Hospitalization in older patients due to adverse drug reactions –the need for a prediction tool

Figures & data

Table 1 Most common ADRs causing hospitalization in the elderly

Most common ADRs	Examples
Gastrointestinal complications^Citation5,Citation18,Citation22^–^Citation24	Gastrointestinal bleeding, peptic ulcer, erosive gastritis, nausea, vomiting
Cardiovascular disorders^Citation12,Citation18,Citation19,Citation22	Hypotension, bradycardia, falls, arrhythmias
Metabolic/endocrine complications^Citation5,Citation12,Citation24	Hypoglycemia
Renal and urinary disorders^Citation22^–^Citation24	Renal impairment, acute renal failure
Electrolyte disorders^Citation20,Citation22	Hypokalemia, hyperkalemia, hyponatremia
Nervous system disorders^Citation12,Citation23	Depressed level of consciousness, mental status changes

Abbreviation: ADRs, adverse drug reactions.

Table 2 Most common drugs causing ADR-related hospital admission in the elderly

Antibacterials^Citation5,Citation18,Citation20

Anticonvulsants^Citation58

Antineoplastic agents^Citation5,Citation35

Antipsychotics^Citation5,Citation35

Antithrombotics (anticoagulants and antiplatelets)^Citation18,Citation20,Citation23,Citation24,Citation35,Citation58

Cardiovascular drugs (diuretics,^Citation5,Citation20,Citation22^–^Citation24,Citation35 cardiac glycosides,^Citation5,Citation18,Citation58 angiotensin-converting enzyme inhibitors,^Citation18,Citation23,Citation24,Citation29,Citation58 beta-blockers,^Citation29,Citation58 antiarrhythmics,^Citation18,Citation24 calcium channel blockers^Citation5)

Corticosteroids^Citation5

Hypoglycemics^Citation35,Citation58

Nonsteroidal anti-inflammatory drugs^Citation5,Citation18,Citation22^–^Citation24,Citation58

Abbreviation: ADR, adverse drug reaction.

Table 3 Studies investigating risk factors for ADR-related hospital admission in older patients

