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ISSN 2147-0634
ISSN 2147-0634
MEDICINE
SCIENCE
www.medicinescience.org
International Medical Journal
Volume 8, Number 2, June 2019, Pages 260-488
Editor-in-Chief
Osman CELBIS
Editors
David O. CARPENTER
Nevzat ERDIL
Yuksel ERSOY
Ədalət HƏSƏNOV
Yunus KARAKOC
Ronald S MacWALTER
Selami Cagatay ONAL
Ibrahim SAHIN
Publishing Editor
Fatih BATI
photo by Serhat Karamanphoto by Osman Celbiş
EDITORIAL BOARD
Editor-in-Chief
➢ Osman CELBIS (MD, Professor), (editor.osmancelbis@gmail.com)
Editors
➢ Yuksel ERSOY (MD, Professor) (editor.yukselersoy@gmail.com)
➢ Yunus KARAKOC (PhD, Professor) (editor.yunuskarakoc@gmail.com)
➢ Selami Cagatay ONAL (MD, Professor) (editor.cagatayonal@gmail.com)
➢ Ibrahim SAHIN (MD, Professor) (editor.ibrahimsahin@gmail.com)
➢ Nevzat ERDIL (MD, Professor) (editor.nevzaterdil@gmail.com)
➢ David O. CARPENTER (MD, Professor)
➢ Ronald S MacWalter (MD, FRCP)
➢ Ədalət Həsənov (MD, Professor)
Publishing Editor
➢ Fatih BATI (MD, Assistant Professor) (editor.fatihbati@gmail.com)
Medicine Science
International
Medical Journal
SCIENTIFIC ADVISORY BOARD
(Alphabetical Order)
• Gökhan Akbulut, İzmir, Turkey
• Murat Alper, MD, Erzincan, Turkey
• Mustafa Altintas, MD, Antalya, Turkey
• Sevil Atasoy, PhD, Istanbul, Turkey
• Aysegul Atmaca, MD, Samsun, Turkey
• Yasar Bayindir, MD, Malatya, Turkey
• Turgay Bork, MD, Malatya,Turkey
• David O. Carpenter, MD, New York, USA
• Chang-Hwei Chen, PhD, New York, USA
• Gurkan Celebi, MD, Ankara, Turkey
• Selcuk Cetin, MD, Tokat, Turkey
• Nefise Oztoprak Cuvalcı, MD, Antalya, Turkey
• Oguzhan Deyneli, MD, İstanbul, Turkey
• Ahmet Hakan Dinc, Ankara, Turkey
• Ali Dogan, MD, Antalya, Turkey
• Teoman Dogru, MD, Balıkesir, Turkey
• Nevzat Erdil, MD, Malatya, Turkey
• Bulent Eren, MD, Bursa, Turkey
• Zerrin Erkol, MD, Bolu, Turkey
• Kadir Ertem, MD, Malatya, Turkey
• Yasemin Ersoy, Malatya, Turkey
• Suraj K George, MD, USA
• Mira R. Gökdoğan, PhD, Girne, North Cyprus
• Ali Gunes, MD, Malatya, Turkey
• Hakan Gunen, MD, Istanbul, Turkey
• Than Than Htwe, MD, Perak, Malaysia
• S.Iqbal, MD, Kerala, India
• Nur Efe Iris, MD, İstanbul, Turkey
• Servet Birgin Iritas, MD, Ankara, Turkey
• Mehmet Yasar Işcan, PhD, Istanbul, Turkey
• Om Prakash Jasuja, PhD, Patiala, India
• Kishore Kumar Jella, PhD, Atlanta GA, USA
• Mehmet Karaca, MD, Antalya, Turkey
• Abdullah Karaer, MD, Malatya, Turkey
• Ersoy Kekilli, MD, Malatya, Turkey
• Mehmet Kelles, MD, Malatya, Turkey
• Inam Danish Khan, MD, CH EC Kolkata, India
• Ferah Kızılay, MD, Antalya, Turkey
• Prakash Kinthada, PhD, Visakhapatnam, India
• Ozkan Kose, MD, Antalya, Turkey
• Zhiqiang Liu, MD, PhD, Houston, TX, USA
• Liu Liu, MD, PhD, New Orleans, LA, USA
• Ronald S MacWalter, MD, Scotland, UK
• Bulent Mızrak, MD, Batumi, Georgia
• Camal Musaev, MD, Azerbaycan
• Musfiq Orucov, MD, Azerbaycan
• Ercument Olmez, MD, Manisa, Turkey
• Bedirhan Sezer Öner, MD, Malatya, Turkey
• Necdet Oz, MD, Antalya, Turkey
• Abdullah Ozgonul, MD, Sanliurfa, Turkey
• Hakan Parlakpinar, MD, Malatya, Turkey
• Erkan Pehlivan, PhD, Malatya, Turkey
• Oguz Polat, MD, Cleveland , USA
• Nilufer Tulin Polat, PhD, Malatya, Turkey
• Nariman Safarli, MD, Baku, Azerbaijan
• Nusret Soylu, MD, Malatya, Turkey
• Maryna Steyn, MD, South Africa
• Hülya Taskapan, MD, Malatya, Turkey
• Mehmet Tokdemir, MD, , Elazig, Turkey
• Nilgun Ulutasdemir, PhD, Gaziantep, Turkey
• Ali Uzunkoy, MD, Sanliurfa, Turkey
• Yingjun Yan, MD, Nashville, TN 37232, USA
• Dilek Yavuz, MD, İstanbul , Turkey
• Ilhan Yetkin, MD, Ankara, Turkey
• Tulay Öner Yıldırım, MD, Malatya, Turkey
• Oguzhan Yıldırım, MD, Malatya, Turkey
• Tuba Duygu Yılmaz, MD, Mersin, Turkey
• Eda Bengi Yılmaz, MD, Mersin, Turkey
• Saim Yologlu, PhD, Malatya, Turkey
• Menizibeya Osain Welcome, MD, Minsk, Belarus
Ronald K Wright BS MD JD, FL , USA
• Pavel Timonov, MD, Bulgaria
• Antoaneta Fasova, MD, Bulgaria
• Robert (Paweł) SUSŁO, MD, Poland
Medicine Science
International
Medical Journal
Available online at www.medicinescience.org
ORIGINAL RESEARCH
Medicine Science 2019;8(2):260-2
Frequency of lysosomal acid lipase deficiency in patients with primary hyperlipidemia
Bahri Evren1
, Yılmaz Bilgic2
, Feyza Firat Atay3
, Ayse Nuransoy Cengiz4
, Yasir Furkan Cagin2
1
Inonu Universty Faculty of Medicine, Department of Endocrinology Malatya Turkey
2
Inonu Universty Faculty of Medicine, Department of Gastroenterology Malatya Turkey
3
Kovancilar State Hospital, Clinic of Internal Medicine, Elazig Turkey
4
Inonu Universty Faculty of Medicine, Department of Internal Medicine Malatya Turkey
Received 27 January 2019; Accepted 17 February 2019
Available online 10.05.2019 with doi:10.5455/medscience.2019.08.9025
Copyright © 2019 by authors and Medicine Science Publishing Inc.
Abstract
The aim of our study was to investigate the prevalence of LAL (lysosomal acid lipase) deficiency in patients with primary hyperlipidemia. Twenty-four patients with
primary hyperlipidemia were included in the study. The gender, age, height, weight, body mass index and waist circumference of the patients were recorded. Lipid profiles,
glucose, transaminases and LAL enzyme profiles were evaluated. LAL enzyme deficiency was not detected in patients with primary hyperlipidemia. In our study, when we
investigated LAL deficiency in primary hyperlipidemic patients, we could not find a relationship between them. As a result of our study, LAL deficiency was not detected
in patients with primary hyperlipidemia. However, in this context, there is a need to work with a large number of patients.
Keywords: Primary hyperlipidemia, lysosomal acid lipase deficiency
Medicine Science
International
Medical Journal
260
Introduction
Lysosome is a membrane-associated, acidic organelle found
in animal-related cells. Its lead to the breakdown of biological
macromolecules (mucopolysaccharides, sphingolipids,
glycoproteins, triglycerides, cholesterol esters) which are produced
both from the outside and within the cell by the acid hydrolases ıts
contain [1]. Lysosomal storage diseases (LSD), which the lack of
enzymes involved in the catabolism of macromolecules is a group
of diseases caused by the defect of the transports that cause the lysis
of the lysosomes to function out of the cell due to the accumulation
of specific substrates. Clinical findings vary according to the
substance stored. Because the accumulated molecules are highly
heterogeneous, clinical presentations are also heterogeneous [2].
Lysosomal Acid Lipase (LAL) deficiency is a rare autosomal
recessive, lysosomal lipid storage group. It is characterized
by progressive cholesterol ester and triglyceride accumulation
in liver, spleen and other organs (central system, gis …) [3].
*Coresponding Author: Yilmaz Bilgiç, Inonu Universty, Faculty of Medicine
Department of Endocrinology Malatya Turkey
E-mail: drybilgic1975@hotmail.com
Material and Methods
Twenty-four patients with primary hyperlipidemia who were
admitted to the endocrinology and metabolism outpatient clinic
of Inonu University between June 2016 and September 2017 and
who were diagnosed with secondary hyperlipidemia such as type
2 diabetes mellitus, nephrotic syndrome, hypothyroidism and
primary biliary cirrhosis were included in the study. The gender,
age, height, weight, body mass index and waist circumference of
the patients were recorded. Lipid profiles, glucose, transaminases
and LAL enzyme profiles were evaluated. LAL enzyme deficiency
was not detected in patients with primary hyperlipidemia.
Exclusion criteria are given in the material method part of our
study. LAL activity was measured by using Dried Blood Spot Test
(DBS). The results are given in nanomol / punch / hour.
In our study, the mean + standard deviations of the data were given
as statistical analysis. Since there was no LAL deficiency in our
patients, no specific statistical method was used.
Results
When the laboratory and anthropometric results of the patients
with primary hyperlipidemia were evaluated, the mean age was
found to be 38.55 ± 10.7 years. The mean weight and body mass
index of the patients were 72.42 ± 11.4 kg and 26.72 ± 5.2 kg
/ m2, respectively. The waist circumference of the patients was
calculated without gender discrimination and the mean was 84.41
± 12.8 in both sexes. For the exclusion of diabetes mellitus, a
cause of secondary hyperlipidemia, fasting blood glucose was also
included in our study and mean fasting glucose was measured as
86 ± 9.5 mg / dl. Liver enzymes were also studied to determine
whether there was a high liver enzyme elevation in LALdeficiency.
The mean AST 27 ± 7.2 UI / L and ALT 24 ± 6.3 UI / L were
determined. In our study, mean blood lipids were 244 ± 54.2 mg /
dl for total cholesterol, 121 ± 44.7 mg / dl for triglyceride, 51.4 ±
10.3 mg / dl for HDL cholesterol and 182 ± 39.4 mg / dl for LDL
cholesterol (Table 1).
Table 1. Laboratory and anthropometric results of patients with primary
hyperlipidemia
Parameters Patients with primary hyperlipidemia (n = 24)
Age (years) 38.55 ± 10.7
Height (cm) 157.2 ± 6.1
Weight (kg) 72.42 ± 11.4
BMI (kg/m2) 26.72 ± 5.2
Waist circumference 84.41 ± 12.8
Glucose (mg/dl) 86 ± 9.5
AST 27 ± 7.2
ALT 24 ± 6.3
Total cholesterol (mg/dl) 244 ± 54.2
Triglyceride (mg/dl) 121 ± 44.7
HDL cholesterol (mg/dl) 51.4 ± 10.3
LDL cholesterol (mg/dl) 182 ± 39.4
LAL (nmol/punch/h.) 0.74 ± 0.68
Discussion
LALisararelipidstoragediseaseanditsprevalenceisapproximately
1 / 40.000 depolama1 / 350.000 in newborns. Diagnostic images
such as liver ultrasound and biopsy are important, which show
changes in hepatic morphology such as microvescular steatosis
with Kupffer cell involvement, fibrosis and cholesterol-ester-
crystal accumulation. These findings should suggest LAL disease.
Because the disease is manifested as idiopathic microvesicular
hepatosteatosis disease [4]. As the disease progresses in patients
with initially indeterminate complaints, some clinical symptoms,
such as rough facial, skeletal dysplasia, and developmental
delay, stimulate a lysosomal depot disorder. Different lysosomal
storage disorders share common symptoms and symptoms
[5]. LAL deficiency is a disease associated with progressive
hepatic insufficiency accompanied by increased atherosclerosis,
cardiovascular disease, hepatomegaly, and increased liver enzyme
deficiency, with dyslipidemia frequently associated with. LAL
deficiency in adults and children shows very different clinical
features and heterogeneous course. While the age at onset may
occur in late age as 44 years in men and 68 years in women, the
mean age at which onset of symptoms is 5 years in both sexes
[3]. Hepatomegaly is the most common clinical manifestation
of lysosomal storage disease. High serum total cholesterol, LDL
cholesterol, triglyceride high together with hepatomegaly are
among the most characteristic findings [6]. Definitive diagnosis
is the measurement of enzyme activity in leukocytes, cutaneous
fibroblasts or dry blood samples from peripheral blood samples.
The values below 0.03 (nmol / punch / h) in LAL activity were
inadequate in LAL activity, values in the range of 0.03-0.15 (nmol /
punch / hour) were defined as LALactivity at the border. The values
between 0.15-0.37 (nmol / punch / hour) with highly reduced LAL
activity, 0.37-0.50 (nmol / punch / hour) values are considered
as LAL activity in the transition zone [7,8]. In the treatment,
cholestyramine and statins can be given. Although hematopoietic
stem cell transplantation is potentially curative in patients with
LAL deficiency, it is often not a good option because it carries high
risks, including fatal complications. The main treatment consists
of the enzyme replacement sebelipase alfa, which was approved
in 2015. Sebelipase alpha is a recombinant human lysosomal acid
lipase that replaces incomplete LAL enzyme activity and thereby
reduces hepatic fat content and elevated transaminases [9].
Conclusion
Lysosomal acid lipase deficiency; in patients with high LDL and /
or low HDL levels, hepatomegaly and / or high transaminase levels
without obesity or metabolic syndrome should be considered.
In our study, the use of lipid electrophoresis in the diagnosis of
primary hyperlipidemia is one of the weaknesses of our study.
In our study, we could not find any relationship between these two
diseases. As a result of our study, LAL deficiency was not detected
in patients with primary hyperlipidemia. However, because the
incidence of LAL deficiency is very low, large-volume clinical
studies are needed to evaluate the frequency of patients with
primary hyperlipidemia.
Competing interests
The authors declare that they have no competing interest.
Financial Disclosure
All authors declare no financial support.
Ethical approval
Ethics committee approval was obtained.
Bahri Evren ORCID: 0000-0001-7490-2937
Yılmaz Bilgic ORCID: 0000-0002-2169-5548
Feyza Firat Atay ORCID 0000-0002-2841-2985
Ayse Nuransoy Cengiz ORCID: 0000-0001-9133-8602
Yasir Furkan Cagin ORCID: 0000-0002-2538-857X
References
1.	 Zeynep Büşra Aksoy, Ege soydemir. Lizozomal aktivite. Güncel
Gastroenteroloji. 2016;4:345-52.
2.	 Futerman AH, Van Meer G. The cell biology of lysosomal storage disorders.
Nat Rev Mol Cell Biol. 2004;5:554-65.
3.	 Bernstein DL, Hulkova H, Bialer MG, et al. Cholesteryl ester storage disease:
review of the findings in 135 reported patients with an underdiagnosed
disease. J Hepatol. 2013;58:1230-43.
4.	 Botero V, Garcia VH, Gomez-Duarte C, et al. Lysosomal acid lipase
deficiency, a rare pathology: The first pediatric patient reported in colombia.
Am J Case Rep. 2018;19:669-72.
5.	 Andria, g.  parini, Lysosomal storage diseases early diagnosıs and new
treatments edited by: rossella parini, generoso andriat. lysosomal storage d
apa (american psychological assoc.). 2010.
6.	 Lipiński P, Ługowska A, Zakharova EY, et al. Diagnostic algorithm for
cholesteryl ester storage disease: Clinical presentation in 19 Polish Patients. J
Pediatr Gastroenterol Nutr. 2018;67:452-47.
doi: 10.5455/medscience.2019.08.9025					 	 Med Science 2019;8(2):260-2
261
doi: 10.5455/medscience.2019.08.9025					 	 Med Science 2019;8(2):260-2
262
7.	 Wierzbicka-Rucińska A, Jańczyk W, Ługowska A, et al. Diagnostic and
therapeutic management of children with lysosomal acid lipase deficiency
(LAL-D). Review of the literature and own experience. Dev Period Med.
2016;20:212-5.
8.	 Hamilton J, Jones I, Srivastava R, et al. A new method for the measurement of
lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin
Chim Acta. 2012;413:1207-10.
9.	 Canbay A, Müller MN, Philippou S, et al. Cholesteryl ester storage disease:
fatal outcome without causal therapy in a female patient with the preventable
sequelae of progressive liver disease after many years of mild symptoms. Am
J Case Rep. 2018;19:577-81.
Available online at www.medicinescience.org
ORIGINAL RESEARCH
Medicine Science 2019;8(2):263-7
Can nutritional status of patients in intensive care unit predict mortality and length of
hospital stay? A single center retrospective case control study
Deniz Avci1
, Ali Cetinkaya1
, Yekta Gulunay2
, Sadik Oluk1
, Abdullah Eyvaz2
1
Health Sciences University, Kayseri Training and Research Hospital, Department of Internal Medicine, Kayseri, Turkey
2
Health Sciences University, Kayseri Education and Research Hospital, Department of Infectious Diseases, Kayseri, Turkey
Received 23 March 2018; Accepted 01 Octaber 2018
Available online 24.12.2018 with doi:10.5455/medscience.2018.07.8941
Copyright © 2019 by authors and Medicine Science Publishing Inc.
Abstract
To compare the hospitalization duration and mortality with the first day nutritional status of the patients who were hospitalized in intensive care unit of internal medicine
department. The files of patients admitted to the ICU between 01-January-2017 and 30-June-2017 were retrospectively reviewed. Those who were not eligible for study
in the selected files were later handed off. The remaining patients (169 patients) were evaluated for age, sex, stay in intensive care unit, APACHE2 and Glasgow scores,
outcomes (exitus or discharge), NRS-2002 values in day of hospitalization, glucose, creatinine, albumin, White Blood Cell, hematocrit, thrombocyte, C-reactive protein
and thyroid stimulating hormone (TSH) values were recorded. In addition, patients need for mechanical ventilation and underlying diseases (Chronic renal failure, cancer,
sepsis, etc.) were recorded. The mean NRS-2002 score of the whole group was 4.28±0.90. The mean NRS-2002 score of discharged patients was 3.98±0.80 while the
mean NRS-2002 score was 4.71±0.86 (p0.001). There were positive correlations between NRS-2002 scores and age (r=0.537, p 0.001), APACHE2 score (r=0.250,
p=0.001), blood creatinine level (r=0.255, p=0.001). There were statistically significant correlations between NRS-2002 scores and serum albumin levels (r=-0.250,
p0.001) and Glasgow coma scores (r=-0.310, p=0.001) in the negative direction. There was a negative correlation between hospitalization and NRS-2002 scores in
cancer patients (r=-0.495, p=0.019). The mean NRS-2002 score was 5.0±0.89 in patients with sepsis who were discharged, while it was 4.36±0.91 in patients with sepsis
who died (p=0.014). The mean NRS-2002 score was 4.22±0.74 in patients with chronic renal disease who were discharged, whereas this value was 4.90±0.70 in exitus
group (p=0.003). In this study, we demonstrated nutritional status of serious patients in ICU related with certain outcomes including mortality and hospitalization length.
Keywords: NRS-2002, Mortality, intensive care unit, nutrition
Medicine Science
International
Medical Journal
263
Introduction
Predicting mortality in intensive care unit patients has been a topic
of study for many years. As a result of these studies commonly
used scoring systems such as Acute Physiology and Chronic
Health Evaluation 2 (APACHE2) and Glasgow coma scale have
been developed and they provided to predict the possibility of
mortality on the time of admission to hospital [1,2].
Various scoring systems have been developed to determine the
nutritional risk. For example, Subjective Global Assessment) [3]
revealed in 1987, MNA(Mini-NutritionalAssessment) [4] in 1999,
MUST (Malnutrition Universal Screening Tool) [5] recommended
by European guidelines to determine nutritional risk in 2002 and
NRS-2002 ( Nutritional Risk Screening 2002)was published in
2003 [6].
*CorespondingAuthor: DenizAvci, Health Sciences University, Kayseri Training
and Research Hospital, Department of Internal Medicine, Kayseri, Turkey
E-mail: denav38@gmail.com
The NRS-2002, which is still the most valid nutritional assessment
test in especially hospitalized patients, was created by evaluating
128 randomized controlled trials. It is a scoring system that takes
into account the deterioration of the nutritional condition of the
patient, the severity of the illness and the age of the patient [6]. For
today, NRS-2002 database is available in Turkey Clinical Enteral
Parenteral Nutrition Society (KEPAN) website [6].
Malnutrition is a common problem in intensive care units.
The degree of malnutrition is positively correlated with the
hospitalization length of patient [7]. Malnutrition increases the risk
of infection and multi organ dysfunction [8]; it is also an important
factor that affects immunity [9]. It has been demonstrated that
immune system is impaired [10] and infectious diseases are badly
affected in the deficiency of micronutrients [11].
