Medication Use in the Elderly

Aka: Medication Use in the Elderly, Beer's List, Beers List, Beers Criteria, Beers' Criteria, Screening Tool of Older Persons' potentially inappropriate Prescriptions, STOPP, Medications to Avoid in Older Adults

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II. Epidemiology

  1. As many as 90% of acute adverse druge events are due to medications not on STOPP or Beers List
    1. Oral Anticoagulants (esp. Warfarin)
    2. Antiplatelet medications
    3. Diabetic medications (esp. Insulin)
    4. Medications with narrow therapeutic window (esp. Digoxin)

III. Background: Sources of information

  1. Beers' Criteria
  2. Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP)

IV. Pathophysiology: Factors in older adults that increase Drug Reaction risk

  1. Hepatic Blood Flow reduced 40% in older adults
    1. Reduced first pass clearance
  2. Renal Blood Flow reduced 50% by age 80 years
    1. Creatinine Clearance decreases by 6-10% per decade after age 40 years old
    2. Chronic Kidney Disease affects 50% of older adults
    3. Check Renal Function before starting agents and periodically (dose adjustment may be needed)
  3. Congestive Heart Failure affects 40% by age 80 years
  4. Drug distribution altered in older adults
    1. Serum Proteins reduced resulting in decreased drug Protein binding
      1. Albumin-bound drugs (Warfarin, Phenytoin, salicylic acid) increase free drug concentrations
    2. Decreased ratio of Lean Body Weight to body fat
      1. Water soluble drugs have decreased volume of distribution
      2. Water soluble drugs (e.g. Digoxin, Alcohol) have increased initial blood concentrations
      3. Fat soluble drugs (e.g. Benzodiazepines, Phenytoin) have prolonged Half-Life and effects
  5. Medication absorption altered in older adults
    1. Increased gastric pH
    2. Decreased intestinal motility
    3. Decreased splanchnic Blood Flow

V. Adverse Effects: Predictors of adverse drug effects in elderly

  1. Age 85 years or older
  2. Multiple chronic medical conditions (6 or more)
  3. Creatinine Clearance <50 ml/min
  4. Low Body Mass Index
  5. Polypharmacy
    1. Medications number nine or more
    2. More than 12 medication doses daily
  6. References
    1. Fouts (1997) Consultant Pharmacist 12:1103-11 [PubMed]

VI. Management: Methods to improve Medication Compliance

  1. Reduce number of daily doses (once daily is best)
  2. Time doses to meal times
  3. Establish partnerships to ensure compliance
    1. Patient
    2. Family (educate on indications and adverse effects)
    3. Pharmacists
    4. Home health aids
  4. Use devices that aid taking of medication
    1. Pill boxes and pill calendars
    2. Label containers with large type
    3. Pill containers should open easily
    4. Keep accurate medication list
  5. Ensure easy access to medications
    1. Affordability
    2. Medication delivery
  6. Evaluate for patient factors affecting compliance
    1. Dementia
    2. Major Depression

VII. Medications: To use lower dosages (decreased clearance)

  1. Decreased Renal Clearance in the elderly
    1. Aminoglycosides
    2. Vancomycin
    3. Fluoroquinolones
    4. Penicillins
    5. Imipenem
    6. Digoxin (limit dose to 0.125 mg/day, consider qod)
    7. ACE Inhibitors
    8. Beta Blockers (Atenolol, Nadolol)
    9. Sotalol
    10. Glyburide (avoid in general)
    11. Ranitidine, Cimetidine, Famotidine
    12. Lithium
  2. Decreased Hepatic Clearance in the elderly
    1. Benzodiazepines (avoid in general - see below)
    2. Calcium Channel Blockers
    3. Lidocaine
    4. Phenytoin
    5. Celecoxib (Celebrex)
    6. Theophylline
    7. Imipramine or Desipramine, Trazodone
    8. Isoniazid
    9. Procainamide

VIII. Medications: Avoid in age >65 - Short List

  1. Beer's List most common items
    1. Sedating Antihistamines (e.g. Diphenhydramine)
    2. Long acting Benzodiazepines (e.g. Diazepam)
    3. Tricyclic Antidepressants (e.g. Amitriptyline)
    4. Antispasmodics (e.g. Oxybutynin, Dicyclomine)
    5. Fick (2003) Arch Intern Med 163:2716 [PubMed]
  2. STOPP List most common items (in addition to those on short Beer's List)
    1. Non-selective Beta Blockers
    2. Proton Pump Inhibitors
    3. Ryan (2009) Br J Clin Pharmacol 68(6): 936-47 [PubMed]

