CURRICULUM VITAE

Academic Profiles:
• Medical Doctor – FMUI, 1986
• Internist – FMUI, 1996
• Post Graduate Education in Geriatric Medicine – Dept. of
Geriatric & Rehab Medicine Royal Adelaide Hospital, Australia,
1997
• Consultant (Subspecialist) in Geriatric Medicine – FMUI, 2000
• Master of Clinical Epidemiology – Universitas Indonesia, 2003
• Doctor of Philosophy (PhD) – Universitas Indonesia, 2006
• Professor of Medicine - Universitas Indonesia, 2013

Current Position:
• Chair – Indonesian Geriatrics Society (PERGEMI)
• Chair – Clinical Epidemiology and Evidence-Based Medicine
(CEEBM) Unit, Cipto Mangunkusumo Hosp-FMUI.
• Vice Chair – The Indonesian Journal of Internal Medicine (Acta
Medica)
• Senior staff in Geriatric Medicine Division – Internal Medicine
Department, FMUI-RSCM
Evidence-based Medicine in The
Very Old Patients
Siti Setiati
s_setiati@yahoo.com
 What is Evidence-based Medicine?
• “The conscientious, explicit,
and judicious use of current
Patients
best evidence in making
decisions about the care of
preferences
individual patients”
• “Pemanfaatan bukti EBM
Best
mutakhir yang terbaik, Clinical
terkini, dalam tatalaksana research
expertise
pasien” evidence
 What the latest
Statement in paper in a
An expert opinion
textbook prestigious journal
says

Traditional Choosing the most

approach – “It’s the Continuing Medical expensive
way we’ve always Education course treatment that
done it” patient can afford

Those are not EBM

 Our textbooks are out-of-date
WHY EBM? • Fail to recommend Rx up to ten years after it’s
been shown to be efficacious.
1. Information overload • Continue to recommend therapy up to ten
2. Keeping current with years after it’s been shown to be useless.
literature
3. Our clinical performance
deteriorates with time
(“the slippery slope”)
4. Traditional CME does not
improve clinical
performance
5. EBM encourages self
directed learning process
which should overcome
the above shortages
On average, the clinically-important knowledge of
physicians deteriorates rapidly after we complete our
training.
 Area of EBM
Diagnosis
• (Determination of disease or problem) Systematic Reviews
Meta-analysis
Treatment
Clinical guidelines
• (Intervention to help the patient)
Economic analysis
Prognosis Clinical decision making
• (Prediction of outcome of disease) Cost-effectiveness analysis
Etiology Qualitative research
• (Cause of an outcome or disease)
 Interpreting the Evidence
❑ Electronic searching
• Patient • Database
Frame Patient Scenario
into a Clinical Question
• Intervention • Keywords & combination of
• Comparison search term(s): AND, OR,
bracket
Systematically retrieve
best evidence available • Outcome ❑ Hand searching
❑ Type of articles: inclusion &
CRITICAL APPRAISE exclusion criteria
EVIDENCE

Is this study Are the result Can the result

Apply results to patient valid? important? help you?

Evaluate decision
making V alidity I mportance A pplicability
Characteristics of Very Old Patient
Decreased
Multimorbidity
organ function

Reduced
Polypharmacy Functional
Status

Poor
Geriatric
Nutritional
Syndrome
Status Halter, JB et al. Hazzard’s Geriatric
Medicine and Gerontology. Edisi
s_setiati@yahoo.com 8 7.
McGraw Hill Education. 2017
 Improving EBM in Elderly:
Generating More Scientific Evidence
• Using a multimorbidity approach guidelines for elderly
Multimorbidity refers to the presence of 2
or more long-term health conditions,
which can include:
• Defined physical and mental health
conditions such as diabetes or
schizophrenia
• Ongoing conditions such as learning
disability
• difficult to manage their treatments or • Symptom complexes such as frailty or
day-to-day activities chronic pain
• have frailty or frequent falls • Sensory impairment such as sight or
• frequently seek unplanned or emergency hearing loss
care
• prescribed multiple regular medicines
 Consequences of Aging:
Tidak aman
Increased Disease Prevalence
Ageing Research Reviews 10 (2011) 430–439

Multiple chronic diseases

(multimorbidity)

Multiple clinical practice

guidelines (multiple PPK)

