IN THE NAME OF ALLAH, THE MOST GRACIOUS, THE MOST …vrgs.ju.edu.sa/files_jen/AUMJ-2-4-2015.pdf · Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4) Content Pages Description

IN THE NAME OF ALLAH, THE MOST GRACIOUS, THE MOST MERCIFUL

AUMJ Editorial Board and Description

Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4): i - ii.

2015

AUMJ EDITORIAL BOARD AND DESCRIPTION

EDITORIAL BOARD

AUMJ Editor-in-Chief

Prof. Dr. Saleh Abdul Allah Al-Damegh, Professor of Radiology, General Supervisor for

Unaizah Colleges New campus at Qassim University,

Founding Dean of Unaizah College of Medicine and

Applied Medical Sciences, Qassim University, Qassim,

Saudi Arabia.

AUMJ Associate Editor-In-Chief

Prof. Dr. Tarek Hassan El-Metwally, Professor of Medical Biochemistry and Molecular

Biology & Consultant Clinical Biochemist,

Biochemistry Division, Department of Pathology,

CME Coordinator, College of Medicine, Aljouf

University, Sakaka, Saudi Arabia.

AUMJ DEVELOPMENT HISTORY

Aljouf University Medical Journal (AUMJ) was

established under the generous patronage of his esteem

Prof. Dr. Ismail M. Al-Beshry, the Rector

of Aljouf University, as an initiative of his esteem

Prof. Dr Najm M. AL-Hosainy, The vice-

Rector of Aljouf University for Graduate Studies and

Scientific Research as the General Supervisor of the

Journal. The inaugural issue of AUMJ first appeared

September 1, 2014 with Prof. Dr. Saleh A. Al-

Damegh, Founding Dean of Unaizah College of

Medicine and Applied Medical Sciences and General

Supervisor for Unaizah Colleges New campus at

Qassim University, Qassim University, Qassim, Saudi

Arabia, as the Founding Editor-In-Chief.

AUMJ Editors

Prof. Dr. Parviz M Pour, Professor of Pathology,

Department of Pathology and Molecular Biology,

UNMC, NE, USA.

Prof. Dr. Ibrahim M. El-Bagory, Professor

Pharmaceutical Technology, Department of

Pharmaceutics, College of Pharmacy, Aljouf

University, Sakaka, Saudi Arabia.

Dr. Adel A. Maklad, Associate Professor,

Department of Neurobiology & Anatomical Sciences,

University of Mississippi Medical Center, MS, USA.

AUMJ DESCRIPTION AND SCOPE

AUMJ (pISSN: 1658-6700) is an online Open-Access

and printed General Medical Multidisciplinary Peer-

Reviewed International Journal that is published

quarterly (every 3 months; March, June, September and

December) by the Deanship for Graduate Studies and

Scientific Research as the official medical journal of

Aljouf University, Sakaka, Saudi Arabia

(http://vrgs.ju.edu.sa/jer.aspx). AUMJ full text articles

and their serial code Digital Object Identifier (DOI)

address number (according to the International DOI

Foundation) are accessible online through searching

Journals for Aljouf University Medical Journal at Al

Manhal Platform

(http://www.almanhal.com/Collections/JournalList.asp

x?type=45). The DOI of AUMJ is 10.12816. AUMJ

welcomes and publishes innovative original

manuscripts encompassing all Basic Biomedical and

Clinical Medical Sciences, Allied Health Sciences -

Dentistry, Pharmacy, Nursing and Applied Medical

Sciences, and biological researches interested in basic

and experimental medical investigations. Such research

includes both academic researches (basic and

translational) and community-based practice

researches.

AUMJ AUDIENCE

Physicians, Clinical Chemists, Microbiologists,

Pathologists, Hematologists, and Immunologists,

Medical Molecular Biologists and Geneticists,

Professional Health Specialists and Policymakers,

Researchers in the Basic Biomedical, Clinical and

Allied Health Sciences, Biological Researchers

interested in Experimental Medical Investigations,

educators, and interested members of the public around

the world.

AUMJ MISSION

AUMJ is dedicated to expanding, increasing the depth,

and spreading of updated internationally competent

peer reviewed genuine and significant medical

knowledge among the journal target audience all over

the world.

AUMJ VISION

To establish AUMJ as an internationally competent

journal within the international medical databases in

publishing peer reviewed research and editorial

manuscripts in medical sciences.

AUMJ OBJECTIVES

1. To evolve AUMJ as a reliable academic reference

within the international databases for researchers

and professionals in the medical arena.

2. Providing processing and publication fee-free

open-access vehicle for publishing genuine and

significant research and editorial manuscripts for

local, regional, and international researchers and

professionals in medical sciences, along with as

AUMJ Editorial Board and Description

Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4): i - ii.

2015

being a means of education and academic

leadership.

3. Expanding, increasing the depth, and spreading of

internationally competent and updated medical

knowledge among the AUMJ target audiences for

the benefit of advancing the medical service to the

local and international communities.

4. Although insuring integrity and declaration of any

conflict of interest, AUMJ is adopting an

unbiased, fast, and comprehensively constructive

one-month peer review cycle from date of

submission to notification of final acceptance.

PUBLICATION FEE & SCHEDULE

AUMJ is processing and publication fee-free as a

strategy of Aljouf University in support of

investigators worldwide. However, subscription to the

journal and reprint (black and white or color) requests

are placed through Deanship of Library Affairs at

Aljouf University. AUMJ is a bimonthly journal.

Average processing time is 2 month; one month from

receipt to issuing the acceptance letter and one month

for providing the paginated final PDF file of the

manuscript. Abstracts and PDF formatted articles are

available to all Online Guests free of charge for all

countries of the world.

EDITORIAL OFFICE & COMMUNICATION

Aljouf University Medical Journal (AUMJ)

Aljouf University, POB: 2014

Sakaka, 42421, Aljouf, Saudi Arabia

Email: [email protected]

Tel: 00966146252271

Fax:00966146247183

SUBSCRIPTION & EXCHANGE

Deanship of Library Affairs

Aljouf University, POB: 2014

Sakaka, 42421, Aljouf, Saudi Arabia

Email: [email protected]

Tel: 00966146242271

Fax: 00966146247183

Price and Shipping Costs of One Issue is 25 SR within

KSA/25 US$ Abroad.

mailto:[email protected]

AUMJ: Table of Contents

Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4): iii.

2015

Table of Contents

Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4)

Content Pages

Description of AUMJ. i-ii

Table of Contents. iii

Comprehensive Instructions for Authors and Reviewers. iv - xvi

Original Articles:

Plasma Prolactin Level in Type 2 Diabetic Patients with and without Retinopathy. Medhat AbdelMoneim, Ahmed Abd-Eltawab, Gomaa Mostafa-

Hedeab, Khaled A. Zaki, Alaa A. Mohamed, Abdulrahman A. Alduraywish, Mahrous A. Ibrahim.

1 - 6

Life Satisfaction with Sleep, Caffeinated Drinks and Physical Exercise among Qassim Medical Students. Fawzy Sharaf.

7 - 16

Determinants of Smoking Cessation-Counseling Practices among Primary Health Care Physicians in Riyadh Military Hospital Kingdom of Saudi Arabia with Special Reference to Their Smoking Status. Nawaf Al-

Shammari.

17 - 26

Spironolactone in Refractory Hypertension: A Retrospective Cross-Sectional Patients' Records-Based Study. Nasser Alotaibi.

27 - 40

Case Report:

Management of Post-Circumcision in Glanzmann`s Thrombasthenia: Case Report and Review of Literatures. Mohammed J. Alenzi, Ahmad N. M.

Shehadeh, Mosaad S. Alruwaily, Bader S. Alwaladali, Fayez S. Alenazi, Eid A.

Aljabbari.

41- 46

AUMJ: Table of Contents

Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4): iii.

2015

AUMJ Comprehensive Instructions For Authors and Reviewers

Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4): v - xviii.

2015

AUMJ Comprehensive Instructions for Authors and Reviewers

INTRODUCTION

Types of submission and criteria

Original Research Communications may be offered as

Full Papers, as Short Communications or as Short

research Paper. The latter format is recommended for

presenting technical evaluations and short clinical

notes, comprising up to 1,500 words of text, 15

references, and two illustrative items (Tables and/or

Figures).

Clinical Trials and Case Reports will be accepted only

where they provide novel insight into disease

mechanisms, management, or diagnostic applications.

Reviews and Minireviews will be welcome but

prospective authors are strongly advised to seek

authorization from the Editor-in-Chief to avoid

conflict with scheduled reviews invited by the

Editorial Board. They should address new topics or

trends in basic biomedical, clinical, and allied health

sciences – Dentistry, Pharmacy, Nursing and Applied

Medical Sciences.

Policy Papers, Study Protocols and Pre-Protocols and

Method Articles.

Medical educational articles, Commentaries (on the

clinical, scientific, social, political, and economic

factors affecting health), Opinion, Meeting Summary

and Book review articles. Please contact the Editor-in-

Chief for consideration.

BEFORE YOU BEGIN

THE JOURNAL PLAGIARISM POLICY

AUMJ employs software for

plagiarism screening to verify the originality of

content submitted before reviewing. We strongly

oppose the practice of duplicate publication or any

type of plagiarism. Plagiarized manuscripts would not

be considered for publication. If plagiarism is found in

any published paper after internal investigation, a

letter would be immediately sent to all the authors,

their affiliated institutes and funding agency, if

applicable and subsequently the paper will be

retracted.

AUMJ Editorial Board trusts that authors understand

why the Journal's integrity must be protected through

preventing plagiarism. The manuscript must be free

from plagiarism according to our iThenticate®

plagiarism detection software - defined as ≤1%

similarity or "Text overlap" from any source including

your published works (self-plagiarism). iThenticate®

checks for plagiarism from world-wide databases,

including internet web sites. Even less than that rate in

the results section - case-dependently - may not be

accepted. Manuscripts with the minor plagiarism

scientific misconduct of ≥2% similarity rate per source

with multiple references will not be processed for

publication till corrected.

On initial submission, the manuscript will be tested for

similarity with iThenticate®. The iThenticate

® report

of your manuscript is color-coded such that each

"source" has a unique color that is used for each

instance of copied text (words, sentences, paragraphs)

from the source. We limit the iThenticate® software

check to Abstract, Introduction, Results, Discussion,

Table Titles and contents and Figure contents and

legends, and, it excludes Title page (including authors

names, communication and affiliations), Methods

section, Acknowledgment section, and Literature Cited

section - since similarities in these sections is expected

to be high. However, how high the accepted similarity

rates in those sections is case-dependent and should be

as low as possible.

AUMJ encourages authors to use the Similarity Report

to write original text for the words, phrases, sentences

and/or paragraphs that have similarity of ≥2% with the

identified source published works. We understand the

importance of keeping specific key words and phrases

(molecules, models, drugs, species, equipment, assay

technique, etc). In cases with similarity of ≥2%, the

author(s) will have One of Two Options; either

withdraw the submission, or, resubmit the manuscript

after removing the indicated plagiarism so as to have

≤1% similarity rate per source as determined by

iThenticate®.

Plagiarism policy of this journal is mainly inspired

from the plagiarism policy of The Nature

(http://www.nature.com/authors/policies/plagiarism.ht

ml) and is summarized as described below:

1. Plagiarism is when an author attempts to pass off

someone else's work as his or her own. This

journal also adopted IEEE definition of plagiarism

to deal such cases. It defines plagiarism as "the

reuse of someone else’s prior ideas, processes,

results, or words without explicitly

acknowledging the original author and source.”

2. Plagiarism can be said to have clearly occurred

when large chunks of text have been cut-and-

pasted. Such manuscripts would not be considered

for publication in the journal. Papers with

confirmed plagiarisms are rejected immediately.



2015

3. But minor plagiarism without dishonest intent is

relatively frequent, for example, when an author

reuses parts of an introduction from an earlier

paper.

4. Duplicate publication, sometimes called self-

plagiarism, occurs when an author reuses

substantial parts of his or her own published work

without providing the appropriate references. This

can range from getting an identical paper

published in multiple journals, to 'salami-slicing',

where authors add small amounts of new data to a

previous paper. Self-plagiarism, also referred to as

‘text recycling’, is a topical issue and is currently

generating much discussion among editors.

Opinions are divided as to how much text overlap

with an author’s own previous publications is

acceptable. We normally follow the guidelines

given in COPE website. Editors, reviewers and

authors are also requested to strictly follow this

excellent guideline (Reference: Text Recycling

Guidelines: http://publicationethics.org/text-

recycling-guidelines).

5. In case of “suspected minor plagiarism”, authors

are contacted for clarification. Depending on all

these reports, reviewers and editors decide final

fate of the manuscript.

6. Use of automated software is helpful to detect the

'copy-paste' problem. All submitted manuscripts

are checked by the help of different databases,

eTBLAST, Plagiarism Detection tools, etc. At the

same time scientific implication of the case

('suspected minor plagiarism'), also judged by

reviewers and editors. Plagiarism Detection tools

are useful, but they should to be used in tandem

with human judgment and discretion for the final

conclusion. Therefore, suspected cases of

plagiarisms are judged by editors on 'case-to-case

basis'.

7. Editors have the final decision power for these

cases.

Ethics in publishing

Policy and ethics

The work described in your article must have been

carried out in accordance with The Code of Ethics of

the World Medical Association (Declaration of

Helsinki) for experiments involving humans

(http://www.wma.net); Uniform Requirements for

manuscripts submitted to Biomedical journals

(http://www.icmje.org) published by the International

Committee of Medical Journal Editors. An official

local authorized body should review the research

project before its beginning and a document

acknowledging the ethical clearance of the research

could be requested from prospective authors. This

must be stated at an appropriate point in the article

(Material and Methods). Research papers based on

animal studies should get a similar ethical clearance

from an official committee for the animal welfare.

Cover letter

A cover letter is required to accompany the manuscript

submission along with the Manuscript

Submission/Copyright Transfer Form. It should

include information about the following points

relevant to the specific type of your article:

Why should AUMJ publish your manuscript?

Relevance to AUMJ publication policy.

Potential competing interests.

Approval of the manuscript by all authors.

Adherence to Simultaneous and Duplicate

Publication Policy.

Conflict of interest

All authors are requested to disclose any actual or

potential conflict of interest including any financial,

supplements, personal or other relationships with other

people or organizations within three years of

beginning the submitted work that could

inappropriately influence, or be perceived to influence,

their work.

Submission declaration and verification

Submission of an article implies that the work

described has not been published previously (except in

the form of an abstract or as part of a published lecture

or academic thesis or as an electronic preprint), that it

is not under consideration for publication elsewhere,

that its publication is approved by all authors and by

the responsible authorities where the work was carried

out, and that, if accepted, it will not be published

elsewhere in the same form, in English or in any other

language, including electronically without the written

consent of the copyright-holder. To verify originality,

your article may be checked by an appropriate

originality detection service.

Authorship

All authors should have made substantial contributions

to all of the following: (1) the conception and design

of the study, or acquisition of data, or analysis and

interpretation of data, (2) drafting the article or

revising it critically for important intellectual content,

(3) final approval of the version to be submitted.

Changes to authorship

This policy concerns the addition, deletion, or

rearrangement of author names in the authorship of

accepted manuscripts before the accepted manuscript

is published in an online and/or printed issue.

http://www.wma.net/

http://www.icmje.org/



2015

Requests to add or remove an author, or to

rearrange the author names, must be sent to the

Journal Manager from the corresponding author

of the accepted manuscript and must include: (a)

the reason the name should be added or removed,

or the author names rearranged and (b) written

confirmation (e-mail, fax, letter) from all authors

that they agree with the addition, removal or

rearrangement.

In the case of addition or removal of authors, this

includes confirmation from the author being

added or removed.

Requests that are not sent by the corresponding

author will be forwarded by the Journal Manager

to the corresponding author, who must follow the

procedure as described above.

Journal Deputy Editor will inform the Journal

Editor-in-Chief of any such requests and

publication of the accepted manuscript in an

online issue is suspended until authorship has

been agreed.

After the accepted manuscript is published in an

online and/or printed issue: Any requests to add,

delete, or rearrange author names in an article

published in an online issue will follow the same

policies as noted above and result in a

corrigendum.

Role of the funding source

You are requested to identify who provided financial

support for the conduct of the research and/or

preparation of the article and to briefly describe the

role of the sponsor(s), if any, in study design; in the

collection, analysis and interpretation of data; in the

writing of the report; and in the decision to submit the

article for publication. If the funding source(s) had no

such involvement then this should be stated.

Open access

Once AUMJ is launched as an open access journal,

articles are freely available to both subscribers and the

wider public with permitted reuse. No Open Access

publication fee. All articles published Open Access

will be immediately and permanently free for everyone

to read, download, distribute and copy the article, and

to include in a collective work (such as an anthology),

as long as they credit the author(s) and provided they

do not alter or modify the article.

The processing and publication fee

No processing or publication fee is required.

Language (usage and editing services)

Please write your text in good English (American or

British usage is accepted, but not a mixture of these).

Authors who feel their English language manuscript

may require editing to eliminate possible grammatical

or spelling errors and to conform to correct scientific

English may wish to use any English Language

Editing service available. The abstract content will be

translated into Arabic to accompany the published

manuscript as an Arabic Abstract. In case the author's

mother language is not Arabic, the Journal will help

preparing it.

Submission

Manuscript submission and follow up to this journal

proceeds totally online through email communications

([email protected]). Complete manuscript with tables

and figures inserted within the text at their final place

should be submitted as a single file in the two; word

and PDF formats. The submission and copyright

transfer form is available on request and is mandatory

to hand fill, sign and date by all authors before any

processing of the submitted material. The form is

provided at the last page of every issue of AUMJ.

Authors are encouraged to print and fill the form and

submit alongside with the manuscript.

Referees

A minimum of six suitable potential reviewers (please

provide their name, email addresses, title, institutional

affiliation, and, ORCID or Scopus ID). When

compiling this list of potential reviewers please

consider the following important criteria: They must

be knowledgeable about the manuscript subject area;

must not be from your own institution; at least two of

the suggested reviewers should be from another

country than the authors'; and they should not have

recent (less than four years) joint publications with any

of the authors. However, the final choice of reviewers

is at the editors' discretion. Excluding peer reviewers:

During submission you may enter details of anyone

who you would prefer not to review your manuscript.

Types of submission and criteria

Original Research Communications may be offered as

Full Papers or as Short Communications. The latter

format is recommended for presenting technical

evaluations and short clinical notes, comprising up to

1,500 words of text, 15 references, and two illustrative

items (Tables and/or Figures).

Case Reports will be accepted only where they

provide novel insight into disease mechanisms,

diagnostic, and management applications.

Critical Reviews will be welcome but prospective

authors are strongly advised to seek authorization from

the Editor-in-Chief to avoid conflict with scheduled

reviews invited by the Editorial Board. They should



2015

address new topics or trends in fields of the Journal

Scope.

Editorial and opinion pieces Please contact the Editor-

in-Chief for consideration.

PREPARATION

NEW SUBMISSIONS

Submit your manuscript as a single PDF file and a

single Word document file, in any format or layout

that can be used by referees to evaluate your

manuscript. It should contain high enough quality

figures for refereeing.

References

There are no strict requirements on reference

formatting at submission. References can be in any

style or format as long as the style is consistent. Where

applicable, author(s) name(s), chapter title/article title,

journal title/book title, year of publication, volume

number-issue number/book chapter and the pagination

must be present. Use of DOI is highly encouraged. The

reference style used by the journal will be applied to

the accepted article at the proof stage. Note that

missing data will be highlighted at proof stage for the

author to correct.