Study	Country Year conducted	Design	Duration	Settings	Mean/median age (years)	Main outcome measures	Predictors/risk factors
Onder et al^Citation5	Italy 1988–1997	Multicenter pharmacoepidemiology survey	10 years	Academic hospitals	70	ADR severity, potentially responsible drugs, predictors	Female sex (OR 1.30, 95% CI 1.10–1.54) Alcohol use (OR 1.39, 95% CI 1.20–1.60) Number of drugs (OR 1.24, 95% CI 1.20–1.27 for each drug increase) Severe ADRs Age (OR 1.50, 95% CI 1.01–2.23 for age 65–79 years and OR 1.53, 95% CI 1.00–2.33 for age ≥80 years) Comorbidity (OR 1.12, 95% CI 1.05–1.20 for each point in the CCI) Number of drugs (OR 1.18, 95% CI 1.11–1.25 for each drug increase)
Marcum et al^Citation12	USA 2004–2006	Retrospective cohort	3 years	All admissions (veterans)	76.4	ADR causality, preventability, predictors	Polypharmacy (≥9 and 5–8 medications) (AOR 3.90, 95% CI 1.43–10.61 and AOR 2.85, 95% CI 1.0–7.85, respectively)
Mannesse et al^Citation17	The Netherlands 1994	Observational cross-sectional	3 months	University hospital	78	Risk indicators for severe ADRs	Fall before admission (OR 51.3, P=0.006) Gastrointestinal bleeding or hematuria (OR 19.8, P<0.00l) Use of three or more drugs (OR 9.8, P=0.04)
Franceschi et al^Citation18	Italy 2004–200S	Prospective cross-sectional	1 year	Geriatric	76.5	ADR prevalence, avoidability	Drug-drug interactions (32.3%) Inappropriate prescription (21.8%)
Wawruch et al^Citation19	Slovakia 2003–2005	Retrospective cross-sectional	1.4 years	Internal medicine	76.6	ADR predictors	Ischemic heart disease (OR 4.50, 95% CI 1.36–14.88) Depression (OR 2.49, 95% CI 1.08–5.77) Heart failure (OR 2.08, 95% CI 1.13–3.81)
Wu et al^Citation21	Canada 2003–2008	Retrospective cohort	5 years	Emergency department	77	Incidence, cost, risk factors	Sex (for females, AOR 0.81, 95% CI 0.72–0.92) Age (AOR 1.03, 95% CI 1.02–1.04) CCI score >3 (AOR 1.86, 95% CI 1.48–2.33) Number of drugs (AOR 1.48, 95% CI 1.13–1.93 for 6–10 drugs and AOR 1.93, 95% CI 1.49–2.51 for > 1 1 drugs) Multiple pharmacies (AOR 1.13, 95% CI 1.00–1.27) Newly prescribed drugs (AOR 1.17, 95% CI 0.93–1.47) Recent hospital admission (AOR 1.47, 95% CI 1.23–1.76) Long-term care residence (AOR 2.08, 95% CI 1.62–2.67)
Pedros et al^Citation23	Spain 2009–2010	Cross-sectional	120 days	Teaching hospital	75	ADR predictors	Age ≥65 years (OR 1.59, 95% CI 1.10–2.29) Number of drugs taken 3–5 (OR 5.07, 95% CI 2.71–9.50), 6–9 (OR 5.90, 95% CI 3.16–1 1.01), and ≥ 10 (OR 8.94, 95% CI 4.73–16.89)
Alexopoulou et al^Citation24	Greece 2005	Prospective cross-sectional	6 months	University hospital	65	Frequency of ADRs, causality, severity, preventability, predictors	Number of drugs (OR 1.064, 95% CI 1.019–1.109)
Olivier et al^Citation35	France 2002–2003	Prospective cross-sectional	4 weeks	Emergency department	80.2	ADR incidence, risk factors	Number of drugs (OR 1.18, 95% CI 1.08–1.29) Self-medication (OR 2.34, 95% CI 1.18–4.66) Use of antithrombotics (OR 2.26, 95% CI 1.33–3.88) Use of antibacterial drugs (OR 4.04, 95% CI 1.50–10.83)
Malhotra et al^Citation37	India 2000	Prospective cross-sectional	7 months	Emergency department	72.5	Risk factors	Number of drugs ≥3 (OR 4.3) Consulting >3 physicians (OR 5.7) Living alone (OR 4.3)
Chen et al^Citation38	Taiwan 2009–2010	Prospective case-control	1 year	Emergency department	65	Risk factors	Number of drugs (AOR 4.1, 95% CI 2.4–6.9 for 3–7 drugs; AOR 6.4, 95% CI 3.7–11.0 for eight or more drugs) and increased concentration of serum creatinine (AOR 1.5, 95% CI 1.1–2.2)
Zhang et al^Citation41	Australia 2005	Retrospective cohort	Records of ADR admission from 1980 to 2000 and followed for 3 years	All public and private hospitals	Mean age not reported, study in patients aged ≥60 years	ADR predictors	Sex(HR 1.08, 95% CI 1.02–1.15, for men) First admission in 1995–1999 (HR 2.34, 95% CI 2.00–2.73) Length of hospital stay (HR 1.1 1, 95% CI 1.05–1.18, for stays ≥ 14 days) CCI (HR 1.71, 95% CI 1.46–1.99, for score ≥7) Comorbid congestive cardiac failure (HR 1.56, 95% CI 1.43–1.71), peripheral vascular disease (HR 1.27, 95% CI 1.09–1.48), chronic pulmonary disease (HR 1.61, 95% CI 1.45–1.79), rheumatological disease (HR 1.65, 95% CI 1.41–1.92), mild liver disease (HR 1.48, 95% CI 1.05–2.07), moderate to severe liver disease (HR 1.85, 95% CI 1.18–2.92), moderate diabetes (HR 1.18, 95% CI 1.07–1.30), diabetes with chronic complications (HR 1.91, 95% CI 1.65–2.22), renal disease (HR 1.93, 95% CI 1.71–2.17), any malignancy including lymphoma and leukemia (HR 1.87, 95% CI 1.68–2.09), and metastatic solid tumors (HR 2.25, 95% CI 1.92–2.64)

Abbreviations: ADR, adverse drug reaction; OR, odds ratio; CI, confidence interval; CCI, Charlson Comorbidity Index; AOR, adjusted odds ratio; HR, hazard ratio.

