タイ東部の地域病院における高齢者の医薬品適正使用のための実態調査

Potentially Inappropriate Medications of Elderlyin Community Hospital in Eastern of Thailand

2018 Dissertation Doctor’s Degreeof Meiji Pharmaceutical University
Vanida, Prasert

Dissertation Advisor
Professor Manabu Akazawa

CONTENTS

Page

LIST OF TABLES

4LIST OF FIGURES

5

LIST OF ABBREVIATIONS USED

6

CHAPTER 1 INTRODUCTION

8Background and significance of the study

8

CHAPTER 2 LITERATURE REVIEW

12

2.1 Situation of Population Aging in Thailand

12

2.2 The Healthcare System for the Aging Population in Thailand

15

2.3 Medication Use in Elderly Patients19

2.4 Potentially Inappropriate Medication (PIM) use in Thai elderly

19

2.5 The screening tools for Identifying PIM

25

2.6 Computerized Decision Support System for PIM Prescriptions

29

CHAPTER 3 APPLYING THE LISTS OF RISK DRUGS FOR THAI ELDERLY

32(LRDTE) AS A MECHANISM TO ACCOUNT FOR PATIENT AGE AND
MEDICINE SEVERITY IN ASSESSING PIMS (THE FIRST PUBLICATION)
3.1 Purpose

32

3.2 Methods

32

3.2.1 Study design and population

32

1

CONTENTS (Cont.)

Page
3.2.2 Data source and variables

34

3.2.3 Measurement of PIM

35

3.2.4 Data analysis

36

3.2.5 Ethics

37

3.3 Results

37

3.3.1. Basic characteristics

37

3.3.2 Prevalence of PIM use identified using the LRDTE

37

3.3.3 The prevalence of the most frequently prescribed PIMs

38

3.3.4 Factors influencing PIM use in elderly patients38

3.4 Discussion

47

3.4.1 Prevalence of PIM use identified using the LRDTE

47

3.4.2 The prevalence of the most frequently prescribed PIMs

47

3.4.3 Factors influencing PIM use in elderly patients

48

CHAPTER 4 EFFECT OF A COMPUTERIZED DECISION SUPPORT SYSTEM

51

ON PIM PRESCRIPTIONS FOR ELDERLY PATIENTS IN THAILAND(THE SECOND PUBLICATION)
4.1 Purpose

51

4.2 Methods

51

2

CONTENTS (Cont.)

Page
4.2.1 Study design and target population

51

4.2.2 CDSS for PIM detection program and outcome measures

54

4.2.3 Data analysis

55

4.2.4 Ethics

56

4.3 Results

56

4.3.1 Basic characteristics of elderly study participants pre- and post-CDSS

56

4.3.2 Effect of a CDSS on PIM prescriptions for elderly patients58

4.4 Discussion

61

CHAPTER 5 CONCLUSIONS, LIMITATION AND RECOMMENDATION

65

5.1 Conclusions

65

5.2 Limitation

66

5.3 Suggestion

66

CHAPTER 6 REFERENCES

68

APPENDIXES78

LRDTE criteria

78

ACKNOWLEDGEMENTS

84

3

LIST OF TABLES

Page
Table
Characteristics and benefit package of three public health insurance schemes

18

The screening tool for identifying PIM

26

Community hospital characteristics in Chonburi Province in fiscal year 201433

Basic characteristics among elderly patients and PIM prevalence

39

Most frequently encountered PIM according to the LRDTE

42

Factors that influenced PIM use in Thai elderly

45

Characteristics of the four participating community hospitals

53

in the ﬁscal year 2017
Basic characteristics of elderly study participants pre- and57

post-CDSS implementation
PIM prevalence of each PIM level pre- and post-CDSS implementation

59

Common PIMs belonging to each level pre- and post-CDSS implementation

60

4

LIST OF FIGURES

Page
Figure
The aging population in Thailand

14

Computerized Decision Support System (CDSS) for PIM

29

Prevalence of the most frequently used PIM in the elderly

41(60-74 years old and ≥ 75 years old)
The study design comprised two phases with a duration of 12 months

52

Screen shot of computerized decision support system for tramadol

55

5

6

LIST OF ABBREVIATIONS USEDABBREVIATIONSFULL WORDS

ACEI

Angiotensin-converting enzyme inhibitors

ADEs

Adverse dug events

ADRs

Adverse drug reactions

AGS

American geriatrics societyATCAnatomical therapeutic chemical

CCBs

Calcium channel blockers

CDSS

Computerized decision support system

CIs

Confidence intervals

CKD

Chronic kidney disease

CPM

Chlorpheniramine maleate

COPD

Chronic obstructive pulmonary disease

CSMBS

Civil servants medical benefit scheme

CVD

Cardiovascular disease

ED

Essential drug

EPS

Extrapyramidal symptoms

FFirst level

FY

Fiscal year

GI

GastrointestinalGP

General practitioner

HDC

Health data center

Hos

Hospital

ICD-10International statistical classification of disease andrelated health problems 10th revision

LRDTE

Lists of risk drugs for Thai elderly criteria

LIST OF ABBREVIATIONS USED (Cont.)
6

ABBREVIATIONSFULL WORDS

M

Middle level

MI

Myocardial infarction

MOPH

Ministry of public healthN

Sample size

NCDs

Non-communicable diseases

NED

Non-essential drug

NLEM

National list of essential medicines

NSAIDs

Non-steroidal anti-inflammatory drugs

ORs

Odds ratios

PIM

Potentially inappropriate medication

PPIs

Proton pump inhibitors

RDU

Rational drug use

SDStandard deviation

SIADH

Syndrome of inappropriate anti-diuretic hormone

SP

Specialist practitioner

SSS

Social security scheme

START

Screening Tool to Alert to Right Treatment

STOPP

Screening tool of older people’s prescription

TCAs

Tricyclic antidepressants

UCS

Universal coverage scheme

WHO

World health organization

7

CHAPTER IINTRODUCTION

Background and Significance of the study
Thailand is an upper-middle income country in South East Asia, whose populationis quickly aging.1 In 2016, approximately 10 million people were aged over 60 years
and this number is expected to double within the next three decades.2 In addition,
the burden of disease in elderly people increasingly shifts to non-communicablediseases.3 Four out of five older Thai citizens have at least one chronic disease andhave been continuously prescribed multiple medicines. Polypharmacy increases therisk of adverse drug reaction (ADRs). These problems are related to potentiallyinappropriate medication (PIM) use in the elderly.4
PIM has been defined as a medication that puts patients at risk rather than having
benefits and includes prescription medications with drug–drug and drug–disease
interactions.5 PIM use has been associated with hospitalization, morbidity, andmortality resulting from ADRs in elderly patients6,7 and is a problem in high income
countries,8,9 including those in Asia. Presently, several screening tools can be used
to identify PIMs in older adults. The original tool was the Beers Criteria, which was
published in 1991 in the United States. An expert panel identified medicines thatshould be avoided in the elderly owing to drug-disease interactions, drug-druginteractions, the need for caution in this population, and effects on kidney function.10
The screening tool of older people’s prescriptions (STOPP) was explicit criteria
published in Europe in which the medication lists were organized by physiologicalorgan systems.11 In Thailand, the Winit-Watjana criteria were developed in 2009 and8included the use of high-risk medications with potential ADRs, drug-disease
interactions, and drug-drug interactions.12 In 2012, the Lists of Risk Drugs for Thai
Elderly (LRDTE) were developed from the 2012 Beers Criteria and 2008 STOPP.
The advantage of the LRDTE was that the medication lists considered the age groupin elderly aged over 60 years and the severity of medication risk. Furthermore, thisis the currently covered standard treatment guideline and hospital formulary for Thai
elderly.13
As for PIM studies in Asian countries, the prevalence of PIM use determined fromthe Beers Criteria in Indonesia was 87% in geriatric patients,14 whereas, in Malaysia,
the reported prevalence of PIM use determined using the STOPP was 33%. 15 For
Thailand, PIM use was identified using the Winit-Watjana criteria and the prevalence
was 58% in elderly patients.16 In addition, a 32% and 28% prevalence was determinedusing the STOPP and Beers Criteria, respectively.17
Irrational prescribing is a problem in the Thai health care system, especially PIM
prescribing to elderly patients. These patients frequently receive medicines without
knowing the indication and follow a polypharmacy pattern of use. In 2011, theMinistry of Public Health (MOPH) launched the rational drug use (RDU) policy toenhance the quality of health services for all people. Reducing PIM use is the oneof the missions of the RDU policy aimed at improving drug safety in the elderly.18, 19
A large-scale prevalence of PIM was found in many community hospitals in Thailand,
and the prevalence was 30–60% among elderly patients.13, 20 Over half of PIM and
ADE problems are associated with the prescribing process by physicians; thus, theimprovement should be made at the prescribing stage to increase patients’ safety
and quality of treatment.21 The MOPH has developed a novel computerized decision
support systems for detecting PIM prescription.22
9

Computerized decision support system (CDSS) is an automated alert system thatis commonly used in healthcare applications globally. This system can alert
physicians when medications with potential problems such as drug allergies andother medication errors are prescribed. CDSS can provide real-time medication
information so that physicians can make appropriate prescription changes.23, 24
A CDSS for detecting PIM is a computerized alert system that automatically detects
PIM prescriptions to guide physicians to make the best decisions for improving drug
safety in elderly patients.25 Several studies have shown that CDSS significantly
decreased PIM prescriptions.26 In a previous study conducted in elderly patients(65 years and older), 1,539 patients pre alert and 1,490 patients post alert wereprescribed PIMs. The outcome measure was reported as the proportion of PIM
prescriptions of the total prescriptions for six months from pre- to post-CDSS.
There was significant reduction from 13 % to 12 %.27 In a prospective before and after
study with a duration of two months, 65 elderly patients were enrolled in theintervention group and 74 elderly patients in the control group. The proportion ofpatients in the intervention group who received at least one PIM decreased from
41.7% to 11.6%. High-dose short-acting benzodiazepines were significantly reduced
from 20% to 6%.28
Chonburi province in eastern Thailand is a large industrial city. The latest Thai
PIM study in this area revealed that approximately 80% of elderly patients incommunity hospitals are confronting the greatest risk of being prescribedinappropriate medications. In addition, physicians increased PIM prescriptions byapproximately 3-fold for elderly patients. Therefore, CDSS should be used tosupport physicians in decision making regarding drug prescription.29 CDSSs are
currently available in the Thai healthcare system for the management of drug related
10

problems. A hypokalaemia-drug alert system study reported that prescription of
medicines related to the reduction of potassium levels was reduced from 7% to
0.63%.30 Moreover, the alert system for kidney disease medication can optimize themedicine–dose calculation to prevent potential harm for patients with kidneydisease.31 However, the effectiveness of this CDSS for PIMs has not been clearly
established and the prevalence of PIM use using the LRDTE has not been
determined in Thailand. Therefore, this study aimed to examine the prevalence of
PIM use based on the LRDTE, to address the PIM problem by identifying factorsthat influenced PIM use and to evaluate the effect of a CDSS on PIM prescriptions
for elderly patients in Thai community hospitals.

