Lembar Jawaban Skill Lab EBM

1. Nilai abnormalitas

Tabel abnormalitas
Parameter Rerata SD Rerata +- 2SD Nilai
abnormalitas
SGOT/SGPT 26,29 13,923
Hemoglobin 12,472 3238
Trigliserid 115,30 20,047
Total Kolesterol 137,23 32,405
HDL 89,44 74,64
LDL 74,64 13,634

Statistics
SGOT/SGPT
Laki-laki Hemoglobin Trigliserid Total Kolestrol HDL LDL
N Valid 200 200 200 200 200 200
Missing 0 0 0 0 0 0
Mean 26,29 12,472 115,30 137,23 89,44 74,64
Std. Deviation 13,923 ,3238 20,047 32,405 17,119 13,634

2. Clinical Scenario

2.1 Tabel PICO

P Elderly adult with early signs/symptoms of cognitive impairment

I Mini-cog screening
C Mini Mental State Examination (MMSE)
O Accurate diagnosis of Alzheimer’s disease of dementia

2.2 Clinical Question

In Older adult with cognitive impairment, is Mini-cog or minicog as accurate as
MMSE or SMMSE in Alzheimers disease or dementia.

2.3 Search Term

(Mini-Cog OR minicog) AND (MMSE or SMMSE) AND (Alzheimer’s disease
OR dementia)

2.4 Lakukan searching

www.tripdatabase.com

2.5 Abstract

In this systematic review and meta-analysis, Tsoi and colleagues from Hong Kong
aimed to assess the relative effectiveness of common cognitive tests at diagnosing
dementia.
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.

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.

Obviously, an exhaustive assessment of a person’s cognitive function would take

a very long time – hours, if not longer! While researchers may have hours to
spend with patients, most busy clinicians do not and so the Holy Grail is finding a
good, brief screening test of cognitive function that allows us to diagnose
dementia.

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 organisations 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
 Compared it to other measures that fell into three categories; tests that took less
than 5 minutes to complete, 10 minutes and 20 minutes
This systematic review compares the MMSE with other tools for detecting
dementia. [Interlocking-Pentagons used in the Mini-Mental State Exam].

Methods

The reviewers included studies that:

 Looked for patients with either Alzheimer’s, vascular dementia or Parkinson’s

disease in any clinical setting
 Assessed patients or carers face-to-face
 Used a standardised diagnostic criteria to diagnose dementia
 Published the outcome measures they were interested in.

They excluded:

 Non-English language papers

 Tests that took longer than 20 minutes to complete
 Tests that were only evaluated in four or less papers
 Any patients who were visually impaired.

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 standardised 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.

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.

People People
tested tested
who do who do
have not have
Disease X Disease X
(n = 50)
(n = 50)
35 10

New test These are These are

came back true false
as positive positives positives
(TP) – (FP) –
this is this is
good bad.
15
40
New test These are
came back
These are
false
true
as negatives
negatives
negative (FN) –
(TN) –
this is
this is
really
good too.
bad!

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.

Sensitivity and specificity

Sensitivity determines what proportion of people who actually have the disease
get a positive test. Or as a formula

 Sensitivity = TP / (TP + FN)

 So, in the example above for Disease X – the sensitivity of the new test is 35/(35+15)
= 0.7 or 70%
Likewise specificity determines what proportions of people who actually do not
have the disease get a negative test. Or as a formula:

 Specificity = TN/ (TN + FP)

 So, in the example above for Disease X – the specificity of the new test is 40/(40+10)
= 0.8 or 80%

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.

Accurate diagnostic tests have high sensitivity and high specificity.

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

 The vast majority of the studies looked at MMSE (108 of 149)

 Sample size was 36,080 of whom 10,263 had dementia
 From these studies the:
o Mean sensitivity was 81% (CI was 78% to 84%)
o Mean specificity was 89% (CI was 87% to 91%)
o All other markers also showed good diagnostic accuracy (LR+ = 7.45, LR- = 0.21,
diagnostic OR was 35.4 and AUC was 92%)

Mini-Cog and ACE-R (the best of the rest)

 Of the 11 remaining tests, two stood out as being ‘better’ than the MMSE
o Mini-Cog (brief test <5 min): sensitivity of 91% and specificity of 86%
o ACE-R (20 min test): sensitivity of 92% and specificity of 89%
 However where the MMSE data was drawn from hundreds of studies:
o Mini-Cog data was drawn from just 9 studies
o 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%
 No data was provided on the other tests presumably because there weren’t enough
studies.

The freely available ACE-R and Mini-Cog instruments may be viable alternatives
to the MMSE for detecting dementia.

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.

Strengths and limitations

What were some of the strengths of this paper?

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
3. The meta-analysis itself appears to have been done well
4. The paper collates a huge amount of data pertinent to the question: data from over
40,000 people were included in the analysis.

What were the limitations?

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.
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.

Final thoughts

It’s important to add that whilst this paper focussed on cognitive screening tests,
which play an important part in diagnosis, a full clinical assessment of someone
with suspected dementia requires a much more detailed approach. Combining
information from the history, examination, investigations and cognitive tests
greatly improve the diagnostic accuracy. Also where the screening tests are not
clear, patients can be referred for much more detailed assessments of cognition
performed by neuropsychologists.

Also it is important to remember that the diagnosis of dementia requires evidence

of a progressive illness. This means that repeating cognitive tests and looking for
change is often more helpful than just a snapshot. This aspect was not covered in
this systematic review.

