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Inappropriate drug use in hospitalized elderly
patients of medicine and cardiology departments at
a tertiary care hospital...
Research Article
Inappropriate drug use in hospitalized elderly
patients of medicine and cardiology departments at
a terti...
therapeutic outcome e including patient experience, health
outcomes, overall performance, and with estimates of the
financi...
3.2. General distribution of disease
The average disease per patient was found to be 3.20 Æ 1.26.
The total number of diag...
comprised of ciprofloxacinandofloxacin were2ndmostwidely
prescribed antibiotic in this study. Moreover, this quinolones
are ...
nervous system. In the study Page JG et al has reported ma-
jority of adverse effects which were related to the anticho-
l...
15. Niwata S, Yamada Y, Ikegami N. Prevalence of inappropriate
medication using beers criteria in Japanese long-term care
...
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Inappropriate drug use in hospitalized elderly patients of medicine and cardiology departments at a tertiary care hospital of Northeast India

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National committee on quality assurance, USA convened an expert consensus panel and identified the list of drugs which should be avoided in the elderly people. This resulting list of drugs after 2003 beers criteria were added to the 2006 Health Plan Employer Data and Information Set (HEDIS) to assess the drug prescribing in elderly people.

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Inappropriate drug use in hospitalized elderly patients of medicine and cardiology departments at a tertiary care hospital of Northeast India

  1. 1. Inappropriate drug use in hospitalized elderly patients of medicine and cardiology departments at a tertiary care hospital of Northeast India
  2. 2. Research Article Inappropriate drug use in hospitalized elderly patients of medicine and cardiology departments at a tertiary care hospital of Northeast India Ratan J. Lihite a,b, *, Mangala Lahkar b a Department of Pharmacy Practice, National Institute of Pharmaceutical Education & Research (NIPER), Guwahati, India b ADR Monitoring Centre (Pharmacovigilance Program of India) and Department of Pharmacology, Gauhati Medical College, Guwahati, India a r t i c l e i n f o Article history: Received 17 April 2013 Accepted 22 June 2013 Available online 10 July 2013 Keywords: HEDIS Inappropriate Drug Hospitalized Elderly a b s t r a c t Background: National committee on quality assurance, USA convened an expert consensus panel and identified the list of drugs which should be avoided in the elderly people. This resulting list of drugs after 2003 beers criteria were added to the 2006 Health Plan Employer Data and Information Set (HEDIS) to assess the drug prescribing in elderly people. Methods: The objective of this study was to determine the prevalence of inappropriate drug use and assess their predictors in the hospitalized elderly patients of tertiary care hospital by using HEDIS 2006 criteria. A 6-month prospective study was conducted in medicine & cardi- ology inpatient department of tertiary care hospital by reviewing prescriptions of 502 elderly patients. The patients of either sex having age more than 60 year were included in this study. Results: It is found that (2.39%) 12 patients received at least 1 inappropriate drug by 2006 HEDIS measure. Out of 12 inappropriate drugs, short acting nifedipine was prescribed to 4 elderly patients followed by dicyclomine to 2 patients and ketorolac to 2 patients each. Increased number (!11) of concurrent medications use during hospital stay (OR: 0.015, CI: 0.001e0.199, P ¼ 0.001) and prolonged (!5 days) length of stay (OR: 0.039, CI: 0.005e0.291, P ¼ 0.002) were found as a predictors of inappropriate medication use. Conclusion: In this study, low prevalence (2.39%) of inappropriate drug prescribing was found. Multiple medications and long duration of hospital stay were the risk factors for inappropriate medication use. Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. 1. Introduction Inappropriate multiple medications use is a major patient safety concern, as this irrational symptomatic prescribing practice not only add to the cost and complexity of therapeutic regimens, but also place patients especially vulnerable geri- atric patient population at greater risk for adverse drug re- actions and drugedrug interactions and jeopardize positive * Corresponding author. Tel.: þ91 9706143510. E-mail address: r.lihite@yahoo.com (R.J. Lihite). Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/apme a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 3 1 8 e3 2 3 0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2013.06.002