Prevalence of multimorbidity (defined as 2+

Polypharmacy, multiple concurrent diseases) widely varied across studies,
appointment, unplanned around 20–30% → whole population; 55 to 98% →
care in older persons
 How the Aging Process Affects EBM Elements
Characteristics Every elderly is very heterogenic due to those
of very old: characteristics
Multimorbidity
Polypharmacy
However, studies need to make their subjects as
homogen as possible
Decreased
physical,
psychological
and social
function We need to critically appraise those studies before
Increased applying them to our elderly patients.
rehospitalization,
adverse events, to prevent OVERTREATMENT of vulnerable patients
mortality and UNDERTREATMENT of fit older patients
 Scientific Evidence in Old Patients
Multimorbidity Inclusion of Age-related physiological
representative changes, multimorbidity,
Polypharmacy older patients polypharmacy

Multidomain Reporting and

Cognitive, functional,
functioning weighing of all four
psychosocial, diseases
geriatric axes

Inclusions of study Physical, psychosocial,

Different endpoints that are or social functioning;
requirements for relevant for elderly quality of life
clinical studies
Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
Scientific Evidence in Old Patients:
Randomized Control Trials
• To study the effects of a drug that is
cleared by the kidney, a patient
population may be required that does
not include patients with renal
failure. Whereas the renal function of
an elderly is commonly reduced,
especially in the very old
 Scientific Evidence in Old Patients:
Randomized Control Trials
• Explicit exclusion criteria:
– An upper age limit
– Exclusion of diseases that are
almost only seen in older
Elderly will be under-
adults (eg. Dementia)
represented in RCTs
– Exclusion of elderly with
mobility problems in a trial
protocol that requires
participants to visit study
center multiple times
Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
 Scientific Evidence in Old Patients:
Randomized Control Trials
• Endpoints in RCTs are often
related to the incidence of Somatic
diseases
disease and mortality,
whereas for elderly patients
Psychological Older Physical
the physical, psychological function adult function
and social functioning may
be considered more Social
important!!!. function

Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
 Scientific Evidence in Old Patients:
Etiological Studies
• Observational studies if
performed in
representative older
patients, may provide Risk factors for aspiration pneumonia:
useful evidence for the • sputum suctioning (OR = 3.276, 95% CI: 1.910–5.619)
• deterioration of swallowing function in the past
: Manabe T, Teramoto S, Tamiya N, Okochi J, Hizawa N (2015) Risk Factors for Aspiration Pneumonia in Older

treatment. Adults. PLoS ONE 10(10): e0140060. doi:10.1371/journal.pone.0140060

3 months
Method:(OR = 3.584, 95% CI: 1.948–6.952)
observational study of 9930 patients (median
• Essential to understand • dehydration
age 86 y.o, (OR = 8.019,
women 95%who
: 76%) CI: 2.720–23.643)
were divided into 2
• dementia
groups :(OR
those who 95%
= 1.618, had CI:
experienced and episode of
1.031–2.539)
how health and disease aspiration pneumonia in the previous 3 months and
work in aging body Thesethose who could
results had not.help
Data improve
on demographics, clinical
clinical
status, activities of daily living (ADL), and major
management
illnesses werefor preventing
compared between repetitive
subjects with and
aspiration pneumonia
without aspiration pneumonia
 Absolute Risk Reduction (ARR)
• Study are often conveyed in terms of relative risk reduction (RRR) rather than ARR,
which often suggest impressive outcomes (eg. a 25% RRR)
• But, RRR is uninterpretable if the baseline risk is not reported.
• ARR is based on the baseline risk minus the risk of the outcome with treatment →
may reflect the difference between two comparator treatments

Trial 1
30 days mortality rate (%)

ARR = 40%-30% =10%

RRR = 1- RR = 1- (0.3/0.4)
= 1-0.75 =0.25 (25%)
Trial 2
ARR = 10%-7.5% =2.5%
RRR = 1- RR = 1- (0.075/0.1) =
1-0.75 =0.25 (25%)
 Time Horizon to Benefit
• Studies often reports results in terms of number needed to treat/harm
without cosideration of time period to outcome
• Time horizon to benefit is the length of time needed to receive and
observable, clinically meaningful risk reduction for a specific outcome.
• For some chronic conditions, certain interventions are beneficial only after
longer durations of treatment.
Example:
“ the NNT to prevent one death was 50 The time horizon to benefit of tight glycemic
patients over 5 years of treatment ” control in DM is believed to be at least 5-7
years

For the very old elderly, do the anticipated benefits outweigh the long-term burden and
potential harms of treatment for the patients?
 Improving EBM in Elderly:
Generating More Scientific Evidence
• For specific diseases and guidelines, existing
evidence can be assessed for validity for elderly in
general and individual patients specifically
• More representative elderly patients should be
included in clinical studies

Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
 Questions to Ask Regarding the Medical Literature
To what extent were older adults with multimorbidity included in the trials? Is there evidence of
effect modification?
What is the quality of the evidence, using accepted EBM methodologies?
What are the hoped- for outcomes of the treatment or intervention? Are these outcomes important
to patients?
Is there meaningful variation in baseline risk for outcomes that the treatment or intervention is
designed to affect?
Are the risks and side effects of the treatments and interventions in older patients with multimorbidity
clearly known, so that a decision can be made whether the treatment for one condition will exacerbate
another?
What are the comparator treatments or management strategies?
Is it known how long it takes to accrue the benefit or harms of the treatment or intervention?
Does the document give absolute risk reductions or merely relative risk reduction? Is it possible to
estimate absolute risk reduction?
How precise are the findings? What are the confidence limits?
 Assessment of Patient’s Medical Conditions

Somatic
▪Cognitive performance
diseases
▪Apathy and depression
▪Level of physical activity
▪Ability to perform ADL
Psychological Older Physical
function adult function

Those four axes may

serve as determinants of
disease and also an Social ▪Presence of a spouse
endpoints function ▪Outdoor social activities with friends
Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do
Better?. The Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
▪Level of support provided by children
 Improving EBM in Elderly:
Systematic Acknowledgement of the Patient Situation
Somatic
diseases

Patient’s preference of
Psychological Older Physical treatment goals !!!....
function adult function

Frailty Assessment
Social
function

Comprehensive Geriatric
Assessment (CGA)
Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
 Patient Preferences
• Older people with multimorbidity are able to evaluate choices and the
prioritize their preferences for care, considering relevant personal and
cultural contexts about health and health care.
• Process of eliciting patient preferences:
– Recognize when the older adult with multimorbidity is facing a “preference sensitive”
decision. Example:
• Therapy that may results in long-term benefits but may cause short term harm (statin may reduce CVD risk but
also may cause cognitive impairment or muscle weakness)
– Ensure that elderly with multimorbidity are adequately informed about the expected
benefits and harms of different treatment options.
 Patient Preferences

• Process of eliciting patient preferences:

– Elicit patient preferences only after the elderly with multimorbidity is
sufficiently informed
• Typical outcomes: living as long as possible, maintaining function,
alleviating pain and other symptoms
• Let the patients speak their mind
• Ask the patients if they want their family/caregiver to be involved in
decision making
• Re-examined those preferences, those may change overtime
• This whole process doesn’t mean that patients has the right to demand
any options without reasonable expectation of some benefits.
 Assess Treatment Costs and Benefits
Slow recovery from an intervention

Inactivation and immobilization

Loss of muscle mass

Symptoms ↓
Lifespan ↑ Risk for falls
Cure
Functional decline
Complication
Side effect Postoperative delirium
Burden
Drug interaction
Higher dose → more side effects
Older Patients
Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Lower dose → undertreatment
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
 Assess Treatment Costs and Benefits
Shorter remaining life expectancy

Smaller restoration of physical function

Symptoms ↓
Lifespan ↑
Cure
Large heterogenicity → Complication
same calendar age, different in Side effect
biological age Burden

Overtreatment of the frail

Undertreatment of the fit Older Patients
Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
 Other things to consider
• Prognosis: • Clinical Feasibility:
The more complex a treatment regimen,
– Remaining life
the higher risk of non-adherence, adverse
expectancy reactions, poor quality of life and
– Functional status economic burden, greater depression in
caregivers
– Quality of life – Treatment complexity and feasibility
▪ Number of medications
▪ Dosage
▪ Frequency of dosing
▪ Administration instruction
 Improving EBM in Elderly:
Increasing Doctor’s Experience and Expertise
• Knowledge of the pathophysiology
of the ageing process and its
implications for treatment effects
• The lack of evidence should be
discussed with the patient in the
light of individual patient situation
and preferences.
• There is no one single “best”
treatment option → shared
decision making

Mooijaart, SP et al. Evidence-based Medicine in Older Patients: How Can We Do Better?. The
Netherlands Journal of Medicine. Vol 73. No. 5. 211-7. June 2015
 Careful and Kind Care
Sensible Resolution Clear Situation

Unhurried
Conversation

Situation alone never tells us what to do, but trustworthy and useful evidence may help
 Trustworthy Evidence

