International Group for Reducing Inappropriate Medication Use & Polypharmacy (IGRIMUP): Position Statement and 10 Recommendations for Action

Drugs and Aging

Volumn 35, Issue 7, 2018, Pages 575-587

  Mangin, Dee ^a,i   Bahat, Gülistan ^b   Golomb, Beatrice A ^c   Mallery, Laurie Herzig ^d   Moorhouse, Paige ^d   Onder, Graziano ^e   Petrovic, Mirko ^f   Garfinkel, Doron ^g,h  

^a MCMASTER UNIVERSITY   (Canada)

^b ISTANBUL UNIVERSITY   (Turkey)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^d DALHOUSIE UNIVERSITY   (Canada)

^e FONDAZIONE POLICLINICO UNIVERSITARIO A GEMELLI IRCCS   (Italy)

^f GHENT UNIVERSITY   (Belgium)

^g WOLFSON MEDICAL CENTER   (Israel)

^h Israel Cancer Association   (Israel)

ⁱ UNIVERSITY OF OTAGO   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

10 STEP DISCONTINUATION GUIDE; ARTICLE; CLINICAL ASSESSMENT TOOL; CLINICAL DECISION MAKING; COMPREHENSIVE GERIATRIC ASSESSMENT; COMPUTER ASSISTED DRUG THERAPY; COMPUTERIZED PROVIDER ORDER ENTRY; CRITERIA TO ASSESS APPROPRIATE MEDICATION USE AMONG ELDERLY COMPLEX PATIENT TOOL; DRUG EFFICACY; DRUG SURVEILLANCE PROGRAM; EVIDENCE BASED MEDICINE; FAMILY ATTITUDE; FAMILY DECISION MAKING; GERIATRIC ASSESSMENT; GOOD PALLIATIVE GERIATRIC PRACTICE ALGORITHM; HEALTH CARE QUALITY; HUMAN; INAPPROPRIATE PRESCRIBING; MEDICAL EDUCATION; MEDICAL RESEARCH; MULTIPLE CHRONIC CONDITIONS; PALLIATIVE AND THERAPEUTIC HARMONIZATION PROGRAM; PATIENT PREFERENCE; POLYPHARMACY; POTENTIALLY INAPPROPRIATE MEDICATION; PRACTICE GUIDELINE; PRESCRIBING OPTIMIZATION METHOD; PRIORITY JOURNAL; PROTOCOL COMPLIANCE; RESEARCH PRIORITY; RISK BENEFIT ANALYSIS; SOFTWARE; SPECIFIC MEASURABLE ACCEPTABLE REALISTIC TIME FRAMED TOOL; SYSTEMATIC REVIEW (TOPIC); ADVERSE DRUG REACTION; AGED; COMORBIDITY; PRESCRIPTION; PREVENTION AND CONTROL; QUALITY OF LIFE; STANDARDS;

AGED; COMORBIDITY; DRUG PRESCRIPTIONS; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HUMANS; INAPPROPRIATE PRESCRIBING; POLYPHARMACY; QUALITY OF LIFE;

EID: 85049853616     PISSN: 1170229X     EISSN: 11791969     Source Type: Journal    
DOI: 10.1007/s40266-018-0554-2     Document Type: Article

References (146)

