Which concept will the nurse consider when integrating Milos framework into nursing practice?

The MAI was designed to assist physicians and pharmacists in assessing the appropriateness of a medication for a given patient. The MAI requires clinicians to rate 10 explicit criteria to determine whether a given medication is appropriate for an individual. For each criterion, the index has operational definitions, explicit instructions and examples, and the evaluator rates whether the particular medication is "appropriate," "marginally appropriate" or "inappropriate" (Table 3).

Medication Appropriateness Index

To assess the appropriateness of the drug, please answer the following questions and circle the applicable score.
1. Is there an indication for the drug? Comments:	1	2	3	9 DK
Indicated		Not Indicated
2. Is the medication effective for the condition? Comments:	1	2	3	9 DK
Effective		Ineffective
3. Is the dosage correct? Comments:	1	2	3	9 DK
Correct		Incorrect
4. Are the directions correct? Comments:	1	2	3	9 DK
Correct		Incorrect
5. Are the directions practical? Comments:	1	2	3	9 DK
Practical		Impractical
6. Are there clinically significant drug‐drug interactions? Comments:	1	2	3	9 DK
Insignificant		Significant
7. Are there clinically significant drug‐disease/condition interactions? Comments:	1	2	3	9 DK
Insignificant		Significant
8. Is there unnecessary duplication with other drug(s)? Comments:	1	2	3	9 DK
Necessary		Unnecessary
9. Is the duration of therapy acceptable? Comments:	1	2	3	9 DK
Acceptable		Unacceptable
10. Is this drug the least expensive alternative compared with others of equal utility? Comments:	1	2	3	9 DK
Least expensive		Most expensive

The 10 explicit criteria are:

Indication: the sign, symptom, disease or condition for which the medication is prescribed.
Effectiveness: producing a beneficial result.
Dosage: total amount of medication taken per 24‐hour period.
Directions: instructions to the patient for proper use of a medication.
Practicality: capability of being used or being put into practice.
Drug–drug interaction: the effect that administration of one medication has on another drug; clinical significance connotes a harmful interaction.
Drug‐disease interaction: the effect that the drug has on a pre‐existing disease or condition; clinical significance connotes a harmful interaction.
Unnecessary duplication: non‐beneficial or risky prescribing of two or more drugs from the same chemical or pharmacological class.
Duration: length of therapy.
Expensiveness: cost of drug in comparison with other agents of equal efficacy and safety.

These are measured on a 3‐point scale (Table 3).

To assess the effects of the interventions on prescribing appropriateness, patient MAI scores may be determined by summing MAI medication scores across all evaluated medications. Thus, this patient MAI score depends on the number of medications taken by the patient and the MAI score per medication.

Furthermore, to determine a single summated score for each drug, in addition to an overall score for the patient, a weighting scheme was developed. A weight of three was given for indication and effectiveness. A weight of two was assigned to dosage, correct directions, drug‐drug interactions and drug‐disease interactions. A weight of one was assigned to practical directions, expense, duplication and duration.

The Beers criteria are consensus explicit criteria used to enhance safe medication use in older adults when precise clinical information is lacking (see Table 4; Table 5; Table 6; Table 7; Table 8). The Beers criteria are based on expert consensus developed through an extensive literature review with a bibliography and a questionnaire evaluated by nationally recognised experts in geriatric care, clinical pharmacology and psychopharmacology using a modified Delphi technique to reach consensus. These criteria have been used to survey clinical medication usage, to analyse computerised administrative data sets and to evaluate intervention studies to decrease medication problems in older adults.

Updated Beers (2003) criteria for potentially inappropriate medication use in older adults: independent of diagnosis or condition

Drug	Concern	Severity rating (high or low)
Propoxyphene (Darvon) and combination products (Darvon with ASA, Darvon‐N and Darvocet‐N)	Offers few analgesic advantages over paracetamol (acetaminophen), yet is associated with the adverse effects of other narcotic drugs	Low
Indomethacin (Indocin and Indocin SR)	Of all available NSAIDs, this drug produces the most CNS adverse effects	High
Pentazocine (Talwin)	Narcotic analgesic that causes more CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs. Additionally, it is a mixed agonist and antagonist	High
Trimethobenzamide (Tigan)	One of the least effective antiemetic drugs, yet it can cause extrapyramidal adverse effects	High
Muscle relaxants and antispasmodics: methocarbamol (Robaxin), carisoprodol (Soma), chlorzoxazone (Paraflex), metaxalone (Skelaxin), cyclobenzaprine (Flexeril) and oxybutynin (Ditropan). Do not consider the extended‐release formulation of Ditropan XL	Most muscle relaxants and antispasmodic drugs are poorly tolerated by elderly patients because they cause anticholinergic adverse effects, sedation and weakness. Additionally, their effectiveness at doses tolerated by elderly patients is questionable	High
Flurazepam (Dalmane)	This benzodiazepine hypnotic has an extremely long half‐life in elderly patients (often days), producing prolonged sedation and increasing the incidence of falls and fracture. Medium‐ or short‐acting benzodiazepines are preferable	High
Amitriptyline (Elavil), chlordiazepoxide‐amitriptyline (Limbitrol) and perphenazine‐amitriptyline (Triavil)	Because of its strong anticholinergic and sedation properties, amitriptyline is rarely the antidepressant of choice for elderly patients	High
Doxepin (Sinequan)	Because of its strong anticholinergic and sedating properties, doxepin is rarely the antidepressant of choice for elderly patients	High
Meprobamate (Miltown and Equanil)	This is a highly addictive and sedating anxiolytic. Those using meprobamate for prolonged periods may become addicted and may need to be withdrawn slowly	High
Doses of short‐acting benzodiazepines: doses greater than lorazepam (Ativan) 3 mg; oxazepam (Serax) 60 mg; iprazolam (Xanax) 2 mg; temazepam (Restoril) 15 mg and triazolam (Halcion) 0.25 mg	Because of increased sensitivity to benzodiazepines in elderly patients, smaller doses may be effective and safer. Total daily doses should rarely exceed the suggested maximum	High
Long‐acting benzodiazepines: chlordiazepoxide (Librium), chlordiazepoxide‐amitriptyline (Limbitrol), clidinium‐chlordiazepoxide (Librax), diazepam (Valium), quazepam (Doral), halazepam (Paxipam) and chlorazepate (Tranxene)	These drugs have a long half‐life in elderly patients (often several days), producing prolonged sedation and increasing the risk of falls and fractures. Short‐ and intermediate‐acting benzodiazepines are preferred if a benzodiazepine is required	High
Disopyramide (Norpace and Norpace CR)	Of all antiarrhythmic drugs, this is the most potent negative inotrope and therefore may induce heart failure in elderly patients. It also has strong anticholinergic effects. Other antiarrhythmic drugs should be used as well	High
Digoxin (Lanoxin) (should not exceed 0.125 mg/d except when treating atrial arrhythmias)	Decreased renal clearance may lead to increased risk of toxic effects	Low
Short‐acting dipyridamole (Persantine). Do not consider the long‐acting dipyridamole (which has better properties than the short‐acting formulation in older adults) except with patients with artificial heart valves	May cause orthostatic hypotension	Low
Methyldopa (Aldomet) and methyldopa‐hydrochlorothiazide (Aldoril)	May cause bradycardia and exacerbate depression in elderly patients	High
Reserpine at doses > 0.25 mg	May induce depression, impotence, sedation and orthostatic hypotension	Low
Chlorpropamide (Diabinese)	It has a prolonged half‐life in elderly patients and could cause prolonged hypoglycaemia. Additionally, it is the only oral hypoglycaemic agent that causes SIADH	High
GI antispasmodic drugs: dicyclomine (Bentyl), hyoscyamine (Levsin and Levsinex), propantheline (Pro‐Banthine), belladonna alkaloids (Donnatal and others) and clidinium‐chlordiazepoxide (Librax)	GI antispasmodic drugs have potent anticholinergic effects and have uncertain effectiveness. These drugs should be avoided (especially for long‐term use)	High
Anticholinergics and antihistamines: chlorpheniramine (Chlor‐Trimeton), diphenhydramine (Benadryl), hydroxyzine (Vistaril and Atarax), cyproheptadine (Periactin), promethazine (Phenergan), tripelennamine, dexchlorpheniramine (Polaramine)	All non‐prescription and many prescription antihistamines may have potent anticholinergic properties. Non‐anticholinergic antihistamines are preferred in elderly patients for the treatment of allergic reactions	High
Diphenhydramine (Benadryl)	May cause confusion and sedation. Should not be used as a hypnotic, and when used to treat emergency allergic reactions, it should be used in the smallest possible dose	High
Ergot mesyloids (Hydergine) and cyclandelate (Cyclospasmol)	Have not been shown to be effective in the doses studied	Low
Ferrous sulphate > 325 mg/d	Doses > 325 mg/d do not dramatically increase the amount absorbed but greatly increase the incidence of constipation	Low
All barbiturates (except phenobarbital) except when used to control seizures	Are highly addictive and cause more adverse effects than most sedative or hypnotic drugs in elderly patients	High
Meperidine (Demerol)	Not an effective oral analgesic in doses commonly used. May cause confusion and has many disadvantages compared with other narcotic drugs	High
Ticlopidine (Ticlid)	Has been shown to be no better than aspirin in preventing clotting and may be considerably more toxic Safer, more effective alternatives exist	High
Ketorolac (Toradol)	Immediate and long‐term use should be avoided in older people, as a significant number have asymptomatic GI pathological conditions	High
Amphetamines and anorexic agents	These drugs have potential for causing dependence, hypertension, angina and myocardial infarction	High
Long‐term use of full‐dosage, longer half‐life, non–COX‐selective NSAIDs: naproxen (Naprosyn, Avaprox and Aleve), oxaprozin (Daypro) and piroxicam (Feldene)	Have the potential to produce GI bleeding, renal failure, hypertension and heart failure	High
Daily fluoxetine (Prozac)	Long half‐life of drug and risk of producing excessive CNS stimulation, sleep disturbances and increasing agitation. Safer alternatives are available	High
Long‐term use of stimulant laxatives: bisacodyl (Dulcolax), cascara sagrada and Neoloid except in the presence of opiate analgesic use	May exacerbate bowel dysfunction	High
Amiodarone (Cordarone)	Associated with QT interval problems and risk of provoking torsades de pointes. Lack of efficacy in older adults	High
Orphenadrine (Norflex)	Causes greater sedation and anticholinergic adverse effects than safer alternatives	High
Guanethidine (Ismelin)	May cause orthostatic hypotension. Safer alternatives are available	High
Guanadrel (Hylorel)	May cause orthostatic hypotension	High
Cyclandelate (Cyclospasmol)	Lack of efficacy	Low
Isoxsurpine (Vasodilan)	Lack of efficacy	Low
Nitrofurantoin (Macrodantin)	Potential for renal impairment. Safer alternatives are available	High
Doxazosin (Cardura)	Potential for hypotension, dry mouth and urinary problems	Low
Methyltestosterone (Android, Virilon and Testrad)	Potential for prostatic hyperplasia and cardiac problems	High
Thioridazine (Mellaril)	Greater potential for CNS and extrapyramidal adverse effects	High
Mesoridazine (Serentil)	CNS and extrapyramidal adverse effects	High
Short‐acting nifedipine (Procardia and Adalat)	Potential for hypotension and constipation	High
Clonidine (Catapres)	Potential for orthostatic hypotension and CNS adverse effects	Low
Mineral oil	Potential for aspiration and adverse effects. Safer alternatives are available	High
Cimetidine (Tagamet)	CNS adverse effects including confusion	Low
Ethacrynic acid (Edecrin)	Potential for hypertension and fluid imbalances. Safer alternatives are available	Low
Desiccated thyroid	Concerns about cardiac effects. Safer alternatives are available	High
Amphetamines (excluding methylphenidate hydrochloride and anorexic agents)	CNS stimulant adverse effects	High
Oestrogens only (oral)	Evidence of the carcinogenic (breast and endometrial cancer) potential of these agents and lack of cardioprotective effects in older women	Low