Table 4 An overview of predictors of ADR-related hospital admission in the elderly

Frequently reported predictors	Other predictors
Number of medications^Citation5,Citation12,Citation17,Citation21,Citation23,Citation24,Citation35^–^Citation38	Drug interactions^Citation18
Comorbid conditions^Citation5,Citation19,Citation21,Citation36,Citation41	Female sex^Citation5
Age^Citation5,Citation21,Citation23	Self-medication^Citation35
Potentially inappropriate medications^Citation44,Citation45	Use of antithrombotics^Citation35
	Use of antibacterial drugs^Citation35
	Alcohol use^Citation5
	Falls before admission^Citation17
	Patients living alone^Citation37
	Increased serum creatinine^Citation38
	Multiple pharmacy visits^Citation21
	More than three consulting physicians^Citation37
	Newly prescribed drugs^Citation21
	Recent hospital admission^Citation21
	Long-term care residence^Citation21
	Patients with diabetes or neoplasms^Citation37
	Gastrointestinal bleeding or hematuria^Citation17
	Ischemic heart disease^Citation19
	Depression^Citation19
	Heart failure^Citation19

Abbreviation: ADR, adverse drug reaction.

Table 5 Features of validated ADR prediction tools for elderly hospitalized patients

Features	Onder et al^Citation49 (GerontoNet ADR risk score)	Tangiisuran et al^Citation48 (BADRI) model
Study design
Developmental stage	Retrospective cohort	Prospective cohort
Validation stage	Prospective cohort	Prospective cohort
Main outcome measure	ADR (6.5%)	ADR (12.5%)
Age of study participants (years)	Mean (SD)	Median (IQR)
	78 (7.2)	85 (81–89)
Most common ADRs	Cardiovascular and arrhythmic complications	–
Predictors of ADRs	≥4 Comorbid conditions	≥8 drugs
	Heart failure	Hyperlipidemia
	Liver disease	Raised white cell count
	Number of drugs	Use of antidiabetic agents
	History of ADR	Length of stay ≥12 days
	Renal failure
Predictive ability of risk score (AUROC)
Developmental stage	0.71 (95% CI 0.68–0.73)	0.74 (95% CI 0.68–0.79)
Validation stage	0.70 (95% CI 0.63–0.78)	0.73 (95% CI 0.66–0.80)
Cutoff score	Between 3 and 4	>1
Sensitivity	68%	80%
Specificity	65%	55%

Abbreviations: ADR, adverse drug reaction; AUROC, area under the receiver operating characteristic curve; CI, confidence interval; SD, standard deviation; IQR, interquartile range.

OnderGPedoneCLandiFAdverse drug reactions as cause of hospital admissions: results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA)J Am Geriatr Soc200250121962196812473007

 PubMed Web of Science ®Google Scholar

FranceschiMScarcelliCNiroVPrevalence, clinical features and avoidability of adverse drug reactions as cause of admission to a geriatric unit: a prospective study of 1756 patientsDrug Saf200831654555618484788

 PubMed Web of Science ®Google Scholar

PirmohamedMJamesSMeakinSAdverse drug reactions as cause of admission to hospital: prospective analysis of 18820 patientsBMJ20043297456151915231615

 PubMed Web of Science ®Google Scholar

AlexopoulouADourakisSPMantzoukisDAdverse drug reactions as a cause of hospital admissions: a 6-month experience in a single center in GreeceEur J Intern Med200819750551019013378

