jhsci-2014-4-3

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Editor-in-Chief Dijana Avdic University of Sarajevo Faculty of Health Studies, Bosnia and HerzegovinaEditorial Board Borut Poljsak, Laboratory of Oxidative Stress Research, University of Ljubljana, Ljubljana, SloveniaEmira Švraka, University of Sarajevo Faculty of Health Studies, Bosnia and HerzegovinaFatima Jusupovic, University of Sarajevo Faculty of Health Studies, Bosnia and HerzegovinaIsabelle Richard, Department of Physical Medicine and Rehabilitation, CHU of Angers Rue des Capucins, Angers, FranceIvan Malcic, Department of Pediatrics, Clinical Hospital Rebro, Zagreb, CroatiaKasim Bajrovic, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and HerzegovinaĽubica Ilievová, Trnava University of Trnava, Slovakia, SlovakiaMaja Miškulin, University of Osijek, Faculty of Medicine, CroatiaMirsada Hukic, Department of Microbiology and Virology, University of Sarajevo, Sarajevo, Bosnia and Herzegovina

Monika Ulamec, Department of Pathology, Clinical Hospital Sestre Milosrdnice Zagreb, CroatiaMuzafer Mujic, Bosnia and HerzegovinaNaris Pojskic, Institute for Genetic Engineering and Biotechnology, Sarajevo, Bosnia and HerzegovinaPayam Behzadi, Faculty Member of Microbiology Department Islamic Azad University Shahr-e-Qods Branch, IranRenata Dobrila Dintinjana, Department of Radiotherapy and Oncology, University of Rijeka Clinical Center, CroatiaReza Ranjbar, Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IranSenka Mesihovic-Dinarevic, University Clinical Center Sarajevo, Bosnia and HerzegovinaYigit Akin, Department of Urology, Harran University School of Medicine, Sanliurfa, TurkeyZarema Obradovic, Institute for Public Health of Canton Sarajevo, Bosnia and Herzegovina

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The significance of psychosocial factors of the working environment in the development of sick building syndromeMaja Miškulin, Marina Matić, Miodrag Beneš, Jelena Vlahović ��136-142

Vitamin B12 deficiency and depression in elderly: Cross-sectional study in Eastern CroatiaMaja Miškulin, Marija Kristić, Jelena Vlahović ��143-148

Average saturated fatty acids daily intake in Sarajevo University studentsAmra Ćatović, Amela Dervisević, Orhan Lepara, Semir Gorčević, Jasna Gorčević ��149-155

Early extubation after congenital heart surgeryMirza Halimić, Senka Mesihović Dinarević, Zijo Begić, Almira Kadić, Sanko Pandur, Edin Omerbašić ��156-161

Effect of Costus igneus: The insulin plant, on pre-diabetes and diabetes in neonatal streptozotocin ratsMurthy EGK Talasila, Hemalatha Bavirisetti, Jithendra Chimakurthy, Mayuren Candasamy ��162-168

A Network for Eating and Nutrition as a platform for cooperation over the organisational borders between healthcare sectors in SwedenZada Pajalic, Albert Westergren ��169-175

The role of natural supplement of apple vinegar and syrup in the management of type 2 diabetes mellitusBećir Heljić, Zelija Velija-Ašimi, Azra Bureković, Vanja Karlović, Azra Avdagić, Murisa Ćemalović ��176-180

Modern treatment of patent ductus arteriosus – Single center experienceSenka Dinarević, Almira Kadić, Zijo Begić, Mirza Halimić, Emina Vukas ��181-185

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RESEARCH ARTICLES

CASE REPORTS

http://www�jhsci�ba Maja Miškulin, et al� Journal of Health Sciences 2014;4(3):136-142

RESEARCH ARTICLE Open Access

The significance of psychosocial factors of the working environment in the development of sick building syndromeMaja Miškulin1*, Marina Matić2, Miodrag Beneš3, Jelena Vlahović1

1University of Osijek Faculty of Medicine, Osijek, Croatia, 2University of Osijek Faculty of Humanities and Social Sciences, Osijek, Croatia, 3Health Centre of the Virovitica-Podravska County, Virovitica, Croatia

ABSTRACT

Introduction: Sick building syndrome (SBS) is a medical condition in which people in a certain buildings suffer from symptoms of illness or feeling unwell� The aim of this study was to determine the frequency of exposure of the employees of public institutions from the city of Osijek to harmful psychosocial factors of the working environment, to assess whether there is a connection between the exposure to these factors and the incidence of SBS symptoms and to clarify the nature of this connection�

Methods: This cross-sectional study was conducted during May 2013 among 178 employees of public insti-tutions in the city of Osijek� An anonymous questionnaire which contained questions relating to demographic data and working status of the participants, their exposure to various harmful psychosocial factors of the working environment and occurrence of certain symptoms of SBS among them was used as a research tool�

Results: 96�1% (171/178) of participants were exposed to harmful psychosocial factors of the working environment� Employees exposed to those factors more frequently expressed symptoms of SBS� The inci-dence and the number of symptoms of SBS among employees simultaneously grew with the increase of the number of harmful psychosocial factors of the working environment to which they were exposed�

Conclusion: The study showed positive connection between the exposure to harmful psychosocial fac-tors of the working environment and the incidence of SBS symptoms, highlighting this issue as a very important subject in the field of occupational medicine and health protection in the workplace�

Keywords: Croatia; employee; health; psychosocial factors of the working environment; sick building syndrome

INTRODUCTIONSick building syndrome (SBS) was defined for the first time by the World Health Organization in

Corresponding Author: Maja Miškulin, University of Osijek, Faculty of Medicine, Josipa Huttlera 4, 31000 Osijek, Croatia� Fax: +385 1 606 76 86, GSM: +385 91 566 08 87� E-mail: miskulin�maja@gmail�com

Submitted August 09 2014 / Accepted: December 20 2014

© 2014 Maja Miškulin, et al�; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distri-bution, and reproduction in any medium, provided the original work is properly cited�

1983 (1). The syndrome includes a group of symp-toms of unknown etiology which are divided to the symptoms of irritation of the mucous membranes (eyes, nose and throat), skin symptoms such as dry skin and/or eczema or a skin rash as well as the general non-specific symptoms such as headache, nausea, dizziness, feeling of exhaustion and chronic fatigue and also difficulties in concentration. All

Maja Miškulin, et al� Journal of Health Sciences 2014;4(3):136-142 http://www�jhsci�ba

the above mentioned symptoms tend to increase in severity as a function of time spent in the building and improve in a few hours or even disappear when people are away from the building (only the skin takes a few days to recover) (2-5). Although the mechanisms involved in the production of symp-toms are largely unknown, in many studies, several factors have been associated with an increased prev-alence of SBS symptoms. Studies have shown that SBS can be linked to some personal characteristics of the people who stay in such “sick” buildings such as female sex (6-10) and personal history of allergies (7,8,11). Furthermore, the syndrome has been connected with the existence of several physi-cal risk factors in the working environment such as the presence of moisture in the building (8,12,13), poor ventilation of the building (6,14) as well as an air pollution of the indoor space (6,15,16). Finally it is related to some psychosocial factors of the employees, such as anxiety, position in the work hierarchy and emotional stability (6,8,17), as well as to some psychosocial factors of the working environment such as work overload, stress, lack of cooperation and support among workers as well as various conflict situations in the workplace(6,8,18). Given the previously mentioned risk factors, it is pointed out that lower position in the work hierar-chy and higher subordination represents a greater risk factor for the SBS development. Contrary, emotional stability is found to be a protective factor since studies have shown that the emotionally sta-ble people complain less about the symptoms that indicate the SBS (6,17).Despite the studies which connected the preva-lence of SBS with various, previously mentioned potential risk factors, to this very day a definitive cause-and-effect relationship between SBS and neither one of them has not been revealed (11). Experts also disagree about which risk factors could be more important in the development of this syn-drome, and while most believe that the syndrome is predominantly related to some physical factors of the working environment, primarily with the poor indoor air quality (7,11,19-23), others point out that in terms of the occurrence of SBS some psy-chosocial factors of the working environment are more significant (18). In Croatia, the issue of SBS is very poorly studied and to this very day only a

few studies of this syndrome were conducted among employees, only from the area of Zagreb and Central Croatia (17,24,25).The aim of this study was to determine the frequency of exposure of the employees of public institutions from the city of Osijek (Eastern Croatia) to harmful psychosocial factors of the working environment, to assess possible connection among the exposure of employees to these factors and to determine the incidence of one or more SBS symptoms between them.

