LEMBAR JAWANAN

SKILL LAB EVIDENCE BASED MEDICINE TGL 23 MEI 2017

Nama : Bima Indra
NIM : 04011181419208
Kelas : Beta 2014

1. DATA ABNORMALITAS

PARAMETER RERATA SD RERATA + 2SD NILAI

ABNORMALITAS
SGOT_SGPT 26,29 13,92 26,29 + 2 (13,923) = 54,13+0,05=54,18
3 54,13 >54,18 dikatakan
abnormal
HEMOGLOBINE 12,472 0,323 12,472-2(0,3238)=11,83 11,83-0,05=11,78
8 <11,78 dikatakan
abnormal
TRIGLYCERYDE 115,30 20,04 115,30+2(20,047)=155,39 155,39+0,05=155,4
7 4
>155,44 dikatakan
abnormal
TOTAL 137,23 32,40 137,23+2(32,405)=202,0 202,04+0,05=202,0
CHOLESTEROL 5 4 9
>202,09 dikatakan
abnormal
HDL 89,44 17,119 89,44-2(17,119)=55,22 55,22-0,05=55,17
<55,17 dikatakan
abnormal
LDL 74,64 13,63 74,64+2(13,634)=101,91 101,91+0,05=
4 >101,96 dikatakan
abnormal

2. Dari Clinical Scenario dibuat:

a. Tabel P.I.C.O
P Older adult with early sign symtomp of cognitive impairment
I Mini-cog screening test
C Mini Mental State Examination (MMSE)
O Accurate diagnosis of dementia or alzheimers disease

b. Buatlah Clinical Question

In older adult with early sign od cognitive impairment, is the mini-cog test as
accurete as MMSE in diagnosis of dementia or Alzheimers disease?

c. Buatlah Search Term/Search/Keyword

 (Mini-cog OR minicog) AND (mini-mental state exam OR MMSE) AND
(Alzheimer OR dementia)
Grafik titik potong diagnostik

d. Lakukan searching
e. Pastekan abstract artikel yang didapat pada lembar jawaban
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 Alzheimers, vascular dementia or Parkinsons 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 diseaseeasier 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?

Lets imagine 100 people come to a GP to get tested for Disease X. The GP decides to
compare a new test hes 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 tested People tested

who do have who do not have
Disease X (n = 50) Disease X
(n = 50)

New test came back 35 10

as positive These are true These are false
positives (TP) this positives (FP) this
is good is bad.
New test came back 15 40
as negative These are false These are true
negatives (FN) negatives (TN) this
this is really bad! is good too.
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. Its probably not worth
going through all the measures they used, but its worth knowing about two: sensitivity and
specificity.
Sensitivity and specificity
Sensitivity determines what proportion of people who actually have the diseaseget
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 didnt 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 werent 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; its 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 Parkinsons disease in the search criteria, but not Lewy
Body dementia or frontotemporal dementia, which I cant understand given how
common they are.
4. I didnt really find the section on mild cognitive impairment very helpful because it
seemed like an afterthought. The search terms used to collect the data didnt seem to be
wide enough to capture all the relevant studies for example.

Final thoughts
Its 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.

f. Lakukan Critical appraisal dari artikel dengan criticla appraisal worksheet

3. Dalam file excel tersedia DATA diagnostik. Data diagnostik terdiri dari variabel LDL
dan kreatinin kinase.
a. Buatlah Grafik titik potong diagnostik pastekan pada lembar jawaban

Classification: MCI
100
90
80
70
60
Sensitivity (%)
50
Specificity (%)
40
30
20
10
0
40 50 60 70 80
Kreatinin Kinase
 b. Perkirakan secara visual nilai titik potong diagnostik dan interpretasikan

Kreatinin Kinase
100

80
Sensitivity
60

40

20

0 nilai diagnostik memakai MeedCalc dan EpiCalc buatlah

c. Hitunglah seluruh
kesimpulan 0 20 40 60 80 100
ROC curve 100-Specificity

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 0.0142

95% Confidence interval b 0.919 to 0.995

z statistic 33.326Excellent

Significance level P (Area=0.5) <0.0001

a
Hanley & McNeil, 1982
b
Binomial exact
Youden index
 Youden index J 0.9195

Associated criterion >69.1098

Sensitivity 100.00

Specificity 91.95
Cut of point
Criterion values and coordinates of the ROC curve [Hide]