Formatting requirements

On initial submission, there are no strict formatting

requirements but all manuscripts must contain the

essential elements needed to convey your manuscript

message; Title, Abstract, Keywords, Introduction,

Materials/Patients and Methods, Results with Artwork,

Figures and Tables with legends and titles (below the

figure and on top of the table, respectively),

Discussion, Limitations of the study and Future

directions, Gain of Knowledge, Conclusions, Conflict

of Interest, Acknowledgement (if any), and

References. Upon final acceptance, the author(s) will

be instructed to reformat their manuscript according to

AUMJ format detailed below.

If your article includes any Videos and/or other

Supplementary material, this should be included in

your initial submission for peer review purposes.

Divide the article into clearly defined sections with

title, subtitles and sub-subtitles on separate lines

whenever applicable.

Figures and tables embedded in text. Please ensure the

figures and the tables included in the single file are

placed next to the relevant text in the manuscript.

All standard and non-standard abbreviations should be

define in full at the fist mention in the text and should

be consistent throughout the paper.

In the initial submission, it is advisable to have

references in names (e.g., Smith et al, 2014) within the

text rather than numbering them. Revision and

correction frequently necessitate dropping or inserting

text with their references. Numbering references in

that stage will create the problem of renumbering them

is the text and list.

ORIGINAL RESEARCH PAPER WRITING TEMPLATE

Papers that include original empirical data that have

not been published anywhere earlier or is not under

consideration for publication elsewhere (except as an

abstract, conference presentation, or as part of a

published lecture or academic thesis), and after

accepted for publication it will not be submitted for

publication anywhere else, in English. Null/negative

findings and replication/refutation findings are also

welcome. If a submitted study replicates or is very

similar to previous work; authors must provide a

sound scientific rationale for the submitted work and

clearly reference and discuss the existing literature.

Submissions that replicate or are derivative of existing

work will likely be rejected if authors do not provide

adequate justification. Studies, which are carried out to

reconfirm/replicate the results of any previously

published paper on new samples/subjects (particularly

with different environmental and/or ethnic and genetic

background) that produces new data-set, may be

considered for publication. But these types of studies

should have a ‘clear declaration’ of this matter. The

English language in submitted articles must be clear,

correct, and unambiguous.

Title page information

Page 1 of the typescript should be reserved for the

title, authors and their affiliation and addresses.

Title. Concise, informative and reflects the study

content. Titles are often used in information-retrieval

systems. Avoid abbreviations and formulae where

possible.

Author names and affiliations. Where the family name

may be ambiguous (e.g., a double name), please

indicate this clearly. Present the authors' affiliation

addresses (where the actual work was done) below the

names. Indicate all affiliations with a superscript

Arabic number immediately after the author's name

and in front of the appropriate address. Provide the full

postal address of each affiliation, including the country

name and the e-mail address and phone number (with

country and area code) of each author.

Corresponding author. The corresponding author

should be indicated in addition with a superscript

asterisk * immediately after his/her affiliation



2015

superscript Arabic number. The corresponding author

will handle correspondence at all stages of refereeing,

publication, and post-publication. Contact details must

be kept up to date by the corresponding author.

Present/permanent address. If an author has moved

since the work described in the article was done, or

was visiting at the time, a 'Present address' (or

'Permanent address') may be indicated as a footnote to

that author's name. The address at which the author

actually did the work must be retained as the main,

affiliation address. Superscript lower-case letters are

used for such footnotes.

Abstract

Page 2 of the typescript should be reserved for the

abstract which should be presented in a structured

format and should not exceed 300 words. The

following headings should be included for research

articles followed by a colon: a) Background, b)

Hypothesis/Objectives: c) Materials/Patients and

Methods: d) Results: e) Conclusions (should be data

justified). Suitable headings could be used for other

types of publications (Case reports, Review articles,

etc).

A concise and factual abstract is required. The abstract

should state briefly the purpose of the research, the

principal results and major conclusions. An abstract is

often presented separately from the article, so it must

be able to stand alone. For this reason, References

should be avoided. Non-standard or uncommon

abbreviations should be avoided, but if essential they

must be defined at their first mention in the abstract

itself.

Keywords

Immediately after the abstract, provide a maximum of

10 keywords for full papers, or 5 keywords for Short

Communications, using American spelling and

avoiding general and plural terms and multiple

concepts (avoid, for example, "and", "of"). Please use

terms from the most current issue of medical subject

headings of Index Medicus. The key words should

cover precisely the contents of the submitted paper and

should give readers sufficient information as to the

relevance of the paper to his/her particular field. Be

sparing with abbreviations: only abbreviations firmly

established in the field may be eligible. These

keywords will be used for indexing purposes.

Introduction

Provide adequate background that highlights the

importance and gap information of your research point

in relation to previous studies, but avoiding a detailed

literature survey. State the hypothesis or rationale and

objectives of the work and a brief description of how

you planned to approach them.

Materials or Patients and Methods

Provide sufficient detail to allow the work to be

reproduced, with details of supplier and catalogue

number when appropriate. Methods already published

should be indicated by a reference: only relevant

modifications should be described.

Patients and Normal Subjects

If human participants were used in the experiment

please make a statement to the effect that this study

has been approved by your Institution Ethics Review

Board for human studies, and, that patients or their

custodians have signed an informed consent that also

states right of withdrawal without any consequences.

Sample sized should be appropriately calculated. The

manuscript should describe how the size of the

experiment was planned. If a sample size calculation

was performed this should be reported in detail,

including the expected difference between groups, the

expected variance, the planned analysis method, the

desired statistical power and the sample size thus

calculated. For parametric data, variance should be

reported as 95% confidence limits or standard

deviations rather than as the standard error of the

mean. Normal participants and patients criteria,

inclusion and exclusion criteria should be stated.

Name and address where the work was done and when

it was done (time period, from …. to …..) should be

clearly stated, too.

Experimental animals

When animals were used in the experiments, a local

Institutional Ethics Review Board for animal studies

should review and approve the experiment and that all

animal procedures were in accordance with the

standards set forth in guidelines for the care and use of

experimental animals by Committee for Purpose of

Supervision of Experiments on Animals (CPCSEA)

and according to National Institute of Health (NIH)

protocol. The precise species, strain, substrain and

source of animals used should be stated. Where

applicable (for instance in studies with genetically

modified animals) the generation should also be given,

as well as the details of the wild-type control group

(for instance littermate, back cross etc). The

manuscript should describe the method by which

animals were allocated (randomized) to experimental

groups, particularly for comparisons between groups

of genetically modified animals (transgenic, knockout

etc), the method of allocation to for instance sham

operation or focal ischemia should be described.



2015

Experimental

Provide sufficient detail to allow the work to be

reproduced. Methods already published should be

indicated by a reference: only relevant modifications

should be described. Where and when the study was

conducted should be stated.

Results

Results should be clear and concise. Data should be

presented in an appropriately organized tables, figures

and/or artworks. The statistical analysis used should be

suitable for the objectives of the study and type of data

analyzed. Prospective authors are highly advised to

consult a biostatician.

Footnotes

Footnotes should be used sparingly. For table

footnotes, indicate each footnote in a table with a

superscript lowercase letter or add them into the title.

Graphical abstract

A Graphical abstract is optional and should summarize

the contents of the article in a concise, pictorial form

designed to capture the attention of a wide readership

online. Authors must provide images that clearly

represent the work described in the article. Please

provide an image with a minimum of 531 × 1328

pixels (h × w) or proportionally more. The image

should be readable at a size of 5 × 13 cm using a

regular screen resolution of 96 dpi. It is preferable to

be inserted at its normal place to the relevant text or

otherwise be submitted as a separate TIFF, EPS, PDF

or MS Office files.

Discussion

This should explore the significance, interpretation and

reasoning of the results of the work vs. other studies.

Do not repeat describing the results in this section. A

combined Results and Discussion section is

acceptable. Avoid extensive citations and discussion of

published literature. In the same time, avoid

speculations without a supporting literature. Avoid

discussion based on "Data not Shown" or "Personal

Communications".

Limitations and Future Prospective

The authors may wish to pinpoint the limitations of the

study and their reason and foresee the next step to go

from their study. This may be presented in a short

Limitations and Future Prospective section standing

alone or as a separate paragraph in the Discussion or

Results/Discussion section.

Conclusions

The main conclusions of the study may be presented in

a short Conclusions section standing alone or as a

separate paragraph at the end of the Discussion or

Results/Discussion section. Conclusions should not be

biased and should be based on the data, presented and

discussed inside the manuscript only.

Gain of Knowledge

Following the conclusion section, it is mandatory for

manuscripts submitted for final publication in AUMJ

to have a Gain of Knowledge section that is consisted

of 2 - 5 bullet points (maximum 90 characters,

including spaces, per bullet point) that convey the core

findings of the article.

Acknowledgements

Collate acknowledgements in a separate section at the

end of the article before the references. List

individuals or organizations that provided help during

the research (e.g., providing language help, writing

assistance or proof reading the article, etc.). Whoever

would be acknowledged should be informed and a

verification for that could be requested by AUMJ

Editor.

Appendices

If there is more than one appendix, they should be

identified as A, B, etc. Formulae and equations in

appendices should be given separate numbering: Eq.

(A.1), Eq. (A.2), etc.; in a subsequent appendix, Eq.

(B.1) and so on. Similarly for tables and figures: Table

A.1; Fig. A.1, etc.

CASE REPORT WRITING TEMPLATE

Title. Include the words “case report” in the title.

Describe the phenomenon of greatest interest (e.g.,

symptom, diagnosis, diagnostic test, intervention, and

outcome).

Abstract. Summarize the following information if

relevant: 1) Rationale for this case report, 2)

Presenting concerns (e.g., chief complaints or

symptoms, diagnoses), 3) Interventions (e.g.,

diagnostic, preventive, prognostic, therapeutic

exchange), 4) Outcomes, and 5) Main lesson(s) from

this case report.

Key Words. Provide 3 - 8 key words that will help

potential readers search for and find this case report.

Introduction. Briefly summarize the background and

context of this case report.

Presenting Concerns. Describe the patient

characteristics (e.g., relevant demographics - age,

gender, ethnicity, occupation) and their presenting



2015

concern(s) with relevant details of related past

interventions.

Clinical Findings. Describe: 1) the medical, family,

and psychosocial history including lifestyle and

genetic information; 2) pertinent co-morbidities and

relevant interventions (e.g., self-care, other therapies);

and 3) the physical examination (PE) focused on the

pertinent findings including results from testing.

Timeline. Create a timeline that includes specific dates

and times (table, figure, or graphic).

Diagnostic Focus and Assessment. Provide an

assessment of the; 1) diagnostic methods (e.g., PE,

laboratory testing, imaging, questionnaires, referral),

2) diagnostic challenges (e.g., financial, patient

availability, cultural), 3) diagnostic reasoning

including other diagnoses considered, and, 4)

prognostic characteristics (e.g., staging) where

applicable.

Therapeutic Focus and Assessment. Describe: 1) the

type(s) of intervention (e.g., preventive,

pharmacologic, surgical, lifestyle, self-care) and 2) the

administration and intensity of the intervention (e.g.,

dosage, strength, duration, frequency.

Follow-up and Outcomes. Describe the clinical course

of this case including all follow-up visits as well as 1)

intervention modification, interruption, or

discontinuation, and the reasons; 2) adherence to the

intervention and how this was assessed; and 3) adverse

effects or unanticipated events. In addition, describe:

1) patient-reported outcomes, 2) clinician-assessed and

‐reported outcomes, and 3) important positive and

negative test results.

Discussion. Please describe: 1) the strengths and

limitations of this case report including case

management, 2) the literature relevant to this case

report (the scientific and clinical context), 3) the

rationale for your conclusions (e.g., potential causal

links and generalizability), and 4) the main findings of

this case report: What are the take-away messages?

Patient Perspective. The patient should share his or

her experience pr perspective of the care in a narrative

that accompanies the case report whenever

appropriate.

Informed Consent. Did the patient or their custodian

give the author of this case report informed consent?

Provide if requested .

Case Report Submission Requirements: 1) Competing

interests, are there any competing interests?, 2) Ethics

Approval, Did an ethics committee or institutional

review board review give approval? If yes, please

provide if requested, 3) De‐Identification, Has all

patient's related data been de-indentified?

RANDOMIZED CLINICAL TRIALS WRITING

TEMPLATE

In this particular type of original study, individuals are

randomly allocated to receive or not receive a

preventive, therapeutic, or diagnostic intervention and

then followed up to determine the effect of the

intervention. All randomized clinical trials should

include a flow diagram and authors should provide a

completed randomized trial checklist (see CONSORT

Flow Diagram and Checklist; http://www.consort-

statement.org) and a trial protocol.

Authors of randomized controlled trials are

encouraged to submit trial protocols along with their

manuscripts.

All clinical trials must be registered (before

recruitment of the first participant) at an appropriate

online public that must be independent of for-profit

interest (http://www.clinicaltrials.gov;

http://www.anzctr.org.au; http://www.umin.ac.jp/ctr;

http://isrctn.org;

http://www.trialregister.nl/trialreg/index.asp).

Each manuscript should clearly state an objective or

hypothesis; the design and methods (including the

study setting and dates, patients or participants with

inclusion and exclusion criteria, or data sources, and

how these were selected for the study); the essential

features of any interventions; the main outcome

measures; the main results of the study; a comment

section placing the results in context with the

published literature and addressing study limitations;

and the conclusions.

Data included in research reports must be original. A

structured abstract not exceeding 300 words is

required. Clinical trials are limited to 2700 words (not

including abstract, tables, figures, and references), 40

references, and no more than 5 tables and figures.

REVIEW, MINIREVIEW AND META-

ANALYSIS PAPERS

These papers will not have empirical data acquired by

the authors but will include historical perspectives,

analysis and discussion of papers published and data

acquired in a specific area.

Systematic reviews and meta-analyses are a particular

type of original articles that perform systematic,

critical assessment of literature and data sources

pertaining to clinical topics, emphasizing factors such

as cause, diagnosis, prognosis, therapy, or prevention.

All articles or data sources should be searched for and

selected systematically for inclusion and critically

http://www.trialregister.nl/trialreg/index.asp



2015

evaluated, and the search and selection process should

be described in detail in the manuscript. The specific

type of study or analysis, population, intervention,

exposure, and tests or outcomes should be described

for each article or data source. A structured abstract of

less than 300 words is required. The text is limited to

3500 words (not including abstract, tables, figures, and

references); about 4 tables (a flow diagram that depicts

search and selection processes as well as evidence

tables should be included) - and no reference limit.

Minireview is a brief historical perspective, or

summaries of developments in fast-moving areas

covered within the scope of the journal. They must be

based on published articles; they are not outlets for

unpublished data. They may address any subject

within the scope of the journal. The goal of the

minireview is to provide a concise very up-to-date

summary of a particular field in a manner

understandable to all readers.

SHORT COMMUNICATION AND SHORT RESEARCH ARTICLE

Short Communications are urgent communications of

important preliminary results that are very original, of

high interest and likely to have a significant impact on

the subject area of the journal. A Short

Communication needs only to demonstrate a ‘proof of

principle’. Authors are encouraged to submit an

Original Research Paper to the journal following their

Short Communication. There is no strict page limit for

a Short Communication; however, a length of 2500-

3500 words, plus 2-3 figures and/or tables, and 15-20

key references is advisable. Short Research Article

may be smaller single-result findings as a brief

summary that include enough information, particularly

in the methods and results sections, that a reader could

understand what was done.

POLICY PAPER

The purpose of the policy paper is to provide a

comprehensive and persuasive argument justifying the

policy recommendations presented in the paper, and

therefore to act as a decision-making tool and a call to

action for the target audience.

COMMENTARIES/OPINION ARTICLES

An opinion-based article on a topical issue of broad

interest, which is intended to engender discussion.

STUDY PROTOCOLS AND PRE-

PROTOCOLS

AUMJ welcomes publishing protocols for any study

design, including observational studies and systematic

reviews. All protocols for randomized clinical trials

must be registered and follow the CONSORT

guidelines; ethical approval for the study must have

been already granted. Study pre-protocols (i.e.,

discussing provisional study designs) may also be

submitted and will be clearly labeled as such when

published. Study protocols for pilot and feasibility

studies may also be considered.

METHOD ARTICLES

These articles describe a new experimental or

computational method, test or procedure, and should

have been well tested. This includes new study

methods, substantive modifications to existing

methods or innovative applications of existing

methods to new models or scientific questions. We

also welcome new technical tools that facilitate the

design or performance of experiments or operations

and data analysis such as software and laboratory and

surgical devices, or of new technologies to assist

medical diagnosis and treatment such as drug delivery

devices.

Maximum length of submissions

Full length original research articles should not

exceed 5000 words (maximum 40 references), and up

to 6 tables and/or figures.

Short communications comprising up to 1800 words of

text, maximum 15 references, and two illustrative

items (Tables and/or Figures).

Letters and Case Reports (provide novel insight into

disease mechanisms, diagnostic and management

applications). Clinical Laboratory Notes (technical

evaluation or important insight into analytical

methodology), or Letters to the Editor (focused on a

specific article that has appeared in Aljouf Medical

Journal within 4 weeks of print issue date of article).

For all 3 types of letters listed above, the text should

not exceed 600 words, with no abstract, a maximum of

1 table or figure and up to 5 references.

Review Articles, Surveys, Essays, and Special Reports

may exceed the word and reference limit for Full-

length articles as per the comprehensive nature of

these articles. However, both of these articles

(Reviews and Special Reports) will still require an

abstract (unstructured, 250 word maximum).

Editorials, Meeting summary, Commentaries, Book

review and Opinion pieces will not require an abstract

and will be limited to 2000 words and up to 20

references. A book review is a brief critical and

unbiased evaluation of a current book determined to be

of interest to the journal audience. Publication of a

submitted book review is at the discretion of the

editor.



2015

Artwork

General points

Make sure you use uniform lettering and sizing of your

original artwork. Preferred fonts: Arial (or Helvetica),

Times New Roman (or Times), Symbol, Courier.

Number the illustrations according to their sequence in

the text. Use a logical naming convention for your

artwork files. Indicate per figure if it is a single, 1.5 or

2-column fitting image. For Word submissions only,

you may still provide figures and their captions, and

tables within a single file at the revision stage.

Formats

Regardless of the application used, when your

electronic artwork is finalized, please 'save as' or

convert the images to one of the following formats

(note the resolution requirements for line drawings,

halftones, and line/halftone combinations given

below). Please do not supply files that are optimized

for screen use (e.g., GIF, BMP, PICT, WPG); the

resolution is too low, supply files that are too low in

resolution, and, submit graphics that are

disproportionately large for the content.

EPS (or PDF): Vector drawings. Embed the font

or save the text as 'graphics'.

TIFF (or JPG): Color or grayscale photographs

(halftones): always use a minimum of 300 dpi.

TIFF (or JPG): Bitmapped line drawings: use a

minimum of 1000 dpi.

TIFF (or JPG): Combinations bitmapped

line/half-tone (color or grayscale): a minimum of

500 dpi is required.

Color artwork

Please make sure that artwork files are in an

acceptable format (TIFF (or JPEG), EPS (or PDF), or

MS Office files) and with the correct resolution. If,

together with your accepted article, you submit usable

color figures the Journal will ensure that these figures

will appear in color on the Web regardless of whether

or not these illustrations are reproduced in color in the

printed version. Because of technical complications

which can arise by converting color figures to 'gray

scale' please submit in addition usable black and white

versions of all the color illustrations.