METHODS

Study designThis cross-sectional study was conducted during May 2013 among employees of public institutions in the area of the city of Osijek (Eastern Croatia).All of the participants voluntarily participated in this study after signing an informed consent, and the entire study was approved by the Ethics Committee of the Osijek Health Centre. Participants were selected randomly among employees of public insti-tutions in the city of Osijek. A total of 300 question-naires were distributed. The overall response rate was 59.3% (178/300). All of the returned questionnaires were statistically analyzed. Within the final sample of 178 participants, there were 33.7% (60/178) males and 66.3% (118/178) females, with a mean age of 39.3±10.4 (range 19-64) years. The sample was stratified according to gender, age or age group (three age groups: 18-32 years, 33-46 years and 47 years and over), length of working experience (3 groups according to length of working experi-ence: 1-9 years, 10-19 years and 20 or more years of working experience) and level of education of the participants (two groups based on the level of education: a group of participants with secondary or higher education and a group of participants with a university degree).The questionnaire used in this study was designed to detect the frequency of exposure of study participants to harmful psychosocial factors of the working envi-ronment and to evaluate the connection between such exposure and the incidence of one or more symptoms of SBS among examinees. It contained questions relat-ing to gender and age, length of working experience,

level of education, frequency of occurrence of certain SBS symptoms (such as fatigue, headaches, etc.) and the frequency of exposure to harmful psychosocial factors of the working environment that included: interestingness of work they do, workload in the workplace, ability of the participants to influence the quality of their own work conditions and social sup-port while performing the work by their co-workers.

Statistical analysisUpon confirming normality of data distribution by Kolmogorov-Smirnov test, all data were processed by the methods of descriptive statistics. The propor-tions were calculated and compared by use of c2-test for independent samples or Fisher’s exact test. In all statistical analyses, two-sided P values of 0.05 were considered significant. Statistical analysis was done by the SPSS Statistical Package for Windows, version 13.0 (SPSS Inc., Chicago, IL, USA).

RESULTSThe study has shown that as many as 96.1% (171/178) of the participants were exposed to harm-ful psychosocial factors of the working environ-ment at their workplace. Study further showed that 97.5% (115/118) female and 93.3% (56/60) male participants were exposed to harmful psychosocial factors of the working environment.Among participants exposed to harmful psycho-social factors of the working environment, 43.9% (75/171) of them have been exposed to one, 45.0% (77/171) of participants have been exposed to two, 8.8% (15/171) of participants have been exposed to three and 2.3% (4/171) of participants have been exposed to four harmful psychosocial factors of the working environment. According to the type of harmful psychosocial factor of the working environment to which participants were exposed, 93.0% (159/171) of them reported excessive work-load, 52.6% (90/171) reported the inability to influence the quality of their own work conditions, 12.9% (22/171) reported the lack of social support from their co-workers while performing the work and 9.9% (17/171) reported performing uninterest-ing work and work that is not motivating.According to the gender and age group in which the participants belonged to and according also to

the length of working experience of the participants and the level of their education, it was found that women, people aged 33-46 years, people with the length of working experience between 1-9 years and people with a university degree were more frequently exposed to all of the observed harmful psychosocial factors of the working environment while the performing uninteresting work and work that is not motivating was only factor that has been more frequently reported by the employees with sec-ondary and higher education.Among participants who were exposed to harmful psychosocial factors of the working environment, there were 62.6% (107/171) of them who had one or more SBS symptoms compared to 42.9% (3/7) of those who were not exposed to such factors, but this difference was not statistically significant (Fisher’s exact test; p=0.430). As the number of harmful psychosocial factors of the working environment to which participants were exposed grew, the number of participants who experienced one or more symp-toms of SBS increased as well but these differences were not statistically significant (Fisher’s exact test; p=0.428) (Table 1).The prevalence of symptoms of SBS as a result of the exposure to each of the observed harmful psychosocial factors of the working environment is shown separately in Table 2. It is evident that the smallest number of participants who have the SBS symptoms was established among participants who performed uninteresting work and work that is not motivating (58.8%), while the largest number of participants with the SBS symptoms was estab-lished among those who did not have an ability to influence the quality of their own work conditions (71.1%), where in the latter case the determined dif-ference was statistically significant (c2=6.689; df=1; p=0.013) (Table 2).When looking at all the participants in whom the existence of symptoms of SBS were determined, it was evident that among them 2.7% (3/110) were those who were not exposed to harmful psycho-social factors of the working environment, 38.2% (42/110) were exposed to one, 46.4% (51/110) were exposed to two, 10.0% (11/110) were exposed to three, and 2.7% (3/110) were exposed to four harm-ful psychosocial factors of the working environment.

Comparing the participants with 1-3 and 4 or more symptoms of SBS according to the number of harm-ful psychosocial factors of the working environment to which these two groups of participants were exposed, it is evident that there were differences in the number of harmful psychosocial factors of the working environment among them, and these dif-ferences were statistically significant (Fisher’s exact test; p= 0.001) (Table 3).

DISCUSSIONThe conducted study has shown that almost all of the employees (96.1%) of public institutions from the city of Osijek (Eastern Croatia) were exposed to one or more harmful psychosocial fac-tors of the working environment in their work-place. According to the frequency of each harmful psychosocial factors of the working environment to which participants at their workplace were exposed, it was established that 93.0% of partic-ipants experienced excessive workload at their workplace, 52.6% had no ability to influence the

quality of their own work conditions, 12.9% did not have social support from their co-workers while performing the work, and 9.9% of them per-formed an uninteresting work and work that is not motivating. These results are comparable with the results of a study conducted in southern Finland,

TABLE 1. Participants according to the gender and existence of symptoms of SBS and according to the exposure to a various number of harmful psychosocial factors of the working environmentGender Existence of

symptoms of SBS

Number of harmful psychosocial factors of the working environment to which participants were exposed

0 1 2 3 4Male participants No/N (%) 2 (50.0) 15 (57.7) 11 (44.0) 0 1 (50.0)

Yes/N (%) 2 (50.0) 11 (42.3) 14 (56.0) 3 (100.0) 1 (50.0)Total 4 26 25 3 2Female participants No/N (%) 2 (66.7) 18 (36.7) 15 (28.8) 4 (33.3) 0

Yes/N (%) 1 (33.3) 31 (63.3) 37 (71.2) 8 (66.7) 2 (100.0)Total 3 49 52 12 2All participants No/N (%) 4 (57.1) 33 (44.0) 26 (33.8) 4 (26.7) 1 (25.0)

Yes/N (%) 3 (42.9) 42 (56.0) 51 (66.2) 11 (73.3) 3 (75.0)Total 7 75 77 15 4

TABLE 2. Participants exposed to a particular harmful psychosocial factor of the working environment according to the existence of symptoms of sick building syndromeHarmful psychosocial factor of the working environment Existence of symptoms of SBS (N (%)) p‑value*

No YesPerforming uninteresting work and work that is not motivating 7 (41.2) 10 (58.8) 0.798Excess workload in the workplace 60 (37.7) 99 (62.3) 0.804Inability to influence the quality of one’s own work conditions 26 (28.9) 64 (71.1) 0.013#

Lack of social support from co‑workers while performing the work 8 (36.4) 14 (63.6) 1.000*χ2‑test; #statistical significant difference

TABLE 3. Participants with a various number of symptoms of sick building syndrome according to the number of harmful psychosocial factors of the working environment to which they were exposedNumber of harmful psychosocial factors of the working environment to which participants were exposed

Participants with a various number of SBS symptoms

(N (%))

Total N (%)

1‑3 symptoms

4 or more symptoms

0 3 (4.4) 0 3 (2.7)1 34 (50.0) 8 (19.0) 42 (38.2)2 27 (39.7) 24 (57.2) 51 (46.4)3 3 (4.4) 8 (19.0) 11 (10.0)4 1 (1.5) 2 (4.8) 3 (2.7)Total 68 42 110

in which it was established that local employees are also often exposed to harmful psychosocial factors of the working environment, but all of these harm-ful psychosocial factors of the working environ-ment were lower represented. Accordingly, 20.0% of Finnish employees experienced excessive work-load at their workplace, 21.0% of them had no ability to influence the quality of their own work conditions, 6.0% of them had no social support from their co-workers while performing the work and only 4.0% of them performed an uninterest-ing work and work that is not motivating (26).When observing the correlation between expo-sure to harmful psychosocial factors of the work-ing environment and gender of participants, this study showed that women are more often exposed to these harmful factors, which is in compliance with the results of studies conducted in Finland and Denmark (26,27). The study further affirmed that persons aged 33-46 years were more frequently exposed to harmful psychosocial factors of the work-ing environment, contrary to the study conducted in Finland according to which elderly employees, aged 45-54 years were more often exposed to these factors (26). The explanation for this result might be hidden in the fact that people in the age group of 33-46 years are in fact people who are in the most productive period of their life, predominantly focused at career advancement. Because of that, this group of employees sometimes consciously work a lot, often performing uninteresting work and work that is not motivating without thinking about the possibilities of influencing the quality of one’s own work conditions and not expecting too much social support from co-workers who often perceived them as a competition because they are also climbing the career ladder. In terms of the length of the working experience of the participants and their level of edu-cation present study showed that people with the length of working experience between 1-9 years and people with a university degree were more frequently exposed to all of the observed harmful psychosocial factors of the working environment. This result is difficult to compare with the results of other similar studies carried out in the world because they have not dealt with the connections between mentioned variables. The possible explanation lies in the fact that employees with the aforementioned length of

working experience and university degree, similar to the above mentioned employees aged between 33-46 years, are in fact people who are in that stage of their life where they are primarily focused at career advancement and because of that sometimes consciously exposed themselves to various harmful psychosocial factors of the working environment.The fact that in our study, employees with sec-ondary and higher level of education have more often reported the performance of an uninteresting work and work that is not motivating can be easily explained by their subordinate position in the work hierarchy, following which they are forced to do all the work assignments that their superiors instruct them to do, while some of these work assignments are sometimes uninteresting and not motivating.This study further showed that participants who were exposed to harmful psychosocial factors of the working environment are more likely to experience SBS symptoms compared to those who were not exposed to such harmful factors in the workplace, which is in compliance with the results of the similar studies conducted in Sweden, the UK, Finland and Denmark (10,18,26-29). Furthermore, the study showed that the increase of the number of harm-ful psychosocial factors of the working environment that participants were exposed to is accompanied by the increase in the number of participants who experienced one or more symptoms of SBS, which is in compliance with the results of similar studies conducted elsewhere in the world (26).Present study established that among the observed harmful psychosocial factors of the working envi-ronment, it is the very inability of participants to influence the quality of their own work conditions that contributes the most to the development of SBS symptoms, which is consistent with the results of the studies conducted elsewhere in the world (18). Finally, this study determined that exposure to a greater number of harmful psychosocial factors of the working environment is associated with a devel-opment of a larger number of SBS symptoms that was also shown in other similar studies (26).Our study has several limitations that should be considered when evaluating the obtained results. One of the limitations refers to the geographi-cal limitations of study in the area of the Eastern