Relation between the prognoses of nutrition in intensive care
patients was studied in many types of intensive care and various
diseases [12,13]. In this study, we investigated the relationship of
NRS-2002, APACHE2, Glasgow coma score calculated in the day
of intensive care admission with mortality and hospitalization time
in patients who were taken to Internal Medicine intensive care unit
(IMICU) with the diagnosis of cancer, chronic kidney disease and
sepsis.
Material and Methods
Files of patients that were hospitalized between 01-January-2017
and 30-June 2017 in Training and Education Hospital were
reviewed retrospectively. The Kayseri Training and Research
Hospital Ethics Committee approved this study. Drug intoxications,
patients hospitalized in intensive care unit less than 24 hours and
patients younger than 18 years were not included in the study.
The remaining 169 patient’s ages, sex, duration of stay in
intensive care unit, APACHE 2 and Glasgow coma scores,
outcomes (discharge or exitus), NRS-2002 values at admission
day; glucose, creatinine, albumin, white blood cell, hematocrit,
platelet, C-reactive protein (CRP), Thyroid stimulating hormone
(TSH) levels were recorded. Besides these, need of patients to
mechanical ventilation and underlying diseases (chronic kidney
disease, sepsis, cancer etc) were also recorded.
The NRS-2002 evaluation of patients was routinely performed
by relevant dieticians in the day of intensive care unit admission.
APACHE 2 scores and Glasgow scores of patients were recorded by
the physicians in the intensive care unit. Patients’ laboratory tests
were the routinely taken values in intensive care unit admission.
Statistical analysis
Statistical analysis was performed using the Statistical Package
for the Social Sciences (SPSS) software version 21.0 (SPSS Inc.,
Chicago, IL, USA). The suitability of the normal distribution of
the data was performed with Shapiro–Wilk test and histograms.
Continuous variables were presented as mean ± standard deviation
or median (minimum-maximum), depending on whether their
distribution is normal or not. Mean values between groups
were compared using Student’s T test, and median values were
compared using Mann-Whitney-U test. Chi-square test was used
to compare categorical data. Pearson correlation analysis was
used for correlation calculations between continuous variables.
The receiver operating characteristic (ROC) curves were used to
evaluate the performance of NRS-2002 to indicate the presence of
mortality in patients. A p-value 0.05 was considered significant.
Results
The mean age of whole group was 69.2±17.1 years. The median
age of discharged patient’s was 67.3±18.8 years and was 72.0±14.0
years for patients with mortality and the difference was not
statistically significant (p=0.057).
Both groups were similar in terms of gender. The male/female ratio
(M/F) of the whole patient group was 58.6% (n = 99)/41.4% (n =
70). There was no statistically significant difference between the
sex-distributions of discharged patient’s M/F: %56. (n=39)/%43.5
(n=30) and mortal patients’ M/F: %60 (n=60)/%40 (n=40)
(p=0.652).
NRS-2002 scores were 4.28±0.90 in the whole group evaluation.
The mean NRS-2002 score was 3.98±0.80 in the discharged
patients. In mortal cases, the mean NRS-2002 score was 4.71±0.86.
The difference between these two mean values were a statistically
significant difference (p0.001).
While 68.8% (n=47) of the cancer cases ended with death in
intensive care unit, this rate was 34.4% (n=22) in the non-cancer
patients (p 0.001).
51.8% (n=26) of patients with sepsis resulted in death in intensive
care unit while the mortality rate in patients without sepsis was
36.4% (n=43) (p=0.078). This difference was tending to be
statistically significant.
Group comparisons are summarized in Table 1.
doi: 10.5455/medscience.2018.07.8941					 	 Med Science 2019;8(2):263-7
264
Table.1 Comparison of variables according to outcomes of patients in intensive care unit
Continuous variables Total
Outcome
p
Exitus Discharge
Age(year) 69.2±17.1 72.0±14.0 67.3±18.8 0.057
APACHE 2 score 23 (3-48) 25 (10-48) 19 (3-44) 0.002
Glasgow coma score 11 (3-15) 10 (3-14) 12 (3-15) 0.001
Hospitalization duration (day) 5 (2-32) 7 (2-37) 5 (2-21) 0.018
NRS-2002 4.28±0.90 4.71±0.86 3.98±0.80 0.001
Glucose (mg/dL) 126.5 (54-818) 129 (54-412) 124 (69-818) 0.772
Creatinine (mg/dL) 1.4 (0,2-14,6) 1.9 (0.3-14.6) 1.3 (0.2-13.2) 0.035
Albumin (g/L ) 2.73±0.71 2.6±0.6 2.8±0.8 0.111
WBC(1/uL) 10500 (600-40000) 11150 (3300-38000) 10200 (600-40000) 0.388
Hematocrit 34.4±9.0 35.1±9.8 34.0±8.5 0.448
Platelet (1/uL) 182000 (4000-488000) 173000 (27000-478000) 195000 (4000-488000) 0.638
TSH (mU/L) 0.9 (0.01-99) 0.9 (0.01-99) 0.9 (0.2-10) 0.479
Categoric variables
Gender M/F (%) 58.6(n=99)/41.4 (n=70) 56.5(n=39)/43.5 (n=30) 60 (n=60)/40 (n=40) 0.652
CRP (mg/dL) 99 (3-212) 121 (9-212) 64 (3-199) 0.010
27 patients were excluded due to
short hospitalization (24
28 patients with drug
intoxication were excluded
169 ICU patients’ records
were remained
225 ICU patients’ records
were reviewed
doi: 10.5455/medscience.2018.07.8941					 	 Med Science 2019;8(2):263-7
265
There were statistically significant correlations in the positive way
between NRS-2002 scores and age (r=0.537, p0.001), APACHE2
score (r=0.250, p=0.001), blood creatinine levels (r=0.255,
p=0.001) and CRP levels (r=0.356, p0.001).
When the whole group is considered: there was no correlation
between NRS-2002 scores and hospitalization duration (r=0.117,
p=0.129).
In order to estimate the power of NRS-2002, APACHE2, Glasgow
coma scoring and CRPas predictors of intensive care unit mortality
area under curve (AUC) was used for ROC analyses. (Figure 1)
(Table 2).
Figure 1. In order to estimate the power of NRS-2002, APACHE2,
GCS and serum CRP as predictors of intensive care unit mortality
area under curves (AUC) were used for ROC analyses
Table 2. Area under curves for NRS-2002, APACHE2 scores, Glasgow Coma
Scores and Serum CRP for predicting mortality in patients admitted to internal
medicine intensive care unit
Variables AUC p
95% Confidence Interval
Lover Upper
NRS-2002 0.728 0.001 0.640 0.815
APACHE2 score 0.630 0.011 0.537 0.723
Glasgow Coma score 0.359 0.006 0.267 0.451
CRP 0.628 0.012 0.535 0.720
Patients with cancer
There were 32 patients with cancer. Twenty-two of these patients
were died in intensive care unit, while 10 of them could be
discharged. The mean NRS-2002 score in survivors was 4.8±0.78
while it was 4.5±0.80 in non-survivals. The difference between
these two means was not statistically significant (p=0.332). In
cancer patients there was a moderate, statistically significant
correlation on the negative direction between the length of hospital
stay and the NRS-2002 scores (r=-0.495, p=0.019). In cancer
patients there was a moderate, statistically significant correlation
on positive direction between the age of the patients and the NRS-
2002 scores (r=0.426, p=0.048).
Patients with sepsis
26 of 51 septic patients were died while 25 of them discharged
from intensive care unit. The mean NRS-2002 score in survivals
was 5.0±0.89, while it was 4.36±0.91 in non-survival septic
patients. The difference between these two values was statistically
significant (p=0.014). In patients with sepsis there was a moderate,
statistically significant correlation on positive way between the
age of the patients and the NRS-2002 scores (r=0.504, p0.001).
In patients with sepsis there was not statistically significant
correlation between the length of hospital stay and the NRS-2002
scores (r=-0.037, p=0.798). In patients with sepsis there was a mild,
statistically significant correlation on positive direction between
blood glucose level and NRS-2002 scores (r=0.288, p=0.049).
Patients with chronic kidney disease
Forty-four patients were diagnosed as chronic kidney disease
(CKD).Twenty-oneofthemwerediedand23ofpatientsdischarged.
The mean NRS-2002 score was 4.22±0.74 in discharged patients
while the value was 4.90±0.70 in non-survivals with CFD. The
difference between these two means was statistically significant
(p=0.003). In patients with CKD there was a strong, statistically
significant correlation on positive direction between the ages
of the patients and the NRS-2002 scores (r=0.701, p0.001). In
patients with CKD there was a moderate, statistically significant
correlation on positive way between serum CRP levels and the
NRS-2002 scores (r=0.484, p0.049).
Patients with mechanical ventilation necessity
There were 54 patients who needed mechanical ventilation. 35
of these patients had mortality while 19 of them discharged from
intensive care unit. The mean NRS-2002 score was 4.58±0.77
in discharged patients while the value was 4.74±0.89 in non-
survival patients. The difference between these two values was not
statistically significant (p=0.500). In patients with mechanically
ventilated there was a moderate, statistically significant correlation
on positive way between the ages of the patients and the NRS-
2002 scores (r=0.672, p0.001). In patients with mechanically
ventilated there was a mild, statistically significant correlation on
negative direction between serum albumin levels and the NRS-
2002 scores (r=-0.336, p=0.033).
Discussion
Malnutrition affects a significant proportion of hospitalized
patients and is associated with increased hospital mortality and
morbidity [14]. The efforts of the discovery of new laboratory/
clinical parameters that may predict mortality in the intensive care
unit are still maintain their importance. A series of scoring systems
have been proposed for predicting mortality. Glasgow coma scale
and APACHE2 models are the best known of these systems. In
addition, many parameters have been studied in some special
patient groups in intensive care units [15-17].
The aim of the present study was to compare the certain outcomes
such as mortality and hospital stay of intensive care patients
with NRS-2002. The mean NRS-2002 score of whole group was
4.28±0.90.The mean NRS-2002 score was 3.98±0.80 in discharged
patients, while it was 4.71±0.86 in patients with mortality. When
all patients were taken into account, the NRS-2002 scores on the
day of admission were significantly higher in patients resulted with
mortality compared to those discharged. The NRS-2002 scores
doi: 10.5455/medscience.2018.07.8941					 	 Med Science 2019;8(2):263-7
266
were generally associated with hospital mortality and morbidity
when the literature was reviewed [14,18].
Patients were also examined in terms of specific disease groups.
In this context, the mortality status of cancer patients did not
seem to be related to the NRS-2002 scores. The mean NRS-2002
score in surviving patients was 4.80±0.79, whereas in cancer
patients resulted with death it was 4.50±0.80. However, there
was a significant correlation between the NRS-2002 scores of
cancer patients and the age (positive direction) and hospitalization
duration (negative direction). In the accumulated literature, the
NRS-2002 score was reported to be associated with increased
mortality and morbidity in hospitalized cancer patients (in ICU or
not) [19,20].
Similarly, patients with chronic kidney disease were examined.
The difference between groups was statistically significant in terms
of mortality. Forty-four patients had chronic kidney disease. 21
of these patients had mortality while 23 of them discharged. The
mean NRS-2002 score was 4.22±0.74 in discharged patients while
the mean NRS-2002 score was 4.90±0.70 in mortal chronic kidney
disease patients. Also in chronic kidney disease patients there were
statistically significant correlations between NRS-2002 scores and
age of patients and serum CRP levels. Rather than randomized
controlled trials working the mortality relation of NRS-2002
scores of patients with chronic kidney disease in intensive care
unit, studies in nephrology services were more intense and in
these studies NRS-2002 scores were associated with mortality and
morbidity [21,22].
The number of sepsis patients in the group was 51. 26 of these
patients were mortal while 25 of patients discharged from intensive
care unit. The mean NRS-2002 score in discharged patients was
5.0±0.89, whereas in septic patients with mortality this value was
4.36±0.91.The difference between this two values was statistically
significant. There was no correlation between NRS-2002 scores
and hospitalization length. However, NRS-2002 scores showed
a statistically significant correlation with both the blood glucose
level and the mean age of the patients. In previous studies, there
were associations between NRS-2002 and sepsis mortality or
hospitalization [13].
It is known that the nutritional support of the patient after admission
is related to the outcome of the patients in the intensive care unit
and hospitalization time [23]. In our study this was confirmed by
another method. Patient entry values were taken and disease states
were examined separately. There should be no escape from the
fact that the diseases are not distributed homogeneously among the
groups. For example, a 10 day hospitalized stomach perforation and
a septic patient who died within 2 days affected the homogeneity
of hospitalization time. Patients with a gastric perforation and
a low NRS-2002 score may stay longer for the treatment of the
primary pathology, but in severe cases this may be different and
the duration of hospitalization may be shorter. Another factor
was the length of hospitalizations was relatively short. Patients’
progress in non-ICU clinics may be more predictable. Associating
malnutrition scores with length of stay in these patients may be
associated with more predictable outcomes [21]. It would not be
wrong to think that patients in intensive care units are more likely
to be close to death. In other words, it is not uncommon for patients
to die from other causes without experiencing the consequences
of malnutrition. For this reason, the statistical significance to be
obtained can be interpreted as valuable.
Limitations
1-The fact that the diseases are not homogenously distributed
among the groups and additionally disease stages are not
standardized could affect the results.
2-Retrospective design may have affected the standard feature of
NRS-2002 evaluations.
Conclusion
Malnutrition is a factor that negatively affects the mortality,
morbidity and hospitalization length of patients in intensive care
units. It was once again shown that the NRS-2002 scores calculated
for patients in Internal medicine-ICU admission is an important
predictor of mortality and hospitalization time, in terms of total
and disease groups. There was a significant correlation between
the NRS-2002 scores of cancer patients and the age (positive
direction) and hospitalization duration (negative direction). The
mean NRS-2002 score in septic patients with mortality was
significantly higher than discharged septic patients’. Also in
chronic kidney disease patients there were statistically significant
correlations between NRS-2002 scores and age of patients and
serum CRP levels.
Competing interests
The authors declare that they have no competing interest
Financial Disclosure
The authors declared that this study has received no financial support
Ethical approval
Before the study, permissions were obtained from local ethical committee
Deniz Avci ORCID: 0000-0001-9220-194X
Ali Cetinkaya ORCID: 0000-0001-8485-0982
Yekta Gulunay ORCID: 0000-0002-9341-4776
Sadik Oluk ORCID: 0000-0001-5837-7706
Abdullah Eyvaz ORCID: 000-0001-6911-299X
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Available online at www.medicinescience.org
ORIGINAL RESEARCH
Medicine Science 2019;8(2):268-73
Is childhood trauma a predictive factor for increased preoperative anxiety levels?
Ayse Vahapoglu1
, Suna Medin Nacar2
, Yagmur Suadiye Dalgic3
Hande Gungor1
1
SBÜ Gaziosmanpaşa Taksim Research and Training Hospital Clinic of Anesthesia and Reanimasyon, Istanbul, Turkey
2
Istanbul Occupational Diseases Hospital Clinic of Psychiatry, Istanbul, Turkey
3
SBÜ Gaziosmanpaşa Taksim Research and Training Hospital Clinic of Psychiatry, Istanbul, Turkey
Received 15 September 2018; Accepted 03 October 2018
Available online 13.11.2018 with doi:10.5455/medscience.2018.07.8928
Copyright © 2019 by authors and Medicine Science Publishing Inc.
Abstract
Childhood trauma is a well-known source of lifelong anxiety and various personality disorders. Also preoperative anxiety is related with perioperative physical and
physicological responses. The aim of this study was to investigate possible relationship –which has not been studied yet- between having a childhood trauma history and
preoperative anxiety levels. A total of 190 patients (aged between 18-65) with a history of childhood trauma presenting for different types of surgery were investigated
prospectively using the Childhood Trauma Questionnaire (CTQ). A childhood trauma questionnaire total score of ≥35 points was accepted as an indicator of significant
childhood trauma history. Preoperative and postoperative anxiety levels of patients were assessed using State Trait Anxiety Inventory (STAI). Also relationship between
childhood trauma types (physical, emotional neglect/abuse, sexual abuse) and pre-postoperative State Trait Anxiety Inventory levels were evaluated. Correlations between
several factors that might effect preoperative anxiety levels including such as; gender, type of surgery, type of anesthesia, educational and maritial levels of patients with or
without a childhood trauma history were investigated. We found significant correlations between higher Childhood Trauma Questionnaire scores and increased preoperative
State Trait Anxiety Inventory trait and state scores (p0.05). Female gender, lower educational level, major surgery, general anesthesia were significantly associated with
higher preoperative anxiety levels in patients with childhood trauma history. Having a childhood trauma history is closely related with increased preoperative anxiety
levels in patients undergoing surgical procedures.
Keywords: Preoperative anxiety, childhood trauma, childhood trauma questionnaire, state trait anxiety inventory
Medicine Science
International
Medical Journal
268
Introduction
Anxiety can be described as a feeling which is unpleasant,
uncomfortable and difficult to deal with that emerges from various
types of stress [1]. Independent from the source of anxiety,
sympathetic, parasympathetic and endocrine system activation
results in several hemodynamical responses such as hypertension,
tachycardia, sweating and tachypnea [1]. It is well known that
many patients scheduled for surgery manifest different degrees
of anxiety during preoperative period [2,3]. Several factors may
affect the degree of preoperative anxiety levels. Age and gender of
patient, type of surgery, education level of patient, surgical history
of patient and patient’s personal susceptibility to anxious conditions
are important factors that determine level of preoperative anxiety
[4,5]. Different studies conducted in various surgical patients
reported different preoperative anxiety with incidence ranging
*Coresponding Author: Ayse Vahapoglurkey, SBÜ Gaziosmanpaşa Taksim
Research and Training Hospital Clinic of Anesthesia and Reanimasyon, Istanbul,
Turkey E-mail: aysevahapoglu@yahoo.com
between 60%-92% [6,7]. Female gender, lower education level,
bein a non-smoker or divorced were found in relation with higher
preoperative anxiety levels [8,9]. Undergoing elective surgery,
possibility of surgery being postponed, harmful mistakes done
by doctor or other caregivers, fear of being unable to awakening
from general anesthesia, awareness during surgery and high levels
of postoperative pain were reported as important reasons for
preoperative anxiety [10,11]. Uncontrolled preoperative anxiety
often results in delayed muscle relaxation, coughing during
anesthesia induction, increased doses of anesthetics and analgesics
include narcotics, rapidly changing hemodynamical responses
to anesthetics and surgical stimuli, postoperative increased pain,
nausea vomiting and delayed recovery [12,13].
Childhood trauma is a wide description of different types of trauma
exposure including emotional and physicial neglect, emotional and
physicial abuse and sexual abuse. Previous studies revealed close
relationship between childhood trauma and impaired emotion
regulation, behavioral instability and developmental lack of healthy
personality [14,15]. Also childhood traumatic events commonly
lead to psychiatric disorders, increased suicide risk, depressive
disorders, obsessions, decreased quality of life, engagement in
high risk behaviors and anxious personality [14,16-19]. Data
regarding child sexual abuse is a good example for ongoing effects
of childhood trauma in adulthood which was shown that 26%-
32% of adult onset disorders (depressive disorders, high levels
of anxiety, drug addiction) were closely related with childhood
sexual abusement [20,21] .
We hypothesized that childhood trauma – a triggering factor for
anxious personality/ high levels of anxiety- might lead to higher
preoperative anxiety levels measured by STAI-state and STAI-
trait scores. So we aimed to investigate possible relationship
between childhood trauma and preoperative anxiety levels in
patients undergoing different types of surgery. Also we measured
effects of several factors include age, gender, educational level,
working status, type of anesthesia and surgery on preoperative and
postoperative anxiety levels in conjunction with having a history
of childhood trauma.
Material and Methods
The study was conducted in Gaziosmanpaşa Taksim Education
and Research Hospital Anesthesiology and Reanimation Clinic
in a period of three month after obtaining ethical commitee
approval of the hospital, using Childhood Trauma Questionnaire
and Spielbergs Situation-Trait Anxiety Inventory tools were
filled on the day before operation by 190 patients who filled out
the written informed consent before being a participant of study.
At postoperative 8th hour, all patients filled STAI forms again.
A blinded psychiathrist to patients’ personal features and other
variables that investigated during study, evaluated CTQ and STAT
scores. Inclusion criteria were patients with age18-65, ASA I-II,
having sufficient mental and educational level for adequately
filling the questionnaries who underwent surgical interventions
under general or regional anesthesia. Exclusion criteria were
patients younger than 18 or older than 65 years, unable to speak
Turkish language, with known psychiatric diseases or any
advanced neurological problem that might limit properly filling
of questionnaries, patients underwent emergency surgery, being
pregnant, blind and/or deaf patients.
The Childhood Trauma Questionnaire
The 28-item Childhood Trauma Questionnaire (CTQ) is a self-
filled questionnaire that asseses abuse and neglect maltreatments
quantitatively using 28 different questions. There are five subscores
derived from either sexual, physical, emotional abuse, emotional
and physical neglect in addition to total score which is the sum of
subscores. Validity and reliability of CTQ have been documented
[22,23] also Turkish version of the questionnaire was accepted as
valid and reliable with a cutoff value ≥35 for total CTQ scores
which indicates significant history of childhood trauma [24].