Updated Beers (2003) criteria for potentially inappropriate medication use in older adults: considering diagnoses or conditions

Disease or condition	Drug	Concern	Severity rating (high or low)
Heart failure	Disopyramide (Norpace) and high‐sodium‐content drugs (sodium and sodium salts (alginate bicarbonate, biphosphate, citrate, phosphate, salicylate, and sulphate))	Negative inotropic effect. Potential to promote fluid retention and exacerbation of heart failure	High
Hypertension	Phenylpropanolamine hydrochloride (removed from the market in 2001), pseudoephedrine; diet pills and amphetamines	May produce elevation of blood pressure secondary to sympathomimetic activity	High
Gastric or duodenal ulcers	NSAIDs and aspirin (> 325 mg) (COXIBs excluded)	May exacerbate existing ulcers or produce new/additional ulcers	High
Seizures or epilepsy	Clozapine (Clozaril), chlorpromazine (Thorazine), thioridazine (Mellaril) and thiothixene (Navane)	May lower seizure thresholds	High
Blood clotting disordersor receiving anticoagulant therapy	Aspirin, NSAIDs, dipyridamole (Persantin), ticlopidine (Ticlid) and clopidogrel (Plavix)	May prolong clotting time and elevate INR values or inhibit platelet aggregation,resulting in increased potential for bleeding	High
Bladder outflowobstruction	Anticholinergics and antihistamines, gastrointestinal antispasmodics, muscle relaxants, oxybutynin (Ditropan), flavoxate (Urispas), anticholinergics, antidepressants, decongestants and tolterodine (Detrol)	May decrease urinary flow, leading to urinaryretention	High
Stress incontinence	α‐Blockers (doxazosin, prazosin and terazosin), anticholinergics, tricyclic antidepressants (imipramine hydrochloride, doxepin hydrochloride and amitriptyline hydrochloride) and long‐acting benzodiazepines	May produce polyuria and worsening of incontinence	High
Arrhythmias	Tricyclic antidepressants (imipramine hydrochloride, doxepin hydrochloride and amitriptyline hydrochloride)	Concern due to proarrhythmic effects and ability to produce QT interval changes	High
Insomnia	Decongestants, theophylline (Theodur), methylphenidate (Ritalin), MAOIs and amphetamines	Concern due to CNS stimulant effects	High
Parkinson's disease	Metoclopramide (Reglan), conventional antipsychotics and tacrine (Cognex)	Concern due to their antidopaminergic/ cholinergic effects	High
Cognitive impairment	Barbiturates, anticholinergics, antispasmodics and muscle relaxants. CNS stimulants: dextroamphetamine (Adderall), methylphenidate (Ritalin), methamphetamine (Desoxyn) and pemolin	Concern due to CNS‐altering effects	High
Depression	Long‐term benzodiazepine use. Sympatholytic agents: methyldopa (Aldomet), reserpine and guanethidine (Ismelin)	May produce or exacerbate depression	High
Anorexia andmalnutrition	CNS stimulants: dextroamphetamine (Adderall), methylphenidate (Ritalin), methamphetamine (Desoxyn), pemolin and fluoxetine (Prozac)	Concern due to appetite‐suppressing effects	High
Syncope or falls	Short‐ to intermediate‐acting benzodiazepine and tricyclic antidepressants (imipramine hydrochloride, doxepin hydrochloride and amitriptyline hydrochloride)	May produce ataxia, impaired psychomotorfunction, syncope and additional falls	High
SIADH/hyponatraemia	SSRIs: fluoxetine (Prozac), citalopram (Celexa), fluvoxamine (Luvox), paroxetine (Paxil) and sertraline (Zoloft)	May exacerbate or cause SIADH	Low
Seizure disorder	Bupropion (Wellbutrin)	May lower seizure threshold	High
Obesity	Olanzapine (Zyprexa)	May stimulate appetite and increase weight gain	Low
COPD	Long‐acting benzodiazepines: chlordiazepoxide (Librium), chlordiazepoxide‐amitriptyline (Limbitrol), clidinium‐chlordiazepoxide (Librax), diazepam (Valium), quazepam (Doral), halazepam (Paxipam) and chlorazepate (Tranxene). β‐Blockers: propranolol	CNS adverse effects. May induce respiratory depression. May exacerbate or causerespiratory depression	High
Chronic constipation	Calcium channel blockers, anticholinergics and tricyclic antidepressant (imipramine hydrochloride, doxepin hydrochloride and amitriptyline hydrochloride)	May exacerbate constipation	Low

Updated Beers (2012) criteria for potentially inappropriate medication usage in older adults: independent of diagnosis or condition