Croatia which somewhat limits the generalization of study results to all the employees in Croatia due to possible differences in the psychosocial factors of the working environment to which employees from the different parts of Croatia are exposed. In addi-tion, since the participation in the study was volun-tary, the possibility that some employees, although exposed to some or all of the studied harmful psy-chosocial factors of the working environment which caused them to experience SBS symptoms, avoided involvement in the study simply because of fear of adverse consequences in the workplace. Besides that the limitation of the study is the lack of analysis of physical environmental conditions of office build-ings and also uneven gender representation of study participants. The latter one is a due to still present traditional labor division in Croatian society where females more often work in offices in comparison to males. Finally, since the study is designed as a cross-sectional study, definitive conclusions about the established cause-effect relationships between the patterns of appearance of symptoms of SBS and the observed harmful psychosocial factors of the working environment cannot be drown.

CONCLUSIONThis study determined a very frequent exposure of the employees of public institutions of Eastern Croatian to harmful psychosocial factors of the working environment, as highly significant risk fac-tors for the development of SBS among employees. The study confirmed that among the employees who were exposed to harmful psychosocial factors of the working environment symptoms of SBS were more common compared to those employees who were not exposed to such influences in the work-place, where the incidence and the number of SBS symptoms was growing in parallel with the increase in the number of harmful psychosocial factors of the working environment to which the employees were exposed. The most important identified harm-ful factors of the working environment in this study were an excessive workload at the workplace and the inability of employees to influence the quality of their own work conditions and it was demonstrated that the exposure to the latter factor contributes the most to the development of SBS symptoms.

Considering the prevalence of Eastern Croatia employees’ exposure to harmful psychosocial fac-tors of the working environment and considering also the proven relationship between these factors and the incidence of SBS symptoms that can sig-nificantly impair the health and productivity of employees, this issue arises as an extremely import-ant issue in the field of occupational medicine and health protection at workplace.Accordingly, it seems that, the continuous implemen-tation of preventive activities in the workplace aimed at preventing and mitigating the impact of harmful psychosocial factors of the working environment, is the most important and most profitable measure for preventing the development of SBS symptoms, that will also, in long term, significantly improve the health, as well as, labor productivity of the employees.

CONFLICT OF INTERESTThe authors declare no conflict of interest.

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28. Skov P, Valbjørn O, Pedersen BV. Influence of personal characteristics, job‑related factors and psychosocial factors on the sick building syndrome. Danish Indoor Climate Study Group. Scand. J. Work. Environ. Health. 1989;15(4):286‑95 http://dx.doi.org/10.5271/sjweh.1851.

29. Runeson-Broberg R, Norbäck D. Sick building syndrome (SBS) and sick house syndrome (SHS) in relation to psychosocial stress at work in the Swedish workforce. Int. Arch. Occup. Environ. Health. 2013;86(8):915‑22 http://dx.doi.org/10.1007/s00420‑012‑0827‑8.

Maja Miškulin et al� Journal of Health Sciences 2014;4(3):143-148 http://www�jhsci�ba

Vitamin B12 deficiency and depression in elderly: Cross-sectional study in Eastern CroatiaMaja Miškulin1*, Marija Kristić2, Jelena Vlahović1

1University of Osijek Faculty of Medicine, Osijek, Croatia, 2Vukovar General Hospital, Vukovar, Croatia

ABSTRACT

Introduction: Vitamin B12 deficiency occurs frequently among elderly patients and it has recently been connected with the occurrence of depressive symptoms in this population� The aim of this study was to determine the frequency of vitamin B12 deficiency among elderly patients from Eastern Croatia and to evaluate whether there is a connection between this deficiency and the occurrence of depressive symp-toms among them�

Methods: This cross-sectional study was conducted from April to June 2013, among 140 elderly patients from Vukovar-Srijem County (47�9%, 67/140 males and 52�1%, 73/140 females; mean age 71�0±6�7 years)� The anonymous questionnaire was used to obtain demographic data, data regarding socio-economic status and personal history of diseases of study participants as well as data pertaining to the existence of depressive symptoms among them� The competitive immunoassay vitamin B12 kit was used to determine serum levels of vitamin B12�

Results: Among all study participants there were 7�1% (10/140) of them with B12 deficiency and 70�0% (98/140) of them with the symptoms of depression� Depressive symptoms occurred in 100�0% (10/10) patients with the vitamin B12 deficiency and 67�7% (88/130) of patients without it�

Conclusion: The study showed positive connection between the existence of depressive symptoms and vitamin B12 deficiency among elderly patients� This finding points to the need for frequent vitamin status evaluation in this age group and its consequent correction that could improve overall health of this pop-ulation subgroup�

Keywords: Croatia; depression; elderly; vitamin B12

INTRODUCTIONVitamin B12 (cobalamin) is one of the water-sol-uble vitamins (1). It is found in meat, fish, milk, milk products and eggs. In fruits and vegetables it is found in negligible quantities. The dietary reference

Corresponding Author: Maja Miškulin, MD, PhD, University of Osijek, Faculty of Medicine, Josipa Huttlera 4, 31000 Osijek, Croatia� E-mail: miskulin�maja@gmail�com

Submitted August 09 2014 / Accepted December 20 2014

© 2014 Maja Miškulin et al.; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distri-bution, and reproduction in any medium, provided the original work is properly cited�

intake for an adult is 3 µg per day, and the reserves in the human body are 2-5 mg. In the circulation vitamin B12 is carried bound to proteins transcobal-amines. Due to the relatively large reserves in the body, a disorder in the metabolism of vitamin B12 can remain hidden for a long time (2).In the human body, vitamin B12 is a cofactor and coenzyme in many biochemical processes. Vitamin B12 together with vitamin B9 is involved in the bio-synthesis of labile methyl groups, which are necessary

http://www�jhsci�ba Maja Miškulin et al� Journal of Health Sciences 2014;4(3):143-148

for the biosynthesis of purine and pyrimidine bases, essential components of nucleic acids. Lack of these vitamins causes deterioration in cell division and changes in protein synthesis (2-6). Vitamin B12 deficiency causes a decrease in the activity of methi-onine synthase, which inhibits the regeneration of tetrahydrofolate and folate remains in a form that human body cannot use. Therefore, the lack of folate and vitamin B12 may interfere with DNA syn-thesis, due to the reduced amount of the active form of vitamin B9. Disturbance in the DNA synthesis have a negative impact on the rapidly dividing cells, especially red blood cells, which results in the pro-duction of large and immature red blood cells. Such condition may result in megaloblastic anemia, and can occur with decreased number of leukocytes and platelets and with an increased number of hyperseg-mented neutrophils. The correlation between folate and vitamin B12 explains why their deficiency results in morphologically identical anemia. Additionally taking folic acid restores sufficient amounts of this vitamin for normal red blood cell production. However, if the cause of anemia is vitamin B12 defi-ciency, additional intake of folate may mask the condition, along with the successful treatment of anemia. Also, larger amounts of folate do not help reducing neurological symptoms caused by vitamin B12 deficiency (2-7).Neurological symptoms of B12 deficiency can occur without anemia, in 75% to 90% of people who are lacking this vitamin. Those symptoms include numbness in hands and feet, difficulty in walking, exacerbated memory, disorientation, dementia, myelopathy, mood swings, irritability, mononeu-ropathy (optical or olfactory), autonomic neurop-athy (impotence, urinary or fecal incontinence), problems with concentration and exacerbated hand coordination and legs. The most common symp-toms in children are irritability, disrupted growth and development, apathy and anorexia. Generally, those symptoms can be cured by vitamin B12 intake, but if you start treatment too late, part of the result-ing damage is irreversible (8,9).Vitamin B12 deficiency in adults is considered the value of 150 pmol/L and below (10). According to a study conducted at the University Hospital of Strasbourg, Strasbourg, France, in 2004, vitamin B12 deficiency was observed in more than 20% of

