CRITICAL APPRAISAL EVIDENCE BASED MEDICINE

BLOCK 18 SCENARIO 4

CREATED BY:
2nd TUTORIAL GROUP

A Rizal Habibi 20160350016

Dita Sozianty 20160350017
Razmi Wulan Diastuti 20160350021
Muhammad Bimbo Al Islami 20160350029
Nuariska Laila Ramadhani 20160350031
Harena Anggun Lakshita 20160350056
Rifa Massufa Alifatuljannah 20160350066
Nopi Ariska 20160350069
Firly Amila Nazar 20160350074
Facheta Intan Pramana 20160350082
Nurafni Octaviani 20160350109

Pharmacy Departement
Faculty Of Medical and Health Science
Muhammadiyah University Of Yogyakarta
2019
 ACKNOWLEDGEMENT
In the Name of Allah, the most Gracious, the most Merciful.

All praises be to Allah, king of the king, the Lord of the world, and the master of the day
after, who has given us blessing and guidance. Because of His graciousness and mercifulness
the writer can write well plenary discussion title “REPORT OF PLENARY DISCUSSION
BLOCK 18 SCENARIO 4” . As the final report of block 17 scenario 2 has been given.
Sholawat and sallam may Allah send them to our Prophet Muhammad SAW, (peace be upon
him), his families, his companions, and his followers. The best messenger for people all over
the world. This world becomes peace because of his hard effort in giving the human being
advices.

The writter realize that this report is far from prefection. So, the writter apologize if there
are some mistakes. And also the writter hope that reader can give us some critical and advice.

On this opportunity, the writer herewith would like to express his profound gratitude, more
than he can express, to:

1. Allah SWT, Who has given us blessing and mercy.

2. Writters’ parents, who always pray, encouraging, giving love and compassion,giving.
3. Mrs. Indriastuti Cahyaningsih, M.Sc., Apt as tutor of 2rd Group .
4. Our beloved friends .
5. All person who helped us to write this report.

May Allah give rewarded for any help that given to us to those who have supported the
writters and may this paper be useful for us and the development of science. May Allah always
protect us. Aamiin

Yogyakarta, June 2019

Writters (All member of group 2 of tutorial)

 CONTENTS

TABLE OF CONTENT

Acknowledgement

Chapter I

A. Background
B. Object of study

Chapter II

A. SCENARIO
B. Analysis of Scenario
C. Seven Jumps
D. Clarifying Unfamiliar Terms
E. Problem Definition
F. Brainstorming
G. Analyzing Problem

Chapter III

A. Discussion
1. Conclusion
2. References
 CHAPTER I

INTRODUCTION

1.1 Background of Study

Research methodology block is the eighteenth block of Pharmacy School, Faculty of
Medicine and Health Science, Muhammadiyah University of Yogyakarta. In the
eighteenth block of plenary discussion scenario explain that students of pharmacy can
explain critical appraisal in the case of the scenario.
1.2 The Object of The Study
1. This report written as a report of scenario four of eighteenth block’ discussion so
that student can understand teoriticaly.
2. The writter be able to finish case that given in scenario with analysis methode and
learning with group discussion
3. Reach the achievement of the purpose of the tutorial learning methods.
 CHAPTER II

THE RESEARCH FINDING

H. SCENARIO

Y a newly graduated pharmacist has the opportunity to intern at a pharmacy X. on

the first day of the internship, a patient came with a prescription containing the drug
vidagliptin. The patient asked the pharmacist about the drug because it was different
from the usual medication metformin. Y pharmacists provide explanations based on
drug leaflets due to lack of knowledge about the drug. After the patient returns home,
the pharmacist tries to find articles related to the drug

I. Analysis of Scenario

In scenario 4 teaches us about find articles related to the drug and critical appraisal

J. Seven Jumps
2.J.1. Clarifying Unfamiliar Terms
-
2.J.2. Problem Definition
1. How to find articles well and good article categories
2. Definition, purpose and benefit of critical appraisal
3. Article level
4. Explanation of vildagliptin and metformin (groups and benefits) and the reason
vildagliptin is used only for type 2 diabetes mellitus
5. Evidence based medicine about the comparison of vildagliptin and metformin
2.J.3. Brainstorming
This should result in ideas to structure the problem. Each individual may express
his/her idea(s) free without immediate discussion: it is important not to discuss an not to
comment the idea(s) of others during this step,but to collect many idea(s) (prior
knowledge). Together, students will compile idea(s) of the underlying circumstances of
the problem (explanatory approach) and/or of implications arising from the problem
(Procedural approach).
2.J.4. Analyzing Problem
A. How to find articles well and good article categories
 To find the good articles you can use Start your Search on the Library
homepage to search across various book and article databases simultaneously. Many
article databases, however, aren’t included in that search tool. To find the best resources
for your topic, you might want to go directly to a specific database. Find a the best
database(s) for your research topic:
1. General article databases are a good place to start since they include both popular and
scholarly journal titles covering numerous disciplines. Simply choose one of those
databases and type in your keywords to begin to find articles.