Figure captions

Ensure that each illustration has a caption (Legend). A

caption should comprise a brief title below the figure

that describes its content and not to be general. Keep

text in the illustrations themselves to a minimum but

explain all symbols and abbreviations used in the

legend. Figure caption should stand for itself (self-

explanatory) without the need for consulting the text.

Tables

Number tables consecutively in accordance with their

appearance in the text. Place footnotes to tables below

the table body and indicate them with superscript

lowercase letters within the table. If necessary, such

footnotes could be placed at the end of the table title.

Avoid vertical rules. Be sparing in the use of tables

and ensure that the data presented in tables do not

duplicate results described elsewhere in the article

(Figures or text). The table caption (Title) should be

brief but describes its content and not to be general.

Explain all symbols and abbreviations used in the table

in the footnote. Table title should stand for itself (self-

explanatory) without the need for consulting the text.

The table structure should be scientifically organized

(columns and rows) and its message should be easily

comprehendible.

The Editor-in-Chief, on accepting a manuscript, may

recommend that additional tables and/or graphs

containing important backup data, too extensive to be

published in the article, may be published as

supplementary material. In that event, an appropriate

statement will be added to the text. However, the

author should submit such material for consideration

with the manuscript.

References

References cited should be relevant, up-to-date and

adequately cover the field without ignoring any

supportive or conflicting publications. Please ensure

that every reference cited in the text is also present in

the reference list (and vice versa). If present,

unpublished results and personal communications may

be mentioned in the text and not in the reference list.

Citation of a reference as 'in press' implies that the

item has been accepted for publication, and shows up

on PubMed literature search or a copy of the title page

of the relevant article must be submitted. DOI of the

references - whenever applicable should be presented.

Reference management software

This journal has standard templates available in key

reference management packages EndNote

(http://www.endnote.com/support/enstyles.asp) and

Reference Manager

(http://refman.com/support/rmstyles.asp). Using plug-

ins to word processing packages, authors only need to

select the appropriate journal template when preparing

their article and the list of references and citations to

these will be formatted according to the journal style,

which is described below.

Reference formatting

There are no strict requirements on reference

formatting at submission but should be consistent,



2015

complete and up-to-date. Where applicable, author(s)

name(s), chapter title/article title, journal title/book

title, year of publication, volume number-issue

number/book chapter and the pagination must be

present. For the book reference, the edition number,

editors (if they are not the authors), publisher and its

main address (City and Country) should be added as

described below in the example. The reference style

used by the journal should be applied to the accepted

article at the proof stage. Note that missing data will

be highlighted at proof stage for the author to correct.

Use peer-reviewed references only except for national

and international organizational reporting and

registers. If you do wish to format the references

yourself they should be arranged according to the

following examples:

Reference style

Indicate references by number(s) in curved brackets as

a bolded superscript at the end of the cited text(s)

before the full stop, e.g., ………. shorter hospital stay

and lower cost(20)

. The actual authors can be referred

to, but the reference number(s) must always be given.

Number the references in the list in the order in which

they appear in the text. The authors list should not be

shortened, all authors’ names should be mentioned.

For further details you are referred to 'Uniform

Requirements for Manuscripts submitted to

Biomedical Journals' (J Am Med Assoc 1997; 277:

927-34) (see also

http://www.nlm.nih.gov/bsd/uniform_requirements.ht

ml).

Examples:

Reference to a journal publication: Format your

journal publications according to the following

examples depending on whether; 1) It is already

published with specific page numbers, 2 and 3) It is

already published with article ID number and pages

from 1 to …, or 4) It is published put ahead of print.

1. Van der Geer J, Hanraads JAJ, Lupton RA. The

art of writing a scientific article. J. Sci.

Commun., 2010;163(1):51-9.

2. Leta S, Dao TH, Mesele F, Alemayehu G.

Visceral Leishmaniasis in Ethiopia: An

Evolving Disease. PLoS Negl Trop Dis., 2014;

8(9):e3131;1-7.

3. Arjmand MH, Ahmad Shah F, Saleh

Moghadam M, Tara F, Jalili A, Mosavi Bazaz

M, Hamidi Alamdari D. Prooxidant-antioxidant

balance in umbilical cord blood of infants with

meconium stained of amniotic fluid. Biochem

Res Int., 2013;2013:ID270545;1-4.

4. Teferra RA, Grant BJ, Mindel JW, Siddiqi TA,

Iftikhar IH, Ajaz F, Aliling JP, Khan MS,

Hoffmann SP, Magalang UJ. Cost

minimization using an artificial neural network

sleep apnea prediction tool for sleep studies.

Ann Am Thorac Soc., 2014 Jul 28 (Epub ahead

of print).

Reference to a book: Strunk Jr W, White EB (Editors).

The elements of style, 4th

Edition, Longman, New

York; 2000, pp. 210-9.

Reference to a chapter in an edited book: Mettam GR,

Adams LB. How to prepare an electronic version of

your article. In: Jones BS, Smith RZ (Editors),

Introduction to the electronic age, 1st Edition, E-

Publishing Inc., New York, 2009, Chapter 2: pp. 281-

304.

Reference to a homepage: It is acceptable to refer to

an Organizational Guidelines, Reports, Forms, Data

sheets, Questionnaires, etc. It should follow the

following format. World Health Organization. Non-

communicable Diseases (NCD) Country Profile, 2014

(http://www.who.int/globalcoordinationmechanism/pu

blications/ncds-country-profiles-eng.pdf; last accessed

June, 3, 2015).

Journal abbreviations source

Journal names should be abbreviated according to the

List of Title Word Abbreviations:

http://www.issn.org/services/online-services/access-to-

the-ltwa/.

Abbreviations and units

Standard abbreviations as listed in the Council of

Biology Editors Style Manual may be used without

definition. Use non-standard abbreviations sparingly,

preceding their first use in the text with the

corresponding full designation. Use units in

conformity with the standard International System (SI)

of units.

Video data

The journal accepts video material and animation

sequences to support and enhance your scientific

research. Authors who have video or animation files

that they wish to submit with their article are strongly

encouraged to include links to these within the body of

the article. This can be done in the same way as a

figure or table by referring to the video or animation

content and noting in the body text where it should be

placed. All submitted files should be properly labeled

so that they directly relate to the video file's content. In

order to ensure that your video or animation material is

directly usable, please provide the files in one of our

recommended file formats with a preferred maximum

size of 50 MB. Video and animation files supplied will

be published online in the electronic version of your

http://www.nlm.nih.gov/bsd/uniform_requirements.html

http://www.nlm.nih.gov/bsd/uniform_requirements.html



2015

article. Since video and animation cannot be

embedded in the print version of the journal, please

provide text for both the electronic and the print

version for the portions of the article that refer to this

content.

AudioSlides

AUMJ encourages authors to create an AudioSlides

presentation with their published article as

supplementary material. This gives authors the

opportunity to summarize their research in their own

words and to help readers understand what the paper is

about. Authors of this journal will automatically

receive an invitation e-mail to create an AudioSlides

presentation after acceptance of their paper.

Supplementary data

AUMJ accepts electronic supplementary material to

support and enhance your scientific research.

Supplementary files offer the author additional

possibilities to publish supporting applications, high-

resolution images, background datasets, sound clips

and more. Supplementary files supplied will be

published online alongside the electronic version of

your article. In order to ensure that your submitted

material is directly usable, please provide the data in

one of our recommended file formats. Authors should

submit the material in electronic format together with

the article and supply a concise and descriptive caption

for each file.

Supplementary material captions

Each supplementary material file should have a short

caption which will be placed at the bottom of the

article, where it can assist the reader and also be used

by search engines.

THE COPYRIGHTS

The copyrights of all papers published in this journal

are retained by the respective authors as per the

'Creative Commons Attribution License'

(http://creativecommons.org/licenses/by/3.0/). The

author(s) should be the sole author(s) of the article and

should have full authority to enter into agreement and

in granting rights to the journal, which are not in

breach of any other obligation. The author(s) should

ensure the integrity of the paper and related works.

Authors should mandatorily ensure that submission of

manuscript to AUMJ would result into no breach of

contract or of confidence or of commitment given to

secrecy.

Submission checklist

The following list will be useful during the final

checking of an article prior to sending it to the journal

for review. Please consult this Guide for Authors for

further details of any item.

To avoid unnecessary errors you are strongly advised

to use the 'spell-check' and 'grammar-check' functions

of your word processor.

Ensure that the following items are present:

One author has been designated as the corresponding

author with contact details for all authors:

• E-mail address.

• Full postal address.

• Telephone.

All necessary files have been uploaded, and contain:

• Keywords.

• All figures and their captions.

• All tables (including title, description, footnotes).

Further considerations

• Manuscript has been 'spell-checked' and

'grammar-checked'.

• All references mentioned in the Reference list are

cited in the text, and vice versa.

• Permission has been obtained for use of

copyrighted material from other sources

(including the Web).

• Color figures are clearly marked as being

intended for color reproduction on and in print,

or to be reproduced in color electronically and in

black-and-white in print.

PEER REVIEW PROCESS

High quality manuscripts are peer-reviewed by

minimum of two peers of the same field along with a

biostatician in the case the study requires. Pre-

reviewing advice and help will be provided by the

Editor-In-Chief on first submission for initial

improvements to meeting the minimum criteria of

peer-reviewing. The journal follows strict double blind

fold constructive review policy to ensure neutral

evaluation. During this review process identity of both

the authors and reviewers are kept hidden to ensure

unbiased evaluation. A cycle of one-month reviewing

process is the target of the journal from submission to

final acceptance. For meeting this goal, the Editor-In-

Chief is expecting strict compliance from author

hastening corrections and replying editorial requests.

Continuous post-publication open peer reviewing is

highly encouraged through submitting comments to

the Editor on any of the published article that will

show up with author reply in the subsequent issue to

the journal.

The reviewers’ comments are sent to authors once

received. With the help of the reviewers’ comments,

FINAL decision (accepted or accepted with minor

revision or accepted with major revision or rejected)



2015

will be sent to the corresponding author. Reviewers are

asked if they would like to review a revised version of

the manuscript. The editorial office may request a re-

review regardless of a reviewer's response in order to

ensure a thorough and fair evaluation.

In order to maintain this journal’s mission of one-

month publication cycle, authors are encouraged to

submit the revised manuscript within one week of

receipt of reviewer’s comment (in case of minor

corrections). However, revised manuscript submission

should not go beyond 2 weeks (only for the cases of

major revision which involves additional experiment,

analysis etc.). Along with corrected manuscript

authors will be requested to submit filled a point-by-

point answers to the reviewers' comments and any

rebuttal to any point raised. The Editor-In-Chief of the

journal will have exclusive power to take final

decision for acceptance or rejection during any

dispute.

Under special circumstance, if the review process

takes more time, author(s) will be informed

accordingly. The editorial board or referees may re-

review manuscripts that are accepted pending revision.

Manuscripts with latest and significant findings will be

handled with the highest priority so that it could be

published within a very short time. The journal is

determined to promote integrity in research

publication. In case of any suspected misconduct, the

journal management reserves the right to re-review

any manuscript at any stages before final publication.

Our massage to AUMJ potential reviewers says

“Although the Manuscript General Evaluation Form is

attached, we like to instigate a policy of constructive

reviewing and to do our best to make the submitted

manuscripts publishable - provided that it is genuine

and contain no major frauds of republication, duplicate

use of self data or plagiarism of intellectual properties

of the others. Please, make your changes and insert

your corrections, comments and suggestions directly

into the manuscript text but in a different color. Please

also make sure that the author(s) presented an

inclusive and updated list of genuine references,

applied proper statistics and extracted justified

conclusions”.

PATIENT CONSENT FORM

Date: ………………...

Place: ………………………….

Title of the article

Name of the Author(s)

Patient’s name:

I give my consent for this material to be published in

Aljouf University Medical Journal and associated

publications without limit on the duration of

publication.

I understand that the material will be published in

Aljouf University Medical Journal will be included in

any reprints of the published article. I understand that

my name will not be included in the published article,

and that every effort will be made to keep my identity

anonymous in the text and in any images. However, I

understand that complete anonymity and control of all

uses cannot be guaranteed.

Signed: …………………………………………

Full name of the relative: …………………..........

Relation: ……………………………………….

Patient’s Name and Contact Address

Corresponding Author’s Name and Contact Address

Alternative:

I have been offered the opportunity to preview the

material in the format it will eventually appear and I

am satisfied with it.

Signed:……………………………………..…………..

Full Name of the Patient:……………………..……….

Manuscript General Revision Form

The Manuscript Assigned Number and Title: ……..

The Manuscript Evaluation Score: Please, score the

manuscript from 0 to 4 (highest) for each of the

following items, and sum the total score. Please, also

check if the statistics of the results require revision.

Items

Scores 0 1 2 3 4

Item

Score

The Study is a Priority

Problem

Originality

Significance of the Work

Research Design

Quality and Clarity of the

English Writing

Standard and Reproducible

Methodology

Results Presentation and

Appropriate Statistics

Relevant Discussion and

Justified Conclusions

Tables/ Illustrations/ Figures

References: Inclusive and

Updated

Total score

Requires Statistical Revision (Mark Please) Yes No

The Decision: Should AUMJ publish the

manuscript? Please, check the appropriate box.



2015

Yes, without any revision: Accepted

Yes, with minor revision

and alterations:

Accepted with

revision

Yes, with major revision

and alterations:

Re-Evaluation after

substantial revision

No, this manuscript should

be denied publication: Denied

Justification for Decision & Feedback for the

Author (REQUIRED): AUMJ recommends the

reviewer to introduce such justifications and feedback

into the text at the appropriate places within the

manuscript (Specific and Comprehensive Revision).

Note to the Editor (WELCOMED): AUMJ welcomes

reviewer writing a note to the Editor including conflict

of interest that will not be disclosed to the Author(s).

AFTER ACCEPTANCE

Online proof correction

Corresponding authors will receive an e-mail with

annotation for correction of MS format proofs and

resend the corrected version. All instructions for

proofing will be given in the e-mail we send to

authors. We will do everything possible to get your

article published quickly and accurately - please

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AbdelMoneim et al - Plasma Prolactin Level in Type 2 Diabetic Patients with and ….

Aljouf University Medical Journal (AUMJ), 2015 December 1; 2(4): 1 - 6.

2015 2015

Original Article

Plasma Prolactin Level in Type 2 Diabetic Patients with and without Retinopathy

Medhat AbdelMoneim1*

, Ahmed Abd-Eltawab2, Gomaa Mostafa-Hedeab

3, Khaled A.

Zaki4, Alaa A. Mohamed

5, Abdulrahman A. Alduraywish

6, Mahrous A. Ibrahim

7

1Department of Medical Biochemistry, Colleges of Medicine, Benha University, Benha, Egypt

and Aljouf University. Departments of 2Physiology, 3Pharmacology and 5Medical Biochemistry,

Colleges of Medicine, Beni-Suef University, Beni-Suef, Egypt and Aljouf University.

Departments of 4Ophthalmology and 7Forensic Medicine and Clinical Toxicology, Colleges of

Medicine, Suez Canal University, Ismailia, Egypt and Aljouf University, and, Department of

Internal Medicine6, College of Medicine, Aljouf University, Sakaka, Saudi Arabia. *Corresponding Author: [email protected]

Abstract

Background: Prolactin (PRL) is expressed in anterior pituitary gland and throughout

retina. The peptide vasoconstrictive antiangiogenic vasoinhibins are PRL-derived and

inversely correlates the development of retinopathy. Objective: The aim of this study

was to assess the relationship between PRL level and development/progression of

retinopathy in type 2 diabetic (T2DM) patients, and their relationship with changes in

lipogram and glycemic control indices. Patients and Methods: This study included 62

male patients with T2DM on metformin and 45 male healthy subjects as a control

group. Diabetic patients were divided into two main groups: diabetic group with

retinopathy included 38 patients and diabetic group without retinopathy included 24

patients. Diabetic retinopathy patients were subdivided into non-proliferative diabetic

retinopathy subgroup (NPDR) included 25 patients and proliferative diabetic

retinopathy subgroup (PDR) included 13 patients. NPDR was further classified into

mild (9 patients), moderate (8 patients) and severe (8 patients). Fasting blood samples

were collected from all participants to recover plasma. Plasma PRL, total cholesterol,

HDL-cholesterol, LDL-cholesterol and blood HbA1c were measured. Results: There

were non-significant differences in plasma PRL levels between diabetic patients with

and without retinopathy and also between the two diabetic groups vs. healthy controls.

There were non-significant differences in plasma PRL levels comparing mild, moderate

and severe non-proliferative retinopathy patients vs. each other or vs. diabetic patients

without retinopathy. There was a significant increase in HbA1c level in diabetic

patients with retinopathy compared to those without retinopathy (p<0.05). Conclusion:

Our results highlight the important role in the development and progression of diabetic

retinopathy that the uncontrolled blood glucose level may play. However, variation in

PRL blood levels may not have a role to play in this concern. AbdelMoneim M, Abd-

Eltawab A, Mostafa-Hedeab G, Zaki KA, Mohamed AA, Alduraywish AA.

Ibrahim MA. Plasma Prolactin Level in Type 2 Diabetic Patients with and without

Retinopathy. AUMJ, 2015 December 1; 2(4): 1 - 6.

Key Words: Prolactin, Retinopathy, Vasoinhibins, Type 2 diabetes, Angiogenesis.




2015 2015

Introduction

Type 2 diabetes mellitus (T2DM) is the

most common chronic disease

worldwide. Its long-term sequealae

include retinopathy, neuropathy,

nephropathy and macrovascular

diseases(1)

. Retinopathy is one of the

common causes of visual loss worldwide.

It is a blinding complication of DM that

damages the retina and occurs within 20

years from diagnosis of diabetic patients.

There are many factors that play a role in

the pathogenesis of retinopathy, viz.:

hyperglycemia, duration of diabetes,

hypertension and age(2)

. Diabetic

retinopathy is characterized by capillary

cell reduction and increased

vasopermeability that induce hypoxia and

ischemia leading to increased

angiogenesis. Disturbance in anti-

angiogenic protection mechanisms can

accelerate neovascularization and

retinopathy(3)

.

Prolactin (PRL) hormone is secreted from

anterior pituitary gland and is expressed

throughout retina. Vasoinhibins are

peptides derived from PRL, growth

hormone and placenta lactogen. These

peptides decrease vasodilatation and

angiogenesis(4)

. Intra-cardiac injection of

radioactive PRL would incorporate into

ocular tissue(5)

. PRL level was reported to

be elevated in diabetic patients. It

decreases in patients with retinopathy

compared to those without retinopathy.

This indicates that induction of

hyperprolactinemia could have a

therapeutic potential against diabetic

retinopathy(6)

.

In this study, we aimed at evaluating the

relationship between blood prolactin level

and presence and absence of retinopathy

in diabetic patients, and, their relationship

with changes in lipogram and glycemic

control indices.

Patients and Methods

Participants and sampling: The local

Research and Ethics Committee of

Faculty of Medicine, Suez Canal

University, Ismailia, Egypt, approved the

study which adhered to the creed of the

Declaration of Helsinki. An informed

consent was secured from each

participant. The current study included all

of the voluntarily participating 62 adult

male patients with type T2DM reviewed

at Cortba Ophthalmic Center, Erashyat-

Masr, Ismailia, Egypt from April -

September, 2015 and 45 normal healthy

adult male controls. Inclusion criteria:

Male patients with T2DM on metformin.

Exclusion criteria: The diabetic patients

with history of hyperprolactinemia,

thyroid disease, renal failure, liver

disease, treatment with drugs that

increase prolactin level, recent

psychological stress and adrenal diseases.