Organ System or Therapeutic Category or Drug	Rationale	Recommendation	Quality of Evidence	Strength of Recommendation
Anticholinergics (excludes TCAs)
First‐generation antihistamines (as single agent or as part of combination products)BrompheniramineCarbinoxamineChlorpheniramineClemastineCyproheptadineDexbrompheniramineDexchlorpheniramineDiphenhydramine (oral)DoxylamineHydroxyzinePromethazine Triprolidine	Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; greater risk of confusion, dry mouth, constipation and other anticholinergic effects and toxicity Use of diphenhydramine in special situations such as short‐term treatment of severe allergic reaction may be appropriate	Avoid	Hydroxyzine and promethazine: high; all others: moderate	Strong
Antiparkinson agentsBenztropine (oral) Trihexyphenidyl	Not recommended for prevention of extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson's disease	Avoid	Moderate	Strong
AntispasmodicsBelladonna alkaloidsClidinium‐chlordiazepoxideDicyclomineHyoscyaminePropantheline Scopolamine	Highly anticholinergic, uncertain effectiveness	Avoid except in short‐term palliative care to decrease oral secretions	Moderate	Strong
Antithrombotics
Dipyridamole, oral short‐acting* (does not apply to extended‐release combination with aspirin)	May cause orthostatic hypotension; more effective alternatives available; intravenous form acceptable for use in cardiac stress testing	Avoid	Moderate	Strong
Ticlopidine*	Safer effective alternatives available	Avoid	Moderate	Strong
Anti‐infective
Nitrofurantoin	Potential for pulmonary toxicity; safer alternatives available; lack of efficacy in patients with CrCl < 60 mL/min due to inadequate drug concentration in the urine	Avoid for long‐term suppression; avoid in patients with CrCl < 60 mL/min	Moderate	Strong
Cardiovascular
Alpha1‐blockersDoxazosinPrazosin Terazosin	High risk of orthostatic hypotension; not recommended as routine treatment for hypertension; alternative agents have superior risk/benefit profile	Avoid use as an antihypertensive	Moderate	Strong
Alpha‐agonists, centralClonidineGuanabenzGuanfacineMethyldopa* Reserpine (> 0.1 mg/d)*	High risk of adverse CNS effects; may cause bradycardia and orthostatic hypotension; not recommended as routine treatment for hypertension	Avoid clonidine as a first‐line antihypertensive Avoid others as listed	Low	Strong
Antiarrhythmic drugs (Class Ia, Ic, III)AmiodaroneDofetilideDronedaroneFlecainideIbutilideProcainamidePropafenoneQuinidine Sotalol	Data suggest that rate control yields better balance of benefits and harms than rhythm control for most older adults Amiodarone is associated with multiple toxicities, including thyroid disease, pulmonary disorders and QT interval prolongation	Avoid antiarrhythmic drugs as first‐line treatment of atrial fibrillation	High	Strong
Disopyramide*	Disopyramide is a potent negative inotrope and therefore may induce heart failure in older adults; strongly anticholinergic; other antiarrhythmic drugs preferred	Avoid	Low	Strong
Dronedarone	Worse outcomes have been reported in patients taking dronedarone who have permanent atrial fibrillation or heart failure. In general, rate control is preferred over rhythm control for atrial fibrillation	Avoid in patients with permanent atrial fibrillation or heart failure	Moderate	Strong
Digoxin > 0.125 mg/d	In heart failure, higher dosages are associated with no additional benefit and may increase risk of toxicity; slow renal clearance may lead to risk of toxic effects	Avoid	Moderate	Strong
Nifedipine, immediate release*	Potential for hypotension; risk of precipitating myocardial ischaemia	Avoid	High	Strong
Spironolactone > 25 mg/d	In heart failure, the risk of hyperkalaemia is higher in older adults, especially if taking > 25 mg/d or taking concomitant NSAID, angiotensin‐converting enzyme inhibitor, angiotensin receptor blocker or potassium supplement	Avoid in patients with heart failure or with a CrCl < 30 mL/min	Moderate	Strong
Central nervous system
Tertiary TCAs, alone or in combination:AmitriptylineChlordiazepoxide‐amitriptylineClomipramineDoxepin > 6 mg/dImipraminePerphenazine‐amitriptyline Trimipramine	Highly anticholinergic, sedating and causing orthostatic hypotension; safety profile of low‐dose doxepin (≤ 6 mg/d) is comparable with that of placebo	Avoid	High	Strong
Antipsychotics, first (conventional) and second (atypical) generation (see AGS 2012 for full list)	Increased risk of cerebrovascular accident (stroke) and mortality in persons with dementia	Avoid use for behavioural problems of dementia unless non‐pharmacological options have failed and patient is threat to self or others	Moderate	Strong
Thioridazine Mesoridazine	Highly anticholinergic and risk of QT interval prolongation	Avoid	Moderate	Strong
BarbituratesAmobarbitalButabarbitalButalbitalMephobarbitalPentobarbitalPhenobarbital Secobarbital*	High rate of physical dependence; tolerance to sleep benefits; risk of overdose at low dosages	Avoid	High	Strong
Benzodiazepines Short‐ and intermediate‐acting:AlprazolamEstazolamLorazepamOxazepamTemazepamTriazolam Long‐acting: ClorazepateChlordiazepoxideChlordiazepoxide‐amitriptylineClidinium‐chlordiazepoxideClonazepamDiazepamFlurazepam Quazepam	Older adults have increased sensitivity to benzodiazepines and slower metabolism of long‐acting agents. In general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures and motor vehicle accidents in older adults May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anaesthesia and end‐of‐life care	Avoid benzodiazepines (any type) for treatment of insomnia, agitation or delirium	High	Strong
Chloral hydrate*	Tolerance occurs within 10 days, and risks outweigh benefits in light of overdose with doses only 3 times the recommended dose	Avoid	Low	Strong
Meprobamate	High rate of physical dependence; very sedating	Avoid	Moderate	Strong
Non‐benzodiazepine hypnoticsEszopicloneZolpidem Zaleplon	Benzodiazepine‐receptor agonists that have adverse events similar to those of benzodiazepines in older adults (e.g. delirium, falls, fractures); minimal improvement in sleep latency and duration	Avoid long‐term use (> 90 days)	Moderate	Strong
Ergot mesylates* Isoxsuprine*	Lack of efficacy	Avoid	High	Strong
Endocrine
AndrogensMethyltestosterone* Testosterone	Potential for cardiac problems and contraindicated in men with prostate cancer	Avoid unless indicated for moderate to severe hypogonadism	Moderate	Weak
Desiccated thyroid	Concerns about cardiac effects; safer alternatives available	Avoid	Low	Strong
Oestrogens with or without progestins	Evidence of carcinogenic potential (breast and endometrium); lack of cardioprotective effect and cognitive protection in older women Evidence that vaginal oestrogens for treatment of vaginal dryness are safe and effective in women with breast cancer, especially at dosages of estradiol < 25 μg twice weekly	Avoid oral and topical patch Topical vaginal cream: acceptable to use low‐dose intravaginal oestrogen for the management of dyspareunia, lower urinary tract infection and other vaginal symptoms	Oral and patch: high Topical: moderate	Oral and patch: strong Topical: weak
Growth hormone	Effect on body composition is small and is associated with oedema, arthralgia, carpal tunnel syndrome, gynaecomastia, impaired fasting glucose	Avoid, except as hormone replacement after pituitary gland removal	High	Strong
Insulin, sliding scale	Higher risk of hypoglycaemia without improvement in hyperglycaemia management regardless of care setting	Avoid	Moderate	Strong
Megestrol	Minimal effect on weight; increases risk of thrombotic events and possibly death in older adults	Avoid	Moderate	Strong
Sulphonylureas, long durationChlorpropamide Glyburide	Chlorpropamide: prolonged half‐life in older adults; can cause prolonged hypoglycaemia; causes syndrome of inappropriate antidiuretic hormone secretion. Glyburide: greater risk of severe prolonged hypoglycaemia in older adults	Avoid	High	Strong
Gastrointestinal
Metoclopramide	Can cause extrapyramidal effects including tardive dyskinesia; risk may be even greater in frail older adults	Avoid, unless for gastroparesis	Moderate	Strong
Mineral oil, oral	Potential for aspiration and adverse effects; safer alternatives available	Avoid	Moderate	Strong
Trimethobenzamide	One of the least effective antiemetic drugs; can cause extrapyramidal adverse effects	Avoid	Moderate	Strong
Pain
Meperidine	Not an effective oral analgesic in dosages commonly used; may cause neurotoxicity; safer alternatives available	Avoid	High	Strong
Non–COX‐selective NSAIDs, oralAspirin > 325 mg/dDiclofenacDiflunisalEtodolacFenoprofenIbuprofenKetoprofenMeclofenamateMefenamic acidMeloxicamNabumetoneNaproxenOxaprozinPiroxicamSulindac Tolmetin	Increase risk of GI bleeding and peptic ulcer disease in high‐risk groups, including those aged > 75 or taking oral or parenteral corticosteroids, anticoagulants or antiplatelet agents. Use of proton pump inhibitor or misoprostol reduces but does not eliminate risk. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occurs in approximately 1% of patients treated for 3 to 6 months and in approximately 2% to 4% of patients treated for 1 year. These trends continue with longer duration of use	Avoid long‐term use unless other alternatives are not effective and patient can take gastroprotective agent (proton pump inhibitor or misoprostol)	Moderate	Strong
Indomethacin Ketorolac, includes parenteral	Increase risk of GI bleeding and peptic ulcer disease in high‐risk groups (see above Non–COX‐selective NSAIDs) Of all the NSAIDs, indomethacin has the most adverse effects	Avoid	Indomethacin: moderate Ketorolac: high	Strong
Pentazocine*	Opioid analgesic that causes CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs; also a mixed agonist and antagonist; safer alternatives available	Avoid	Low	Strong
Skeletal muscle relaxantsCarisoprodolChlorzoxazoneCyclobenzaprineMetaxaloneMethocarbamol Orphenadrine	Most muscle relaxants are poorly tolerated by older adults because of anticholinergic adverse effects, sedation, risk of fracture; effectiveness at dosages tolerated by older adults is questionable	Avoid	Moderate	Strong
Source: AGS 2012. CNS = central nervous system; COX = cyclo‐oxygenase; CrCl = creatinine clearance; GI = gastrointestinal; NSAID = non‐steroidal anti‐inflammatory drug; TCA = tricyclic antidepressant. *Infrequently used drugs.