2. Browse for databases by subject (such as Economics, Electrical Engineering, or Art

History) if you want to dig deeper into resources covering a specific discipline. If you
aren’t sure what subject to choose, look for the academic department that your class is
listed under. Once you’ve chosen a subject, search for your topic in one or two of the
recommended databases that are listed on the top of the subject list.

3. Browse for databases by type if you want to find other kinds of formats, such as
encyclopedias, newspapers, government information sources, statistics, maps, images
and more.

If you have an article citation:

The Citation Linker will look across various databases to find whether or not we have
access to the article online or in a journal on the library shelves. You need a journal title and
publication date to use the Citation linker. If you don’t have that information try Googling the
article title and author name. For knowing about the good articles check the following points

1. Where is the article published?

The journal (academic publication) where the article is published says something about
the quality of the article. Journals are ranked in the Journal Quality List (JQL). If the journal
you used is ranked at the top of your professional field in the JQL, then you can assume
that the quality of the article is high. So, if a journal is not listed in the Journal Quality
List then it is worthwhile to google it. You will then find out more about the quality of the
journal.

2. Who is the author?

The next step is to look at who the author of the article is:
  What do you know about the person who wrote the paper?

 Has the author done much research in this field?

 What do others say about the author?

 What is the author’s background?

 At which university does the author work? Does this university have a good
reputation?

3. What is the date of publication?

In which year is the article published? The more recent the research, the better. If the
research is a bit older, then it’s smart to check whether any follow-up research has taken
place. Maybe the author continued the research and more useful results have been
published.

If you’re searching for an article in Google Scholar, then click on ‘Since 2014’ in the
left hand column. If you can’t find anything (more) there, then select ‘Since 2013’. If you
work down the row in this manner, you will find the most recent studies.

4. What do other researchers say about the paper?

Find out who the experts are in this field of research. Do they support the research, or
are they critical of it?

5. Determine the quality

Now look back: how did the article score on the points mentioned above? Based
on that, you can determine quality.

B. Definition, Objectives, and Benefits of critical review

 critical appraisal is a process of evaluating and interpreting evidence systematically by
considering its validity, results, and relevance.
 The purpose of critical appraisal is to test the validity of the results and the relevance
of scientific evidence or research results before being used to make decisions.
 Benefits critical appraisal is :
 Determine the solution or clinical decision.
 Add knowledge about journal contents and add insight in conducting critical
journal appraisal.
C. Level of evidence based medicine
The evidence-based medical literature is usually represented graphically as being
arranged in a pyramid shape, the idea being that it is spread over several levels, with the
higher ones, towards the top of the pyramid, being equated with higher standards and thus,
implicitly, better quality evidence. In actual fact, this pyramid-shaped arrangement has
given rise to many misconceptions over the years, and has certainly helped to create a sort
of ranking not just of scientific output, but also of the producers of scientific research;
indeed, those whose work is supported by a higher level of evidence are considered to
occupy the higher echelons of the pyramid and thus to be good researchers, while those
whose work positions them at the base are considered mediocre ones.

 Information and expert opinion:

The first level of the Evidence-Based Pyramid is the foundation. This background
information is important and helpful. However, when viewed on its own, this type of
evidence can be heavily influenced by beliefs, opinions, or even politics. This level might
also include anecdotal evidence.

 Case control studies or case series reports

This level represents the first stage of testing an observation. Case Series reports usually
include only a few participants who are given a similar intervention and follow-up. Case
Control Studies are similar to case series, except it looks retrospectively at individuals and
compares with a similar group who did not have the intervention. These studies are
conducted in the early stages of research to help identify variables that might predict a
condition. One of the weaknesses in these designs is that there are small numbers of
participants and they are frequently not randomized or controlled for confounding
variables.

 Cohort studies

Also called longitudinal or epidemiological studies, Cohort studies follow a large group
of people over an extended period of time to see how their exposures affect their outcomes.
This type of study is normally used to look at the effect of suspected risk factors that cannot
be controlled experimentally – for example, the effect of smoking on lung cancer. These
studies are frequently used to determine long term effects of a lifestyle, diet, or other
interventions. Cohort studies may include a second group that did not engage in the same
intervention as a control comparison. Although these studies are a step up in reliability and
generalizability, they can be difficult to blind, can’t be controlled for outside variables, and
are usually not randomized.