11

CHAPTER 2
LITERATURE REVIEW

Prescribing medication for elderly patients can be particularly challenging due tochanges in pharmacokinetics, pharmacodynamics, and multiple co-morbidities. As
such, elderly patients have increased risks from adverse drug effects (ADEs) andpotentially inappropriate medicines (PIMs). This chapter is the result of an extensive
study of relevant literature on this subject. The details are divided into the following
six parts: the current situation of population aging, the healthcare system for the
aging population in Thailand, medication use in elderly patients, PIM use in Thai
elderly, screening tools for Identifying PIM, and a computerized decision support
system (CDSS) with regard to PIM prescriptions

2.1 Situation of Population Aging in Thailand
In recent years, the elderly population has grown rapidly, and it isestimated that by 2050, the percentage of the worldwide population older
than 60 years will be about 2 billion. 32 The United Nations announced 20012100 to be the century of an aging society. They defined “the elderly” as
the population, both male and female, who were aged 60 years and above.
The aging societies were classified into three levels: 1) the level of entering
the aging society, meaning the societies or countries with people aged 60
years and above comprising more than 10% of the national population, or
those with people aged 65 years and above comprising more than 7% of thenational population; 2) the level of Aged Society, meaning the societies or
12

countries that have people aged 60 years and above equaling more than
20%, or people aged 65 years and above equaling more than 14% of the total
population of the country; and 3) the level of Super -aged Society, meaning
the societies or countries that have people aged 65 years and above
equaling more than 20% of the total population of the country 33 The World
Health Organization (WHO) defines “elderly” to mean people aged 60 years
or above. Those from 65 through 74 years old are referred to as “early
elderly,” those aged 75-84 years old are referred to as “middle old,” andthose over 85 years old are referred to as “late elderly.” All countries do
not have the same age brackets for determining these categories, but mostdeveloped countries use 65 years old as the marked beginning of the elderly
ages. 32 In Asia, Japan defined the term “elderly” to mean those aged 75
years or more, while most developing countries have defined the term tomean those aged 60 years or more. 34,3 5 According to world population
statistics, all the countries referred to as developed countries, such as theUnited States of America and countries in Europe, and even some countries
in Asia (such as Japan) have higher average life expectancy than othercountries. On average, developed countries have a life expectancy of 77.2 81.5 years. In the African continent, on the other hand, the average life
expectancy is 41.5-50.7 years. 33
Thailand is an upper-middle income country in Southeast Asia, and has the most
rapid rates of population aging.1 In 2016, the number of people aged 60 and above
was about ten million, accounting for 13% of the population, and this number is
expected to double within the next three decades. Generally, in Thailand, the terms“older population” or “elderly” refer to persons aged 60 and above. Currently,
13

Thailand go to the aging society that there are the elderly aged 60 years and older
comprising more than 10 % of the national population. For the next four years,
Thailand will become to aged society that mean people aged 60 years and older
equaling more than 20 % of the national population.2, 36, 37 (Figure 1)

Figure 1 The aging population in Thailand 2

The Thai elderly patients have been facing an increase in non-communicablediseases (NCDs). NCDs is the chronic disease such as diabetes mellitus,
hypertension, cardiovascular disease, and cancer. Four out of five older adults haveat least one chronic disease. The increase of elderly population related to theserious chronic disease problem in Thailand. Almost half of Thai elderly patients
have hypertension, follow by diabetes and osteoarthritis.4 The percentage of chronic
diseases death among the elderly population compared to the younger generation is
expected to increase from 74% in 2015 to 80% in 2025. The main causes of morbidity
and mortality among the Thai elderly population over the next few decades are
predicted to be related to chronic diseases.38

14

2.2 The Healthcare system for the aging population in Thailand
2.2.1 The Healthcare system in Thailand
The Ministry of Public Health (MOPH) is the main health care provider of most allof the public health services. The public health hospital are divided 3 levels, as
following,
1) Primary care level is the Tambon (Sub district) health promoting hospitals or
sub district hospitals were not intended to be inpatient facilities with staffed beds
and without physician, but rather a type of polyclinic focus on preventive medicine,
health promotion and treatment for minor trauma. This hospital level is the firstcontact point for the beneficiaries to receive medical services. The beneficiaries are
not allowed to go directly to secondary or tertiary care facilities without referral
from the primary medical care unit except accidental or emergency situations.
2) Secondary care level is the district hospital as the community hospital that has
the variety of hospital. The middle hospital level (M1 and M2) provide 120 beds forservice. For the first hospital level (F1 to F3) have 10 to 90 beds for service andare small hospitals. Each level has the different number of beds, number of medicines,
and types of specialist. For the first hospital level, the physicians consist of generalpractitioner, family medicine, and the small number of specialist. The district hospital
have been used as the key referral points and the link between the health centers
and the tertiary care hospital level.
3) Tertiary care level, there are standard level as the provincial hospital level,
which provide 300-400 beds and has the specific specialist in all major. For advancelevel as the university hospital have 800 beds and more. In addition, there are many
specific specialists in all major and advance technology for treatment and high cost.

15

2.2.2 The Health Insurance System in Thailand
The public healthcare benefit system in Thailand is divided into three major
schemes: the Civil Servant Medical Benefit Scheme (CSMBS), the Social Security
Scheme (SSS), and the Universal Coverage Scheme (UCS, also known as the
National Health Security Program or the 30-Baht Scheme). The CSMBS was
created to finance the provision of healthcare services for civil servants and theirfamilies. Overall, 10% of the total population is covered under CSMBS. This healthinsurance scheme is fully paid for by the government (taxation) and state enterprises.
The Ministry of Finance is responsible for the CSMBS and the state enterprises are
responsible for the medical bills of their employees. In Thailand, civil servants’
medical benefits are superior to those enjoyed by anyone but the most affluent, who
are likely to have substantial private insurance. CSMBS are still the best in Thailand
because CSMBS get free choice of the contractor providers and can access bothessential drug and non-essential drug. Any drug not in the ED is generally allowed
to be reimbursed under the criteria of rational drug use policy. The SSS aims toprovide health and social welfare for private employees, and covers 13% of the
population. The people in the SSS pay up to 5% of their earnings for full healthcoverage.38 Drugs, treatments, surgeries, and care are fully covered, except for somemedicine list drugs such as newer drugs or drugs currently being researched. People
covered under the SSS will choose one hospital where they will be treated (maincontractor). If a patient needs to be admitted in an emergency somewhere else, thecontracted hospital will pay the bills to the emergency hospital. For UCS was fully
implemented in April 2002 to provide healthcare coverage for the rest of the
population. The remaining 75% of the Thai population, who do not benefit fromCSMBS, are covered by the informal sector, state enterprise benefits, or the social
16

security scheme. Under this scheme, people pay 30 Baht (approximately $1) per
visit or admission. This scheme has been transformed and renamed UCS in 2009. It
is now free, which means there is no co-payment. Almost of all elderly patients werecovered by UCS found that about 90% of elderly patients. About 1-2% benefited fromthe civil servants medical scheme either as retirees and the parents of civil
servants.39 Table 1 provided summary of each characteristics and benefit packageof health insurance scheme.
2.2.3 Thai National List of Essential Medicine (Essential Drug, ED)
Thai National List of Essential Medicine was published by the Ministry of Public
Health and its use was extended to cover all public hospitals. The responsible agency
to decide and update the ED is the Sub Committee on National Essential Medicine.
The essential drug was updated every 2 years. Currently, the number of medicines
in essential drug including all active pharmaceutical ingredients is 831 formularies.
The hospital formularies are developed by the pharmacy and Therapeutics
Committee (PTC) consisting of various clinical specialties and pharmacists. The
selection of medicines in the hospital formularies are also claimed to be based onneeds, safety, efficacy and cost effectiveness for Thai population. Most of thehospital formularies also include medicinal products that are ED and not listed in
the ED depending on hospital level and specialist.40

17

Table 1 Characteristics and benefit package of three health insurance schemes
Characteristic

Beneficiaries

Civil servant

Social security

Universal

benefit scheme

schemeCoverage scheme(CSMBS).

(SSS)

(UCS)

Government

Private sector

The remaining

employees

employees

population who are

and their family

not covered by
CSMBS, SSS

Population coverage
Source of finance

10%

13%

75%

General tax

Tripartite

General tax

revenuepayrollrevenuecontribution by
employee,employers andthe government
Essential Drug (ED)ED and non ED

Choice of provider

Free choiceED

ED

Contracted

Primary care

hospital or its

contractor

network

services,
plus referral

Ambulatory services Free choice public

Public and

Designatedprivateproviders, mostly

contractors

Primary Care Unit

Free choice Public

Public and

Designatedand private

privateproviders, mostly

contractors

starting first with

only
Inpatient services

District Hospitalwith referral
Annual physical

Yes

No

No

No

No

Yes

check-up
Prevention, Healthpromotion18

2.3 Medication Use in Elderly Patients
Elderly people are at greater risks for potentially harmful medication effects due
to changes that occur as the body age. There are age related changes topharmacokinetics and pharmacodynamics of medicines that lead to a reduction inphysiological reserves.41 The normal aging process is associated with physiologicalchanges that can affect drug absorption, distribution, metabolism, and excretion(pharmacokinetics), as well as drug action at receptor sites (pharmacodynamics).
These changes lead to drugs having prolonged durations of activity, greater risks of
toxicity, increased frequencies of adverse effects, and greater or lesser effects than
anticipated from a given dose. In addition to the physiologic changes that occur,
elderly people are often treated for multiple chronic and acute conditions.42 Thisrequires them to take many medications, otherwise called polypharmacy. The riskof potential ADEs increases with the number of medications prescribed, rising froman incidence of 13% if two drugs are prescribed, to 38% with four drugs prescribed
and to 82% if seven or more drugs are prescribed43. Thai elderly patients use an
average of five medications on a regular basis and polypharmacy is present
in 40% of elderly patients. 44 The prevalence of adverse drug reactions wasfound in 40% of those aged 70 and above. The ADE rate in the elderly is atleast three times that of the general population. 45,46 Additionally, up to 20%
of re-admissions of geriatric patients were found to be medication related. 4

2.4 Potentially Inappropriate Medication use in (PIM) Thai elderly
Potentially inappropriate medication (PIM) use is a major healthcare problem
worldwide, and it increases the risk of adverse events and greater healthcare
expenditure of elderly patients. Presently, there are many PIM studies in developed
19countries, with varying PIM definitions. One study defined PIMs as drugs with a highrate of ineffectiveness or a high risk–benefit ratio47 Fouquet et al. defined PIM use
as overuse (the use of medicine without valid indication) or misuse (e.g.,
inappropriate dose or duration) of medications, as well as underuse of
potentially beneficial medications. 48 Another study held PIMs to include
drugs considered inappropriate for older adults with certain chronic conditions.49
In this study, PIM has been defined as medication that puts patients at risk rather
than having benefits and includes prescription medications with drug–drug and drug–disease interactions.5 In Thailand, irrational drug use is a major problem in the Thai
healthcare system, especially PIMs prescribed among older people. The PIM list
includes drugs with a risk of ADE exceeding their expected clinical benefit inpatients.18, 19 The sub-sections below indicate the various criteria that may lead todrugs being considered as PIMs.
2.4.1 Anticholinergics medications
Anticholinergics have been shown to increase th e risk of side effects
such as urinary retention, constipation, visual disturbance, and hypotension,
which can be especially harmful in an elderly population. It is crucial toconsider cognitive side effects in the often cognitively impaired elderly
patients. In addition, the elderly have increased risk of falls as well as higher
risks of fracture due to decreased bone density and poorl y functioning
musculature. 50 PIMs in this group are tricyclic antidepressants drugs likeamitriptyline, and antihistamine drugs such as chlorpheniramine, cyproheptadine,
promethazine, hydroxyzine, and diphenhydramine. Patients with chronic constipation,
dementia, cognitive impairment, a history of falls and fractures, and benign prostatic
hyperplasia should be cautioned against using such drugs.51
20

2.4.2 Antiparkinson medications
Trihexyphenidyl as the drug in this group was not recommended for prevention of
extrapyramidal symptoms with antipsychotics because there are more effective
agents available for treatment of Parkinson’s disease.52 This medicine should be
avoided whenever possible in the elderly and especially in those suffering fromdementia. Moreover, this drug should be avoided in patients of chronic constipation,
dementia, cognitive impairment, and history of falls and fractures.53
2.4.3 Antispasmodics medications
Hyoscine, Dicyclomide, and Belladonna alkaloids (in the antispasmodic drug group)
were highly anticholinergic and inconsistent in their effectiveness. Adverse effects
in elderly patients included dry mouth, constipation, blurred vision, and urinary
retention. Their efficacy at tolerated doses is unclear. Moreover, this drug should
be avoided in patients of chronic constipation, dementia, cognitive impairment, andhistory of falls and fractures.54
2.4.4 Sulfonylureas Medications (Chlorpropamide, Glyburide and Glibenclamide)
Because of the prolonged half-life of the medicines of the Sulfonylureas group,
they can lead to severe hypoglycemia in older adults, which may result in coma andmay require hospitalization.55 In addition, this medicine can cause the syndrome of
inappropriate anti-diuretic hormone (SIADH), which is characterized by impaired
water excretion leading to hyponatremia with hypervolemia or euvolemia.56
2.4.5 Barbiturate medications (Phenobarbital)
The use of barbiturates in the elderly over age 65 should be monitored
closely. Elderly patients must be carefully monitored for confusion,agitation, delirium, and excitement. Barbiturates drugs should be avoided in21