State-Trait Anxiety Inventory
Spielberg’s State Trait Anxiety Inventory is a commonly used and
validated self report instrument that measures anxiety depending on
personal features (trait anxiety inventory) and anxiety depending
on changing environmental events (state anxiety inventory). State
anxiety inventory is used to determine feelings –anxiety- of a
person in a special situation and environment. On the other hand
trait anxiety inventory is used to determine feelings –anxiety- of
the person independent from the situation and environment that
surround the person. Turkish version of STAI is validated and
accepted as a reliable tool for patients as its true for original
version of instrument [25,26].
Statistical Analysis
The statistical package SPSS 22.0 for Windows (SPSS, Chicago,
IL) was used for statistical analyses. Descriptive statistics of
numerical variables were expressed as mean ±standard deviation
where categorical variables were expressed as numbers and
percentage. Correlations between categorical variables were
evaluated using Pearson X2 test or Fisher-Freeman-Halton Exact
test. Pearson correlation analyses was used in order to evaluate
continuous variables. Independent Sample t-test and One Way
ANOVA were used in order to compare intergroup mean values
of numerical variables. Two-Way Repeated Measures ANOVA
test was used to compare preoperative and postoperative STAI
values. For all statistical analysis, a p value 0.05 was accepted
as significant.
Results
A total of 190 patients were enrolled in the study whose mean
age was 39,8 ±13.02 years (ranged between 18 to 65). 76 female
(40%) and 114 male (60%) patients data was investigated. 141
patients (74.21%) were classified as ASA I where 49 patients
(25.79%) patients were classified as ASA II. Majority of patients
(63.68%) were primary school graduates while the proportion
of university graduates was 13.68%. 58 patients (30.52%) were
housewifes, 57 patients (30%) were self-employed. Majority of
patients (73.68%) were married.
Preoperative and postoperative mean STAI scores, CTQ
subscores and total CTQ scores were demonstrated in Table 1.
Table 1. Preoperative and postoperative mean STAI scores, CTQ subscores and
total CTQ scores of all patients.
Mean ± SS Min - Max
Preoperative STAI-State 38.38 ± 10.18 20 - 66
Preoperative STAI-Trait 42.18 ± 7.61 22 - 64
Postoperative STAI-State 38.00 ± 11.21 20 - 72
Postoperative STAI-Trait 40.83 ± 7.47 21 - 59
Physical neglect 10.14 ± 2.10 6 - 19
Emotional neglect 10.04 ± 4.27 5 - 25
Physical abuse 5.85 ± 2.49 5 - 24
Emotional Abuse 6.52 ± 2.74 5 - 23
Sexual Abuse 5.27 ± 1.20 5 - 17
Total CTQ Score 37.82 ± 9.54 29 - 102
Trauma subscores and total CTQ scores for evaluated patients
were shown in Table 2.
269
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270
Table 2. Trauma subscores and total CTQ scores of patients
n (%)
Physical neglect 7 186 (97.9)
Emotional neglect12 43 (22.6)
Physical abuse 5 36 (18.9)
Emotional abuse7 44 (23.2)
Sexual abuse5 17 (8.9)
Total CTQ Score35 91 (47.9)
We accepted a CTQ cutoff value of ≥35 according to study
conducted by Sar et al. [24] The CTQ cut off values were physical
neglect ≥7, emotional neglect ≥12, physical abuse ≥5, emotional
abuse ≥7 and sexual abuse ≥5 (Cutoff score for Total score ≥35).
We found positive correlation between higher CTQ total score and
preoperative STAI-State and STAI-Trait scores and postoperative
STAI-Trait scores (Table 3). Also positive correlations were
found between CTQ subscores and STAI scores (Table 4).
Table 3. Correlations between CTQ scores and STAI scores
Preop.
STAI-State
Preop.
STAI-Trait
Postop
STAI-State
Postop
STAI-Trait
Physical
neglect
R 0.061 0.106 -0.065 0.031
P 0.405 0.145 0.374 0.669
Emotional
neglect
R 0.121 0.196 0.044 0.151
P 0.096 0.007 0.550 0.038
Physical
Abuse
R 0.134 0.167 0.017 0.094
P 0.065 0.021 0.819 0.199
Emotional
Abuse
R 0.173 0.220 0.007 0.182
P 0.017 0.002 0.927 0.012
Sexual Abuse
R 0.111 0.154 0.006 0.106
P 0.126 0.034 0.936 0.146
CTQ Total
Score
R 0.166 0.237 0.007 0.164
p 0.022 0.001 0.924 0.024
We found that both of preoperative STAI-trait scores in CTQ35
and CTQ≥35 groups were significantly higher than postoperative
STAI-trait scores (p=0.002). On the other hand, preoperative and
postoperative STAI-trait scores found in CTQ≥35 group were
significantly higher than those found in CTQ35 group (p0.05).
Table 4. Pre and postoperative STAI scores in groups created using CTQ cutoff
value of ≥35
CTQ35 (n=99) CTQ ≥35 (n=91) p
Preop. STAI-state 37.03±9.81 39.85±10.43 0.05
Postop. STAI-state 37.60±10.36 38.44±12.10 0.05
Preop. STAI-trait 40.42±7.63 44.10±7.14 0.05
Postop. STAI-trait 39.62±7.40 42.15±7.35 0.05
We analysed correlations between gender and CTQ subscores
and total CTQ scores. We found significantly higher preoperative
STAI-Trait scores in physically neglected female patients
(p=0.026). Preoperative STAI-Trait scores were significantly
higher in emotionally neglected male patients (p=0.014).
Physically abused female patients had higher preoperative and
postoperative STAI-Trait scores. Emotionally abused female
patients had higher preoperative and postoperative STAI-Trait
scores where higher preoperative STAI-State scores were found
in emotionally abused male patients (p0.05). Sexually abused
male patients had higher preoperative STAI-State and Trait scores
(p=0.030 and 0.006 respectively). Also postoperative STAI-Trait
scores were higher in this group (p=0.050). Female patients with
a total CTQ score ≥35 stated higher preop and postoperative
STAI-Trait scores where preoperative STAI-State scores were
higher in male patients (p0.05).
Correlations were investigated between type of anesthesia
(general versus regional anesthesia) and CTQ scores. We found
that emotionally neglected or physically abused patients who
were operated under general anesthesia had significantly higher
preoperative STAI-Trait scores (p=0.036 and 0.038 respectively).
Emotionally abused patients who were operated under general
anesthesia had higher preoperative and postoperative STAI-
State scores (p=0.012 and 0.038 respectively). In terms of CTQ
total scores, general anesthesia was found to have a positive
correlation with increased preoperative and p ostoperative STAI-
Trait scores.
We examined possible correlations between type of surgery
(major or minor) and trauma subscores and total CTQ scores.
We found that major surgery was strongly correlated with
increased STAI scores in patients with a history of physical
neglect, emotional neglect, physical abuse and emotional abuse
(p=0.016, 0.001, 0.012 and 0.009 respectively). Minor surgery
was correlated higher preoperative and postoperative STAI-Trait
scores in patients with a history of sexual abuse (p=0.001 and
0.006 respectively). Also major surgery was found in correlation
with increased preoperative STAI-state and postoperaitve STAI-
trait scores (p=0.017 and 0.010 respectively).
We evaluated the correlations between CTQ subscores STAI
scores and educational level of patients. We found significantly
lower preoperative and postoperative STAI-Trait scores in
university graduated patients (p=0.005 and 0.002 respectively).
Also trauma scores including physical and emotional neglect,
physical and emotional abuse and total CTQ scores of university
graduates were significantly lower than those measured in other
patiens (p0.05).
In another analysis, correlation between CTQ and STAI scores
and occupational status of patients were investigated. We
found that housewifes reported higher scores in all STAI scores
(p0.05). On the other hand there was no significant differences
of CTQ scores in all occupation types (p0.05).
We compared marital status of patients in terms of CTQ subscores,
STAI scores. We couldn’t find any significant difference between
single patients and married patients in terms of CTQ and STAI
scores (p0.05).
Also there was no significant difference between ASA I and ASA
II patients in terms of CTQ subscores, STAI scores (p0.05).
Finally, we compared STAI scores of patients with or without
doi: 10.5455/medscience.2018.07.8928					 	 Med Science 2019;8(2):268-73
271
any relatives during perioperative period and found lower
preoperative and postoperative STAI-State scores in patients
without any relatives during perioperative period (p=0.026 and
0.002 respectively).
Discussion
In this study we found significant correlation between higher CTQ
scores and preoperative STAI scores –both Trait and State- which
indicates close relationship between having a history of childhood
trauma and increased prepoperative anxiety.
STAI is a very commonly used, validated with high reliability
inventory that measures levels of anxiety. It has two categories
-trait and state anxiety which trait anxiety is closely related with
feature of personality (an anxious personality) where state anxiety
indicates the level of the anxiety at the time of assessment [4]. We
used this inventory because of advantage of two way measurement
regarding trait and state anxiety levels which are good indicators
of showing anxious personality and preoperative anxiety [27,28].
There are many environmental and personal factors that influence
and trigger preoperative anxiety. Fear of death, being in an
unfamiliar condition, feeling vulnerable, feeling of loss of control,
extent of surgery (major surgeries like coronary artery bypass
surgery etc), fear of awareness during operation, postoperative
pain, female gender, low educational level are prominent factors
that influence prepoperative anxiety [4,11,28]. Also without a
previous history of surgery, younger or middle ages, non-smokers,
being divorced are other factors might have effects on preoperative
anxiety [9,29]. There are large number of studies investigating
preoperative anxiety provoking factors however –to the best of
our knowledge- there is no study investigating possible correlation
between childhood traumas and preoperative anxiety.
Childhood trauma is closely associated with inception, severity and
course of anxiety disorders [30-32]. Physical, emotional neglect,
abuse, sexual abuse are important types of childhood trauma which
can result in adulthood anxiety, depression, personality disorders
and other psychopathologic diseases [33,34]. Although exact
pathways that provoke anxiety are not clear, cognitive-behavioral
approach suggests threat and danger in childhood as triggering
factor for anxiety [35]. Impaired hypothalamo pituitary axis (HPA)
and corticotropin releasing factor (CRF) stress systems following
biological effect of trauma have been shown [30].As a consequence
increased stress sensitivity leads to decreased threshold which
provoke anxiety [30]. In this context our findings those indicating
positive correlation between an anxious personality with higher
STAI scores and having childhood trauma history indicated by
higher CTQ scores become more important.
Beyond total CTQ score, we evaluated correlation between each
of childhood trauma questionnaire subscores and STAI scores.
Preoperative STAI-state scores were higher in only emotionally
abused patients where preoperative STAI-trait scores were higher
in all childhood trauma types except physical neglect (Table 3).
As mentioned above, STAI-trait inventory investigates anxious
personality and the correlation between high preoperative STAI-
trait scores and childhood trauma types is evidence of prolonged
effect of childhood trauma in adulthood. Generally childhood
physical and sexual abuse are accepted as primary causative
factors for various psychological disorders include depression,
substance dependency, dissociation, anxiety disorders however
there is accumulating data indicating important role of emotional
abuse on psychological disorders [36-38]. Similarly Huh et al.[30]
showed effects of different types of childhood abuse and neglect
on depression, state-trate anxiety and anxiety sensitivity. The
authors reported significant correlations between emotional abuse,
neglect and sexual abuse and interpersonal problems in adulthood
[30]. They concluded that co-occurence of emotional and physical
trauma –not only physical trauma- lead more to severe trait anxiety
and state anxiety. In line with previous studies we showed that
emotional abuse is the only trauma type that correlates with
increased preoperative STAI-state scores.
Manypreviousstudiesshowedthatfemaleshadhigherpreoperative
STAI-trait and state scores than males [39-41]. In contrast there
are several studies unable to show any correlation between gender
and preoperative anxiety. In this manner we evaluated correlation
between gender and preoperative anxiety in patients with history
of childhood trauma. We found significantly higher preoperative
STAI-trait scores in emotionally neglected female patients
in addition to higher pre and postoperative STAI-trait scores
in physically abused females. On the other hand emotionally
neglected male patients had higher preoperative STAI-trait scores
and sexually abused males had higher preoperative STAI-state
scores. Also female patients with a CTQ total score of ≥35 had
higher preop and postoperative STAI-trait scores where male
patients with a CTQ total score of ≥35 had higher preoperative
STAI-state scores.
Type of anesthesia (either general or regional) is another important
factor for preoperative anxiety [42,43]. Also awareness during
surgery is a well documented triggering factor for anxiety [4].
In the present study we evaluated correlation between type of
anesthesia, STAI scores and childhood trauma questionnaire
sub- and total scores. We found significantly higher preoperative
STAI-trait scores in patient having history of emotional neglect or
physically abuse who underwent surgery under general anesthesia.
Also pre- and postoperative STAI-state scores of patients having
history of emotional abuse who underwent surgery under general
anesthesia were significantly higher than those measured in other
group. Finally we showed positive correlation between general
anesthesia and increased pre and postoperative STAI-trait scores in
patient with a CTQ score≥35. These findings indicate that general
anesthesia has more powerful effect than regional anesthesia in
terms of provoking preoperative anxiety in patients with history of
childhood trauma.
Major surgery is a well known anxiety increasing factor [39] and
we investigated association between type of surgery and STAI
scores in patients with history of childhood trauma. We found
that major surgery (debulking surgery, hip replacement, whipple
surgery etc) was strongly correlated with increased STAI scores in
patients with a history of physical or emotional neglect, physical
or emotional abuse. Also patients with a CTQ score≥35 had
significantly increased preoperative STAI-state and postoperative
STAI-trait scores.
Positive correlation between lower educational level and
preoperative anxiety was shown in previous studies [44-46]. Low
education level is related with insufficient accurate information
about possible risks of interventions, decreased consciousness
level which help to cope with anxious situations [44]. In the
present study we found lower pre- and postoperative STAI-trait
scores in patients graduated from university.Additionally, physical
or emotional neglect, physical or emotional abuse and total CTQ
scores of university graduated patients were found significantly
lowerthanothers.Similarlywhenweevaluatedcorrelationbetween
occupational status and STAI scores, we found significantly higher
STAI scores in patients who were housewifes. Although we did
not make any additional analysis to determine the relationship
between being a housewife and having a low education level,
previous studies considered being a housewife as an anxiety
triggering factor [44]. In line with previous studies we suggest that
this finding of study is in correlation with findings that showed
positive correlation between low educational level and increased
STAI scores.
When we compared CTQ sub- and total scores, STAI scores
and marital status of patients, we couldn’t find any significant
difference between these two groups. However Nigussie et al.
[4] reported – independent from childhood trauma history of
patients- that being divorced was significantly related with higher
preoperative anxiety, also the authors considered being single as
an anxiety promoting factor.
Interestingly when we compared CTQ sub- and total scores, STAI
scores of patients with or without any relatives during perioperative
period, there was no significant difference in terms of CTQ scores
however we found lower pre and postoperative STAI-state scores
in patients without any relatives. This finding is in contrast with
previous study results that indicate higher preoperative anxiety
levels in single patients than with relatives/family/friends [44].
Several studies showed positive correlations between anesthetists’
preoperative visit and anxiety reduction [1,47,48]. Fitzgerald et
al. [49] reported over 40% reduction of patients anxiety levels
following anesthetists visit. An attempt to inform patients about
diagnosis, treatment, surgery, anesthesia type, risks of interventions
and important features of perioperative care may help reducing
preoperative anxiety. Although preoperative anesthetist visit of
all patients was performed on the day before surgery during our
study, we did not evaluate its effect on patients and this seems a
shortcoming of our study.
Limitations
CTQ and STAI are widely used and validated tools however using
these tools can sometimes provide inaccurate information because
of self-report design of them. Especially patients with a history of
childhood trauma which may lead a traumatic memory might have
given inaccurate or insufficient responses to questions.
Conclusion
In conclusion we suggest that the present study indicates important
relationship between having a childhood trauma history and
preoperative (also postoperative) anxiety. Findings of the study
have to be supported by future larger scaled studies and after
sufficient accumulation of scientific data, any type of childhood
trauma may be accepted as a preoperative anxiety promoting
factor that will be managed by multidisiplinary attempts.
Competing interests
The authors declare that they have no competing interest
Financial Disclosure
The financial support for this study was provided by the investigators themselves.
Ethical approval
Our study was approved by the local ethics review board.
Ayse Vahapoglu ORCID:0000-0002-6105-4809
Suna Medin Nacar ORCID: 0000-0003-4426-1862
Yagmur Suadiye Dalgic ORCID: 0000-0001-9094-8513
Hande Gungor ORCID: 0000-0002-8920-1516
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doi: 10.5455/medscience.2018.07.8928					 	 Med Science 2019;8(2):268-73
Available online at www.medicinescience.org
ORIGINAL RESEARCH
Medicine Science 2019;8(2):274-6
Our experience and results of clinical incidental gallbladder carcinomas
Oguz Catal, Bahri Ozer, Mustafa Sit
Bolu Abant Izzet Baysal Univercity Medical Faculty, Depertmant of General Surgery, Bolu, Turkey
Received 03 October 2018; Accepted 21 October 2018
Available online 2018 with doi:10.5455/medscience.2018.07.8952
Copyright © 2019 by authors and Medicine Science Publishing Inc.
Abstract
This study aimed to eveluate our experience in incidental gallbladder carcinomas the effect of resection on life time .We suggest that liver resection may contribute to the
disease free survival of the patients with incidental gallbladder carcinomas. Between January 2012 and December 2017, 3691 patients who underwent cholecystectomy
in the Department of General Surgery of Abant Izzet Baysal University Medical Faculty and who did not consider biliary stricture in their preoperative evaluation were
evaluated retrospectively.Patients were grouped according to age, sex, stone size, bile duct wall thickness and histopathological results. The preoperative diagnosis of
all patients undergoing cholecystectomy was cholelithiasis. Of the 3691 patients, gallbladder cancer was detected in the evaluation of the pathology specimens of 16
patients (0.50%) of the patients who were diagnosed with gallbladder carcinomas, 12 had female gender and 4 had male gender. All of the patients were found to have
adenocarcinoma when the pathology specimens were examined. In the pathology specimens, 2 patients had carcinoma insitu, 2 patients had T1, 5 patients had T2, 7
patients had T3. In this study we share our experience in incidental gallbladder carcinomas and suggest that liver resection may contribute to the disease free survival of
the patients with incidental gallbladder carcinomas.
Keywords: Incidental gallbladder carcinomas,gallbladder stones,liver resection,disase free survival,cholecyctectomy
Medicine Science
International
Medical Journal
274
Introduction
Gallbladder carcinomas are rare tumors with poor prognosis.
Biliary tree tumors are one of the most common cancers, and the
5th most common cancers of the gastrointestinal tract. Biliary
cancer is 2-3 times more frequent in males than females, and most
commonly seen in 7th decade. It is seen 0.4% in autopsy series and
approximately 1% of patients who underwent cholecystectomy
because of bile stone. Geographically, biliary incident cancers are
more common in the USA, Mexico, Chile, Israel, Poland, India and
Japan. The greatest risk factor for the development of gallbladder
cancer is gallbladder stones and gallbladder stones and have been
found in 95% of patients with gallbladder cancer [1]. The risk of
developing cancer within 20 years in patients with biliary stones
is less than 0.5% for the entire population, while it is 1.5% for
the high-risk group. Although the pathogenesis is unknown, it is
associated with chronic inflammation. It is associated with a 10-
fold increased risk of cancer in large stones  3cm [2]. Other risk
factors for gallbladder carcinoma include: female sex, obesity,
*Coresponding Author: Oguz Catal, Bolu Abant Izzet Baysal Univercity Medical
Faculty, Depertmant of General Surgery, Bolu, Turkey
E-mail: otuzogur@hotmail.com
advanced age, porcelain gall bladder, typhus carriage, mono-
silent ( 10 mm) polyps, scleroderma colonitis and exposure to
carcinogens. The use of laparoscopic cholecystectomy for benign
biliary diseases today has dramatically increased the incidence
of incidental gallbladder cancer. This also increased the rate of
gallbladder cancer, which had a good prognosis when detected in
early stage.
After simple cholecystectomy for benign conditions, the rate
of malignancy detected in the pathology specimen varies from
0.3% to 2% and often provides complementary surgical radical
treatment.
We aim to evaluate our clinical experience incidental gallbladder
carcinomas and we evaluate the patients disase free survival after
which we apply resection procedure.
Material and Methods
Between January 2012 and December 2017, 3691 patients who
underwent cholecystectomy in the Department of General Surgery
of Abant Izzet Baysal University Medical Faculty and who did not
consider gallbladder cancer in their preoperative evaluation were
evaluated retrospectively. Patients were grouped according to
age, sex, stone size, bile duct wall thickness and histopathological
results. The preoperative diagnosis of all patients undergoing
cholecystectomy was cholelithiasis. Preoperative hemogram,
cholestasis enzymes, ultrasonography results and pathology
results of the patients were evaluated. All of the emergency and
elective patients were included in the study. Ultrasonography
results were classified as 3 cm stone, 1-2 cm stone and 1 cm
stone size according to stone dimensions. Again, the biliary tree
was classified as having wall thickness 3 mm and wall thickness
3 mm according to wall thickness. Examination of the specimens
used according to TNM staging of AJCC in cancer stage. The
contribution of T wall invasion to survival and life time of liver
resection was evaluated in cases with gallbladder cancer.
Results
Of the 3691 patients with cholecystectomy who were evaluated
retrospectively, 1022 were men gender and 2669 were women.
