U.S. in 2013, by age group." Statista. (Accessed 10 Sep 2016.) http://www.statista.com/statistics/315476/prescriptions-in-us-per-capita-by-age-group/
- 9. Farrell B, Szeto W, Shamji S. "Drug-related problems in the frail elderly." Can Fam Physician. 2011 Feb;57(2):168-9. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038805/
- 10. John P. Cunha, "Coronary Heart Disease Medications." RxList. (Accessed 16 Sep 2016.) http://www.rxlist.com/coronary_heart_disease_medications-page2/drugs-condition.htm
- 11. "Cholesterol & Triglycerides Health Center." WebMD (Accessed 16 Sep 2016.) http://www.webmd.com/cholesterol-management/side-effects-of-statin-drugs?page=2
- 12. L. Anderson, "Common Side Effects, Allergies and Reactions to Antibiotics." Drugs.com. June 16, 2013. (Accessed 16 Sep 2016.) https://www.drugs.com/article/antibiotic-sideeffects-allergies-reactions.html
- 13. Annette (Gbemudu) Ogbru, Jay W. Marks. "Diuretics." RxList. (Accessed 16 Sep 2016.) http://www.rxlist.com/diuretics-page4/drugs-condition.htm
- 14. "Coumadin Side Effects." Drugs.com. (Accessed 16 Sep 2016.) https://www.drugs.com/sfx/coumadin-side-effects.html
- 15. "Oral Diabetes Medications Summary Chart." Joslin Diabetes Center. (Accessed 16 Sep 2016.) http://www.joslin.org/info/oral_diabetes_medications_summary_chart.html
- 16. "Side Effects Soar for Newer Classes of Diabetes Drugs." drugwatch. May 12, 2014. (Accessed 16 Sep 2016.)https://www.drugwatch.com/2014/05/12/increasing-side-effects-diabetes-drugs/
- 17. Theodore R. Fields. "Steroid Side Effects: How to Reduce Corticosteroid Side Effects." Hospital for Special Surgery. 7/17/2009. (Accessed 16 Sep 2016.) https://www.hss.edu/conditions_steroid-side-effects-how-to-reduce-corticosteroid-side-effects.asp
- 18. "Steroids to Treat Arthritis." MedicineNet.com. (Accessed 16 Sep 2016.) http://www.medicinenet.com/steroids_to_treat_arthritis/page4.htm
- 19. Jacquelyn Cafasso, George Krucik. healthline June 4, 2013. (Accessed 16 Sep 2016.) http://www.healthline.com/health/anticholinergics#Overview1
- 20. Annette (Gbemudu) Ogbru, Jay W. Marks. "NSAIDs (Nonsteroidal Antiinflammatory Drugs)." RxList. (Accessed 16 Sep 2016.) http://www.rxlist.com/nsaids_nonsteroidal_antiinflammatory_drugs-page2/drugs-condition.htm
- 21. Benyamin R, Trescot AM, Datta S, et al. "Opioid complications and side effects." Pain Physician. 2008 Mar;11(2 Suppl):S105-20. http://www.ncbi.nlm.nih.gov/pubmed/18443635
- 22. Zhou S1, Chan E, Pan SQ, Huang M, Lee EJ. "Pharmacokinetic interactions of drugs with St John's wort." J Psychopharmacol. 2004 Jun;18(2):262-76. http://www.ncbi.nlm.nih.gov/pubmed/15260917
- 23. Kimura Y1, Ito H, Hatano T. "Effects of mace and nutmeg on human cytochrome P450 3A4 and 2C9 activity." Biol Pharm Bull. 2010;33(12):1977-82. https://www.jstage.jst.go.jp/article/bpb/33/12/33_12_1977/_pdf
- 24. Martin NJ, Stones MJ, Young JE, et al. "Development of delirium: a prospective cohort study in a community hospital." International Psychogeriatrics. 2000;12:117--27. http://www.ncbi.nlm.nih.gov/pubmed/10798458
- 25. Jyrkka J, Enlund H, Lavikainen P, et al. "Association of polypharmacy with nutritional status, functional ability and cognitive capacity over a three-year period in an elderly population." Pharmacoepidemiol Drug Saf. 2010;20:514--522. http://www.ncbi.nlm.nih.gov/pubmed/21308855
- 26. Magaziner J, Cadigan DA, Fedder DO, Hebel JR. "Medication use and functional decline among community-dwelling older women." J Aging Health. 1989;1:470--484. http://jah.sagepub.com/content/1/4/470.abstract
- 27. Crenstil V, Ricks MO, Xue QL, Fried LP. "A pharmacoepidemiologic study of community-dwelling, disabled older women: factors associated with medication use." Am J Geriatr Pharmacother. 2010;8:215--224. http://www.ncbi.nlm.nih.gov/pubmed/20624611
- 28. Jyrkka
- 29. Rosso AL, Eaton CB, Wallace R, et al. "Geriatric syndromes and incident disability in older women: results from the Women's Health Initiative Observational Study." J Am Geriatr Soc. 2013 Mar; 61(3): 371--379. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602348/
- 30. Stel VS, Smit JH, Plujim SM, Lips P. "Consequences of falling in older men and women and risk factors for health service use and functional decline." Age Aging. 2004;33:58--65. http://ageing.oxfordjournals.org/content/33/1/58.long
- 31. Fletcher PC, Berg K, Dalby DM, Hirdes JP. "Risk factors for falling among community-based seniors." J Patient Saf. 2009;5:61--66. http://www.ncbi.nlm.nih.gov/pubmed/19920442
- 32. Kojima T, Akishita M, Nakamura T, et al. "Association of polypharmacy with fall risk among geriatric outpatients." Geriatr Gerontol Int. 2011;11:438--444. http://www.ncbi.nlm.nih.gov/pubmed/21545384
- 33. Tromp AM, Plujim SM, Smit JH, et al. "Fall-risk screening test: a positive study of predictors for falls in community-dwelling elderly." J Clin Epidemiol. 2001;54:837--844. http://www.ncbi.nlm.nih.gov/pubmed/11470394
- 34. Lee CY, Chen LK, Lo YK, et al. "Urinary incontinence: an under-recognized risk factor for falls among elderly dementia patients." Neurourol Urodyn. 2011;30:1286--90. http://www.ncbi.nlm.nih.gov/pubmed/21538498
- 35. Damian J, Pastor-Barriuso R, Valderrama-Gama E, de Pedro-Cuesta J. "Factors associated with falls among older adults living in institutions." BMC Geriatr. 2013;13:6. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566955/