Lembar Jawaban Skill Lab Evidence Based Medicine Tanggal 23 Mei 2017
Lembar Jawaban Skill Lab Evidence Based Medicine Tanggal 23 Mei 2017
Lembar Jawaban Skill Lab Evidence Based Medicine Tanggal 23 Mei 2017
1. DATA ABNORMALITAS
a. Hitung harga rerata!
b. Hitung harga standar deviasi!
c. Hitung nilai abnormalitas (> rerata + 2SD)
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2. DARI CLINICAL SCENARIO DIBUAT:
a. Tabel PICO
c. Search Term/Search/Keyword!
(Mini-Cog OR minicog) AND (Mini Mental State Exam OR MMSE OR SMMSE) AND
(Alzheimer OR Dementia)
d. Searching
www.tripdatabase.com
Dementia is an umbrella term for a number of different brain diseases that progressively
affect a person’s ability to think and function independently. Alzheimer’s disease, for
example, is the commonest cause of dementia. The symptoms and the impairment caused
by dementia are a result of progressive damage to the brain and a loss of brain cells and
connections.
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The symptoms a particular person with dementia develops depends on where in the brain
the disease is affecting. For example, early on in the disease course Alzheimer’s affects an
area of the brain called the hippocampus, which is involved in storing memories about our
lives. For this reason, patients with Alzheimer’s disease get memory problems early on. By
comparison, frontotemporal dementia affects the frontal area of the brain first and, as a
result, these patients often have changes in personality and difficulties in planning long
before they have difficulties with memory.
The way we diagnose and detect dementia, therefore, is by systematically assessing the
function of various brain regions by using cognitive tests. ‘Cognitive’ here means the
‘higher brain functions’ I alluded to earlier; things like memory, numeracy, visual
perception, personality change and planning, to name a few.
The commonest cognitive test used is called the Mini-Mental State Examination
(MMSE). In this test, you can score up to 30 points by answering a range of questions that
test your orientation to time and place, your memory, attention and so on. The test itself
takes about 10 minutes to complete. As the authors of this paper state, the performance of
the MMSE in detecting dementia as compared to other tests has not been systematically
assessed and so, that is what they set out to do. One of the reasons to assess the relative
merits of the MMSE is that it is a proprietary instrument, owned by ‘Psychological
Assessment Resources’ meaning that it is not actually free for organizations to use.
In this paper, the authors completed a systematic review of the literature for studies that:
• Assessed the performance of the MMSE at being able to correctly detect dementia;
and
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• Compared it to other measures that fell into three categories; tests that took less
than 5 minutes to complete, 10 minutes and 20 minutes
Methods
They excluded:
In terms of how the search was performed, it looks very thorough. They searched
MEDLINE, EMBASE, PsychoINFO and Google Scholar from the earliest available dates
stated in the individual databases until 1 Sep 2014. Two authors independently assessed
the search results and used a standardized data extraction sheet. The studies were also
screened for quality and bias.
As outcomes, they chose several different measures of diagnostic accuracy that can get a
bit confusing. The perfect test should be able to tell you everyone who has the disease and
correctly identify everyone who does not have the disease…easier said than done.
To understand what the results of this paper mean it is worth running through an imaginary
scenario.
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How do diagnostic tests work?
Let’s imagine 100 people come to a GP to get tested for ‘Disease X’. The GP decides to
compare a new test he’s just bought with the gold-standard perfect test. Using the gold
standard, he finds out that 50 people have the dreaded ‘Disease X’ and 50 people do not.
He then compares these results with his new test, which you can see in the table below.
New test 35 These are true positives 10 These are false positives
came back (TP) – this is good (FP) – this is bad.
as positive
New test 15These are false negatives 40 These are true negatives
came back (FN) – this is really bad! (TN) –this is good too.
as
negative
From these kinds of tables, you can work out how good a new/alternative diagnostic test
is. As you can see from this imaginary scenario, the new test misdiagnosed 20 of the 100
people.