elderly patients who are receiving drugs for other mental disorders such as
schizophrenia or depression. These medications can be addictive. Over time,they get less effective in helping older adults sleep. They are more likely
to cause an overdose even at relatively lower doses than alternative drugs.57
2.4.6 Meperidine medication
Meperidine (pethidine) is one of the most commonly used opioid analgesics. This
medicine poses a higher risk to those aged 65 years and above, as they are moresensitive to its side effects and may have diminished renal function, which leads tothe accumulation of Meperidine. The side effects are delirium, drowsiness, and postoperative pain in elderly patients. In addition, it is not a remarkably effective pain
reliever and may cause seizures.58
2.4.7 Diuretic medications
Diuretic medications are commonly used to treat numerous conditions
highly prevalent among older adults including hypertension, heart failure,and edema 59 However, this drug can cause hypokalemia, which may precipitate
cardiac arrhythmias and sudden death.60 Muscle weakness associated withhypokalemia can increase fall risks for older adults61 Moreover, the risk ofhyponatremia appears to be particularly common in elderly patients. Hyponatremia
can lead to confusion, delirium, and dementia.62
2.4.8 Antithrombotic medications (Dipyridamole, Ticlopidine)
The short-acting form of Dipyridamole is taken by mouth that may make patients’blood pressure drop when they stand up. This can make them dizzy and haveorthostatic hypotension, which may in turn lead to dangerous falls63 More effective
alternatives are available. The form of dipyridamole that is injected, however, can be22effective when used during a cardiac stress test.64
2.4.9 Benzodiazepines medications
Benzodiazepine drugs are classified two categories: 1) short- and intermediateacting: alprazolam, estazolam, lorazepam, oxazepam, temazepam and triazolam and2) long-acting: chlorazepate, chlordiazepoxide, chlordiazepoxide-amitriptyline,
clidinium-chlordiazepoxide, clonazepam, diazepam, flurazepam, and quazepam. Olderadults have increased sensitivity to benzodiazepines and slower metabolisms oflong-acting agents. In general, all benzodiazepines increase the risk of cognitive
impairment, delirium, falls, fractures, and motor vehicle accidents in older adults.
Despite these risks, they may be appropriate, in certain cases, for treating seizures,certain sleep disorders, and anxiety disorders.65
2.4.10 Non-selective Oral or NSAID medications
Nonsteroidal anti-inflammatory drugs (NSAIDs) constitutes one of the mostcommonly prescribed classes of medication for pain and inflammation.66 They are
responsible for approximately 5-10% of all medications prescribed eachyear.67 The prevalence of NSAID use in patients over 65 years old is as high as 96%
in the general practice setting.68 Approximately 7.3% of elderly patients over 60 years
old filled at least one NSAID prescription in a one-year period.69. Regarding acutekidney injury associated with NSAID use in the elderly, medication combinations
such as NSAIDs and diuretics can predict acute kidney injury70 Gastrointestinal
bleeding and ulceration due to NSAID use tend to increase in severity and frequency
with increasing age. NSAID use leads to a fourfold increase in the risk of GI bleedingin the elderly71.In addition, NSAIDs can also increase the risk of falls, geriatric
psychiatric events, and the risk of stroke. The use of a proton pump inhibitor (PPI)or misoprostol reduces, but does not eliminate, the risk.72
23

2.4.11 Calcium Channel Blocker medications
Calcium channel blockers (CCBs) are effective in lowering blood pressure,relieving angina symptoms, and improving exercise tolerance in older and younger
patients with coronary artery disease. However, there are higher rates of cardiac
death associated with diltiazem treatment in patients with myocardial infarction (MI)and pulmonary congestion. More recently, a meta-analysis of nifedipine therapy after
acute MI identified higher mortality associated with nifedipine therapy.73 The elderly
taking amlodipine have a high risk of developing chronic constipation approximately
four times more than those not taking it. Moreover, elderly patients taking CCBs
were significantly more likely than those using other agents to experience cognitive
decline.74
2.4.12 Gastrointestinal medications
2.4.12.1 Metoclopramide and Prochlorperazine
Metoclopramide can penetrate the blood brain barrier and affect dopaminergic andcholinergic neuron functions. It can cause extrapyramidal symptoms and cognitive
impairment, and may exacerbate Parkinsonian symptoms. Therefore, administering
metoclopramide to Parkinson’s patients should be avoided.75
2.4.12.2 Diphenoxylate, Loperamide, and Codeine Phosphate
With these, there is a risk of delayed diagnosis, which may exacerbate constipation
with overflow diarrhea, may precipitate toxic megacolon in inflammatory bowel
disease, and may delay recovery in unrecognized gastroenteritis.76
2.4.12.3 Proton Pump Inhibitor (PPI) medications
PPI is commonly used for uncomplicated peptic ulcer disease or erosive peptic
esophagitis. Elderly patients should not use it for more than eight weeks unless they24are high-risk patients (e.g., oral corticosteroids or chronic NSAID use) with erosive
esophagitis, Barrett’s esophagitis, pathological hypersecretory condition, ordemonstrated need for maintenance treatment (e.g., due to failure of drug
discontinuation trial or H2 blockers).77 This medicine poses high risks of Clostridium
difficile infection, and bone loss and fractures.78

2.5 The screening tools for Identifying Potentially Inappropriate
Medication
Currently, there are various screening tools for the assessment ofappropriateness of prescriptions. According to many PIM studies, different countries
reported the percentage of inappropriate prescribing as ranging from 7.8% to over
50% of all prescriptions. The different explicit criteria for the assessment of theappropriateness of prescriptions for the elderly have specific characteristic features.
Moreover, each of them has its own advantages and disadvantages. Some of them
are now modified or merged with others for use by the elderly in their countries.79
Currently, many tools are being used to evaluate inappropriate prescriptions to theelderly. These include the 2015 Beers Criteria10, the Screening Tool of Older
Persons’potentially inappropriate Prescriptions (STOPP),11 the Criteria for high-risk
medication use in Thai older patients12 and Lists of Risk Drugs for Thai Elderly.13.
Table 2 showed the summary of the screening tools for Identifying PIM.

25

Table 2 The screening tool for identifying PIM
DetailBeer’s criteria

Screening tool ofolder people’s potentiallyinappropriate prescription(STOPP)

Criteria for High-risk
Medication use inThai older Patients(Winit-Watjana)

List of risk Drugfor Thai elderly(LRDTE)

PublishUSA, 19912015 (the latest version)

European, 20082014 (the latest version)

Thailand, 2007

Thailand, 2012

Number of medication

127 medications
8 medication classes

81 medication
10 Physiological Systems

77 medications

76 medication
8 medication classes

Classification of PIM

1. Drug–Drug Interaction
2. Drug–Disease Interaction
3. High risk of ADR
4. Drugs to Be Used with
Caution
5. Drugs for which dose
adjust is require basedon kidney function

1. Drug-Drug interaction
2. Drug-Disease interaction
3. Drugs which ADR in older
patients at risk of falls
4. Duplicate drug classprescriptions

Three medication risk groups
1. High risk medications
with potential ADR
2. Drug–Drug Interaction
3. Drug–Disease Interaction

Two age groups
1. Age at 60-74 years
2. Age at ≥ 75 years

Four severities of medicine
1. Medicine to be avoided
2. Medicine that is rarely
appropriate
3. Medicine that needs
indication
4. Medicine that is
unclassified
26

Three severities of
medicine risk
1. Mild level:
short term use
2. Moderate level:
avoiding by using
alternative choices
3. Severe level:
not recommend, nobenefit2.5.1 Beers Criteria
The most widely used criteria in the United States for assessing potentiallyinappropriate prescribing the elderly are the “Beers Criteria.” They were originallydeveloped in 1991 by 13 experts on a consensus panel in geriatric medicine, longterm care, geriatric and psychogeriatric pharmacology, and pharmacoepidemiology,
using a modified Delphi method. The instrument method was revised several times
for general use among older adults. The 2015 American Geriatrics Society (AGS)
Beers Criteria represents the latest version. The changes in the 2015 update were
not as extensive as those of the 2012 AGS Beers Criteria. However, in addition to
updating the existing criteria, two major components were added: 1) drugs for which
dose adjustment is required based on kidney function, and 2) drug–drug interactions
documented to be associated with harm in older adults. PIMs were classified as
inappropriate in five categories: 1) medications to be avoided in older adults,2) medications to be avoided in older adults with certain diseases and syndromes,3) medications to be used with caution in older adults, 4) drugs for which dose
adjustment is required based on kidney function, and 5) drug–drug interactions.10
Using Beers Criteria, rates of inappropriate prescribing were found to range from
7.9% to 60% among elderly patients of different countries80, 81
2.5.2

Screening

Tool

of

Older

Persons’

Potentia lly

Inappropriate

Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START)
Criteria
The STOPP and START criteria were first published in 2008 and were developedby a multidisciplinary team of geriatricians, pharmacists, pharmacologists, andprimary care physicians. The criteria are organized by body system for ease of use
and are designed to be used together to ensure a comprehensive assessment of27

older persons’ medications. In the updated 2014 version, 81 STOPP and 34 START
criteria were organized by physiological organ systems. STOPP lists instances of
PIMs that should be avoided, drug interactions, and drugs that increase the risk offalls, while START lists instances of potential prescribing omissions where clinicallyindicated medicines are not prescribed. The STOPP and START tools have beenused to describe rates of PIM prescribing in a range of international settings acrossEurope, Asia, and Northern America.11 These criteria were successfully applied, withgood inter-rater reliability, in a number of settings, revealing PIM rates of 22% inprimary care clinics, 35% in acute hospital settings, and 60% in nursing homes. 82,83
The advantages of the STOPP consist of good inter-rater reliability and structure
based physiological systems. However, evaluation of this tool requires additional
studies from different settings of different countries.11
2.5.3 Criteria for High-risk Medication use in Thai older Patients
In Thailand, Winit-Watjana et al. developed a list of high-risk medication use among
the elderly was published 2008, using a Delphi technique with the three-round surveyof 16 geriatric medicine experts. They identified 77 criteria, divided into three groups:
1) high-risk medications with potential adverse reactions, 2) high-risk medications
with drug-disease interactions, and 3) high-risk medications with drug–druginteractions. The high-risk medications in each group were categorized according tofour levels: 1) medicine to be avoided, 2) medicine that is rarely appropriate,3) medicine that needs indication, and 4) medicine that is unclassified. Although thislist has addressed different issues of inappropriate prescribing, this tool is not tested
in different clinical settings and lacks inter-rater reliability.12

28

2.5.4 Lists of Risk Drugs for Thai Elderly (LRDTE)
The LRDTE is the new explicit criteria for identifying PIM in Thai elderly patients.
In 2012 Ploylearmsang C et al. developed this screening tool from the 2012 Beers
Criteria and 2008 STOPP. The LRDTE criteria consist of 76 medications and eight
medication classes (anticholinergic, antithrombotics, anti-infective, cardiovascular,
central nervous system, endocrine, gastrointestinal, and pain management). These
criteria are categorized by age and severity of medicine. Age is divided into two
categories, as follows: 1) 60-74 years and 2) 75 years and above. Medicine wascategorized into three severity levels, as follows: 1) mild - use within certain
conditions or over a short term or with intensive monitoring; 2) moderate - avoid byusing alternative choices; and, 3) severe - not recommended and has no benefit.13(Appendix 1)This study identified PIM by using the LRDTE because this new Thai PIM
screening tool currently covered standard treatment guideline and hospital formulary
for the Thai elderly.29

2.6 Computerized Decision Support System for PIM Prescriptions

Figure 2 Computerized Decision Support System (CDSS) for PIM 89
29

Computerized decision support systems (CDSS) are being built to improvemedication use in addition to the traditional prescribing interventions. A clinicaldecision support system is defined as software that integrates information on thecharacteristics of individual patients with a computerized knowledge base, for the
purpose of generating patient-specific assessments or recommendations designed
to aid clinicians in making clinical decisions. These systems can help alert, interpret,
assist, critique, diagnose, and manage a patient’s care.84 Alerting systems within
CDSS inform prescribers of prescription problems based on patientcharacteristics, allergies, or interactions with other medications. The
clinician may accept the alert and cancel the order 85 In one study, the use of
CDSS decreased the rate of medication errors by 81%.86 Several Institute ofMedicine reports have emphasized the need to adopt CDSS as an importantpart of the national strategy for improving medication safety.87 CDSS has proved
successful in improving PIM prescribing. A study stated that computerized
pharmacy alert systems for pharmacists along with collaboration between
healthcare professionals led to a decrease in PIM use in elderly patients.
Another study showed that computer-based access to a complete
medication profile combined with alerts to the pharmacist regardi ng
potential prescribing problems, followed by a call to the physic ian, reduced
the number of PIMs 88 CDSS of PIM integrated into electronic prescribing
could support the prescriber to consider assessing or changing “high -risk”
medications and could serve as a good reminder of contra -indications suchas ages or disease states. It provides extensive and ad vanced functionality
for managing PIM use by physicians. When alerts are used and triggered onorder entry, physicians should suggest an appropriate alternative that can30be directly ordered through the alert. They should construct the alert sothat the “reason to avoid use” is prominent. An example of an ideal alert
is as follows: “Caution in older patients: Has a long half -life in the elderly,
producing prolonged sedation and increasing the risk for falls and fractures.
Alternative medications are preferred. Here is the list of medications with
options to order directly in order to avoid PIM. 89
Specific alerts embedded into a CDSS used on inpatients 65 years or older canquickly lead to a decrease in the number of PIM orders. Melissa L et al. found thatthe mean rate of ordering PIMs dropped from 12% to 10% after the implementationof a CDSS of PIM.90 In addition, David H et al. found there was a large and persistent
reduction (5.1 prescriptions per 10,000, P=.004), and a 22% relative decrease fromthe month before CDSS of PIM implementation in the exposure of elderly patients
to non-preferred medications.91 One small Canadian study in the outpatient setting
examined the effectiveness of the CDSS for PIMs and found a reduction of 13%(relative rate, 0.77; 95% confidence interval, 0.59-1.00) in inappropriate prescribingof long-acting benzodiazepines and active metabolites of Tricyclic antidepressant.21
CDSS for PIMs provides an opportunity for intervention to change prescribing
practices before potentially inappropriate medications are ordered. A CDSS of PIM
with specific, targeted, and straightforward warnings can dramatically, yet selectively,
reduce the prescription of potentially inappropriate medications in vulnerable
hospitalized elders. This may represent a tool for improving the safety of hospitalized
older adults9 (Figure 2).