the elderly. The most common causes of deficiency of this vitamin according to this study were: mal-absorption syndrome (in 60% of cases), followed by pernicious anemia and inadequate intake of this vitamin with food (10).Depression is a mental illness which leads the patient in a state of helplessness and hopelessness. It always occurs as a reaction to a loss-physical or men-tal, real or imaginary. Older age, stress, alienation, disaffection, retirement, loss of a spouse, the depar-ture of children, reducing the need and motivation for activities that used to be a normal part of life, are additional factors that can trigger depressive reac-tion in elderly people. Symptoms of depression are only worsened by the presence of somatic diseases, and it is very common in the elderly that depression develop as a side effect of medications. Depression can occur due to the lack of some essential nutri-ents in the diet or because of malnutrition (11). Typical symptoms of depression include depressed mood, loss of interest and enjoyment, and reduced energy (decreased activity and increased fatigue). Other common symptoms include reduced concen-tration and attention, reduced self-confidence and self-esteem, feelings of guilt and worthlessness, sleep disturbances, pessimistic and gloomy views of life, loss of appetite and suicidal or self-harm ideas. The diagnosis of depression is set based on the number of symptoms, duration of symptoms, the impact of depressive disorders in social, family and work func-tioning and the circumstances that led to the disor-der. The literature states that depression comprises 10-15% of the elderly population, and according to some authors, even up to 40%. Although often occurs in elderly people, depression is a pathological process and certainly not part of normal aging (11).Deficiency of vitamin B12 has a well-established association with a wide variety of neurologic and psychiatric manifestations with depression being one of the most frequent of them (12). Considering the older age, it is especially important to emphasize that low serum vitamin B12 level is one of the risk factors of geriatric depression (13). Study conducted in Norway confirmed that there is a connection between low serum vitamin B12 level and occurrence of depressive symptoms in the group of 1935 study participants, aged 71 to 74 years (14) while the study conducted in Germany showed that taking

> 50 mg of vitamin B12 per day could reduce the occurrence of vascular and neurological disorders and depressive symptoms in elderly persons (15).The aim of this study was to determine the frequency of vitamin B12 deficiency among elderly patients from Eastern Croatia and to evaluate whether there is a connection between this deficiency and the occurrence of depressive symptoms among them.

METHODSThis cross-sectional study was conducted in the County General Hospital Vukovar, Croatia during April to June 2013 period. Participation in the study was voluntary, and the study was approved by the Ethics Committee of the County General Hospital Vukovar. Elderly patients who performed blood tests in the Department of Laboratory Diagnostics of the County General Hospital Vukovar as an integral part of their preventive medical examination were asked to participate in this study. The convenience sample used in this study consisted of all elderly patients who performed blood tests in the Department of Laboratory Diagnostics of the County General Hospital Vukovar during April to June 2013 period. The self-administered anonymous questionnaire was used to obtain demographic data (age, gender, mar-ital status, place of living), data regarding socio-eco-nomic status (way of living – living alone in one’s own household, living in joint household with younger family members where those living alone were considered to be of lower socio-economic status than those living in joint household with younger family members), data regarding habit of taking vita-mins and mineral as dietary supplements and per-sonal history of diseases of study participants (pres-ence of some sort of chronic disease) as well as data pertaining to the existence of depressive symptoms among them. The Anxiety and Depression Detector (the ADD), composed of five questions was used as the screening device for fast detection of depressive symptoms in study population (16). Total vitamin B12 serum concentrations were determined using a competitive immunoassay vitamin B12 kit with a measuring range between 22 and 1476 pmol/L (Roche Diagnostics GmbH, Mannheim, Germany) on a Cobas e601 immunoassay analyzer (Roche Diagnostics GmbH, Mannheim, Germany) (17).

Statistical analysisStatistical analysis included data obtained by the laboratory analysis of participants’ blood and by the anonymous questionnaire. Upon confirming normality of data distribution by Kolmogorov-Smirnov test, all data were processed by the meth-ods of descriptive statistics. The proportions were calculated and compared by use of Fisher’s exact test. P<0.05 was considered statistically significant. Statistical analysis was done by the SPSS Statistical Package for Windows, version 13.0 (SPSS Inc., Chicago, IL, USA).

RESULTSThe study sample consisted of 140 elderly people from the Vukovar-Srijem County, 47.9% (67/140) males and 52.1% (73/140) females, mean age 71.0±6.7 years. According to marital status, there were 65.0% (91/140) married and 35.0% (49/140) single (divorced or widowed) study participants. According to the place of living there were 28.6% (40/140) participants who lived in villages and 71.4% (100/140) participants who lived in town. Considering the chronic diseases, among all study participants there were 85.7% (120/140) of them who suffered from at least one chronic disease and 14.3% (20/140) participants who did not suffer from chronic diseases. When analyzing study pop-ulation according to the habit of taking vitamins and mineral as dietary supplements, among all of them there were 35.7% (50/140) of those who took these supplements and 64.3% (90/140) participants who did not take them. According to the estab-lished presence of depressive symptoms among all study participants, there were 70.0% (98/140) of them with the existence of depression and 30.0% (42/140) of them without depressive symptoms.According to the competitive immunoassay vita-min B12 kit manufacturer the reference range of vitamin B12 in serum was 141 to 489 pmol/L (17), and these values were used for the classification of the measured concentration of vitamin B12 in serum samples of study participants. Accordingly, among all study participants there were 7.1% (10/140) of them whose measured serum concentrations of vitamin B12 were below the reference range, 87.2% (122/140) of participants whose measured serum

concentrations of vitamin B12 were within the refer-ence range, and 5.7% (8/140) of participants whose measured serum concentrations of vitamin B12 were above the reference range.When analyzing the existence of depressive symp-toms among study participants in relation to mea-sured serum concentrations of vitamin B12 it was established that depressive symptoms existed in 67.7% (88/130) of study participants whose mea-sured serum concentrations of vitamin B12 were within or above the reference range and in 100.0% (10/10) of study participants whose serum vitamin B12 concentrations were below the reference range, and this difference in the existence of depression beteween the groups was statistically significant (Fisher’s exact test; p=0.033) (Table 1).Elderly patients with coexisted vitamin B12 defi-ciency and depression mainly lived in town (90.0%, 9/10), alone in their own household (90.0%, 9/10) and were mainly married (60.0%, 6/10) living in one generation family. Majority of them suffered from some kind of chronic disease (90.0%, 9/10) and 30.0% (3/10) of them had been taking vitamins and minerals as dietary supplements.

DISCUSSIONThis study revealed that 7.1% of elderly from Eastern Croatia had vitamin B12 deficiency, which is in compliance with the majority of studies that found 5-15% prevalence of this deficiency among elderly (18-21) although there are studies that discovered even higher prevalence of vitamin B12

deficiency in this age group (10). The explanation of determined prevalence of vitamin B12 deficiency is probably connected with the fact that more than third (35.7%) of study participants were regularly taking vitamins and mineral as dietary supplements thus improved their vitamin B12 status. This study also revealed extremely high prevalence (70.0%) of depression among study population that is much higher than the determined prevalence of depression among elderly in other studies in which the preva-lence rates varies between 10 and 40% (11,22-24). A plausible explanation for this extremely high prev-alence of depression in the studied population is the impact of recent history and past war events and the overall economic situation in the society, par-ticularly in the Eastern Croatia, while it is known that war and poor economic situation leads to the increase in the prevalence of depression and all its disastrous consequences (25,26).When analyzing the existence of depressive symp-toms among study participants in relation to measured serum concentrations of vitamin B12 this study established the statistically significant difference (p<0.05) in the existence of depression between group of study participants whose mea-sured serum concentrations of vitamin B12 were within or above the reference and the group of study participants whose serum vitamin B12 con-centrations were below the reference range. In the latter group all participants (100.0% of them) scored positive on the ADD regarding the exis-tence of depressive symptoms, while the depres-sion was detected in 67.7% of study participants whose measured serum concentrations of vitamin B12 were within or above the reference range. This finding points to the positive connection between vitamin B12 deficiency and depression confirming previously highlighted possibility that vitamin B12 deficiency is a significant risk factor of geriatric depression (13,14). Considering the connection between vitamin B12 and depression it is important to emphasize that the associations between vitamin B12 status and cognitive function scores are stron-ger in patients with depression than in participants without depression (14,27,28). Decreased perfor-mance on visual memory and verbal fluency tests has been reported in depressed elderly people with low vitamin B12 levels (28).