IX. Medications: Neuropsychiatric Agents to avoid in age >65

  1. General
    1. Avoid combining 3 or more neuropsychiatric agents
  2. Anticholinergic Agents
    1. See Anticholinergic Medication
    2. See First Generation Antihistamines, antispasmodics, Tricyclic Antidepressants and antiparkinson agents below
  3. Selective Serotonin Reuptake Inhibitors (SSRI)
    1. Associated with increased Fall Risk more than TCA agents
      1. Boyle (2010) Clin Geriatr Med 26(4): 583-605 [PubMed]
    2. Prozac is no longer contraindicated in the elderly despite long Half-Life (as safe as other SSRIs)
    3. Avoid SSRIs if non-iatrogenic Hyponatremia with Serum Sodium <130 mmol/L in last 2 months (STOPP)
  4. Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
    1. Risk of falls, Fracture
  5. Tricyclic Antidepressants (TCA)
    1. Avoid TCA Agents in general due to potent Anticholinergic and sedating effects
      1. Most Anticholinergic and sedating agents: Amitriptyline, Doxepin, Imipramine
      2. Nortriptyline may be slightly less Anticholinergic
      3. Consider less sedating alternatives for pain management: Neurontin, Lyrica
      4. Newer Antidepressants are preferred (e.g. SSRI, SNRI)
    2. Indications to avoid TCA agents (STOPP)
      1. Dementia due to Cognitive Impairment
      2. Glaucoma due to exacerbation risk
      3. Cardiac conduction abnormalities due to pro-arrhythmic effect
      4. Constipation or in combination with Opioids or Calcium Channel Blockers due to exacerbation risk
      5. Benign Prostatic Hyperplasia due to urinary obstruction risk
  6. First-Generation Sedating Antihistamines
    1. Examples: Brompheniramine, Diphenhydramine (Benadryl), Hydroxyzine (Atarax), Chlorpheniramine, Cyproheptadine
      1. Includes combination products (e.g Tylenol PM)
    2. Avoid use longer than one week (STOPP)
    3. Use newer Non-Sedating Antihistamines (e.g. Claritin, Allegra, Zyrtec) in place of Sedating Antihistamines
    4. Avoid Antihistamines for Insomnia management
    5. Avoid if at least one fall in the last 3 months (STOPP)
  7. Barbiturates (e.g. Butalbital such as Fiorinal, Nembutal, Secobarbital or Seconal, Pentobarbital, Phenobarbital)
    1. High risk of dependence and tolerance
  8. Benzodiazepines (Librium or Chlordiazepoxide, Valium or Diazepam, Ativan or Lorazepam, Xanax or Alprazolam)
    1. Increased risk of physical performance decline, confusion, sedation, falls
      1. Older adults are more sensitive to the effects of Benzodiazepines
    2. Avoid longer acting agents (e.g. Clonazepam) or those with long acting metabolites (e.g. Diazepam)
      1. Older adults have decreased metabolism of longer-acting Benzodiazepines
      2. Librium (Chlordiazepoxide) may be indicated in specific cases
        1. Examples: Seizure Disorders, Benzodiazepine or Alcohol Withdrawal
      3. Use shorter acting agents if Benzodiazepine use is not avoidable (e.g. Ativan, Restoril)
    3. Use Benzodiazepines only with caution
      1. Use lower doses (<1 mg Ativan, <15 mg Restoril)
      2. Avoid use longer than 1 month (STOPP)
      3. Avoid if at least one fall in the last 3 months (STOPP)
    4. Avoid Benzodiazepine analogs used in Insomnia (e.g. Ambien, Sonata, Lunesta)
      1. Avoid these agents for any duration (previously limited to 3 months)
      2. Increased risk of Delirium, falls, Fractures, MVAs resulting in increased ED visits, hospitalizations
      3. Minimal improvement in Sleep Latency and sleep duration
      4. See Insomnia for alternative agents
    5. References
      1. Gray (2003) J Am Geriatr Soc 51:1563-70 [PubMed]
  9. Neuroleptics (first and second generation Antipsychotics)
    1. Avoid Haloperidol (Haldol) due to two fold increase in mortality in older Nursing Home residents
      1. Consider Quetiapine (Seroquel) as alternative
      2. Huybrechts (2012) BMJ 344:e977 [PubMed]
    2. Avoid longterm use >1 month
    3. Avoid Antipsychotics in Parkinsonism (STOPP)
      1. If used, Primavanserin, Quetiapine and Clozapine are preferred over other Antipsychotics
    4. Avoid Anticholinergic Medications to treat Extrapyramidal Side Effects of Antipsychotic agents (STOPP)
    5. Avoid if at least one fall in the last 3 months (STOPP)
    6. Avoid Antipsychotics as first-line agent for behavioral problems in Dementia and acute Delirium
      1. See Agitation in Dementia
      2. Increased risk of CVA and in Dementia, greater cognitive decline and mortality risk
      3. Limit Antipsychotics to cases of failed non-pharmacologic measures and careful evaluation
  10. Meprobamate
    1. Highly addictive and sedating
  11. Stimulants
    1. Amphetamines
    2. Methylphenidate (Ritalin)
  12. Skeletal Muscle Relaxants
    1. Cyclobenzaprine (Flexeril)
    2. Carisoprodolor (Soma)
    3. Methocarbamol (Robaxin)
    4. Poorly tolerated in elderly (Anticholinergic, sedating) with significant Fall Risk
  13. Thioridazine (Mellaril)
  14. Cholinesterase Inhibitors (e.g. Aricept) in patients with Syncope
  15. Antiparkinsonism agents
    1. Benztropine
    2. Trihexyphenidyl
  16. Scopolamine