• Independently
produced
• Error-proofed
• Spin-free
• Fully reported

de Vries YA, Roest AM, de Jonge P, Cuijpers P, Munafò

MR, Bastiaansen JA (2018). The cumulative effect of
reporting and citation biases on the apparent efficacy of
treatments: the case of depression. Psychological
Medicine 1–3. https://doi.org/
10.1017/S0033291718001873
 Conclusions
• Before applying the evidence to help us treating elderly patients, we need
to understand about the consequences of ageing and consider the “cost
and benefit” of applying the evidence in elderly patients, especially in the
very old.
• We must fully aware that there are many trials (studies) which didn’t
include the very old group as participant; some prognostic tools and
guidelines are also not validated in the very old group.
• To improve EBM in elderly, we need to fully assessed our patients (by
doing CGA, frailty assessment, and discuss about patient’s preferences);
use only trustworthy and useful evidence; and provide careful and kind
care.
Thank You
 Case Example
• Current Concerns and Objectives for This Visit
– Mr. X 87 y.o man accompanied by his son and daughter to your clinic
– They are concerned that Mr. X is excessively fatigued and is taking too
many medicines
– They need to make sure that their father is safe and will be able to
stay alone in his own home
– He has an health insurance to cover some of his prescribed
medications, but the expense of other medicines is a financial burden.
 Review of the Overall Clinical Management Plan
• What are the current medical conditions and interventions?
Current medical conditions Current medical data Medications and Interventions

Probable Alzheimer’s MMSE score today 23/30; 6 months ago 1. Metformin 2x500mg
disease 25/30 2. Glyburide 1x10 mg
CHF BP sitting 110/70, standing 100/60; pulse 3. Enteric coated aspirin 1x325 mg
OA sitting 54 bpm, standing 56 bpm 4. Donepezil 1X10 mg bedtime
Osteoporosis HbA1c today 6.8%; 3 months ago 7% 5. Memantine 2x10 mg
Insomnia Echocardiogram: 1 year ago EF 30% 6. Furosemide 2x40 mg
Type 2 DM Total Chol 180 mg/dl; LDL 70 mg/dl; HDL 7. Metoprolol 2x100mg
BPH 50 mg/dl; TG 300 mg/dl 8. Lisinopril 2x20 mg
BUN 40 mg/dl; Cr 1.7 mg/dl; Glucose 100 9. Tamsulosin 1x0.4 mg evening
mg/dl 10. PCT 2x650 mg
11. Tramadol 2x50 mg prn severe pain
12. Calcium/vit D3 600mg/500IU 2x1 tab
13. Alendronate 70 mg/weekly
14. Zolpidem 1x10 mg bedtime
15. Simvastatin 1x40 mg evening
16. Blood sugar checked 3x/week
17. Exercise 1-2 mile walk/day
 Is the patient comfortable with, and adherent
to, the clinical management plan?
• Tn X. admits that
– He often forgets his evening medications because
he is tired
– He doesn’t check his blood sugar regularly
because the fingerstick hurts
 What are the preferences of the individual and
his family?
• Mr. X and his children express the following
priorities:
– To stay alive
– To optimize quality of life
– To reduce out-of-pocket expenses since the patient lives
on a fixed income
– To remain safely in his home despite the mild Alzheimer’s
disease (first noted 3 years ago)
 What evidences are available regarding
intervention effects?
• Cholinesterase inhibitor, donepezil, has had only modest success in
delaying institutionalization and in maintaining functional status, and
results are mixed.
• Memantine has shown no benefit alone or in combination therapy for
mild Alzheimer’s disease
• Data from the Fracture Intervention Trial Long-term Extension (FLEX) study
of women with osteoporosis taking alendronate for longer than 5 years
suggest that fracture protection exists for up to 5 more years after
stopping it.
• Tight glycemic control may result in more harm than benefit, and the
appropriate HbA1c target may be 8-9%.
 What is the prognosis?
• Given this individual’s age and multimorbidity,
life expectancy is estimated to be 2-3 years.
• Ongoing cognitive decline is likely, with
average loss on the MMSE of 2-3 points/year
• He will probably experience progressive
dependence in his IADL
 Are there interactions with medications and
medical conditions?
• Fatigue:
– Mr. X enjoy exercise but has been feeling more fatigued
lately.
– increased dose of metoprolol + donepezil → slow heart
rate
– Glyburide should be avoided in elderly because of the
greater risk of hypoglycemia
– May be an adverse effect of statin → statin therapy for
dyslipidemia need to be reevaluated.
 Are there interactions with medications and
medical conditions?
• Insomnia:
– Donepezil may cause nightmares, especially when
taken bedtime
– Zolpidem helpful for falling asleep, but may not
keeping him asleep for the night, cause excessive
somnolence during the day +hallucinations
 Are there interactions with medications and
medical conditions?
• CHF:
– Metformin : should be avoided in CHF and CKD because of the risk of
lactic acidosis
• Alzheimer’s disease:
— Zolpidem may worsen dementia, increase risk of falls → primary
safety concern for elderly with osteoporosis living alone