The mean age of the patients was 54.86 (range 19-92)Of the 3691
patients, gallbladder cancer was detected in the evaluation of the
pathology specimens of 16 patients (0.50%). The mean age of this
group was 61.5 (50-86), which was significantly higher than the
mean age of the remaining group (table 1). Of the patients who were
diagnosed with gallbladder carcinomas, 12 had female gender and
4 had male gender (table 1). All of the patients were found to have
adenocarcinoma when the pathology specimens were examined.
In the pathology specimens, 2 patients had carcinoma insitu, 2
patients had T1, 5 patients had T2, 7 patients had T3 (table 1).
Eleven patients were electively treated (Table 1), while 5 of the 16
patients who were incidentally diagnosed with gallbladder stone
pathology specimens were treated with acute cholecystitis. Of
these 16 patients, 2 were operated on before ERCP and stent was
inserted.
Patients who underwent cholecystectomy due to the presence of
stone at the gallbladder when two of 16 patients were opposed
to colon cancer and concomitant gallbladder carcinomas. When
the degrees of differentiation in the pathology specimens of
patients with incidental gallbladder stones cancer were examined,
it was found that 6 had good differentiation, 4 had moderate
differentiation, and 6 had worse differentiation (table 1).
In our study, the thickness of the gallbladder wall was found to be
3 mm or less in 4 patients, whereas it was seen that the thickness
of the wall was 4 mm or more in 12 patients.
The size of stones were larger than 30mm in 10 patients and 30mm
or smaller in 6 patients (table 1).
A lymph node dissection was performed with resection of
liver tumor segment 4B and 5 with T2 tumor. The number of
patients with T3 is 7. Four patients did not accept resection after
cholecystectomy. We performed liver resection 7 of 12 patients
with t2 and t3 cancer. One patient was unable to be performed liver
resection due to cardiac and pulmoner problems who underwent
cholecystectomy performed during advanced colon cancer surgery
Two patients underwent segment 4,5,8 resection and lymph node
dissection.
One patient who underwent resection in T2 was treated for 5 years,
1 patient for 4 years, 1 patient for 2 years and 1 patients for disease
free survival for one year. 1 patient who underwent resection of T3
complained of peritoneal carcinomatosis and liver metastases after
completing 3 year disease-free survival period and deceased at 4th
year of follow up. The other two patients with T3 disease were
completed their 1.5 and 1 year disease-free survival.
Table 1. Demographic and pathological distributions of incidental gallbladder
cancer
Age
≥60 years 13 81.25%
60 years 3 18.75%
Gender
Women (n) 12 75.00%
Men (n) 4 25.00%
Wall thickness (mm)
≤3 5 31.25%
3 11 68.75%
Stone size (cm)
3 6 37.50%
3 10 62.50%
Elective /Emergent Surgery
Elective 11 68.75%
Emergent 5 31.25%
Differentiation
worse 6 37.50%
moderate 4 25.00%
good 6 37.50%
T Stage
Tis 2 12.50%
T1 2 12.50%
T2 5 31.25%
T3 7 43.75%
Resection
Yes 7 58.33%
No 5 41.67%
Discussion
Most of the gallbladder carcinomas are unresectable at the time of
diagnosis. Due to their aggressive attitudes, the 5 year life span is
below 5% and the median life span is about 6 months [3]. Clinical
signs and symptoms in gallbladder carcinomas are similar to those
of cholelithiasis and cholecystitis. More than half of gallbladder
cancer can not be diagnosed preoperatively. Diagnosis is made
by examination of the specimens of patients who have benign
diseases, for example gallbladder stones, polyps, etc., by the
most common diagnostic pathologists [4,5]. The high rate of use
of ultrasonography and the worldwide progress of laparoscopic
cholecystectomy as a widespread surgical procedure are expected
to increase the number of incidentally found gallbladder cancer
over time [6,7]. The main goal of treatment in gallbladder
carcinomas is surgical resection of the intended R0 without
leaving the residual tissue behind. Patients undergoing resection in
gallbladder carcinomas have also shown that the 5-year survey rate
doi: 10.5455/medscience.2018.07.8952					 	 Med Science 2019;8(2):274-6
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doi: 10.5455/medscience.2018.07.8952					 	 Med Science 2019;8(2):274-6
276
ranges from 0-100%. This change is strongly related to the stage
of the patient. Simple colecystectomy is sufficient for carcinoma
in situ and T1a cases [5,8,9]. Resection (radical cholecystectomy
with regional lymph node dissection) should be performed in the
patient group of T1b and over in order to perform resection of R0
[8,10].
Our patient found incidence of incidental gallbladder carcinomas
0.5%, which was 0.19% -2.8% in literature [11,12]. In our study,
the mean age of the benign patient group who were operated on
for gallbladder stones was 54.86 (range 19-92), whereas the mean
age of the patients with incidental gallbladder cancer was 61.50
(range 50-86) it is seen that there is a further age group. The gender
distribution of gallbladder cancer is three times higher in females
than in males [13]. In our study, it was observed that 12 of the 16
patients were female and 4 were male, and the ratio was 3: 1.
Concerning the stone size and number of incidentally detected
gallbladder cancers, it was found to be a risk factor for gallbladder
cancer, which is a multiple stone in stone and gallstones over 3
cm in previous studies [13,14]. In our study, 16 preliminary
ultrasonographic findings of incidentally detected gallbladder
cancer patients were found to have a stone size of 3 cm in 10
gallbladder stones and multiple gallbladder stones in all patients
except one. Patients with pathologic end-stage carcinoma in situ
in patients with gallbladder cancer and those with T1 results do
not require additional treatment for cholecystectomy and 5-year
survival is 90-100% in this patient group. Similar results were
obtained in our patient series. More than simple cholecystectomy
is needed in T2 cancers. Segment 4B and segment 5 resection is
the appropriate treatment approach, as the resection of the liver
bed adjacent to the biliary tree at a depth of 2 cm is acceptable. In
addition, regional lymphadenectomy is needed. When T2 cancer
cases are treated with radical cholecystectomy, the 5-year survival
rate is 80-90%. Our patient underwent lymphadenectomy with
segment 4B and 5 resection in our series and we obtained a similar
survival result. In patients without resection, the survey is between
6 and 8 months.
In the last decade in patients with T3 cancer, most centers have
reported that aggressive surgery provides 25-50% longer survival
in locally advanced disease. In our study, 1 patient who underwent
resection of T3 complained of peritoneal carcinomatosis and liver
metastases after completing 3 year disease-free survival period and
deceased at 4th year of follow up. The other two patients with T3
disease were completed their 1.5 and 1 year disease-free survival.
When the pathologies of patients after resection were evaluated,
lymph node metastasis was reported in 1 patient of 7 resected
patients, while the lymph node pathologies of other patients were
reactive.
Conclusion
In conclusion, we suggest that liver resection may contribute to
the disease free survival of the patients with incidental gallbladder
carcinomas.
Competing interests
The authors declare that they have no competing interest
Financial Disclosure
The financial support for this study was provided by the investigators themselves.
Ethical approval
Bolu Abant Izzet Baysal Education and Reserch Ethics commite accept our
study in 05.01.2018 and 00060010850 serial number
Oguz Catal ORCID: 0000-0002-4067-251X
Bahri Ozer ORCID: 0000-0002-4326-2101
Mustafa Sit ORCID: 0000-0002-7475-7298
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8.	 Pawlik TM, Gleisner AL, Vigano L, et al. Capussotti, Incidence of finding
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Available online at www.medicinescience.org
ORIGINAL RESEARCH
Medicine Science 2019;8(2):277-81
Assessment of readability level of informed consent forms used in intensive care units
Munise Yildiz, Betul Kozanhan, Mahmut Sami Tutar
University of Health Sciences, Konya Education and Research Hospital, Clinic of Anesthesiology and Reanimation, Konya, Turkey
Received 08 October 2018; Accepted 23 October 2018
Available online 04.11.2018 with doi:10.5455/medscience.2018.07.8933
Copyright © 2019 by authors and Medicine Science Publishing Inc.
Abstract
Informed consent forms are printed forms prepared to assist patients in the treatment process by explaining the indications, benefits and possible risks of medical practices.
Readability describes understanding difficulty and is calculated by mathematical formulas. The study aimed to assess the readability level of “Informed Consent Forms”
used in intensive care units. The informed consent forms from 45 hospitals in our country have been gathered. In each average form number of words, the average number
of syllables and the average number of words with 4 or more syllables were manually calculated using the “Microsoft Office Excel 2016®” program. Their readability
levels have been assessed with Atesman and Bezirci-Yılmaz readability formulas. The readability level of forms was “difficult” according to the Atesman readability
formula and at “undergraduate level” according to the Bezirci-Yilmaz readability formula. The readability level of forms used in private hospitals was found to be
significantly lower than that used in state and university hospitals (p=0.019, p=0.012). The average number of words and the average number of words with 4 or more
syllables in forms were found to be significantly higher in private hospitals compared to state and university hospitals (p=0.004, p=0.01). It has been determined that the
readability level of informed consent forms was at academic literacy level. To protect patient rights and to regulate patient-physician relationships by taking into account
individuals rights, informed consent forms should be reviewed and that their readability levels should be adjusted to cover the overall educational level of individuals in
the general population.
Keywords: Intensive care, informed consent form, readability
Medicine Science
International
Medical Journal
277
Introduction
Informed consent forms are printed forms containing the diagnosis
of disease, the proposed treatment method and the risks of this
method for the patient’s health, the use and possible side effects
of medical treatments and the outcomes of disease if the proposed
treatment is refused [1]. The informational obligation is a debt for
the physician and a right for the patient regarding the physician-
patient relationship. Although the patient’s right to be informed
is mentioned in the “Patients Rights Regulation” which has been
put into force in Turkey in 1998, it is specified that the mentioned
information should be clear and understandable enough and then
must answer all possible questions. Before obtaining a patient’s
informed consent for any medical intervention, the patient should
be informed about the type, prognosis and possible side effects
of the medical intervention, the outcomes of disease in case of
*Coresponding Author: Munise Yildiz, University of Health Sciences, Konya
Education and Research Hospital, Clinic of Anesthesiology and Reanimation,
Konya, Turkey
E-mail: drmunise@hotmail.com
treatment refusal [2]. However, the reliability and update of, as
well as their “readability” and “understandability,” are somewhat
important because the value of information is limited by the ability
of individuals to comprehend.
Although readability has been popular in recent years, it was based
on past studies. It is a concept that provides some numerical data
about texts and gives information about whether the text is easy to
be understood by the reader at a certain level using characteristic
features of syllables, words, and sentences of the language.
Although this concept has been used mostly in inter-institutional
correspondence, military organizations and healthcare companies
in the past, today, it has become a concept which is used by
linguistic scientists as well as other scientists and on which studies
are performed frequently [3]. Besides the average number of words,
the average number of syllables and the average number of words
with 4 or more syllables, various criteria such as number synonym
words must be placed in mathematical formulas to determine
the readability level of a written text. To perform readability
analysis, different formulas have been developed in Turkish as
well as many foreign languages such as English and Spanish
[4-7]. The Atesman and Bezirci-Yilmaz readability formulas,
which have been described for determining the readability level
of Turkish texts [5,6] and the Gunning-Fog and Flesch–Kincaid
readability formulas, which measure the overall readability, [7,8]
are commonly used readability formulas.
There is a limited number of studies on informed consent forms
used in intensive care units in our country. The study aimed to
assess the readability level of “Informed Consent Forms” that are
mandatory to be obtained regarding both legal and ethical issues
before any medical intervention performed in intensive care units.
Materials and Methods
The study has been approved by the Education Planning Board
of University of Health Sciences Konya Training and Research
Hospital (Decision No: 1 March 2018/13-17). There are informed
consent forms that are created according to certain standards and
are routinely used in intensive care units of hospitals in our country.
For the study, informed consent forms that were regularly used in
intensive care units of 45 hospitals including university hospitals
and training and research hospitals (n=15), state hospitals (n=15),
and private hospitals (n=15) have been gathered. Each informed
consent form was transferred to the “Microsoft Word 2016®” in
the electronic environment. The institutional knowledge sections
have been deleted to keep objectiveness of readability results. The
average number of words, the average number of syllables and the
average number of words with 4 or more syllables in these forms
have been manually calculated using the “ Microsoft Office Excel
2016®” program. For the calculation of the readability levels of
each informed consent form, using Atesman and Bezirci-Yilmaz
formulas data have been transferred to a computer software
program [5,6]. The rate of medical terms within these 100 words
has been determined as a percentage (%).
Atesman Readability Formula:
It has been adapted into Turkish from Flesch’s Reading Ease
Formula by Atesman (1997). It is a formula based on word and
sentence length [5]. The Atesman readability formula gives a score
on a scale ranging from 0–100; a higher score indicates that the
text is easier to read while a lower number suggests that the text is
more difficult to understand (Table 1).
Atesman readability formula:
Readability Score = 198.825 – 40.175 x (total number of syllables/
total number of words) – 2.610 x (total number of words/total
number of sentences)
Bezirci-Yilmaz Readability Formula:
This formula was developed in 2010 based on the length of
sentences in a text, the number of syllables in a word, and the
statistical properties of Turkish language [6]. When the readability
level is calculated, the number of syllables in each word is
multiplied by its number. The readability level is formulated as
follows:
√(ANW×((H3×0,84) + (H4×1,5) + (H5×3,5) + (H6× 26,25))
ANW: average number of words
H3: average number of 3-syllable words
H4: average number of 4-syllable words
H5: average number of 5-syllable words
H6: average number of words with 6 or more syllables
According to this formula, the readability level becomes more
difficult as the length of sentences increases in texts. Moreover, an
increase in the number of syllables in words makes it difficult to
read words and indirectly sentences. This formula explains which
class level a text represents according to the education system in
our country: 1-8= primary school; 9-12= secondary school (high
school); 12-16 = undergraduate level, and ˃16 = higher education.
Statistical Analysis:
The SPSS® 21 (IBM Inc, USA) software was used to analyze
the data. Categorical data were expressed as frequency and
percentage. Numerical data were expressed as a mean ± standard
deviation. The One Way ANOVA and Kruskal-Wallis tests were
used to compare numerical data between independent groups. All
statistical analyzes have been performed bidirectionally at the 5%
significance level and the 95% confidence interval.
Results
Informed consent forms which were used in intensive care units
of 45 medical institutions in our country have been included in the
study. The mean readability value of these forms according to the
Atesman and Bezirci-Yilmaz readability formulas as well as the
average number of words, the average number of syllables and the
average number of words with 4 or more syllables in these forms
are shown Table 2. The mean readability value of these forms
according to the Atesman readability formula was calculated as
41.8 for university hospitals and training and research hospitals,
43.0 for state hospitals and 35.7 for private hospitals, respectively.
The readability level of informed consent forms was “difficult”
according to the Atesman readability formula. The readability
level of informed consent forms used in private hospitals was
found to be significantly lower than those of informed consent
forms used in state and university hospitals (p=0.019). The mean
readability value of these forms according to the Bezirci-Yilmaz
readability formula was calculated as 14.9 for university hospitals
and training and research hospitals, 14.4 for state hospitals and
17.7 for private hospitals, respectively. The readability level of
informed consent forms was at “undergraduate level” according to
the Bezirci-Yilmaz readability formula. According to the Bezirci-
Yilmaz readability formula, there was a significant difference
between the mean readability values of informed consent forms
used in intensive care units of university hospitals and training and
research hospitals, state hospitals and private hospitals (p=0.012).
The average number of words and the average number of words
with 4 or more syllables in informed consent forms were found to
be significantly higher in private hospitals compared to state and
university hospitals (p=0.004, p=0.01). There was no significant
difference between these institutions regarding the average
number of syllables (p=0.361). There was no significant difference
between these institutions regarding the rate of medical terms in
the 100-word text.