Overnight fasting blood samples were

collected from all participants for whole

blood (for HbA1c) and recovering plasma

(for other parameters) in heparin tubes.

Ophthalmological examination: Patients

underwent thorough ophthalmic

examination comprising corrected

distance visual acuity (CDVA),

uncorrected distance visual acuity

(UDVA), Goldman Applanation

Tonometry, and dilated fundus

examination. Fundus examination was

done by direct and indirect

ophthalmoscope and by slit lamb

biomicroscopic examination with +90

non-contact lens. Fundus was

photographed to document any abnormal

findings appropriate. Grouping: The

diabetic patients were classified



2015 2015

according to fundus examination (Table

1). Diabetes group with retinopathy

included 38 patients with the mean age of

58.6 ± 7 years and disease duration of 13

± 2.6, and, diabetes group without

retinopathy included 24 patients with the

mean age of 54.1 ± 10 years and disease

duration of 12 ± 2.6. Diabetic retinopathy

group was subdivided into non-

proliferative (25 patients) and

proliferative (13 patients). Non-

proliferative diabetic retinopathy group

(NPDR) was further classified into mild

(9 patients), moderate (8 patients) and

severe (8 patients) according to

Wilkinson et al(7)

.

Table 1: Classification of Diabetic Retinopathy (DR)(7).

Stages of DR Clinical Criteria

Mild non-proliferative DR At least one microaneurysm. Criteria not met for other level

of retinopathy

Moderate non-proliferative DR Hemorrhages or microaneurysm, venous beading, cotton-

wool spots, and intraretinal microvascular abnormality

(IRMA).

Severe non-proliferative DR Hemorrhages or microaneurysm in all four quadrants, or

venous beading in at least 2 quadrants, or IRMA in at least 2

quadrants.

Proliferative DR Neovascularization in optic disc or retina, preretinal

hemorrhages, vitreous hemorrhages, traction retinal

detachments, and, neovascular glaucoma.

Biochemical investigations were done

using Semi-Autoanalyser utilizing kits

supplied by Human Glesellschaft Fur

Biochemica und Diagnostics mbH,

Wiesbaden, Germany. Colorimetrically,

fasting blood glucose (FBG) was

measured using glucose oxidase

method(8)

, total cholesterol was measured

by cholesterol oxidase method(10)

, HDL-

Cholesterol (HDL-C)(11)

, LDL-

Cholesterol (LDL-C) was calculated

using Friedwald formula(12)

and

creatinine(13)

were measured. HbA1c was

measured using G8 Tosoh Automated

HPLC Glycohemoglobin Analyser HLC-

723G8 (cat#021560 and cat#021848 for

the ion-exchange column, Tosoh

Bioscience Inc., King of Prussia, PA

19406, USA(9)

. Plasma prolactin was

measured by specific ELISA kit (cat#DS-

EIA-Prolactin, DSI S.r.l., Saronno,

Volonterio, Italy - with a lower detection

limit of 10 mIU/L)(14)

. Statistical

analysis: Data were collected, tabulated,

subjected to analysis using SPSS

(Version 17, Chicago, USA) using the

student's "t" test or ANOVA. Data were

presented as mean ± standard deviation

(SD). P value is considered statistically

significant if ˂0.05.

Results

The current study included 45 normal

healthy adult male controls with a mean

age of 52 ± 12.4 and 62 adult male

patients with type T2DM and a mean age

of 56 ± 10.7. Their mean disease duration

was 14 ± 3.5 years.

Plasma levels of prolactin, total

cholesterol, HDL-C, and creatinine were

of non-significant difference comparing

diabetic and healthy control groups but

plasma LDL-C and creatinine levels were

significantly higher in the two diabetic



2015 2015

groups vs. controls (Table 2). Mean

fasting plasma glucose and HbA1c were

significantly higher in diabetic groups

with retinopathy and without retinopathy

than that in control group. Mean fasting

plasma glucose and HbA1c were

significantly increased in diabetic group

with retinopathy when compared to

diabetic group without retinopathy (Table

2).

Table 2: Mean plasma prolactin, total cholesterol, HDL-Cholesterol (HDL-C), LDL-Cholesterol

(LDL-C), creatinine, fasting blood glucose (FBG) and HbA1c in type II diabetic patients with

retinopathy (DM-WRP) and without retinopathy (DM-WoutRP) vs. healthy control participants.

Data presented are mean ± standard deviation, n and p value. a = significance of difference

comparing healthy controls vs. each of the two diabetic subgroups, and, b = significance of

difference comparing the two diabetic groups against each other.

DM-WRP

(n = 24)

DM-WoutRP

(n = 38)

Controls

(n = 45)

Parameter

6.92 ± 0 .65 7.03 ± 0.91 6.95 ± 0.62 Prolactin, ng/mL

210.38 ± 13.40 200.25 ± 14.86 195.82 ±

17.77 Total cholesterol, mg/dL

45.65 ± 6.78 45.75 ± 6.11 44.59 ± 5.49 HDL-C, mg/dL

128.65 ± 12.12 (p =

0.02)a (p = 0.015)b

121.67 ± 11.41 (p =

0.017)a

90.84 ± 9.24 LDL-C, mg/dL

1.09 ± 0.20 (p = 0.034)a 1.09 ± 0.19 (p =

0.014)a

0.91 ± 0.17 Creatinine, mg/dL

228.59 ± 24.34 (p =

0.011)a (p = 0.002)b

212.0 ± 27.69 (p =

0.015)a

82.60 ± 9.30 FBG, mg/dL

9.07 ± 0.22 (p = 0.011)a

(p = 0.01)b

7.32 ± 0.62 (p =

0.022)a

4.55 ± 0.29 HbA1c, %

Plasma prolactin levels showed non-

significant difference comparing diabetic

patients with non-proliferative

retinopathy (6.98 ± 0.79) vs. those with

proliferative retinopathy (6.87 ± 0.71).

Also, the mean prolactin plasma levels

were non-significantly different among

the three sub-grades of non-proliferative

retinopathy; mild = 7.17 ± 0.75, moderate

= 6.98 ± 0.45, and, severe = 6.79 ± 0.43.

Mean prolactin plasma levels were non-

significant different comparing each of

these sub-grades of diabetic non-

proliferative retinopathy vs. diabetic

patients without retinopathy (7.03 ±

0.91).

Discussion

The aim of this study was to assess the

relationship between plasma prolactin

and the extent, type and severity of

retinopathy in diabetic patients. The

rationale was based on the fact that

prolactin is the main source of specific

vasoconstrictive and antiangiogenic

vasoinhibins(4)

. Our results showed a non-

significant difference in plasma prolactin

levels between diabetic patients with vs.

without retinopathy and comparing each

of them vs. healthy controls. Also, there

were non-significance changes in plasma

prolactin comparing diabetic patients

with non-proliferative retinopathy vs.

those with proliferative retinopathy.

http://www.omicsonline.org/2155-6156/2155-6156-3-173.php?aid=4777#6



2015 2015

Moreover, the three sub-grades of non-

proliferative diabetic retinopathy, viz.:

mild, moderate and severe, showed non-

significant decreases in plasma prolactin

in severe retinopathy. These non-

significant changes may suggest that

prolactin does not play a significant

protective role against the development of

diabetic retinopathy. This is in agreement

with study of Bonakdaran et al(15)

.

However, Triebel et al(3)

showed that

diabetic patients with retinopathy had

lower level of serum prolactin-V

(vasoinhibin) that could contribute to the

development of diabetic retinopathy. Our

results are in contradiction with those of

Arnold et al(6)

who reported a significant

increase in serum prolactin in diabetic

patients compared with the controls and

in those without retinopathy than patients

with proliferative retinopathy. They

elaborated that prolactin is converted

intraocularly into vasoinhibins, which

block angiogenesis, permeability and

vasodilatation by its direct action on

endothelial cells and by stimulation of

vascular regression mediated by

apoptosis.

In our study, duration of diabetes was

more than 10 years in patients with

retinopathy. We suggested that

abnormally high blood sugar in these

diabetic patients is an important risk

factor for this complication. Diabetes

duration independent of blood glucose

level was the main factor responsible for

retinopathy(16)

. In our study we found that

HbA1C was significantly higher in

retinopathy group compared to non-

retinopathy group. Such results run in

parallel with those reported by

Bonakdaran et al(15)

. Our results also

showed that high cholesterol level is not a

predictor of retinopathy because there

were non-significant changes between

diabetic patients and healthy controls. In

the light of the previously published

strong evidences connecting prolactin-

derived vasoinhibins against the

development and progression of diabetic

retinopathy(15-20)

, our results may point to

discordance between levels of prolactin

as a hormone and its vasoinhibins - if

reproducible on larger scale multi-centric

studies.

Conclusion

Plasma prolactin does not correlate with

the extent, type and severity of diabetic

retinopathy and may not have a role in its

development, whereas, glycemic control

indices and disease duration may have the

salient role in its development and/or

progression.

Limitations of the Study

Although we included all the

voluntarily participating diabetic

patients in our medical center, the

sample size was small particularly

upon subgrouping within the short

study time.

We wished if we could have afforded

measuring the prolactin-derived

vasoinhibins along with the hormone.

Conflict of Interest: The authors

declared no conflict of interests.

References

1. Cheung N, Mitchell P, Wong TY.

Diabetic retinopathy. Lancet, 2010;

376:124-136.

2. Frank RN. Diabetic retinopathy: current

concepts of evaluation and treatment. Clin

Endocrinol Metab., 1986;15(4):933-69.

3. Triebel J, Macotela Y, de la Escalera GM,

Clapp C. Prolactin and vasoinhibins:

Endogenous players in diabetic





2015 2015

retinopathy. IUBMB Life, 2011;

63(10):806-10.

4. Zamorano M, Ledesma-Colunga MG,

Adán N, Vera-Massieu C, Lemini M,

Méndez I, et al. Prolactin-derived

vasoinhibins increase anxiety- and

depression-related behaviors.

Psychoneuroendocrinology, 2014;44:123-

32.

5. O'Steen WK, Sundberg DK. Patterns of

radioactivity in the eyes of rats after

injection of iodinated prolactin.

Ophthalmic Res., 1982;14(1):54-62.

6. Arnold E, Rivera JC, Thebault S, Moreno-

Páramo D, Quiroz-Mercado H, Quintanar-

Stéphano A, et al. High levels of serum

prolactin protect against diabetic

retinopathy by increasing ocular

vasoinhibins. Diabetes, 2010;

59(12):3192-7.

7. Wilkinson CP, Ferris FL 3rd, Klein RE,

Lee PP, Agardh CD, Davis M, et al;

Global Diabetic Retinopathy Project

Group. Proposed international clinical

diabetic retinopathy and diabetic macular

edema disease severity scales.

Ophthalmology, 2003;110(9):1677-82.

8. Trinder P. Determination of blood glucose

using an oxidase-peroxidase system with a

non-carcinogenic chromogen. J Clin

Pathol., 1969;22(2):158-61.

9. Trivelli LA, Ranney HM, Lai HT.

Hemoglobin components in patients with

diabetes mellitus. N Engl J Med.,

1971;284(7):353-7.

10. Richmond W. Preparation and properties

of a cholesterol oxidase from Nocardia sp.

and its application to the enzymatic assay

of total cholesterol in serum. Clin Chem.,

1973;19(12):1350-6.

11. Fruchart JC. LDL Cholesterol

determination after separation of low

density lipoprotein. Rev. Fr. Des Lab.,

1982;103:7-17.

12. William TF, Levy RL, Fredrickson DS.

Estimation of low density lipoprotein.

Clinical Chemistry, 18(6):499-502.

13. Husdan H, Rapoport A. Estimation of

creatinine by the Jaffe reaction. A

comparison of three methods. Clin Chem.,

1968; 14(3):222-38.

14. Chieregatti G. The soluble sandwich for

immunoassay, methodological and

instrumental applications, 1989; 5th

European Edit. - Oak Ridge Conference.

15. Bonakdaran S, Shoeibi N, Mojtaba A,

Rokni H. Serum prolactin level and

diabetic retinopathy in type 2 diabetes. J

Diabetes Metab., 2012: 3(1):1-3

16. Davis MD, Fisher MR, Gangnon RE,

Barton F, Aiello LM. Risk factors for high

risk proliferative diabetic retinopathy and

severe visual loss: Early treatment diabetic

retinopathy study report. Invest

Ophthalmol. Vis. Sci., 1998;39(2):233-52.

17. Triebel J, Bertsch T, Bollheimer C, Rios-

Barrera D, Pearce CF, Hüfner M, et al.

Principles of the prolactin/vasoinhibin

axis. Am J Physiol Regul Integr Comp

Physiol., 2015;309(10):R1193-203.

18. Perimenis P, Bouckenooghe T,

Delplanque J, Moitrot E, Eury E, Lobbens

S, et al. Placental antiangiogenic prolactin

fragments are increased in human and rat

maternal diabetes. Biochim Biophys Acta,

2014;1842(9):1783-93.

19. García C, Nuñez-Anita RE, Thebault S,

Arredondo Zamarripa D, Jeziorsky MC,

Martínez de la Escalera G, Clapp C.

Requirement of phosphorylatable

endothelial nitric oxide synthase at Ser-

1177 for vasoinhibin-mediated inhibition

of endothelial cell migration and

proliferation in vitro. Endocrine,

2014;45(2):263-70.

20. Ramírez M, Wu Z, Moreno-Carranza B,

Jeziorski MC, Arnold E, Díaz-Lezama N,

et al. Vasoinhibin gene transfer by

adenoassociated virus type 2 protects

against VEGF- and diabetes-induced

retinal vasopermeability. Invest

Ophthalmol Vis Sci., 2011;52(12):8944-

50.

http://www.ncbi.nlm.nih.gov/pubmed/9477980





Sharaf - Life Satisfaction with Sleep, Caffeinated Drinks and Physical Exercise ….


2015 2015

Original Article

Life Satisfaction with Sleep, Caffeinated Drinks and Physical Exercise among Qassim Medical Students

Fawzy Sharaf

Department of Community and Family Medicine, College of Medicine, Qassim

University, Burydah, Saudi Arabia.

For Correspondence: [email protected]

Abstract

Background: Satisfaction with life reflects on physical fitness and academic

performance. It is essential to check for its extent among our medical students to set

measures that would abort foreseeable drawbacks on their life, academic performance

and quality of future clinical service they would provide. Objective: This study aimed

at exploring the life satisfaction considering sleep, physical activity and consuming

energy and caffeinated beverages among 1st and 2

nd year medical students, Qassim

University, Burydah, Saudi Arabia. Participants and Methods: A cross-sectional

study was conducted during the academic year 2014 – 2015. A questionnaire of

eighteen items was developed and modified by a focus group discussion with students

and medical education experts. The questionnaire was distributed to the students by e-

mail with a link designed by Google Drive. SPSS (version 17 for Windows) for

descriptive statistics, Chi-Square and Student's t-tests were used for the statistical

analysis. Results: Respondents from 1st year were 106 (57%), and from 2

nd year were

80 (43%). Mean satisfaction score among 2nd

year was higher than 1st year students.

The two groups were significantly different regarding consumption of energy and

coffee drinks, and duration and nature of their physical exercise. The other parameters

(Sleep required each night, asleep during academic activities, extra hours of sleep

during weekends, type of exercise performed, your overall rate of physical fitness,

exercising affects your life satisfaction, have gotten the important things I wanted in

life, my life is close to ideal and I change almost nothing in my life) did not differ

between the two groups. Females were significantly different in the naps during the

day, daily exercise and energy and coffee/Tea/Caffeinated drinks intake than males.

Conclusion: Reduced sleep hours, the increase consumption of caffeinated beverages

and reduced physical exercising were common habits among medical students of both

genders. These habitats had significant impact on their overall satisfaction of life and

may affect their academic performance and general health. Sharaf F. Life Satisfaction

with Sleep, Caffeinated Drinks and Physical Exercise among Qassim Medical

Students. AUMJ, 2015 December 1; 2(4): 7 - 16.

Key Words: Sleep, Energy drinks, Caffeinated drinks, Physical exercises, Medical

students, Qassim, Saud Arabia, Life satisfaction.

Introduction

Stress of medical education, particularly

in the student-centered systems, could

affect the quality of students' life(1,2)

.

Stress affects students' academic

achievement and the quality of education




2015 2015

and clinical skill development. Such

stressors include sleep disturbances,

frequent intake of caffeinated and energy

drinks and unsatisfactory practice of

physical exercise(3)

. It is a vicious circle

of stressful academic activities and exams

particularly in the self-directed

curriculum that lead to more sleep

disturbance and consumption of

alertness-improving drinks without real

relaxation time for an enjoyable physical

exercise. Frequent intake of caffeinated

drinks not only affect sleep and academic

performance on the long run but also

hinder the absorption of essential

nutrients, reduce the blood flow to the

brain, reduces insulin efficacy, and may

induce heartburn(4-6)

. Among Taiwanese

university students, compared to females,

males showed nonsignificantly higher

body mass index, higher rate of

exercising, better sleep quality, better

quality of life, and higher reporting of

good self-perceived health. Moreover,

there was a strong positive correlation

between exercise frequency, sleep

quality, and quality of life. Self-perceived

health and satisfaction with exercise

participation significantly predicted

quality of sleep and physical quality of

life. Exercise frequency positively

correlated, and exercise intensity

negatively associated with physical

quality of life(7)

.

Information about contributing causes to

the epidemic of poor sleep in medical

trainees is essential to improve the overall

quality of medical students’ life and their

academic performance and the

foreseeable quality of health care they

would provide. Moreover, since sleep

self-awareness and general knowledge

appear insufficient in the published

studies, increasing education about sleep

for students is urgent(8,9)

. Sleep

disturbances may be a marker of current

or future psychiatric problems in medical

students and vice versa. Likewise, the

presence of psychiatric illness may

complicate the diagnosis and treatment of

sleep disorders(10,11)

. Adequate physical

activity and physical fitness are important

for students since they improve their

academic performance, through

improving the executive functions of the

brain as well as attention, memory, and

knowledge retention(3,12)

.

In this study, a scale of life satisfaction

that considered various components of

subjective well-being in light of students'

sleep habit, physical activity and intake

of energy/caffeinated drinks was

investigated using a structured self-

administered questionnaire(1)

. Students in

the transition phase from high school to

self-directed medical education were

targeted since it is the most stressful stage

of such education.

Participants and Methods

Setting: A cross-sectional study was

conducted during 2014-2015 academic

year among 1st and 2

nd year medical

students, College of Medicine, Qassim

University, Burydah, Saudi Arabia. Data

collection spanned 1 month. A

satisfaction of life scale questionnaire of

eighteen items was used (Appendix 1)

adopted from the University of Kentucky

College of Medicine (13)

. The questions

were grouped into 3 categories: sleep,

physical exercise and intake of

caffeinated drinks. A focus group

discussion with medical graduates, senior

medical students and of medical

education experts at the College was

carried out to assess the understandability

and applicability of the questionnaire and



2015 2015

the recommended modification were

adopted. Assuming that participants'

satisfaction p = 0.5, q = 1 - p = 0.5, d =

0.1, sample size was calculated to be

95(14)

. The Questionnaire was distributed

to all 1st and 2

nd year students of both

genders. The questionnaire starts with a

section that collects demographic data of

the participants (age, gender and marital

status). The questionnaire was distributed

and collected through a link designed by

Google drive. Data entry and analysis

was carried out using SPSS (version 17

for Windows). Descriptive statistics were

expressed as frequencies, percentages and

mean ± SDM. Chi-Square (X2) test was

used to compare between categorical

variables and Student's t-test was used to

compare between means of variables of

the two groups. Inclusion criteria: 1st and

2nd

year Saudi students of both genders

from Qassim College of Medicine who

voluntarily and verbally accepted to

participate in this study. There were no

specific exclusion criteria. Ethical

approval was obtained from the local

Research and Ethics Committee.