 The Randomized Control Trial (RCT)

Now we have reached a major point in the Pyramid – the Randomized Control Trial,
the true experimental design. In this study design, individuals are assigned by special
randomization techniques into two or more groups, where one group receives the
intervention under investigation and the other(s) receives no treatment, a placebo, or a
standard intervention.

A large Double Blinded Randomized Control Trial is the most reliable “test” or study
design and provides the strongest support of a cause and effect relationship. However, these
studies are expensive and can be ethically problematic.

 Critically appraised topics

Critically appraised topics are not actually a study design. They are short summaries of
the best available evidence. Basically, these are an abbreviated systematic review created
to answer a specific question.
  The systematic reviews

Now we have finally arrived at the pinnacle of the Evidence-Based Medicine Pyramid.
From this dizzying height, we take in a panoramic view of all of the evidence about an
intervention. Systematic reviews take a bird’s eye view by comparing the results of studies
side by side, typically on a forest plot. Systematic reviews are considered the strongest and
highest quality of evidence.

We could also include meta-analysis here as well. This is where multiple studies are
reviewed and a statistical summary is made that represents the effect of the intervention
across multiple studies.The Cochrane Collaboration takes systematic reviews to the next
level. They are the experts of the systematic review and have an added a level of rigor as
an independent voice, as well as developing special techniques to identify bias in studies.

D. Explanation of vildagliptin and metformin (groups and benefits) and the reason
vildagliptin is used only for type 2 diabetes mellitus
 Metformin

Diabetes mellitus is a group of metabolic disorders in which the blood glucose is

higher than normal levels, due to insufficiency of insulin release or improper response
of cells to insulin, resulting in high blood pressure. The resultant hyperglycemia
produces the classical symptoms of polyuria, polydipsia and polyphagia. It may also
cause nerve problems, kidney problems, and blindness, loss of limbs, and sexual
dysfunction, increase in heart attack or stroke.

Metformin (a biguanide derivative), by controlling blood glucose level decreases

these complications. Metformin works by helping to restore the body's response to
insulin. It decreases the amount of blood sugar that the liver produces and that the
intestines or stomach absorb. Metformin, other than hypoglycemic activity, has been
taken with diet and exercise changes to prevent diabetes in people who are at high risk
for becoming diabetic. It is also used in women with polycystic ovarian syndrome.
Metformin may make menstrual cycles more regular and increase fertility.

Metformin is primarily used for the treatment of type 2 diabetes mellitus,

particularly in obese patients. Metformin has been shown to reduce diabetes mortality
and complications by thirty percent compared to insulin, glibenclamide and
chlorpropamide.
 Metformin reduces serum glucose level by several different mechanisms, notably
through nonpancreatic mechanisms without increasing insulin secretion. It increases
the effects of insulin; hence, it is termed “insulin sensitizer”. Metformin also suppresses
the endogenous glucose production by the liver, which is mainly due to a reduction in
the rate of gluconeogenesis and a small effect on glycogenolysis. Moreover, metformin
activates the enzyme adenosine monophosphate kinase (AMPK) resulting in the
inhibition of key enzymes involved in gluconeogenesis and glycogen synthesis in the
liver while stimulating insulin signaling and glucose transport in muscles. AMPK
regulates the cellular and organ metabolism and any decrease in hepatic energy, leads
to the activation of AMPK.

Furthermore, metformin increases the peripheral glucose disposal that arises largely
through increased non-oxidative glucose disposal into skeletal muscle. It usually does
not cause hypoglycemia and this cause to be considered as a unique anti-diabetic drug.

Metformin was first synthesized and found to decrease the blood glucose level in
the 1920s; however, it was not used for a long time. The use of metformin was rekindled
in 1957, when the results of a clinical trial were published confirming its effect on
diabetes. Metformin is now widely prescribed as an anti-diabetic drug; however, there
have been serious concerns about its adverse effects, especially ketoacidosis. Recently,
not only some implications have been discovered for metformin, but also there are
reports indicating that its adverse effects are negligible when its benefits are brought
into account. Theoretically, its use has been prohibited in a large group of patients with
type 2 diabetes mellitus due to the risk of lactic acidosis. However, it has been shown
that several diabetic patients who are considered to be at risk have received metformin
with no increased risk of lactic acidosis.