TABLE 1. The presence of depression among study participants according to the measured serum concentrations of vitamin B12

Study participants according to the measured serum concentrations of vitamin B12

The presence of depression among study

participants

YesN (%)

NoN (%)

Below the reference range

10 (100.0) 0 10

Within and above the reference range

88 (67.7) 42 (32.3) 130

Total 98 42 140

However, several limitations should be taken into considerations. The study’s cross-sectional design does not allow interpretation of causality and can-not demonstrate whether the observed association with vitamin B12 status precedes or results from the depression. Furthermore, results for tests with rela-tively small sample sizes could be affected by selection bias and should be interpreted cautiously. Around 7.000 elderly people gravitate to this Hospital thus our sample represents 2% of the study population. Because elderly people are less prone to participate in such surveys we consider that this study is quite valuable despite such small sample size. Besides pre-viously mentioned limitations there are limitations considering the convenience sample used in this study and the fact that we did not precisely mea-sure the socio-economic status of study participants. The last mentioned is especially important know-ing that there is a significant influence of socio-eco-nomic status on nutritional habits (for example meat availability) and also ability of study partici-pants to obtain supplementation. Considering the fact that Eastern part of Croatia especially Vukovar-Srijem County is one of the least developed area in Croatia we did not specifically investigated this aspect but merely try to establish the actual situa-tion in the field. Nevertheless this study can serve as a database for future studies related to this issue in Croatia, especially bearing in mind that the studies in the world pointed to a possible therapeutic use of vitamin B12, which could reduce the occurrence of vascular and neurological disorders and depressive symptoms in elderly (15). This is especially import-ant for the Croatia and the majority of EU coun-tries that are considered to be old because they have more than 11% of population older than 65 years of age (11). The percentage of elderly persons in Croatia is 17.3% and it is considered that by 2050 it will go up to more than 20% (11). Older persons are able to function as very useful community mem-bers. They have usable potential for transmission of knowledge, skills, abilities and work experience to younger and other older generations, so that unnec-essary mistakes would not be repeated (11). In order to elderly fulfill such an important societal role and to actively participate in social life of a community above all, it is important to prevent depression and other vascular and neurological disorders whose

occurrence can potentially be reduce with a vita-min B12 supplementation. Further long-term trials in elderly patients with low vitamin B12 status are required to assess the relevance of vitamin B12 sup-plementation in that sense.

CONCLUSIONThe study showed positive connection between the existence of depressive symptoms and vitamin B12 deficiency among elderly patients. This finding points to the need for frequent vitamin status evalu-ation in this age group and its consequent correction that could improve overall health of this population subgroup and potentially reduce the occurrence of depression and other vascular and neurological dis-orders among elderly enabling them to more actively participate in social life of a community.

CONFLICT OF INTERESTThe authors declare no conflict of interest.

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11. Kralj-Vasilj M, Degmečić D, Včev A, Mikšić Š.Loneliness, grieving process and depression affecting people of old age. SEEHSJ. 2013;3(1):19-26.

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13. Heok KE, Ho R. The many faces of geriatric depression. Curr.

Opin. Psychiatry. 2008;21(6):540‑5 http://dx.doi.org/10.1097/YCO.0b013e328311cdae.

14. Vogiatzoglou A, Smith AD, Nurk E, Drevon CA, Ueland PM, Vollset SE, et al. Cognitive function in an elderly population: Interaction between vitamin B12 status, depression, and apolipoprotein E ε4: The Hordaland Homocysteine Study. Psychosom. Med. 2013;75(1):20‑9 http://dx.doi.org/10.1097/PSY.0b013e3182761b6c.

15. Wolters M, Ströhle A, Hahn A. Cobalamin: A critical vitamin in the elderly. Prev. Med. 2004;39(6):1256‑66 http://dx.doi.org/10.1016/j.ypmed.2004.04.047.

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27. Garrod MG, Green R, Allen LH, Mungas DM, Jagust WJ, Haan MN, et al. Fraction of total plasma vitamin B12 bound to transcobalamin correlates with cognitive function in elderly Latinos with depressive symptoms. Clin. Chem. 2008;54(7):1210‑7 http://dx.doi.org/10.1373/clinchem.2007.102632.

28. Bell IR, Edman JS, Marby DW, Satlin A, Dreier T, Liptzin B, et al. Vitamin B12 and folate status in acute geropsychiatric inpatients: Affective and cog‑nitive characteristics of a vitamin nondeficient population. Biol. Psychiatry. 1990;27(2):125‑37 http://dx.doi.org/10.1016/0006‑3223(90)90642‑F.

Amra Ćatović et al�� Journal of Health Sciences 2014;4(3):149-155 http://www�jhsci�ba

Average saturated fatty acids daily intake in Sarajevo University studentsAmra Ćatović1*, Amela Dervisević2, Orhan Lepara2, Semir Gorčević3, Jasna Gorčević4

1Department of Hygiene, Faculty of Medicine, University of Sarajevo, Bosnia and Herzegovina, 2Department of Human Physiology, Faculty of Medicine, University of Sarajevo, Bosnia and Herzegovina, 3Cantonal Institute for Occupational Health and Sports Medicine in The Zenica-Doboj Canton, Bosnia and Herzegovina, 4Health Center Zenica, Bosnia and Herzegovina

ABSTRACT

Introduction: There are wide variations in diet patterns among population subgroups� Macronutrients content analyses have become necessary in dietary assessment� The purpose of this study is to analyze dietary saturated fatty acids intake in students, detect differences between men and women, and com-pare with nourish status and nutrition recommendations�

Methods: A cross-sectional survey of 60 graduate students was performed during the spring 2013, at the Sarajevo University� Food-frequency questionnaire was conducted during seven days� Body mass index was used to assess students’ nourish status� Statistical analyses were performed using the Statistical Package for Social Sciences software (version 13�0)�

Results: Mean age of males was 26�00±2�72, and of females was 27�01±3�93 years� The prevalence of overweight was more common among males compared to females (55�56% vs� 6�06%)� Median of total fat average intake for men and women was 76�32(70�15;114�41) and 69�41(63�23;86�94) g/d, respec-tively� Median of saturated fatty acids average intake for men and women was 28�86(22�41;36�42) and 24�29(20�53;31�60) g/d, respectively� There was significant difference in average intake of total fat between genders (Mann-Whitney U test: p=0�04)� Macronutrient data were related to requirement of reference person� Total fat intake was beyond recommended limits in 37�04% of males and 54�55% of females� Saturated fatty acids intake was beyond the upper limit in 55�56% of males and 51�52% of females�

Conclusion: Diet pattern of the average student is not in accordance with the recommendations of sat-urated fatty acids contribution as a percentage of energy�

Keywords: Dietary assessment; energy intake; recommendations;

Corresponding Author: Amra Ćatović, Department of Hygiene, Faculty of Medicine, University of Sarajevo, Čekaluša 90, 71000 Sarajevo, Bosnia and Herzegovina� E-mail: amra�catovic@mf�unsa�ba

Submitted September 25 2014 / Accepted December 15 2014

© 2014 Amra Ćatović et al; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distri-bution, and reproduction in any medium, provided the original work is properly cited�

INTRODUCTIONThe deficiency of macro- and micronutrients was the major nutrition problem relating to health. Beyond this traditional aspect of health, excess of some food with lack of others has become opposite disease risk (1). As the incidence of noncommuni-cable diseases rise, relationship between health and

http://www�jhsci�ba Amra Ćatović et al�� Journal of Health Sciences 2014;4(3):149-155

food consumption, dietary patterns, nutrition and lifestyles has been recognized (2). At the level of individuals macronutrients contribution in energy supply is as follow: carbohydrate 55-75%, protein 10-15% and total fat 15-30%. Contribution of sin-gle fat in energy intake ought to be: saturated fatty acids <10%, polyunsaturated fatty acids 6-10%, monounsaturated fatty acids 10-14% (3).There are wide variations in diet patterns among subgroups within a population, so excess of some macronutrients are responsible for health risk. Macronutrients content analyses has become neces-sary in nutrition pattern evaluation.Characteristics of student diet are: little number of daily meal, insufficient vitamins and minerals intake, excess in density energy drinks and food, high consummations of junk food.The purpose of this study is to analyze dietary sat-urated fatty acids intake in students, detect differ-ences between men and women, and compare with nourish status and nutrition recommendations.

METHODS

Study designThe study was designed as a cross-sectional survey conducted at the Sarajevo University during the spring 2013. A sample of 60 graduate students in 2012/13 generation recruited randomly.

Data CollectionFood-frequency questionnaire (FFQ) was con-ducted during seven days. In the first part of ques-tionnaires students gave data about their anthropo-metrics measures (body height and weight). Body mass index (BMI) was used to assess students’ nour-ish status. BMI was calculated using the standard formula (weight (kg)/height (m2)). According to guidelines stated by the World Health Organization (WHO), nourish status was classified into four cat-egories: underweight (BMI ≤ 18.5), normal weight (BMI 18.5 – 24.9), overweight (BMI 25–29.9), and obese (BMI ≥ 30) (3).In second part examiners registered their estimated food intake, as well as time of meals during seven days. According to United States Department of

Agriculture (USDA) National Database (4) daily total fat intake was calculated, as well as saturated fatty acids intake. From seven days summarized value average daily intake was estimated.