Table 1. Atesman Turkish Readability Formula
Level Readability range
Very easy 90-100
Easy 70-89
Moderate 50-69
Difficult 30-49
doi: 10.5455/medscience.2018.07.8933					 	 Med Science 2019;8(2):277-81
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Medicine Science I International Medical Journal; E- Journal of June 2019; Volume 8, Issue 2

  • 1. ISSN 2147-0634 ISSN 2147-0634 MEDICINE SCIENCE www.medicinescience.org International Medical Journal Volume 8, Number 2, June 2019, Pages 260-488 Editor-in-Chief Osman CELBIS Editors David O. CARPENTER Nevzat ERDIL Yuksel ERSOY Ədalət HƏSƏNOV Yunus KARAKOC Ronald S MacWALTER Selami Cagatay ONAL Ibrahim SAHIN Publishing Editor Fatih BATI photo by Serhat Karamanphoto by Osman Celbiş
  • 2. EDITORIAL BOARD Editor-in-Chief ➢ Osman CELBIS (MD, Professor), (editor.osmancelbis@gmail.com) Editors ➢ Yuksel ERSOY (MD, Professor) (editor.yukselersoy@gmail.com) ➢ Yunus KARAKOC (PhD, Professor) (editor.yunuskarakoc@gmail.com) ➢ Selami Cagatay ONAL (MD, Professor) (editor.cagatayonal@gmail.com) ➢ Ibrahim SAHIN (MD, Professor) (editor.ibrahimsahin@gmail.com) ➢ Nevzat ERDIL (MD, Professor) (editor.nevzaterdil@gmail.com) ➢ David O. CARPENTER (MD, Professor) ➢ Ronald S MacWalter (MD, FRCP) ➢ Ədalət Həsənov (MD, Professor) Publishing Editor ➢ Fatih BATI (MD, Assistant Professor) (editor.fatihbati@gmail.com) Medicine Science International Medical Journal
  • 3. SCIENTIFIC ADVISORY BOARD (Alphabetical Order) • Gökhan Akbulut, İzmir, Turkey • Murat Alper, MD, Erzincan, Turkey • Mustafa Altintas, MD, Antalya, Turkey • Sevil Atasoy, PhD, Istanbul, Turkey • Aysegul Atmaca, MD, Samsun, Turkey • Yasar Bayindir, MD, Malatya, Turkey • Turgay Bork, MD, Malatya,Turkey • David O. Carpenter, MD, New York, USA • Chang-Hwei Chen, PhD, New York, USA • Gurkan Celebi, MD, Ankara, Turkey • Selcuk Cetin, MD, Tokat, Turkey • Nefise Oztoprak Cuvalcı, MD, Antalya, Turkey • Oguzhan Deyneli, MD, İstanbul, Turkey • Ahmet Hakan Dinc, Ankara, Turkey • Ali Dogan, MD, Antalya, Turkey • Teoman Dogru, MD, Balıkesir, Turkey • Nevzat Erdil, MD, Malatya, Turkey • Bulent Eren, MD, Bursa, Turkey • Zerrin Erkol, MD, Bolu, Turkey • Kadir Ertem, MD, Malatya, Turkey • Yasemin Ersoy, Malatya, Turkey • Suraj K George, MD, USA • Mira R. Gökdoğan, PhD, Girne, North Cyprus • Ali Gunes, MD, Malatya, Turkey • Hakan Gunen, MD, Istanbul, Turkey • Than Than Htwe, MD, Perak, Malaysia • S.Iqbal, MD, Kerala, India • Nur Efe Iris, MD, İstanbul, Turkey • Servet Birgin Iritas, MD, Ankara, Turkey • Mehmet Yasar Işcan, PhD, Istanbul, Turkey • Om Prakash Jasuja, PhD, Patiala, India • Kishore Kumar Jella, PhD, Atlanta GA, USA • Mehmet Karaca, MD, Antalya, Turkey • Abdullah Karaer, MD, Malatya, Turkey • Ersoy Kekilli, MD, Malatya, Turkey • Mehmet Kelles, MD, Malatya, Turkey • Inam Danish Khan, MD, CH EC Kolkata, India • Ferah Kızılay, MD, Antalya, Turkey • Prakash Kinthada, PhD, Visakhapatnam, India • Ozkan Kose, MD, Antalya, Turkey • Zhiqiang Liu, MD, PhD, Houston, TX, USA • Liu Liu, MD, PhD, New Orleans, LA, USA • Ronald S MacWalter, MD, Scotland, UK • Bulent Mızrak, MD, Batumi, Georgia • Camal Musaev, MD, Azerbaycan • Musfiq Orucov, MD, Azerbaycan • Ercument Olmez, MD, Manisa, Turkey • Bedirhan Sezer Öner, MD, Malatya, Turkey • Necdet Oz, MD, Antalya, Turkey • Abdullah Ozgonul, MD, Sanliurfa, Turkey • Hakan Parlakpinar, MD, Malatya, Turkey • Erkan Pehlivan, PhD, Malatya, Turkey • Oguz Polat, MD, Cleveland , USA • Nilufer Tulin Polat, PhD, Malatya, Turkey • Nariman Safarli, MD, Baku, Azerbaijan • Nusret Soylu, MD, Malatya, Turkey • Maryna Steyn, MD, South Africa • Hülya Taskapan, MD, Malatya, Turkey • Mehmet Tokdemir, MD, , Elazig, Turkey • Nilgun Ulutasdemir, PhD, Gaziantep, Turkey • Ali Uzunkoy, MD, Sanliurfa, Turkey • Yingjun Yan, MD, Nashville, TN 37232, USA • Dilek Yavuz, MD, İstanbul , Turkey • Ilhan Yetkin, MD, Ankara, Turkey • Tulay Öner Yıldırım, MD, Malatya, Turkey • Oguzhan Yıldırım, MD, Malatya, Turkey • Tuba Duygu Yılmaz, MD, Mersin, Turkey • Eda Bengi Yılmaz, MD, Mersin, Turkey • Saim Yologlu, PhD, Malatya, Turkey • Menizibeya Osain Welcome, MD, Minsk, Belarus Ronald K Wright BS MD JD, FL , USA • Pavel Timonov, MD, Bulgaria • Antoaneta Fasova, MD, Bulgaria • Robert (Paweł) SUSŁO, MD, Poland Medicine Science International Medical Journal
  • 4. Available online at www.medicinescience.org ORIGINAL RESEARCH Medicine Science 2019;8(2):260-2 Frequency of lysosomal acid lipase deficiency in patients with primary hyperlipidemia Bahri Evren1 , Yılmaz Bilgic2 , Feyza Firat Atay3 , Ayse Nuransoy Cengiz4 , Yasir Furkan Cagin2 1 Inonu Universty Faculty of Medicine, Department of Endocrinology Malatya Turkey 2 Inonu Universty Faculty of Medicine, Department of Gastroenterology Malatya Turkey 3 Kovancilar State Hospital, Clinic of Internal Medicine, Elazig Turkey 4 Inonu Universty Faculty of Medicine, Department of Internal Medicine Malatya Turkey Received 27 January 2019; Accepted 17 February 2019 Available online 10.05.2019 with doi:10.5455/medscience.2019.08.9025 Copyright © 2019 by authors and Medicine Science Publishing Inc. Abstract The aim of our study was to investigate the prevalence of LAL (lysosomal acid lipase) deficiency in patients with primary hyperlipidemia. Twenty-four patients with primary hyperlipidemia were included in the study. The gender, age, height, weight, body mass index and waist circumference of the patients were recorded. Lipid profiles, glucose, transaminases and LAL enzyme profiles were evaluated. LAL enzyme deficiency was not detected in patients with primary hyperlipidemia. In our study, when we investigated LAL deficiency in primary hyperlipidemic patients, we could not find a relationship between them. As a result of our study, LAL deficiency was not detected in patients with primary hyperlipidemia. However, in this context, there is a need to work with a large number of patients. Keywords: Primary hyperlipidemia, lysosomal acid lipase deficiency Medicine Science International Medical Journal 260 Introduction Lysosome is a membrane-associated, acidic organelle found in animal-related cells. Its lead to the breakdown of biological macromolecules (mucopolysaccharides, sphingolipids, glycoproteins, triglycerides, cholesterol esters) which are produced both from the outside and within the cell by the acid hydrolases ıts contain [1]. Lysosomal storage diseases (LSD), which the lack of enzymes involved in the catabolism of macromolecules is a group of diseases caused by the defect of the transports that cause the lysis of the lysosomes to function out of the cell due to the accumulation of specific substrates. Clinical findings vary according to the substance stored. Because the accumulated molecules are highly heterogeneous, clinical presentations are also heterogeneous [2]. Lysosomal Acid Lipase (LAL) deficiency is a rare autosomal recessive, lysosomal lipid storage group. It is characterized by progressive cholesterol ester and triglyceride accumulation in liver, spleen and other organs (central system, gis …) [3]. *Coresponding Author: Yilmaz Bilgiç, Inonu Universty, Faculty of Medicine Department of Endocrinology Malatya Turkey E-mail: drybilgic1975@hotmail.com Material and Methods Twenty-four patients with primary hyperlipidemia who were admitted to the endocrinology and metabolism outpatient clinic of Inonu University between June 2016 and September 2017 and who were diagnosed with secondary hyperlipidemia such as type 2 diabetes mellitus, nephrotic syndrome, hypothyroidism and primary biliary cirrhosis were included in the study. The gender, age, height, weight, body mass index and waist circumference of the patients were recorded. Lipid profiles, glucose, transaminases and LAL enzyme profiles were evaluated. LAL enzyme deficiency was not detected in patients with primary hyperlipidemia. Exclusion criteria are given in the material method part of our study. LAL activity was measured by using Dried Blood Spot Test (DBS). The results are given in nanomol / punch / hour. In our study, the mean + standard deviations of the data were given as statistical analysis. Since there was no LAL deficiency in our patients, no specific statistical method was used. Results When the laboratory and anthropometric results of the patients with primary hyperlipidemia were evaluated, the mean age was found to be 38.55 ± 10.7 years. The mean weight and body mass index of the patients were 72.42 ± 11.4 kg and 26.72 ± 5.2 kg
  • 5. / m2, respectively. The waist circumference of the patients was calculated without gender discrimination and the mean was 84.41 ± 12.8 in both sexes. For the exclusion of diabetes mellitus, a cause of secondary hyperlipidemia, fasting blood glucose was also included in our study and mean fasting glucose was measured as 86 ± 9.5 mg / dl. Liver enzymes were also studied to determine whether there was a high liver enzyme elevation in LALdeficiency. The mean AST 27 ± 7.2 UI / L and ALT 24 ± 6.3 UI / L were determined. In our study, mean blood lipids were 244 ± 54.2 mg / dl for total cholesterol, 121 ± 44.7 mg / dl for triglyceride, 51.4 ± 10.3 mg / dl for HDL cholesterol and 182 ± 39.4 mg / dl for LDL cholesterol (Table 1). Table 1. Laboratory and anthropometric results of patients with primary hyperlipidemia Parameters Patients with primary hyperlipidemia (n = 24) Age (years) 38.55 ± 10.7 Height (cm) 157.2 ± 6.1 Weight (kg) 72.42 ± 11.4 BMI (kg/m2) 26.72 ± 5.2 Waist circumference 84.41 ± 12.8 Glucose (mg/dl) 86 ± 9.5 AST 27 ± 7.2 ALT 24 ± 6.3 Total cholesterol (mg/dl) 244 ± 54.2 Triglyceride (mg/dl) 121 ± 44.7 HDL cholesterol (mg/dl) 51.4 ± 10.3 LDL cholesterol (mg/dl) 182 ± 39.4 LAL (nmol/punch/h.) 0.74 ± 0.68 Discussion LALisararelipidstoragediseaseanditsprevalenceisapproximately 1 / 40.000 depolama1 / 350.000 in newborns. Diagnostic images such as liver ultrasound and biopsy are important, which show changes in hepatic morphology such as microvescular steatosis with Kupffer cell involvement, fibrosis and cholesterol-ester- crystal accumulation. These findings should suggest LAL disease. Because the disease is manifested as idiopathic microvesicular hepatosteatosis disease [4]. As the disease progresses in patients with initially indeterminate complaints, some clinical symptoms, such as rough facial, skeletal dysplasia, and developmental delay, stimulate a lysosomal depot disorder. Different lysosomal storage disorders share common symptoms and symptoms [5]. LAL deficiency is a disease associated with progressive hepatic insufficiency accompanied by increased atherosclerosis, cardiovascular disease, hepatomegaly, and increased liver enzyme deficiency, with dyslipidemia frequently associated with. LAL deficiency in adults and children shows very different clinical features and heterogeneous course. While the age at onset may occur in late age as 44 years in men and 68 years in women, the mean age at which onset of symptoms is 5 years in both sexes [3]. Hepatomegaly is the most common clinical manifestation of lysosomal storage disease. High serum total cholesterol, LDL cholesterol, triglyceride high together with hepatomegaly are among the most characteristic findings [6]. Definitive diagnosis is the measurement of enzyme activity in leukocytes, cutaneous fibroblasts or dry blood samples from peripheral blood samples. The values below 0.03 (nmol / punch / h) in LAL activity were inadequate in LAL activity, values in the range of 0.03-0.15 (nmol / punch / hour) were defined as LALactivity at the border. The values between 0.15-0.37 (nmol / punch / hour) with highly reduced LAL activity, 0.37-0.50 (nmol / punch / hour) values are considered as LAL activity in the transition zone [7,8]. In the treatment, cholestyramine and statins can be given. Although hematopoietic stem cell transplantation is potentially curative in patients with LAL deficiency, it is often not a good option because it carries high risks, including fatal complications. The main treatment consists of the enzyme replacement sebelipase alfa, which was approved in 2015. Sebelipase alpha is a recombinant human lysosomal acid lipase that replaces incomplete LAL enzyme activity and thereby reduces hepatic fat content and elevated transaminases [9]. Conclusion Lysosomal acid lipase deficiency; in patients with high LDL and / or low HDL levels, hepatomegaly and / or high transaminase levels without obesity or metabolic syndrome should be considered. In our study, the use of lipid electrophoresis in the diagnosis of primary hyperlipidemia is one of the weaknesses of our study. In our study, we could not find any relationship between these two diseases. As a result of our study, LAL deficiency was not detected in patients with primary hyperlipidemia. However, because the incidence of LAL deficiency is very low, large-volume clinical studies are needed to evaluate the frequency of patients with primary hyperlipidemia. Competing interests The authors declare that they have no competing interest. Financial Disclosure All authors declare no financial support. Ethical approval Ethics committee approval was obtained. Bahri Evren ORCID: 0000-0001-7490-2937 Yılmaz Bilgic ORCID: 0000-0002-2169-5548 Feyza Firat Atay ORCID 0000-0002-2841-2985 Ayse Nuransoy Cengiz ORCID: 0000-0001-9133-8602 Yasir Furkan Cagin ORCID: 0000-0002-2538-857X References 1. Zeynep Büşra Aksoy, Ege soydemir. Lizozomal aktivite. Güncel Gastroenteroloji. 2016;4:345-52. 2. Futerman AH, Van Meer G. The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol. 2004;5:554-65. 3. Bernstein DL, Hulkova H, Bialer MG, et al. Cholesteryl ester storage disease: review of the findings in 135 reported patients with an underdiagnosed disease. J Hepatol. 2013;58:1230-43. 4. Botero V, Garcia VH, Gomez-Duarte C, et al. Lysosomal acid lipase deficiency, a rare pathology: The first pediatric patient reported in colombia. Am J Case Rep. 2018;19:669-72. 5. Andria, g. parini, Lysosomal storage diseases early diagnosıs and new treatments edited by: rossella parini, generoso andriat. lysosomal storage d apa (american psychological assoc.). 2010. 6. Lipiński P, Ługowska A, Zakharova EY, et al. Diagnostic algorithm for cholesteryl ester storage disease: Clinical presentation in 19 Polish Patients. J Pediatr Gastroenterol Nutr. 2018;67:452-47. doi: 10.5455/medscience.2019.08.9025 Med Science 2019;8(2):260-2 261
  • 6. doi: 10.5455/medscience.2019.08.9025 Med Science 2019;8(2):260-2 262 7. Wierzbicka-Rucińska A, Jańczyk W, Ługowska A, et al. Diagnostic and therapeutic management of children with lysosomal acid lipase deficiency (LAL-D). Review of the literature and own experience. Dev Period Med. 2016;20:212-5. 8. Hamilton J, Jones I, Srivastava R, et al. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin Chim Acta. 2012;413:1207-10. 9. Canbay A, Müller MN, Philippou S, et al. Cholesteryl ester storage disease: fatal outcome without causal therapy in a female patient with the preventable sequelae of progressive liver disease after many years of mild symptoms. Am J Case Rep. 2018;19:577-81.
  • 7. Available online at www.medicinescience.org ORIGINAL RESEARCH Medicine Science 2019;8(2):263-7 Can nutritional status of patients in intensive care unit predict mortality and length of hospital stay? A single center retrospective case control study Deniz Avci1 , Ali Cetinkaya1 , Yekta Gulunay2 , Sadik Oluk1 , Abdullah Eyvaz2 1 Health Sciences University, Kayseri Training and Research Hospital, Department of Internal Medicine, Kayseri, Turkey 2 Health Sciences University, Kayseri Education and Research Hospital, Department of Infectious Diseases, Kayseri, Turkey Received 23 March 2018; Accepted 01 Octaber 2018 Available online 24.12.2018 with doi:10.5455/medscience.2018.07.8941 Copyright © 2019 by authors and Medicine Science Publishing Inc. Abstract To compare the hospitalization duration and mortality with the first day nutritional status of the patients who were hospitalized in intensive care unit of internal medicine department. The files of patients admitted to the ICU between 01-January-2017 and 30-June-2017 were retrospectively reviewed. Those who were not eligible for study in the selected files were later handed off. The remaining patients (169 patients) were evaluated for age, sex, stay in intensive care unit, APACHE2 and Glasgow scores, outcomes (exitus or discharge), NRS-2002 values in day of hospitalization, glucose, creatinine, albumin, White Blood Cell, hematocrit, thrombocyte, C-reactive protein and thyroid stimulating hormone (TSH) values were recorded. In addition, patients need for mechanical ventilation and underlying diseases (Chronic renal failure, cancer, sepsis, etc.) were recorded. The mean NRS-2002 score of the whole group was 4.28±0.90. The mean NRS-2002 score of discharged patients was 3.98±0.80 while the mean NRS-2002 score was 4.71±0.86 (p0.001). There were positive correlations between NRS-2002 scores and age (r=0.537, p 0.001), APACHE2 score (r=0.250, p=0.001), blood creatinine level (r=0.255, p=0.001). There were statistically significant correlations between NRS-2002 scores and serum albumin levels (r=-0.250, p0.001) and Glasgow coma scores (r=-0.310, p=0.001) in the negative direction. There was a negative correlation between hospitalization and NRS-2002 scores in cancer patients (r=-0.495, p=0.019). The mean NRS-2002 score was 5.0±0.89 in patients with sepsis who were discharged, while it was 4.36±0.91 in patients with sepsis who died (p=0.014). The mean NRS-2002 score was 4.22±0.74 in patients with chronic renal disease who were discharged, whereas this value was 4.90±0.70 in exitus group (p=0.003). In this study, we demonstrated nutritional status of serious patients in ICU related with certain outcomes including mortality and hospitalization length. Keywords: NRS-2002, Mortality, intensive care unit, nutrition Medicine Science International Medical Journal 263 Introduction Predicting mortality in intensive care unit patients has been a topic of study for many years. As a result of these studies commonly used scoring systems such as Acute Physiology and Chronic Health Evaluation 2 (APACHE2) and Glasgow coma scale have been developed and they provided to predict the possibility of mortality on the time of admission to hospital [1,2]. Various scoring systems have been developed to determine the nutritional risk. For example, Subjective Global Assessment) [3] revealed in 1987, MNA(Mini-NutritionalAssessment) [4] in 1999, MUST (Malnutrition Universal Screening Tool) [5] recommended by European guidelines to determine nutritional risk in 2002 and NRS-2002 ( Nutritional Risk Screening 2002)was published in 2003 [6]. *CorespondingAuthor: DenizAvci, Health Sciences University, Kayseri Training and Research Hospital, Department of Internal Medicine, Kayseri, Turkey E-mail: denav38@gmail.com The NRS-2002, which is still the most valid nutritional assessment test in especially hospitalized patients, was created by evaluating 128 randomized controlled trials. It is a scoring system that takes into account the deterioration of the nutritional condition of the patient, the severity of the illness and the age of the patient [6]. For today, NRS-2002 database is available in Turkey Clinical Enteral Parenteral Nutrition Society (KEPAN) website [6]. Malnutrition is a common problem in intensive care units. The degree of malnutrition is positively correlated with the hospitalization length of patient [7]. Malnutrition increases the risk of infection and multi organ dysfunction [8]; it is also an important factor that affects immunity [9]. It has been demonstrated that immune system is impaired [10] and infectious diseases are badly affected in the deficiency of micronutrients [11]. Relation between the prognoses of nutrition in intensive care patients was studied in many types of intensive care and various diseases [12,13]. In this study, we investigated the relationship of NRS-2002, APACHE2, Glasgow coma score calculated in the day
  • 8. of intensive care admission with mortality and hospitalization time in patients who were taken to Internal Medicine intensive care unit (IMICU) with the diagnosis of cancer, chronic kidney disease and sepsis. Material and Methods Files of patients that were hospitalized between 01-January-2017 and 30-June 2017 in Training and Education Hospital were reviewed retrospectively. The Kayseri Training and Research Hospital Ethics Committee approved this study. Drug intoxications, patients hospitalized in intensive care unit less than 24 hours and patients younger than 18 years were not included in the study. The remaining 169 patient’s ages, sex, duration of stay in intensive care unit, APACHE 2 and Glasgow coma scores, outcomes (discharge or exitus), NRS-2002 values at admission day; glucose, creatinine, albumin, white blood cell, hematocrit, platelet, C-reactive protein (CRP), Thyroid stimulating hormone (TSH) levels were recorded. Besides these, need of patients to mechanical ventilation and underlying diseases (chronic kidney disease, sepsis, cancer etc) were also recorded. The NRS-2002 evaluation of patients was routinely performed by relevant dieticians in the day of intensive care unit admission. APACHE 2 scores and Glasgow scores of patients were recorded by the physicians in the intensive care unit. Patients’ laboratory tests were the routinely taken values in intensive care unit admission. Statistical analysis Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) software version 21.0 (SPSS Inc., Chicago, IL, USA). The suitability of the normal distribution of the data was performed with Shapiro–Wilk test and histograms. Continuous variables were presented as mean ± standard deviation or median (minimum-maximum), depending on whether their distribution is normal or not. Mean values between groups were compared using Student’s T test, and median values were compared using Mann-Whitney-U test. Chi-square test was used to compare categorical data. Pearson correlation analysis was used for correlation calculations between continuous variables. The receiver operating characteristic (ROC) curves were used to evaluate the performance of NRS-2002 to indicate the presence of mortality in patients. A p-value 0.05 was considered significant. Results The mean age of whole group was 69.2±17.1 years. The median age of discharged patient’s was 67.3±18.8 years and was 72.0±14.0 years for patients with mortality and the difference was not statistically significant (p=0.057). Both groups were similar in terms of gender. The male/female ratio (M/F) of the whole patient group was 58.6% (n = 99)/41.4% (n = 70). There was no statistically significant difference between the sex-distributions of discharged patient’s M/F: %56. (n=39)/%43.5 (n=30) and mortal patients’ M/F: %60 (n=60)/%40 (n=40) (p=0.652). NRS-2002 scores were 4.28±0.90 in the whole group evaluation. The mean NRS-2002 score was 3.98±0.80 in the discharged patients. In mortal cases, the mean NRS-2002 score was 4.71±0.86. The difference between these two mean values were a statistically significant difference (p0.001). While 68.8% (n=47) of the cancer cases ended with death in intensive care unit, this rate was 34.4% (n=22) in the non-cancer patients (p 0.001). 51.8% (n=26) of patients with sepsis resulted in death in intensive care unit while the mortality rate in patients without sepsis was 36.4% (n=43) (p=0.078). This difference was tending to be statistically significant. Group comparisons are summarized in Table 1. doi: 10.5455/medscience.2018.07.8941 Med Science 2019;8(2):263-7 264 Table.1 Comparison of variables according to outcomes of patients in intensive care unit Continuous variables Total Outcome p Exitus Discharge Age(year) 69.2±17.1 72.0±14.0 67.3±18.8 0.057 APACHE 2 score 23 (3-48) 25 (10-48) 19 (3-44) 0.002 Glasgow coma score 11 (3-15) 10 (3-14) 12 (3-15) 0.001 Hospitalization duration (day) 5 (2-32) 7 (2-37) 5 (2-21) 0.018 NRS-2002 4.28±0.90 4.71±0.86 3.98±0.80 0.001 Glucose (mg/dL) 126.5 (54-818) 129 (54-412) 124 (69-818) 0.772 Creatinine (mg/dL) 1.4 (0,2-14,6) 1.9 (0.3-14.6) 1.3 (0.2-13.2) 0.035 Albumin (g/L ) 2.73±0.71 2.6±0.6 2.8±0.8 0.111 WBC(1/uL) 10500 (600-40000) 11150 (3300-38000) 10200 (600-40000) 0.388 Hematocrit 34.4±9.0 35.1±9.8 34.0±8.5 0.448 Platelet (1/uL) 182000 (4000-488000) 173000 (27000-478000) 195000 (4000-488000) 0.638 TSH (mU/L) 0.9 (0.01-99) 0.9 (0.01-99) 0.9 (0.2-10) 0.479 Categoric variables Gender M/F (%) 58.6(n=99)/41.4 (n=70) 56.5(n=39)/43.5 (n=30) 60 (n=60)/40 (n=40) 0.652 CRP (mg/dL) 99 (3-212) 121 (9-212) 64 (3-199) 0.010 27 patients were excluded due to short hospitalization (24 28 patients with drug intoxication were excluded 169 ICU patients’ records were remained 225 ICU patients’ records were reviewed