1. Kaufman DW, et al. Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA. 2002;287(3):337–44
2. Lombardi TP, Kennicutt JD. Promotion of a safe medication environment: focus on the elderly and residents of long-term care facilities. Medsc Pharm. 2001;2(1):23–8
3. Thomsen LA, et al. Systematic review of the incidence and characteristics of preventable adverse drug events in ambulatory care. Ann Pharmacother. 2007;41(9):1411–26
4. Topinkova E. Aging, disability and frailty. Ann Nutr Metab. 2008;52(Suppl. 1):6–11
5. Gill TM, Robison JT, Tinetti ME. Predictors of recovery in activities of daily living among disabled older persons living in the community. J Gen Intern Med. 1997;12(12):757–62
6. Alagiakrishnan K, Wiens C. An approach to drug induced delirium in the elderly. Postgrad Med J. 2004;80(945):388–93
7. Larson EB, et al. Adverse drug reactions associated with global cognitive impairment in elderly persons. Ann Intern Med. 1987;107(2):169–73
8. Moore AR, O’Keeffe ST. Drug-induced cognitive impairment in the elderly. Drugs Aging. 1999;15(1):15–28
9. Huffman GB. Evaluating and treating unintentional weight loss in the elderly. Am Fam Physician. 2002;65(4):640–50
10. Jyrkka J, et al. Association of polypharmacy with nutritional status, functional ability and cognitive capacity over a three-year period in an elderly population. Pharmacoepidemiol Drug Saf. 2011;20(5):514–22
11. Gnjidic D, 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(9):989–95
12. Lai SW, et al. Polypharmacy correlates with increased risk for hip fracture in the elderly: a population-based study. Medicine (Baltimore). 2010;89(5):295–9
13. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc. 1999;47(1):40–50
14. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc. 1999;47(1):30–9
15. Thapa PB, et al. Antidepressants and the risk of falls among nursing home residents. N Engl J Med. 1998;339(13):875–82
16. Talasz H, Lechleitner M. Polypharmacy and incontinence. Z Gerontol Geriatr. 2012;45(6):464–7
17. Akazawa M, et al. Potentially inappropriate medication use in elderly Japanese patients. Am J Geriatr Pharmacother. 2010;8(2):146–60
18. Lopez-Sendon JL, Mena MA, de Yebenes JG. Drug-induced parkinsonism in the elderly: incidence, management and prevention. Drugs Aging. 2012;29(2):105–18
19. Onder G, et al. Adverse drug reactions as cause of hospital admissions: results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA). J Am Geriatr Soc. 2002;50(12):1962–8
20. Ernst FR, Grizzle AJ. Drug-related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc (Wash). 2001;41(2):192–9
21. Bates DW, et al. The costs of adverse drug events in hospitalized patients: Adverse Drug Events Prevention Study Group. JAMA. 1997;277(4):307–11
22. Fick DM, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716–24
23. Johnson JA, Bootman JL. Drug-related morbidity and mortality: a cost-of-illness model. Arch Intern Med. 1995;155(18):1949–56
24. Perry DP. When medicine hurts instead of helps. Consult Pharm. 1999;14:1326–30
25. Gurwitz JH, et al. Incidence and preventability of adverse drug events in nursing homes. Am J Med. 2000;109(2):87–94
26. Han BH, et al. Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: the ALLHAT-LLT randomized clinical trial. JAMA Intern Med. 2017;177(7):955–65
27. Jyrkka J, et al. Patterns of drug use and factors associated with polypharmacy and excessive polypharmacy in elderly persons: results of the Kuopio 75+ study: a cross-sectional analysis. Drugs Aging. 2009;26(6):493–503
28. Steinman MA, Hanlon JT. Managing medications in clinically complex elders: “There’s got to be a happy medium”. JAMA. 2010;304(14):1592–601
29. Fu AZ, et al. Potentially inappropriate medication use and healthcare expenditures in the US community-dwelling elderly. Med Care. 2007;45(5):472–6
30. Hug BL, et al. The costs of adverse drug events in community hospitals. Jt Comm J Qual Patient Saf. 2012;38(3):120–6
31. Rochon PA, TJ, Gill SS, Gurwitz JH. In: Halter JB, Tinetti ME, Studenski S, High KP, Asthana S, editors. Hazzard’s Geriatric Medicine and Gerontology. New York (NY): McGraw-Hill; 2009. p. 289–302
