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Potentially inappropriate medication use in elderly patients: A study of prevalence and predictors in two teaching hospitals A Harugeri1, J Joseph1, G Parthasarathi1, M Ramesh1, S Guido21 Department of Pharmacy Practice, J.S.S. College of Pharmacy and J.S.S. Medical College Hospital, J.S.S. University, Mysore, India 2 Department of Pharmacology, St. John's Medical College Hospital, Bangalore, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.68642
Background: Geriatrics is an emerging clinical specialty in India. Information about the appropriateness of prescription medication use among the elderly in India is limited. Aims: To determine the prevalence and predictors of potentially inappropriate medication (PIM) use, and assess the relationship between PIM use and adverse drug reactions (ADRs) in the hospitalized elderly. Settings: Medicine wards at two teaching hospitals. Design: Prospective observational study. Materials and Methods: Patients aged > 60 years admitted to medicine wards between January 2008 and June 2009 were included and reviewed for PIM use according to the Beers Criteria 2003 (BC). Severity of PIM use was classified as per BC as 'high' or 'low'. ADRs observed in the study patients were also recorded. Statistical Analysis: Association between ADRs and PIM use was assessed using Chi Square test. Bivariate analysis and subsequently multivariate logistic regression was used to identify predictors of PIM use. Results: PIM use was observed in 191 of 814 enrolled patients. At least one PIM at admission and during hospital stay was received by 2.4% (20) and 22.1% (180) patients respectively. High-severity PIM use showed a higher prevalence compared to low severity [26.8% (218) vs. 5.5% (45)]. Amongst the patients who received polypharmacy (> 5 concurrent medications), 1.4% (5/362) and 22.1% (163/736) patients received PIMs at admission and during hospital stay respectively. Use of aspirin/clopidogrel/diclofenac in the presence of blood clotting disorder or anticoagulant therapy (8.3%) was the most commonly encountered PIM use. Medications not listed in BC were associated with increased occurrence of ADRs compared to medications listed in BC (349 vs. 11) (χ2 =98.4, P<0.001). Increased number of concurrent medications' use (≥9) during the stay in medicine wards was identified as an influential predictor of PIM use [Odds ratio: 1.9, 95% Confidence Interval: 1.34-2.69, P<0.001) in the hospitalized elderly. Conclusion: PIM use was common (23.5%) among the elderly patients during their stay in medicine wards in two tertiary care hospitals. Measures targeted only at BC medications may do little to change the risk of ADRs in elderly. Keywords: Adverse drug reaction, aged, drug utilization review, geriatrics, India, prescriptions
Several factors contribute to greater propensity of adverse drug reactions (ADRs) in the elderly, including potentially inappropriate medication (PIM) use. Elderly patients are prescribed PIMs in an ambulatory setting and during hospitalization. [1],[2],[3],[4],[5] About one-fourth of the adverse outcomes in the elderly are estimated to be due to PIM use. [5],[6] Geriatrics is an emerging clinical specialty in India. Information related to quality of medication use among the elderly in India is limited. There is a need for prospective studies that evaluate PIM use and burden of adverse events due to PIM use in India. [7] Our study presents and discusses the prevalence and predictors of PIM use, and association between PIM use and ADRs in patients aged > 60 years at admission and during their stay in medicine wards.