  • 9. doi: 10.5455/medscience.2018.07.8941 Med Science 2019;8(2):263-7 265 There were statistically significant correlations in the positive way between NRS-2002 scores and age (r=0.537, p0.001), APACHE2 score (r=0.250, p=0.001), blood creatinine levels (r=0.255, p=0.001) and CRP levels (r=0.356, p0.001). When the whole group is considered: there was no correlation between NRS-2002 scores and hospitalization duration (r=0.117, p=0.129). In order to estimate the power of NRS-2002, APACHE2, Glasgow coma scoring and CRPas predictors of intensive care unit mortality area under curve (AUC) was used for ROC analyses. (Figure 1) (Table 2). Figure 1. In order to estimate the power of NRS-2002, APACHE2, GCS and serum CRP as predictors of intensive care unit mortality area under curves (AUC) were used for ROC analyses Table 2. Area under curves for NRS-2002, APACHE2 scores, Glasgow Coma Scores and Serum CRP for predicting mortality in patients admitted to internal medicine intensive care unit Variables AUC p 95% Confidence Interval Lover Upper NRS-2002 0.728 0.001 0.640 0.815 APACHE2 score 0.630 0.011 0.537 0.723 Glasgow Coma score 0.359 0.006 0.267 0.451 CRP 0.628 0.012 0.535 0.720 Patients with cancer There were 32 patients with cancer. Twenty-two of these patients were died in intensive care unit, while 10 of them could be discharged. The mean NRS-2002 score in survivors was 4.8±0.78 while it was 4.5±0.80 in non-survivals. The difference between these two means was not statistically significant (p=0.332). In cancer patients there was a moderate, statistically significant correlation on the negative direction between the length of hospital stay and the NRS-2002 scores (r=-0.495, p=0.019). In cancer patients there was a moderate, statistically significant correlation on positive direction between the age of the patients and the NRS- 2002 scores (r=0.426, p=0.048). Patients with sepsis 26 of 51 septic patients were died while 25 of them discharged from intensive care unit. The mean NRS-2002 score in survivals was 5.0±0.89, while it was 4.36±0.91 in non-survival septic patients. The difference between these two values was statistically significant (p=0.014). In patients with sepsis there was a moderate, statistically significant correlation on positive way between the age of the patients and the NRS-2002 scores (r=0.504, p0.001). In patients with sepsis there was not statistically significant correlation between the length of hospital stay and the NRS-2002 scores (r=-0.037, p=0.798). In patients with sepsis there was a mild, statistically significant correlation on positive direction between blood glucose level and NRS-2002 scores (r=0.288, p=0.049). Patients with chronic kidney disease Forty-four patients were diagnosed as chronic kidney disease (CKD).Twenty-oneofthemwerediedand23ofpatientsdischarged. The mean NRS-2002 score was 4.22±0.74 in discharged patients while the value was 4.90±0.70 in non-survivals with CFD. The difference between these two means was statistically significant (p=0.003). In patients with CKD there was a strong, statistically significant correlation on positive direction between the ages of the patients and the NRS-2002 scores (r=0.701, p0.001). In patients with CKD there was a moderate, statistically significant correlation on positive way between serum CRP levels and the NRS-2002 scores (r=0.484, p0.049). Patients with mechanical ventilation necessity There were 54 patients who needed mechanical ventilation. 35 of these patients had mortality while 19 of them discharged from intensive care unit. The mean NRS-2002 score was 4.58±0.77 in discharged patients while the value was 4.74±0.89 in non- survival patients. The difference between these two values was not statistically significant (p=0.500). In patients with mechanically ventilated there was a moderate, statistically significant correlation on positive way between the ages of the patients and the NRS- 2002 scores (r=0.672, p0.001). In patients with mechanically ventilated there was a mild, statistically significant correlation on negative direction between serum albumin levels and the NRS- 2002 scores (r=-0.336, p=0.033). Discussion Malnutrition affects a significant proportion of hospitalized patients and is associated with increased hospital mortality and morbidity [14]. The efforts of the discovery of new laboratory/ clinical parameters that may predict mortality in the intensive care unit are still maintain their importance. A series of scoring systems have been proposed for predicting mortality. Glasgow coma scale and APACHE2 models are the best known of these systems. In addition, many parameters have been studied in some special patient groups in intensive care units [15-17]. The aim of the present study was to compare the certain outcomes such as mortality and hospital stay of intensive care patients with NRS-2002. The mean NRS-2002 score of whole group was 4.28±0.90.The mean NRS-2002 score was 3.98±0.80 in discharged patients, while it was 4.71±0.86 in patients with mortality. When all patients were taken into account, the NRS-2002 scores on the day of admission were significantly higher in patients resulted with mortality compared to those discharged. The NRS-2002 scores
  • 10. doi: 10.5455/medscience.2018.07.8941 Med Science 2019;8(2):263-7 266 were generally associated with hospital mortality and morbidity when the literature was reviewed [14,18]. Patients were also examined in terms of specific disease groups. In this context, the mortality status of cancer patients did not seem to be related to the NRS-2002 scores. The mean NRS-2002 score in surviving patients was 4.80±0.79, whereas in cancer patients resulted with death it was 4.50±0.80. However, there was a significant correlation between the NRS-2002 scores of cancer patients and the age (positive direction) and hospitalization duration (negative direction). In the accumulated literature, the NRS-2002 score was reported to be associated with increased mortality and morbidity in hospitalized cancer patients (in ICU or not) [19,20]. Similarly, patients with chronic kidney disease were examined. The difference between groups was statistically significant in terms of mortality. Forty-four patients had chronic kidney disease. 21 of these patients had mortality while 23 of them discharged. The mean NRS-2002 score was 4.22±0.74 in discharged patients while the mean NRS-2002 score was 4.90±0.70 in mortal chronic kidney disease patients. Also in chronic kidney disease patients there were statistically significant correlations between NRS-2002 scores and age of patients and serum CRP levels. Rather than randomized controlled trials working the mortality relation of NRS-2002 scores of patients with chronic kidney disease in intensive care unit, studies in nephrology services were more intense and in these studies NRS-2002 scores were associated with mortality and morbidity [21,22]. The number of sepsis patients in the group was 51. 26 of these patients were mortal while 25 of patients discharged from intensive care unit. The mean NRS-2002 score in discharged patients was 5.0±0.89, whereas in septic patients with mortality this value was 4.36±0.91.The difference between this two values was statistically significant. There was no correlation between NRS-2002 scores and hospitalization length. However, NRS-2002 scores showed a statistically significant correlation with both the blood glucose level and the mean age of the patients. In previous studies, there were associations between NRS-2002 and sepsis mortality or hospitalization [13]. It is known that the nutritional support of the patient after admission is related to the outcome of the patients in the intensive care unit and hospitalization time [23]. In our study this was confirmed by another method. Patient entry values were taken and disease states were examined separately. There should be no escape from the fact that the diseases are not distributed homogeneously among the groups. For example, a 10 day hospitalized stomach perforation and a septic patient who died within 2 days affected the homogeneity of hospitalization time. Patients with a gastric perforation and a low NRS-2002 score may stay longer for the treatment of the primary pathology, but in severe cases this may be different and the duration of hospitalization may be shorter. Another factor was the length of hospitalizations was relatively short. Patients’ progress in non-ICU clinics may be more predictable. Associating malnutrition scores with length of stay in these patients may be associated with more predictable outcomes [21]. It would not be wrong to think that patients in intensive care units are more likely to be close to death. In other words, it is not uncommon for patients to die from other causes without experiencing the consequences of malnutrition. For this reason, the statistical significance to be obtained can be interpreted as valuable. Limitations 1-The fact that the diseases are not homogenously distributed among the groups and additionally disease stages are not standardized could affect the results. 2-Retrospective design may have affected the standard feature of NRS-2002 evaluations. Conclusion Malnutrition is a factor that negatively affects the mortality, morbidity and hospitalization length of patients in intensive care units. It was once again shown that the NRS-2002 scores calculated for patients in Internal medicine-ICU admission is an important predictor of mortality and hospitalization time, in terms of total and disease groups. There was a significant correlation between the NRS-2002 scores of cancer patients and the age (positive direction) and hospitalization duration (negative direction). The mean NRS-2002 score in septic patients with mortality was significantly higher than discharged septic patients’. Also in chronic kidney disease patients there were statistically significant correlations between NRS-2002 scores and age of patients and serum CRP levels. Competing interests The authors declare that they have no competing interest Financial Disclosure The authors declared that this study has received no financial support Ethical approval Before the study, permissions were obtained from local ethical committee Deniz Avci ORCID: 0000-0001-9220-194X Ali Cetinkaya ORCID: 0000-0001-8485-0982 Yekta Gulunay ORCID: 0000-0002-9341-4776 Sadik Oluk ORCID: 0000-0001-5837-7706 Abdullah Eyvaz ORCID: 000-0001-6911-299X References 1. Campbell NN, Tooley MA, Willatts SM. APACHE II scoring system on a general intensive care unit: audit of daily APACHE II scores and 6-month survival of 691 patients admitted to a general intensive care unit between May 1990 and December 1991. J R Soc Med.1994;87:73-7. 2. Knox DB, Lanspa MJ, Pratt CM, et al. Glasgow Coma Score dominates the association between admission Sequential Organ Failure Assessment score and 30-day mortality in a mixed ICU population. J Crit Care. 2014;29:780-5. 3. Detsky AS, McLaughlin JR, Baker JP et al. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr. 1987;11:8-13. 4. Vellas B, Guigoz Y, Garry PJ, et al. The Mini Nutritional Assessment (MNA) and its use in grading the nutritional state of elderly patients. Nutrition. 1999;15:116-22. 5. MAG—Guidelines for detection and management of malnutrition. Malnutrition Advisory Group (MAG) Redditch, UK: British Association for Parenteral and Enteral Nutrition; 2000. 6. Kondrup J, Rasmussen HH, Hamberg O, et al. Nutritional Risk Screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr.2003;22:321-36. 7. LeivaBadosa E, BadiaTahull M, Virgili Casas N, et al. Hospital malnutrition screening at admission: malnutrition increases mortality and length of stay. Nutr Hosp. 2017;34:907-13.
  • 11. 8. Stratton RJ, Hackston A, Longmore D, et al. Malnutrition in hospital outpatients and inpatients: Prevalence, concurrent validity and ease of use of the “malnutrition universal screening tool” (“MUST”) for adults. Br. J. Nutr. 2004;92:799-808. 9. Keusch, G.T. The history of nutrition: Malnutrition, infection and immunity. J. Nutr. 2003;133:336-40. 10. Bhaskaram, P. Micronutrient malnutrition, infection, and immunity: An overview. Nutr. Rev. 2002;60:40-5. 11. Dizdar OS, Baspınar O, Kocer D,et al. Nutritional risk, micronutrient status and clinical Outcomes: A prospective observational study in an infectious disease clinic. Nutrients. 2016;8:124. 12. Kimiaei-Asadi H, Tavakolitalab A. The assessment of the malnutrition in traumatic ICU patients in Iran. Electron Physician. 2017;9:4689-93. 13. Kosałka K, Wachowska E, Słotwiński R. Disorders of nutritional status in sepsis - facts and myths. Prz Gastroenterol. 2017;12:73-82. 14. Mercadal-Orfila G, Lluch-Taltavull J, Campillo-Artero C, et al. Association between nutritional risk based on the NRS-2002 test and hospital morbidity and ortality. Nutr. Hosp. 2012;27:1248-54. 15. KuvandikG,UcarE,BorazanA.etal.Markersofinflammationasdeterminants of mortality in intensive care unit patients Adv Ther. 2007;24:1078-84. 16. Cetinkaya A, Erden A, Avci D, et al. Is hypertriglyceridemia a prognostic factor in sepsis? Ther Clin Risk Manag. 2014;10:147-50. 17. Fuhrmann V, Kneidinger N, Herkner H. et al. Impact of hypoxic hepatitis on mortality in the intensive care unit. Intensive Care Med. 2011;37:1302-10. 18. Masopust J, Kratochvíl J, Martínková V, et al. The relation between nutritional risk category identified by the modified Nutritional Screening 2002 and mortality in metabolic intensive care unit. Vnitr Lek. 2008;54:817-20. 19. Planas M, Álvarez-Hernández J, León-Sanz M, Celaya-Pérez S, et al. Prevalence of hospital malnutrition in cancer patients: a sub-analysis of the PREDyCES® study. Support Care Cancer. 2016;24:429-35. 20. Schwegler I, von Holzen A, Gutzwiller JP, et al. Nutritional risk is a clinical predictor of postoperative mortality and morbidity in surgery for colorectal cancer. Br J Surg. 2010;97:92-7. 21. Borek P, Chmielewski M, Małgorzewicz S et al. Analysis of Outcomes of the NRS 2002 in Patients Hospitalized in Nephrology Wards. Nutrients. 2017;9:287. 22. R Tan, J Long, S Fang, et al. Nutritional Risk Screening in CKD patients.Asia Pac J Clin Nutr. 2016;25:249-56 23. Caccialanza R, Klersy C, Cereda E, et al. Nutritional parameters associated with prolonged hospital stay among ambulatory adult patients. CMAJ. 2010;182:1843-9. 267 doi: 10.5455/medscience.2018.07.8941 Med Science 2019;8(2):263-7
  • 12. Available online at www.medicinescience.org ORIGINAL RESEARCH Medicine Science 2019;8(2):268-73 Is childhood trauma a predictive factor for increased preoperative anxiety levels? Ayse Vahapoglu1 , Suna Medin Nacar2 , Yagmur Suadiye Dalgic3 Hande Gungor1 1 SBÜ Gaziosmanpaşa Taksim Research and Training Hospital Clinic of Anesthesia and Reanimasyon, Istanbul, Turkey 2 Istanbul Occupational Diseases Hospital Clinic of Psychiatry, Istanbul, Turkey 3 SBÜ Gaziosmanpaşa Taksim Research and Training Hospital Clinic of Psychiatry, Istanbul, Turkey Received 15 September 2018; Accepted 03 October 2018 Available online 13.11.2018 with doi:10.5455/medscience.2018.07.8928 Copyright © 2019 by authors and Medicine Science Publishing Inc. Abstract Childhood trauma is a well-known source of lifelong anxiety and various personality disorders. Also preoperative anxiety is related with perioperative physical and physicological responses. The aim of this study was to investigate possible relationship –which has not been studied yet- between having a childhood trauma history and preoperative anxiety levels. A total of 190 patients (aged between 18-65) with a history of childhood trauma presenting for different types of surgery were investigated prospectively using the Childhood Trauma Questionnaire (CTQ). A childhood trauma questionnaire total score of ≥35 points was accepted as an indicator of significant childhood trauma history. Preoperative and postoperative anxiety levels of patients were assessed using State Trait Anxiety Inventory (STAI). Also relationship between childhood trauma types (physical, emotional neglect/abuse, sexual abuse) and pre-postoperative State Trait Anxiety Inventory levels were evaluated. Correlations between several factors that might effect preoperative anxiety levels including such as; gender, type of surgery, type of anesthesia, educational and maritial levels of patients with or without a childhood trauma history were investigated. We found significant correlations between higher Childhood Trauma Questionnaire scores and increased preoperative State Trait Anxiety Inventory trait and state scores (p0.05). Female gender, lower educational level, major surgery, general anesthesia were significantly associated with higher preoperative anxiety levels in patients with childhood trauma history. Having a childhood trauma history is closely related with increased preoperative anxiety levels in patients undergoing surgical procedures. Keywords: Preoperative anxiety, childhood trauma, childhood trauma questionnaire, state trait anxiety inventory Medicine Science International Medical Journal 268 Introduction Anxiety can be described as a feeling which is unpleasant, uncomfortable and difficult to deal with that emerges from various types of stress [1]. Independent from the source of anxiety, sympathetic, parasympathetic and endocrine system activation results in several hemodynamical responses such as hypertension, tachycardia, sweating and tachypnea [1]. It is well known that many patients scheduled for surgery manifest different degrees of anxiety during preoperative period [2,3]. Several factors may affect the degree of preoperative anxiety levels. Age and gender of patient, type of surgery, education level of patient, surgical history of patient and patient’s personal susceptibility to anxious conditions are important factors that determine level of preoperative anxiety [4,5]. Different studies conducted in various surgical patients reported different preoperative anxiety with incidence ranging *Coresponding Author: Ayse Vahapoglurkey, SBÜ Gaziosmanpaşa Taksim Research and Training Hospital Clinic of Anesthesia and Reanimasyon, Istanbul, Turkey E-mail: aysevahapoglu@yahoo.com between 60%-92% [6,7]. Female gender, lower education level, bein a non-smoker or divorced were found in relation with higher preoperative anxiety levels [8,9]. Undergoing elective surgery, possibility of surgery being postponed, harmful mistakes done by doctor or other caregivers, fear of being unable to awakening from general anesthesia, awareness during surgery and high levels of postoperative pain were reported as important reasons for preoperative anxiety [10,11]. Uncontrolled preoperative anxiety often results in delayed muscle relaxation, coughing during anesthesia induction, increased doses of anesthetics and analgesics include narcotics, rapidly changing hemodynamical responses to anesthetics and surgical stimuli, postoperative increased pain, nausea vomiting and delayed recovery [12,13]. Childhood trauma is a wide description of different types of trauma exposure including emotional and physicial neglect, emotional and physicial abuse and sexual abuse. Previous studies revealed close relationship between childhood trauma and impaired emotion regulation, behavioral instability and developmental lack of healthy personality [14,15]. Also childhood traumatic events commonly
  • 13. lead to psychiatric disorders, increased suicide risk, depressive disorders, obsessions, decreased quality of life, engagement in high risk behaviors and anxious personality [14,16-19]. Data regarding child sexual abuse is a good example for ongoing effects of childhood trauma in adulthood which was shown that 26%- 32% of adult onset disorders (depressive disorders, high levels of anxiety, drug addiction) were closely related with childhood sexual abusement [20,21] . We hypothesized that childhood trauma – a triggering factor for anxious personality/ high levels of anxiety- might lead to higher preoperative anxiety levels measured by STAI-state and STAI- trait scores. So we aimed to investigate possible relationship between childhood trauma and preoperative anxiety levels in patients undergoing different types of surgery. Also we measured effects of several factors include age, gender, educational level, working status, type of anesthesia and surgery on preoperative and postoperative anxiety levels in conjunction with having a history of childhood trauma. Material and Methods The study was conducted in Gaziosmanpaşa Taksim Education and Research Hospital Anesthesiology and Reanimation Clinic in a period of three month after obtaining ethical commitee approval of the hospital, using Childhood Trauma Questionnaire and Spielbergs Situation-Trait Anxiety Inventory tools were filled on the day before operation by 190 patients who filled out the written informed consent before being a participant of study. At postoperative 8th hour, all patients filled STAI forms again. A blinded psychiathrist to patients’ personal features and other variables that investigated during study, evaluated CTQ and STAT scores. Inclusion criteria were patients with age18-65, ASA I-II, having sufficient mental and educational level for adequately filling the questionnaries who underwent surgical interventions under general or regional anesthesia. Exclusion criteria were patients younger than 18 or older than 65 years, unable to speak Turkish language, with known psychiatric diseases or any advanced neurological problem that might limit properly filling of questionnaries, patients underwent emergency surgery, being pregnant, blind and/or deaf patients. The Childhood Trauma Questionnaire The 28-item Childhood Trauma Questionnaire (CTQ) is a self- filled questionnaire that asseses abuse and neglect maltreatments quantitatively using 28 different questions. There are five subscores derived from either sexual, physical, emotional abuse, emotional and physical neglect in addition to total score which is the sum of subscores. Validity and reliability of CTQ have been documented [22,23] also Turkish version of the questionnaire was accepted as valid and reliable with a cutoff value ≥35 for total CTQ scores which indicates significant history of childhood trauma [24]. State-Trait Anxiety Inventory Spielberg’s State Trait Anxiety Inventory is a commonly used and validated self report instrument that measures anxiety depending on personal features (trait anxiety inventory) and anxiety depending on changing environmental events (state anxiety inventory). State anxiety inventory is used to determine feelings –anxiety- of a person in a special situation and environment. On the other hand trait anxiety inventory is used to determine feelings –anxiety- of the person independent from the situation and environment that surround the person. Turkish version of STAI is validated and accepted as a reliable tool for patients as its true for original version of instrument [25,26]. Statistical Analysis The statistical package SPSS 22.0 for Windows (SPSS, Chicago, IL) was used for statistical analyses. Descriptive statistics of numerical variables were expressed as mean ±standard deviation where categorical variables were expressed as numbers and percentage. Correlations between categorical variables were evaluated using Pearson X2 test or Fisher-Freeman-Halton Exact test. Pearson correlation analyses was used in order to evaluate continuous variables. Independent Sample t-test and One Way ANOVA were used in order to compare intergroup mean values of numerical variables. Two-Way Repeated Measures ANOVA test was used to compare preoperative and postoperative STAI values. For all statistical analysis, a p value 0.05 was accepted as significant. Results A total of 190 patients were enrolled in the study whose mean age was 39,8 ±13.02 years (ranged between 18 to 65). 76 female (40%) and 114 male (60%) patients data was investigated. 141 patients (74.21%) were classified as ASA I where 49 patients (25.79%) patients were classified as ASA II. Majority of patients (63.68%) were primary school graduates while the proportion of university graduates was 13.68%. 58 patients (30.52%) were housewifes, 57 patients (30%) were self-employed. Majority of patients (73.68%) were married. Preoperative and postoperative mean STAI scores, CTQ subscores and total CTQ scores were demonstrated in Table 1. Table 1. Preoperative and postoperative mean STAI scores, CTQ subscores and total CTQ scores of all patients. Mean ± SS Min - Max Preoperative STAI-State 38.38 ± 10.18 20 - 66 Preoperative STAI-Trait 42.18 ± 7.61 22 - 64 Postoperative STAI-State 38.00 ± 11.21 20 - 72 Postoperative STAI-Trait 40.83 ± 7.47 21 - 59 Physical neglect 10.14 ± 2.10 6 - 19 Emotional neglect 10.04 ± 4.27 5 - 25 Physical abuse 5.85 ± 2.49 5 - 24 Emotional Abuse 6.52 ± 2.74 5 - 23 Sexual Abuse 5.27 ± 1.20 5 - 17 Total CTQ Score 37.82 ± 9.54 29 - 102 Trauma subscores and total CTQ scores for evaluated patients were shown in Table 2. 269 doi: 10.5455/medscience.2018.07.8928 Med Science 2019;8(2):268-73