32. Bootman JL, Harrison DL, Cox E. The health care cost of drug-related morbidity and mortality in nursing facilities. Arch Intern Med. 1997;157(18):2089–96
33. Hoonhout LH, et al. Direct medical costs of adverse events in Dutch hospitals. BMC Health Serv Res. 2009;9:27
34. Rottenkolber D, Hasford J, Stausberg J. Costs of adverse drug events in German hospitals: a microcosting study. Value Health. 2012;15(6):868–75
35. Santibanez-Beltran S, et al. Economic cost of polypharmacy in the elderly in primary health care. Rev Med Inst Mex Seguro Soc. 2013;51(2):192–9 (in Spanish)
36. Mangin D, Heath I, Jamoulle M. Beyond diagnosis: rising to the multimorbidity challenge. BMJ. 2012;44:e3526
37. de Ruijter W, et al. Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study. BMJ. 2009;338:a3083
38. Golomb BA, Bui AK. Fasting glucose positively predicts word memory performance in older men. Circulation. 2014;130(Suppl. 2):A13365
39. BA, G. The starving cell: metabolic syndrome as an adaptive process. Available from: Nature Precedings; 2011
40. The Action to Control Cardiovascular Risk in Diabetes. Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59
41. Tinetti ME, et al. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults. JAMA Intern Med. 2014;174(4):588–95
42. Lipska KJ, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med. 2014;174(7):1116–24
43. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200–5
44. Makary MA, Daniel M. Medical error: the third leading cause of death in the US. BMJ. 2016;353:i2139
45. Garfinkel D. Geriatric boom catastrophe: a major medical, economic and social nightmare of the 21st century. Proceedings of the 16th Congress of the International Association of Gerontology 1997; 364
46. Boyle P. Global burden of cancer. Lancet. 1997;349(Suppl. 2):23–6
47. Ershler WB. Geriatrics and medical oncology: finding the common ground. J Gerontol A Biol Sci Med Sci. 1997;52(6):M327–8
48. Garfinkel D. The tsunami in 21st century healthcare: the age-related vicious circle of co-morbidity. J Nutr Health Aging. 2013;17(Suppl. 1):SS24, 227–C1, S96–7
49. Bahat G, et al. Comorbidities, polypharmacy, functionality and nutritional status in Turkish community-dwelling female elderly. Aging Clin Exp Res. 2014;26(3):255–9
50. Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults: addressing polypharmacy. Arch Intern Med. 2010;170(18):1648–54
51. Garfinkel D. Poly-de-prescribing to treat polypharmacy: efficacy and safety. Ther Adv Drug Saf. 2018;9(1):25–43
52. Potter K, et al. Deprescribing in frail older people: a randomised controlled trial. PLoS One. 2016;11(3):e0149984
53. Page AT, et al. Deprescribing in older people. Maturitas. 2016;91:115–34
54. Gnjidic D, et al. Deprescribing trials: methods to reduce polypharmacy and the impact on prescribing and clinical outcomes. Clin Geriatr Med. 2012;28(2):237–53
55. Lynch T. Management of drug–drug interactions: considerations for special populations: focus on opioid use in the elderly and long term care. Am J Manag Care. 2011;17(Suppl. 11):S293–8
56. Wolfstadt JI, et al. The effect of computerized physician order entry with clinical decision support on the rates of adverse drug events: a systematic review. J Gen Intern Med. 2008;23(4):451–8
57. Ancker JS, et al. Effects of workload, work complexity, and repeated alerts on alert fatigue in a clinical decision support system. BMC Med Inform Decis Mak. 2017;17(1):36
58. Garfinkel D, Ilhan B, Bahat G. Routine deprescribing of chronic medications to combat polypharmacy. Ther Adv Drug Saf. 2015;6(6):212–33
59. Chang CB, Chan DC. Comparison of published explicit criteria for potentially inappropriate medications in older adults. Drugs Aging. 2010;27(12):947–57
60. Beers MH, et al. Explicit criteria for determining inappropriate medication use in nursing home residents: UCLA Division of Geriatric Medicine. Arch Intern Med. 1991;151(9):1825–32
61. American Geriatrics Society. 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46
62. Gallagher P, Barry P, O’Mahony D. Inappropriate prescribing in the elderly. J Clin Pharm Ther. 2007;32(2):113–21