Criterion Sensitivit 95% CI Specificit 95% CI +LR 95% CI -LR 95% CI

y y

40.088 100.00 75.3 - 10 0.00 0.0 - 4.2 1.00 1.0 - 1.0

6 0.0

>40.088 100.00 75.3 - 10 2.30 0.3 - 8.1 1.02 1.0 - 1.1 0.00
6 0.0

>42.233 100.00 75.3 - 10 4.60 1.3 - 11.4 1.05 1.0 - 1.1 0.00
5 0.0

>43.934 100.00 75.3 - 10 6.90 2.6 - 14.4 1.07 1.0 - 1.1 0.00
2 0.0

>44.526 100.00 75.3 - 10 9.20 4.1 - 17.3 1.10 1.0 - 1.2 0.00
5 0.0

>45.340 100.00 75.3 - 10 11.49 5.7 - 20.1 1.13 1.0 - 1.2 0.00
3 0.0

>45.993 100.00 75.3 - 10 13.79 7.3 - 22.9 1.16 1.1 - 1.3 0.00
0.0

>46.543 100.00 75.3 - 10 16.09 9.1 - 25.5 1.19 1.1 - 1.3 0.00
8 0.0

>46.711 100.00 75.3 - 10 18.39 10.9 - 28. 1.23 1.1 - 1.4 0.00
3 0.0 1

>46.823 100.00 75.3 - 10 20.69 12.7 - 30. 1.26 1.1 - 1.4 0.00
2 0.0 7

>49.567 100.00 75.3 - 10 22.99 14.6 - 33. 1.30 1.2 - 1.5 0.00
2 0.0 2

>51.201 100.00 75.3 - 10 25.29 16.6 - 35. 1.34 1.2 - 1.5 0.00
7 0.0 7

>51.433 100.00 75.3 - 10 27.59 18.5 - 38. 1.38 1.2 - 1.6 0.00
4 0.0 2

>51.504 100.00 75.3 - 10 29.89 20.5 - 40. 1.43 1.2 - 1.6 0.00
2 0.0 6
>51.599 100.00 75.3 - 10 32.18 22.6 - 43. 1.47 1.3 - 1.7 0.00
2 0.0 1