 PubMed Web of Science ®Google Scholar

MarcumZAAmuanMEHanlonJTPrevalence of unplanned hospitalizations caused by adverse drug reactions in older veteransJ Am Geriatr Soc2012601344122150441

 PubMed Web of Science ®Google Scholar

WawruchMZikavskaMWsolovaLAdverse drug reactions related to hospital admission in Slovak elderly patientsArch Gerontol Geriatr200948218619018313773

 PubMed Web of Science ®Google Scholar

ConfortiACostantiniDZanettiFMorettiUGrezzanaMLeoneRAdverse drug reactions in older patients: an Italian observational prospective hospital studyDrug Healthc Patient Saf20124758022888275

 PubMedGoogle Scholar

PedrosCQuintanaBRebolledoMPortaNVallanoAArnauJMPrevalence, risk factors and main features of adverse drug reactions leading to hospital admissionEur J Clin Pharmacol201470336136724362489

 PubMed Web of Science ®Google Scholar

WuWKPantaleoNEvaluation of outpatient adverse drug reactions leading to hospitalizationAm J Health Syst Pharm200360325325912613234

 PubMed Web of Science ®Google Scholar

OlivierPBertrandLTuberyMLauqueDMontastrucJLLapeyre-MestreMHospitalizations because of adverse drug reactions in elderly patients admitted through the emergency department: a prospective surveyDrugs Aging200926647548219591522

 PubMed Web of Science ®Google Scholar

AhernFSahmLJLynchDMcCarthySDetermining the frequency and preventability of adverse drug reaction-related admissions to an Irish University Hospital: a cross-sectional studyEmerg Med J2014311242923389832

 PubMed Web of Science ®Google Scholar

MannesseCKDerkxFHde RidderMAMan in ‘t VeldAJvan der CammenTJContribution of adverse drug reactions to hospital admission of older patientsAge Ageing2000291353910690693

 PubMed Web of Science ®Google Scholar

WuCBellCMWodchisWPIncidence and economic burden of adverse drug reactions among elderly patients in Ontario emergency departments: a retrospective studyDrug Saf201235976978122823502

 PubMed Web of Science ®Google Scholar

MalhotraSKaranRSPandhiPJainSDrug related medical emergencies in the elderly: role of adverse drug reactions and non-compliancePostgrad Med J20017791370370711677279

 PubMed Web of Science ®Google Scholar

ChenYCFanJSChenMHRisk factors associated with adverse drug events among older adults in emergency departmentEur J Intern Med2014251495524200546

 PubMed Web of Science ®Google Scholar

ZhangMHolmanCDPriceSDSanfilippoFMPreenDBBulsaraMKComorbidity and repeat admission to hospital for adverse drug reactions in older adults: retrospective cohort studyBMJ2009338a275219129307

 PubMed Web of Science ®Google Scholar

VenturaMTLaddagaRCavalleraPAdverse drug reactions as the cause of emergency department admission: focus on the elderlyImmunopharmacol Immunotoxicol201032342642920095805

 PubMed Web of Science ®Google Scholar

PriceSDHolmanCDSanfilippoFMEmeryJDAssociation between potentially inappropriate medications from the Beers criteria and the risk of unplanned hospitalization in elderly patientsAnn Pharmacother201448161624396090

 PubMed Web of Science ®Google Scholar

FickDMMionLCBeersMHL WallerJHealth outcomes associated with potentially inappropriate medication use in older adultsRes Nurs Health2008311425118163447

 PubMed Web of Science ®Google Scholar

OnderGPetrovicMTangiisuranBDevelopment and validation of a score to assess risk of adverse drug reactions among in-hospital patients 65 years or older: the GerontoNet ADR risk scoreArch Intern Med2010170131142114820625022

 PubMedGoogle Scholar

TangiisuranBScuttGStevensonJDevelopment and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) modelPLoS One2014910e11125425356898

 PubMed Web of Science ®Google Scholar