  3. 3. therapeutic outcome e including patient experience, health outcomes, overall performance, and with estimates of the financial consequences of the healthcare services.1 Although, Beers criteria is the foundation of 2006 HEDIS quality measures, clinicians contend that Beers criteria is too broad and sometimes drugs may be appropriate for specific patients in certain circumstances. The Beers criteria were derived from expert consensus, some experts and clinicians argue that they are not strictly evidence based.2 In some cases; patients may be in the process of being treated successfully with a potentially inappropriate drug. Thus, Beers criteria have been controversial since their original publication in 1991.3 Despite controversy about which explicit criteria should be used, there is a strong body of evidence showing that suboptimal prescribing is disturbingly common in elderly patients.4 Based on Beers criteria, National Committee on Quality Assurance, USA have developed a 2006 Healthcare Effectiveness Data and Information Set (HEDIS) criteria by using modified Delphi process to identify rates of inappro- priate prescribing in the elderly.5 To assess the healthcare quality for elderly people, this measures included the drugs that should usually avoided in the elderly.6 HEDIS is the most widely reported set of performance measures in the industry, used by health plans, medical groups, federal and state gov- ernments.7 Thus, we have used 2006 HEDIS measures to determine the prevalence of inappropriate drugs and assessed the predictors in hospitalized elderly patient of medicine and cardiology department of the tertiary care hospital in North- east region of India. 2. Patients and methods 2.1. Study design and setting The Institutional Ethic Committee approval was taken prior the initiation of study. The prospective study was carried out in an inpatient setting of medicine and cardiology department of the Gauhati Medical College and Hospital (GMCH), Guwa- hati, Assam. GMCH is the largest and major tertiary care government hospital of the entire northeast region of India, catering to millions of people in this region. This hospital has geriatric clinical setting in medicine department and more- over; elderly patients are more prevalent to cardiovascular diseases; therefore to comprise maximum number of elderly hospitalized patients in this study we have conducted our study in medicine and cardiology departments. The study data was collected for the period of 6 months from July to December 2010. The elderly patients of either sex were included in the study and written informed consent was taken at the time of enrollment. Each prescription was checked individually from the wards of medicine and cardi- ology department of hospital for inappropriate drug by 2006 HEDIS Criteria. The inappropriate drugs were collected from the prescriptions of elderly patients and it includes all the medications prescribed, right from admission to discharge of the patient. At the time of data collection the study form was completed with regards to patient’s age, diagnosis, all the drugs prescribed during hospital stay, length of hospitaliza- tion and study form was updated daily until the patient was discharged. Patients were also interviewed to get the infor- mation regarding any self medication and past history of illness. A prescription was said to be inappropriate if it con- tained one or more drugs included in 2006 HEDIS drug list of inappropriateness. The patients having incomplete informa- tion were excluded from the study. The results were repre- sented as average Æ standard deviation (SD) and percentages as applicable; age, sex, diagnosis, number of medications and duration of treatments were the variables for determination of predictors. Odds ratio was calculated to assess the most common predictors for inappropriate drug prescribing. Sta- tistical significance (P < 0.05) was determined at 95% level of confidence. The data were analyzed using Statistical Package for Social Science (SPSS) Ver. 16.0. 