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JOURNAL

PRESENTATION
Supervisor : dr. Sabar P.
Siregar, Sp.KJ

Kepaniteraan Klinik Psikiatri


RSJ Prof dr. Soeroyo, Magelang
Program Studi Profesi Dokter
Fakultas Kedokteran Universitas Tanjungpura,
Pontianak
Periode 25 Juli-27 Agustus 2016
JOURNAL PRESENTATION

Baseline Characteristics and Treatment-emergent Risk


Factors Associated with Cerebrovascular Event and
Death with Risperidone in Dementia Patients
1. Division of Psychiatry, University College London,and Department of Old Age
Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, Kings College
London
2. Division of Psychiatry, University College London, London, UK
3. Janssen Research & Development, Titusville,New Jersey, USA

2
BACKGROUNDS
Use of antipsychotics to treat behavioural symptoms of dementia
has been associated with increased risks of mortality and stroke.

Aims
We examined the risperidone clinical trial data with these adverse
outcomes
METHODS
Double-blind randomised controlled trial of risperidone in dementia
patients (Risperidone n=1009 V Placebo n=712)
Analysed Crude Insidences
Cox Proportional Hazards Regression
BACKGROUND
Risperidone Persistent aggression in patients with moderate to
severe alzheimers with moderate to severe alzheimers dementia
unresponsive to non-pharmacological approachs
Identifying patients characteristics and treatment emergent events
stroke and death risperidone and placebo
METHODS
Included men and womeb aged 55 years / over with Alzheimers
vascular or mixed dementia
In our analysis all risperidone doses were combined into a single
group
VARIABLES
Age ( < 80 years V 80 years)
Gender, ethnicity, diagnosis, BMI, MMSE

Statistical Analysis
SAS Version 9.2
Fishers exact test was used to compared the crude incidences of
CVAE and mortality
RESULTS
There was statistically significant different in the crude incidence of
all CVAE across all studies
Risperidone; 4,9% V Placebo; 1,5% (p<0,001)

Placebo group risk factors


Patient characteristics
Crude incidence analysis : Participants over 80 years old (p=0,02)
and with baseline depressed mood (p=0,047) were at
increased risk of CVAE
Exposure-adjusted incidence rates
Analyses based on EAIR differences identified age over 80 years
(p=0,004) and BEHAVE-AD global rating less than severe (p=0,045)
as significant risk factors for CVAE

Crude incidence analysis


Factors associated with increased mortality included dehydration
(p<0,001), infection (p<0,001) and pulmonary conditions
(p=0,012)
Exposure-adjusted incidence rates
For mortality, dehydration (p=0,042) and infection (p=0,007)
emerged as significant but pulmonary conditions (p=0,056) failed to
reach significance.
Analysis with 7-day offset
Significant factors identified included dehydration (p=0,013),
infection (p=0,004) and pulmonary condition (p=0,05)
Patients with dementia indicate that individual antipsychotic drugs
have different mortality risks, with quetiapine being associated with
the highest risk of death.
Treatment-emergent associated incidence of mortality
dehydration, infection and pulmonary conditions
depressed mood was associated a reduced risperidone mortality
The association of delusions or depression with reduced CVAE risk and
depression with reduced mortality in risperidone-treated compared
with placebo-treated patients may indicate that specific psychiatric
symptoms rather than clusters of behaviours such as agitation mark
patients for whom atypical antipsychotic treatment carries less risk
A meta-analysis of atypical trials in dementia, however, reported
smaller treatment effect sizes for patients selected on the basis of
psychosis symptoms
Delusions may represent a target symptom in Alzheimers disease
where potential treatment benefits are significant and risks of CVAE
smaller
The increased relative mortality in patients taking risperidone who
were also treated with anti-inflammatory medications represents an
easily modifiable risk factor in clinical practice
CONCLUSION
Study Limitation :
Risk factors for stroke and death in people with dementia treated
with an atypical antipsychotic
This journal did not make statistical correction of our results for the
effects of multiple comparisons
CONCLUSION
Clinical implication :
Consider antipsychotic short-term treatment for behavioural and
psychiatric symptoms in dementia symptoms cause significant
distress or carry risk of harm to the patient or others, and when
alternative, nonpharmacological interventions are unavailable or
have failed
The presence of some psychiatric symptoms was associated with
reduced risk of CVAE and mortality within the population of people
with dementia treated with risperidone in the pivotal trials.
CRITICAL APPRAISAL
JOURNAL
TITLE
Baseline characteristics and treatment-emergent risk
factors associated with cerebrovascular event and death
with risperidone in dementia patients
The title contains 17
words
LESS than 12 words in
the title