X. Medications: Cardiovascular Agents to avoid in age >65

  1. Amiodarone
    1. Risk of QT Prolongation and Torsade de Pointes
    2. Not a first line agent in Atrial Fibrillation, unless rhythm control and comorbid LVH or CHF
  2. Disopyramide (Norpace)
    1. Highly Anticholinergic and risk of Congestive Heart Failure
  3. Dronedarone
    1. Avoid in permanent Atrial Fibrillation or severe CHF (or recent decompensation)
  4. Alpha Adrenergic Central Agonist (e.g. Methyldopa, Reserpine >0.1 mg/day, Guanabenz, Guanfacine, Clonidine)
    1. High risk of CNS effects, and may cause Orthostatic Hypotension and Bradycardia
    2. Clonidine may be used, but avoid as a first-line agent
  5. Alpha Adrenergic Antagonist (e.g. Prazosin, Doxazosin, Terazosin)
    1. High risk of Orthostatic Hypotension
    2. Other Antihypertensive agents are preferred for better efficacy
  6. Digoxin >125 mcg daily
    1. Avoid longterm use at >125 mcg if GFR <50 ml/min (STOPP)
    2. Limit use to Congestive Heart Failure and Atrial Fibrillation
      1. Not a first-line agent in either CHF or Atrial Fibrillation
  7. Loop Diuretic
    1. Avoid use for Lower Extremity Edema only (e.g. no history of Heart Failure, STOPP)
    2. Avoid use as first-line monotherapy for Hypertension (STOPP)
  8. Thiazide Diuretic
    1. Avoid use in Gouty Arthritis (STOPP)
  9. Beta Blockers
    1. Avoid Non-selective Beta Blockers such as Propranolol in COPD (STOPP)
    2. Avoid Beta Blocker in combination with Verapamil due to AV Nodal block risk (STOPP)
    3. Avoid in Diabetes Mellitus with more than 1 hypoglycemic episode monthly (STOPP)
      1. Risk of masking hypoglycemic symptoms
  10. Calcium Channel Blockers
    1. Avoid Diltiazem or Verapamil in NYHA Class III or Class IV Heart Failure due to exacerbation risk (STOPP)
    2. Avoid short acting Nifedipine (Hypotension, Myocardial Ischemia risk)
  11. Vasodilators
    1. Avoid in persistent Postural Hypotension
      1. SBP drop on standing >20 mmHg if at least one fall in the last 3 months (STOPP)