Results

As shown in Table 1, the total number of

respondents was 186; first year, 106

(57%) and second year 80 (43%), among

which males were 127 (68.3%) and

females were 59 (31.7). The mean age of

males and females were 19 ± 0.09 and

18.4 ± 0.38 years, respectively (p =

0.004). Marital status showed that 3

students were married (1.6%) and 183

were unmarried (98.4%).

Table 1: Academic year, gender, age and marital status distribution of participants. Data shown

are frequencies (n and %) and mean ± SDM as appropriate, and p value. Total number of

respondents = 186.

Characteristic n (%) P value

Academic Year: First year/Second year 106 (57)/80 (43) <0.001

Gender: Male/Female 127 (68.3)/59 (31.7) <0.001

Age: Males/Females 19 ± 0.1/18.4 ± 0.56 0.004

Marital status: Married/Single 3 (1.6)/183 (98.4) 0.24

Results in Table 2 showed that second

year students had a non-significant better

quality of sleep at night (3.5 ± 1.15 and

3.1 ± 1.6, respectively). There were

significant difference in the frequency of

energy drink consumption (0.38 ± 1 and

0.19 ± 0.46, respectively; p = 0.03),

coffee/tea/caffeinated drink intake (0.58 ±

0.9 and 1.64 ± 0.75, respectively; p =

0.05), duration of exercise (6.3 ± 0. 48

and 7. 9 ± 0.55, respectively; p = 0.04)

and nature of exercise (1.36 ± 0.55 and

1.51 ± 0.68, respectively; p = 0.005)

comparing 1st and 2

nd year students. The

remaining parameters were nearly equal

among students of both years, i.e.,

required sleeping hrs/night/weekends (6.5

± 0.45 and 6.6 ± 0.45, respectively), fall

asleep during academic activities (2.2 ±

0.6 and 2.3 ± 0.91, respectively), naps

during the day (0.85 ± 0.85 and 0.91 ±

0.91, respectively), type of exercise (1.6

± 1.57 and 1.5 ± 1.14, respectively)

physical fitness (3.35 ± 0.70 and 3.1 ±

0.84, respectively), exercising affect your

life satisfaction 3.2 ± 1.1and 3.0 ± 1.07,

respectively), gotten the important things

I wanted in life (2.9 ± 2.9 and 2.8 ± 1.14,



2015 2015

respectively), live as it is close to ideal

(3.2 ± 1.26 and 3.2 ± 1. 21, respectively)

and I change almost nothing in my life

(4.47 ± 1.38 and 3.5 ± 0.99, respectively).

Table 2: Satisfaction scores among the 1st and 2nd year medical students, Qassim University

college of Medicine. Data shown are mean ± SD and p value.

Item Mean ± SD P

value 1st year 2nd year

1. How many hours of sleep do you get each night?

Hrs

3.1 ± 1.6 3.5 ± 1.15 0.64

2. How many hours of sleep do you require each

night? Hrs

6.5 ± 0.45 6.6 ± 0.45 0.82

3. Do you fall asleep during academic activities?

Yes/No

2.2 ± 0.6 2.3 ± 0.91 0.29

4. Do you take naps during the day? Times/Day 0.85 ± 0.85 0.91 ± 0.91 0.28

5. On weekends, how many extra hours of sleep per

night do you take? Hrs

2.4 ± 0.75 2.3 ± 0.77 0.07

6. Currently, How many energy drinks do you take?

Cans/Day

0.38 ± 1 0.19 ± 0.46 0.03

7. Currently, How much coffee/Tea/Caffeinated

drinks do you take? Glass/Day

0.58 ± 0.9 1.64 ± 0.78 0.05

8. Which type of exercise do you perform?

(Anaerobic = 1, aerobic = 2, both = 3)

1.6 ± 1.57 1.5 ± 1.14 0.81

9. For how long do you exercise daily? Minutes/day 6.3 ± 0.48 7.9 ± 0.55 0.04

10. What is the nature of the exercise you perform?

(Mild = 1-3, moderate = 4-7, strenuous exercise =

8-10)

1.36 ± 0.55 1.51 ± 0.68 0.005

11. How would you rate your overall physical fitness?

(Excellent = 4, good = 3, average = 2, poor = 1)

3.35 ± 0.70 3.1 ± 0.84 0.44

12. Did exercising affect your life satisfaction?

(Strongly agree = 5, agree = 4, neutral = 3, disagree

= 2, strongly disagree = 1)

3.2 ± 1.1 3.0 ± 1.07 0.17

13. I have gotten the important things I wanted in life.

Yes/No

2.9 ± 2.9 2.8 ± 1.14 0.1 9

14. Generally, my life is close to ideal. (Strongly agree

= 5, agree = 4, neutral = 3, disagree = 2, strongly

disagree = 1).

3.2 ± 1.26 3.2 ±1.21 0.79

15. If I could live my life over, I would change almost

nothing in my life. Yes/no.

4.47 ± 1.38 3.5 ± 0.99 0.54

Results in Table 3 show that males had a

non-significantly better total score than

females concerning the quality of sleep at

night (3.8 ± 1.13 and 3.1 ± 1.25,

respectively). There was a significant

difference in napping during the day

(0.86 ± 0.6 and 0.92 ± 0.38 respectively;

p = 0.001). Males had significant



2015 2015

difference compared to females

concerning each of energy drink intake

(0.38 ± 10.19 ± 0.46, respectively; p =

0.03), how much coffee/Tea/Caffeinated

drink are taken (0.58 ± 0.9 and 1.64 ±

0.78, respectively; p = 0.001), and

exercise daily (7.74 ± 0.62 and 5.9 ± 0.48

minutes/day, respectively; p = 0.03).

Table 3: Satisfaction scores comparing male vs. female medical students of the 1st and 2nd

academic years, Qassim University college of Medicine. Data shown are mean ± SD and p value.

Item Mean ± SD P

value Males Females

1. How many hours of sleep do you get each night?

Hrs

3.8 ± 1.13 3.1 ± 1.25 0.93

2. How many hours of sleep do you require each

night? Hrs

6.6 ± 0.59 6.5 ± 0.7 0.8

3. Do you fall asleep during academic activities?

Yes/No

2.3 ± 0.58 2.2 ± 0.6 0.17

4. Do you take naps during the day? Times/Day 0.86 ± 0.6 0.92 ± 0.38 0.001

5. On weekends, how many extra hours of sleep per

night you take? Hrs

2.3 ± 0.76 2.5 ± 0.75 0.97

6. Currently, How many energy drinks do you take?

Cans/Day

0.38 ± 1 0.19 ± 0.46 0.03

7. Currently, How much coffee/Tea/Caffeinated

drinks do you take? Glass/Day

0.58 ± 0.9 1.64 ± 0.78 0.05

8. Which type of exercise do you perform?

(Anaerobic = 1, aerobic = 2, both = 3)

1.5 ± 0.68 1.6 ± 0.7 0.73

9. For how long do you exercise daily? Minutes/day 7.4 ± 0.62 5.9 ± 0.48 0.03

10. What is the nature of exercise you perform? (Mild

=1, Moderate = 2, Strenuous = 3)

11. How would you rate your overall physical fitness?

(Excellent = 4, good = 3, average = 2, poor =1)

3.25 ± 0.81 3.3 ± 0.67 0.8

12. Did exercising affect your life satisfaction?

(Strongly agree = 5, agree = 4, neutral = 3, disagree

= 2, strongly disagree = 1)

3.2 ± 1.10 3.0 ± 1.09 0.25

13. I have gotten the important things I wanted in life;

Yes/No

2.8 ± 1.19 3 ± 1.22 0.77

14. Generally, my life is close to ideal. (Strongly agree

= 5, agree = 4, Neutral = 3, disagree = 2, strongly

disagree = 1).

3.1 ± 1.24 3.3 ±1.23 0.56

15. If I could live my life over, I would change almost

nothing in my life; Yes/no.

4.47 ± 1.38 3.5 ± 0.99 0.54

The other parameters were nearly equal

among students of both genders, i.e.,

sleep required each night, asleep during

academic activities, extra hrs of sleep on

weekend, type of exercise performed,

overall rate of physical fitness, exercising

affects your life satisfaction, have gotten



2015 2015

the important things I wanted in life, my

life is close to ideal and I change almost

nothing in my life correlating the shift to

medical education.

Discussion

The general effect of sleep deprivation on

cognitive performance is well-known.

Staying awake longer than 18

consecutive hours deteriorates reaction

speed, short-term and long-term memory,

ability to focus, decision-making

capacity, math processing, cognitive

speed, and spatial orientation. Cut sleep

back to five or six hours a night for

several days in a row, and the

accumulated sleep deficit magnifies these

negative effects. Moreover, sleep

deprivation is implicated in all kinds of

physical maladies too, from high blood

pressure to obesity (5,6,15)

. Medical

students in the early years spend long

time studying late night and may

experience insomnia due to their

academic worries and intake of large

amounts of caffeinated beverages (16)

.

Despite caffeinated beverages helping

with short-term memory, may lead to less

productive and less effective with long-

term memory (17)

.

The present results revealed that our

medical students do not receive adequate

time of sleep and that they compensate by

sleeping more hours during weekends. A

previous study found that the medical

students in their early years of study,

sleep an average of 6.3 hours per night(3)

.

The recommended number of hours of

sleep per night in another study was eight

hours(18)

. Inadequate sleep hours

adversely affects concentration, impairs

memory and weakens physical fitness(19)

.

In a confirmation, the present study found

that the first year students drunk

significantly more energy (p = 0.03) and

coffee (p = 0.05) beverages than second

year's. Contrary to their belief, these

drinks increase the levels of adenosine,

adrenaline, cortisol, inflammatory

cytokines and dopamine in the blood,

decrease the blood flow to the brain and

decrease the academic performance(20-22)

.

It is to note than coffee is the world’s

second-most widely sold commodity,

after oil(23)

. Among Puerto Rican 1st and

2nd

years medical students, most of them

perceived their academic loads as being

heavy with moderate academic stress

levels that significantly correlated with

stress level. To stay awake, 88% of

students consumed caffeinated beverages

mainly soft drinks and coffee and the

intake is increased to cope with periods

of high stress. Energy drinks were

consumed significantly more often by

males compared to females(24)

.

As it may be expected, the present results

showed that the second year students,

who manage their medical education

better than 1st years students, significantly

perform more exercise than first year

medical students (p = 0.04). Such

exercise was also more strenuous type (p

= 0.005). Reportedly, a single bout of

aerobic moderate-intensity activity

improves the academic performance(25)

.

The time spent in physical activity is

related not only to a healthier body but

also a healthier mind(26,27)

. University

students experience high levels of study-

related fatigue with a negative impact of

fatigue on health and academic

performance. Applying a low-intensity

exercise program significantly decreased

in two of the three indicators of study-

related fatigue (i.e., overall fatigue and

need for recovery). Additionally, sleep

quality and some indicators of cognitive



2015 2015

functioning improve more among

exercisers than among controls(28)

.

The present results revealed that males

got non-significantly more hours of sleep

each night than females. Sleeping 6 - 7

hours is currently the population

average(29,30)

. A study on medical students

and interns from three Saudi medical

colleges stated that males get more sleep

each night than females(31)

. The exact

prevalence of poor sleep among healthy

medical students varies between studies

based on the measurement tools used,

cultural differences and the differences in

baseline demographics (age, gender, and

marital status). Although medical

students around the world frequently

report symptoms of either insomnia or

sleepiness than the general population,

the effect of gender is inconsistent(32)

.

Among healthy medical students in King

Saud University of Saudi Arabia, students

with “average” performance were

subjectively sleepier during class and

reported higher Epworth Sleepiness Score

compared to “excellent” students who

reported earlier bedtimes and higher sleep

duration during weekdays(33)

. Moreover,

the present study showed that males

consumed more energy drinks (p = 0.003)

and coffee (p = 0.05) than females.

Reportedly, male medical students starts

the habit of drinking energy drinks at a

younger age compared to females, while

females consume more sugar-free

varieties of energy drink(29-31)

. A

Pakistani study among medical students

reported ~43% energy drinks users

particularly to reducing sleep hours for

studying and as refreshment. However,

they experienced fatigue and weight gain

as side-effects(34)

. The present results

indicate that male medical students are

more than females in daily exercising (p

= 0.03). Social barriers may hinder

females from practicing physical

exercises in Saudi Arabia(35,36)

. A study

on female students from Colleges of

Applied Medical Sciences at Riyadh,

Saudi Arabia showed reduced level of

exercising(37)

. Even among males,

motivation towards physical fitness is

weak among third world college students

particularly due to weak culture of

sporting and non-essentiality of such

fitness for competitive employment(36)

.

The proportion of Australian medical

students who experience high levels of

psychological distress is significantly

greater than that found in the general

population. Females had non-

significantly higher levels of

psychological distress than males. Social

support and the personality traits of

emotional resilience and self-control were

major predictors among psychological

distress indicators. Therefore, embedding

emotional resilience skills training into

the medical school curriculum could

reduce psychological distress among

medical students(38)

.

Conclusion

Although their overall life satisfaction in

good, our medical students in 1st and 2

nd

academic years do get enough sleep

hours, have high rate of caffeinated

beverage consumption, and reduced time

of physical exercising. Such drawbacks

are expected to impact their physical

fitness and academic performance.

Measures to raise their awareness of the

side-effects of such energy and

caffeinated beverages, increase the

quality and duration of sleep, and

encouraging their physical exercising are

urgent to ensure the improvement of their



2015 2015

general life satisfaction and academic

performance.


The study timing was not the most

stressful during the targeted academic

year to guard against miniaturizing

the response rate.

The academic performance was not

correlated with the life satisfaction

indicators investigated because of

difficulties exposing student's

academic performance.

Causes of not exercising are

speculative since the questionnaire

did not ask from hindering factors.

Conflict of Interest: The author


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Alshammari & Alshammari - Determinants of smoking cessation-counseling …..


2015 2015

Original Article

Determinants of Smoking Cessation-Counseling Practices among Primary Health Care Physicians in Riyadh Military

Hospital Kingdom of Saudi Arabia with Special Reference to Their Smoking Status

Nawaf Alshammari, Reem Alshammari

Department of Family Medicine, 1King Abdul-Aziz Medical City, NGHA, and

2Ministry of health, Riyadh, Saudi Arabia.


Abstract

Background: Smoking is a critical international issue that highlights the critical

preventive role of the primary healthcare physicians (PHCPs). Objectives: To assess

the smoking status of PHCPs working in primary healthcare centers belonging to the

Military Hospital (MH) in Riyadh City, Saudi Arabia and determine its influence on

their smoking cessation-counseling practice. Participants and Methods: A validated

questionnaire with 6 sections was distributed to 180 PHCPs, working in the primary

health care centers belonging to MH. Results: Out of the 180 PHCPs, 132 replies were

received with a response rate of 73%. Of the 132 respondents, 66% were men and

18.7% were current smokers. Male physicians reported a much higher rate of smoking

than did female physicians (24.1% vs. 8.9%; p = 0.037). Nearly half of respondents

believed that their current knowledge (57%) and skills (55%) were sufficient for

helping patients to stop smoking. Only (42%) of the respondents had read any smoking

cessation guidelines. Of the 132 respondents, 124 (93%) asked every patient about their

smoking status, 106 (80%) recorded smoking status in the medical record, 91 (68%)

advised smokers to quit and 44 (33%) arranged follow up to their patients. Multivariate

regression analysis showed that there was significant model for advising patient to quit

and record patient smoking status. But there were no significant model for asking about

smoking and arranging follow up to the patient. Conclusion: This study concluded that

physician's age and smoking status were associated with the content of their cessation

interventions with patients who smoke. Taking physician age and smoking status into

consideration in the design of cessation training programs may improve cessation-

counseling interventions. Al-shammari N, Al-shammari R. Determinants of

smoking cessation-counseling practices among primary health care physicians in

Riyadh Military Hospital Kingdom of Saudi Arabia with special reference to their

smoking status. AUMJ, 2015 December 1; 2(4): 17 - 26.

Key words: Smoking cessation, Counseling practices, Primary healthcare physicians,

Saudi Arabia.

Introduction

Smoking represents a critical

international issue for public health

policy makers and strategists. According

to the World Health Organization,

tobacco is the second major cause of

death and the fourth most common risk

factor for disease worldwide. If current




2015 2015

trends continue, it will be causing around

10 million deaths each year by 2020, with

approximately 650 million fatalities

overall(1)

. Smoking is also considered the

single most preventable cause of

premature death in some industrial

countries(2)

. It is a major risk factor for a

range of diseases and disabling

conditions. These include cardiovascular

diseases, stroke, and many cancers,

including cancer of lungs, throat, cervix,

bladder and tongue. It adversely affects

male sexual life, and women who smoke

can suffer reduced fertility and/or

menstrual problems(3)

. Smoking during

pregnancy increases the risk of abruptio

placentae, bleeding during pregnancy,

premature rupture of membranes, fetal

death, and neonatal mortality(4,5)

.

Smoking tobacco not only predisposes to

the development of disease, but it also

increases disease severity and treatment

failure rates(6)

.

Smoking represents a key issue in the

medical profession, as physicians play a

leading role in tobacco usage prevention

in the community(7)

. Physicians also can

play a key role in smoking cessation(8,9)

.

In 1979, Russell and colleagues published

what would become one of the most cited

and inspirational papers in the history of

research into stopping smoking. They

found that doctors who gave their patients

brief advice and “warned” that they

would follow them up could expect a

5.1% increase in the number who stopped

smoking for at least 12 months beyond

that in controls who received no

advice(10)

.

Physicians can also serve as role models

for healthy behaviors by not smoking.

Smoke-free hospitals are important for

the health of patients and health care

workers, and can help with smoking

cessation. Physician education is

important, particularly on counseling

smokers about active and passive

smoking harms, as physicians who

believe such counseling is effective are

significantly more likely to ask about

smoking status and to advise smokers to

quit(11)

. A multi-country literature review

about the factors influencing European

General Practitioners (GPs') engagement

in smoking cessation was published in

2009. It showed that most GPs in Europe

question the smoking status of all new

patients but fewer routinely ask this from

regular patients, or advise smokers to

quit. The proportion offering intensive

interventions or prescribing treatments is

still lower. Factors influencing GPs'

engagement in smoking cessation include

GPs' own smoking status and their

attitudes towards giving smoking

cessation advice.

Although smoking remains a problem of

considerable magnitude in the Kingdom

of Saudi-Arabia, studies with respect to

smoking cessation activities among

physicians are not available. The current

study aimed to explore the determinants

of smoking cessation counseling practices

among primary care physicians with

special reference to their smoking status.

Participants and Methods

Study design and period: This

questionnaire-based cross-sectional study

was conducted between January to June

2012 in Riyadh City, Saudi Arabia. Study

population and setting: All family

physicians registered with the Saudi

Commission for Health specialties

(SCHS) working in the primary health

care centers belonging to the Military

Hospital in Riyadh City (n = 180) were



2015 2015

considered eligible to be included in the

study. The centers where the study was

conducted included the main center of

Al-Wazarat and the peripheral centers of

Officers' Clinic, Senior Officers' Clinic,

Noncommissioned Officers' Clinic and

Al-Morooj Clinic. Given that the study

population is relatively limited, all

physicians who met the inclusion criteria

(being a family physician registered with

SCHS) and present at the time of the

study were invited to be enrolled in the

study.