Updated Beers (2012) criteria for potentially inappropriate medication usage in older adults due to drug–disease or drug–syndrome interactions that may exacerbate the disease or syndrome

Disease or syndrome	Drug	Rationale	Recommendation	Quality of evidence	Strength of recommendation
Cardiovascular
Heart failure	NSAIDs and COX‐2 inhibitorsNon‐dihydropyridine CCBs (avoid only for systolic heart failure)DiltiazemVerapamilPioglitazone, rosiglitazoneCilostazol Dronedarone	Potential to promote fluid retention and exacerbate heart failure	Avoid	NSAIDs: moderateCCBs: moderateThiazolidinediones (glitazones): highCilostazol: low Dronedarone: moderate	Strong
Syncope	AChEIsPeripheral alpha‐blockersDoxazosinPrazosinTerazosinTertiary TCAs Chlorpromazine, thioridazine and olanzapine	Increase risk of orthostatic hypotension or bradycardia	Avoid	Alpha‐blockers:highTCAs, AChEIs and antipsychotics: moderate	AChEIs and TCAs: strongAlpha‐blockers and antipsychotics: weak
Central nervous system
Chronic seizures or epilepsy	BupropionChlorpromazineClozapineMaprotilineOlanzapineThioridazineThiothixene Tramadol	Lower seizure threshold; may be acceptable in patients with well‐controlled seizures in whom alternative agents have not been effective	Avoid	Moderate	Strong
Delirium	All TCAs Anticholinergics (see AGS 2012 for full list)BenzodiazepinesChlorpromazineCorticosteroids H2‐receptor antagonist MeperidineSedative‐hypnotics Thioridazine	Avoid in older adults with or at high risk of delirium because of inducing or worsening delirium in older adults; if discontinued drugs used long‐term, taper to avoid withdrawal symptoms	Avoid	Moderate	Strong
Dementia and cognitive impairment	Anticholinergics (see AGS 2012 for full list)Benzodiazepines H2‐receptor antagonists Zolpidem Antipsychotics, long‐term and as‐needed use	Avoid because of adverse CNS effects Avoid antipsychotics for behavioural problems of dementia unless non‐pharmacological options have failed and patient is a threat to himself or others. Antipsychotics are associated with increased risk of cerebrovascular accident (stroke) and mortality in persons with dementia	Avoid	High	Strong
History of falls or fractures	AnticonvulsantsAntipsychoticsBenzodiazepinesNon‐benzodiazepine hypnoticsEszopicloneZaleplonZolpidem TCAs and selective serotonin reuptake inhibitors	Ability to produce ataxia, impaired psychomotor function, syncope and additional falls; shorter‐acting benzodiazepines are not safer than long‐acting ones	Avoid unless safer alternatives are not available; avoid anticonvulsants except for seizure disorders	High	Strong
Insomnia	Oral decongestantsPseudoephedrinePhenylephrineStimulantsAmphetamineMethylphenidatePemolineTheobrominesTheophylline Caffeine	CNS stimulant effects	Avoid	Moderate	Strong
Parkinson's disease	All antipsychotics (see AGS 2012 for full list, except for quetiapine and clozapine)AntiemeticsMetoclopramideProchlorperazine Promethazine	Dopamine receptor antagonists with potential to worsen parkinsonian symptoms Quetiapine and clozapine appear to be less likely to precipitate worsening of Parkinson's disease	Avoid	Moderate	Strong
Gastrointestinal
Chronic constipation	Oral antimuscarinics for urinary incontinenceDarifenacinFesoterodineOxybutynin (oral)SolifenacinTolterodineTrospiumNon‐dihydropyridine CCBDiltiazemVerapamilFirst‐generation antihistamines as single agent or part of combination productsBrompheniramine (various)CarbinoxamineChlorpheniramineClemastine (various)CyproheptadineDexbrompheniramineDexchlorpheniramine (various)DiphenhydramineDoxylamineHydroxyzinePromethazineTriprolidine Anticholinergics and antispasmodics (see AGS 2012 for full list of drugs with strong anticholinergic properties) AntipsychoticsBelladonna alkaloidsClidinium‐chlordiazepoxideDicyclomineHyoscyaminePropanthelineScopolamine Tertiary TCAs (amitriptyline, clomipramine, doxepin, imipramine and trimipramine)	Can worsen constipation; agents for urinary incontinence: Antimuscarinics overall differ in incidence of constipation; response variable; consider alternative agent if constipation develops	Avoid unless no other alternatives	For urinary incontinence: high All others: moderate to low	Weak
History of gastric or duodenal ulcers	Aspirin (> 325 mg/d) Non–COX‐2–selective NSAIDs	May exacerbate existing ulcers or cause new or additional ulcers	Avoid unless other alternatives are not effective and patient can take gastroprotective agent (proton pump inhibitor or misoprostol)	Moderate	Strong
Kidney and urinary tract
Chronic kidney disease Stages IV and V	NSAIDs Triamterene (alone or in combination)	May increase risk of kidney injury	Avoid	NSAIDs: moderate Triamterene: low	NSAIDs: strong Triamterene: weak
Urinary incontinence (all types) in women	Oestrogen oral and transdermal (excludes intravaginal oestrogen)	Aggravate incontinence	Avoid in women	High	Strong
Lower urinary tract symptoms, benign prostatic hyperplasia	Inhaled anticholinergic agents Strongly anticholinergic drugs, except antimuscarinics for urinary incontinence (see AGS 2012 for complete list)	May decrease urinary flow and cause urinary retention	Avoid in men	Moderate	Inhaled agents: strong All others: weak
Stress or mixed urinary incontinence	Alpha‐blockersDoxazosinPrazosin Terazosin	Aggravate incontinence	Avoid in women	Moderate	Strong
Source: AGS 2012. CCB = calcium channel blocker; AChEI = acetylcholinesterase inhibitor; CNS = central nervous system; COX = cyclo‐oxygenase; NSAID = non‐steroidal anti‐inflammatory drug; TCA = tricyclic antidepressant.

Updated Beers (2012) criteria for potentially inappropriate medications to be used with caution in older adults

Drug	Rationale	Recommendation	Quality of evidence	Strength of recommendation
Aspirin for primary prevention of cardiac events	Lack of evidence of benefit versus risk in individuals aged ≥ 80	Use with caution in adults aged ≥ 80	Low	Weak
Dabigatran	Greater risk of bleeding than with warfarin in adults aged ≥ 75; lack of evidence of efficacy and safety in individuals with CrCl < 30 mL/min	Use with caution in adults aged ≥ 75 or if CrCl < 30 mL/min	Moderate	Weak
Prasugrel	Greater risk of bleeding in older adults; risk may be offset by benefit in highest‐risk older adults (e.g. with prior myocardial infarction or diabetes mellitus)	Use with caution in adults aged ≥ 75	Moderate	Weak
AntipsychoticsCarbamazepineCarboplatinCisplatinMirtazapineSerotonin–norepinephrine reuptake inhibitorSelective serotonin reuptake inhibitorTricyclic antidepressants Vincristine	May exacerbate or cause syndrome of inappropriate antidiuretic hormone secretion or hyponatraemia; need to monitor sodium level closely when starting or changing dosages in older adults because of increased risk	Use with caution	Moderate	Strong
Vasodilators	May exacerbate episodes of syncope in individuals with history of syncope
Source: AGS 2012. CrCl = creatinine clearance.

The most recent version of Beers criteria (AGS 2012) comprises three lists. The first list comprises 34 individual medications or classes of medications that should be avoided in older adults and their concerns (Table 6). The second list includes diseases or conditions and drugs that should be avoided in older adults with these conditions (Table 7). The third list provides medications to be used with caution in older adults (Table 8). The statements in each list are rated on the basis of quality of evidence and the strength of recommendations using the American College of Physicians' Guideline Grading System.