XI. Medications: Endocrine Agents to avoid in age >65

  1. Chlorpropamide (Diabinese)
    1. Prolonged half life in elderly with risk of prolonged Hypoglycemia (STOPP)
    2. May also cause SIADH
  2. Sulfonylureas
    1. Avoid Sulfonylureas overall in older patients
    2. Risk of Hypoglycemia, cardiovascular events and all cause mortality
    3. Greatest risk is with Glyburide and Glimepiride (Sulfonylureas)
      1. Risk of severe, prolonged Hypoglycemia (esp. if combined with trimethoprim-sulfamethoxazole, Alcohol, Insulin)
    4. Lowest risk is with Glipizide
      1. Lower risk of Hypoglycemia and also has a shorter duration
  3. Pioglitazone (Actos)
    1. Avoid in Heart Failure
  4. Sliding Scale Insulin
    1. Risk of Hypoglycemia when Insulin Sliding Scale is used as only Insulin regimen
    2. Does not apply to scheduled bolus Insulin Dosing per Carbohydrate with correction Insulin
      1. Typically additional units added for current Hyperglycemia (e.g. 1 unit/50 over 150)
  5. SGLT2 Inhibitors
    1. Exercise caution due to adverse effects (e.g. Urinary Tract Infection, Euglycemic DKA)
    2. Benefits (e.g. renal protection, CHF) often outweigh risks
  6. Desiccated Thyroid (Armour Thyroid)
    1. Safer Thyroid Replacement alternatives exist (without the same Cardiovascular Risks)
  7. Methyltestosterone or Testosterone
    1. Avoid unless significant symptomatic, confirmed Hypogonadism
    2. May increase Cardiovascular Risk
    3. Provokes BPH and contraindicated in Prostate Cancer
  8. Megestrol
    1. Low efficacy for stimulation of appetite
    2. Risk of thrombosis
  9. Estrogens
    1. Avoid Estrogen if history of VTE or Breast Cancer (STOPP)
    2. Avoid Unopposed Estrogen without Progesterone with intact Uterus (STOPP)
    3. Vaginal Estrogens are effective for localized symptoms
      1. Offer instead of systemic Estrogens
    4. Avoid systemic Estrogens (transdermal, oral) in older patients
      1. If systemic Estrogens are used, limit to lowest effective dose
  10. Growth Hormone
    1. Only indicated for replacement after Pituitary Gland removal
    2. Avoid use for effects on body composition (minimal efficacy and adverse effects)

XII. Medications: Analgesic Agents to avoid in age >65

  1. Opioids
    1. Maximize non-medication pain therapy and non-Opioids
    2. Opioids have higher adverse effects in elderly (e.g. Delirium)
      1. However, untreated pain is also associated with adverse effects (e.g. Delirium)
    3. Start low dose (less than the standard Morphine Equivalent dose of 0.1 mg/kg)
    4. Avoid longterm Opioids if at least one fall in the last 3 months (STOPP)
    5. Avoid longterm high potency Opioids (e.g. Morphine, Fentanyl)
      1. Do not use as first-line management of mild to moderate pain (STOPP)
    6. Avoid regular Opioids for more than 2 weeks if Chronic Constipation without bowel regimen (STOPP)
      1. Use prophylactic bowel regimen
      2. See Constipation Prophylaxis in Chronic Opioid Use
    7. Avoid longterm Opioids in Dementia patients
      1. Exception: Palliative Care or moderate-severe Chronic Pain (STOPP)
    8. Avoid in combination with Benzodiazepines, Gabapentin, Pregabalin (sedation and Overdose risk)
    9. Avoid Tramadol (Hyponatremia risk due to SIADH)
    10. Avoid Meperidine (Demerol) completely
      1. Lower efficacy, and neurotoxicity risk (including Seizure, Delirium) especially in CKD
    11. Avoid Propoxyphene (Darvon) completely
    12. Avoid Pentazocine (Talwin)
      1. CNS Adverse effects (confusion, Hallucinations) more than other Opioid Analgesics
  2. Corticosteroids
    1. Avoid use longer than 3 months as monotherapy for Rheumatoid Arthritis, gout or Osteoarthritis (STOPP)
  3. NSAIDs
    1. NSAIDS risk Upper GI Bleed at 1% with use at 3-6 months, and 2-4% with use at 12 months
      1. Concurrent PPI or Misoprostol reduces GI Bleeding risk, but does not eliminate it
    2. Limit to low dose, short duration, short Half-Life
      1. Avoid use longer than 3 months for mild osteoarthritic pain (STOPP)
      2. Avoid prolonged use for gout prevention in place of Allopurinol when not contraindicated (STOPP)
      3. Use alternative management (e.g. Acetaminophen, Contrast Bath)
      4. If an NSAID is used, Naproxen is preferred over Ibuprofen or Ketorolac
    3. NSAIDs to avoid completely
      1. Indomethacin (CNS and gastrointestinal effects)
      2. Ketorolac (Toradol)
        1. Even Parenteral use increases GI Bleed and acute injury risk in the elderly
        2. Other NSAIDs are preferred over oral Ketorolac
      3. Long-acting NSAIDs (Feldene, Naprosyn, Daypro)
    4. Avoid use completely in high risk patients
      1. Over age 75 years
      2. GFR <50 ml/min (STOPP)
      3. Concurrent Corticosteroid use
      4. Concurrent Anticoagulant use such as Warfarin or DOAC such as Xarelto or Pradaxa (STOPP)
      5. Concurrent antiplatelet agent (e.g. Clopidogrel or Plavix)
      6. History of PUD or GI Bleeding and no GI prophylaxis with H2 Blocker, PPI, or Misoprostol (STOPP)
      7. Moderate to Severe Hypertension with BP >160/100 mmHg due to exacerbation risk (STOPP)
      8. Congestive Heart Failure history due to exacerbation risk (STOPP)

