OPERAM - A European multicenter randomised clinical trial

The activities in OPERAM are concentrated around multimorbidity, polypharmacy and drug-related hospital admissions (DRA).

MULTIMORBIDITY
Multimorbidity is the coexistence of several chronic diseases.¹ It is associated with higher rates of drug prescriptions, decreased quality of life, increased healthcare utilisation, hospital admissions² and increased mortality.³ Multimorbid patients are usually older, have more activity limitations, and present with more complex clinical pictures – rendering medical care a real challenge and going along with considerable cost (two-thirds of the overall healthcare expenditures).² Despite the large number of patients with multimorbidity, they are excluded in more than 60% of the randomised controlled clinical trials (RCT) published during the last 15 years, and only 2% of RCTs explicitly included patients with multimorbidity.⁴ Therefore, evidence and guidelines for diagnostics and treatment of multimorbid patients are sparse and mainly adopted and merged from isolated diseases.

POLYPHARMACY
Polypharmacy is defined as the concurrent use of multiple drugs.  A clear and consistent definition is lacking, but taking ≥ 5 chronic medications is a common used approach. ⁵ Multimorbidity is associated with polypharmacy, illustrated by the following numbers: 50% of patients with ≥ 3 chronic conditions are polypharmacised, and 10% of patients with  ≥ 5 chronic conditions take at least 10 different drugs. ⁶ Appropriate polypharmacy can improve quality of life and prevent consequences of diseases, whereas inappropriate polypharmacy is harmful and can have detrimental effects, especially in elderly patients. ⁵ It is associated with an increased risk of interactions with other drugs and diseases, adverse drug events (ADE), and drug-related hospital admissions (DRA) as well as prescribing errors. ^7,8  The estimated prevalence of inappropriate prescribing (overuse, underuse) for three different settings (primary care, hospital care, nursing home care) is reported in figure 1. ^9-12

Figure 1. Prevalence of inappropriate prescribing (overuse, underuse) in primary care, hospital care, and nursing home care. ^9-12

DRUG-RELATED HOSPITAL ADMISSIONS (DRA)
Multimorbidity, polypharmacy, and old age are important risk factors for DRAs (Figure 2). ⁷ The reported incidence of DRAs in the elderly are as high as 30% of all acute cases, and about half of DRAs are likely to be preventable. ^7,13 It is estimated that 3% of all deaths are due to DRA, therefore DRA are the 5th most common cause of death. ¹⁴ Furthermore, in the US, the overall costs of drug related morbidity and mortality have been estimated to more than 170 billion, of which nearly 70 % are due to DRA. ¹⁵ As a result of the epidemiological trend, multimorbidity, polypharmacy and DRAs will be even more important in the future and will pose a great challenge on the already hampered health care system.

FIGURE 2. Association multimorbidity, polypharmacy, and drug-related hospital admissions

REFERENCES

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2) Chronic Care: Making the Case for Ongoing Care. 2010.

3) Menotti A, Mulder I, Nissinen A, Giampaoli S, Feskens EJ, Kromhout D. Prevalence of morbidity and multimorbidity in elderly male populations and their impact on 10-year all-cause mortality: The FINE study (Finland, Italy, Netherlands, Elderly). J Clin Epidemiol 2001;54:680-6.

4) Jadad AR, To MJ, Emara M, Jones J. Consideration of multiple chronic diseases in randomized controlled trials. JAMA 2011;306:2670-2.

5) Gnjidic D, Hilmer SN, Blyth FM, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol 2012;65:989-95.

6) Aubert C, Rodondi N. Manuscript in preparation.

7) Leendertse AJ, Egberts AC, Stoker LJ, van den Bemt PM. Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands. Arch Intern Med 2008;168:1890-6.

8) Patterson SM, Hughes C, Kerse N, Cardwell CR, Bradley MC. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev 2012;5:CD008165.

9) Gillespie U, Alassaad A, Henrohn D, et al. A comprehensive pharmacist intervention to reduce morbidity in patients 80 years or older: a randomized controlled trial. Arch Intern Med 2009;169:894-900.

10) Howard RL, Avery AJ, Slavenburg S, et al. Which drugs cause preventable admissions to hospital? A systematic review. Br J Clin Pharmacol 2007;63:136-47.

11) Beers MH, Ouslander JG, Rollingher I, Reuben DB, Brooks J, Beck JC. Explicit criteria for determining inappropriate medication use in nursing home residents. UCLA Division of Geriatric Medicine. Arch Intern Med 1991;151:1825-32.

12) Gallagher P, O'Mahony D. STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers' criteria. Age Ageing 2008;37:673-9.

13) Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ 2004;329:15-9.

14) Wester K, Jönsson AK, Spigset O, Druid H, Hägg S. Incidence of fatal adverse drug reactions: a population based study. Br J Clin Pharmacol. 2008;65(4):573-9.

15) Ernst FR, Grizzle AJ. Drug-related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc (Wash) 2001;41:192-9.