 DP4 Inhibitor

Vildagliptin is the antihiperglicemic/antidiaberic oral from DPP -4 inhibitors group.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, which have been widely used as outstanding
blood glucose-dependent antidiabetic agents for patients with type 2 diabetes mellitus
(T2DM), show promise. These inhibitors prevent the degrada-tion of incretin
(glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide
(GIP)) bydipeptidyl peptidase-4 enzymes and therefore elevate endogenous GLP-1
levels. GLP-1 stimulates insulin secretion from β-cells in a glucose-dependent manner,
suppresses glucagon secretion from α-cells, and inhibits hepatic glucose production,
eventually contributing to the antihyperglycemic effect. In addition, DPP-4 inhibitors
preserve the β-cell mass. There is a systematic review and Meta - Analysis which says
that DPP-4 inhibitors in (T2DM) :

From that systematic review and meta-analysis we can conclude that DPP-4
inhibitors may be beneficial for T1DM, existing studies do not strongly support these
positive effects in clinical practice. Further optimized clinical trials are needed.

 Mechanisms Action of the Dipeptidyl Deptidase-4 (DPP-4) Inhibitor

Vildagliptin in Humans

The DPP-4 inhibitor vildagliptin blocks the inactivation of GLP-1 and GIP resulting
in sustained elevations in plasma levels of intact GLP-1 and GIP. GIP and GLP-1
represent the physiologically important incretins in humans. The finding that GLP-1
rendered glucose-insensitive β-cells glucose competent made it an attractive therapeutic
target. However, the peptidic nature of GLP-1 together with its very short plasma half-
life was hurdles that needed to be overcome in order to make use of the potential
therapeutic effects of GLP-1. Both GLP-1 and GIP are rapidly degraded in plasma, with
half-lives of 2–5 min and 7–9 min, respectively. When DPP-4 was identified as the
enzyme responsible for the degradation and inactivation of both GLP-1 and GIP, the
possibility of creating an orally available inhibitor of DPP-4 became a realistic
approach to leveraging the increasingly apparent therapeutic utility of the incretin
hormones.

Vildagliptin improves the sensitivity of both the α- and β-cells to glucose leading
to improved glucose tolerance. These effects largely explain the improved A1c levels
without increased hypoglycaemia associated with chronic treatment. In addition to the
improved insulin sensitivity associated with improved glycaemia, there is improved
insulin sensitivity due to reduced glucagon during meals. Furthermore, with vildagliptin
there is reduced lipotoxicity, secondary to reduced fasting lipolysis, which may be
mediated via increased fasting intact incretin hormone levels. The glucose-sensitive
regulation of the endocrine pancreas by DPP-4 inhibitors presumably attenuates the
defensive eatinginduced weight gain associated with SU therapy. Vildagliptin reduces
apo B-48 production and thus presumably fat extraction from the gut and mobilizes and
burns fat during meals. Vildagliptin’s effect to protect against hypoglycaemia appears
to be mediated by the enhanced glucagon response to hypoglycaemia. Overall, the
favourable profile of vildagliptin is due to both pancreatic and extrapancreatic effects
of GLP-1 and GIP.
Figure 1. (A) Covalent interaction between vildagliptin and the active site of DPP-4 enzyme
(Ser630 of DPP-4). (B) Schematic depiction of enzyme (DPP-4) interaction with competitive
inhibitor, natural substrate (GLP-1) or substrate-blocker (covalent modifier of enzyme
activity).

E. Evidence based medicine about the comparison of vildagliptin and metformin

This is article explains about the using comparison between vildagliptin and metformin
to patients with type 2 diabetes.
 The method used in this study is Randomized Control Trial. Randomized Control Trial are
types of epidemiological research in which subjects from a population are randomly grouped
into groups commonly referred to as study groups and control groups. This type of research is
commonly used for the effectiveness of a drug.

Conclusion from this article Vildagliptin is an effective and well-tolerated treatment option
in elderly patients with type 2 diabetes, demonstrating similar improvement in glycaemic
control as metformin, with superior GI tolerability.
 CHAPTER III
CONCLUSION AND REFERENCES

1.1 Conclusion

1.2 Refernce

Nasri H , Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci.

2014 Jul; 19(7): 658–664. [NCBI]

Akobeng AK. Principles of evidence based medicine. Arch Dis Child

2005;90:837-40.

Ahren, B. et al. (2011) ‘Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin

in Man’, Diabetes Obes.Metab., %20. doi:, pp. 10–1326. doi: 10.1111/j.1463-
1326.2011.01414.x.