The prospective observational study was conducted in the medicine wards of two teaching hospitals located in the state of Karnataka, southern India. The study was approved by the ethics committees at both the hospitals. Patients aged > 60 years admitted to medicine wards receiving at least one medication at admission and /or prescribed with at least one medication during hospital stay were randomly (convenience sample collected opportunistically) included between January 2008 and June 2009 after obtaining written informed consent. The included patients were reviewed from the day of admission to discharge for PIM use and ADRs. Beers Criteria 2003 (BC) were used to assess PIM use. [8] The BC classifies PIM use into two types, the first type includes medications which should be avoided in general, regardless of the diseases/conditions, in the elderly because of their risk of adverse effects and the second type includes medications in doses considered as higher than normal for the elderly and which should be avoided in the presence of specific diseases/conditions. Considering the severity of adverse outcome, the BC classifies PIM use as 'high' or 'low'. Causality of the ADRs was assessed using Naranjo's algorithm. [9] Patients' records, medication history and where appropriate, discussion with patients' attendants and healthcare professionals formed the source of data for the identification, documentation and assessment of PIM use and ADRs. Similar to previous studies, [10],[11] polypharmacy was defined as concurrent use of five or more medications. Prevalence of PIM use among patients with specific characteristics was calculated by considering the number of patients receiving PIM as numerator and number of patients with specific characteristic as denominator. Prevalence of PIM use at admission/during the stay in medicine wards, considering/regardless of diseases/conditions, and their severity was calculated by considering the number of patients with PIM use as numerator and total number of patients included in the study as denominator. Association between ADRs and PIM use was assessed using the Chi Square test. Using bivariate analysis, predictors associated with PIM use were identified (independent variables). Multivariate logistic regression by enter method was used to evaluate the influence of these independent variables on PIM use. Statistical analysis was carried out using Statistical Package for Social Science (SPSS) Version 17.0; a P value <0.05 was considered as statistically significant.
A total of 814 patients were included. Of the included patients, 59.9% (488) were in the age group of 60-69 years, 31.3% (255) were in the age group 70-79 years and 8.7% (71) were aged ≥80 years. The median age of the study population was 66 years (range 60-95 years). The study population comprised of 60.6% males [Table 1]. Average number of concurrent medications received by the patients at admission and during stay was 2.9 (range 1 to 12) and 9.4 (range 1 to 22) per patient respectively. The majority of the patients (58.1%) stayed in the medicine ward for 5 to 9 days while a small number of patients (4%) stayed for 15 days or longer. On an average 7.6, 9.2 and 11.5 medications were used during hospital stay in patients who stayed for ≤ 4, 5 to 9, and >10 days respectively. Most of the patients were diagnosed to have two diseases (32.6%) followed by three (26%), four or more (22.4%) and one (19%) disease. Essential hypertension (41.5%), non-insulin-dependent diabetes mellitus (34%) and chronic obstructive pulmonary disease (18.5%) were the three most frequent diagnoses in the study population.
PIMs were received by 191 (23.5%) patients. At least one PIM at admission and during hospital stay was received by 20 (2.4%) and 180 (22.1%) patients respectively. PIM use was observed both at admission and during hospital stay in nine (1.1%) patients. One, two and three PIMs were received by 134, 46 and 11 patients respectively. Polypharmacy was observed in 44.5% and 90.4% of patients at admission and during hospital stay. Amongst the patients who received polypharmacy, 1.4% and 22.1% patients received PIMs at admission and during hospital stay respectively. High-severity PIM use showed a higher prevalence compared to low severity (26.8% vs. 5.5%). Also, considering or without considering the diseases/conditions, prevalence of high-severity PIM use was more than low severity (9.3% vs. 0.1% and 17.4% vs. 5.4%). Considering both at admission and during hospital stay, the prevalence of PIM use regardless of the diseases/conditions was higher than considering the diseases/conditions (22.8% vs. 9.5%). The most common PIMs identified, regardless of the diseases/conditions, at admission were digoxin (0.5%) and nifedipine (0.5%) while mineral oil (liquid paraffin) (6.4%) and propoxyphene (usually in combination with paracetamol) (2.5%) were the most common PIMs used during the hospital stay [Table 2]. Considering the diseases/conditions, the most frequently observed PIM use at admission was use of diclofenac/ibuprofen in the presence of gastric ulcer (0.4%). Use of asprin/clopidogrel/diclofenac in the presence of an anticoagulant (8.3%) was the most commonly encountered PIM use during hospital stay [Table 3].