Data collection: A structured self-

administered questionnaire was used as

the tool for data collection. The

questionnaire consisted of selected

questions from a previously validated

instrument that measured physicians

smoking status and cessation counseling

practices in a study done among Chinese

physicians(12)

. The questionnaire had six

sections that included the following. The

first section included demographic data

of respondents such as age, gender,

nationality, grade, qualifications and

years of experience. The second section

was about cigarette use by the physicians.

The smoking status was classified as

current, former, or never smokers

according to WHO classification(13)

.

Current smokers were defined as those

who had smoked for at least six months

during their lifetime and were smoking at

the time of the survey. Former smokers

were defined as those who had smoked

for at least six months during their

lifetime but had not smoked for at least

six months before the survey. Never

smokers were defined as those who had

never smoked or had smoked for fewer

than six months during their lifetime. For

this study, former and never smokers

were collapsed into the category

“nonsmokers. The third section consisted

of four questions, each with three

possible answers which explored attitude

towards smoking cessation

guidelines/practices. The fourth section

was about knowledge regarding smoking

cessation and confidence in advising

patients. A Likert scoring system was

used to categorize the responses from 1

for “strongly agree” through 5 for

“strongly disagree.” The fifth section was

about worksite practice. It explored

simple evidence based clinical guideline

for physician to use with their patients

who smoke. The sixth section consisted

of two questions about smoking cessation

training.

Approval was taken from the Research

Committee of Family and Community

Medicine Department. All data were

maintained in a secure and confidential

manner. The questionnaire was pilot

tested among 18 doctors and its clarity,

language and un-ambiguity were tested

and appropriate changes made, these

doctors were excluded from the final

analysis. Anonymity of the questionnaire

was assured to ensure confidentiality of

the responses.

Written consent of the respondents was

considered as a prerequisite to be enrolled

in the study. To ensure an acceptable

response rate, the researcher by himself

distributed the questionnaire to the

respondents and was available at the time

of filling the questionnaire for any

clarification. The researcher further took

initiative to visit the respondents outside

busy hours without disturbing the flow of

work in the health centers.

Data analysis: Data entry and statistical

analysis were done using SPSS 15.0



2015 2015

statistical software package, and quality

control was conducted at the stages of

coding and data entry. Descriptive

statistics in the form of frequencies and

percentages for qualitative variables, and

means ± standard deviations for

quantitative variables were calculated.

Chi-Square test was used for categorical

data. Statistical significance was

considered at p<0.05 with a 95%

confidence level.

Results

Out of the 180 primary care physicians

working in Riyadh Military Hospital, 132

replies were received with a response rate

of 73%. Table 1 presents the

demographic characteristics of

participating physicians. The mean age of

the study sample was 35.3 ± 8.52 ranging

from 24 to 60 years. Of the respondents,

66% were men, 60% were Saudi and 56%

were board certified.

In this study most of the primary care

physicians, 54 (41%) were registrars,

followed by 52 (39%) who were

residents. 60 (45.5%) of the doctors had

an experience of working as primary care

physicians for less than five years and

only 24 (18.2%) doctors had 15 or more

experience years.

The prevalence of smoking in this study

was 19%. Male physicians reported a

significantly higher rate of smoking than

did female physicians (24.1% vs. 8.9%; p

= 0.037). None of the other demographic

features like age, nationality, grade,

experience, qualification reached

statistical significance between smokers

and non-smokers (Table 2).

Table 3 shows the attitude towards

smoking cessation guidelines/practices

among 132 participant physicians.

Seventy nine percent of all physicians

think that a guideline will be helpful in

managing patients who smoke. Ninety

one percent of all physicians feel that

smoking cessation advice is part of the

doctor’s role. Smokers are less likely than

nonsmokers to have such attitude (80%

vs. 93.5%; p = 0.035).

Only 76% of all physicians think that an

advice to quit is helpful in smoking

cessation. Also smokers are less likely

than nonsmokers to have such attitude

(56% vs. 80.4%; p˂0.01). The table also

shows that 54 physicians (41%) think that

special incentives (like additional

payment) would change their current

practice regarding smoking cessation

counseling.

Table 1: Socio-demographic characteristics of

participants. Data shown are frequencies (n

and %) or Mean ± SD (Range) and p value.

Senior house officer = SHO.

Characteristic n (%) p<

Age: Years 35.29 ± 8.52

(24 – 60)

-

Gender:

Male/Female

87 (65.9)/

45 (34.1)

0.000

Nationality:

Saudi/Non-Saudi

80 (60.6)/

52 (39.4)

0.015

Holding Board

Certificate: Yes/No

58 (43.9)/

74 (56.1)

0.164

Physician Rank:

SHO

6 (4.5) 0.000

Resident 52 (39.4)

Registrar 54 (40.9)

Consultant 20 (15.2)

Experience: Years

1 - 5

60 (45.5) 0.000

5 - 9 29 (22.0)

10 - 14 19 (14.4)

˃15 24 (18.2)



2015 2015

Table 2: Comparison of demographic characteristics between smokers and non-smokers. Data

shown are frequencies (n and %) or Mean ± SD and p value.

Characteristic n = 132 Non-Smokers

n = 107

Smokers

n = 25

p =

n (%) n (%)

Age, Years 35.15 ± 8.67 35.88 ± 7.97 0.701

Gender: Female/Male 45/87 41 (91.1)/66 (75.9) 4 (8.9)/21 (24.1) 0.037

Nationality: Saudi/Non-Saudi 80/52 65 (81.3)/42 (88.8) 15 (18.8)/10

(19.2)

0.945

Holding Board Certificate:

No/Yes

58/74 48 (82.8)/59 (79.7) 10 (17.2)/15

(20.3)

0.659

Physician Rank: SHO/ Resident 58 43 (82.7) 11 (21.2)

0.969 Registrar 54 44 (81.5) 10 (18.5)

Consultant 20 16 (80.0) 4 (20.0)

Experience: Years 1-5 60 51 (85.0) 9 (15.0)

0.612 5-9 29 22 (75.9) 7 (24.1)

10-14 19 16 (84.2) 3 (15.8)

˃15 24 18 (75.0) 6 (25)

Table 3: Attitude towards smoking cessation guidelines/practices among participant’s physicians

according to smoking status. Data shown are frequencies (n and %) and p value.

Attitude n (%) Non-Smokers Smokers p =

n (%) n (%)

Do you think that a guideline will be helpful

in managing your smoking patients?

104 (79) 83 (77.6) 21 (84.0) 0.594

Do you feel that smoking cessation advice is

a part of the doctors' role?

120 (91) 100 (93.5) 20 (80) 0.035

Do you feel that advice to quit is helpful in

smoking cessation?

100 (76) 86 (80.4) 14 (56.0) 0.010

Do you think that special incentives (like

additional payment) would change your

current practice regarding smoking cessation

counseling?

54 (41) 44 (41.1) 10 (40.0) 0.918

Table 4 shows that most of the

participants (71%) believe that they can

explain the risks attributed to smoking in

detail to the patient; but only nearly half

of them believe that their current

knowledge and skills are sufficient for

helping patients to stop smoking and also

half of them feel that they are well-

prepared in counseling patients on how to

stop smoking. The same table shows that

39% can assess smokers different stages

of readiness to quit, only 7% can assess

smokers' level of nicotine dependence

using Fagerstrom score, and 32% know

how to prescribe medication to treat

tobacco dependency. We noticed that



2015 2015

there is no statistically significant

difference between smokers and

nonsmokers in the perception of

knowledge regarding smoking cessation

and also in the confidence in advising

patients.

Table 4: Perception of knowledge regarding smoking cessation and confidence level in advising

patients among participant’s physicians according to smoking status. Data shown are frequencies

(n and %) and p value.

Knowledge & Confidence (strongly agree or

agree)

n (%) Non-Smokers

n = 107

Smokers

n = 25

p =

n (%) n (%)

My current knowledge is sufficient for helping

patients to stop smoking.

75 (57) 62 (57.9) 13 (52.0) 0.727

I can explain the risks attributed to smoking in

detail to patients.

94 (71) 76 (71.0) 18 (72.0) 1.000

My current skills are sufficient for helping

patients to stop smoking.

68 (52) 59 (55.1) 9 (36.0) 0.329

I know how to prescribe medication (nicotine

replacement therapy or bupropion) to treat

tobacco dependency.

42 (32) 38 (35.5) 4 (16.0) 0.096

I can assess smokers' different stages of

readiness to quit.

52 (39) 45 (42.1) 7 (28.0) 0.157

I can assess smoker level of nicotine

dependence using Fagerstrom score.

9 (7) 8 (7.5) 1 (4.0) 0.679

I can help smoker to quit even if the smoker

thinks that it is difficult to give up.

40 (30) 35 (32.7) 5 (20.0) 1.000

I feel I am well prepared when counseling

patient on how to stop smoking.

74 (56) 59 (55.1) 15 (60.0) 0.755

Table 5 shows that a higher proportion of

nonsmokers (84%) than smokers (64%)

record smoking status (p = 0.023) and

advised patients to quit (p = 0.001). A

higher proportion of non-Saudi (100%)

than Saudi physicians (91%) asked

patients about their smoking status and

arranged follow up with their patients.

The same table shows a difference in

smoking cessation counseling practices

between those doctors who are board

certified and those who are not, mainly in

asking about smoking status (p = 0.043)

and in arranging follow up with their

patients (p = 0.002). More physicians

who had read any smoking cessation

guidelines followed all four smoking

cessation practices (asking about smoking

status, recording smoking status in the

medical record, advising patients to quit

and arranging follow up with their

patients). More physicians who had

training in smoking cessation advised

their patients to quit and arranged follow

up with them. Physician’s age and

smoking status are associated with the

content of their cessation interventions

with patients who smoke. Age was a

significant independent positive predictor

while being smoker is a significant

independent negative predictor (not

shown in the table).



2015 2015

Table 5: Comparison of cessation counseling practices among participants. Data shown are

frequencies (n and %) and p value.

Characteristic Ask about

smoking

Record

smoking status

Advice patients

to quit

Arrange follow

up

n (%) p = n (%) p = n (%) p = n (%) p =

Gender:

Female/Males

81 (93)/

44 (98)

0.422 70 (80)/

36 (80)

0.950 57 (66)/

34 (76)

0.237 31 36)/

13 (29)

0.436

Smoking Status:

Smoker/Non-

smoker

24 (96)/

101(94)

1.00 16(64)/

90 (84)

0.023 10 (40)

81 (76)

0.001 4 (16)

40 (37)

0.058

Nationality: Saudi/

Non-Saudi

73 (91)/

52 (100)

0.042 61 (76)/

45 (87)

0.147 51(64)/

40 (77)

0.110 19(24)/

25 (48)

0.004

Holding Board

Certificate: No/Yes

52 (90)/ 73 (99)

0.043 43 (74)/ 63 (85)

0.115 35 (60)/ 56 (76)

0.059 11 (19)/ 33 (45)

0.002

Physician Rank:

Resident

52 (89.7)

0.069

42 (72) 0.070 36 (62) 0.154 10 (17) 0.001

Registrar 53 (98.1) 45 (83) 38 (70) 22 (41)

Consultant 20 (100) 19 (95) 17 (85) 12 (60)

Experience: Years

1-5 Years

54 (90) 0.155 44 (73) 0.027 38 (63) 0.023 10 (17) 0.001

5-9 Years 28 (97) 21 (72) 16 (55) 10 (34)

10-14 Years 19 (100) 18 (95) 17 (89) 11 (58)

˃ 15 Years 24 (100) 23 (96) 20 (83) 13 (54)

Training on

Smoking Cessation:

Yes/No

21 (95)/ 104 (95)

1.00 20 (91)/ 86 (78)

0.244 20 (91)/ 71 (65)

0.021 14 (30)/ 30 (27)

0.001

Read any smoking

cessation

guidelines: Yes/No

56 (100)/ 69 (91)

0.021 53 (95)/ 53 (76)

0.000 49 (88)/ 42 (55)

0.000 30 (54)/ 14 (18)

0.000

Discussion

The response rate in the current study

was 73%, which is higher than the

response rate observed in other studies

like the Canadian study 63%(14)

. The high

response rate in this study is probably due

to self collection of the questionnaires by

the researcher himself. Another

explanation of high response rate could

be that physicians themselves in our area

were interested in this topic. This study

shows that the smoking rate among

physicians was 18.7%, which is nearly

consistent with a previous study among

primary health care physicians in Riyadh

City (17%)(15)

, but it is lower than the rate

recorded in the study of Behbehani et al

in two Gulf Arab states (34%)(16)

. Such

difference may be partially explained by

the definition of smoker, the reliability of

self reporting, the year in which the study

took place and the specialty of the



2015 2015

physicians. Also the smoking rate

recorded in this study is lower than those

of observational studies conducted among

physicians in United Arab Emirates

(43%) and Kuwait (31%)(17)

, china

(26%)(12)

, and Canada (42%)(14)

.

The current study shows that smoking is

more prevalent among male physicians

than among female physicians, which

reflects the smoking pattern among Saudi

population(15)

. This is largely due to the

social unacceptability of female smoking

in traditional societies. When the attitude

of physicians to smoking cessation advice

was considered, it was apparent that

smokers were less likely to even consider

such advice as a part of their roles as

doctors. Further they were less likely to

have any trust in their ability to influence

others by advice perhaps recognizing

their own inability to influence

themselves.

The current study shows that there was

no difference between male and female

physicians in following smoking

cessation counseling practices, which

differs from results found in studies done

in Canada and China(12,14)

where they

found a higher proportion of female than

male physicians following smoking

cessation practices. This may be

explained by the fact that female

physicians in our society may feel

embarrassed to ask patients about this

culturally unacceptable habit and also the

patients themselves feeling ashamed to

seek medical advice from female doctors

to help them to stop this bad habit of

smoking. The present study revealed a

significant difference in smoking

cessation counseling practices between

those doctors who are board certified and

those who are not. This, if confirmed in

further studies demonstrates the value of

postgraduate reinforcement of smoking

cessation practices in family medicine

department in improving doctors'

knowledge and behavior in dealing with

smokers

Also the study found a significant relation

between primary care physicians' years of

experience and smoking cessation

counseling practices mainly in recording

smoking status, advising patients to quit

and arranging follow-up. This is to be

expected as doctors become more aware

about the vast array of ill health effects of

smoking with greater experience. The

present study results show a decreasing

trend of doctors going through all four

phases of smoking cessation practice

from 93% asking, 80% recording, 68%

advising to and 33% arranging follow-up

for smokers. This could perhaps be

explained by the fact that a vast majority

of doctors while recognizing that

smoking cessation advice was a part of

their role did not find either the

enthusiasm or the time to go through all

phases of this activity. This raises the

issues of the value of longer consultation

time and measures to combat physician

burnout in maintaining good practices in

this very important area of

prevention(18,19)

.

According to the current study results,

reading any guideline about counseling

patients to quit smoking is positively

associated with asking about smoking

status, recording smoking status, advising

smokers to quit, and arranging follow-up

for smokers. It is not clear whether this is

due to a direct effect of doctors being

influenced by what they read or whether

doctors interested in smoking cessation

taking the trouble to read some guideline.



2015 2015

However, we believe that developing

smoking cessation counseling practice

guidelines in Saudi Arabia and promoting

it to the physicians would be useful.

Finally, smoking doctors are less likely to

record smoking status of patients or to

advise them.

Conclusion

The study findings suggest that

physicians in primary health care centers

belonging to the Military Hospital in

Riyadh need more formal training in

smoking cessation counseling since few

have received such training. The study

concludes that physician’s age and

smoking status are associated with the

content of their cessation interventions

with patients who smoke. Age is a

significant independent positive predictor

while being smoker is a significant

independent negative predictor. Taking

physician age and smoking status into

consideration in the design of cessation

training programs may improve cessation

counseling interventions. Research

comparing ex-smokers with none and

current smokers' counseling practice is

proposed.


First, the study was confined to one

hospital which may not be

representative of all hospitals in Saudi

Arabia given its vast resources.

Second, the response rate of 73% may

have been higher if we had delivered

a second survey.

Finally, respondents may have under

reported behaviors viewed as deviant

or socially undesirable.



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Alotaibi - Spironolactone in Refractory Hypertension: A retrospective cross- …………


2015 2015

Original Article

Spironolactone in Refractory Hypertension: A Retrospective Cross-Sectional Patients' Records-Based Study

Nasser Hadal Alotaibi

Al-Kharj Armed Forces Hospital, Al-Kharj, Saudi Arabia.


Abstract

Background: Refractory hypertension means that blood pressure (BP) continues to be

higher despite the prescription of three or more different antihypertensive agent classes.

Generally, one of these classes should be a diuretic. Spironolactone is a diuretic agent

that was recommended as a step-four therapy in the treatment of refractory

hypertension with other agents. Objectives: The purpose of this study is to investigate

the effect of spironolactone on refractory hypertension when added to other

antihypertensive agents in secondary or tertiary referral populations. In particular, the

study will look for: (1) How much of the target BP was achieved? (2) To what extent

was spironolactone tolerated? And, 3) Were there any patients’ characteristics that

predicted response to spironolactone? Materials and Methods: Data for this study

were collected from the Glasgow Blood Pressure Clinic’s computerized database

between 1972 and 2009. BP was measured in two different positions, i.e., seated and

lying position, by well calibrated mercury sphygmomanometers. The mean BP

measurement was taken after patients visited clinic from one to three visits. Results:

Data of 109 refractory hypertensive patients were included in this study. Blood

pressure on-spironolactone treatment was significantly decreased from 163.2/94.8 to

143.5/85.8 mmHg (p <0.0001). The BP on-spironolactone was significantly reduced in

both males and females. Also, the BP on-spironolactone was significantly decreased in

patients who were 70 years of age or older and who were younger than 70 years of age.

Among 109 patients with refractory hypertension, five patients had gynecomastia, four

patients had hyperkalemia, and one patient had flushing. Blood potassium levels

increased significantly in refractory hypertensive patients during treatment with

spironolactone (mean: 4.1 ± 0.6 - 4.4 ± 0.6 mmol/L; p = 0.001) but did not reach the

level of hyperkalemia. Conclusion: Spironolactone as add-on therapy is effective in

reducing blood pressure in refractory hypertensive patients. This reduction was to the

target level in the diastolic BP but not in the systolic BP, although it was close to the

target systolic BP. This was not entirely unexpected, though, since it is known that

diastolic BP is easier to control than systolic BP. Although there were side-effects in a

minority of patients, the drug was largely well tolerated. Such side-effects include

hyperkalemia and gynecomastia, where these two side-effects led to the discontinuation

of spironolactone. Alotaibi NH. Spironolactone in Refractory Hypertension: A

retrospective cross-sectional patients' records-based study. AUMJ, 2015

December 1; 2(4): 27 - 40.

Key Words: Spironolactone, Refractory hypertension, Resistance hypertension, Blood

pressure, Clinical trials.




2015 2015

Introduction

Refractory hypertension means that blood

pressure (BP) continues to be high (i.e.,

≥140/90 mmHg for the general

population and >130/80 mmHg for renal

disease and diabetic patients) despite the

prescription of three or more different

antihypertensive agent classes(1-5)

.

Generally, one of these classes should be

a diuretic(6)

.