63. 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(6):673–9
64. Gallagher PF, O’Connor MN, O’Mahony D. Prevention of potentially inappropriate prescribing for elderly patients: a randomized controlled trial using STOPP/START criteria. Clin Pharmacol Ther. 2011;89(6):845–54
65. Hamilton H, et al. Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med. 2011;171(11):1013–9
66. O’Mahony D, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44(2):213–8
67. Holt S, Schmiedl S, Thürmann PA. Potentially inappropriate medications in the elderly: the PRISCUS list. Dtsch Ärztebl Int. 2010;107(31–32):543–51
68. Laroche ML, Charmes JP, Merle L. Potentially inappropriate medications in the elderly: a French consensus panel list. Eur J Clin Pharmacol. 2007;63(8):725–31
69. Rognstad S, et al. The Norwegian General Practice (NORGEP) criteria for assessing potentially inappropriate prescriptions to elderly patients: a modified Delphi study. Scand J Prim Health Care. 2009;27(3):153–9
70. Naugler CT, et al. Development and validation of an improving prescribing in the elderly tool. Can J Clin Pharmacol. 2000;7(2):103–7
71. McLeod P, et al. Defining inappropriate practices in prescribing for elderly people: a national consensus panel. CMAJ. 1997;156:385–91
72. Rancourt C, et al. Potentially inappropriate prescriptions for older patients in long-term care. BMC Geriatr. 2004;4:9
73. Basger BJ, Chen TF, Moles RJ. Inappropriate medication use and prescribing indicators in elderly Australians: development of a prescribing indicators tool. Drugs Aging. 2008;25(9):777–93
74. Basger BJ, Chen TF, Moles RJ. Validation of prescribing appropriateness criteria for older Australians using the RAND/UCLA appropriateness method. BMJ Open. 2012;2(5):e001431
75. Winit-Watjana W, Sakulrat P, Kespichayawattana J. Criteria for high-risk medication use in Thai older patients. Arch Gerontol Geriatr. 2008;47(1):35–51
76. Shrank WH, Polinski JM, Avorn J. Quality indicators for medication use in vulnerable elders. J Am Geriatr Soc. 2007;55(Suppl. 2):S373–82
77. Shekelle P, Maclean C, Morton S, Wenger N. ACOVE quality indicators. Ann Intern Med. 2001;135:653–67
78. Hanlon JT, et al. Use of inappropriate prescription drugs by older people. J Am Geriatr Soc. 2002;50(1):26–34
79. Lapane KL, et al. Effect of a pharmacist-led multicomponent intervention focusing on the medication monitoring phase to prevent potential adverse drug events in nursing homes. J Am Geriatr Soc. 2011;59(7):1238–45
80. Salahudeen MS, Hilmer SN, Nishtala PS. Comparison of anticholinergic risk scales and associations with adverse health outcomes in older people. J Am Geriatr Soc. 2015;63(1):85–90
81. Tosato M, et al. Potentially inappropriate drug use among hospitalised older adults: results from the CRIME study. Age Ageing. 2014;43(6):767–73
82. Wehling M. Multimorbidity and polypharmacy: how to reduce the harmful drug load and yet add needed drugs in the elderly? Proposal of a new drug classification: fit for the aged. J Am Geriatr Soc. 2009;57(3):560–1
83. Wehling M, et al. VALFORTA: a randomised trial to validate the FORTA (Fit fOR The Aged) classification. Age Ageing. 2016;45(2):262–7
84. Kuhn-Thiel AM, Weiss C, Wehling M. Consensus validation of the FORTA (Fit fOR The Aged) list: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging. 2014;31(2):131–40
85. BPAC. A practical guide to stopping medicines in older people. Best Pract J. 2010;27;10–23
86. Scott IA, et al. Minimizing inappropriate medications in older populations: a 10-step conceptual framework. Am J Med. 2012;125(6):529–37.e4
87. Farrell B, et al. What are priorities for deprescribing for elderly patients? Capturing the voice of practitioners: a modified delphi process. PLoS One. 2015;10(4):e0122246
88. Onder G, et al. Strategies to reduce the risk of iatrogenic illness in complex older adults. Age Ageing. 2013;42(3):284–91
89. Petrovic M, van der Cammen T, Onder G. Adverse drug reactions in older people: detection and prevention. Drugs Aging. 2012;29(6):453–62
90. Ellis G, et al. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials. BMJ. 2011;343:d6553
