use of potentially inappropriate medications in people with …€¦ · use of potentially...

Quality Use of Medicines and Pharmacy Research Centre

Sansom Institute, University of South Australia

Use of potentially inappropriate

medications in people with dementia in

Vietnam and its associated factors

33rd International Conference of Alzheimer’s Disease International

26 – 29 July 2018, Chicago, USA

Tuan A. Nguyen1, Thang Pham2, …, Elizabeth E. Roughead1

1Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences,

University of South Australia2National Geriatric Hospital of Vietnam

Corresponding author: Tuan Anh Nguyen, NHMRC-ARC Dementia Research Development Fellow

(Grant identification number APP1103860)

[email protected]



Disclosure: Nothing to declare



Outline

Methods

Background

Discussion and conclusion

Results



Background

Dementia: 60% of the dementia

cases are in LMICs1

Health system in LMICs: Not well

developed or funded2

1Prince et al. World Alzheimer Report 20152Price et al. World Alzheimer Report 20163Nguyen et al. American Journal of Alzheimer’s Disease & Other Dementias 2018

Vietnam: up to 2.4 million by 20503



Multi-symptoms

An umbrella term → a syndrome: over 100

diseases

Deterioration

– cognition (memory, thinking, etc.)

– behaviour and personality

– the ability to perform everyday activities

→ Co-occurrence of multi-symptoms



Primarily a disease of old age

1. WHO 2017. Dementia Fact sheet

2. AIHW 2012. Dementia in Australia

Younger onset (<65 years) - up to 9% globally1

In Australia2

Age <65 65-74 75-84 85+ 65+

Percent 8% 18.1% 32.7% 41.1% 92%

Rate/100

population

0.1 3.2 9.7 29.5 8.8



Age-related changes

1Mangoni AA, Jackson SHD. Br J Clin Pharmacol 2004;57(1):6-142Reeve E, et al. Expert Opin. Drug Metab. Toxicol 2017;13(6):651-6683Farrall AJ, Wardlaw JM. Neurobiol Aging 2009;30:337-3524van Assema DME, et al. Brain 2012;135:181-95Mehta DC, et al. Pharm. Res 2015;32:819-39

Age-related changes in pharmacokinetics1,2

– ↓ P-glycoprotein activity at the BBB4 (P-gp transport

substances immediately out of the brain, restricting

uptake)

– These changes → ↑ risk of ADR5

– ↑ in blood-brain-barrier (BBB) permeability: allows

more meds to enter CNS at higher levels3



Age-related changes

1. Mangoni AA, Jackson SHD. Br J Clin Pharmacol 2004;57(1):6-14; 2. Kruse WH. Drug Saf 1990; 5: 328–34

3. Gregory C, McKenna P. Drugs Aging 1994; 5: 254–62; 4. Maixner SM et al. J Clin Psychiatry 1999; 60(Suppl 8): 29–41

Age-related changes in pharmacodynamics1

More susceptible to side effects of meds (e.g.

Parkinsonism, disorders of movement, QT

prolongation)

More sensitive to effects of meds on cognition

– Altered sensitivity to several classes of meds due

to changes in receptors and binding affinity of med Increased sensitivity to CNS effects of benzodiazepines2 and

antipsychotics3,4



Multi-morbidities

AIHW 2012. Dementia in Australia

Table: Average number of health conditions for those with dementia and all people,

by sex, age and residency, 2009



Polypharmacy

1 Bosboom P et al. Dement Geriatr Cogn Disord Extra 2012;2:361–371; 2 Somers M et al. Australian Family Physician 2010; 39(6): 413-6; 3 Cross et al. Drugs Aging 2016; 33:37–44; 4 Montastruc F et al. Eur J Clin Pharmacol 2013; 69: 1589-97; 5 Lau DT et al. Alzheimer Dis Assoc Disord 2010; 24: 56-63; 6 Barry, H. E et al. Journal of Alzheimer's Disease 2016; 52(4): 1503-13

>90% in RACFs use ≥ 5 meds1,2

~68% in memory clinics use ≥ 5 meds3

43-52% in community use ≥ 5 meds4,5; 85%

use ≥ 4 meds6

On average use 10 different meds2



Risk of drug interaction

Karas S. Ann Emerg Med 1981; 10:627-630



Treatment conflict

~92% PWD in RACFs: BPSD1

Pharmacotherapy: Antidepressants,

antipsychotics3, antimuscarinics →

anticholinergic property

1 Edvardsson D. International Psychogeriatrics 2008, 20(4), 764–776; 2 https://www.bladderandbowel.org/associated-illness/alzheimers-and-incontinence/3 CDPC 2016. Clinical Practice Guidelines and Principles of Care for People with Dementia