31

CHAPTER 3
Applying the Lists of Risk Drugs for Thai Elderly (LRDTE) as a mechanism toaccount for patient age and medicine severity in assessing
potentially inappropriate medication use(The first publication)

3.1 PURPOSE
The main purpose of this study was to examine the prevalence of PIM use basedon the LRDTE. In addition, this aimed to address the PIM problem by identifying
factors that influenced PIM use among elderly patients in Thailand.

3.2 METHODS
3.2.1 Study design and population
This was a retrospective, cross-sectional descriptive study of PIM use among
elderly patients in community hospitals in Chonburi Province, Thailand. Chonburi
Province is located in Eastern Thailand and has the highest population density.93
Four of nine hospitals in the province were selected in the study after they agreed
to provide the required information. Three hospitals were small hospitals in rural
areas, especially, hospital D was the relative new and smallest hospital and anotherwas a medium hospital in an urban area. Each had a different number of beds, numberof medicines, medicine list, and types of specializations (Table 3).94
The population studied included elderly patients aged 60 years and older who had
at least 2 pharmacy claims and visited as an outpatient over a 1-year period during
fiscal year 2014 (FY 2014). Missing or irretrievable medication data were excluded.

32

Table 3 Community hospital characteristics in Chonburi Province in fiscal year 2014
Characteristic

Hospital A Hospital B Hospital C Hospital D

Hospital level

F1

F2

F2

F2

Established period

1969

1983

1983

2013

Number of doctors

SP 7

GP 6

GP 4

GP 4

GP 7

Dentist 3

Dentist 4

Dentist 2

Dentist 8
Number of beds

64

60

30

30

Number of outpatient visit/year

247,703

95,18574,947

47,120

Number of inpatients visit/year

6,956

4,466

1,641

628

Number of medicines in the hospitala 287

262

224

208

ED:NED(273:14)(253:9)(216:8)(203:5)

Number of PIM lists in the hospitalb

33

29

27

28

% of PIMc

12

11

12

14

PIM = Potential inappropriate medication
F1 = The medium community hospital where was comprised 60 beds or more andthere was specialist,
F2 = The small community hospital where is comprised 30 beds or more and there
was without specialist.
GP: General practitioner and SP: Specialist.
ED = Essential drug, NED = Non-Essential drugaNumber of medicine in the hospital is the number of all modern medicines in thehospital (excluding duplicated medication).
b
Number of PIM list in the hospital is PIM list in the hospital was identified fromLists of risk medicines for Thai elderly.
c% of PIM = (Number of PIM list in the hospital x 100)/ Number of medicine in thehospital

33

3.2.2 Data source and variables
The secondary data were collected from four hospitals using medical andpharmacy claims from the Health Data Center (HDC) database between April 1, 2014
and March 31, 2015 (FY 2014). The HDC database included all claims data of patientcharacteristics, health service utilization, and Thai region-specific characteristics.
According to a literature review, patient characteristics, age category (60-74 or ≥75 years) based on the LRDTE criteria,13 gender (male or female), and comorbidities
were identified from International Statistical Classification of Disease and Related
Health Problems 10th Revision (ICD-10) code95 and the Elixhauser classification
system.96
For health service utilization characteristics, the number of outpatient visits wasclassified as 1-3 or ≥ 4 visits; the number of hospitalizations was categorized 0 or
≥ 1; and the number of diagnoses was utilized as a categorical variable (1-2, 3-4, or≥ 5), as described in a previous Thai study.16 Medication dispensed, including genericor brand name, strength, form, number of medicines, and dispensing date, wasdetermined. Prescription and non-prescription medications were coded according
to the Anatomical Therapeutic Chemical (ATC) classification system recommended
by the World Health Organization.97 Each patient's total number of medications was
categorized as 1-5 or ≥ 6, based on prior studies.98
As for the Thai region-specific characteristics, we considered health insurance
schemes, hospital characteristics, and prescribers. Health insurance schemes
consisted of the civil servants medical benefit scheme (CSMBS) for government
employees, the universal coverage scheme (UCS) for the remaining population, thesocial security scheme (SSS) for private employees, and out-of-pocket. The
beneficiaries for each health insurance were different. CSMBS and out-of-pocket
34

allowed the use of both essential and non-essential medicines, whereas SSS andUCS allowed the use of only essential medicine.99
Hospital characteristics were classified by community hospital levels. The hospital
formulary in each hospital was different based on the hospital level. In addition, thehospitals were described by the number of beds and physicians (F1: medium level
hospital having 60 beds or more and specialists or F2: small level hospital having 30
beds or more and no specialists) using the geographic information system inThailand.94
Prescribers were general practitioners, specialists, or other health personnel(including dentists and nurses). Each prescriber has a different role in prescribing:specialists have more authority than other prescribers in that they can prescribe
specialized medicines, general practitioners can prescribe common medicines, andother health personnel can prescribe only limited medicines.100
3.2.3 Measurement of potentially inappropriate medicines
PIMs were defined using the LRDTE; the new explicit criteria consisted of
76 medications or 8 medication classes that should generally be avoided in all elderly
patients. The LRDTE is categorized by age and severity of medicine. Age wasseparated into two categories: 60-74 years and 75 years and over. Medicine wascategorized into 3 severity levels: level 1 (mild) is used within condition or over the
short term or with intensive monitoring, level 2 (moderate) is avoid by using
alternative choices, and level 3 (severe) is not recommended and no benefit.19(Appendix 1)

35

3.2.4 Data analysis
The main objective of this study was to examine the prevalence of PIM use among
elderly patients based on the LRDTE. The prevalence for all PIM and separately foreach medicines were calculated as the number of elderly patients who used at least
one PIM during FY 2014 divided by the number of elderly patients who received any
service at the four hospitals during FY 2014.
Risk factors predicting PIM use were identified using multivariate logistic
regression models. In model 1, common risk factors were patient and health service
utilization factors. In model 2, Thai region-specific factors, including health insurance
schemes, hospitals, and physicians, were added. Each health insurance scheme wasdifferent for its beneficiaries; therefore, the PIM prescribing rate was compared
between the different health insurance schemes. For hospitals, we reported theresults for each hospital individually to account for potential biases from differencesin the proportions of older adults. A physician factor was included if a generalpractitioner or others prescribed PIM to patients at least one time during the one
year period.
The results from the two models were compared to determine whether the Thairegion-specific characteristics were independent risk factors after adjustment forthe common factors and described as unadjusted and adjusted odds ratios (ORs)and 95% confidence intervals (CIs). A p-value < 0.05 was considered statisticallysignificant. All analyses were carried out using STATA software version 13 (Stata,
College Station, TX, USA).

36

3.2.5 Ethics
The study was approved by the Research Ethic Committee of Sirindhorn Collegeof Public Health, Chonburi Province, Thailand on July 21, 2016. In addition, the data
use was officially approved by each hospital.
3.3 RESULTS
3.3.1. Basic characteristics
A total of 13274 elderly patients aged ≥ 60 years were included during FY 2014.
The basic characteristics of these patients are presented in Table 4. The top fivecomorbidities were hypertension, diabetes mellitus, musculoskeletal conditions,dyslipidemia, and gastrointestinal disease.
For health service utilization, the average number of outpatient visits was 4.9 ±
4.5 (range 1-88), whereas the average number of hospitalizations was 0.2 ± 0.7(range 0-11). In addition, the average number of diagnoses and medications used
was 3.5 ± 4.0 (range 1-43) and 7.2 ± 5.9 (range 1-43), respectively.
As for Thai regional factors, most patients were covered under the UCS (77.4%),
visited hospital A (48.8%), and were prescribed medicines by general practitioners(86.9%).
3.3.2 Prevalence of PIM use identified using the LRDTE
The prevalence of PIM use was 79.3% (10,536/13,274) in elderly patients during
FY 2014 (Table 4). More elderly patients aged 75 years and older were prescribed
PIMs than those aged 60-74 years. Female patients received more PIMs than malepatients. Moreover, the highest prevalence of PIM use was in relation to
gastrointestinal disease and musculoskeletal conditions. PIM was frequently
prescribed for those with multiple outpatient visits (≥ 4 visits), at least one
37hospitalization, multiple comorbidities (≥ 5 diagnoses), and polypharmacy (≥ 6
medicines). The majority of PIM users received CSMBS and UCS. PIM wasprescribed most often in hospital D. Additionally, PIMs were commonly prescribedby general practitioners and specialists.
3.3.3 The prevalence of the most frequently prescribed PIMs
Table 5 showed all medications on the ED were included in LRDTE criteria as PIM
and Figure 3 presents the prevalence of the 10 most frequently prescribed PIMs for
those aged 60-74 years and ≥ 75 years. The results indicated that elderly patients
aged ≥ 75 years received more PIMs than those aged 60-74 years. The mostcommon PIMs identified by LRDTE criteria were amlodipine (60-74 years: 31% vs ≥75 years: 35%), omeprazole (27% vs 36%), tramadol (17% vs 22%), lorazepam (11% vs15%), hyoscine (10% vs 12%), amitriptyline (9% vs 11%), and hydroxyzine (6% vs 8%).
3.3.4 Factors influencing PIM use in elderly patients
After adjustment for patient and utilization factors (model 1), positive associations
were identified between female gender, all comorbidities except COPD/asthma, 4 ormore outpatient visits, 5 or more diagnoses, and 6 or more medications (Table 6).
By adding Thai region-specific factors (model 2), most factors remained statisticallysignificant predictors (excluding female and outpatient visits). Moreover, Hospital D[OR 1.24; 95% CI 1.07-1.43] and general practitioner prescribers [OR 2.80; 95%CI
2.44-3.21] were independent predictors for PIM use as Thai region-specific factors.
Health insurance schemes were not independent predictors after adjustment forcommon factors.