91. Schmader KE, et al. Effects of geriatric evaluation and management on adverse drug reactions and suboptimal prescribing in the frail elderly. Am J Med. 2004;116(6):394–401
92. Hanlon JT, et al. A method for assessing drug therapy appropriateness. J Clin Epidemiol. 1992;45(10):1045–51
93. Schmader KE, et al. Inappropriate prescribing and health outcomes in elderly veteran outpatients. Ann Pharmacother. 1997;31(5):529–33
94. Drenth-van Maanen AC, et al. Prescribing optimization method for improving prescribing in elderly patients receiving polypharmacy: results of application to case histories by general practitioners. Drugs Aging. 2009;26(8):687–701
95. Vogt-Ferrier N. Reviewing a complicated geriatric drug regimen. Eur Geriatr Med. 2010;1(3):198–202
96. Olsson IN, Curman B, Engfeldt P. Patient focused drug surveillance of elderly patients in nursing homes. Pharmacoepidemiol Drug Saf. 2010;19(2):150–7
97. Onder G, et al. Recommendations to prescribe in complex older adults: results of the CRIteria to assess appropriate Medication use among Elderly complex patients (CRIME) project. Drugs Aging. 2014;31(1):33–45
98. Moorhouse P, Mallery LH. Palliative and therapeutic harmonization: a model for appropriate decision-making in frail older adults. J Am Geriatr Soc. 2012;60(12):2326–32
99. Dalhousie University. Faculty of Medicine continuing medical education. 8 Jan 2014. Available from: http://cme.medicine.dal.ca/ADS.htm. Accessed 2 May 2018
100. Mallery LH, et al. Evidence-informed guidelines for treating frail older adults with type 2 diabetes: from the Diabetes Care Program of Nova Scotia (DCPNS) and the Palliative and Therapeutic Harmonization (PATH) program. J Am Med Dir Assoc. 2013;14(11):801–8
101. Mallery LH, et al. Promoting higher blood pressure targets for frail older adults: a consensus guideline from Canada. Cleve Clin J Med. 2014;81(7):427–37
102. Scott IA, et al. Deciding when to stop: towards evidence-based deprescribing of drugs in older populations. Evid Based Med. 2013;18(4):121–4
103. Pollock M, Bazaldua OV, Dobbie AE. Appropriate prescribing of medications: an eight-step approach. Am Fam Physician. 2007;75(2):231–6
104. Scott IA, Gray LC, Martin JH, et al. Effects of a drug minimisation guide on prescribing intentions in elderly persons with polypharmacy. Drugs Aging. 2012;29:659–67
105. Garfinkel D, Zur-Gil S, Ben-Israel J. The war against polypharmacy: a new cost-effective geriatric-palliative approach for improving drug therapy in disabled elderly people. Israel Med Assoc J. 2007;9(6):430–4
106. Sackett DL, et al. Evidence based medicine: what it is and what it isn’t. BMJ. 1996;312(7023):71–2
107. Canadian Institute for Health Information. Seniors and the health care system: what Is the impact of multiple chronic conditions? 2011. Available from: https://secure.cihi.ca/free_products/air-chronic_disease_aib_en.pdf. Accessed 2 May 2018
108. Reeve E, et al. People’s attitudes, beliefs, and experiences regarding polypharmacy and willingness to deprescribe. J Am Geriatr Soc. 2013;61(9):1508–14
109. Tannenbaum C, et al. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med. 2014;174(6):890–8
110. Starfield B. Threads and yarns: weaving the tapestry of comorbidity. Ann Fam Med. 2006;4(2):101–3
111. Tinetti ME, Fried T. The end of the disease era. Am J Med. 2004;116(3):179–85
112. May C, Montori VM, Mair FS. We need minimally disruptive medicine. BMJ. 2009;339:b2803
113. Mangin D, Heath I. Multimorbidity and quaternary prevention (P4). Revista Brasileira de Medicina de Família e Comunidade. 2015;10(35):5
114. Starfield B, Mangin D. An international perspective on the basis for payment for performance. Qual Prim Care. 2010;18:399–404
115. Chutka DS, Takahashi PY, Hoel RQW. Inappropriate medications for elderly patients. Mayo Clin Proc. 2004;79(1):122–39
116. Morton A. Inappropriately defining “inappropriate medication for the elderly”. J Am Geriatr Soc. 2004;52(9):1580
117. Steinman MA, et al. Agreement between drugs-to-avoid criteria and expert assessments of problematic prescribing. Arch Intern Med. 2009;169(14):132632