2.2. Modifications The criteria used in this study required certain modifications which were necessary in the Indian setting. The life expec- tancy at birth for Indian males and females corresponding to the mid year 2003 was 62.3 and 63.9 years respectively, giving an overall life expectancy as 63.2 years.8 Thus the modifications were: 1) The cut off age considered in this study was 60 years or more instead of age 65 years or more and 2) the following drugs were not considered in this study as they were excluded from the drug list of 2006 HEDIS criteria (Table 3). These drugs were Amitriptyline, Doxepin, Indomethacin, Ticlopidine, Methyldopa, Reserpine, Disopyramide, Oxybutynin, Nap- roxen, Oxaprozin, Piroxicam, Fluoxetine, Amiodarone, Dox- azosin, Clonidine, Mineral Oil, Cimetidine, Ethacrynic acid and long term use of stimulant laxatives except with opiate use. 3. Results 3.1. Population characteristics Out of the 502 patients, 308 (61.35%) were males and 194 (38.64%) were females. The average age of the patients was 66.87 Æ 4.71 years, the overall age range being 60e84 years. More than half of the 386 (76.89%) patients belonged to the age group 60e69 years while 105 (20.91%) of the patients belonged to the age group 70e79 years and the remaining 11 (2.19%) patients were more than 80 years of age. Table 1 e Inappropriate drug use identified by 2006 HEDIS. Sr. no. Name of drugs Severity No. of patients (n ¼ 12) 1 Short acting nifedipine High 4 2 Dicyclomine High 2 3 Ketorolac High 2 4 Nitrofurantoin High 2 5 Promethazine High 1 6 Chlorpheniramine High 1 a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 3 1 8 e3 2 3 319
  4. 4. 3.2. General distribution of disease The average disease per patient was found to be 3.20 Æ 1.26. The total number of diagnosis was 1604 in 502 prescriptions. Out of 502 prescriptions, 74 (14.74%) patient were diagnosed to have 1 disease followed by 153 (30.47%) patients were having 2 diseases and 275 (54.78%) patients were found to have more than 3 diseases. On the system wise analysis of 1604 disorders, it was found that circulatory system disorders (26.43%) were in the first rank followed by the endocrine system disorders (17.14%), Infection & parasitic disorder (16.70%) and digestive system disorders (9.28%). This finding can be attributed to the fact that cardiovascular diseases are most prevalent among the elderly patients. 3.3. General prescription pattern The average number of medicine per prescription was 9.29 Æ 3.29 and the average duration of prescribed medication in hospitalized elderly patient was 6.97 Æ 3.65 days. The total numbers of prescribed drugs were 4664 in 502 prescriptions. On the category-wise distribution of prescribed drugs, it was found that antimicrobials drugs (18.84%) were most frequently prescribed drugs, followed by drugs acting on car- diovascular system (15.45%), endocrine system (9.60%), gastrointestinal system (9.47%), analgesic & anti- inflammatory drugs (9.06%) and vitamin, minerals & dietary supplements (7.69%). Among the different drug classes, anti- biotics were the most widely prescribed class of drugs; approximately 2 antibiotics were prescribed to each patient. Among the cephalosporin, ceftriaxone was the most widely prescribed antibiotic followed by quinolones like ciprofloxacin and ofloxacin. Among drugs acting on central nervous system (5.93%), benzodiazepines, comprising of alprazolam and lor- azepam were commonly prescribed anti-anxiety and seda- tives in recommended daily dose. 3.4. Analysis of inappropriate drug use by 2006 HEDIS measures The overall 502 elderly patients aged over 60 year were admitted during the study period in the medicine and cardiology department of tertiary care hospital. Of the 502 elderly patients, 288 (57.37%) were from medicine department and 214 (42.62%) were from cardiology department. In medi- cine department 8 elderly patients had inappropriate pre- scription while in cardiology department 4 elderly patients having inappropriate prescription. In our study, 12 (2.39%) each patient had received only 1 inappropriate drug identified by 2006 HEDIS measure and severity of an adverse outcome due to exposure of this medication (high vs. low) were ranked and shown in Table 1. Of the 12 inappropriate drugs, short acting nifedipine having high severity was prescribed to 4 elderly patients each. 3.5. Predictors of inappropriate drug use In this study, elderly patients’ age of range 60e69 received maximum number of inappropriate drugs. It is also observed that patient with !11 number of medication and stay !11 number of days along with !3 number of diagnosis were received high number of inappropriate drugs (Table 2). Using logistic regression analysis, identified that increased number (!11) of concurrent medications use during hospital stay (OR: 0.015, CI: 0.001e0.199, P ¼ 0.001) and prolonged (!5 days) length of stay (OR: 0.039, CI: 0.005e0.291, P ¼ 0.002) were the predictors of inappropriate medication use. There wasn’t any statistical significance in inappropriate drug prescribing to male and female patients (OR ¼ 4.538; CI ¼ 0.940e21.918, P ¼ 0.060). Different age groups and number of diseases does not predict any inappropriate drug use (Table 2). 