  • 14. doi: 10.5455/medscience.2018.07.8928 Med Science 2019;8(2):268-73 270 Table 2. Trauma subscores and total CTQ scores of patients n (%) Physical neglect 7 186 (97.9) Emotional neglect12 43 (22.6) Physical abuse 5 36 (18.9) Emotional abuse7 44 (23.2) Sexual abuse5 17 (8.9) Total CTQ Score35 91 (47.9) We accepted a CTQ cutoff value of ≥35 according to study conducted by Sar et al. [24] The CTQ cut off values were physical neglect ≥7, emotional neglect ≥12, physical abuse ≥5, emotional abuse ≥7 and sexual abuse ≥5 (Cutoff score for Total score ≥35). We found positive correlation between higher CTQ total score and preoperative STAI-State and STAI-Trait scores and postoperative STAI-Trait scores (Table 3). Also positive correlations were found between CTQ subscores and STAI scores (Table 4). Table 3. Correlations between CTQ scores and STAI scores Preop. STAI-State Preop. STAI-Trait Postop STAI-State Postop STAI-Trait Physical neglect R 0.061 0.106 -0.065 0.031 P 0.405 0.145 0.374 0.669 Emotional neglect R 0.121 0.196 0.044 0.151 P 0.096 0.007 0.550 0.038 Physical Abuse R 0.134 0.167 0.017 0.094 P 0.065 0.021 0.819 0.199 Emotional Abuse R 0.173 0.220 0.007 0.182 P 0.017 0.002 0.927 0.012 Sexual Abuse R 0.111 0.154 0.006 0.106 P 0.126 0.034 0.936 0.146 CTQ Total Score R 0.166 0.237 0.007 0.164 p 0.022 0.001 0.924 0.024 We found that both of preoperative STAI-trait scores in CTQ35 and CTQ≥35 groups were significantly higher than postoperative STAI-trait scores (p=0.002). On the other hand, preoperative and postoperative STAI-trait scores found in CTQ≥35 group were significantly higher than those found in CTQ35 group (p0.05). Table 4. Pre and postoperative STAI scores in groups created using CTQ cutoff value of ≥35 CTQ35 (n=99) CTQ ≥35 (n=91) p Preop. STAI-state 37.03±9.81 39.85±10.43 0.05 Postop. STAI-state 37.60±10.36 38.44±12.10 0.05 Preop. STAI-trait 40.42±7.63 44.10±7.14 0.05 Postop. STAI-trait 39.62±7.40 42.15±7.35 0.05 We analysed correlations between gender and CTQ subscores and total CTQ scores. We found significantly higher preoperative STAI-Trait scores in physically neglected female patients (p=0.026). Preoperative STAI-Trait scores were significantly higher in emotionally neglected male patients (p=0.014). Physically abused female patients had higher preoperative and postoperative STAI-Trait scores. Emotionally abused female patients had higher preoperative and postoperative STAI-Trait scores where higher preoperative STAI-State scores were found in emotionally abused male patients (p0.05). Sexually abused male patients had higher preoperative STAI-State and Trait scores (p=0.030 and 0.006 respectively). Also postoperative STAI-Trait scores were higher in this group (p=0.050). Female patients with a total CTQ score ≥35 stated higher preop and postoperative STAI-Trait scores where preoperative STAI-State scores were higher in male patients (p0.05). Correlations were investigated between type of anesthesia (general versus regional anesthesia) and CTQ scores. We found that emotionally neglected or physically abused patients who were operated under general anesthesia had significantly higher preoperative STAI-Trait scores (p=0.036 and 0.038 respectively). Emotionally abused patients who were operated under general anesthesia had higher preoperative and postoperative STAI- State scores (p=0.012 and 0.038 respectively). In terms of CTQ total scores, general anesthesia was found to have a positive correlation with increased preoperative and p ostoperative STAI- Trait scores. We examined possible correlations between type of surgery (major or minor) and trauma subscores and total CTQ scores. We found that major surgery was strongly correlated with increased STAI scores in patients with a history of physical neglect, emotional neglect, physical abuse and emotional abuse (p=0.016, 0.001, 0.012 and 0.009 respectively). Minor surgery was correlated higher preoperative and postoperative STAI-Trait scores in patients with a history of sexual abuse (p=0.001 and 0.006 respectively). Also major surgery was found in correlation with increased preoperative STAI-state and postoperaitve STAI- trait scores (p=0.017 and 0.010 respectively). We evaluated the correlations between CTQ subscores STAI scores and educational level of patients. We found significantly lower preoperative and postoperative STAI-Trait scores in university graduated patients (p=0.005 and 0.002 respectively). Also trauma scores including physical and emotional neglect, physical and emotional abuse and total CTQ scores of university graduates were significantly lower than those measured in other patiens (p0.05). In another analysis, correlation between CTQ and STAI scores and occupational status of patients were investigated. We found that housewifes reported higher scores in all STAI scores (p0.05). On the other hand there was no significant differences of CTQ scores in all occupation types (p0.05). We compared marital status of patients in terms of CTQ subscores, STAI scores. We couldn’t find any significant difference between single patients and married patients in terms of CTQ and STAI scores (p0.05). Also there was no significant difference between ASA I and ASA II patients in terms of CTQ subscores, STAI scores (p0.05). Finally, we compared STAI scores of patients with or without
  • 15. doi: 10.5455/medscience.2018.07.8928 Med Science 2019;8(2):268-73 271 any relatives during perioperative period and found lower preoperative and postoperative STAI-State scores in patients without any relatives during perioperative period (p=0.026 and 0.002 respectively). Discussion In this study we found significant correlation between higher CTQ scores and preoperative STAI scores –both Trait and State- which indicates close relationship between having a history of childhood trauma and increased prepoperative anxiety. STAI is a very commonly used, validated with high reliability inventory that measures levels of anxiety. It has two categories -trait and state anxiety which trait anxiety is closely related with feature of personality (an anxious personality) where state anxiety indicates the level of the anxiety at the time of assessment [4]. We used this inventory because of advantage of two way measurement regarding trait and state anxiety levels which are good indicators of showing anxious personality and preoperative anxiety [27,28]. There are many environmental and personal factors that influence and trigger preoperative anxiety. Fear of death, being in an unfamiliar condition, feeling vulnerable, feeling of loss of control, extent of surgery (major surgeries like coronary artery bypass surgery etc), fear of awareness during operation, postoperative pain, female gender, low educational level are prominent factors that influence prepoperative anxiety [4,11,28]. Also without a previous history of surgery, younger or middle ages, non-smokers, being divorced are other factors might have effects on preoperative anxiety [9,29]. There are large number of studies investigating preoperative anxiety provoking factors however –to the best of our knowledge- there is no study investigating possible correlation between childhood traumas and preoperative anxiety. Childhood trauma is closely associated with inception, severity and course of anxiety disorders [30-32]. Physical, emotional neglect, abuse, sexual abuse are important types of childhood trauma which can result in adulthood anxiety, depression, personality disorders and other psychopathologic diseases [33,34]. Although exact pathways that provoke anxiety are not clear, cognitive-behavioral approach suggests threat and danger in childhood as triggering factor for anxiety [35]. Impaired hypothalamo pituitary axis (HPA) and corticotropin releasing factor (CRF) stress systems following biological effect of trauma have been shown [30].As a consequence increased stress sensitivity leads to decreased threshold which provoke anxiety [30]. In this context our findings those indicating positive correlation between an anxious personality with higher STAI scores and having childhood trauma history indicated by higher CTQ scores become more important. Beyond total CTQ score, we evaluated correlation between each of childhood trauma questionnaire subscores and STAI scores. Preoperative STAI-state scores were higher in only emotionally abused patients where preoperative STAI-trait scores were higher in all childhood trauma types except physical neglect (Table 3). As mentioned above, STAI-trait inventory investigates anxious personality and the correlation between high preoperative STAI- trait scores and childhood trauma types is evidence of prolonged effect of childhood trauma in adulthood. Generally childhood physical and sexual abuse are accepted as primary causative factors for various psychological disorders include depression, substance dependency, dissociation, anxiety disorders however there is accumulating data indicating important role of emotional abuse on psychological disorders [36-38]. Similarly Huh et al.[30] showed effects of different types of childhood abuse and neglect on depression, state-trate anxiety and anxiety sensitivity. The authors reported significant correlations between emotional abuse, neglect and sexual abuse and interpersonal problems in adulthood [30]. They concluded that co-occurence of emotional and physical trauma –not only physical trauma- lead more to severe trait anxiety and state anxiety. In line with previous studies we showed that emotional abuse is the only trauma type that correlates with increased preoperative STAI-state scores. Manypreviousstudiesshowedthatfemaleshadhigherpreoperative STAI-trait and state scores than males [39-41]. In contrast there are several studies unable to show any correlation between gender and preoperative anxiety. In this manner we evaluated correlation between gender and preoperative anxiety in patients with history of childhood trauma. We found significantly higher preoperative STAI-trait scores in emotionally neglected female patients in addition to higher pre and postoperative STAI-trait scores in physically abused females. On the other hand emotionally neglected male patients had higher preoperative STAI-trait scores and sexually abused males had higher preoperative STAI-state scores. Also female patients with a CTQ total score of ≥35 had higher preop and postoperative STAI-trait scores where male patients with a CTQ total score of ≥35 had higher preoperative STAI-state scores. Type of anesthesia (either general or regional) is another important factor for preoperative anxiety [42,43]. Also awareness during surgery is a well documented triggering factor for anxiety [4]. In the present study we evaluated correlation between type of anesthesia, STAI scores and childhood trauma questionnaire sub- and total scores. We found significantly higher preoperative STAI-trait scores in patient having history of emotional neglect or physically abuse who underwent surgery under general anesthesia. Also pre- and postoperative STAI-state scores of patients having history of emotional abuse who underwent surgery under general anesthesia were significantly higher than those measured in other group. Finally we showed positive correlation between general anesthesia and increased pre and postoperative STAI-trait scores in patient with a CTQ score≥35. These findings indicate that general anesthesia has more powerful effect than regional anesthesia in terms of provoking preoperative anxiety in patients with history of childhood trauma. Major surgery is a well known anxiety increasing factor [39] and we investigated association between type of surgery and STAI scores in patients with history of childhood trauma. We found that major surgery (debulking surgery, hip replacement, whipple surgery etc) was strongly correlated with increased STAI scores in patients with a history of physical or emotional neglect, physical or emotional abuse. Also patients with a CTQ score≥35 had significantly increased preoperative STAI-state and postoperative STAI-trait scores. Positive correlation between lower educational level and preoperative anxiety was shown in previous studies [44-46]. Low education level is related with insufficient accurate information
  • 16. about possible risks of interventions, decreased consciousness level which help to cope with anxious situations [44]. In the present study we found lower pre- and postoperative STAI-trait scores in patients graduated from university.Additionally, physical or emotional neglect, physical or emotional abuse and total CTQ scores of university graduated patients were found significantly lowerthanothers.Similarlywhenweevaluatedcorrelationbetween occupational status and STAI scores, we found significantly higher STAI scores in patients who were housewifes. Although we did not make any additional analysis to determine the relationship between being a housewife and having a low education level, previous studies considered being a housewife as an anxiety triggering factor [44]. In line with previous studies we suggest that this finding of study is in correlation with findings that showed positive correlation between low educational level and increased STAI scores. When we compared CTQ sub- and total scores, STAI scores and marital status of patients, we couldn’t find any significant difference between these two groups. However Nigussie et al. [4] reported – independent from childhood trauma history of patients- that being divorced was significantly related with higher preoperative anxiety, also the authors considered being single as an anxiety promoting factor. Interestingly when we compared CTQ sub- and total scores, STAI scores of patients with or without any relatives during perioperative period, there was no significant difference in terms of CTQ scores however we found lower pre and postoperative STAI-state scores in patients without any relatives. This finding is in contrast with previous study results that indicate higher preoperative anxiety levels in single patients than with relatives/family/friends [44]. Several studies showed positive correlations between anesthetists’ preoperative visit and anxiety reduction [1,47,48]. Fitzgerald et al. [49] reported over 40% reduction of patients anxiety levels following anesthetists visit. An attempt to inform patients about diagnosis, treatment, surgery, anesthesia type, risks of interventions and important features of perioperative care may help reducing preoperative anxiety. Although preoperative anesthetist visit of all patients was performed on the day before surgery during our study, we did not evaluate its effect on patients and this seems a shortcoming of our study. Limitations CTQ and STAI are widely used and validated tools however using these tools can sometimes provide inaccurate information because of self-report design of them. Especially patients with a history of childhood trauma which may lead a traumatic memory might have given inaccurate or insufficient responses to questions. Conclusion In conclusion we suggest that the present study indicates important relationship between having a childhood trauma history and preoperative (also postoperative) anxiety. Findings of the study have to be supported by future larger scaled studies and after sufficient accumulation of scientific data, any type of childhood trauma may be accepted as a preoperative anxiety promoting factor that will be managed by multidisiplinary attempts. Competing interests The authors declare that they have no competing interest Financial Disclosure The financial support for this study was provided by the investigators themselves. Ethical approval Our study was approved by the local ethics review board. Ayse Vahapoglu ORCID:0000-0002-6105-4809 Suna Medin Nacar ORCID: 0000-0003-4426-1862 Yagmur Suadiye Dalgic ORCID: 0000-0001-9094-8513 Hande Gungor ORCID: 0000-0002-8920-1516 References 1. Matthias AT, Samarasekera DN. Preoperative anxiety in surgical patients – experience of a single unit. 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J Clin Nurs. 2011;21:956-64. 9. McMurray A, Johnson P, Wallis M, et al. General surgical patients’ perspectives of the adequacy and appropriateness of discharge planning to facilitate health decision‐making at home. J Clin Nurs. 2007;16:1602-9. 10. Ebirim L, Tobin M. Factors responsible for pre-operative anxiety ın elective surgical patients at a university teaching hospital: A pilot study. Internet J Anesthesiol. 2010;29:2. 11. Masood Z, Haider J, Jawaid M, et al. Preoperative anxiety in female patients: the issue needs to be addressed. Khyber Med Univ J. 2009;1:38-41. 12. Pokharel K, Bhattarai B, Tripathi M, et al. Nepalese patients anxiety and concerns before surgery. J Clin Anesth. 2011;23:372-8. 13. Fauza A K, Shazia N. Assessment of pre operative anxiety in patients for elective surgery. J Anaesthesiol Clin Pharmacol. 2007;23:259-62. 14. Evren C. Cinar O. Evren B, et al. The mediator roles of trat anxiety, hostility, and impulsivity in the association between childhood trauma and dissociation in male substance-dependent inpatients. Compr Psychiatry. 2013;54:158-66. 15. Shipman K, Edwards A, Brown A, et al. Managing motion in a maltreating context: a pilot study examining child neglect. Child Abuse Negl. 2005;29:1015-29. 16. Hovens JG, Giltay EJ, Wiersma JE, et al. Impact of childhood life events and trauma on the course of depressive and anxiety disorders. Acta Psychiatr Scand, 2012. 17. Briere J. The long-term clinical correlates of childhood sexual victimization. Ann N Y Acad Sci. 1988;528:327-34. 18. Beitchman JH, Zucker KJ, Hood JE, et al. A review of the longterm effects of child sexual abuse. Child Abuse Negl. 1992;16:101-18. 19. Widom CS, Kuhns JB. Childhood victimization and subsequent risk for promiscuity, prostitution, and teenage pregnancy: a prospective study. 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  • 17. 20. Molnar BE, Buka SL, Kessler RC. Child sexual abuse and subsequent psychopathology: results from the national comorbidity survey. Am J Public Health. 2001;91:753-60. 21. Green JG, McLaughlin KA, Berglund PA, et al. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry. 2010; 67:113-23. 22. Bernstein DP, Fink L, Handelsman L, et al. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry. 1994;151:1132-6. 23. Bernstein DP, Fink L. Childhood trauma questionnaire. San Antonio, TX, Psychological Corporation, 1998. 24. Sar V, Ozturk E, Ikikardes E. Validity and reliability of the Turkish version of childhood trauma questionnaire. Turk Klin J Med Sci. 2012;32:1054-63. 25. Oner N, Le CompteA. Durumluk Sürekli Kaygı Envanteri El Kitabı. İstanbul: Boğaziçi Üniversitesi Yayınları, 1985. 26. Spielberger C, Gorsuch R, Lushene R. Manual for the state-trait anxiety inventor. Palo Alto (Calif): Consulting Psychologist Press; 1970. 27. Carr E, Brockbank K, Allen S, et al. Patterns and frequency of anxiety in women undergoing gynaecological surgery. J Clin Nurs. 2006;15:341-52. 28. Moser D. Critical care nursing practice regarding patient anxiety assessment and management. Intensive Crit Care Nurs. 2003;19:276-88. 29. Atanassova M. Assessment of preoperative anxiety in patients awaiting operation on thyroid gland. Khirurgiia (Sofiia). 2009;4:36-9. 30. Huh HJ, Kim SY, Yu JJ, et al. Childhood trauma and adult interpersonal relationship problems in patients with depression and anxiety disorders. Ann Gen Psychiatry. 2014;16;13:26. 31. Friis RH, Wittchen HU, Pfister H, et al. Life events and changes in the course of depression in young adults. Eur Psychiatry. 2002;17:241-53. 32. Gibb BE, Chelminski I, Zimmerman M. Childhood emotional, physical, and sexual abuse, and diagnoses of depressive and anxiety disorders in adult psychiatric outpatients. Depress Anxiety. 2007;24:256-63. 33. Gamble SA, Talbot NL, Duberstein PR, et al. Childhood sexual abuse and depressive symptom severity: the role of neuroticism. J Nerv Ment Dis. 2006;194:382-5. 34. van Veen T, Wardenaar KJ, Carlier IV, et al. Are childhood and adult life adversities differentially associated with specific symptom dimensions of depression and anxiety? Testing the tripartite model. J Affect Disord 2013;146:238-45. 35. Etain B, Aas M, Andreassen OA, et al. Childhood trauma is associated with severe clinical characteristics of bipolar disorders. J Clin Psychiatry. 2013;74:991-8. 36. Schaefer I, Reininghaus U, Langeland W, et al. Dissociative symptoms in alcohol dependent patients: associations with childhood trauma and substance abuse characteristics. Compr Psychiatry. 2007;48:539-45. 37. Schäfer I, Langeland W, Hissbach J, et al. TRAUMAB-Study group. Childhood trauma and dissociation in patients with alcohol dependence, drug dependence, or both—a multi-center study. Drug Alcohol Depend. 2010;109:84-9. 38. Evren C, Ustunsoy S, Cakmak D. Dissociative symptoms among alcohol and substance dependents and its relationship with childhood trauma history, depression, anxiety, and alcohol/substance use. Anatol J Psychiatry. 2003;4:30-7. 39. Ramesh B, Nayak S, Pai VB, et al. Pre-operative anxiety in patiens undergoing coronary artery bypass graft surgery-A cross sectional study. Int J Africa Nursing Sci. 2017;7:31-6. 40. Gallagher R, McKinley S. Anxiety, depression and perceived control in patients having coronary artery bypass grafts. J Adv Nurs. 2009;65:2386- 96. 41. Tung HH, Hunter A, Wei J, et al. Gender differences in coping and anxiety in patients after coronary artery bypass graft surgery in Taiwan. Heart Lung. 2009;38:469-79. 42. Maheshwari D, Ismail S. Preoperative anxiety in patients selecting either general or regional anesthesia for elective cesarean section. J Anaesthesiol Clin Pharmacol. 2015;31:196-200. 43. Papanikolaou MN, Voulgari A, Lykouras L, et al. Psychological factors influencing the surgical patients’ consent to regional anaesthesia Acta Anaesthesiol Scand. 1994;38:607-11. 44. Ay AA, Ulucanlar H, Ay A, et al. Risk factors for perioperative anxiety in laparoscopic surgery. JSLS. 2014;18:e2014.00159. 45. Moerman N, van Dam FS, Muller MJ, et al. The amsterdam preoperative anxiety and information scale (APAIS). Anaesth Analg. 1996;82:445-51. 46. Carr E, Brockbank K, Allen S, et al. Patterns and frequency of anxiety in women undergoing gynaecological surgery. J Clin Nurs. 2006;15:341-52. 47. Hepner LD, Bader MA, Hurwitz S, et al. Patient satisfaction with preoperative assessment in a preoperative assessment testing clinic. Anesth Analg. 2004;98:1099-105. 48. Kouki P, Matsota P, Christodoulaki K, et al. 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  • 18. Available online at www.medicinescience.org ORIGINAL RESEARCH Medicine Science 2019;8(2):274-6 Our experience and results of clinical incidental gallbladder carcinomas Oguz Catal, Bahri Ozer, Mustafa Sit Bolu Abant Izzet Baysal Univercity Medical Faculty, Depertmant of General Surgery, Bolu, Turkey Received 03 October 2018; Accepted 21 October 2018 Available online 2018 with doi:10.5455/medscience.2018.07.8952 Copyright © 2019 by authors and Medicine Science Publishing Inc. Abstract This study aimed to eveluate our experience in incidental gallbladder carcinomas the effect of resection on life time .We suggest that liver resection may contribute to the disease free survival of the patients with incidental gallbladder carcinomas. Between January 2012 and December 2017, 3691 patients who underwent cholecystectomy in the Department of General Surgery of Abant Izzet Baysal University Medical Faculty and who did not consider biliary stricture in their preoperative evaluation were evaluated retrospectively.Patients were grouped according to age, sex, stone size, bile duct wall thickness and histopathological results. The preoperative diagnosis of all patients undergoing cholecystectomy was cholelithiasis. Of the 3691 patients, gallbladder cancer was detected in the evaluation of the pathology specimens of 16 patients (0.50%) of the patients who were diagnosed with gallbladder carcinomas, 12 had female gender and 4 had male gender. All of the patients were found to have adenocarcinoma when the pathology specimens were examined. In the pathology specimens, 2 patients had carcinoma insitu, 2 patients had T1, 5 patients had T2, 7 patients had T3. In this study we share our experience in incidental gallbladder carcinomas and suggest that liver resection may contribute to the disease free survival of the patients with incidental gallbladder carcinomas. Keywords: Incidental gallbladder carcinomas,gallbladder stones,liver resection,disase free survival,cholecyctectomy Medicine Science International Medical Journal 274 Introduction Gallbladder carcinomas are rare tumors with poor prognosis. Biliary tree tumors are one of the most common cancers, and the 5th most common cancers of the gastrointestinal tract. Biliary cancer is 2-3 times more frequent in males than females, and most commonly seen in 7th decade. It is seen 0.4% in autopsy series and approximately 1% of patients who underwent cholecystectomy because of bile stone. Geographically, biliary incident cancers are more common in the USA, Mexico, Chile, Israel, Poland, India and Japan. The greatest risk factor for the development of gallbladder cancer is gallbladder stones and gallbladder stones and have been found in 95% of patients with gallbladder cancer [1]. The risk of developing cancer within 20 years in patients with biliary stones is less than 0.5% for the entire population, while it is 1.5% for the high-risk group. Although the pathogenesis is unknown, it is associated with chronic inflammation. It is associated with a 10- fold increased risk of cancer in large stones 3cm [2]. Other risk factors for gallbladder carcinoma include: female sex, obesity, *Coresponding Author: Oguz Catal, Bolu Abant Izzet Baysal Univercity Medical Faculty, Depertmant of General Surgery, Bolu, Turkey E-mail: otuzogur@hotmail.com advanced age, porcelain gall bladder, typhus carriage, mono- silent ( 10 mm) polyps, scleroderma colonitis and exposure to carcinogens. The use of laparoscopic cholecystectomy for benign biliary diseases today has dramatically increased the incidence of incidental gallbladder cancer. This also increased the rate of gallbladder cancer, which had a good prognosis when detected in early stage. After simple cholecystectomy for benign conditions, the rate of malignancy detected in the pathology specimen varies from 0.3% to 2% and often provides complementary surgical radical treatment. We aim to evaluate our clinical experience incidental gallbladder carcinomas and we evaluate the patients disase free survival after which we apply resection procedure. Material and Methods Between January 2012 and December 2017, 3691 patients who underwent cholecystectomy in the Department of General Surgery of Abant Izzet Baysal University Medical Faculty and who did not consider gallbladder cancer in their preoperative evaluation were