60-70% people with Alzheimer’s disease:

incontinence2

CEIs and anticholinergics: potential to

antagonise each other



Potentially inappropriate meds

Prevalence of use of PIM in PWD: 10.2% to

64.4%1, 2,3, depending on the tools, settings

1O'Mahony D et al. Age and Ageing 2015;44(2):213-8; 2 Johnell K. Current Clinical Pharmacology 2015;10(3):178-84; 3 Renom-Guiteras A et al. Age and Ageing 2017:1-7. doi: 10.1093/ageing/afx147

PIM: risk from med use outweighs clinical

benefit, safer alternative is available 1

Little is known about QUM in people with

dementia in Vietnam



Objectives

to examine the use of potentially inappropriate

medicines that may affect cognition in people

with dementia and its associated factors

to examine the prevalence of concomitant use of

CEIs and anticholinergics, as well as

antipsychotic use



Data source and study design

Database of patients with dementia in the

national dementia care program at National

Geriatric Hospital of Vietnam

Med use: 1st, Jan 2015 to 31st, Dec 2016



Data source and study design

– A list of med considered potentially

inappropriate for patients with cognitive

impairment (PIMcog)1 according to the Beers

and STOPP criteria

1Cross AJ et al. Drugs Aging. 2016;33:37-44.

Med use was assessed against:



Statistical analyses

Descriptive statistics: Demographics and

medicine use

Multiple logistic regressions: association of

different variables and having a PIMcog

– Age, gender, dementia type, severity, number of

comorbidities, number of medicines used other than

PIMcog, number of hospital visits, and number of

treating specialists.

– Missing data: imputed using the fully conditional

method in a multiple imputation approach



Outline

Methods

Background

Discussion and conclusion

Results



Logistic regression model

for PIM use

Number of treating specialists (adjusted OR

0.61; 95% CI 0.45 – 0.83)

Number of hospital visits during the study

period: adjusted OR 1.08 (1.02 – 1.16)

Female gender: adjusted OR 1.55 (0.72 –

3.30)

Older age: adjusted OR 1.02 (0.99 – 1.06)



Discussion

A high level use of medicines that can

– further impair cognition (41%)

– reduce the effectiveness of CEIs in people with

dementia (39%)

95% on anti-dementia medicines

– 82% for longer than 6 months

– 27% were at severe stage of dementia

18% on antipsychotics

– most common: sulpiride - extrapyramidal

symptoms (# haloperidol)



Limitations

Small sample size

They were in a national dementia care

program

– Special insurance cap that limits the total cost of

medicines per prescription → this is likely to affect

the prescribing practice.

Patients attending 1 tertiary teaching hospital



Conclusions

PIMcog use, anticholinergics and sedatives

use, and concurrent use of CEIs with

anticholinergics: prevalent

Efforts to improve quality use of medicines for

this population are warranted

– Raising awareness of medicines that further impair

cognition

– Providing the alternative options



Acknowledgements

China-Australia Centre for Health Sciences

Research seed funding grant (T.A.N, S.Q,

E.E.R, L.K.E, M.G, and H.W).

Australian NHMRC-ARC Dementia Research

Development Fellowship (T.A.N Grant

identification number APP1103860)



Thang Pham2, Huyen Thi Thanh Vu2, Thanh Xuan Nguyen2, Trinh Thi Vu2, Binh

Thi Thanh Nguyen2, Ngoc Quynh Nguyen2, Binh Thanh Nguyen2, Binh Thanh

Nguyen2, Tam Ngoc Nguyen2, Sinh Viet Phan2, Anh Trung Nguyen2, Tuan Le

Pham3, Ha Thu Dang1, Lisa Kalisch-Ellett1, Marianne Gillam1, Nicole Pratt 1, Sun

Qiang4, Haipeng Wang4, Tipaporn Kanjanarach5, Mohamed Azmi Ahmad

Hassali6, Zaheer-Ud-Din Babar7, Asrenee Ab Razak8, Dujrudee Chinwong9,

Elizabeth E. Roughead1

1Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences,

University of South Australia, Adelaide SA, Australia2National Geriatric Hospital of Vietnam, 1A Phuong Mai Street, Dong Da District, Hanoi, Vietnam3 Hanoi Medical University and Ministry of Health of Vietnam, Hanoi, Vietnam4Center for Health Management and Policy, School of Health Care Management, Shandong University,

128# Wenhua Xi Rd 44, Jinan, Shandong 250012, China5Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand6School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia7Department of Pharmacy, University of Huddersfield, Queensgate, HD1 3DH Huddersfield, United

Kingdom8Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia,11800 Penang,

Malaysia9Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand

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