Requirements of reference personIntake data were related to requirement of reference person. By WHO definition reference male person has average weight of 65 kg, while reference female person of 55 kg (5). According to the National Academies Press (NAP) definition, the reference man has average weight of 70 kg, while reference female person of 58 kg (6). Reference person is 25 years old and its lifestyle is low active.Basal Metabolic Rate (BMR) was predicted using age and gender specific equations (7), tak-ing into account reference weights (healthy): BMR=14.9xW+496 kcal/d (reference female per-son aged 25); BMR=15.3xW+679 kcal/d (reference male person aged 25).The total daily energy expenditure (TEE) are related to the amount of physical activity expended in the course of everyday life, so BMR ought to be mul-tiplied with Physical Activity Level (PAL). For life style which involves low activity, PAL value is 1.4 - 1.69. In this study PAL assigned a value of 1.55:- Reference female:TEE=BMR * PAL= (14.9x55+496) x1.55=1315.5 x1.55=2039.025≈2000 kcal/d (WHO)TEE=BMR * PAL= (14.9x58+496) x1.55=1360.2x 1.55=2108.310≈2100 kcal/d (NAP)- Reference male:TEE =BMR * PAL= (15.3x65+679) x1.55=1673. 5x1.55=2593.925≈2600 kcal/d (WHO)TEE =BMR * PAL= (15.3x70+679) x1.55=1750. 0x1.55=2712.500≈2700 kcal/d (NAP)According to recommended range (WHO and NAP) total fat intake (15-30% of daily energy intake) can vary from 42 to 87 g in daily meal of reference mail person, and from 32 to 68 g in daily meal of reference female person. The intake of sat-urated fatty acids (SFA) has to be < 10% of daily energy intake. It means SFA has to be restricted to less than 29 g in mails, and 23 g in females as it is showed in Table 1.

Statistical analysisData is presented by using means and SDs (for nor-mally distributed continuous variables), medians and interquartile ranges (for abnormal distributed continuous variables), and frequencies and percent-ages (for categorical variables). Differences between variables were tested by using either an independent t test or the non-parametric Mann-Whitney U test. Correlation between variables was assessed by non-parametric Spearman’s rank correlation coefficient. P≤0.05 was considered statistically significant. Statistical analysis was performed using SPSS (ver-sion 13.0, SPSS).

RESULTS

Age characteristics of the students’ sampleMean age of male examiners was 26.00±2.72 years. Maximum was 32 year, and minimum was 22 year. Mean age of female examiners was 27.01±3.93 years. Maximum was 36 year, and minimum was 22 year. A independent t test showed no significant difference in age structure between gender (p=0.22).

Students’ nourish status based on BMI categoriesFor male participated students BMI median was 25.96(24.88; 29.53) kg/m2. Maximum was 31.02 kg/m2, and minimum was 20.35 kg/m2. For female participated students BMI median was 20.94(20.20; 22.22) kg/m2. Maximum was 29.02 kg/m2, and minimum was 18.07 kg/m2.The majority of the students (60.00%) was of nor-mal weight (25.92% of the male students compared to 87.88% of the female students). Based on BMI

classification, the prevalence of overweight was more common among male students compared to females (55.556% vs. 6.06%). Obesity was found in 18.52% male students. In contrast, 6.06% female students were underweight as it showed in Table 2.Mann-Whitney U test (p<0.0005) showed signifi-cant difference in BMI value between genders.

Fat intakeAverage intakes of total fat and saturated fatty acids are showed in Table 3.There was significant difference in average intake of total fat (Mann-Whitney U test: p=0.04; p<0.05), but no significant difference in average saturated fatty acids intake between genders (Mann-Whitney U test: p=0.17; p>0.05).None of male students had average intake of total fat below recommendations. Total fat intake was between recommended limits in 62.96%, and beyond in 37.04% of males. One of female students had average intake of total fat below recommended values. Total fat intake was between recommended limits in 42.42%, and beyond in 54.55% of females (Table 4).In group of male students whose average intakes of total fat were beyond recommended value, 40.00% had normal nourish status, 40.00% were over-weight, and 20.00% were obese. In group of male students whose average intakes of total fat were in accordance with the recommendations, 17.65% had normal nourish status, 64.70% were overweight, and 17.65% were obese (Table 5).

TABLE 1. Recommended restrictions of total fat and saturated fatty acids daily intakeTotal energy expenditure and restrictions for total fat and SFA

Reference Man

Reference Woman

WHO NAP WHO NAPEnergy, kcal/d 2600 2700 2000 2100Total fat, g/d (15‑30% TEE) 42‑84 44‑87 32‑65 34‑68SFA, g (<10% TEE) 28 29 22 23TEE: The total daily energy expenditure, SFA: Saturated fatty acids, WHO: World health organization, NAP: National academies press

TABLE 2. Prevalence of obesity among students based on BMI by genderNourish status Males Females All

n % n % n %Underweight (BMI ≤18.5)

‑ ‑ 2 6.06 2 3.33

Normal (BMI between 18.5‑24.9)

7 25.92 29 87.88 36 60.00

Overweight (BMI between 25‑29.9)

15 55.56 2 6.06 17 28.34

Obese (BMI ≥30) 5 18.52 ‑ ‑ 5 8.33Total 27 100.00 33 100.00 60 100.00BMI: Body mass index

In group of female students whose average intakes of total fat were beyond recommended value normal nourish status was detected in 94.44%. In group of female students whose average intakes of total fat were in accordance with the recommendations, 85.71% had normal nourish status, and 14.29% were overweight (Table 6).The contribution of total fat as an energy source between students varied as it is indicated by Figure 1 and Figure 2.Correlation between average daily intake of total fat and nourish status was not established (Males: Spearman’s rho Correlation Coefficient = - 0.36

and p = 0.06; Females: Spearman’s rho Correlation Coefficient = - 0.29 and p = 0.11).

TABLE 3. Average intakes of total fat and saturated fatty acidsAverage intake Males Females P value

Median IQR Max Min Median IQR Max MinTotal fat (g/d) 76.32 70.15‑114.41 141.64 59.58 69.41 63.23‑86.94 136.63 28.55 0.04SFA (g/d) 28.86 22.41‑36.42 52.54 17.09 24.29 20.53‑31.60 47.71 7.25 0.17SFA: Saturated fatty acids, IQR: Interquartile ranges, Max: Maximum, Min: Minimum, P values were estimated by using a Mann-Whitney U test

TABLE 4. Comparison dated total fat intake with recommendation by genderTotal fat intake (g/d) Gender

Males* Females**n % n %

Below recommendations ‑ ‑ 1 3.03Between recommended limits 17 62.96 14 42.42Beyond recommendations 10 37.04 18 54.55Total 27 100.00 33 100.00*recommended limits for males: 42‑87 g/d, **recommended limits for females: 32‑68 g/d

TABLE 5. Average total fat intake of males compared with recommendationNourish status Males average intake of total fat (g)

<42 42‑87 >87n % n % n %

Underweight (BMI ≤18.5) ‑ ‑ ‑ ‑ ‑ ‑Normal (BMI between 18.5‑24.9)

‑ ‑ 3 17.65 4 40.00

Overweight (BMI between 25.0‑29.9)

‑ ‑ 11 64.70 4 40.00

Obese (BMI ≥30) ‑ ‑ 3 17.65 2 20.00Total ‑ ‑ 17 100.00 10 100.00BMI: Body mass index

TABLE 6. Average total fat intake of females compared with recommendationNourish status Females average intake of total fat (g)

<32 32‑68 >68n % n % n %

Underweight (BMI ≤18.5) 1 100 ‑ ‑ 1 5.56Normal (BMI between 18.5‑24.9)

‑ ‑ 12 85.71 17 94.44

‑ ‑ 2 14.29 ‑ ‑

Obese (BMI ≥30) ‑ ‑ ‑ ‑ ‑ ‑Total 1 100.00 14 100.00 18 100.00BMI: Body mass index

FIGURE 1. Link between BMI and total fat intake in male students

FIGURE 2. Link between BMI and total fat intake in female students

Saturated fatty acids intake was beyond the upper limit in 55.56% of males and 51.52% of females (Table 7).In group of male students whose average intakes of saturated fatty acids intake were below the upper limit, 16.67% had normal nourish status, 58.33% were overweight, and 25.00% were obese. In group of male students whose average intake of saturated fatty acids intake was beyond the upper limit, 33.34% had normal nourish status, 53.33% were overweight, and 12.33% were obese (Table 8).In group of female students whose average intakes of saturated fatty acids were below the upper limit, 12.50% were underweight, 75.00% had normal nourish status, and 12.50% were overweight. All female students with average intakes of saturated fatty acids intake beyond the upper limit had nor-mal nourish status (Table 9).The contribution of saturated fatty acids as an energy source between students varied as it is indicated by Figure 3 and Figure 4.

Correlation between average daily intake of saturated fatty acids and nourish status was not established (Males: Spearman’s rho Correlation Coefficient = - 0.25 and p = 0.21; Females: Spearman’s rho Correlation Coefficient = - 0.18 and p = 0.33).Correlation between average saturated fatty acids and average total fat intake in males and females are showed by Figure 5 and Figure 6.