It is not in accordance with the


contents
ABSTRACT
Structured abstract
Abstract contains : Background, aims, method, results, and
conclusions
Consists 169 words less than 250 words
There arent keywords in the abstract
Did the study address a clearly focused
question/issue ?
The issues that discussed in this journal were
focus but not really clear and consistent
This journal included the benefits of the research

Is the research method (study design) appropriate


for answering the research question ?
Yes, it is
Was the cases recruite precisely (based on
external, objective and validated criteria) ?
Yes, it was

Was the controls recruited rightly (based on


external, objective and validated criteria) ?
Yes, it was
How well was the study done to minimise the risk
of bias or confounding ?
Controls for bias
Categories within group defined clearly such
as :
(age, gender, weight, creatinine clearance,
diastolic blood pressure, sedation, EPS,
medications, etc )
Observers or interviewers were already trained
Possibility of loss to follow up is low
Has the exposure been measured to minimize
bias ?
Yes it has been measured rightly

Control for Bias


Bias controlled by randomization, double blinded,
placebo controlled studies
In this study, subjects were men and women
aged 55 years or over with Alzheimers, vascular
or mixed dementia as classified by DSM-IV
As for the healthy individuals involved in this
study, they were volunteers who didnt fulfill
exclusion criteria
Blinding didnt applied in this research. All
participants provided signed informed
consents
CONFOUNDING FACTORS
Confounding factors controlled by :
Restriction restrict the subject in the same level of confounder
Multivariat analysis

Role of chance
Random error can be caused by :
Patients medication adherence
Rate of medication changes
WHAT WERE THE RESULTS
OF THIS RESEARCHES ?
Baseline complications of depression (treatment by
risk factor interaction on cerebrovascular adverse
event (CVAE) hazard ratio (HR): P = 0.025) and
delusions (P = 0.043) were associated with a lower
relative risk of CVAE in risperidonetreated patients
(HR = 1.47 and 0.54, respectively) compared to not
having the complication (HR = 5.88 and 4.16). For
mortality, the only significant baseline predictor in
patients treated with risperidone was depression,
which was associated with a lower relative risk
HOW PRECISE THE RESULTS
OF THE STUDY ?
It was not really precise because it did not consider
the combination of the drug and drug dose. This
study did not explain the reasons to categorizing the
patients who taking typical and atypical
antipsychotic to the typical antipsychotic
Risk factors for stroke and death in people with
dementia treated with an atypical antipsychotic not
analysed
Then this study have not explained precisely on
WAS THE RESULTS CAN BE
TRUSTED ?
The results can be trusted
WAS THE RESULTS CAN BE
APPLIED IN THE LOCAL
CONTEXT ?
Can not be, because this study used
a sample of 100% from Europe, in
this case the races and culture can
affect the differences in drug dosage
and social environment
WERE THE RESULTS
CONVENIENT ACCORDING
TO THE PREVIUS SCIENTIFIC
EVIDENCE ?
Clinicians will continue to consider antipsychotic
short-term treatment for behavioural and
psychiatric symptoms in dementia when those
symptoms cause significant distress or carry risk
of harm to the patient or others, and when
alternative, nonpharmacological interventions
are unavailable or have failed