In this paper, they chose to look at a number of different options for assessing the
effectiveness of each of the cognitive tests they were interested in. It’s probably not worth
going through all the measures they used, but it’s worth knowing about two: sensitivity and
specificity.
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Sensitivity and specificity
Sensitivity determines what proportion of people who actually have the disease get
a positive test. Or as a formula
For both sensitivity and specificity; the higher the number, the better. The paper also looks
at other measures of the diagnostic accuracy but they are derived from the sensitivity and
specificity. Without going into detail, the paper also reports Likelihood Ratios, diagnostic
odds ratio and ‘AUC’ or area-under-the-curve.
Results
The initial search yielded 26,380 papers! After applying the inclusion/exclusion criteria
they were left with 149 studies, which covered 11 different diagnostic tests and over 40,000
people from around the world.
MMSE
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• All other markers also showed good diagnostic accuracy (LR+ = 7.45, LR-
= 0.21, diagnostic OR was 35.4 and AUC was 92%)
• Of the 11 remaining tests, two stood out as being ‘better’ than the MMSE
• Mini-Cog (brief test <5 min): sensitivity of 91% and specificity of 86%
• ACE-R (20 min test): sensitivity of 92% and specificity of 89%
• However, where the MMSE data was drawn from hundreds of studies:
• Mini-Cog data was drawn from just 9 studies
• ACE-R was drawn from just 13 studies
For all three of the above tests, there was found to be a high degree of heterogeneity. In
essence, this is a statistical test telling us that between studies included in the analyses, the
results were quite different from one study to another. Heterogeneity is not a good thing in
systematic reviews.
Further analyses
The reviewers showed that the accuracy of the MMSE was not affected by geographical
location or clinical site (i.e. it was as effective for hospital patients as community patients).
Finally, they looked at the accuracy of diagnosing mild cognitive impairment (MCI); a
risk state that precedes dementia. They didn’t really go into much detail in the methods of
how they found the studies or how they defined MCI.
Only 21 studies using MMSE were used to assess diagnostic accuracy for MCI giving:
o a sensitivity of only 62%
o and a specificity of 87%.
An alternative test, the MoCA, was found to perform better (in 9 studies) with:
o a sensitivity of 89%
o and a specificity of 75%
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No data was provided on the other tests presumably because there weren’t enough studies.
Conclusions
In short, the MMSE is not a bad screening tool for dementia but it is not miles better than
the rest; it’s just really commonly used, probably for historical reasons. The ACE-R and
the Mini-Cog are both free to use and may be viable alternatives. The MMSE is less good
in mild cognitive impairment.
1. The literature search was done well. The authors should be commended for going
through so many papers in such a systematic way
2. The criteria for inclusion and exclusion were made clear and papers were assessed for
quality and data was extracted in a reliable way by two authors
4. The paper collates a huge amount of data pertinent to the question: data from over
40,000 people were included in the analysis.
1. All meta-analyses inherit the limitations of the papers they include. In this case the
most obvious limitation is the relative lack of data on alternative cognitive tests like
the ACE or Mini-Cog
2. The authors mention that the cut-off scores for diagnosing dementia change from
study to study. Unlike the example I gave earlier these tests are not simply positive or
negative. They give a score (from 0 to 30 in the case of the MMSE) and so the cut-off
needs to be determined by the user. In the case of the MMSE, the commonest cut-off
was less than 23 or 24, but this was not the case in all of the studies included. This has
obvious effects on diagnostic accuracy.
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3. The authors chose to include Parkinson’s disease in the search criteria, but not Lewy
Body dementia or frontotemporal dementia, which I can’t understand given how
common they are.
4. I didn’t really find the section on mild cognitive impairment very helpful because it
seemed like an afterthought. The search terms used to collect the data didn’t seem to
be wide enough to capture all the relevant studies for example.