A total of 360 ADRs were observed in 292 patients. Of these, 11 (3%) ADRs observed in 11 patients were due to medications listed in BC. All 11 ADRs due to medications listed in BC were due to PIM use regardless of the diseases/conditions during hospital stay. Of these 11 ADRs, three were due to clonidine, two each were due to amiodarone, diazepam, hydroxyzine and digoxin. Among the ADRs due to medications not listed in BC (349), insulin (14%, 49), furosemide (6.3%, 22) and prednisolone (5.1%, 18) were the most frequently implicated medications in ADRs. Medications not listed in BC resulted in more number of ADRs than medications listed in BC [χ2 =98.4, P<0.001 (df=1)] [Odds ratio (OR): 13.51 {95% confidence interval (CI): 7.19-25}; P<0.001]. Bivariate analysis identified increased number (≥9) of concurrent medications' use during hospital stay (OR: 2.33, CI: 1.58-3.43, P<0.001) and prolonged length of stay (≥10 days) in medicine wards (OR: 1.95, CI: 1.19-3.21, P=0.006) as predictors of PIM use [Table 4]. Among these predictors, increased number (≥9) of concurrent medications' use during hospital stay (OR: 1.9, CI: 1.34-2.69, P<0.001) was found as the only influential predictor of PIM use [Table 5]. Gender, age, number of diseases and number of concurrent medications used at admission did not predict PIM use.
A PubMed and OvidSP search using 'elderly', 'drug utilization' and 'India' as the search terms found that ours is the largest prospective study of PIM usage evaluation in the hospitalized elderly in India. The main findings of the study are that 23.5% of study patients received at least one PIM (at admission or during hospital stay) and more than one-third of these patients were prescribed aspirin/non-steroidal anti-inflammatory drug (NSAID) in presence of bleeding disorder or along with an anticoagulant . Medications not listed in BC were associated with increased occurrence of ADRs compared to medications listed in BC (χ2 =98.4, P<0.001). Furthermore, multivariative analysis showed that patients concurrently receiving ≥9 medications during the hospital stay was the influential predictor of PIM use. The prevalence of PIM use observed at admission was low compared to that reported at admission/in ambulatory patients in other studies conducted in France (66%), [12] Switzerland (22.1%), [13] Taiwan (23.7%) [14] and United States (US) {(32%), [15] (7.8%), [16] and (32%) [17]}. This may be due to few medications received at admission. Prevalence of PIM use during hospital stay was less compared to that reported in other studies conducted in France (43.6%) [12] and US {(56%), [15] (40.7%), [18] (49.6%), [19] and (27.5%) [20]} while it was more compared to that reported in studies conducted in India (17.9%) [21] and Switzerland (15.9%). [13] The difference in prevalence is possibly due to differences in patient and disease characteristics, prescribing patterns, study settings and availability of medications listed in BC. In contrast to the reports in other studies, [12],[22] we found that the prevalence increased by nearly 20% after hospitalization. PIMs at admission were discontinued after hospitalization in all patients. However, 45% (9) of these patients received other PIMs during hospital stay. Increased prevalence of PIM use during hospital stay highlights the need of practicing geriatrics as a medical specialty in India and the scope of continuing medical education on quality use of medicines in the hospitalized elderly. The BC are applicable to patients aged >65 years. The cutoff age for the elderly in India and other developing countries is 60 years. [23] The cutoff age for the elderly is also supported by the low life expectancy of the Indian population compared to developed countries [64 years vs. 78 years (US) and 80 years (United Kingdom)], normal age for retirement, age boundary for senior citizenship qualification in India, and literature reports. [21],[24],[25],[26],[27],[28] Similar to other studies, [14],[16],[29] older age (≥80 years) was associated with increased use of PIMs (OR:1.68, CI: 0.93-3.04, P=0.062). In contrast to the findings of other studies, [5],[14] the number of diagnoses was not a predictor of PIM use. This could be due to very few medications used in treating the most common diagnoses in the study population that are listed in BC. Polypharmacy observed was higher than that reported internationally. [30],[31] Increased likelihood of PIM use observed with increased medication use during hospital stay was similar to other studies. [5],[12],[14],[16],[29] In contrast with the findings of another study, [20] ≥10 days of hospitalization was associated with increased likelihood of PIM use. This is due to the proportional relationship between length of stay and number of medications used. Although increased number of medications' use may point to the likelihood of exposure to PIMs, it may not necessarily reflect the irrational use of medicines as in a few patients it may be appropriate to use more number of medications. Increased prevalence of PIM use regardless of the diseases/conditions was due to the disease characteristics of the study population. Hypertension and chronic obstructive pulmonary disease were the only