XIII. Medications: Gastrointestinal and Genitourinary Agents to avoid in age >65

  1. Antiemetics
    1. Avoid Phenergan and Tigan
    2. Avoid Metoclopramide (Reglan)
      1. Risk of Extrapyramidal Side Effects (e.g. Tardive Dyskinesia), esp. in frail elderly
      2. May be continued in Gastroparesis (but avoid use longer than 12 weeks)
    3. Avoid Prochlorperazine (Compazine) in Parkinsonism due to exacerbation risk (STOPP)
    4. Avoid Pheothiazines (e.g. Compazine) in Epilepsy due to exacerbation risk (STOPP)
  2. Gastrointestinal antispasmodics (e.g. Donnatal, Bentyl or Dicyclomine, Levsin or Hyoscyamine, Clidinium)
    1. Avoid Anticholinergic antispasmodic drugs in Chronic Constipation (STOPP)
  3. Antidiarrheal agents (Lomotil, Imodium, Codeine)
    1. Avoid antidiarrheals in Diarrhea of unknown cause
      1. Risk of Toxic Megacolon and exacerbation of overflow Diarrhea (STOPP)
    2. Avoid antidiarrheals in Dysentery (bloody Diarrhea, fever, toxicity) due to risk of exacerbation (STOPP)
  4. Proton Pump Inhibitors (PPIs e.g. Omeprazole)
    1. Avoid >8 weeks at high dose Peptic Ulcer Disease management doses (STOPP)
    2. Consider H2 Receptor Antagonists (e.g. Ranitidine) instead
    3. Stop or if continuation indicated (e.g. severe GERD, Barrett's Esophagus), decrease to standard dosing
    4. PPIs increase the risk of Clostridium difficile, Fractures and Pneumonia
  5. Laxatives
    1. Avoid Stimulant Laxatives
      1. Worsen bowel function in elderly
    2. Mineral Oil
      1. Avoid oral Mineral Oil due to aspiration risk
  6. Urinary Antispasmodics (e.g. Ditropan)
    1. Typically marginal benefit does not outweigh significant Anticholinergic effects
    2. Look for other causes of Urinary Incontinence (e.g. Cholinesterase Inhibitors such as Aricept)
    3. Avoid use if contraindicating conditions (STOPP)
      1. Dementia
      2. Chronic Glaucoma
      3. Chronic Constipation
      4. Benign Prostatic Hyperplasia (BPH) with obstruction
    4. Manage with non-medication measures
      1. Limit Caffeine
      2. Limit fluids before bedtime
      3. Consider Bladder TrainingExercises
  7. Alpha-Blockers
    1. Avoid alpha-blockers with one or more episodes of daily Incontinence due to exacerbation risk (STOPP)
    2. Indwelling Urinary Catheter present >2 months due to lack of indication (STOPP)
  8. Desmopressin
    1. Avoid for Nocturia
    2. Risk of Hyponatremia