The prevalence of refractory hypertension

can be estimated, although it is not

known exactly(2,6,7)

. However, a study

suggested that the prevalence of

refractory hypertension has been raised in

the last decade(8)

. The prevalence of

refractory hypertension increases with

age, i.e., patients over the age of 60 years

have a higher risk than younger

patients(3)

. Some studies suggest that 10%

of hypertensive patients are refractory(8)

,

whereas other studies suggest that as

many as 50% of hypertensive patients are

refractory(9)

. In addition, the prevalence

of refractory hypertension was reported to

be ≥50% in nephrologic clinics(10)

. It

seems that systolic hypertension is more

resistant to treatment than diastolic

hypertension(3)

.

There are several reasons for refractory

hypertension, including causes related to

drugs, such as drug-drug interaction,

inadequate drug selection, and the

prescription of a very low dose(6,10)

. Also,

refractory hypertension may be due to

secondary causes, such as

hyperaldosteronism, obstructive sleep

apnea, and chronic kidney disease(2,

6,10,11). In addition, lifestyle factors, such

as obesity, excessive dietary sodium

intake, heavy alcohol consumption, and

smoking, are conditions, which contribute

to refractory hypertension. Moreover,

refractory hypertension can be due to

pseudo-reasons, e.g., poor patient

compliance and white coat

syndrome(2,10,11,12,13)

. Also, genetic factors

may contribute to refractory

hypertension(6)

.

The treatment of refractory hypertension

with optimal treatment reduces

complications(14)

. Generally, patients with

refractory hypertension are treated with

three or more antihypertensive agents.

Therefore, antihypertensive agents when

used in combination enhance efficacy and

reduce adverse effects(15,16)

. An optimal

antihypertensive regimen, which is used

to treat refractory hypertension, includes

drugs from different classes, such as

diuretics, angiotensin-converting enzyme

(ACE) inhibitors or angiotensin receptor

blockers (ARB), and calcium channel

blockers, alpha-blockers, or beta-

blockers(3,17)

.

Spironolactone is a diuretic agent that

was recommended by the British

Hypertension Society as a step-four

therapy in the treatment of refractory

hypertension with other agents(18)

.

Spironolactone is a potassium-sparing

diuretic and an aldosterone

(mineralocorticoid) antagonist. This drug

acts in the distal tubule and collecting

ducts by inhibiting the effect of

aldosterone, thus increasing the excretion

of water and sodium, and inhibits the

potassium and hydrogen ion secretion(19)

.

The purpose of this study was to

investigate the effect of spironolactone on

refractory hypertension when added to

other antihypertensive agents in

secondary or tertiary referral populations.

Specifically, I wanted to answer the

following questions; 1) How much of the

target BP was achieved? 2) To what



2015 2015

extent was spironolactone tolerated? And,

3) Were there any patients’ characteristics

that predicted response to spironolactone?

Materials and Methods

Data for hypertensive patients were

recorded at the Glasgow Blood Pressure

Clinic. This clinic was established in

1968. Patients with hypertension were

seen at specialist hypertension clinics in

the four following hospitals: Western

Infirmary, Royal Infirmary, Southern

General Hospital, and Stobhill

Hospital(20,21)

. Patients were referred to

these clinics by hospital physicians or

usually by general practitioners(22)

.

Clinical details and prescribed treatments

were recorded at each visit, and then,

these records were checked and

transferred to a main computer system by

a medical information editor(20)

.

More than 11,000 hypertensive patients

are in the Glasgow Blood Pressure

Clinic’s computerised database with up to

40 years of follow up [23]. Data for this

study (the efficacy of spironolactone in

refractory hypertensive patients) were

collected from the database spanning

1972 to 2009. Out of 524 patients treated

with spironolactone, 109 met the

inclusion criteria for this cross-sectional

retrospective patients' record-based study.

The included patients' data was treated

anonymously and was approved by the

local Ethical Committee at the University

of Glasgow.

Well-calibrated mercury

sphygmomanometers were the

instruments used for measuring BP in two

different positions, i.e., seated and lying

position. The mean BP measurement was

taken after patients visited clinic from

one to three visits(20)

. Blood pressure was

measured at the Glasgow Blood Pressure

Clinic, after the patient has been in a

seating position for five minutes and a

standing position for two minutes. In

addition, heart rate was recorded.

Furthermore, the patients’ medical

history was recorded, e.g., ischemic heart

disease (IHD), heart failure (HF),

myocardial infarction (MI), left

ventricular disease (LVD), airway

disease, cerebrovascular disease (stroke

or transient ischemic attack (TIA)), renal

impairment, secondary hypertension, and

diabetes. Other recorded information

included age, gender, smoking habits,

weight, alcohol intake, and current

medications used.

Inclusion/Exclusion Criteria: Inclusion

criteria were any patients on

spironolactone, but who received at least

three antihypertensive agents before

adding spironolactone. Also, patients

should have systolic BP of ≥140 mmHg

or diastolic BP of ≥90 mmHg. Exclusion

criteria were any patients who did not

receive spironolactone or administered

spironolactone as a monotherapy, or as a

second antihypertensive. In addition, any

patients who have congestive heart

failure, liver cirrhosis, polycystic ovarian

syndrome, and primary

hyperaldosteronism were excluded.

Statistical Analysis: The MINITAB

programme was used to perform the

statistical analysis. The results were

expressed as means ± SDM. A paired t-

test was used to compare the mean BP

before and after spironolactone treatment.

Two sample t-test was used to compare

the response to spironolactone treatment

between male and female patients. The

difference between the two groups was

considered significant at p value <0.05.



2015 2015

Results

From 1972 to 2009, 524 patients with

hypertension were treated with

spironolactone, as add-on therapy in the

case of most of the patients, or as

monotherapy treatment in a few patients.

Out of 524 hypertensive patients, 415

patients were excluded from the study

and 109 patients were included (Figure

1). A total of 109 refractory hypertensive

patients were included in this study; 48%

of them were male patients and 52% were

female patients. The ages of the patients

ranged from 36 to 97 years (69.7 ± 14.3)

(Table 1).

Figure 1: Scheme of patients’ recruitments.

Table 1: Summary of the patients’ criteria. Data shown are frequencies (n and %) and Mean ±

SDM.

Characteristic Male Female Total

Patients, n (%) 52 (48%) 57 (52%) 109 (100%)

Age, Year 67.4 ± 14 71.9 ± 14.3 69.7 ± 14.3

Baseline Systolic BP, mmHg 156.8 ± 20.8 169.1 ± 27 163.2 ± 24.9

Baseline Diastolic BP, mmHg 95 ± 13.3 94.7 ± 14 94.8 ± 13.6

Last Systolic BP, mmHg 136.7 ± 21.1 149.8 ± 28.9 143.5 ± 26.2

Last Diastolic BP, mmHg 86.1 ± 13.8 85.7 ± 14.7 85.8 ± 14.2

Anti-hypertensives with spironolactone, n 4.3 ± 0. 54 4.4 ± 0.59 4.4 ± 0. 57



2015 2015

Out of the 109 patients with refractory

hypertension, 75 patients (68.8%)

received spironolactone as a fourth-line

therapy, 29 patients (26.6%) received

spironolactone as a fifth-line therapy, and

five patients (4.6%) received

spironolactone as a sixth-line therapy.

Spironolactone was used in doses

between 25 and 200 mg daily.

Refractory hypertensive patients used a

combination of different classes of

antihypertensive agents. Antihypertensive

classes that were prescribed in addition to

spironolactone included thiazide diuretics

(78%), beta-blockers (67.9%), calcium

channel blockers (59.6%), angiotensin

converting enzyme inhibitors (49.5%),

alpha-blockers (46.8%), and angiotensin

II receptor antagonists (40.4%). Also,

other drugs were used, such as loop

diuretic agents (18.3%), potassium-

sparing diuretics and non-competitive

aldosterone antagonist (i.e., amiloride)

(4.6%), centrally acting antihypertensive

drugs (16.5%), and vasodilator

antihypertensive drugs.

The mean systolic BP for the 109

refractory hypertensive patients before

adding spironolactone as add-on therapy

was 163.2 ± 24.9 mmHg (range: 122 -

262; median: 160). The mean diastolic

BP was 94.8 ± 13.6 mmHg (range: 58 -

132; median: 94) before adding

spironolactone.

Two refractory hypertensive patients

were switched from treatment with

spironolactone to eplerenone. One was

due to breast pain, but the reason was not

stated for the second patient. Twenty-one

patients discontinued spironolactone; five

(4.6%) patients had gynecomastia, four

(3.7%) had hyperkalemia, and one (0.9%)

had flushing. Four (3.7%) patients

discontinued treatment due to

ineffectiveness of spironolactone in

reducing BP. While in seven (6.4%)

patients, the reasons for discontinuation

of spironolactone were not stated.

Effect of Spironolactone on the Whole

Study Population (109 patients)

Forty patients on-spironolactone

treatment were reported with reduction in

both systolic and diastolic BP to the

target level, whereas, systolic BP reduced

to the target level in 13 patients and

diastolic BP in 24. The mean pre-

spironolactone BP was 163.2/94.8

mmHg, and the mean BP on-

spironolactone treatment was 143.5/85.8

mmHg. Systolic and diastolic BP showed

a significant reduction of 19.7 mmHg and

9 mmHg, respectively, on-spironolactone

(p<0.0001). The distribution of pre-

spironolactone and on-spironolactone

systolic BP shown in Figure 2

demonstrates the reduction in systolic BP

brought about by the addition of

spironolactone with a shift in the

distribution means to the left.

Figure 3 (Left part) shows the scatterplot

of the systolic BP pre- and on-treatment

with spironolactone. It shows that most

patients had a systolic BP that was

greater than 150 mmHg before adding

spironolactone but less than 150 mmHg

after adding spironolactone. Figure 3

(Left part) shows the scatterplot of the

diastolic BP pre- and on-treatment with

spironolactone. It shows that most

patients had a diastolic BP that was

greater than 90 mmHg before adding

spironolactone but less than 90 mmHg

after adding spironolactone.



2015 2015

Figure 2: Histograms of systolic blood pressure (SBP) pre- and on-treatment with spironolactone.

Figure 3: Left) Scatterplot of Systolic blood pressure (SBP) pre- and on-treatment with

spironolactone. It shows that most of patients had SBP greater than 150 mmHg before adding

spironolactone, but less than 150 mmHg after adding spironolactone. Right) Sactterplot of

diastolic blood pressure (DBP) pre- and on-treatment with spironolactone. It shows that most of

patients had DBP greater than 90 mmHg before adding spironolactone, but less than 90 mmHg

after adding spironolactone.

Multivariable Regression Analysis of

Systolic BP Reduction On-spironolactone

Multivariate regression using age, gender,

systolic BP pre-spironolactone, potassium

pre-spironolactone, and total number of

antihypertensive drugs showed that only

pre-spironolactone systolic BP was

significantly associated with the

magnitude of systolic BP reduction on-

spironolactone (beta = -0.78; R2 = 0.45,

p<0.0001) (Table 2).



2015 2015

Table 2: Multivariable regression analysis of systolic blood pressure (SBP) reduction on-

spironolactone. Data shown are beta, standard error (SE), p value and lower and upper bound

values for 95% confidence intervals (CI) of beta.

Model Beta SE P-value 95% CI for Beta

Lower

Bound

Upper

Bound

Constant 60.486 30.405 0.052 -0.499 121.472

Age 0.455 0.266 0.092 -0.077 0.988

Pre-spironolactone SBP -0.784 0.125 <0.0001 -1.035 -0.534

Gender 7.750 6.143 0.213 -4.571 20.071

Pre-treatment Potassium 0.784 6.180 0.900 -11.611 13.179

Pre-spironolactone Anti-hypertensives, n -0.172 3.659 0.963 -7.512 7.167

Effect of Patients' Characteristics on the

Response to Spironolactone

Gender: Spironolactone reduced BP in

both males and females of the population

(Table 1). The mean reduction in systolic

BP in male patients (n = 52) was -20.1 ±

23.3 mmHg, i.e., reduced from 156.8 ±

20.8 to 136.7 ± 21.1 mmHg. This

reduction in systolic BP was significant

(p <0.0001). The mean of males’ diastolic

BP was reduced from 95 ± 13.3 to 86.0 ±

13.8 mmHg. The mean diastolic BP

difference was -9 ± 10.5 mmHg, and this

reduction was significant (p <0.0001).

Female refractory hypertensive patients

(n = 57) had a reduction in systolic BP by

19.3 ± 30.4 mmHg (i.e., from 169.1 ± 27

to 149.8 ± 28.9 mmHg; p <0.0001). Their

diastolic BP was reduced by a mean of -9

± 13.6 mmHg (i.e., from 94.7 ± 14 to

85.7 ± 14.7 mmHg; p <0.0001).

Age: Refractory hypertensive patients

who were 70 years of age or older (n =

54) responded to treatment with

spironolactone. Spironolactone reduced

BP from a mean of 173.6 ± 25.6/92.1 ±

16.4 to 152.8 ± 27.5/84.7 ± 16 mmHg.

The mean reduction in BP was significant

by -20.7 ± 32.3/-7.4 ± 14 mmHg (p

<0.0001). In addition, refractory

hypertensive patients who were younger

than 70 years of age (n = 55) also

responded to treatment with

spironolactone. The mean systolic BP

reduction was -18.6 ± 21.2 mmHg, i.e.,

reduced from 153.1 ± 19.6 to 134.4 ±

21.4 mmHg. This reduction was

significant (p <0.0001). Also, the mean

diastolic BP was reduced from 97.5 ± 9.5

to 87 ± 12.1 mmHg. The mean significant

reduction was -10.5 ± 9.9 mmHg (p

<0.0001).

Smoking: Spironolactone was effective to

reduce systolic BP in smoker patients (n

= 7). The mean of systolic BP reduction

was -18 ± 17.2 mm Hg, i.e.,

spironolactone significantly reduced

systolic BP from 158.7 ± 22.6 to 140.7 ±

23 mm Hg (p = 0.032). The mean of

diastolic BP non-significant reduction

was -7.8 ± 10 mm Hg (from 96.4 ± 4.5 to

88.6 ± 10.9 mm Hg; p = 0.084). But this

failure to reach statistical significance

may have been due to the small subgroup

size.

Diabetes: In diabetic patients (n = 6),

spironolactone reduced systolic BP from

154.3 ± 24 to 124.8±21.2 mm Hg. The

mean of reduction was -29.5 ± 34.2 mm

Hg. This reduction was not significant (p



2015 2015

= 0.088) possibly due to small subgroup

size. On the other hand, the reduction in

diastolic BP was -13.7 ± 10.4 mm Hg,

i.e., diastolic BP was significantly

reduced from 89.5 ± 8.9 to 75.8 ± 10.3

mm Hg (p = 0.024.

Potassium Levels: In this study, four

(3.7%) female patients had hyperkalemia.

The maximum reported potassium level

was 5.7 mmol/L. Blood potassium levels

increased significantly in refractory

hypertensive patients during treatment

with spironolactone but did not reach the

level of hyperkalemia. The mean of

potassium levels increased from 4.1 ± 0.6

to 4.4 ± 0.6 mmol/L. The mean

significant difference in potassium levels

was 0.3 ± 0.6 mmol/L (p = 0.001; Table

3).

Table 3: Effect of spironolactone on potassium levels (PL) compared to pre-spironolactone (PS).

Data shown are n, mean ± SEM, p value and 95% confidence intervals from mean differences

(CI FMD).

Patients, n PL PS PL on-spironolactone PL (pre- vs. On-) P value 95% CI FMD

49 4.1 ± 0.6 4.4 ± 0.6 0.3 ± 0.6 0.001 (0.1, 0.5)

Discussion

In the refractory hypertensive patients in

this study, spironolactone was added to

three or more drugs. Of the 109 refractory

hypertensive patients, 78% used thiazide

diuretics, which are considered as a

foundation of multidrug regimens in

refractory hypertension. Also, around

68% of patients used beta-blockers and

almost all were elderly. A combination of

antihypertensive agents is usually

necessary to achieve target BP for

hypertensive patients(24)

. Target BP for

the general population is less than 140/90

mm Hg and for patients with renal

disease and diabetes mellitus is less than

130/80 mm Hg, which was recommended

by The Seventh Report of the Joint

National Committee on Prevention,

Detection, Evaluation, and Treatment of

High Blood Pressure (JNC 7)(1)

. Almost

37% of 109 refractory hypertensive

patients treated with spironolactone

achieved the target BP level (both

systolic and diastolic), 12% of patients

achieved target systolic BP only, and

22% of patients achieved target diastolic

BP only. The results of this study show

that spironolactone was clearly effective

as an add-on therapy in reducing the BP

of refractory hypertensive patients, which

answers the primary objective of this

study. This finding is in agreement with

the findings of Williams et al (2015)(25)

,

Vaclavik et al (2011)(26)

, Chapman et al

(2007)(27)

, Quzan et al (2002)(14)

, Lane et

al. (2007)(28)

, Mahmud et al (2005)(29)

,

Nishizaka et al (2003)(30)

, and Sharabi et

al (2006)(31)

, which showed the

effectiveness of spironolactone in

refractory hypertensive patients when

used as add-on therapy.

Statistically, spironolactone reduced

systolic BP significantly, but not to the

targeted systolic BP (i.e., <140 mmHg).

However, the mean systolic BP on-

spironolactone was 143.5 ± 26.2 mmHg,

which is close to the target systolic BP.

Also, this mean systolic BP on-

spironolactone (143.5 ± 26.2 mmHg) was

not statistically significantly different

from the upper limit for the target BP

(i.e., 139 mmHg). Out of 109 refractory

hypertensive patients, only 48.7%



2015 2015

achieved the target systolic BP on-

spironolactone treatment and it is

noteworthy to mention that around 30%

had on average a higher pre-

spironolactone treatment systolic BP. The

overall systolic BP reduction was,

however, close to the target. Regarding

previous studies, some found that

spironolactone was able to reduce

systolic BP to the target level such as

Williams et al (2015)(25)

, Chapman et al

(2007)(27)

, Quzan et al (2002)(14)

,

Mahmud et al (2005)(29)

, and Nishizaka et

al (2003)(30)

. Whereas, others found that

spironolactone, although reduced the

systolic BP, was not able to reduce it to

the target level such as Lane et al

(2007)(28)

, and Sharabi et al. (2006)(31)

. It

seems that the ability of spironolactone to

reduce the systolic BP to the target level

depends on the baseline systolic BP (pre-

spironolactone), i.e., the higher the

baseline systolic BP, the less likely to

achieve the target systolic BP level.

Increasing systolic BP is considers a risk

factor for both cardiovascular and kidney

disease(32)

. Reducing systolic BP is

important to reduce these risk factors.

On the other hand, spironolactone was

able to reduce diastolic BP significantly

to the targeted diastolic BP (i.e., <90

mmHg). This reduction in diastolic BP to

the target level is consistent with

Williams et al (2015)(25)

, Vaclavik et al

(2011)(26)

, Chapman et al. (2007)(27)

,

Quzan et al (2002)(14)

, Lane et al

(2007)(28)

, Mahmud et al (2005)(29)

,

Nishizaka et al (2003)(30)

, and Sharabi et

al. (2006)(31)

(See Table 4 for a summary

of the findings of these previous studies).

Table 4: Summary of the previous studies findings on the effect of spironolactone as add-on

therapy in patients with refractory hypertension. Data shown are mean blood pressure (MBP)

pre- and post-spironolactone (Pre-S and Post-S, respectively) usage and the mean reduction of

blood pressure (MR-BP) in mmHg.