MEDLINE (Ovid)

Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE 1946 to Present

Search date: 5 May 2016

1	polypharmacy/	2956
2	inappropriate prescribing/	1360
3	potentially inappropriate medication list/	20
4	deprescriptions/	10
5	medication errors/	11203
6	polypharma*.ti,ab.	4661
7	((beer* or shan? or mcleod?) adj3 criter*).ti,ab.	407
8	("fit for the aged" adj3 (criter* or list? or instrument or classif*)).ti,ab.	8
9	((forta or rasp or priscus) adj3 (criter* or list? or instrument)).ti,ab.	45
10	(stopp criter* or stopp list?).ti,ab.	79
11	((concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) adj1 (medicine? or medicat or prescrib* or prescription* or drug*)).ti,ab.	21859
12	((over adj1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" adj (medication or prescrib* or prescript*))).ti,ab.	1792
13	((under adj1 prescrib) or underprescrib or under‐prescrib*).ti,ab.	425
14	(deprescrib* or deprescript*).ti,ab.	85
15	"medication appropriateness index*".ti,ab.	83
16	(quality adj2 (prescribing or prescription* or medication*)).ti,ab.	1025
17	(improv* adj2 (prescrib* or pharmaco* or prescription*)).ti,ab.	5217
18	(prescrib* adj cascade*).ti,ab.	24
19	("assessing care of vulnerable elders" or acove).ti,ab.	84
20	((multi‐drug* or multidrug) adj2 (prescrib or prescription* or regimen? or therap* or treatment?)).ti,ab.	3761
21	or/1‐20	49368
22	exp aged/	2558759
23	geriatrics/	27917
24	(elder* or geriatric*).ti,ab.	228974
25	((old* or aged) adj (person* or adult* or people or patient* or inpatient* or outpatient*)).ti,ab.	138495
26	aged care.ti,ab.	1737
27	veterans/	11908
28	veteran*.ti,ab.	26177
29	or/22‐28	2700505
30	21 and 29	12684
31	exp *polypharmacy/	1274
32	31 and 29	842
33	randomized controlled trial.pt.	415781
34	controlled clinical trial.pt.	90679
35	multicenter study.pt.	201068
36	pragmatic clinical trial.pt.	312
37	(randomis* or randomiz* or randomly).ti,ab.	663942
38	groups.ab.	1577286
39	(trial or multicenter or multi center or multicentre or multi centre).ti.	180301
40	(intervention? or effect? or impact? or controlled or control group? or (before adj5 after) or (pre adj5 post) or ((pretest or pre test) and (posttest or post test)) or quasiexperiment* or quasi experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or time series or time point? or repeated measur*).ti,ab.	7470667
41	non‐randomized controlled trials as topic/	57
42	interrupted time series analysis/	142
43	controlled before‐after studies/	129
44	or/33‐43	8354420
45	exp animals/	20155558
46	humans/	15916618
47	45 not (45 and 46)	4238940
48	review.pt.	2114984
49	meta analysis.pt.	65371
50	news.pt.	176499
51	comment.pt.	662585
52	editorial.pt.	402997
53	cochrane database of systematic reviews.jn.	12298
54	comment on.cm.	662584
55	(systematic review or literature review).ti.	76420
56	or/47‐55	7298360
57	44 not 56	5788963
58	30 and 57	6760
59	32 or 58	7209
60	(20131* or 2014* or 2015* or 2016*).dc,dp,ed,ep,yr.	3528154
61	59 and 60	1876

Embase (Ovid)

Embase 1974 to 2016 May 04

Search date: 5 May 2016

1	polypharmacy/	9311
2	inappropriate prescribing/	2174
3	medication error/	14470
4	polypharma*.ti,ab.	7297
5	((beer* or shan? or mcleod?) adj3 criter*).ti,ab.	692
6	("fit for the aged" adj3 (criter* or list? or instrument or classif*)).ti,ab.	13
7	((forta or rasp or priscus) adj3 (criter* or list? or instrument)).ti,ab.	79
8	(stopp criter* or stopp list?).ti,ab.	194
9	((concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) adj1 (medicine? or medicat or prescrib* or prescription* or drug*)).ti,ab.	33028
10	((over adj1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" adj (medication or prescrib* or prescript*))).ti,ab.	2678
11	((under adj1 prescrib) or underprescrib or under‐prescrib*).ti,ab.	601
12	(deprescrib* or deprescript*).ti,ab.	108
13	"medication appropriateness index*".ti,ab.	125
14	(quality adj2 (prescribing or prescription* or medication*)).ti,ab.	1614
15	(improv* adj2 (prescrib* or pharmaco* or prescription*)).ti,ab.	7311
16	(prescrib* adj cascade*).ti,ab.	32
17	("assessing care of vulnerable elders" or acove).ti,ab.	131
18	((multi‐drug* or multidrug) adj2 (prescrib or prescription* or regimen? or therap* or treatment?)).ti,ab.	4674
19	or/1‐18	72518
20	aged/	2406413
21	frail elderly/	7267
22	very elderly/	87611
23	aged hospital patient/	557
24	veteran/	14932
25	exp geriatrics/	46527
26	(elder* or geriatric*).ti,ab.	313574
27	((old* or aged) adj (person* or adult* or people or patient* or inpatient* or outpatient*)).ti,ab.	178986
28	aged care.ti,ab.	1777
29	veteran*.ti,ab.	31673
30	or/20‐29	2618872
31	*polypharmacy/	2108
32	30 and 31	1082
33	19 and 30	16095
34	randomized controlled trial/	402955
35	controlled clinical trial/	393267
36	quasi experimental study/	2895
37	pretest posttest control group design/	254
38	time series analysis/	16880
39	experimental design/	12369
40	multicenter study/	136615
41	(randomis* or randomiz* or randomly).ti,ab.	879958
42	groups.ab.	2061105
43	(trial or multicentre or multicenter or multi centre or multi center).ti.	243864
44	(intervention? or effect? or impact? or controlled or control group? or (before adj5 after) or (pre adj5 post) or ((pretest or pre test) and (posttest or post test)) or quasiexperiment* or quasi experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or time series or time point? or repeated measur*).ti,ab.	9311234
45	or/34‐44	10393792
46	(systematic review or literature review).ti.	89371
47	"cochrane database of systematic reviews".jn.	3951
48	exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/	23072412
49	human/ or normal human/ or human cell/	17208417
50	48 not (48 and 49)	5910759
51	46 or 47 or 50	6003257
52	45 not 51	7854630
53	33 and 52	10126
54	32 or 53	10609
55	(20131* or 2014* or 2015* or 2016*).dp,dd,yr,em.	4637633
56	54 and 55	3269

The Cochrane Library (Wiley)

Search date: 5 May 2016

#1	[mh polypharmacy]	126
#2	[mh "inappropriate prescribing"]	71
#3	[mh "potentially inappropriate medication list"]	0
#4	[mh deprescriptions]	0
#5	[mh "medication errors"]	331
#6	polypharma*:ti,ab	234
#7	((beer* or shan* or mcleod) near/3 criter):ti,ab	23
#8	("fit for the aged" near/3 (criter* or list* or instrument or classif*)):ti,ab	1
#9	((forta or rasp or priscus) near/3 (criter* or list* or instrument)):ti,ab	5
#10	(stopp criter* or stopp list*):ti,ab	24
#11	((concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) near/1 (medicine or medicat* or prescrib* or prescription* or drug*)):ti,ab	2379
#12	((over near/1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" near/1 (medication or prescrib* or prescript*))):ti,ab	154
#13	((under near/1 prescrib) or underprescrib or under‐prescrib*):ti,ab	20
#14	(deprescrib* or deprescript*):ti,ab	6
#15	(quality near/2 (prescribing or prescription* or medication*)):ti,ab	151
#16	(improv* near/2 (prescrib* or pharmaco* or prescription*)):ti,ab	476
#17	(prescri* near/1 cascade*):ti,ab	0
#18	("assessing care of vulnerable elders" or acove):ti,ab	10
#19	((multi‐drug* or multidrug) near/2 (prescrib or prescription* or regimen* or therap* or treatment*)):ti,ab	364
#20	{or #1‐#19}	3932
#21	[mh aged]	993
#22	[mh geriatrics]	216
#23	(elder* or geriatric*):ti,ab	19391
#24	((old* or aged) near/1 (person* or adult* or people or patient* or inpatient* or outpatient*)):ti,ab	21045
#25	aged next care:ti,ab	130
#26	[mh veterans]	614
#27	veteran*:ti,ab	2559
#28	{or #21‐#27}	39695
#29	#20 and #28 Publication Year from 2013 to 2016	165

CINAHL (EBSCO)

Search date: 5 May 2016

No.	Search terms	Results
S1	(MH "Polypharmacy")	1,832
S2	(MH "Inappropriate Prescribing")	491
S3	(MH "Medication Errors")	8,808
S4	polypharma*	2,376
S5	(beer* or shan* or mcleod) N3 criter	171
S6	"fit for the aged" N3 (criter* or list* or instrument or classif*)	3
S7	(forta or rasp or priscus) N3 (criter* or list* or instrument)	3
S8	stopp criter* or stopp list*	28
S9	(concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) N1 (medicine or medicat* or prescrib* or prescription* or drug*)	7,963
S10	((over N1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" N0 (medication or prescrib* or prescript*)))	1,551
S11	(under N1 prescrib) or underprescrib or under‐prescrib*	107
S12	deprescrib* or deprescript*	28
S13	"medication appropriateness index*"	25
S14	quality N2 (prescribing or prescription* or medication*)	427
S15	prescrib* N0 cascade*	11
S16	"assessing care of vulnerable elders" or acove	44
S17	(multi‐drug* or multidrug) N2 (prescrib or prescription* or regimen* or therap* or treatment*)	616
S18	improv* N2 (prescrib* or pharmaco* or prescription*)	1,003
S19	S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18	21,470
S20	(MH "Aged+")	373,520
S21	(MH "Geriatrics")	2,766
S22	(MH "Veterans")	7,998
S23	elder* or geriatric*	74,995
S24	(old* or aged) N0 (person* or adult* or people or patient* or inpatient* or outpatient*)	57,731
S25	"aged care"	2,138
S26	veteran*	15,551
S27	S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26	415,048
S28	S19 AND S27	5,108
S29	(MM "Polypharmacy")	765
S30	S27 AND S29	538
S31	PT randomized controlled trial	30,497
S32	PT clinical trial	52,762
S33	PT research	988,005
S34	(MH "Randomized Controlled Trials")	26,240
S35	(MH "Clinical Trials")	84,279
S36	(MH "Intervention Trials")	5,986
S37	(MH "Nonrandomized Trials")	170
S38	(MH "Experimental Studies")	14,818
S39	(MH "Pretest‐Posttest Design+")	26,855
S40	(MH "Quasi‐Experimental Studies+")	8,473
S41	(MH "Multicenter Studies")	11,426
S42	(MH "Health Services Research")	7,374
S43	TI ( randomis* or randomiz* or randomly) OR AB ( randomis* or randomiz* or randomly)	111,004
S44	TI (trial or effect* or impact* or intervention* or before N5 after or pre N5 post or ((pretest or "pre test") and (posttest or "post test")) or quasiexperiment* or quasi W0 experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or "time series" or time W0 point* or repeated W0 measur) OR AB (trial or effect or impact* or intervention* or before N5 after or pre N5 post or ((pretest or "pre test") and (posttest or "post test")) or quasiexperiment* or quasi W0 experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or "time series" or time W0 point* or repeated W0 measur*)	762,000
S45	S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44	1,297,160
S46	S28 AND S45	3,669
S47	S30 OR S46	3,901
S48	S47 Limiters ‐ Exclude MEDLINE records	726
S49	S48 Limiters ‐ Published Date: 20131001‐20161231	141