4. Discussion In this study antimicrobial drugs and drug acting on cardio- vascular system were highly prescribed to the elderly patients. Overall2 antibiotics per patientwereprescribed to hospitalized elderly patients. Among the different classes of antibiotic; 3rd generation cephalosporin i.e., ceftriaxone was most widely prescribed drug to the elderly hospitalized patients and have long half life as compared to other parenteral cephalosporin, which permit once-daily dosing. Whereas, quinolones Table 2 e Analysis of predictors associated with inappropriate drug use. Predictors Total (n ¼ 502) Patients with inappropriate drug use (n ¼ 12) Significance (P < 0.05) Odd ratio 95% confidence interval 1 Age 60e69 386 9 0.032 1 e 70e79 105 2 0.009 0.014 0.001e0.339 !80 11 1 0.021 0.019 0.001e0.546 2 Sex Female 194 6 1 e Male 308 6 0.060 4.538 0.940e21.918 3 No. of medication 5 137 0 0.006 1 e 5e10 192 1 0.997 <0.001 0.000e>0.001 !11 173 11 0.001 0.015 0.001e0.199 4 Length of stay 5 209 2 0.002 1 e 5e10 219 4 0.002 0.039 0.005e0.291 !11 74 6 0.002 0.067 0.012e0.372 5 No. of diagnosis 1 74 1 0.706 1 e 2 153 1 0.701 1.564 0.159e15.344 !3 275 10 0.486 0.442 0.044e4.409 a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 3 1 8 e3 2 3320
  5. 5. comprised of ciprofloxacinandofloxacin were2ndmostwidely prescribed antibiotic in this study. Moreover, this quinolones are well absorbed and had a considerable spectrum of anti- bacterial activity. The excessive use of antibiotics has led to the emergence of bacterial resistance. The inappropriate and ir- rational use of antibiotic in the clinical medicine is widespread, sometime at inadequate dosages and often, for non-bacterial diseases.9 Thus, the antimicrobials drug must be consider while preparing such quality tools in elderly patient to avoid the drug resistance and inappropriate prescribing. In our study, alprazolam and lorazepam were prescribed in recommended daily dose i.e., 1e2 mg/day and 1e3 mg/day respectively. Benzodiazepines should be prescribed to the elderly, only with caution and for a short period at recom- mended doses.10 While prescribing benzodiazepines, daily doses should not exceed 2 mg for alprazolam, 3 mg for lor- azepam, 60 mg oxazepam and 15 mg for temazepam. 4.1. Inappropriate medication use The prevalence of potentially inappropriate drug in our study was low (2.39%) by 2006 HEDIS criteria as compared to Pugh et al study as they have reported prevalence of about 19.6% of potentially inappropriate drugs by HEDIS 2006 drug list.11 Several commonly used drugs from the 1997 Beers criteria were not included in 2006 HEDIS measure. The low prevalence of inappropriate drug use in our study may be due to less number of drugs being enlisted in HEDIS criteria and our study was limited to inpatient setting of medicine and cardiology department which may exclude inappropriate drugs pre- scribed to elderly patients attending in outpatient setting and other departments of hospital. Moreover, geographical varia- tion among physicians in the awareness of the existence of list of inappropriate drugs might also account for low preva- lence in this study. Therefore, our prevalence rate may un- derestimate the true level of potential inappropriate drug use. Prescriptions of drugs that are considered to be inappro- priate are deemed to be an important cause of adverse drug reactions in the elderly population.12 In this study, we haven’t considered the inappropriate drug induced adverse events therefore our finding lack the reporting of adverse drug reactions. In our study, short acting nifedipine was prescribed to 4 elderly patients likewise of the 114 inappropriate drugs; the 4 drugs were nifedipine detected in Portuguese elderly outpatient.13 In 11 European countries the study was con- ducted and it is found that 0.7% (19 patients) of patients had received nifedipine14 whereas, 2% of patients were received nifedifine in the study conducted in 17 long term care facil- ities of Japan.15 Similarly, The French consensus panel ex- perts also, considered nitrofurantoin, short acting nifedipine and stimulant laxatives as inappropriate in the elderly pa- tients.16 Thus, short acting nifedipine is frequently pre- scribed in elderly hypertensive patients, despite warnings of possible harmful cardiovascular effects. It is also reported that short acting nifedipine increased the risk of stroke within 7 days in the newly diagnosed elderly hypertensive patient.17 Because of the potential to cause hypotension and constipation, short acting nifedipine was considered as a potentially inappropriate drug in the beers and HEDIS criteria. Cardiovascular system disorder like hypertension and angina was more prevalent in our study thus short acting nifedipine was prescribed in the elderly hospitalized patients. In our study, 2 elderly patients had received dicyclomine as an inappropriate drug. In United States, the study was