common diseases listed in BC observed in our study population. Similar to other studies we observed increased prevalence of high-severity PIM use. [15],[21],[32] We compared our study findings with the only published study [13] to our knowledge that included medical ward patients and analyzed PIM use similar to our study. Most commonly used PIMs regardless of the diseases/conditions in the study by Egger et al., [13] were anticholinergic antispasmodics or anticholinergics and amiodarone both at admission and during the hospital stay. In our study, digoxin and nifedipine were the most commonly used PIMs at admission, and mineral oil and propoxyphene during hospital stay. The most commonly used PIMs considering the diseases/conditions at admission in the study by Egger et al., [13] were use of benzodiazepine for >2 weeks or sympatholytics in presence of depression and use of NSAIDs or platelet aggregation inhibitors in presence of blood clotting disorders or anticoagulant. While, in our study it was use of diclofenac in presence of gastric ulcer. During hospital stay, use of NSAIDs or platelet aggregation inhibitors in presence of blood clotting disorders or anticoagulant was the most common PIM use in both, in the study by Egger et al., [13] and in our study. However, comparisons with this study [13] must be interpreted carefully for reasons that include differences in patient characteristics, sample size and availability of medications listed in BC. Similar to the other studies, use of NSAIDs or platelet aggregation inhibitors in presence of blood clotting disorders or anticoagulant was the most widely identified PIM use. [13],[21] In a recent study from the US, warfarin alone accounted for 17.3% of all emergency department visits for adverse events. [33] However, not a single case of NSAIDs or platelet aggregation inhibitors' use in presence of blood clotting disorders or anticoagulant was observed in the study. [33] The difference in observation compared to our study may be due to difference in study settings and prescribing practices. The aspiration of liquid paraffin causes exogenous lipoid pneumonia. [34] In a French study, duration of exposure to liquid paraffin that caused lipoid pneumonia (one month to 9.5 years), [35] was longer compared to our study (3 to 12 days). None of our study patients experienced lipoid pneumonia. Classification of dextropropoxyphene as a PIM and its efficacy at doses <65 mg has been questioned. [12],[36] In our study, 70% of the patients who received dextropropoxyphene, received 32.5 mg of dextropropoxyphene in combination with 500 mg of paracetamol. Though 23.5% of the patients received PIMs, only 3% of the study patients experienced an ADR due to PIM use as per BC. Low frequency of occurrence of ADRs due to medications listed in BC is reported in the literature (3.6-11.6%). [7],[20],[33] This was also evident from our study. Interventions targeted only at BC medications may do little to change the risk of ADRs in the elderly. Interventions that are more comprehensive like targeting the medications commonly implicated in ADRs could reduce the risk of ADRs in the elderly. [7] The study involved only two tertiary care hospitals and thus the results can neither be generalized nor extrapolated. BC does not include all medications that cause potential adverse outcomes in the elderly. This may have resulted in underestimation of prevalence of PIM use. The study did not intervene in the PIM use and did not evaluate the continuation of PIMs that were prescribed during hospital stay. Pharmacotherapy in the elderly requires a balance between inappropriate medication use and under-treatment. PIM use was found to be common among the hospitalized elderly of medicine wards in two tertiary care hospitals of south India and was associated with patients' age, number of concurrent medications used and length of hospital stay. Measures to reduce the risk of ADRs in the elderly should target medications commonly implicated in ADRs rather than focusing only on medications listed in BC. Interventions aimed at rational medication use in elderly Indians should focus on the predictors of PIM use. There is a great scope for conducting intense research to determine inappropriate medication use and its health-related adverse consequences in the increasing Indian elderly population.
The authors sincerely thank the staff of the Department of Medicine at St. John's Medical College, Bangalore and JSS Medical College Hospital, Mysore for their help and cooperation in access to patients and treatment charts during the study period, as well as Mr. Rohan Elliot, Geriatric Clinical Pharmacist, Austin Repatriation Hospital, Melbourne, Australia for his comments and suggestions on the earlier versions of the manuscript. Our thanks to Indian Council of Medical Research for the Senior Research Fellowship awarded to Mr. Harugeri during the conduct of this study. We also extend our thanks to St. John's National Academy of Health Sciences, Bangalore, JSS Mahavidyapeetha, and Principal, JSS College of Pharmacy, Mysore for their support and encouragement.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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