2.6 Critical Appraisal (VIA) -> Homework

3. Data Diagnostik

3.1 Buat 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

3.2 Perkiraan secara visual nilai titik potong diagnostik dan interpretasikanf
Cut of point = 60 sampai kurang dari 70
Kreatinin Kinase
100

80
Sensitivity

60

40

20

0
0 20 40 60 80 100
100-Specificity

ROC curve
Variable Kreatinin_kinase
Kreatinin Kinase

Classification variable MCI

MCI

Sample size 100

Positive group a 13 (13,00%)

Negative group b 87 (87,00%)

a
MCI = 1
b
MCI = 0

Disease prevalence (%) Unknown

Area under the ROC curve (AUC)

Area under the ROC curve (AUC) 0,973

Standard Error a 0,0140

95% Confidence interval b 0,919 to 0,995

z statistic 33,901

Significance level P (Area=0.5) <0,0001

a DeLong et al., 1988

b Binomial exact

Youden index
Youden index J 0,9195

Associated criterion >69,1098

Sensitivity 100,00

Specificity 91,95

Criterion values and coordinates of the ROC curve [Hide]

Criterion Sensitivity 95% CI Specificity 95% CI +LR -LR

≥40,0886 100,00 75,3 - 100,0 0,00 0,0 - 4,2 1,00

>69,1098 100,00 75,3 - 100,0 91,95 84,1 - 96,7 12,43 0,00

>70,1641 92,31 64,0 - 99,8 93,10 85,6 - 97,4 13,38 0,083

>72,9038 76,92 46,2 - 95,0 93,10 85,6 - 97,4 11,15 0,25

>73,2495 69,23 38,6 - 90,9 94,25 87,1 - 98,1 12,05 0,33

>75,2407 69,23 38,6 - 90,9 96,55 90,3 - 99,3 20,08 0,32

>76,5148 61,54 31,6 - 86,1 97,70 91,9 - 99,7 26,77 0,39

>76,8872 53,85 25,1 - 80,8 98,85 93,8 - 100,0 46,85 0,47

>77,4574 38,46 13,9 - 68,4 98,85 93,8 - 100,0 33,46 0,62

>77,995 30,77 9,1 - 61,4 100,00 95,8 - 100,0 0,69

>78,6751 0,00 0,0 - 24,7 100,00 95,8 - 100,0 1,00

Area under curve -> 0,973, bermakna karena di atas 0,001

Sensitivitas 100
Spec 82
Criteria lebih dari 69,1098

Case Processing Summary

Cases
Valid Missing Total
N Percent N Percent N Percent
Kategori Kreatinin Kinase * 100 100,0% 0 0,0% 100 100,0%
MCI

Kategori Kreatinin Kinase * MCI Crosstabulation

Count
MCI
MCI Negatif MCI Positif Total
Kategori Kreatinin Kinase Tinggi 78 0 78
Rendah 9 13 22
Total 87 13 100

Tables - 2-by-2 unstratified

11:20:36, 24/05/2018

| + - | Total
-------+-------------+-------
+ | 13 7 | 20
- | 0 80 | 80
-------+-------------+-------
Total | 13 87 | 100

Tests of significance
Fisher exact test (one tailed) : 0,000000
Fisher exact test (two tailed) : 0,000000
Uncorrected chi-square : 59,77
p-value : 0,000001
Yates corrected Chi-square : 54,16
p-value : 0,000001

Measures of exposure effect [95% CI]

Risk ratio : **** [****; ****]
Odds ratio : **** [****; ****]
Risk difference : 0,65 [0,44; 0,86]
Proportional attributable risk : **** [****; ****]
Population proportional attr. risk : **** [****; ****]

Vaccine efficacy [95% CI]

Vaccine efficacy : **** [****; ****]

Screening [95% CI]

Prevalence : 0,13 [0,07; 0,22]
Sensitivity : 1,00 [0,72; 0,99]
Specificity : 0,92 [0,84; 0,96]
Accuracy : 0,93 [0,86; 0,97]
Predictive value of +ve result : 0,65 [0,41; 0,84]
Predictive value of -ve result : 1,00 [0,94; 1,00]

Matched data
Z : 2,27
One-sided p-value : 0,011671
Two-sided p-value : 0,023342
McNemar Chi-square : 5,14
p-value : 0,023342
McNemar odds ratio [95% CI] : **** [1,28; 74,55]
Difference in proportions [95% CI] : 0,07 [0,02; 0,12]

Interpretasi

1. Sensitivity 100% artinya

2. Specificity 92% artinya
3. PVP
4. PVN
5. LR
6. AUC 0,974 (97,4%)..... excellent

Kesimpulan

4. Data therapy bad outcome

Kelompok * MCI Crosstabulation

Count
MCI
Meninggal Hidup Total
Kelompok Ace Inhibitor 6 44 50
Placebo 13 37 50
Total 19 81 100
 5. Data TherapyEffectiveness

Kelompok * Outcome Crosstabulation

Count
Outcome
Sembuh Tidak Sembuh Total
Kelompok Enalapril + ASA 26 24 50
Isossorbid Prodiprogrel + 9 41 50
Deuretik
Total 35 65 100
Kesimpulan: zat asam penting dalam penyembuhan atau pengendalian hipertensi
dengan keluhan klinis sebesar