References n MBP pre-S MBP post-S MR-BP

Williams et al(25) 285 157/90 134.9/78.9 22.1/11.1

Vaclavik et al(26) 59 154.9/92.6 140.3/86 14.6/6.6

Chapman et al(27) 1411 157/85.3 135.1/75.8 21.9/9.5

Ouzan et al(14) 23 152/86 128/76 24/10

Lane et al(28) 119 182.3/94.9 160.6/86.4 21.7/8.5

Mahmud et al(29) 39 167/95 139/82 28/13

Nishizaka et al(30) 76 163/91 138/79 25/12

Sharabi et al(31) 42 165/93.5 142/81 23.5/12.5

The effect of refractory hypertensive

patient characteristics (gender, age,

smoking, and diabetes) on the response to

spironolactone was investigated.

Spironolactone was statistically effective

in the male and female subgroups of the

population. The mean of systolic BP in

male patients on treatment with

spironolactone achieved the target level.

On other hand, the mean of systolic BP in

female patients was not to the target

level. However, spironolactone reduced

systolic BP in male patients by -20.1 ±

23.3 mmHg and in female patients by -

19.3 ± 30.4 mmHg - that are very close to

each other. Therefore, it seems that



2015 2015

spironolactone failed to reduce systolic

BP in female patients to the target level

because the baseline systolic BP (pre-

spironolactone) was higher (169.1 ± 27

mmHg) and not because spironolactone

was less effective in females. Regarding

diastolic BP, on average spironolactone

was able to reduce it to the target level in

both male and female patients.

The findings of age subgroup patients

showed that spironolactone reduced BP

significantly in both patients under 70

years old and ≥70. However,

spironolactone reduced average BP

(systolic and diastolic BP) to the target

level only in patients under 70 years old.

Also, spironolactone reduced average

diastolic BP to the target level in patients

70 and older, but systolic BP was still

high in this group (not in the target level).

This may be influenced by isolated

systolic hypertension (ISH) that

predominates in elderly patients(32)

. The

mean of baseline systolic BP is higher in

patients 70 and older (173.6 ± 25.6

mmHg) than in those under 70 years old

(153.1 ± 19.6 mmHg), which suggests

that the failure of spironolactone to

reduce systolic BP to the target level in

patients 70 and older was due to the

higher baseline systolic BP in this

subgroup.

Among smokers, spironolactone reduced

systolic BP significantly, but the mean of

systolic BP reduction was not in the

clinical target. However, the mean of

systolic BP pre-spironolactone was 158.7

± 22.6 mmHg and on-spironolactone was

140.7 ± 23 mmHg, which is close to the

target systolic BP. Also, spironolactone

reduced the mean of diastolic BP to the

target level, but the change was not

statistically significant. However, these

result in smokers may not be reliable

because of the small sample size (n = 7).

In diabetic refractory hypertensive

patients, the mean of systolic and

diastolic BP was reduced to the target

level (<130/80 mm Hg). But statistically,

the mean change in systolic BP was not

significant. Three diabetic patients on-

spironolactone had systolic BP higher

than the target level. However, as in

smokers, these results in diabetics may

not be reliable because of the small

sample size (n = 6).

When comparing the patients subgroups,

the mean systolic BP pre-spironolactone

was higher in female patients and in

patients who were 70 years of age and

older. The reduction in systolic BP was

higher in diabetic patients than other

subgroups (males, females, smokers,

patients 70 years of age and older, and

patients younger than 70 years old).

Spironolactone reduced systolic BP to the

target level in male patients, diabetic

patients, and patients younger than 70

years old. In contrast, spironolactone

failed to reduce systolic BP to the target

level in females, smokers, and patients

that were 70 years of age and older

because of the higher baseline systolic BP

in these subgroups.

The common adverse effects due to

spironolactone are hyperkalemia and

gynecomastia or breast discomfort(33)

.

Hyperkalemia was not reported any

patients in Williams’s study(25)

. In

contrast, the present finding illustrated

that hyperkalemia was seen in almost 4%

of patients which led to the

discontinuation of spironolactone

treatment. This was twice as high as the

incidence found (2%) by Chapman and

colleagues(27)

. The mean serum potassium



2015 2015

level increased significantly with

spironolactone treatment. Regardless of

increasing serum potassium levels, serum

potassium level remained in the normal

clinical range (3.5 - 5.5 mmol/L).

Hyperkalemia can be overcome by using

a thiazide diuretic with spironolactone,

reducing spironolactone dose, or

discontinuing spironolactone use until the

potassium returns to normal level, then

restarting spironolactone at a lower

dose(34)

. The risk of hyperkalemia is

increased in patients with chronic kidney

disease, diabetes mellitus, congestive

heart failure, or elderly patients especially

those who use the combination of ACE

inhibitors and spironolactone(35)

.

Regarding this, all the four patients with

hyperkalemia were elderly; three of them

used a combination that included an ACE

inhibitor and spironolactone.

Gynecomastia is dependent on

spironolactone dose(31)

. In the present

findings, the development of

gynecomastia was illustrated in roughly

5% of patients which was similar to what

has been found in previous studies

(around 6%)(27,36)

. On the other hand,

Williams et al (2015) reported no

evidence of any cases with

gynecomastia(25)

. In the present findings,

gynecomastia was led to discontinue

spironolactone treatment. This may be

due to high dose or long-term treatment

with spironolactone. One patient of those

who had gynecomastia changed to

eplerenone, which is said to be a more

selective aldosterone antagonist.

Eplerenone is used instead of

spironolactone to overcome

spironolactone’s adverse effects(34)

.

Twenty-one (19%) of refractory

hypertensive patients discontinued

spironolactone, but unfortunately the

reasons for this discontinuation were only

known for 14 of these patients; ten

patients due to side-effects;

hyperkalemia, gynecomastia and

flushing. It is notable that these side-

effects occurred in some patients who

received small doses of spironolactone.

Since these ten patients out of the twenty-

one patients who discontinued the

spironolactone represent around 9% of

the study population, this suggests that

spironolactone treatment had a significant

incidence of side effects.

Conclusion

The present study has investigated the

effectiveness of spironolactone as add-on

therapy in refractory hypertensive

patients, which was the primary objective

of this study. Secondary objectives

included investigating how well the target

BP was achieved, the tolerability of

spironolactone, and the effect of patients’

characteristics on the response to

spironolactone. The results of this study

showed that spironolactone is effective in

reducing BP in patients with refractory

hypertension. This reduction was to the

target level in the diastolic BP but not in

the systolic BP, although it was close to

the target systolic BP. This was not

entirely unexpected, though, since it is

known that diastolic BP is easier to

control than systolic BP. In investigating

subgroups of the study, spironolactone

reduced systolic BP to the target level in

male patients and patients younger than

70 years of age, but not in female patients

and patients who were 70 years of age or

older. This could be explained by the fact

that baseline (starting) BP was higher in

the latter groups than in the former

groups. Although there were side-effects



2015 2015

in a minority of patients, the drug was

largely well-tolerated. These side-effects

included hyperkalemia and gynecomastia,

where these two side-effects led to the

discontinuation of spironolactone.

Further work needs to be done to

establish the effectiveness of fixed dose

spironolactone. More broadly, research is

also needed to conduct randomized trials

based on using spironolactone in low

dose vs. other antihypertensive agents in

patients with refractory hypertension. It

would be interesting to compare the

effect of spironolactone as fourth-line

therapy with other agents such as

doxazosin. Considerably more work will

need to be done to evaluate causes of

refractory hypertension, and then base the

treatment on these causes.


The most important limitation is that

the present study was retrospective.

This limited the strength of the

present study. Therefore, this study

was not a randomized trial.

There is no control group in this

study.

The number of smoker and diabetic

patients in this primary study was

very small. It was not possible to

reliably verify the effects of smoking

and diabetes on the response to

spironolactone because the numbers

of participants in their subgroups were

too small (7 smokers and 6 diabetics).

The doses of spironolactone were

varied among refractory hypertensive

patients and not fixed within limited

range, i.e., some patients were

administered high dose of

spironolactone (100 - 200 mg), some

were administered low dose (25 - 50

mg), or some patients were

administered low dose initially then

the dose increased gradually to high

dose (or vice-versa).

Patients who were resistant to

spironolactone were not confirmed by

24-hour ambulatory blood pressure

monitoring. Therefore, those patients

may have pseudo-resistance (e.g.,

white coat hypertension).

This study lacked the results of

measuring levels of renin and

aldosterone in most cases and,

consequently, this study was unable to

analyze these variables.



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2015 2015

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Alenzi et al Management of Post-Circumcision in Glanzmann`s Thrombasthenia …..


2015 2015

Case Report

Management of Post-Circumcision Bleeding in Glanzmann`s Thrombasthenia: Case Report and Review of Literatures

Mohammed J. Alenzi1*

, Ahmad N. M. Shehadeh2, Mosaad S. Alruwaily

2,

Bader S. Alwaladali2, Fayez S. Alenazi

2, Eid A. Aljabbari

2

1Department of Urology, College of Medicine, Aljouf University, and,

2Ministry of

Health, Sakaka, Saudi Arabia. *Correspondent author: [email protected]

Abstract

Background: Fatal bleeding episodes due to spontaneous mucocutaneous bleeding are

common in Glanzmann`s thrombasthenia (GT). The unanticipated rare genetic GT

hematological disorder of platelet function is life-threatening particularly from the

surgical interventions. Control of its bleeding with imperative approaches remains

challenging. It is regularly controlled by medical therapies (including; systemic

recombinant factor VIIa, local anti-fibrinolytic agents and blood/platelet transfusions)

and surgical therapies (including; electrocautery, laser coagulation, and embolization).

Case Description and Management: Here we describe, for the first time in the

country, an uncircumcised 10-years old Saudi boy with GT diagnosed during a regular

circumcision surgical intervention for relieving paraphimosis due to edematous

enlargement of glans penis with bluish skin coloration. The post circumcision life-

threatening bleeding - that necessitated redoing the surgery with deep suturing - was

confirmed upon hematological consultation to be a GT bleeding disorder. Effective

cessation of bleeding was achieved after repeated transfusion of packed red blood cells

reaching 8 units within 24 hours, discharge within 72 and complete wound healing

without complications within a week. Conclusions: Although very rare, GT should be

anticipated upon surgical intervention with secured packed red blood cells, concentrated

platelets and/or rFVIIa (the latter two were not available for our case). This case report

represents the first description for successful management of life-threatening

hemorrhage in a GT patient in Saudi Arabia and molecular investigations are planned

since his sisters gave a history of profuse menstruation. Alenzi MJ, Shehadeh ANM,

Alruwaily MS, Alwaladali BS, Alenazi FS, Aljabbari EA. Management of Post-

Circumcision in Glanzmann`s Thrombasthenia: Case Report and Review of

Literatures. AUMJ, 2015 December 1; 2(4): 41 - 46.

Key Words: Glanzmann`s thrombasthenia, Circumcision, Paraphimosis, Saudi Arabia.

Introduction

Glanzmann's thrombasthenia (GT) is the

most frequent congenital platelet function

disorder(1)

. GT is an autosomal recessive

disorder that is caused by abnormal

quantitative/qualitative platelet function

due to mutation in the genes for

glycoproteins IIb/IIIa that disturb the

structure and signaling function of

integrin αIIbβ3 on the surface of platelets.

These protein platelet membrane

receptors function as fibrinogen receptor.

Dysfunctional platelets do not aggregate

properly at the site of injury and result in

prolonged clotting time and liability for

easy bleeding ensue(2-4)

. The disease is

usually associated with mild bleeding, but

severe fatal hemorrhage may occur(5)

.

Rarely an acquired form of the disease

could be caused by inhibitory effect of

autoantibodies against glycoprotein

IIbIIIa(6)

.



2015 2015

GT was first described by Swiss

pediatrician Eduard Glanzmann in 1918.

Patients typically present before 6 years

of age with purpura, gingival bleeding,

epistaxis, and bruisability. However, chief

complaints of gastrointestinal bleeding

may also be reported(7-13)

. GT has an

incidence of about 1/1.000.000 but is

more common in populations where

consanguineous marriage is common –

like ours. Two types of GT have been

identified; the more-severe type I has no

glycoprotein IIb/IIIa receptor complex,

and the less-severe type II has varied

amounts of the receptor molecules(9)

.

The diagnostic criteria for GT include: 1)

Normal prothrombin time (PT), 2)

Normal partial thromboplastin time

(PTT), 3) Normal absolute platelet count,

4) Normal platelet size on peripheral

smear, 5) Prolonged bleeding time, and,

6) Absence of platelet aggregation on

peripheral smear. In particular, control of

hemorrhage has been a frequent and

challenging problem for patients with GT.

Clinical researchers recently reported that

~82% of bleeding events in patients with

GT involved the nasal cavity, i.e.,

epistaxis(10)

. Recent literature reports

describe medical therapies that use

systemic recombinant factor VIIa

(rFVIIa), local anti-fibrinolytic agents, or

platelet transfusions (with or without red

blood cells) to control bleeding(10-16)

.

Those medical therapies are often used in

a neo-adjuvant or concurrent fashion with

surgical techniques. Surgical therapies

include electrocautery, laser coagulation,

and, embolization. The degree of

therapeutic success, whether medical,

surgical, or combined, varies from very

low to very high with respect to

recurrence rates(11)

.

Case Description

An uncircumcised 10-years old Saudi boy

with the history of sever penile pain was

brought to Emergency Department,

Gurayyat General Hospital (Gurayyat, Al-

Jouf, Saudi Arabia), September 12, 2015

and was referred to the General Surgery

Department. The boy's father gave an

informed consent for anonymously

reporting of the case. The pain started

incidentally associated with a swelling in

anterior shaft of penis. The patient had no

history of fever, trauma or bleeding. On

physical examination, the boy was

anxious and irritable, while vital signs

were normal. The abdomen was soft, lax

and no organomegally. There was no

bruising. Scrotum looked normal but

penis glans was edematous with slightly

bluish color and the preputial skin was

constricted around it. The abdomen was

lax with no organomegally. The patient

was diagnosed with paraphimosis and

prepared for an emergency operation after

failed conservative treatments.

Laboratory tests; complete blood count

(CBC), blood biochemistry, PT, PTT,

INR and platelets count were within the

normal range. Circumcision was

performed and compressing dressing was

done post-circumcision around the wound

in order to guard against infection and

prevent bleeding. Later in recovery room,

an oozing was noticed around the wound

dressing which was cleaned and tough

dressing was done. After the patient felt

normal, he was transferred to the ward.

After five hours, patient was inspected for

any hematoma or bleeding through the

dressing site. A big hematoma was

identified once the dressing was removed.

Patient was returned to the operation

theater. At the time of operation, one unit

of packed red blood cells (PRBCs) was

kept ready for urgent transfusion.

Upon repeat surgery, the sutures were

removed, hematoma was cleaned and

deep bites of sutures were done. Foly`s

catheter was inserted and in the recovery

room, the patient was observed for more

than one hour then transferred to his bed

in the ward. On first day post-operation,

there was some bleeding around the glans

which came out through the dressing

without clotting (Figure 1). One unit

PRBCS blood transfusion was done



2015 2015

because of his low hemoglobin of 8

gm/dL. To rule out any undiscovered

bleeding disorders after 8 units of PRBCS

transfusion, a hematologist was consulted.

Hemophilia A and B, factors II, V, VII,

X, XII and von Wilbrand`s factor

deficiencies were excluded upon

investigations. Platelet aggregation test

was abnormal. Therefore, the boy was

diagnosed to have GT. After two days of

observation, bleeding stopped completely.

Figure 1: 10-years old Saudi boy diagnosed with Glanzmann's thrombasthenia causing penis glans

hematoma after first circumcision (A), after secondary sutures (B), and, fully recovered with dry

wound a week after (C).

Patient was discharged on oral

amoxicillin and paracetamol and complete

bed rest was recommended. Aspirin and

non-steroidal anti-inflammatory and

popular traditional local herbs with

anticoagulant activities (e.g., Cardamom)

were advised to be strictly avoided. After

one week on his next visit for follow up in

urology clinic, he was looking very well

with dry wound where Foly`s catheter

was removed (Figure 1). He was advised

to visit hematology clinic with his family.

Upon detailed investigation, it was found

that his sister also is affected with the

same disease.

Discussion

GT Registry gathers worldwide

information on the effectiveness and

safety of platelet transfusion, rFVIIa

and/or anti-fibrinolytics for control of GT

bleeding. It includes 829 non-surgical

bleeding episodes data (severe/moderate:

216/613; spontaneous/post-traumatic:

630/199(1)

. Currently, the developed

understanding of coagulation physiology

permits advanced therapeutic

interventions. Impaired cytoskeletal

remodeling caused by reduced surface

expression (due to enhanced

internalization) and constitutive activation

of integrin αIIbβ3 is the main effector of

platelet dysfunction and

macrothrombocytopenia leading to

bleeding in dominant GT variants caused

by gain-of-function deletion mutations of

ITGB3 or ITGA2B(16)

.

Other than the molecular and inheritance

pattern analyses, the diagnosis of GT

depends on identifying the dysfunction of

the platelets with bleeding assessment

tools, light transmission aggregometry

using different adhesion surfaces and

other techniques such as whole blood

impedance multiplate analyzer and

labeled surface protein expression

flowcytometry subtype analysis(17-19)

.

Fatal bleeding episodes due to

spontaneous mucocutaneous bleeding are

common in GT. Control of such bleeding

remains challenging with imperative

approaches. The latter include; local anti-

fibrinolytic therapy along with platelet

transfusions. Treating and preventing GT

hemorrhage with a good clinical safety

profile achieved advancements with

injection of human rFVIIa(2,20,21)

.

Noninvasive medical therapies such as

anti-fibrinolytic agents, replacement or

supplementation of coagulation factors,

and platelets transfusion offer potential

benefit, but are not without complications.

For example, elicitation of isoantibodies

against platelet integrin complex happens

in most patients receiving frequent red

blood cell and/or platelet transfusions.



2015 2015

Once formed, the antibodies are a

formidable barrier to subsequent

transfusion therapies, platelet aggregation

is blocked and platelets are rapidly

removed by the immune system(8)

.

Although platelet transfusion is the

standard treatment for GT, rFVIIa was

also successful particularly for those

patients refractory to platelet transfusions

or developed platelet antibodies(15,22)

.

The efficacy of anti-fibrinolytic agents

and coagulation factors is an ongoing area

of research that requires refinement

before standardized approaches can be

implemented. Topical application of the

herbal hemostatic agent Ankaferd Blood

Stopper that is independent of the clotting

factors was not tried in similar cases

before despite being successful with other

presentations of GT(13,14)

. Surgical

interference approaches vary and there is

no one technique with a greater efficacy

than another(8)

. Therefore, a therapeutic

dilemma exists as to the most effective

intervention with the least risk of side

effects(11)

. As an envisioned future

promise, gene therapy and stem cell

transplantation could help cure GT(2).

Allogeneic hematopoietic stem cell

transplant is the only curative method of

treatment(5,23,24)

. The present case and his

family required molecular genetic

diagnosis and dissection of the nature of

mutations they suffer, currently planned

for – after which stem cell approaches

could be thought of.

Conclusion

The very rare inherited GT should be

anticipated upon surgical intervention

with secured packed red blood cells,

concentrated platelets and rFVIIa (the

latter two were not available for our case).

This case report represents the first

description for successful treatment of

life-threatening hemorrhage in a GT

patient in Saudi Arabia and molecular

genetic investigations were planned since

his sisters gave a history of profuse

menstruation.

Conflict of Interest

The authors declared no conflict of

interests.

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