38

Table 4 Basic characteristics among elderly patients and PIM prevalence
Characteristics

Total

(%)

n = 13,274

PIM prevalence (%)
10,536 (79.3)

Patient characteristics
Age, Mean ± SD (Range)

69.8 ± 8.1 (60-114)

60–74 years

9,599 (72.3)

78.4≥ 75 years

3,675 (27.7)

81.9

Female7,881 (59.4)

81.6

Male

5,393 (40.6)

76.1

Hypertension

2,705 (20.4)

94.7

Diabetic Mellitus

2,561 (19.3)

90.8

Musculoskeletal conditions

2,063 (15.5)

96.4

Dyslipidemia

1,904 (14.3)

90.4

Gastrointestinal disease

1,825 (13.8)

96.6

Acute respiratory disease

1,807 (13.6)

86.1

COPD/Asthma

478 ( 3.6)

71.3

Cardiovascular disease

343 ( 2.6)

87.8

Gender§Comorbidities

Health service utilization characteristics (Per year)
Number of outpatient visits, Mean ± SD (Range)
1-3

6,157 (38.3)

65.5

≥4

7,117 (61.7)

87.6

Number of hospitalizations Mean ± SD (Range)§

4.9 ± 4.5 (1-88)

0.2 ± 0.7 (0-11)

011,602 (86.4)

78.4

≥1

1,672 (13.6)

85.9

Elderly patients had more than one comorbidity, total was more than 100%

39

Table 4 Basic characteristics among elderly patients and PIM prevalence (cont.)
Characteristic

Total

(%)

n= 13,274

PIM prevalence (%)
10,536 (79.3)

Health service utilization characteristics (Per year)
Number of diagnoses, Mean ± SD (Range)

3.5 ± 4.0 (1-43)

1-2

7,685 (57.9)

72.8

3-4

2,701 (20.4)

83. 8

≥5

2,888 (21.8)

92.7

Number of medications, Mean ± SD (Range)

7.2 ± 5.9 (1-43)

1-5

6,710 (50.5)

64.2

≥6

6,564 (49.5)

94.9

1,863 (14.0)

80.6

10,275 (77.4)

80.3

Social Security Scheme

280 (2.1)

77.9

Out-of-pocket

856 (6.5)

65.9

Hospital A

6,480 (48.8)

80.5

Hospital B

2,733 (20.6)

76.3

Hospital C

1,339 (10.1)

77.6

Hospital D

2,722 (20.5)

81.0

11,542 (86.9)

84.9

Specialist

822 (6.2)

87.1

Other health personnel

6,025 (45.4)

74.8

Thai region specific characteristic
Health insurance scheme
Civil Servants Medical Benefit
SchemeUniversal Coverage Scheme

Hospital characteristics* Prescriber characteristics
General practitioner(Dentist, Nurse)* Elderly patients visited the physician more than once, total was more than 100
40

%
40

Prevalence of PIMs

35

60-74

30

≥ 75

25
20
15
10
5
0

Figure 3 Prevalence of the most frequently used potentially inappropriate
medications in the elderly (60-74 years old and ≥ 75 years old)41

Table 5 Most frequently encountered PIM according to the LRDTE
Medicatione

ATC code

Thai
NLEM

PIM level
60-74

≥75

years

years

n=13,274 (%)

PIM user

10,536(79.3)Non PIM user

2,738

(20.6)

Pain management

7,140(53.8)

Tramadol

N02AX02ED

L 1 (Mild)

2,432(18.3)

Diclofenac

S01BC0ED

L 1 (Mild)

1,679(12.7)

Ibuprofen

M01AE01ED

L 1 (Mild)

1,610(12.1)

Naproxen

M01AE02ED

L 1 (Mild)665( 5.0)Colchicine

M04AC01ED

L 1 (Mild)466( 3.5)

Aspirin >325 mg/day

N02BA01ED

L 1 (Mild)190( 1.4)

Pethidine

N02AB02ED

L 2 (Moderate)47( 0.4)

Etoricoxib

M01AH05

NED

L 1 (Mild)33( 0.3)

Celecoxib

M01AH05

NED

L1 (Mild)18( 0.1)

5,755(43.3)

Gastrointestinal

e

Total

Omeprazole

A02BC01ED

L 1 (Mild)

3,958(29.8)

Hyoscine

A03BB01ED

L 3 (Severe)

1,448(10.9)

Metoclopramide

A03FA01ED

L 2 (Moderate)337( 2.5)

Loperamide

A07DA03ED

L 1 (Mild)12( 0.1)

Elderly patients receive PIM more than one.

% Most frequently PIM = (Number of patients who received PIM x 100)/ total patients
ATC = Anatomical Therapeutic Chemical Classification System.
NLEM = National list Essential medicine
ED= Essential drug, NED = Non-essential drug
Level 1(Mild): use within condition or short term use or with intensive monitoring
Level 2 (Moderate): not recommend, avoid by using alternative choices
Level 3 (Severe): not recommend, no benefit
L= level

42

Table 5 Most frequently encountered PIM according to the LRDTE (cont.)
Medication*

ATC code

Thai
NLEM

PIM level
60-74

≥75

years

years

Cardiovascular system

Total
n= 13,274 (%)

5,451(41.0)

Amlodipine

C08CA01ED

L 2 (Moderate)

4,259(32.1)

Prazosin

C02CA01ED

L 2 (Moderate)446( 3.4)

Nifedipine

C08CA05

ED

L 2 (Moderate)337( 2.5)

Digoxin

C01AA05

ED

L 2 (Moderate)151( 1.1)

Spironolactone

C03DA01ED

L 2 (Moderate)

96( 0.7)Doxazosin

C02CA04ED

L 2 (Moderate)73( 0.5)

Methyldopa

C02AB01ED

L 2 (Moderate)42( 0.3)

Verapamil

C08DA01ED

L 2 (Moderate)24( 0.2)

Amiodarone

C01BD01ED

L 2 (Moderate)18( 0.1)

Diltiazem

C08DB01ED

L 2 (Moderate)5( 0.1)

3,626(27.3)

1,574(11.9)

1,280( 9.6)

760( 5.7)

12( 0.1)

3,053(23.0)

1,622(12.2)

887( 6.7)

508( 3.8)

36( 0.3)

Central Nervous System
Lorazepam

N05BA06ED

L 1 (Mild)

L2(Moderate)

Amitriptyline

N06AA09

ED

Diazepam

N05BA01ED

L 2 (Moderate)
L 1 (Mild)

L2(Moderate)

Phenobarbital

N03AA02ED

L 2 (Moderate)

Anticholinergics (excluded Tricyclic antidepressants)
Chlorpheniramine

R06AB04ED

L 1 (Mild)

L2(Moderate)

Hydroxyzine

N05BB01ED

L 1 (Mild)

L2(Moderate)

Cyproheptadine

R06AX02ED

L 1 (Mild)

L2(Moderate)

Diphenhydramine

R06AA02ED

L 1 (Mild)

L2(Moderate)

43

Table 5 Most frequently encountered PIM according to the LRDTE (cont.)
Medication*

ATC code

Thai
NLEM

PIM level
60-74

≥75

years

years

Endocrine System

Total
n= 13,274 (%)

803

(6.1)

Pioglitazone

A10BG03ED

L 2 (Moderate)

530

(4.0)

Glibenclamide

A10BB01ED

L 2 (Moderate)

273

(2.1)

186

(1.4)

Other
Codeine

R05DA04ED

L 2 (Moderate)

110

(0.8)

Trihexyphenidyl

N04AA01

ED

L1

L2

76

(0.6)

(Mild)(Moderate)

44

Table 6 Factors that influenced potentially inappropriate medication use in Thai elderly
Variable

Unadjusted OR

Adjusted OR (95%CI)(95%CI)

Model 1Model 2

Patient factors
Age
60–74 years

1.00

1.00

1.00

≥ 75 years

1.25(1.13-1.37)

1.02(0.92-1.17)

1.01(0.89-1.14)

1.39(1.28-1.52)

1.13(1.02-1.26)

1.10(0.99-1.22)

GenderFemaleComorbidities
Gastrointestinal disease 8.53

(6.61-11.00) 9.80

(7.43-12.73) 9.79

(7.44-12.88)

Musculoskeletal

8.38(6.62-10.61) 9.91

(7.72-12.72) 8.56

(6.65-11.03)

Hypertension

5.78(4.86-6.88)

6.01(4.96-7.29)

4.99(4.11-6.08)

Dyslipidemia

2.72(2.32-3.19)

2.37(1.96-2.86)

1.87(1.54-2.26)

Diabetic Mellitus

3.02(2.62-3.48)

1.94(1.62-2.32)

1.62(1.35-1.94)

Acute respiratory

1.72(1.49-1.98)

1.39(1.16-1.65)

1.14(0.95-1.36)

COPD/Asthma

0.64(0.52-0.78)

0.34(0.26-0.44)

0.30(0.23-0.39)

Cardiovascular disease

1.89(1.36-2.61)

1.64(1.12-2.41)

1.60(1.07-2.36)

conditions

diseaseHealth service utilization factors
Number of outpatient visits
1-3

1.00

≥4

5.60

1.00
(5.08-6.18)

COPD: Chronic obstructive pulmonary disease

45

1.23

1.00
(1.06-1.42)

1.13(0.98-1.31)

Table 6 Factors that influenced potentially inappropriate medication use in Thai elderly (cont.)

Variable

Unadjusted OR

Adjusted OR (95%CI)(95%CI)

Model 1Model 2

Health service utilization factors
Number of hospitalizations
0

1.00

≥1

1.67

(1.45-1.93)

1.00

1.00

1.12 (0.93-1.34)

1.09

1.00

1.00

(0.91-1.31)

Number of diagnoses
1-2

1.00

3-4

1.93

(1.72-2.16)

0.93 (0.81-1.08)

1.03(0.87-1.22)

≥5

4.73

(4.08-5.50)

3.72 (3.10-4.46)

4.22(3.28-5.42)

Number of medications
1-5

1.00

1.00

1.00

≥6

10.45

(9.26-11.80) 8.26 (7.08-9.64)

7.50

CSMBS

1.00

-

-

1.00

UCS

1.02

(0.90-1.15)

-

-

1.01

(0.86-1.18)

SSS

0.86

(0.65-1.15)

-

-

1.24

(0.85-1.81)

Out-of-pocket

0.47(0.41-0.55)

-

-

1.25

(0.99-1.56)

-

-

1.00

(6.38-8.82)

Thai region-specific factors
Health insurance scheme

Hospitals
Hospital A

1.00

Hospital B

0.78(0.70-0.87)

-

-

0.96

(0.79-1.18)

Hospital C

0.84(0.73-0.97)

-

-

0.93

(0.78-1.13)

Hospital D

1.02(0.91-1.14)

-

-

1.24

(1.07-1.43)

7.61(6.83-8.48)

-

-

2.80

(2.44-3.21)

Prescriber
General practitioner

CSMBS: Civil Servants Medical Benefit Scheme, UCS: Universal Coverage Scheme,
SSS: Social Security Scheme
46

3.4 DISCUSSION
3.4.1 Prevalence of PIM use identified using the LRDTEThis was the first study evaluating PIM use using the LRDTE criteria in Thailand.
We found that 79% of elderly Thai patients were at risk of PIM use. The prevalenceof PIM use was higher than that found in previous Thai PIM use studies: 32% using
STOPP,101 28% using 2012 Beers Criteria,17 and 58% using Winit-Watjana criteria.16
The prevalence of PIM may not be directly comparable to other studies because ofhealth setting and methodological differences. The medicine lists in the LRDTE
criteria covered current standard treatment guidelines and hospital formularies.13
Therefore, the high PIM prevalence in this study suggested the importance of using
the new LRDTE criteria to fulfill the RDU policy to reduce irrational drug use forThai elderly.18
3.4.2 Prevalence of the most frequently used potentially inappropriate medications
The top three most common PIMs prescribed to elderly patients aged ≥ 60 years
were amlodipine (32%), omeprazole (30%), and tramadol (18%). Amlodipine has beencommonly prescribed for hypertension in Thai elderly patients aged ≥ 75 years.102
The previous Thai PIM study that used the Beers Criteria did not report theprevalence of amlodipine use because this medicine was not listed in the criteria.20
Amlodipine was added to the LRDTE criteria to avoid ADRs, including an increased
risk of edema, falls, and fractures.103 In addition, constipation was a common ADR in
elderly patients.104 Meanwhile, a PIM use study in the Netherlands revealed a lower
prevalence of amlodipine use from the use of STOPP because this medicine was
not widely prescribed among elderly patients in this country.105
A prior study conducted in Thai elderly did not report the prevalence ofomeprazole because it was not listed in the Winit-Watjana criteria.16 Omeprazole was47

included in LRDTE criteria because it reduces calcium absorption over the longterm.13 Omeprazole was continuously prescribed for peptic ulcer and preventing
NSAID-induced ulceration, particularly in Thai elderly patients who wereconcurrently using aspirin, corticosteroids, or anticoagulants.106 This was consistent
with a study performed in Ireland using STOPP, which indicated that omeprazole
was commonly prescribed to prevent potential ADRs from continuous aspirin use.107
Therefore, elderly patients should be continuously monitored.
Tramadol was frequently prescribed for chronic pain in elderly patients because
elderly patients are at risk of developing peptic ulcers from chronic NSAID use.108
Conversely, a study performed in Taiwan using the Beers Criteria indicated thattramadol was prescribed less often because it was indicated for the treatment ofmoderate or severe pain in those who have not responded to other analgesic
medications or NSAIDS. Therefore, this medicine was not prescribed as a first line
treatment.109
3.4.3 Factors influencing PIM use in elderly patients for drug policy perspective
According to the adjusted logistic regression models, the factors positively
associated with PIM use in this study were multiple comorbidities, increased numberof diagnoses, frequency of outpatient visits, and polypharmacy. This was similar to
most previous studies, in which those factors showed a strong effect on PIM use in
Ireland, Utah, and Japan.110,111,112
After including the Thai region-specific factors in the model, the hospital factor
was an important predictor of PIM use. Hospital D was associated with an increased
likelihood of PIM use compared to other hospitals because it was a relatively new
hospital and its formulary was restricted (Table 3). All hospitals have their own
formularies, which include medications on the Essential drug (ED), a list of48