Referensi
Nair, Akshay. "Cognitive Tests for Dementia: MMSE, Mini-Cog & ACE-
R". National Elf Service. N.p., 2014. Web. 24 May 2017.
http://www.nationalelfservice.net/mental-health/dementia/cognitive-tests-for-dementia-
mmse-mini-cog-and-ace-r/?referer=TripDatabase&keywords=%28Mini-
cog%20OR%20minicog%29%20AND%20%28Mini-
Mental%20State%20Exam*%20OR%20MMSE%20OR%20SMMSE%29%20AND%20
%28Alzheimer*%20OR%20dementia%29#sthash.Z5CWe2mF.dpuf
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Dalam penelitian ini tidak tertulis mengenai concealment
karena bukan merupakan uji klinis
d. Angka DO
Tidak dijelaskan mengenai angka DO pada sistematik
review/meta analisis ini.
e. Jenis analisis
Jenis tulisan berupa sistematik review/meta analisis yang
menggunakan metode cross sectional.
2. Validitas pengontrolan perancu
Pada tulisan ini, validitas pengontrolan perancu cukup baik
karena memberikan informasi mengenai kriteria inklusi dan
kriteria eklusi pasien yang dimuat dalam penelitian.
3. Validitas informasi
a. Blinding
-
b. Komponen pengukuran variabel penelitian
Variabel yang diukur pada penelitian yang masuk dalam
sistematik review/meta analisis adalah hasil pengujian pasien
demensia dengan menggunakan mini-cog dibandingkan
dengan menggunakan MMSE
4. Validitas analisis
Tulisan ini berupa sistematik review/meta analisis dengan hasil
dan interpretasi yang baik, sehingga validitas analisis tulisan ini
baik.
5. Validitas internal kausal
Tidak terdapat validitas eksterna karena bukan merupakan uji
klinis
6. Validitas eksterna
Validitas eksterna pada tulisan ini baik karena menggunakan
metode sistematik review/meta analisis dengan jumlah sampel
yang besar yang berasal dari seluruh dunia dengan data primer
(data diambil secara langsung/face to face)
Importance MMSE:
sensitifitas 62%
spesifisitas 87%.
Mini-Cog:
Sensitifitas 91%
Spesifisitas 86%
Penelitian ini penting karena selanjutnya Mini-Cog dapat digunakan
untuk skrining MCI mengingat sensitifitasnya yang tinggi.
Applicability Hasil penelitian dapat diterapkan
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3. DATA DIAGNOSTIK
Data diagnostik terdiri dari variable Keratinin Kinase dan MCI
a. Buatlah Grafik Titik Potong Diagnostik
Classification: MCI
100
90
80
70
60
Sensitivity (%)
50
Specificity (%)
40
30
20
10
0
40 50 60 70 80
Kreatinin Kinase
Kreatinin Kinase
100
Sensitivity: 100.0
Specificity: 92.0
Criterion : >69.1098
80
Sensitivity
60
40
20
0
0 20 40 60 80 100
100-Specificity
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Variable Kreatinin_kinase
Kreatinin Kinase
Classification variable MCI
MCI
Youden index
Youden index J 0.9195
Associated criterion >69.1098
b. Perkiraan secara visual nilai titik potong Kreatinin Kinase dan MCI dan interpretasikan!
Dari grafik diatas secara visual dapat ditentukan nilai potong kreatinin kinase lebih dari 80
dan kurang dari 90 adalah cut of point.
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c. Hitung seluruh nilai diagnostik Kreatinin Kinase dan MCI dan buat kesimpulan!
Kesimpulan
Validitas dilihat dari sensitivity 100%, specificity 92%, akurasi dilihat dari ROC curve
hasilnya 0.973 (diantara 0,9 – 1,00 excellent) pada cut of point 60.1098.
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Data diagnostik terdiri dari variable LDL dan MCI
a. Buatlah grafik titik potong diagnostic
Classification: MCI
100
90
80
70
60
50
40
30
20
10
0
80 100 120 140 160 180 200
LDL
LDL
100
80 Sensitivity: 84.6
Specificity: 47.1
Criterion : ≤143.002
Sensitivity
60
40
20
0
0 20 40 60 80 100
100-Specificity
Variable LDL
LDL
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Sample size 100
z statistic 1.178
Youden index
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≤135.632 30.77 9.1 - 61.4 62.07 51.0 - 72.3 0.81 1.12
b. Perkirakan secara visual nilai titik potong LDL dan MCI dan interpretasikan
Dari grafik diatas, secara visual dapat ditentukan nilai potong LDL lebiih dari 50 dan
kurang dari 70 adalah cut of point.