con- ducted in outpatient prescription claims database and it was found that 4.2% of the beneficiaries and 4% claims patients had received dicyclomine.18 Similarly, study conducted in U.S. health maintenance organization; reported that at least 1% of elderly members received belladonna alkaloids (2.3%), dicy- clomine (1.1%), and hyoscyamine (1.2%).19 Gastrointestinal antispasmodic drugs are highly anticholinergic and have un- certain effectiveness. The elderly appear to be more prone to the anticholinergic effects of dicyclomine on the central Table 3 e 2006 HEDIS drug list. Sl. no. Drugs list Severity of adverse effects 1 Barbiturates High 2 Flurazepam High 3 Meprobamate High 4 Chlorpropamide High 5 Meperidine High 6 Pentazocine High 7 Trimethobenzamide High 8 Belladonna alkaloids High 9 Dicyclomine High 10 Hyoscyamine High 11 Propantheline High 12 Chlordiazepoxide High 13 Diazepam High 14 Quazepam, halazepam, chlorazepate High 15 Propoxyphene Low 16 Carisoprodol High 17 Chlorzoxazone High 18 Cyclobenzaprine High 19 Metaxalone High 20 Methocarbamol High 21 Dipyridamole Low 22 Chlorpheniramine High 23 Cyproheptadine High 24 Diphenhydramine High 25 Hydroxyzine High 26 Promethazine High 27 Tripelennamine High 28 Dexchlorpheniramine High 29 Ketorolac High 30 Orphenadrine High 31 Guanethidine High 32 Guanadrel High 33 Cyclandelate Low 34 Isoxsuprine Low 35 Nitrofurantoin High 36 Methyltestosterone High 37 Thioridazine High 38 Mesoridazine High 39 Short acting nifedipine High 40 Desiccated thyroid High 41 Amphetamines High 42 Estrogens Low a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 3 1 8 e3 2 3 321
  6. 6. nervous system. In the study Page JG et al has reported ma- jority of adverse effects which were related to the anticho- linergic activity of the dicyclomine.20 Thus, the dicycloamine prescribing should be avoided especially in elderly patients to prevent anticholinergic effects. In our study, nitrofurantoin was prescribed to 2 elderly hospitalized patients. Nitrofurantoins are potential for renal and hepatic impairment. Forty-four cases of nitrofurantoin associated hepatic injury were reported to the Danish Center for Monitoring of Adverse Drug reactions from 1968 to 1998. Forty-one were women with a median age of 69 years.21 In our study, ketorolac was prescribed to 2 elderly hospi- talized patients. Ketorolac on immediate and long term use should be avoided in older persons, since a significant number have asymptomatic gastrointestinal pathologic conditions. 4.2. Predictors of inappropriate medication use In our study, elderly women and men were not having any significant difference to receive inappropriate medication and different age groups of elderly patients don’t predict any inappropriate drug prescribing. Polypharmacy is the common and is significantly associated with inappropriate prescrib- ing.22 The clinical relevance of polypharmacy is always questionable. This is especially pertinent in the case of elderly patients, who are particularly vulnerable to adverse drug events due to their compromised physiological function. In this study, patients prescribed with !11 medications were having more prevalence of inappropriate drug use and high- level of polypharmacy was observed with 52.78% of patients receiving ! 6 medications. Similarly, in Singapore nursing homes study significantly higher (70.04%) inappropriate drug use along with the high (58.59%) prevalence of polypharmacy was observed.23 In our study, it was also observed that if the patients hospitalized for !11 days then they are more likely to receive inappropriate drugs. It is also shown by Mandavi et al in Indian elderly hospitalized patient that age over 70 years, number of medications prescribed more than 5 and longer length of stay in the hospital are the three important predictors for inappropriate prescribing in elderly patients.24 Number of diagnoses also has significant impact on the inappropriate prescribing. It was observed that as the num- ber of diagnosis increases, number of medications to treat each particular disease condition also increases which may leads to polypharmacy and more likely to receive inappro- priate medication.25 In our study, 54.78% of the patients suffered from !3 diseases. The majority of the diagnoses in our study pertained to cardiovascular system (26.43%) which denoted the higher occurrence of cardiovascular diseases world-wide. In conclusion, elderly hospitalized patients those having multiple medications and long duration of hospital stay were more likely to receive inappropriate drugs. The finding of this study also suggests that antimicrobial agents should be included in drug list of such quality measures to avoid irra- tional and inappropriate use of antibiotic in elderly patients. Moreover, the drug list included in such criteria should be updated periodically and implemented in clinical practice to avoid inappropriate drug use. Conflicts of interest All authors have none to declare. Acknowledgments Authors would like to acknowledge the Principal and HODs of Medicine & Cardiology Department of GMCH, Guwahati for providing permission to collect the data from elderly patients in the wards. r e f e r e n c e s 1. Willcox SM, Himmelstein DU, Woolhandler S. Inappropriate drug prescribing for the community-dwelling elderly. JAMA. 1994;272:292e296. 