medications used in the hospitals in Thailand (ED: 70-90%), and those not on the ED(10-30%).40 Most medications on the ED were included in LRDTE criteria as PIM(Table 5). In fact, medicine selection in hospitals is claimed to be based on need,safety, efficacy, and cost-effectiveness for all patients, but it might not be focused
specifically on elderly patients.107 Consistently, the study by Gallagher et al., whichused the Beers Criteria and STOPP in Europe, concluded that differences in hospitalcharacteristics was a key factor in PIM use based on the hospital formulary andpolicy.113 Therefore, hospital formularies should be revised by recognizing potential
risks for elderly patients.
For the prescriber factor, prescription from a general practitioner affected theincrease in PIM use. The restriction of the hospital formulary and RDU policy
affected the physician’s prescribing decisions. The policy requires the use of
medication listed on the ED; therefore, general practitioners must choose
medications listed in the ED as first line medicines. Similarly, the study of Barnett
et al.,114 which used the Beers Criteria in Canada, indicated that general practitioners
were the biggest predictors of PIM use in elderly patients.114 Furthermore, the PIM
issue was not widely known by physicians, so they might not have been familiar with
PIM criteria.16 Consistently, in the prior studies, physicians focused on drug
duplication and compliance more than considering PIM risk.24 To improve rational
drug use, continuing medical training for physicians should focus on PIM prescribing.
The three health insurance schemes differed with respect to prescribing andreimbursement conditions.40 Therefore, these factors might be associated with PIM
use. In the unadjusted model, those covered by the out-of-pocket scheme had
decreased PIM use compared with those covered by the CSMBS. Those covered by
the out-of-pocket scheme could receive medications regardless of whether they49

were listed in the ED, so elderly patients had more choices than those covered by
CSMBS and thereby, could avoid PIM use. The previous Thai PIM study that applied
the Winit-Watjana criteria indicated that the UCS was associated with increased
PIM use compared with the CSMBS.16 The adjusted models found no statisticallysignificant association. This might have been caused by differences in the numbersof elderly people covered by each health insurance. Most used UCS and a few used
SSS. Consistently, RDU policy tries to promote the use of medications listed on the
ED for all health insurance schemes as first line treatment.39 Therefore, there wereno significant differences between the health insurance schemes regarding PIM
prescriptions. According to the study by Donohue et al., which used the Beers
Criteria in the United States, drug coverage limitations influenced elderly patients’
likelihood of PIM use.115

50

CHAPTER 4
Effect of a computerized decision support system on potentially inappropriate
medication prescriptions for elderly patients in Thailand(The second publication)

4.1 PURPOSE
The aim of this study was to evaluate the effect of a CDSS on PIM prescriptions
for elderly patients in Thai community hospitals.

4.2 METHODS
4.2.1 Study design and target population
The retrospective cohort study design comprised two phases with a duration of
12 months design comprised two phases with a duration of 12 months eachobservational phase (October 2015 to March 2016) and intervention phase (October
2016 to March 2017) (Figure 4) to evaluate the effect of a CDSS for PIM prescriptions
by comparing the prevalence of PIMs pre and post implementation of CDSS. Medical
services and prescription claims data were retrieved from the Health Data Center,
which is a national database in Thailand. To evaluate the impact of hospitalcharacteristics on the ability of the CDSS on reducing PIM prescriptions, we selectedfour community hospitals located in Chonburi province in eastern Thailand. This
province is an industrial city with diverse population. A high PIM prevalence was foundin this area.116 According to the information provided by the hospitals and personal
interviews conducted by us, each hospital had different characteristics in terms ofphysician type, hospital formulary, and CDSS. As shown in Table7, hospital A was afirst-level hospital (F1), which has 60 beds and more, general practitioners (GP), and51

specialized practitioners (SP). The other three hospitals were second-level hospitals(F2), which have 30 beds and more and only GPs.117
Our study included elderly patients aged 60 years and older who received any
treatment at the hospital at least once and visited the outpatient department at thefour community hospitals during the study period. Missing or irretrievable medication
data were excluded. Patient data, including gender and age category (60–74 or ≥ 75
years), were collected based on the LRDTE criteria13. Comorbidities were classified
according to the 10th revision of the International Statistical Classification of Disease
and Related Health Problems (ICD-10).95,96 We also recorded the date of hospital visits
and medication dispensation characteristics, including the generic or brand name,strength, dosage, number of medications, and date of dispensation. Medicines werecoded according to the Anatomical Therapeutic Chemical (ATC) classification systemrecommended by the World Health Organization.97

Figure 4 The study design comprised two phases with a duration of 12 months

52

TABLE 7 Characteristics of the four participating community hospitals in the ﬁscal year 2017

Characteristics

Hospital A

Hospital B

Hospital C

Hospital D(6 GP and 5 SP)(6 GP)(4 GP)(5 GP)

Hospital level

F1

F2

F2

F2

Number of medicines

310

292

219

243

296 (95.5)

284 (97.3)

210 (95.9)

228 ( 93.8)

14 (4.5)

8 (2.7)9 (4.1)9 (3.7)

Number of PIM lists

32

32

29

30

%of PIM

10

11

13

12

5

7

4

6

Drug allergy,
drug interaction,
nursing note,
PIM

Drug allergy,
drug interaction,
drug pregnancy,
ADR, nursing
note, PIM

Physician type
Number of physicians
Hospital characteristics

NLEM (%(
Non-NLEM (%(CDSS characteristicsa

Total number of CDSS

Drug allergy,
drug interaction,
nursing note,
ADR, warfarin,high alert drug,
PIMaThis information was obtained from physician interviewsbbType of CDSS

Drug allergy,
drug interaction,
CKD, warfarin,
PIM

The same CDSS for PIM detection was implemented in the four participating hospitals.

Abbreviations: ADR: adverse drug reaction, CKD: chronic kidney disease,
CDSS: computerized decision support system, F1: first level hospital, F2: second-level
hospitals, NLEM: National List of Essential Medicines, PIM: potentially inappropriate
medication, SP: specialist practitioner, GP: general practitioner.

53

4.2.2 CDSS for PIM detection program and outcome measures
The CDSS for PIM detection in this study was the alert system at four community
hospitals that was developed by Ploylearmsang et al.22 This CDSS was incorporated
with LRDTE criteria as the latest Thai PIM screening tool. The advantage of LRDTE
was that it covered the current standard treatment guidelines and hospital formulary
for Thai elderly patients. LRDTE criteria were developed by a 15-member
interdisciplinary panel of experts using focus group method to systematically review
the evidence and reach a consensus on Thai PIM criterion. 13 With the support of the
Ministry of Public Health, this alert system was installed on HOSxp (HOSxp, BMS,
Thailand), a hospital software used widely in public hospitals across Thailand for the
management of electronic health records. The alert system uses the LRDTE criteria
to automatically check for PIM prescriptions and presents three medication severity
levels: a mild PIM alert indicates that the drug may be used for short term or withintensive monitoring; moderate PIM alert indicates that it is best to avoid drug usage
and consider alternative choices; and severe PIM alert indicates that drug usage is notrecommended and offers no benefit to the patient. All medicines were ordered byphysicians through the hospital software. When the alert system identifies a PIM, amessage describing the possible consequences and suggesting alternative therapies isshown on the physician’s computer screen. The physician could then decide to accept
or override the alert message.22 As shown in Figure 5, an alert is raised when tramadol
is prescribed to patients with high risk, including patients with chronic seizures or
epilepsy. Physicians could see the information on PIM regarding its short term use withindication of pain management. Introduction of the CDSS for PIM detection wasapproved by the Pharmacy and Therapeutic Committee at the four community
hospitals for this research study, and was initiated on October 1, 2016.
54

The prevalence of PIM prescriptions six months before the start of the study(October 2015 to March 2016) was compared to that after the implementation of thealert system (October 2016 to March 2017). The same months were compared tocontrol for seasonal effects on medical prescriptions. In addition, the commonlyprescribed PIMs pre- and post-implementation were noted.

Figure 5 Screen shot of computerized decision support system for tramadol

4.2.3 Data analysis
The CDSS for PIM prescriptions was evaluated in patients 60 years and older who
had received a PIM at least once. The prevalence of PIM prescriptions was calculated
as the number of elderly patients who received at least one PIM (numerator) divided
by the number of elderly patients receiving any treatment at the hospital at least once
(denominator). A descriptive analysis was used to analyse the common PIMs used ineach PIM level pre- and post-CDSS. The common PIMs belonging to each level preand post-CDSS implementation was calculated by the number of elderly who received
each common PIM divided by the number of elderly patients receiving any treatment
55

at the hospital pre- and post-CDSS. Chi-square tests were used to compare the rateof PIM prevalence in each PIM level pre- and post-CDSS implementation. A statisticalsignificance threshold of p-value < 0.05 was used. All analyses were conducted using
the STATA software version 13 (StataCorp LP, Texas, USA).
4.2.4 Ethics
The protocol was approved by the Research Ethics Committee of Sirindhorn Collegeof Public Health, Chonburi Province, Thailand, on July 21, 2016, as well as by eachhospital included in the study.

4.3 RESULTS
4.3.1 Basic characteristics of elderly study participants pre- and post-CDSS
The characteristics of elderly patients who visited each hospital at least once arepresented in Table 8. A total of 11,258 patients were included in the period prior to
CDSS implementation and 11,915 patients were included in post-CDSS implementation.
The median age of the pre-CDSS and post-CDSS was 69.0 and 70.0 years,
respectively. Most of the patients were women. The median number of diagnoses was
4.0 (IQR = 5.0) in the pre-CDSS and 4.0 (IQR = 4.0) in the post-CDSS. The median
number of medications prescribed was 7.0 (IQR = 7.0) each in pre-CDSS and postCDSS. There were significant differences between the pre- and post-CDSS groups interms of patient age, number of diagnoses, and number of medications (p < 0.05).
However, there were no significant differences in gender between the groups (p = 0.76).

56

TABLE 8 Basic characteristics of elderly study participants pre- and post-CDSS
implementation
Patient characteristics

Pre-CDSS

Post-CDSS

N =11,258

N =11,915

P

69.0, 13.0

(60–99)70.0, 13.0

(60–99)< 0.05 c

60–74 years (%)

7,506(66.7)

8,159(68.5)< 0.05b≥ 75 years (%)

3,752(33.3)

3,756(31.5)

Female (%)

6,715(59.7)

7,130(59.8)

Male (%)

4,543(40.3)

4,785(40.2)

Number of diagnoses median,4.0, 5.0(1–31)

4.0, 4.0(1–31)< 0.05 c

7.0, 7.0(1–49)

7.0, 7.0(1–42)< 0.05 c

Age median, IQR (Range)

Gender
0.76 b

IQR (Range)aNumber of medications median,

IQR (Range)aMedications selected across the four participating community hospitals pre-CDSS(October 2015–March 2016) and post-CDSS (October 2016–March 2017)b

2 test, p < 0.05, c Mann-Whitney U test, p < 0.05

Abbreviations: CDSS: computerized decision support system, N: sample size,
IQR: Interquartile range

4.3.2 Effect of a computerized decision support system on potentially inappropriate
57

medication prescriptions for elderly patients.
The overall prevalence of PIM prescriptions post-CDSS implementation significantly
decreased from 87.7% pre-CDSS to 74.4% post-CDSS (p < 0.05). Comparison of PIM
prescriptions between pre and post CDSS for PIM in each hospital showed that PIM
prevalence of the four hospitals significantly decreased (p < 0.05) as follows: hospital
A (PIM prevalence: 89.5% pre-CDSS vs. 76.8% post-CDSS); hospital B (83.9% preCDSS vs. 72.6% post-CDSS); hospital C (83.9% pre-CDSS vs. 66.7% post-CDSS); andhospital D (90.1% pre-CDSS vs. 75.6% post-CDSS) (Table 9). The tendency of PIM
prevalence between each hospital and overall PIM prevalence were similar reduced.
The overall severities of mild and moderate PIMs in all hospitals significantly
decreased (p < 0.05). The severity of mild PIM (71.9% pre-CDSS vs. 49.0% post-CDSS)
and moderate PIM (64.5% pre-CDSS vs. 48.7% post-CDSS) significantly reduced. All
hospitals had only one severe PIM, which was hyoscine, and its severity was not
significantly reduced (4.7 % pre-CDSS vs. 1.5% post-CDSS, p = 0.74) (Table 10). The
proportion of frequently prescribed PIMs in all PIM severity levels significantly
decreased (p < 0.05), regardless of existing alternative medications (Table 10).