c. Hitung seluruh nilai diagnostik LDL dan MCI dan buat kesimpulan
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e) Predictive value of +ve result : 0.05 [0.01, 0.17]
f) Predictive value of -ve result : 0.81 [0.68, 0.90]
g) PLR : 0.326454
h) NLR : 1.600334
Manual
a) Sensitivity [ a/(a+c) ] : 15.38%
b) Specificity [ d/(b+d) ] : 52.87%
c) Akurasi [ a+d/a+b+c+d ] : 48%
d) Positive Predictive Value [ a/(a+b) ] : 4.65%
e) Negative Predictive Value [ c/(c+d) ] : 19.29%
f) Positive Likelihood Ratio [ sens/(1-spec) ] : 0.3263314
g) Negative Likelihood Ratio [ (1-sens)/spec ] : 1.6005296
h) Likelihood Ratio Test [ PLR/NLR ] : 0.2038896
i) Area Under Curve (AUC) : 0,598
Kesimpulan
LDL dapat mendiagnosis MCI dengan sensitivity 15.38%, specificity 52.87%, akurasi
dilihat dai ROC curve 0,598 (diantara 0,5 – 0,6 fail) pada cut of point 143.002.
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4. Bad Outcome
a. Nilai Importance
b. Buatlah Kesimpulan!
RR = 0.46 berarti kemungkinan subjek pada kelompok terapi ACE inhibitor dengan
kematian adalah sebesar 0.46 kali dibandingkan dengan kelompok placebo. Dengan kata
lain pemberian ACE inhibitor mengurangi risiko kematian pada MCI. RRR = 0.54 artinya
apabila ACE inhibitor digunakan sebagai terapi maka jumlah insiden MCI yang mati dapat
diturunkan sebesar 54% dari insiden sebelumnya. ARR = 0.14 artinya apabila ACE
inhibitor digunakan sebagai terapi maka selisih jumlah insiden mati antara ACE inhibitor
dengan placebo sebesar 14%. NNT = 7.14 artinya kita perlu melakukan terapi ACE
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inhibitor kepada 7.14 pasien untuk mencegah terjadinya satu kematian MCI. Cost of
preventing bad outcome, misalnya satu pasien cost ACE inhibitor Rp.100.000 maka cost
of preventing bad outcome 7.14 x 100.000 = Rp.7.140.000. Artinya untuk mencegah
terjadinya kematian MCI diperlukan dana sebesar Rp.7.140.000.
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5. Therapy Effectiveness
a. Nilai Importance
b. Buatlah Kesimpulan!
RR = 2.88 artinya kemungkinan subjek pada kelompok terapi Enalapril + ASA
mengalami kesembuhan adalah sebesar 2.88 kali dibandingkan dengan kelompok
Isosorbide + Diuretik. Dengan kata lain terapi Enalapril + ASA lebih efektif 2.88 kali
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dibandingkan terapi Isosorbide + Diuretik. RBI = 1,88 artinya apabila Enalapril + ASA
digunakan sebagai terapi maka jumlah insiden sembuh dapat ditingkatkan sebesar
188.9% dari insiden kesembuhan sebelumnya. ABI = 0.34 artinya apabila Enalapril +
ASA digunakan sebagai terapi maka selisih jumlah insiden sembuh antara Enalapril +
ASA dengan Isosorbide + Diuretik sebesar 34%. NNT = 2.94 artinya kita perlu
melakukan terapi Enalapril + ASA kepada 2.94 pasien untuk meningkatkan
kesembuhan. Cost of increasing good outcome, misalnya satu paseil cost Enalapril +
ASA Rp.1.000.000, maka cost of increasing good outcome 2.94 x 1.000.000 =
Rp.2.940.000. Artinya untuk menambah 1 kesembuhan perlu dana sebesar
Rp.2.9400.000.
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