2. Crownover BK. Referral bias and other perspectives on the HEDIS measuring stick for quality of care in depression treatment. J Manag Care Pharm. 2006;12:76e77. 3. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the beers criteria for potentially inappropriate medication use in older adults: results of a US Consensus Panel of Experts. Arch Intern Med. 2003 Dec 8- 22;163:2716e2724. 4. Rancourt C, Moisan J, Baillargeon L, Verreault R, Laurin D, Gregoire JP. Potentially inappropriate prescriptions for older patients in long-term care. BMC Geriatr. 2004;4:9. 5. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern Med. 1997;157:1531e1536. 6. Zhan C, Sangl J, Bierman AS, et al. Potentially inappropriate medication use in the community-dwelling elderly: findings from the 1996 Medical Expenditure Panel Survey. JAMA. 2001;286:2823e2829. 7. HEDIS Measures. National Committee on Quality Assurance (NCQA)’s 20 Years of Experience with Measurement. Available from: URL: http://www.ncqa.org. 8. Population Reference Bureau’s 2000 World Data Sheets. Available from: URL: http://www.prb.org/. 9. Otoom S, Culligan K, Al-Assoomi B, Al-Ansari T. Analysis of drug prescriptions in primary health care centres in Bahrain. East Mediterr Health J. 2010;16:511e515. 10. Bogunovic OJ, Greenfield SF. Practical geriatrics: use of benzodiazepines among elderly patients. Psychiatr Serv. 2004;55:233e235. 11. Pugh MJV, Hanlon JT, Zeber JE, Bierman A, Cornell J, Berlowitz DR. Assessing potentially inappropriate prescribing in the elderly veterans affairs population using the HEDIS 2006 quality measure. J Manag Care Pharm. 2006;12:537e545. 12. Lindley CM, Tully MP, Paramsothy V, et al. Inappropriate medication is a major cause of adverse drug reactions in elderly patients. Age Ageing. 1992;21:294e300. 13. MartinsSO,SoaresMA,FoppevanMilJW,CabritaJ.Inappropriate drug use by Portuguese elderly outpatients e effect of the beers criteria update. Pharm World Sci. 2006;28:296e301. 14. Fialova D, Topinkova E, Gambassi G, et al. Potentially inappropriate medication use among elderly home care patients in Europe. JAMA. 2005;293:1348e1358. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 3 1 8 e3 2 3322
  7. 7. 15. Niwata S, Yamada Y, Ikegami N. Prevalence of inappropriate medication using beers criteria in Japanese long-term care facilities. BMC Geriatr. 2006;6:1e7. 16. Laroche ML, Charmes JP, Merle L. Potentially inappropriate medications in the elderly: a French consensus panel list. Eur J Clin Pharmacol. 2007;63:725e731. 17. Jung SY, Choi NK, Kim JY, Chang Y, Song HJ. Short-acting nifedipine and risk of stroke in elderly hypertensive patients. Neurology. 2011;77:1229e1234. 18. Curtis LH, Ostbye T, Sendersky V, et al. Inappropriate prescribing for elderly Americans in a large outpatient population. Arch Intern Med. 2004;164:1621e1625. 19. SimonSR,ChanKA, SoumeraiSB, etal. Potentiallyinappropriate medication use by elderly persons in U.S. Health maintenance organizations, 2000e2001. J Am Geriatr Soc. 2005;53:227e232. 20. Page JG, Dirnberger GM. Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride). J Clin Gastroenterol. 1981;3:153e156. 21. Dam-Larsen S, Kromann-Andersen H. Hepatic toxicity of nitrofurantoin. Cases reported to the Center for Monitoring Adverse Drug Reactions 1968e1998. Ugeskrift for Laeger. 1999;161:6650e6652. 22. Junius-Walker U, Theile G, Hummers-Pradier E. Prevalence and predictors of polypharmacy among older primary care patients in Germany. Fam Pract. 2007;24:14e19. 23. Mamun K, Lien CTC, Ang WST. Polypharmacy and inappropriate medication use in Singapore Nursing Homes. Ann Acad Med Singap. 2004;33:49e52. 24. Mandavi Tiwari P, Kapur V. Inappropriate drug prescribing identified among Indian elderly hospitalized patients. Int J Risk Saf Med. 2007;19:111e116. 25. Lau DT, Mercaldo ND, Harris AT, Trittschuh E, Shega J, Weintraub S. Polypharmacy and potentially inappropriate medication use among community-dwelling elders with dementia. Alzheimer Dis Assoc Disord. 2010;24:56e63. a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 3 1 8 e3 2 3 323
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