ClinicalTrials.gov, US National Institutes of Health (NIH)http://clinicaltrials.gov/

Search date: 5 May 2016

polypharmacy \| senior	69
"inappropriate prescribing" \| senior	26
appropriate prescribing \| senior	5
"inappropriate medication" \| senior	30
"appropriate medication" \| senior	16
deprescribing \| senior	1
Total=	147

WHO International Clinical Trials Registry Platform (ICTRP)

Search date: 5 May 2016

polypharmacy	60
inappropriate prescribing	11
appropriate prescribing	6
inappropriate medication	12
appropriate medication	4
deprescribing	6
Total=	99

MEDLINE (Ovid)

Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE 1946 to January 31, 2018

Search date: 7 February 2018

1	polypharmacy/	3668
2	inappropriate prescribing/	2046
3	potentially inappropriate medication list/	158
4	deprescriptions/	124
5	medication errors/	12019
6	polypharma*.ti,ab.	5918
7	((beer* or shan? or mcleod?) adj3 criter*).ti,ab.	517
8	("fit for the aged" adj3 (criter* or list? or instrument or classif*)).ti,ab.	13
9	((forta or rasp or priscus) adj3 (criter* or list? or instrument)).ti,ab.	64
10	(stopp criter* or stopp list?).ti,ab.	119
11	((concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) adj1 (medicine? or medicat or prescrib* or prescription* or drug*)).ti,ab.	24793
12	((over adj1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" adj (medication or prescrib* or prescript*))).ti,ab.	2119
13	((under adj1 prescrib) or underprescrib or under‐prescrib*).ti,ab.	475
14	(deprescrib* or deprescript*).ti,ab.	226
15	"medication appropriateness index*".ti,ab.	102
16	(quality adj2 (prescribing or prescription* or medication*)).ti,ab.	1177
17	(improv* adj2 (prescrib* or pharmaco* or prescription*)).ti,ab.	6106
18	(prescrib* adj cascade*).ti,ab.	34
19	("assessing care of vulnerable elders" or acove).ti,ab.	90
20	((multi‐drug* or multidrug) adj2 (prescrib or prescription* or regimen? or therap* or treatment?)).ti,ab.	4237
21	or/1‐20	56288
22	exp aged/	2764427
23	geriatrics/	28541
24	(elder* or geriatric*).ti,ab.	251719
25	((old* or aged) adj (person* or adult* or people or patient* or inpatient* or outpatient*)).ti,ab.	160088
26	aged care.ti,ab.	2117
27	veterans/	13542
28	veteran*.ti,ab.	29692
29	or/22‐28	2927447
30	21 and 29	14942
31	exp *polypharmacy/	1667
32	31 and 29	1152
33	randomized controlled trial.pt.	452912
34	controlled clinical trial.pt.	92140
35	multicenter study.pt.	227930
36	pragmatic clinical trial.pt.	653
37	(randomis* or randomiz* or randomly).ti,ab.	754378
38	groups.ab.	1761063
39	(trial or multicenter or multi center or multicentre or multi centre).ti.	209759
40	(intervention? or effect? or impact? or controlled or control group? or (before adj5 after) or (pre adj5 post) or ((pretest or pre test) and (posttest or post test)) or quasiexperiment* or quasi experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or time series or time point? or repeated measur*).ti,ab.	8289310
41	non‐randomized controlled trials as topic/	277
42	interrupted time series analysis/	372
43	controlled before‐after studies/	299
44	or/33‐43	9255407
45	exp animals/	21288035
46	humans/	16865486
47	45 not (45 and 46)	4422549
48	review.pt.	2339655
49	meta analysis.pt.	84382
50	news.pt.	185450
51	comment.pt.	704566
52	editorial.pt.	449644
53	cochrane database of systematic reviews.jn.	13415
54	comment on.cm.	704563
55	(systematic review or literature review).ti.	105999
56	or/47‐55	7800161
57	44 not 56	6467868
58	30 and 57	8109
59	32 or 58	8711
60	(2016* or 2017* or 2018*).dt,dp,ed,ep,yr.	3317707
61	59 and 60	2095

Embase (Ovid)

Embase 1974 to 2018 February 6

Search date: 7 February 2018

1	polypharmacy/	11990
2	inappropriate prescribing/	2980
3	medication error/	16294
4	polypharma*.ti,ab.	9660
5	((beer* or shan? or mcleod?) adj3 criter*).ti,ab.	939
6	("fit for the aged" adj3 (criter* or list? or instrument or classif*)).ti,ab.	20
7	((forta or rasp or priscus) adj3 (criter* or list? or instrument)).ti,ab.	106
8	(stopp criter* or stopp list?).ti,ab.	287
9	((concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) adj1 (medicine? or medicat or prescrib* or prescription* or drug*)).ti,ab.	39145
10	((over adj1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" adj (medication or prescrib* or prescript*))).ti,ab.	3297
11	((under adj1 prescrib) or underprescrib or under‐prescrib*).ti,ab.	712
12	(deprescrib* or deprescript*).ti,ab.	353
13	"medication appropriateness index*".ti,ab.	157
14	(quality adj2 (prescribing or prescription* or medication*)).ti,ab.	1958
15	(improv* adj2 (prescrib* or pharmaco* or prescription*)).ti,ab.	8783
16	(prescrib* adj cascade*).ti,ab.	52
17	("assessing care of vulnerable elders" or acove).ti,ab.	143
18	((multi‐drug* or multidrug) adj2 (prescrib or prescription* or regimen? or therap* or treatment?)).ti,ab.	5382
19	or/1‐18	86092
20	aged/	2658763
21	frail elderly/	8640
22	very elderly/	125021
23	aged hospital patient/	679
24	veteran/	19187
25	exp geriatrics/	38812
26	(elder* or geriatric*).ti,ab.	351560
27	((old* or aged) adj (person* or adult* or people or patient* or inpatient* or outpatient*)).ti,ab.	210594
28	aged care.ti,ab.	2241
29	veteran*.ti,ab.	37456
30	or/20‐29	2888742
31	*polypharmacy/	2833
32	30 and 31	1516
33	19 and 30	19946
34	randomized controlled trial/	485990
35	controlled clinical trial/	454228
36	quasi experimental study/	4178
37	pretest posttest control group design/	325
38	time series analysis/	20120
39	experimental design/	15072
40	multicenter study/	174951
41	(randomis* or randomiz* or randomly).ti,ab.	1034240
42	groups.ab.	2380261
43	(trial or multicentre or multicenter or multi centre or multi center).ti.	290689
44	(intervention? or effect? or impact? or controlled or control group? or (before adj5 after) or (pre adj5 post) or ((pretest or pre test) and (posttest or post test)) or quasiexperiment* or quasi experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or time series or time point? or repeated measur*).ti,ab.	10531597
45	or/34‐44	11748867
46	(systematic review or literature review).ti.	124542
47	"cochrane database of systematic reviews".jn.	7188
48	exp animals/ or exp invertebrate/ or animal experiment/ or animal model/ or animal tissue/ or animal cell/ or nonhuman/	25510736
49	human/ or normal human/ or human cell/	19263193
50	48 not (48 and 49)	6295394
51	46 or 47 or 50	6425940
52	45 not 51	8956795
53	33 and 52	12699
54	32 or 53	13345
55	limit 54 to yr="2016 ‐Current"	2944

The Cochrane Library (Wiley)