• Osetoporosis:
— Cr 1.7 BUN 40 → bisphosphonate administration needs to be
reevaluated
Benefits and Harms of the Intervention
• Reevaluation in treatment
of: Treatment complexity
√ Type II DM Medication burden
√ Insomnia
√ Dyslipidemia Feasibility

√ CHF Adherence
√ Cognitive decline
Quality of life
√ Osteoporosis
 Communicate and discuss decisions about
clinical management with the patient and family
• Consider: “ We understand that you:
– Feasibility of the approach • Prefer to remain at home and in your
community and avoid hospitalization
– Patient’s and family’s •Are not concerned about outcomes 5-10
preferences years in the future
– Outcome priorities •Are at risk of low blood sugar and its
consequences
– Make sure the patient
•Would like to feel more energetic
understands and agree with •Would like to decrease expenses
clinician’s recommendations Therefore, we suggest that you reduce
some of your medications and relax your
effort to achieve tight control of your
blood sugar levels ”
 Possible revisions to the treatment plan, with
consideration of the patient and family preferences
Medications and Interventions
HbA1c target should be less restrictive → 8-9%, so both drugs can be discontinued
Metformin 2x500mg or changed to only one drug at lower dose to lower risk for hypoglycemia. Published evidence doesn’t
Glyburide 1x10 mg support the use of
To improve adherence, aspirin reduced to 81 mg/day memantine in the mild stages
Enteric coated aspirin 1x325 mg
of AD. But the family strongly
Donepezil 1X10 mg bedtime To reduce insomnia, donepezil should be taken in the morning believe that it will help him
Memantine 2x10 mg gaining independence, so
Furosemide 2x40 mg To improve adherence, furosemid reduced to 40 mg/day memantine will be continued,
Metoprolol 2x100mg to minimize bradychardia → metoprolol reduced to 50 mg in the morning only but reduced to 10 mg/day in
Lisinopril 2x20 mg To improve adherence → 1x20 mg in the morning the morning. (considering the
CrCl = 30 ml/min)
Tamsulosin 1x0.4 mg evening
PCT 2x650 mg
Tramadol 2x50 mg prn severe pain Check vit D levels, to improve adherence → take medicine once daily in the morning + greater dietary
Calcium/vit D3 600mg/500IU 2x1 tab intake of calcium and vitamin D
Alendronate 70 mg/weekly Stop alendronate because it may still give fracture protection for 5 years (beyond Tn. X’s life expectancy)
Zolpidem 1x10 mg bedtime To reduce insomnia, zolpidem will be reduce to 5 mg at bedtime prn →the goal is complete discontinuation
Simvastatin 1x40 mg evening Weighing prognosis, uncertain benefit, unreliable adherence, complains of fatigue → discontinue simvastatin
Blood sugar checked 3x/week Patient has been avoiding fingerstick glucose monitoring 3x/wks → changed to monitor only when symptomatic
Exercise 1-2 mile walk/day
 Possible revisions to the treatment plan, with
consideration of the patient and family preferences
• Medication management:
– Choose 1 of the children to have responsibility
for filling pillboxes each week
– Give written instructions detailing new regimen
– Except for zolpidem, medications should be stored
in family member’s house, rather than with the
patient.
 Translating Evidence into Practice
Clinical studies

Systematic Clinical quality improvement

reviews

aware accepted applicable able acted on agreed to adhered to

Glasziou and Haynes EBN 2005; 8:36-38 Evidence-based medicine Clinical decision making
 Trustworthy Evidence

• Independently
produced
• Error-proofed
• Spin-free
• Fully reported

de Vries YA, Roest AM, de Jonge P, Cuijpers P, Munafò

MR, Bastiaansen JA (2018). The cumulative effect of
reporting and citation biases on the apparent efficacy of
treatments: the case of depression. Psychological
Medicine 1–3. https://doi.org/
10.1017/S0033291718001873