  • 19. evaluated retrospectively. Patients were grouped according to age, sex, stone size, bile duct wall thickness and histopathological results. The preoperative diagnosis of all patients undergoing cholecystectomy was cholelithiasis. Preoperative hemogram, cholestasis enzymes, ultrasonography results and pathology results of the patients were evaluated. All of the emergency and elective patients were included in the study. Ultrasonography results were classified as 3 cm stone, 1-2 cm stone and 1 cm stone size according to stone dimensions. Again, the biliary tree was classified as having wall thickness 3 mm and wall thickness 3 mm according to wall thickness. Examination of the specimens used according to TNM staging of AJCC in cancer stage. The contribution of T wall invasion to survival and life time of liver resection was evaluated in cases with gallbladder cancer. Results Of the 3691 patients with cholecystectomy who were evaluated retrospectively, 1022 were men gender and 2669 were women. The mean age of the patients was 54.86 (range 19-92)Of the 3691 patients, gallbladder cancer was detected in the evaluation of the pathology specimens of 16 patients (0.50%). The mean age of this group was 61.5 (50-86), which was significantly higher than the mean age of the remaining group (table 1). Of the patients who were diagnosed with gallbladder carcinomas, 12 had female gender and 4 had male gender (table 1). All of the patients were found to have adenocarcinoma when the pathology specimens were examined. In the pathology specimens, 2 patients had carcinoma insitu, 2 patients had T1, 5 patients had T2, 7 patients had T3 (table 1). Eleven patients were electively treated (Table 1), while 5 of the 16 patients who were incidentally diagnosed with gallbladder stone pathology specimens were treated with acute cholecystitis. Of these 16 patients, 2 were operated on before ERCP and stent was inserted. Patients who underwent cholecystectomy due to the presence of stone at the gallbladder when two of 16 patients were opposed to colon cancer and concomitant gallbladder carcinomas. When the degrees of differentiation in the pathology specimens of patients with incidental gallbladder stones cancer were examined, it was found that 6 had good differentiation, 4 had moderate differentiation, and 6 had worse differentiation (table 1). In our study, the thickness of the gallbladder wall was found to be 3 mm or less in 4 patients, whereas it was seen that the thickness of the wall was 4 mm or more in 12 patients. The size of stones were larger than 30mm in 10 patients and 30mm or smaller in 6 patients (table 1). A lymph node dissection was performed with resection of liver tumor segment 4B and 5 with T2 tumor. The number of patients with T3 is 7. Four patients did not accept resection after cholecystectomy. We performed liver resection 7 of 12 patients with t2 and t3 cancer. One patient was unable to be performed liver resection due to cardiac and pulmoner problems who underwent cholecystectomy performed during advanced colon cancer surgery Two patients underwent segment 4,5,8 resection and lymph node dissection. One patient who underwent resection in T2 was treated for 5 years, 1 patient for 4 years, 1 patient for 2 years and 1 patients for disease free survival for one year. 1 patient who underwent resection of T3 complained of peritoneal carcinomatosis and liver metastases after completing 3 year disease-free survival period and deceased at 4th year of follow up. The other two patients with T3 disease were completed their 1.5 and 1 year disease-free survival. Table 1. Demographic and pathological distributions of incidental gallbladder cancer Age ≥60 years 13 81.25% 60 years 3 18.75% Gender Women (n) 12 75.00% Men (n) 4 25.00% Wall thickness (mm) ≤3 5 31.25% 3 11 68.75% Stone size (cm) 3 6 37.50% 3 10 62.50% Elective /Emergent Surgery Elective 11 68.75% Emergent 5 31.25% Differentiation worse 6 37.50% moderate 4 25.00% good 6 37.50% T Stage Tis 2 12.50% T1 2 12.50% T2 5 31.25% T3 7 43.75% Resection Yes 7 58.33% No 5 41.67% Discussion Most of the gallbladder carcinomas are unresectable at the time of diagnosis. Due to their aggressive attitudes, the 5 year life span is below 5% and the median life span is about 6 months [3]. Clinical signs and symptoms in gallbladder carcinomas are similar to those of cholelithiasis and cholecystitis. More than half of gallbladder cancer can not be diagnosed preoperatively. Diagnosis is made by examination of the specimens of patients who have benign diseases, for example gallbladder stones, polyps, etc., by the most common diagnostic pathologists [4,5]. The high rate of use of ultrasonography and the worldwide progress of laparoscopic cholecystectomy as a widespread surgical procedure are expected to increase the number of incidentally found gallbladder cancer over time [6,7]. The main goal of treatment in gallbladder carcinomas is surgical resection of the intended R0 without leaving the residual tissue behind. Patients undergoing resection in gallbladder carcinomas have also shown that the 5-year survey rate doi: 10.5455/medscience.2018.07.8952 Med Science 2019;8(2):274-6 275
  • 20. doi: 10.5455/medscience.2018.07.8952 Med Science 2019;8(2):274-6 276 ranges from 0-100%. This change is strongly related to the stage of the patient. Simple colecystectomy is sufficient for carcinoma in situ and T1a cases [5,8,9]. Resection (radical cholecystectomy with regional lymph node dissection) should be performed in the patient group of T1b and over in order to perform resection of R0 [8,10]. Our patient found incidence of incidental gallbladder carcinomas 0.5%, which was 0.19% -2.8% in literature [11,12]. In our study, the mean age of the benign patient group who were operated on for gallbladder stones was 54.86 (range 19-92), whereas the mean age of the patients with incidental gallbladder cancer was 61.50 (range 50-86) it is seen that there is a further age group. The gender distribution of gallbladder cancer is three times higher in females than in males [13]. In our study, it was observed that 12 of the 16 patients were female and 4 were male, and the ratio was 3: 1. Concerning the stone size and number of incidentally detected gallbladder cancers, it was found to be a risk factor for gallbladder cancer, which is a multiple stone in stone and gallstones over 3 cm in previous studies [13,14]. In our study, 16 preliminary ultrasonographic findings of incidentally detected gallbladder cancer patients were found to have a stone size of 3 cm in 10 gallbladder stones and multiple gallbladder stones in all patients except one. Patients with pathologic end-stage carcinoma in situ in patients with gallbladder cancer and those with T1 results do not require additional treatment for cholecystectomy and 5-year survival is 90-100% in this patient group. Similar results were obtained in our patient series. More than simple cholecystectomy is needed in T2 cancers. Segment 4B and segment 5 resection is the appropriate treatment approach, as the resection of the liver bed adjacent to the biliary tree at a depth of 2 cm is acceptable. In addition, regional lymphadenectomy is needed. When T2 cancer cases are treated with radical cholecystectomy, the 5-year survival rate is 80-90%. Our patient underwent lymphadenectomy with segment 4B and 5 resection in our series and we obtained a similar survival result. In patients without resection, the survey is between 6 and 8 months. In the last decade in patients with T3 cancer, most centers have reported that aggressive surgery provides 25-50% longer survival in locally advanced disease. In our study, 1 patient who underwent resection of T3 complained of peritoneal carcinomatosis and liver metastases after completing 3 year disease-free survival period and deceased at 4th year of follow up. The other two patients with T3 disease were completed their 1.5 and 1 year disease-free survival. When the pathologies of patients after resection were evaluated, lymph node metastasis was reported in 1 patient of 7 resected patients, while the lymph node pathologies of other patients were reactive. Conclusion In conclusion, we suggest that liver resection may contribute to the disease free survival of the patients with incidental gallbladder carcinomas. Competing interests The authors declare that they have no competing interest Financial Disclosure The financial support for this study was provided by the investigators themselves. Ethical approval Bolu Abant Izzet Baysal Education and Reserch Ethics commite accept our study in 05.01.2018 and 00060010850 serial number Oguz Catal ORCID: 0000-0002-4067-251X Bahri Ozer ORCID: 0000-0002-4326-2101 Mustafa Sit ORCID: 0000-0002-7475-7298 References 1. Serra I, Calvo A, Baez S, et al. Risk factors for gallbladder cancer. An international collaborative case control study. Cancer Cancer. 1996;78:1515- 7. 2. Lowenfels AB, Walker AM, Althaus DP, et al. Gallstone growth, size and risk of gallbladder cancer: An interracial study. Int J Epidemiol. 1998;18:50-4. 3. Noshiro H, Chijiiwa K,Yamaguchi K, et al. Factors affecting surgical outcome for gallbladder carcinoma. Hepatogastroenterology. 2003;50:939-44. 4. Shih SP, Schulick RD, Cameron JL, et al. Gallbladder cancer: the role of laparoscopy and radical resection, Ann Surg. 2007;245:893-901. 5. Fuks D, Regimbeau JM, Le Treut YP, et al. Incidental gallbladder cancer by the AFC-GBC-2009 Study Group, World J Surg. 2011;35:1887-97. 6. Jensen EH, Abraham A, Habermann EB, et al. A critical analysis of the surgical management of earlystage gallbladder cancer in the United States, J Gastrointest Surg. 2009;13:722-7. 7. de Aretxabala XA, Roa IS, Mora JP, et al. Wanebo, Laparoscopic cholecystectomy: its effect on the prognosis of patients with gallbladder cancer. World J Surg. 2004;28:544-7. 8. Pawlik TM, Gleisner AL, Vigano L, et al. Capussotti, Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re- resection, J Gastrointest Surg. 2007;11:1478-86. 9. Shimizu H, Kimura F, Yoshidome H, et al. Aggressive surgical approach for stage IV gallbladder carcinoma based on Japanese Society of Biliary Surgery classification. J Hepatobiliary Pancreat Surg. 2007;14:358-65. 10. Yagi H, Shimazu M, Kawachi S, et al. Retrospective analysis of outcome in 63 gallbladder carcinoma patients after radical resection. J Hepatobiliary Pancreat Surg. 2006;13:530-6. 11. Misra S, Chaturvedi A, Misra NC, et al. Carcinoma of the gallbladder. Lancet Oncol. 2003;4:167-76. 12. Tian YH, Ji X, Liu B, et al. Surgical treatment of incidental gallbladder cancer discovered during or following laparoscopic cholecystectomy. World J Surg. 2015;39:746–52. 13. Hamdani NH, Qadri SK, Aggarwalla R, et al. Clinicopathological study of gall bladder carcinoma with special reference to gallstones: our 8- year experience from eastern India. Asian Pac J Cancer Prev. 2012;13:5613-7 14. Vitetta L, Sali A, Little P, et al. Gallstones and gall bladder carcinoma. J Surg. 2000;70:667-73.
  • 21. Available online at www.medicinescience.org ORIGINAL RESEARCH Medicine Science 2019;8(2):277-81 Assessment of readability level of informed consent forms used in intensive care units Munise Yildiz, Betul Kozanhan, Mahmut Sami Tutar University of Health Sciences, Konya Education and Research Hospital, Clinic of Anesthesiology and Reanimation, Konya, Turkey Received 08 October 2018; Accepted 23 October 2018 Available online 04.11.2018 with doi:10.5455/medscience.2018.07.8933 Copyright © 2019 by authors and Medicine Science Publishing Inc. Abstract Informed consent forms are printed forms prepared to assist patients in the treatment process by explaining the indications, benefits and possible risks of medical practices. Readability describes understanding difficulty and is calculated by mathematical formulas. The study aimed to assess the readability level of “Informed Consent Forms” used in intensive care units. The informed consent forms from 45 hospitals in our country have been gathered. In each average form number of words, the average number of syllables and the average number of words with 4 or more syllables were manually calculated using the “Microsoft Office Excel 2016®” program. Their readability levels have been assessed with Atesman and Bezirci-Yılmaz readability formulas. The readability level of forms was “difficult” according to the Atesman readability formula and at “undergraduate level” according to the Bezirci-Yilmaz readability formula. The readability level of forms used in private hospitals was found to be significantly lower than that used in state and university hospitals (p=0.019, p=0.012). The average number of words and the average number of words with 4 or more syllables in forms were found to be significantly higher in private hospitals compared to state and university hospitals (p=0.004, p=0.01). It has been determined that the readability level of informed consent forms was at academic literacy level. To protect patient rights and to regulate patient-physician relationships by taking into account individuals rights, informed consent forms should be reviewed and that their readability levels should be adjusted to cover the overall educational level of individuals in the general population. Keywords: Intensive care, informed consent form, readability Medicine Science International Medical Journal 277 Introduction Informed consent forms are printed forms containing the diagnosis of disease, the proposed treatment method and the risks of this method for the patient’s health, the use and possible side effects of medical treatments and the outcomes of disease if the proposed treatment is refused [1]. The informational obligation is a debt for the physician and a right for the patient regarding the physician- patient relationship. Although the patient’s right to be informed is mentioned in the “Patients Rights Regulation” which has been put into force in Turkey in 1998, it is specified that the mentioned information should be clear and understandable enough and then must answer all possible questions. Before obtaining a patient’s informed consent for any medical intervention, the patient should be informed about the type, prognosis and possible side effects of the medical intervention, the outcomes of disease in case of *Coresponding Author: Munise Yildiz, University of Health Sciences, Konya Education and Research Hospital, Clinic of Anesthesiology and Reanimation, Konya, Turkey E-mail: drmunise@hotmail.com treatment refusal [2]. However, the reliability and update of, as well as their “readability” and “understandability,” are somewhat important because the value of information is limited by the ability of individuals to comprehend. Although readability has been popular in recent years, it was based on past studies. It is a concept that provides some numerical data about texts and gives information about whether the text is easy to be understood by the reader at a certain level using characteristic features of syllables, words, and sentences of the language. Although this concept has been used mostly in inter-institutional correspondence, military organizations and healthcare companies in the past, today, it has become a concept which is used by linguistic scientists as well as other scientists and on which studies are performed frequently [3]. Besides the average number of words, the average number of syllables and the average number of words with 4 or more syllables, various criteria such as number synonym words must be placed in mathematical formulas to determine the readability level of a written text. To perform readability analysis, different formulas have been developed in Turkish as well as many foreign languages such as English and Spanish
  • 22. [4-7]. The Atesman and Bezirci-Yilmaz readability formulas, which have been described for determining the readability level of Turkish texts [5,6] and the Gunning-Fog and Flesch–Kincaid readability formulas, which measure the overall readability, [7,8] are commonly used readability formulas. There is a limited number of studies on informed consent forms used in intensive care units in our country. The study aimed to assess the readability level of “Informed Consent Forms” that are mandatory to be obtained regarding both legal and ethical issues before any medical intervention performed in intensive care units. Materials and Methods The study has been approved by the Education Planning Board of University of Health Sciences Konya Training and Research Hospital (Decision No: 1 March 2018/13-17). There are informed consent forms that are created according to certain standards and are routinely used in intensive care units of hospitals in our country. For the study, informed consent forms that were regularly used in intensive care units of 45 hospitals including university hospitals and training and research hospitals (n=15), state hospitals (n=15), and private hospitals (n=15) have been gathered. Each informed consent form was transferred to the “Microsoft Word 2016®” in the electronic environment. The institutional knowledge sections have been deleted to keep objectiveness of readability results. The average number of words, the average number of syllables and the average number of words with 4 or more syllables in these forms have been manually calculated using the “ Microsoft Office Excel 2016®” program. For the calculation of the readability levels of each informed consent form, using Atesman and Bezirci-Yilmaz formulas data have been transferred to a computer software program [5,6]. The rate of medical terms within these 100 words has been determined as a percentage (%). Atesman Readability Formula: It has been adapted into Turkish from Flesch’s Reading Ease Formula by Atesman (1997). It is a formula based on word and sentence length [5]. The Atesman readability formula gives a score on a scale ranging from 0–100; a higher score indicates that the text is easier to read while a lower number suggests that the text is more difficult to understand (Table 1). Atesman readability formula: Readability Score = 198.825 – 40.175 x (total number of syllables/ total number of words) – 2.610 x (total number of words/total number of sentences) Bezirci-Yilmaz Readability Formula: This formula was developed in 2010 based on the length of sentences in a text, the number of syllables in a word, and the statistical properties of Turkish language [6]. When the readability level is calculated, the number of syllables in each word is multiplied by its number. The readability level is formulated as follows: √(ANW×((H3×0,84) + (H4×1,5) + (H5×3,5) + (H6× 26,25)) ANW: average number of words H3: average number of 3-syllable words H4: average number of 4-syllable words H5: average number of 5-syllable words H6: average number of words with 6 or more syllables According to this formula, the readability level becomes more difficult as the length of sentences increases in texts. Moreover, an increase in the number of syllables in words makes it difficult to read words and indirectly sentences. This formula explains which class level a text represents according to the education system in our country: 1-8= primary school; 9-12= secondary school (high school); 12-16 = undergraduate level, and ˃16 = higher education. Statistical Analysis: The SPSS® 21 (IBM Inc, USA) software was used to analyze the data. Categorical data were expressed as frequency and percentage. Numerical data were expressed as a mean ± standard deviation. The One Way ANOVA and Kruskal-Wallis tests were used to compare numerical data between independent groups. All statistical analyzes have been performed bidirectionally at the 5% significance level and the 95% confidence interval. Results Informed consent forms which were used in intensive care units of 45 medical institutions in our country have been included in the study. The mean readability value of these forms according to the Atesman and Bezirci-Yilmaz readability formulas as well as the average number of words, the average number of syllables and the average number of words with 4 or more syllables in these forms are shown Table 2. The mean readability value of these forms according to the Atesman readability formula was calculated as 41.8 for university hospitals and training and research hospitals, 43.0 for state hospitals and 35.7 for private hospitals, respectively. The readability level of informed consent forms was “difficult” according to the Atesman readability formula. The readability level of informed consent forms used in private hospitals was found to be significantly lower than those of informed consent forms used in state and university hospitals (p=0.019). The mean readability value of these forms according to the Bezirci-Yilmaz readability formula was calculated as 14.9 for university hospitals and training and research hospitals, 14.4 for state hospitals and 17.7 for private hospitals, respectively. The readability level of informed consent forms was at “undergraduate level” according to the Bezirci-Yilmaz readability formula. According to the Bezirci- Yilmaz readability formula, there was a significant difference between the mean readability values of informed consent forms used in intensive care units of university hospitals and training and research hospitals, state hospitals and private hospitals (p=0.012). The average number of words and the average number of words with 4 or more syllables in informed consent forms were found to be significantly higher in private hospitals compared to state and university hospitals (p=0.004, p=0.01). There was no significant difference between these institutions regarding the average number of syllables (p=0.361). There was no significant difference between these institutions regarding the rate of medical terms in the 100-word text. Table 1. Atesman Turkish Readability Formula Level Readability range Very easy 90-100 Easy 70-89 Moderate 50-69 Difficult 30-49 doi: 10.5455/medscience.2018.07.8933 Med Science 2019;8(2):277-81 278