Search date: 7 February 2018

#1	[mh polypharmacy]	174
#2	[mh "inappropriate prescribing"]	110
#3	[mh "potentially inappropriate medication list"]	5
#4	[mh deprescriptions]	7
#5	[mh "medication errors"]	413
#6	polypharma*:ti,ab	415
#7	((beer* or shan* or mcleod) near/3 criter):ti,ab	42
#8	("fit for the aged" near/3 (criter* or list* or instrument or classif*)):ti,ab	5
#9	((forta or rasp or priscus) near/3 (criter* or list* or instrument)):ti,ab	7
#10	(stopp criter* or stopp list*):ti,ab	52
#11	((concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) near/1 (medicine or medicat* or prescrib* or prescription* or drug*)):ti,ab	3473
#12	((over near/1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" near/1 (medication or prescrib* or prescript*))):ti,ab	230
#13	((under near/1 prescrib) or underprescrib or under‐prescrib*):ti,ab	37
#14	(deprescrib* or deprescript*):ti,ab	23
#15	(quality near/2 (prescribing or prescription* or medication*)):ti,ab	224
#16	(improv* near/2 (prescrib* or pharmaco* or prescription*)):ti,ab	654
#17	(prescri* near/1 cascade*):ti,ab	1
#18	("assessing care of vulnerable elders" or acove):ti,ab	12
#19	((multi‐drug* or multidrug) near/2 (prescrib or prescription* or regimen* or therap* or treatment*)):ti,ab	441
#20	{or #1‐#19}	5560
#21	[mh aged]	1214
#22	[mh geriatrics]	227
#23	(elder* or geriatric*):ti,ab	23878
#24	((old* or aged) near/1 (person* or adult* or people or patient* or inpatient* or outpatient*)):ti,ab	28530
#25	aged next care:ti,ab	188
#26	[mh veterans]	770
#27	veteran*:ti,ab	3200
#28	{or #21‐#27}	51051
#29	#20 and #28	814
#30	#20 and #28 Publication Year from 2016 to 2018	243

CINAHL (EBSCO)

Search date: 7 February 2018

S1	(MH "Polypharmacy")	2,245
S2	(MH "Inappropriate Prescribing")	900
S3	(MH "Medication Errors")	9,416
S4	polypharma*	2,980
S5	(beer* or shan* or mcleod) N3 criter	232
S6	"fit for the aged" N3 (criter* or list* or instrument or classif*)	7
S7	(forta or rasp or priscus) N3 (criter* or list* or instrument)	8
S8	stopp criter* or stopp list*	55
S9	(concomitant* or concurrent* or inappropriat* or appropriat* or suboptim* or sub‐optim* or unnecessary or incorrect* or excess* or multip* or inadvert* or discontinu) N1 (medicine or medicat* or prescrib* or prescription* or drug*)	9,773
S10	((over N1 (prescrib* or prescript)) or (over‐prescrib or overprescrib) or ("or more" N0 (medication or prescrib* or prescript*)))	1,968
S11	(under N1 prescrib) or underprescrib or under‐prescrib*	136
S12	deprescrib* or deprescript*	107
S13	"medication appropriateness index*"	33
S14	quality N2 (prescribing or prescription* or medication*)	529
S15	prescrib* N0 cascade*	15
S16	"assessing care of vulnerable elders" or acove	47
S17	(multi‐drug* or multidrug) N2 (prescrib or prescription* or regimen* or therap* or treatment*)	705
S18	improv* N2 (prescrib* or pharmaco* or prescription*)	1,262
S19	S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18	24,995
S20	(MH "Aged+")	420,836
S21	(MH "Geriatrics")	3,197
S22	(MH "Veterans")	9,527
S23	elder* or geriatric*	85,606
S24	(old* or aged) N0 (person* or adult* or people or patient* or inpatient* or outpatient*)	73,337
S25	"aged care"	2,662
S26	veteran*	18,258
S27	S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26	474,552
S28	S19 AND S27	6,315
S29	(MM "Polypharmacy")	966
S30	S27 AND S29	692
S31	PT randomized controlled trial	42,401
S32	PT clinical trial	55,753
S33	PT research	1,173,449
S34	(MH "Randomized Controlled Trials")	39,459
S35	(MH "Clinical Trials")	92,614
S36	(MH "Intervention Trials")	6,848
S37	(MH "Nonrandomized Trials")	248
S38	(MH "Experimental Studies")	17,542
S39	(MH "Pretest‐Posttest Design+")	30,465
S40	(MH "Quasi‐Experimental Studies+")	10,104
S41	(MH "Multicenter Studies")	34,001
S42	(MH "Health Services Research")	7,958
S43	TI ( randomis* or randomiz* or randomly) OR AB ( randomis* or randomiz* or randomly)	139,254
S44	TI (trial or effect* or impact* or intervention* or before N5 after or pre N5 post or ((pretest or "pre test") and (posttest or "post test")) or quasiexperiment* or quasi W0 experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or "time series" or time W0 point* or repeated W0 measur) OR AB (trial or effect or impact* or intervention* or before N5 after or pre N5 post or ((pretest or "pre test") and (posttest or "post test")) or quasiexperiment* or quasi W0 experiment* or pseudo experiment* or pseudoexperiment* or evaluat* or "time series" or time W0 point* or repeated W0 measur*)	954,170
S45	S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 OR S41 OR S42 OR S43 OR S44	1,556,024
S46	S28 AND S45	4,714
S47	S30 OR S46	4,974
S48	S47 Limiters ‐ Exclude MEDLINE records	1,336
S49	S48 Limiters ‐ Published Date: 20160101‐20181231	566

ClinicalTrials.gov, US National Institutes of Health (NIH)http://clinicaltrials.gov/

Search date: 7 February 2018

polypharmacy \| senior	106
"inappropriate prescribing" \| senior	20
appropriate prescribing \| senior	9
"inappropriate medication" \| senior	16
"appropriate medication" \| senior	8
deprescribing \| senior	25
Total=	184

WHO International Clinical Trials Registry Platform (ICTRP)

Search date: 7 February 2018

polypharmacy
inappropriate prescribing
appropriate prescribing
inappropriate medication
appropriate medication
deprescribing
Total=	209

(1) Fulton MM, Allen ER. Polypharmacy in the elderly: a literature review. Journal of the American Academy of Nurse Practitioners 2005 Apr;17(4):123‐32. (2) Garcia RM. Five ways you can reduce inappropriate prescribing in the elderly: a systematic review. Journal of Family Practice 2006 Apr;55(4):305‐12. (3) George J, Elliott RA, Stewart DC. A systematic review of interventions to improve medication taking in elderly patients prescribed multiple medications. Drugs & Aging 2008;25(4):307‐24. (4) Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. American Journal of Geriatric Pharmacotherapy 2007;5(4):345‐51.

(5) Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication adherence. Cochrane Database of Systematic Reviews 2008;2({"type":"entrez-nucleotide","attrs":{"text":"CD000011","term_id":"30294530","term_text":"CD000011"}}CD000011).

(6) Holland R, Desborough J, Goodyer L, Hall S, Wright D, Loke YK. Does pharmacist‐led medication review help to reduce hospital admissions and deaths in older people? A systematic review and meta‐analysis. British Journal of Clinical Pharmacology 2008 Mar;65(3):303‐16. (7) Huss A, Stuck AE, Rubenstein LZ, Egger M, Clough‐Gorr KM. Multidimensional preventive home visit programs for community‐dwelling older adults: a systematic review and meta‐analysis of randomized controlled trials. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences 2008;63(3):298‐307. (8) Jano E, Aparasu RR. Healthcare outcomes associated with Beers' criteria: a systematic review. The Annals of Pharmacotherapy 2007 Mar;41(3):438‐47. (9) Kaur S, Mitchell G, Vitetta L, Roberts MS. Interventions that can reduce inappropriate prescribing in the elderly: a systematic review. Drugs & Aging 2009;26(12):1013‐28. (10) Maeda K. Systematic review of the effects of improvement of prescription to reduce the number of medications in the elderly with polypharmacy. Yakugaku Zasshi 2009 May;129(5):631‐45. (11) Milton JC, Hill‐Smith I, Jackson SH. Prescribing for older people. BMJ 2008 Mar 15;336(7644):606‐9. (12) Rollason V, Vogt N. Reduction of polypharmacy in the elderly: a systematic review of the role of the pharmacist. Drugs & Aging 2003;20(11):817‐32. (13) Royal S, Smeaton L, Avery AJ, Hurwitz B, Sheikh A. Interventions in primary care to reduce medication related adverse events and hospital admissions: systematic review and meta‐analysis. Quality & Safety in Health Care 2006 Feb;15(1):23‐31. (14) Spinewine A, Schmader KE, Barber N, Hughes C, Lapane KL, Swine C, et al. Appropriate prescribing in elderly people: how well can it be measured and optimised? Lancet 2007;370(9582):173‐84. (15) Wenger NS, Roth CP, Shekelle P, ACOVE I. Introduction to the assessing care of vulnerable elders‐3 quality indicator measurement set. Journal of the American Geriatrics Society 2007 Oct;55(Suppl 2):S247‐s52.

(16) Yourman L, Concato J, Agostini JV. Use of computer decision support interventions to improve medication prescribing in older adults: a systematic review. American Journal of Geriatric Pharmacotherapy 2008 Jun;6(2):119‐29.