118. de Souto Barreto P, Ferrandez AM, Saliba-Serre B. Are older adults who volunteer to participate in an exercise study fitter and healthier than nonvolunteers? The participation bias of the study population. J Phys Act Health. 2013;10(3):359–67
119. Golomb BA, et al. The older the better: are elderly study participants more non-representative? A cross-sectional analysis of clinical trial and observational study samples. BMJ Open. 2012;2(6):e000833
120. Kaiser C, et al. Selection bias of elderly patients with chronic angina referred for catheterization. Int J Cardiol. 2006;110(1):80–5
121. Sugisawa H, Kishino H, Sugihara Y, Okabayashi H, Shibata H. Comparison of characteristics between respondents and nonrespondents in a national survey of Japanese elderly using six year follow-up study. Nihon Koshu Eisei Zasshi. 1999;46(7):551–62 (in Japanese)
122. Sugisawa H, Kishino H, Sugihara Y, Shibata H. Characteristics of dropouts and participants in a twelve-year longitudinal research of Japanese elderly. Nihon Koshu Eisei Zasshi. 2000;47(4):337–49 (in Japanese)
123. Boyd CM, et al. Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance. JAMA. 2005;294(6):716–24
124. Tinetti ME, Bogardus ST Jr, Agostini JV. Potential pitfalls of disease-specific guidelines for patients with multiple conditions. N Engl J Med. 2004;351(27):2870–4
125. Starfield B, Gérvas J, Mangin D. Clinical care and health disparities. Annu Rev Public Health. 2012;33:89–106
126. Angell M. The truth about drug companies: how they deceive us and what to do about it. Random House; 2005
127. Golomb BA. Conflict of Interest in Medicine. 5 Oct 2008. Available from: http://thesciencenetwork.org/programs/beyond-belief-candles-in-the-dark/beatrice-golomb. Accessed 2 May 2018
128. Gotzsche P. Deadly medicines and organised crime. London: Radcliffe Medical Press; 2013
129. Healy D. Let them eat Prozac: the unhealthy relationship between the pharmaceutical industry and depression. New York: New York University Press; 2006
130. Healy D. Pharmageddon. California: University of California Press; 2012
131. Healy D, Cattel D. Interface between authorship, industry and science in the domain of therapeutics. Br J Psychiatry. 2003;183(1):22–7
132. Doshi P, et al. Restoring invisible and abandoned trials: a call for people to publish the findings. BMJ. 2013;346:f2865
133. Chan A, et al. Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. J Am Med Assoc. 2004;291(20):2457–65
134. Bero L, et al. Factors associated with findings of published trials of drug–drug comparisons: why some statins appear more efficacious than others. PLoS Med. 2007;4(6):e184
135. Ciani O, et al. Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study. BMJ. 2013;346:f457
136. Choudhry NK, Stelfox HT, Detsky AS. Relationships between authors of clinical practice guidelines and the pharmaceutical industry. J Am Med Assoc. 2002;287(5):612–7
137. Gordon J. The under-representation of elderly patients in a problem-based medical school curriculum. Med Teach. 2007;29(8):844
138. Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315(7115):1096–9
139. Gill SS, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med. 2005;165(7):808–13
140. Anderson K, et al. Prescriber barriers and enablers to minimising potentially inappropriate medications in adults: a systematic review and thematic synthesis. BMJ Open. 2014;4(12):e006544
141. Reeve E, et al. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793–807
142. Checkland K, et al. Biomedicine, holism and general medical practice: responses to the 2004 General Practitioner contract. Sociol Health Illn. 2008;30(5):788–803
143. Marengoni A, et al. Prevalence of chronic diseases and multimorbidity among the elderly population in Sweden. Am J Public Health. 2008;98(7):1198–200
144. Barnett K, et al. Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. Lancet. 2012;380(9836):37–43
145. Mangin D, Sweeney K, Heath I. Preventive health care in elderly people needs rethinking. BMJ. 2007;335(7614):285–7
146. Multimorbidity: clinical assessment and management, National Institute For Health and Care Excellence guideline [NG56]. 2016 : United Kingdom nice.org.uk/guidance/ng56