>53.277 100.00 75.3 - 10 34.48 24.6 - 45. 1.53 1.3 - 1.8 0.00
9 0.0 4

>53.452 100.00 75.3 - 10 36.78 26.7 - 47. 1.58 1.3 - 1.9 0.00
5 0.0 8

>53.565 100.00 75.3 - 10 39.08 28.8 - 50. 1.64 1.4 - 1.9 0.00
0.0 1

>53.650 100.00 75.3 - 10 41.38 30.9 - 52. 1.71 1.4 - 2.0 0.00
1 0.0 4

>53.903 100.00 75.3 - 10 43.68 33.1 - 54. 1.78 1.5 - 2.1 0.00
7 0.0 7

>54.792 100.00 75.3 - 10 45.98 35.2 - 57. 1.85 1.5 - 2.2 0.00
3 0.0 0

>55.622 100.00 75.3 - 10 48.28 37.4 - 59. 1.93 1.6 - 2.4 0.00
2 0.0 2

>56.428 100.00 75.3 - 10 50.57 39.6 - 61. 2.02 1.6 - 2.5 0.00
2 0.0 5

>56.684 100.00 75.3 - 10 52.87 41.9 - 63. 2.12 1.7 - 2.7 0.00
6 0.0 7

>56.784 100.00 75.3 - 10 55.17 44.1 - 65. 2.23 1.8 - 2.8 0.00
9 0.0 9

>56.898 100.00 75.3 - 10 57.47 46.4 - 68. 2.35 1.8 - 3.0 0.00
9 0.0 0

>57.436 100.00 75.3 - 10 59.77 48.7 - 70. 2.49 1.9 - 3.2 0.00
1 0.0 1

>61.514 100.00 75.3 - 10 62.07 51.0 - 72. 2.64 2.0 - 3.4 0.00
2 0.0 3

>61.687 100.00 75.3 - 10 64.37 53.4 - 74. 2.81 2.1 - 3.7 0.00
0.0 4

>62.139 100.00 75.3 - 10 66.67 55.7 - 76. 3.00 2.2 - 4.0 0.00
2 0.0 4

>63.366 100.00 75.3 - 10 68.97 58.1 - 78. 3.22 2.4 - 4.4 0.00
5 0.0 5

>64.247 100.00 75.3 - 10 71.26 60.6 - 80. 3.48 2.5 - 4.8 0.00
2 0.0 5

>65.371 100.00 75.3 - 10 73.56 63.0 - 82. 3.78 2.7 - 5.4 0.00
7 0.0 4

>65.405 100.00 75.3 - 10 75.86 65.5 - 84. 4.14 2.9 - 6.0 0.00
0.0 4

>65.642 100.00 75.3 - 10 78.16 68.0 - 86. 4.58 3.1 - 6.8 0.00
4 0.0 3

>65.879 100.00 75.3 - 10 80.46 70.6 - 88. 5.12 3.3 - 7.8 0.00
0.0 2

>67.114 100.00 75.3 - 10 82.76 73.2 - 90. 5.80 3.7 - 9.2 0.00
1 0.0 0

>67.900 100.00 75.3 - 10 85.06 75.8 - 91. 6.69 4.1 - 11. 0.00
9 0.0 8 0

>68.421 100.00 75.3 - 10 87.36 78.5 - 93. 7.91 4.6 - 13. 0.00
9 0.0 5 7

>69.054 100.00 75.3 - 10 89.66 81.3 - 95. 9.67 5.2 - 17. 0.00
6 0.0 2 9

>69.109 100.00 75.3 - 10 91.95 84.1 - 96. 12.4 6.1 - 25. 0.00
8 0.0 7 3 3

>70.164 92.31 64.0 - 99. 93.10 85.6 - 97. 13.3 6.1 - 29. 0.08 0.01 - 0.
1 8 4 8 4 3 5

>72.903 76.92 46.2 - 95. 93.10 85.6 - 97. 11.1 4.9 - 25. 0.25 0.09 - 0.
8 0 4 5 5 7

>73.249 69.23 38.6 - 90. 94.25 87.1 - 98. 12.0 4.8 - 30. 0.33 0.1 - 0.7
5 9 1 5 4

>75.240 69.23 38.6 - 90. 96.55 90.3 - 99. 20.0 6.2 - 64. 0.32 0.1 - 0.7
7 9 3 8 7

>76.514 61.54 31.6 - 86. 97.70 91.9 - 99. 26.7 6.4 - 112 0.39 0.2 - 0.8
8 1 7 7 .5

>76.887 53.85 25.1 - 80. 98.85 93.8 - 10 46.8 6.3 - 350 0.47 0.3 - 0.8
2 8 0.0 5 .6

>77.457 38.46 13.9 - 68. 98.85 93.8 - 10 33.4 4.2 - 264 0.62 0.4 - 1.0
4 4 0.0 6 .2

>77.995 30.77 9.1 - 61.4 100.00 95.8 - 10 0.69 0.5 - 1.0

0.0

>78.361 15.38 1.9 - 45.4 100.00 95.8 - 10 0.85 0.7 - 1.1

9 0.0
 >78.675 0.00 0.0 - 24.7 100.00 95.8 - 10 1.00 1.0 - 1.0
1 0.0

Grup kreatinin kinase * Grup MCI Crosstabulation

Count
Grup MCI
Positif negatif Total
Grup kreatinin kinase Kreatini kinase > 69,1098 13 7 20
kreatinin kinase <= 69,1098 0 80 80
Total 13 87 100

Tables - 2-by-2 unstratified

10:54:15 AM, 5/23/2017

| + - | 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]