(17) Alldred DP, Raynor DK, Hughes C, Barber N, Chen TF, Spoor P. Interventions to optimise prescribing for older people in care homes. Cochrane Database of Systematic Reviews 2013; 2:{"type":"entrez-nucleotide","attrs":{"text":"CD009095","term_id":"30325833","term_text":"CD009095"}}CD009095.

(18) Christensen M, Lundh A. Medication review in hospitalised patients to reduce morbidity and mortality. Cochrane Database of Systematic Reviews 2013;2:{"type":"entrez-nucleotide","attrs":{"text":"CD008986","term_id":"30325724","term_text":"CD008986"}}CD008986.

(19) Clyne B, Bradley MC, Hughes C, Fahey T, Lapane KL. Electronic prescribing and other forms of technology to reduce inappropriate medication use and polypharmacy in older people: a review of current evidence. Clinics in Geriatric Medicine 2012;28(2):301‐22.

(20) Fleming A, Browne J, Byrne S. The effect of interventions to reduce potentially inappropriate antibiotic prescribing in long‐term care facilities: a systematic review of randomised controlled trials. Drugs & Aging 2013;30(6):401‐8.

(20) Forsetlund L, Eike MC, Gjerberg E, Vist GE. Effect of interventions to reduce potentially inappropriate use of drugs in nursing homes: a systematic review of randomised controlled trials. BMC Geriatrics 2011;11:16.

(21) Frazier SC. Health outcomes and polypharmacy in elderly individuals: an integrated literature review. Journal of Gerontological Nursing 2005;31(9):4‐11.

(22) George J, Elliott RA, Stewart DC. A systematic review of interventions to improve medication taking in elderly patients prescribed multiple medications. Drugs & Aging 2008;25(4):307‐24.

(23) Loganathan M, Singh S, Franklin BD, Bottle A, Majeed A. Interventions to optimise prescribing in care homes: systematic review. Age and Ageing 2011;40(2):150‐62.

(24) Maeda K. Systematic review of the effects of improvement of prescription to reduce the number of medications in the elderly with polypharmacy. Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan 2009;129(5):631‐45.

(25) Tani H, Uchida H, Suzuki T, Fujii Y, Mimura M. Interventions to reduce antipsychotic polypharmacy: a systematic review. Schizophrenia Research 2013;143(1):215‐20.

(26) Tjia J, Velten SJ, Parsons C, Valluri S, Briesacher BA. Studies to reduce unnecessary medication use in frail older adults: a systematic review. Drugs & Aging 2013;30(5):285‐307.

(27) Alldred DP, Kennedy M, Hughes C, Chen TF, Miller P. Interventions to optimise prescribing for older people in care homes. Cochrane Database of Systematic Reviews 2016;2:{"type":"entrez-nucleotide","attrs":{"text":"CD009095","term_id":"30325833","term_text":"CD009095"}}CD009095.

(28) Christensen M, Lundh A. Medication review in hospitalised patients to reduce morbidity and mortality. Cochrane Database of Systematic Reviews 2016;2: {"type":"entrez-nucleotide","attrs":{"text":"CD008986","term_id":"30325724","term_text":"CD008986"}}CD008986.

(29) Curtain C, Peterson G. Review of computerized clinical decision support in community pharmacy. J Clin Pharm Ther 2014;39(4):343‐348.

(30) Desborough J, Twigg M. Pharmacist‐led medication reviews in primary care. Reviews in Clinical Gerontology 2014;24(01):1‐9.

(31) Fried TR, O'Leary J, Towle V, Goldstein MK, Trentalange M, Martin DK. Health Outcomes Associated with Polypharmacy in Community‐Dwelling Older Adults: A Systematic Review. J Am Geriatr Soc 2014;62(12):2261‐2272.

(32) Hill‐Taylor B, Walsh K, Stewart S, Hayden J, Byrne S, Sketris I. Effectiveness of the STOPP/START (Screening Tool of Older Persons' potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria: systematic review and meta‐analysis of randomized controlled studies. J Clin Pharm Ther 2016;41(2):158‐169.

(33) Lehnbom EC, Stewart MJ, Manias E, Westbrook JI. Impact of medication reconciliation and review on clinical outcomes. Ann Pharmacother 2014 Oct;48(10):1298‐1312.

(34) Lonsdale DO, Baker EH. Understanding and managing medication in elderly people. Best Practice & Research Clinical Obstetrics & Gynaecology 2013;27(5):767‐788.

(35) Maher RL, Hanlon J, Hajjar ER. Clinical consequences of polypharmacy in elderly. Expert opinion on drug safety 2014;13(1):57‐65.

(36) Penge J, Crome P. Appropriate prescribing in older people. Reviews in Clinical Gerontology 2014;24(01):58‐77.

(37) Petrovic M, Somers A, Onder G. Optimization of geriatric pharmacotherapy: role of multifaceted cooperation in the hospital setting. Drugs Aging 2016;33(3):179‐188.

(38) Shade MY, Berger AM, Chaperon C. Potentially inappropriate medications in community‐dwelling older adults. Research in gerontological nursing 2014;7(4):178‐192.

(39) Walsh KA, O'Riordan D, Kearney PM, Timmons S, Byrne S. Improving the appropriateness of prescribing in older patients: a systematic review and meta‐analysis of pharmacists' interventions in secondary care. Age Ageing 2016;45(2):201‐209.

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Pharmaceutical care compared with usual care for older people receiving polypharmacy

Patient or population: older people receiving polypharmacy Settings: community, nursing home, hospital Intervention: pharmaceutical care Comparison: usual care
Outcomes	Effect estimate	Relative Risk effect (95% CI)	No. of participants (studies)	Certainty of evidence (GRADE)	Comments
Usual care	Pharmaceutical care
Medication appropriateness (as measured by an implicit tool)From baseline to follow‐up Follow‐up: 0 to 6 months	Medication appropriateness (as measured by an implicit tool) across control groups ranged from ‐0.49 to 2.86	Medication appropriateness (as measured by an implicit tool) in the intervention groups was 4.76lower (0.33 to 9.20 lower)		517 (5 studies)	⊕⊝⊝⊝ very low a,b,c,d	MAI used as implicit tool in the pooled studies A sensitivity analysis showed that medication appropriateness (as measured by an implicit tool) in the intervention group was 0.50 lower (2.27 lower to 1.28 higher)e Heterogeneity: I2 = 57%, P = 0.10
Potentially inappropriate medications
The number of potentially inappropriate medications (PIMs) Follow‐up: 0 to 12 months	The number of PIMs (Standardised mean§) across control groups ranged from 0.04 to 1.29	The number of PIMs (Standardised mean§) in the intervention groups was 0.22lower (0.05 to 0.38 lower)		1832 (7 studies)	⊕⊝⊝⊝ very lowa,b,c	STOPP and Beers criteria used as explicit tools in the pooled studies
The proportion of patients with one or more potentially inappropriate medications (PIMs) Follow‐up: 0 to 12 months	421 per 1000	333 per 1000 (257 to 430)	RR 0.79 (0.61 to 1.02)	3079 (11 studies)	⊕⊝⊝⊝ very lowa,b,c	STOPP and Beers criteria used as explicit tools in the pooled studies A sensitivity analysis showed that the proportion of patients with one or more potentially inappropriate medications in the intervention group was lower (333 per 1000)f Heterogeneity: I2 = 75%, P = 0.24
Potential prescribing omissions
The number of potential prescribing omissions (PPOs) Follow‐up: 0 to 12 months	The number of PPOs (Standardised mean§) across control groups ranged from 0.63 to 0.85	The number of PPOs (Standardised mean§) in the intervention groups was 0.81 lower (0.64 to 0.98 lower)		569 (2 studies)	⊕⊕⊝⊝ lowa	START and ACOVE used as explicit tools in the pooled studies
The proportion of patients with one or more potential prescribing omissions (PPOs) Follow‐up: 0 to 24 months	387 per 1000	155 per 1000 (70 to 329)	RR 0.40 (0.18 to 0.85)	1310 (5 studies)	⊕⊝⊝⊝ very lowa,c	START and ACOVE used as explicit tools in the pooled studies
Hospital admissions Follow‐up: 0 to 12 months	Pharmaceutical care may make little or no difference in hospital admissions	4052 (12 studies)	⊕⊕⊝⊝ lowa
Quality of Life Follow‐up: 0 to 12 months	Pharmaceutical care may make little or no difference in quality of life	3211 (12 studies)	⊕⊕⊝⊝ lowa
GRADE Working Group grades of evidence High: This research provides a very good indication of the likely effect. The likelihood that the effect will be substantially different‡ is low. Moderate: This research provides a good indication of the likely effect. The likelihood that the effect will be substantially different‡ is moderate. Low: This research provides some indication of the likely effect. However, the likelihood that it will be substantially different‡ is high. Very low: This research does not provide a reliable indication of the likely effect. The likelihood that the effect will be substantially different‡ is very high. ‡Substantially different = a large enough difference that it might affect a decision