58

Table 9 PIM prevalence of each PIM level pre- and post-CDSS implementation
PIM level

No .elderly

Pre-CDSS %PIM

No .elderlyof PIMa

Post-CDSS

%PIM

Pc

74.4

< 0.05of PIMb

Comparing overall PIM prescription of 4 hospitals
Overall

11,2589,868 87.7

11,915

8,869

Mild

8,090 71.9

5,833 49.0

< 0.05Moderate

7,265 64.5

5,803 48.7

< 0.05

Severe

523

183

4.7

1.5

0.74

4,126 76.8

< 0.05Comparing PIM prescription in each hospital
Hospital A

4,663 89.5

5,371

Mild

3,760 72.2

2,612 48.6

< 0.05Moderate

3,629 69.7

2,949 54.9

< 0.05

Severe141

Hospital B

2,579

2.7

21

2,163 83.9

2,816

0.8

0.79

2,045 72.6

< 0.05

Mild

1,765 68.4

1,347 47.8

< 0.05Moderate

1,472 57.1

1,231 43.7

< 0.05

Severe141

Hospital C

1,319

5.5

83

1,106 83.9

1,358

3.0

0.50

906 66.7< 0.05

Mild913 69.2

603 44.4< 0.05Moderate

754 57.2

547 40.3< 0.05

Severe112

23

Hospital D

a

5,210

2,150

8.5

1,936 90.1

2,370

1.7

0.11

1,792 75.6

< 0.05

Mild

1,652 76.8

1,271 53.6

< 0.05Moderate

1,410 65.6

1,076 45.4

< 0.05

Severe

129

6.0

56

2.4

0.15

Pre-CDSS (October 2015–March 2016) and bPost-CDSS (October 2016–March 2017) test of the difference in PIM prescriptions pre- and post-CDSS implementation,c 2

p < 0.05
Abbreviation: CDSS: computerized decision support system, PIM: potentially inappropriate
medication, Mild level alert shows that the drug may be used for short term or with intensive
monitoring. Moderate level alert shows that it is best to avoid drug usage and consider
alternative choices. Severe level alert shows that drug usage is not recommended andoffers no benefit to the patient.
59

TABLE 10 Common PIMs belonging to each level pre- and post-CDSS implementation
PIMa

PIM level

ATC code

Thai

Pre-CDSS

Post-CDSS

NLEM

Number (%)

Number (%)

n=11,258

n=11,915

P

Alternatives of
medications in LRDTE

Omeprazole a

Mild

A02BC01

ED

4,219 37.5

2,616 22.0

< 0.05 No

Tramadol

Mild

N02AX02ED2,829 25.1

1,247 10.5

< 0.05 No

Diclofenac

Mild

S01BC0ED

1,899 16.9

567

4.8

< 0.05 Paracetamol

Amlodipine b

Moderate

C08CA01

ED

4,823 42.8

4,016 33.7

< 0.05 Diuretic, ACEI

Pioglitazonec

Moderate

A10BG03

ED

695

6.2

460

3.9

< 0.05 No

Prazosin

Moderate

C02CA01

ED

580

5.2

396

3.1

< 0.05 Diuretic, ACEI

Dimenhydrinate

Mild &Moderated

R06AA52

ED

3,761 33.4

1,911 15.9

< 0.05 Betahistine mesylate, NED

Lorazepam

Mild & Moderate

N05BA06

ED

2,122 18.8

1,204 10.1

< 0.05 No

Chlorpheniramine Mild & moderate

R06AB04

ED

1,637 14.5

607

5.1

< 0.05 Loratadine

Hyoscine

A03BB01

ED

523

183

1.5

Severe4.7

0.74 Drotaverine, NED

Omeprazole should be used for short term (≤ 8 weeks), bAmlodipine should be monitored for development of chronic constipation.

c

Pioglitazone should be monitored for patients with heart failure or cardiovascular disease,
Mild & Moderate: Mild level for elderly patients aged 60–74 years and Moderate level for elderly patients aged ≥ 75 years.
Abbreviations: ACEI: angiotensin-converting enzyme inhibitors, ATC: Anatomical Therapeutic Chemical classiﬁcation system,
CDSS: computerized decision support system, ED: essential drug, NED: non-essential drug, NLEM: National List of Essential Medicines,
PIM: potentially inappropriate medication.
d60

4.4 DISCUSSION
In this study, we aimed to evaluate the effect of a CDSS on PIM prescriptions for
elderly patients in Thai community hospitals. A signiﬁcant reduction in PIM
prescription from 87.7% pre-CDSS to 74.4% post-CDSS implementation wasobserved. Elderly patients were still at risk although PIM prescription was reduced.
A study conducted in 331 elderly patients at a hospital in the United States reported
that despite the decrease in PIM prescription from 89% to 47% via CDSS
implementation, more than half of elderly patients and those with severe renal
insufficiency still received PIM.118 The benefits of CDSS were ease of access andthe provision of specific warnings to physicians when prescribing PIMs; however,polypharmacy have been continuously prescribed in elderly patients that is
associated with a higher prevalence of PIM. These issues should be addressed bydeprescribing to minimize prescription of multiple medicines and to withdraw PIM in
elderly patients.119,120 The tendency of PIM prevalence post-CDSS between overall
and each hospital were similarly reduced but PIM was still high prescription. The
main cause might be the restriction of hospital formulary. Physician have noalternative medicine to avoid PIM prescription. Therefore, the hospital formulary
should be revised for preventing PIM prescription.
Notably, CDSS in this study was integrated with LRDTE criteria and categorized
into three PIM levels. The results showed that the overall severity of mild andmoderate PIMs was significantly reduced, including the commonly prescribed PIM in
mild and moderate PIMs. However, severe PIM was not significantly decreased.
Although the prescription of mild level PIMs was substantially reduced from 72% to50% post-CDSS, this PIM level still had a high proportion of PIM prescriptions
because this medicine had more benefits than risk. In this study, mild PIMs were61

drugs prescribed for short term course and most of them have no alternative
medications in LRDTE. Hence, physicians considered the balance of benefits andharms of PIMs to take a decision on discontinuing PIM prescription. In addition,these drugs should be continuously monitored for preventing long-term prescription.
The study by Simon showed the reduction of PIM in short term therapy post-CDSS
implementation via continuous follow-up to improve prescribing quality, thereby
reducing the incidence of ADRs in elderly patients.95 Alternative medications to avoid
PIMs, such as herbal medicine, and health education should be considered.121
The prescription of moderate level PIMs decreased to approximately 16% postCDSS; thus, their prescription should be avoided and alternative choices should beconsidered. However, this PIM level did not have any alternative medications in
LRDTE but this PIM level was decreased. Therefore, CDSS can change physician’sprescription behaviour to avoid inappropriate medications. Physicians must
intensively monitor elderly patients who have a high risk. For example, chronic
constipation was the common ADR in elderly patients who use amlodipine andpioglitazone for underlying heart failure or cardiovascular disease.10,13,105 In addition,
the revision of hospital formulary should be reconsidered to improve and avoid PIM
prescription.
Although this severe PIM was not significantly decreased, this PIM was rarely
prescribed post-CDSS. For the CDSS on severe PIM, PIM level was not significantly
reduced. The prevalence of severe PIM in pre-CDSS was very small because only
limited elderly patients received it. When considering the relative reduction, a bigchange was observed between pre-and post-CDSS accounting for 60% reduction.
Even though, severe PIM in each hospital should be zero, this PIM was stillprescribed. All hospital has only Hyoscine (Antispasmodic medicine) as severe PIM
62

so physicians have no alternative medicine to avoid PIM prescription. Therefore,
formulary should be revised to avoid PIM. A previous Thai PIM study showed that
20% of elderly patients received hyoscine as severe PIM, and ADRs were observedin most of elderly patients.22 Nevertheless, this severe PIM was associated withstrong anticholinergic effects (urinary retention, constipation, and visual
disturbance) and serious adverse drug effects in patients with underlying cardiac
disease.122 CDSS for PIM detection should provide specific alerts by focusing onelderly patients who are at high risk. Drotaverine is a non-essential drug that wasprescribed as a substitute for hyoscine. According to the restriction of medicine
policy, elderly patients need to use essential drugs as the first line medicine.40
Therefore, health policy makers should revise the Thai National list of essential
medicines to address the restriction of hospital formulary for preventing PIM
prescription among elderly patients.
The comparison of PIM prevalence at four hospital between pre- and post-CDSS
was found the significant reduction of the overall of PIM and PIM prevalence in all
hospitals. Mild and moderate PIM were significantly decreased, but severe PIM was
not significantly decreased. CDSS showed advantages in detecting PIM in all
hospitals. Although each hospital was different in terms of hospital type andphysician characteristics, there was not much difference. This potential CDSS for
PIM showed specific medication warnings, was easy to use, feasible, and provided
real-time alerts to physicians for preventing PIM in elderly patients. Previous studies
on CDSS for PIM detection showed its effectiveness in reducing PIM prescription
in community hospitals123 however, CDSS showed less efficiency in ambulatory caresetting.124, 125 The success of CDSS for PIM detection depended on the right balance
between the risk of PIM severity and beneficial treatment. In addition, CDSS for PIM
63

should be easy, non-interruptive, and offer specific alerts to increase physician
acceptance.126 However, the restriction of hospital formulary was the prescriber
barrier for discontinuing PIM prescription.127 Thus, the revision of formulary was very
importance to avoid PIM prescription. Several studies have presented many
strategies for reducing PIM prescription, such as revision of formulary, educational
campaigns, and deprescribing process for addressing PIM problem.29,128

64

CHAPTER 5
CONCLUSIONS, LIMITATION AND SUGGESTION

5.1 CONCLUSIONSThis chapter reflects on the key findings of this dissertation that were to examine
the prevalence of PIM use based on the LRDTE, and to identifying factors that
influenced PIM use among elderly patients in Thailand. In addition, thisdissertation described the effect of a CDSS on PIM prescriptions for elderly
patients in Thai community hospitals. However, the effectiveness of thisCDSS for PIMs has not been clearly established. As follows;
The prevalence of PIM use in this study, identified using LRDTE criteria, was 79%
in Thai elderly patients. The hospital and general practitioners were Thai regionspecific factors associated with PIM use. The revision of hospital formularies andeducational programs for physicians are needed to improve prescribing habits. The
evaluation of drug use using the LRDTE criteria detected PIM prescriptions in Thai
elderly, these criteria should be applied in the computer assisted decision support
system to prevent PIM use.
The sophisticated CDSS for PIM detection used in this study decreased PIM
prescription in elderly patients. This CDSS can change physician’s prescription
behaviour to avoid inappropriate medications. Even though, PIM prevalence was
reduced post CDSS implementation, PIM prescription was still high proportion.
Therefore, the effort to revise hospital formulary is very important to avoid PIM.

65

5.2 LIMITATION
The limitations, recommendation and future research of this work were includedin this chapter. There were several limitations to this study. First, this study
was conducted in only four community hospitals in Thailand. Therefore, thestudy results might not be able to be completely extrapolated to allcommunity hospitals in Thailand. Second, the limitation of the study
database is the lack of information on clinical outcomes . The data were notsufficient to identify other patient conditions, such as constipation or
history of falls and fracture. Therefore, the results might be overestimatedor underestimated. Finally, our study was conducted in one group pre- andpost-CDSS implementation without comparison to a reference group .
Hence, these findings could not reveal the obvious impact of CDSS in
reducing PIM.

5.3 SUGGESTION
Suggestion for the health policy maker and hospitals
The LRDTE criteria covered current standard treatment guidelines and hospital
formularies. This screening tool could detect the high PIM prevalence. Therefore,
the new LRDTE criteria should be suggested to reduce irrational drug use for Thai
elderly to fulfil the RDU policy in Thailand.
The benefits of CDSS for PIM showed specific warnings, was easy to use, feasible,
and provided real-time alerts to physicians for preventing PIM in elderly patients.
Therefore, this CDSS could be used alert system for changing physician prescription
behaviour to avoid inappropriate medications in Thai hospitals.