XIV. Medications: Respiratory Agents to avoid in age >65

  1. Inhaled Anticholinergics (Atrovent, Spiriva)
    1. Avoid in men with severe BPH
    2. Avoid nebulized Ipratropium in Glaucoma due to exacerbation risk (STOPP)
  2. Theophylline
    1. Avoid as monotherapy for COPD due to safer alternatives with better efficacy (STOPP)
  3. Systemic Corticosteroids
    1. Avoid in place of Inhaled Corticosteroids as maintenance therapy in moderate to severe COPD (STOPP)

XV. Medications: Hematologic Agents to avoid in age >65

  1. Avoid antiplatelet agents such as Aspirin, Dipyridamole or Clopidogrel in concurrent Bleeding Disorder (STOPP)
  2. Aspirin
    1. Avoid for primary prevention in over age 80 years old (and with caution over age 70 yo)
    2. Avoid without cardiovascular indication such as CAD, PAD, CVA (STOPP)
    3. Avoid as treatment for undifferentiated Dizziness
    4. Avoid dose >150 mg daily due to increased bleeding risk without added efficacy (STOPP)
    5. Avoid without the use of GI Protection (e.g. H2 Blocker or Proton Pump Inhibitor, STOPP)
      1. Concurrent Warfain use
      2. History of Peptic Ulcer Disease in the last year
  3. Warfarin
    1. Direct Oral Anticoagulants (DOACs) are preferred unless Warfarin is specifically indicated (e.g. Mechanical Heart Valve)
    2. Avoid >6 months for first uncomplicated DVT or >12 months for first uncomplicated PE (STOPP)
    3. Multiple significant Drug Interactions (e.g. Amiodarone, Anticholinergics)
  4. Rivaroxaban (Xarelto)
    1. If DOAC is needed, Apixaban (Eliquis) may be preferred age >75 due to Lower Gastrointestinal Bleeding risk
  5. Dabigatran (Pradaxa)
    1. Avoid in severe Chronic Kidney Disease
    2. If DOAC is needed, Apixaban (Eliquis) may be preferred age >75 due to Lower Gastrointestinal Bleeding risk
  6. Ticagrelor (Brilinta) and Prasugrel (Effient)
    1. Clopidogrel (Plavix) is preferred when Platelet ADP Receptor Antagonist is indicated
    2. Avoid in over age 75 years old due to higher bleeding risk than with Clopidogrel
  7. Ticlopidine
    1. Use safer alternatives
  8. Dipyridamole (short-acting agent)
    1. Avoid as monotherapy for cardiovascular secondary prevention (STOPP)
      1. Lack of efficacy and risk of Orthostatic Hypotension
      2. Does not apply to intravenous use during Pharmacologic Stress Testing
    2. Does not apply to long acting combination product with Aspirin (Aggrenox) if specific indications

XVI. Medications: Antibiotics to avoid in age > 65

  1. Nitrofurantoin (Macrobid)
    1. May worsen Renal Insufficiency and risk interstitial fibrosis
      1. See Acute Nitrofurantoin Pulmonary Toxicity
    2. Avoid if Creatinine Clearance <30 ml/min (previously not recommended if <60 ml/min)
    3. Avoid for longterm UTI prophylaxis in the elderly
  2. Trimethoprim-Sulfamethoxazole
    1. Hyperkalemia risk when combined with ACE Inhibitor (or Angiotensin Receptor Blocker) or with reduced Renal Function

XVII. References

  1. (2023) Presc Lett 30(8): 44
  2. (2017) Presc Lett 24(8): 48
  3. (2015) Presc Lett 22(12): 67-8
  4. (2012) Presc Lett 19(6): 35
  5. (2011) Presc Lett 18(12): 69
  6. Pham (2018) Crit Dec Emerg Med 32(5):19-28
  7. (2023) J Am Geriatr Soc 71(7): 2052-81 [PubMed]
  8. Curtis (2004) Arch Intern Med 164:1621-5 [PubMed]
  9. Fick (2003) Arch Intern Med 163:2719-20 [PubMed]
  10. Fick (2019) J Am Geriatr Soc 67(4):674-94 [PubMed]
  11. Gallagher (2008) Age Ageing 37:673-9 [PubMed]
  12. Mcleod (1997) CMAJ 156:385-91 [PubMed]
  13. Pretorius (2013) Am Fam Physician 87(5): 331-6 [PubMed]
  14. Williams (2002) Am Fam Physician 66(10):1917-24 [PubMed]

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