66

The restriction of the hospital formulary affected the physician’s prescribing
decisions. Therefore, hospital formularies should be revised by recognizing potential
risks for elderly patients.
Suggestion for the health professional
The PIM issue was not widely known for physicians, so they might not have beenfamiliar with PIM criteria. Thus, physicians should be continue received medical
training by focusing on PIM prescribing to improve rational drug use.
Polypharmacy have been continuously prescribed in elderly patients that is
associated with a higher prevalence of PIM. Therefore, deprescribing process tominimize prescription of multiple medicines and to withdraw PIM in elderly patients.
Physicians considered the balance of benefits and harms of PIMs to take adecision on discontinuing PIM prescription. In addition, these drugs should becontinuously and intensively monitored for preventing long-term prescription.
Alternative medications to avoid PIMs, such as herbal medicine, and healtheducation should be considered.
Future studies are warranted to understand physician’s behaviour to accept
CDSS for PIM detection to increase medicine safety for elderly patients. And to
study economic aspects of PIM in older people. In addition, the PIM prevalence
between pre – and post- CDSS should focus on specific population such as
hypertensions or diabetes patients. The reduction of PIM prevalence might show
the large change reduction between pre – and post- CDSS.

67

CHAPTER 6
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Appendix 1 Lists of Risk Drugs for Thai Elderly (LRDTE criteria)
Medicine lists
1. Anticholinergics

60-74 year old≥ 75 year old

Level 1 Mild

Level 2 Moderate

1.1 First-generation

Recommendation:

Recommendation:

antihistamine

Short term use

Short term use(excluded, TCAs)(<1 week)

Alternative choice:1.1.1 Brompheniramine-

Loratadine for1.1.2 Chlorpheniramine

reducing

1.1.3 Cyproheptadine

anticholinergic

1.1.4 Diphenhydramine

effects

1.1.5 Hydroxyzine
1.1.6 Triprolidine
1.1.7 Carbinoxamine
1.1.8 Cyproheptadine
1.1.9 Hydroxyzine
1.1.10 Triprolidine
1.1.11 Carbinoxamin
1.2 Antiparkinson agents

Level 1 Mild

Level 2 Moderate

1.2.1 Trihexyphenidyl

Recommendation:

Recommendation:

Short term use with

Short term use (<1low dosemonth) with low dose

Indication: tremor andIndication: tremor and

EPS from antipsychotic

EPS from antipsychotic

agentsagentsAlternative choice:atypical antipsychotic
agent such as
risperidone

1.3. Antispasmodics

Level 1 Mild

1.3.1 Belladonna

Recommendation: Short term use for symptomatic

alkaloids

treatment

1.3.2 Dicyclomide
EPS: Extrapyramidal Symptoms, TCAs: Tricyclic antidepressants78

Appendix 1 Lists of Risk Drugs for Thai Elderly (LRDTE criteria) (Cont.)
Medicine lists

60-74 year old≥ 75 year old

1.4. Oral decongestantLevel 1 Mild

Level 2 Moderate

1.4.1 Pseudoephedrine

Not recommend

1.4.2 Phenylephrine

Contraindication: stroke,
seizure, head trauma

2. Antithrombotics

Level 2 Moderate

2.1 Dipyridamole, oral

Not recommend

short-acting (does not

Alternative choice: Aspirin or Clopidogrel

apply to the extendedrelease combination withaspirin)
2.2 Ticlopidine
3. Anti-infective
3.1 Nitrofurantoin

Level 2 Moderate
Not recommend
Alternative choice: Norfloxacin or Ciprofloxacin

4. Cardiovascular
4.1 Alpha blockers

Level 2 Moderate
Not recommend to use as a first-line or

4.1.2 Doxazosin

monotherapy as hypertensive agent

4.1.3 Prazosin(use add on)

4.1.4 Terazosin

Alternative choices: Diuretics, ACEIs and CCBs)

4.2 Alpha agonists

Level 2 Moderate

4.2.1 Clonidine

Not recommend to use as a first-line or

4.2.2 Methyldopa

monotherapy for hypertensive agent(use add on)
Alternative choices: - Diuretics, ACEIs, CCBs

4.3 Antiarrhythmic drugs

Level 2 Moderate

4.3.1 Amiodarone

Not recommend for Atrial fibrillation (AF)

4.3.2 Flecainide

Alternative choice: Adenosine Monitor QT

4.3.3 Propafenone

interval

ACEIs: Angiotensin-converting enzyme inhibitors, CCBs: Calcium-channel blockers

79

Appendix 1 Lists of Risk Drugs for Thai Elderly (LRDTE criteria) (Cont.)
Medicine lists

60-74 year old

4.4 Digoxin>0.125 mg/day≥ 75 year old

Level 2 Moderate
Not recommend use < 0.125 mg/day (strength
0.0625 mg) Monitor in renal failure
Level 3 Severe

4.5 Nifedipine, immediate
releaseNot recommend

4.6 Spironolactone > 25
mg/dayLevel 2 Moderate
Not recommend Indication: Use < 25 mg/day
Recommendation: Monitor K before start firstdose

4.7 Calcium channel
Blockers (CCBs)

Level 2 Moderate
Not recommend for patients with chronic
constipation

5 Central Nervous System

Level 2 Moderate

5.1 Tertiary TCAs, alone or Not recommend
in combination:

Indication: Neuropathic pain prefer Nortriptyline

5.1.1 Amitriptyline

start with low dose

5.1.2.Chlordiazepoxide-

Recommendation: Not use as a first-line for

Amitriptyline

anxiety and depression,

5.1.3 Clomipramine

Recommend to use Selective serotonin reuptake

5.1.4 Doxepin >6 mg/

inhibitors (SSRI) and trazodone

day
5.1.5 Imipramine
5.1.6 Perphenazineamitriptyline
5.2 Thioridazine

Level 2 Moderate
Recommendation: use atypical antipsychotics or
low dose of Haloperidol, Perphenazine,
Trifluoperazine or Flupenthixol

5.3 Barbiturates
5.3.1 Phenobarbital

Level 2 Moderate
Not recommend, except: with indication of seizure

80Appendix 1 Lists of Risk Drugs for Thai Elderly (LRDTE criteria) (Cont.)
Medicine lists

60-74 year old≥ 75 year old

5.4 Benzodiazepines

Level 1 Mild

Level 2 Moderate

Short and intermediate acting

Recommendation:

Recommendation:

5.4.1 Alprazolam

Lorazepam and Alprazolam Low dose and short term

5.4.2 Lorazepam

were not recommend foruse (2 week)

5.4.3 Temazepam

hypnotic indication- Lorazepam for anxiety

Short term use:

- Alprazolam for panic

Long acting
5.4.4 Clidinium
chlordiazepoxide(1-2 months)- Lorazepam for anxiety

5.4.5 Clonazepam- Alprazolam for panic

5.4.6 Diazepam- Clonazepam for
insomnia
Level 2 Moderate

5.5 Chloral hydrate

Not recommend to use as a first-line drug andshould use < 10 days
Level 2 Moderate

5.6 Nonbenzodiazepine
hypnotics
5.6.1 Zolpidem
6. Endocrine medicine
6.1 Androgens

Recommendation:
Short term use of Benzodiazepines such as Lorazepam
Level 2 Moderate

Level 1 Mild
Indication: Andropause

Recommendation:

6.1.2 Methyltestosterone

short term use and6.1.3 Testosterone

monitor

6.2 Estrogens with orLevel 2 Moderate

Level 2 Moderate

without progestins

Recommend to use topical Recommend to use topicaloral and patch form

vaginal cream

6.3 Growth hormone

vaginal cream

Level 1 Mild

Level 3 Severe

Not use except as

Not recommend

hormone replacement
after pituitary gland
removalLevel 3 Severe

6.4 Insulin, sliding scale
Not recommend
81

Appendix 1 Lists of Risk Drugs for Thai Elderly (LRDTE criteria) (Cont.)
Medicine lists
6.5 Megestrol
6.6 Sulfonylureas, long acting
6.6.1 Chlorpropamide
6.6.2 Glyburide
6.6.3 Glibenclamide

60-74 year old
Level 2 Moderate
Not recommend≥ 75 year old
Level 2 Moderate
Not recommend

Level 2 Moderate
Not recommend
Alternative choice: short acting sulfonylurea
or metformin

6.7 Pioglitazone

Level 2 Moderate
Not recommend to use as a first-line drug forpatient with Heart failure or cardiovasculardisease

7. Gastrointestinal medicines
7.1 Metoclopramide

Level 2 Moderate
Not recommend to use as a first-line drug and
Not use in Parenteral form (injection)
Recommendation : short term use

7.2 Mineral oil, given orally

Level 2 Moderate
Not recommend to use as a first-line drug
Indication: Use for pre-operation or patient withno response for other laxatives

7.3 Diphenoxylate

Level 3 Severe
Not recommend

7.4 Loperamide

Level 1 Mild
Indication: short term use in acute diarrhea or
use ORS

7.5 Codeine phosphate

Level 2 Moderate
Not recommend. Alternative choice:dextromethorphan short term use for coughsuppressant or dry coug

7.6 Prochlorperazine

Level 3 Severe
Not recommend

7.7 Proton Pump Inhibitor(PPI)

Level 1 MildLong term use concern with the reduction of
calcium absorption.
Recommendation use < 8 weeks

7.8 Hyoscine

Level 3 Severe
Not recommend
82

Appendix 1 Lists of Risk Drugs for Thai Elderly (LRDTE criteria) (Cont.)
Medicine lists

60-74 year old

Level 2 Moderate

8. Pain management
8.1 Meperidine (pethidine)≥ 75 year old

Recommendation: Use alternative choice such asmorphine

8.2 NSAIDs

Level 1 Mild

8.2.1 Aspirin >325 mg/day

For Osteoarthritis: Paracetamol as first choice or

8.2.2 Diclofenac

short term NSAIDs use (< 3 months) with PPI or

8.2.3 Diflunisal

use topical NSAIDs.

8.2.4 Ibuprofen

Contraindication: patients with cardiovascular

8.2.5 Ketoprofen

disease such as myocardial infarction, stroke,

8.2.6 Mefenamic acidheart failure

8.2.7 Meloxicam

For cardiovascular disease risk: Naproxen (prefer)

8.2.8 Naproxen+ PPI For gastrointestinal risk: NSAIDs in COX-II

8.2.9 Piroxicam

inhibitors + PPI

8.2.10 Sulindac

Indication of Indomethacin parenteral: acute post

8.2.11 COX-2 inhibitor

operation

8.2.12 Indomethacin
parenteral
8.3 Skeletal muscle
relaxant
8.3.1 Orphenadrine

Level 2 Moderate
Recommendation: Not use as a first-line drug formuscle spasm.
Contraindication for Myasthenia gravis

8.4 Antigout
8.4.1 Colchicine

Level 1 Mild
Not recommend to use as a first-line for primary
gout prophylaxis, and short term use
Indication: gout attack prophylaxis
Monitor: renal function and rhabdomyolysis

8.5 Tramadol

Level 1 Mild
Recommendation: short term use with indicationof pain management and contraindication: head
injury trauma

NSAIDs: Nonsteroidal anti-inflammatory drugs，PPIｓ: Proton pump inhibitor83

ACKNOWLEDGEMENTS

I would like to acknowledge the support of JSPS RONPAKU (Dissertation PhD)
program and Meiji Pharmaceutical University, Japan, whose research grant funded
to conduct this research. This research dissertation would not have been possible
without the help and encouragement of so many individuals. Firstly, I would like tothank my supervisory team for supporting me through this dissertation, Professor
Manabu Akazawa, Dr. Aiko Shono at Department of Public Health and Epidemiology,
Meiji Pharmaceutical University, Tokyo, Japan and Dr. Farsai Chanjaruporn at Socialand Administrative Pharmacy, Excellence Research Unit, Faculty of Pharmacy,
Mahidol University, Bangkok, Thailand for all generous guidance and support
throughout every step of this research. Completion of this dissertation in a timely
manner would not have been possible without your help and encouragement. Sincere
and grateful appreciation is also expressed to Assistant Professor Chanuttha
Ploylearmsang at Social Pharmacy Research Unit, Faculty of Pharmacy,
Mahasarakham University, Thailand for her helpful guidance the lists of risk drugs
for Thai elderly criteria and a computerized decision support system on potentiallyinappropriate medication prescriptions for Thai elderly patients.
A special thank you to all staff at the public health office for retrieving the data.
I would like to thank the Pharmacy and Therapeutic Committee and all staff at thefour participating community hospitals for facilitating this research.
Finally, I could not forget to say thank you to my beloved family. Their support,
encouragement and belief motivate me until succeed in my dissertation. In addition,
I would like to thank you to all people in our laboratory in Meiji Pharmaceutical
University for all help and moral support.
84