TABLE 7. Comparison dated SFAs intake with recommendation by genderSaturated fatty acids intake (g/d)

GenderMales* Females**

n % n %Below the upper limit 12 44.44 16 48.48Beyond the upper limit 15 55.56 17 51.52Total 27 100.00 33 100.00*upper limit for males: 29 g/d, ** upper limit for females: 23 g/d

TABLE 8. Average saturated fatty acids intake of males compared with recommendationNourish status Males average intake of

saturated fatty acids (g)≤29 >29

n % n %Underweight (BMI ≤18.5) ‑ ‑ ‑ ‑Normal (BMI between 18.5‑24.9)

2 16.67 5 33.34

7 58.33 8 53.33

Obese (BMI ≥30) 3 25.00 2 12.33Total 12 100.00 15 100.00BMI‑body mass index

TABLE 9. Average saturated fatty acids intake of females compared with recommendationNourish status Females average intake of

saturated fatty acids (g)≤23 >23

n % n %Underweight (BMI ≤18.5) 2 12.50 ‑ ‑Normal (BMI between 18.5‑24.9)

12 75.00 17 100.00

2 12.50 ‑ ‑

Obese (BMI ≥30) ‑ ‑ ‑ ‑Total 16 100.00 17 100.00BMI‑body mass index

FIGURE 3. Link between BMI and SFAs intake in male students

FIGURE 4. Link between BMI and SFAs intake in female students

There was strong positive correlation between aver-age daily intake of saturated fatty acids and total fat in males (Spearman’s rho Correlation Coefficient = 0.85 and p < 0.0005), as well as in females (Spearman’s rho Correlation Coefficient = 0.95 and p < 0.0005).

DISCUSSIONThe purpose of this study was to assess dietary sat-urated fatty acids intake in a sample of Sarajevo University students, detect differences between men and women, and compare with nourish status and nutrition recommendations. Nourish status was assessed by using BMI. Based on BMI classification,

findings of this study indicate that normal nourish status was more prevalent among females (87.88%) as compared to males (25.92%). None of female stu-dent was obese and none of male student was under-weight. Overweight nourish status was more com-mon among male than female students. Prevalence of overweight was 55.56% in males as compared to 6.06% in females. Significant difference in average BMI between genders is common in student popu-lation as it is reported in other studies. A cross-sec-tional survey in the Lebanese American University (LAU) campus during the fall 2006 semester of 220 students (43.6% male and 56.4% female), aged 20 ± 1.9 years showed the prevalence of overweight and obesity was more common among male students compared to females (37.5% and 12.5% vs. 13.6% and 3.2%, respectively) (8).Diet is recognized as a key determinant of over-weight and obesity. Eating behaviors that have been linked to overweight and obesity include snacking/eating frequency, binge-eating patterns, eating out (2). Researches of the possible health impact of diet composition (percentage energy intake from macronutrients) have introduced recommendation of macronutrients contribution in energy supply as follow: carbohydrate 55-75%, protein 10-15% and total fat 15-30%. Contribution of single fat in energy intake ought to be: saturated fatty acids <10%, polyunsaturated fatty acids 6-10%, mono-unsaturated fatty acids 10-14% (3). In this study macronutrient data were related to requirement of reference person.Total fat intake was beyond recommended value in 37.04% of males and 54.55% of females. In group of male students whose average intakes of total fat were beyond recommended value, 40.00% had nor-mal nourish status, 40.00% were overweight, and 20.00% were obese. In group of female students whose average intakes of total fat were beyond rec-ommended value one student was underweight, normal nourish status was detected in 94.44%, and overweight was detected in 5.56%. Significant cor-relation between nourish status and average intake of total fat was not found.Saturated fatty acids intake was beyond upper limit in 55.56% of males and 51.52% of females. In group of male students whose average intakes of

FIGURE 5. Link between SFAs and total fat intake in male students

FIGURE 6. Link between SFAs and total fat intake in female students

saturated fatty acids were beyond the upper limit, 33.34% had normal nourish status, 53.33% were overweight, and 12.33% were obese. All female stu-dents with average intakes of saturated fatty acids intake beyond the upper limit had normal nourish status. Significant correlation between nourish sta-tus and average intake of saturated fatty acids was not found.Although diet pattern has recognized as adiposity development risk factor (3), effect of diet quality on body weight, is insufficiently understood. The role of specific nutrients, particularly carbohydrates (9) and fats (10, 11), is controversial. Patterns of long-term weight changes differ by age, sex, physi-cal activity and smoking status (12). Lowering total fat intake in adults compared with not lowering fat intake was associated with reductions in body mass index. On the other hand, each additional 5 kg/m2 was associated with 30% greater total mortality (with contributions from deaths related to vascular, renal, hepatic, and respiratory disease, cancer, and diabetes) (13).Results of this study has revealed the tendency of overweight and obesity among students, particularly males. Increase of total fat intake has been associ-ated with increase of saturated fatty acids intake. Although there is no evidence of direct link between an increased risk of obesity and the quantity of daily total fat or saturated fatty acids intake, satu-rated fatty acids consumption should be limited to enable the goals of reduced intake of total fat. Total fat energy of at least 20% is consistent with good health. Highly active groups with diets rich in veg-etables, legumes, fruits and wholegrain cereals may sustain a total fat intake of up to 35% without the health risk (3).

CONCLUSIONThe tendency of overweight and obesity among students, particularly males was established. The association between consumption of dietary fat or saturated fatty acids and obesity in students is not very important. Diet pattern of the average student

is not in accordance with the recommendations of saturated fatty acids contribution as a percentage of energy. This diet, loaded with saturated fatty acids might, over time, lead to more excess body fat depo-sition. These finding suggest individual measures ought to be done in correction eating habits in stu-dent population.

COMPETING INTERESTSThe authors declare that they have no competing interests.

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3. WHO: Diet, nutrition and the prevention of chronic diseases. Technical ReportSeries No. 916, WHO Geneva, 2003.

4. US Department of Agriculture, Agricultural Research Service, 2013, USDA National Nutrient Database for Standard Reference, Release 26. Nutrient Data Laboratory Home Page [cited 2013 August]. Available from: http//www.ars.usda.gov/ba/bhnrc/ndl.

5. WHO: Energy and protein requirements. Technical Report Series No. 724, WHO Geneva, 1985.

6. NAP: Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC, 2005.

7. Stanosavljević D, Danojević D, Bojanić J, Jandrić Lj. Vodič za pravilnu ish‑ranu za zdravstvene profesionalce, Banja Luka, 2004.

8. Yahia N, Achkar A, Abdallah A, Rizk S. Eating habits and obesity among Lebanese university students. Nutrition Journal 2008;7:32 http://dx.doi.org/10.1186/1475‑2891‑7‑32.

9. van Dam RM, Seidell JC. Carbohydrate intake and obesity. Eur J Clin Nutr. 2007;61 Suppl 1:S75–99 http://dx.doi.org/10.1038/sj.ejcn.1602939.

10. Willett WC. Dietary fat plays a major role in obesity: no. Obes Rev. 2002;3:59–68 http://dx.doi.org/10.1046/j.1467‑789X.2002.00060.x.

11. Bray GA, Paeratakul S, Popkin BM. Dietary fat and obesity: a review of ani‑mal, clinical and epidemiological studies. Physiol Behav. 2004;83:549–55 http://dx.doi.org/10.1016/j.physbeh.2004.08.039.

12. Kimokoti RW, Newby PK, Gona P, Zhu L, Jasuja GK, Pencina MJ, et al. Diet Quality, Physical Activity, Smoking Status, and Weight Fluctuation Are Associated with Weight Change in Women and Men. J. Nutr. 2010;140:1287–12 http://dx.doi.org/10.3945/jn.109.120808.

13. Hooper L, Abdelhamid A, Moore HJ, Douthwaite W, Skeaff CM, Summerbell CD. Effect of reducing total fat intake on body weight: system‑atic review and meta‑analysis of randomised controlled trials and cohort studies. BMJ 2012;345:e7666 http://dx.doi.org/10.1136/bmj.e7666.

http://www�jhsci�ba Mirza Halimić, et al� Journal of Health Sciences 2014;4(3):156-161

Early extubation after congenital heart surgeryMirza Halimić1*, Senka Mesihović Dinarević1, Zijo Begić1, Almira Kadić1, Sanko Pandur2, Edin Omerbašić2

1Pediatric Clinic, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina, 2Clinic for Cardiac surgery, University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina

ABSTRACT

Introduction: Despite recent advances in anesthesia, cardiopulmonary bypass and surgical techniques, children undergoing congenital heart surgery require postoperativemechanical ventilation� Early extuba-tion was definedas ventilation shorter than 12 hours� Aim of this study is to identify factors associated with successful early extubation after pediatric cardiac surgery�

Methods: The study was performed during period from January 2006 to January 2011 at Pediatric Clinic and Heart Center University Clinical center Sarajevo� One hundred children up to 5 years of age, who have had congenital heart disease, with left–right shunt and obstructive heart disease were included in the study� Patients were divided into two groups: Group I - patients extubated within 12 hours after surgery and Group II - patients extubated 12 or more hours after surgery�

Results: The most frequently encountered preoperative variables were age with odds ratio 4% 95%CI (1-7%), Down’s syndrome 8�5 95%CI (1�6-43�15), failure to thrive 4�3 95%CI (1-18)� Statistically signifi-cant postoperative data included lung disease (reactive airways, pneumonia, atelectasis, pneumothorax) and with odds ratio 35�1 95 %CI (4-286) and blood transfusion with odds ratio 4�6 95%CI (2-12)� Blood transfusion (p=0�002) (Wald=9�2) 95%CI (2-12), during as well as after operation procedure has statistically significant influence on prediction time of extubation� Proven markers were age with cut of 21�5 months (sensitivity 74% and specificity 70%) and extracorporeal circulation (ECC) with cut-of 45�5 minutes (sensitivity 71% and specificity 65%)�

Conclusion: Early extubation is possible in many children undergoing congenital heart surgery� Younger age and prolonged ECC time are markers associated with prolonged mechanical ventilation�

Keywords: Early extubation; congenital heart disease; congenital heart surgery

INTRODUCTIONDespite technological progress in diagnostic cardiol-ogy, anesthesia, surgical, extracorporeal techniques

*Corresponding Author: Mirza Halimić, Pediatric clinic, University Clinical Center Sarajevo, Patriotske Lige 81, 71000 Sarajevo, Bosnia and Herzegovina� E-mail: halimicm@hotmail�com

Submitted July 14 2014 / Accepted September 24 2014

© 2014 Mirza Halimić; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distri-bution, and reproduction in any medium, provided the original work is properly cited�

and improvements in the perioperative manage-ment strategies, that all contributed to successful outcome of surgical procedures performed on neo-nates, infants and children with congenital heart disease (CHD), still, almost all children under-going congenital heart surgery require postoper-ativemechanical ventilation. Patients with CHD in postoperative period depend on balance of the pathophysiological and compensatory mechanisms that often decreased cardiopulmonary reserves.

Mirza Halimić, et al� Journal of Health Sciences 2014;4(3):156-161 http://www�jhsci�ba

Early extubation was defined as mechanical venti-lation in period shorter than 24 hours (practically shorter than 24 hours, usually 4-8 hours) (1-4). Determination of the optimal moment for extuba-tion is based on clinically and laboratory factors, that indicates possibility of appropriate blood gas exchange during spontaneously breathing. Early extubation may be a component of the fast-track process as a method for reducing length of hos-pitalization for surgical patients (5,6). The aim of this study was to investigate prevalence and type of the treated congenital heart disease and to identify preoperative, intraoperative, postoperative factors associated with successful early extubation after operation.

METHODS

Study designThe study was performed in Pediatric Clinic and Heart Center University Clinical Centre Sarajevo from 01.01.2006 to 01.01.2011. The institutional Ethics committee approved the study.We included 100 children up to 5 years of age who had congenital heart disease with left–right (L-R) shunt and obstructive congenital heart disease. Patients were divided into two groups: Group I - patients extubated within 12 hours after surgery and Group II - patients extubated more than 12 hours after surgery.Evaluated factors were divided into: preoperative, intraoperative and postoperative. Preoperative data included: age, gender, history of prematurity (<36 weeks gestation), time of mechanical venti-lation, lung disease, lesion type, prior cardiac sur-gery, pulmonary hypertension, Down’s syndrome, recent viral infection, anemia (hematocrit <35%), congestive heart failure, failure to thrive (less than fifth percentile for weight) and renal failure. Intraoperative data evaluated duration of extracor-poreal circulation, intraoperative arrhythmias, tho-racotomy vs. sternotomy, type of the anesthetic, type of the operation (complete vs. palliative) and complexity (simple vs. complex), blood transfusion. Analyzed postoperative data were: infection (posi-tive culture or increased C reactive protein), lung disease (reactive airways, pneumonia, atelectasis

and chronic lung disease), arrhythmias, inotropes longer than 48 hours postoperatively, pH <7.25, pCO2 <45 mmHg pO2 50-100 mmHg, potassium >5.0 mEq/L, ionized calcium <1.0 mmol/L, blood transfusion. Criteria for extubation were: blood gas analyses: pH 7.32-7.47, pCO2<50 mmHg, pO2 >60 mmHg, with blood oxygen saturation 95%, adequate oxygenation with fraction of inspired oxy-gen (FiO2)≤50%, PEEP (positive end-expiratory pressure) ≤7 cm H2O, ventilatory frequency ≤8, air leak around endotracheal tube, hemodynamic stabil-ity, without signs of myocardial ischemia or signifi-cant hypotension, consistent level of consciousness with adequate protective reflexes, body temperature <38.5 C, level of the hemoglobin >80 g/dl.

Statistical analysisNominal and ordinal variables were analyzed with X2 test and in case of lack of the expected frequency Fisher test has been used. For continuous variables first symmetric of the distribution was analyzed with Kolmogorov-Smirnov test, then arithmetic mean and standard deviation (for symmetric distribution) and for comparison these variables parametric test (Student t-test). In case of asymmetric distribution, median and interquartile ranges were used and for comparison of these variables nonparametric tests (Mann-Whitney U test, Kruskal-Wallis test). The Pearson correlation method measures the strength of the linear relationship between normally distrib-uted variables. When the variables are not normally distributed or the relation between the variables is not linear the Spearman rank correlation method was used. ROC curve determinated if some specific variable could be good marker we used. For statisti-cal analysis SPSS for Windows (version 13.0, SPSS Inc, Chicago, Illinois, USA) and Microsoft Excel (version 11. Microsoft Corporation, Redmond,WA, USA) were used. A two-tailed p<0.05 was consid-ered statistically significant.

RESULTSFrom total of 100 patients (Figure 1), 54 patients were extubated within 12 hours and 46 patients were extubated more than 12 hours after surgery, without significant difference between these two groups (χ2 = 0.640; df=1; p=0.424).

Extubation time and gender affiliation (Table 1) were independent (p=0.07) and doesn´t depend of history of prematurity (p=0.117). Median age of the patient extubated within 12 hours after surgery was 36 months Med=36 (18-48) and >12 hours 14 months Med=14 (6-24).Down syndrome (p<0.0005) 95% CI (1.6-43.15), younger age (U=608.0 p<0.0005) 95%CI (1-7), failure to thrive 95%CI (1-18), congestive heart failure, pulmonary hypertension (p<0.0005) have statistically significant influence on prediction of extubation time. Anemia (p=0.09) and viral infec-tion (p=0.54) independently did not show statisti-cally significant influence on prediction of extuba-tion time. Median values of laboratory parameters did not deviate in both groups.Presence of the lung diseases in preoperative (p=0.048) and postoperative period Wald=11.04 95% CI (4-286) is significant parameter for prolonged mechanical ventilation.

TABLE 1. Extubation and demographic dataExtubation (h)

<=12.00 12.01+ TotalGender

FemaleCount 32 18 50% within gender 64.0 36.0 100.0

MaleCount 22 28 50% within gender 44.0 56.0 100.0

TotalCount 54 46 100% within gender 54.0 46.0 100.0

FIGURE 1. Histogram frequency age of the patients and time of the extubation.

FIGURE 2. Age as marker for prediction successful early extu‑bation, with a cutoff 21.5 months (sensitivity 74% and specificity 70%).

FIGURE 3. Extracorporeal circulation (ECC) time as marker for prediction successful early extubation, with cut off 45.5 minutes (sensitivity 71% and specificity 65%).

Younger age (Figure 2) and prolonged duration of the extracorporeal circulation (Figure 3) (Wald 11.7 p=0.001) CI (1-3%) are proven markers for distinc-tion patients according to time of the extubation. Cut off for duration of the extracorporeal circula-tion is 45.5 minutes, with sensitivity 71% and spec-ificity 65%. Cut off for age is 21.5 months, with sensitivity 74% and specificity 70%.Blood transfusion (p=0.002) (Wald=9.2) 95%CI (2-12), during as well as after operation procedure

has statistically significant influence on prediction of extubation time.In group of patients extubated in first 12 hours the most common CHD were: patent ductus arterio-sus 16/54 (29.6%), ventricular septal defect (VSD) 14/54 (26%), atrial septal defect (ASD secundum) 10/54 (18.5%) (Table 2). In group of patients extu-bated 12 hours after operation the most common CHD were VSD 17/46 (37%), atrioventricular sep-tal defect (AVSD) 9/46 (19.5%) and ASD secun-dum with VSD 7/46 (15.2%) (Table 3).

Time of the extubation and type of the congenital heart disease are independent parameters (p=0.405). There was no reintubation in the early extubation cases.

DISCUSSIONDespite significant advances in perioperative tech-nology debate continues regarding appropriate weaning strategies. There are large institutional differences with respect to pediatric cardiac patient management. While certain centers adopted a fast-tracking concept and attempted extubation in the operating room or within a few hours following surgery, others still routinely continue mechanical ventilation and deep sedation postoperatively for a day or two in the intensive care unit. There is some evidence, mostly from retrospective analyses, that fast-tracking can be beneficial; however, prospec-tive randomized studies are required to determine if fast-tracking improves outcome in children under-going surgery for CHD (1). Several studies report on factors that prevented early extubation in chil-dren following surgery for CHD (1).Our research pointed that patients age >/=6 months with absence of the Down syndrome, pulmonary hypertension, congestive heart failure, lung disease, failure to thrive with short time of the extracorporeal circulation, without blood transfusion in perioperative period, were predictive of successful early extubation.

TABLE 2. Time of the extubation and type of the congenital heart disease

Congenital heart disease TotalObstructive Non‑obstructive

Extubation (h)<=12.00

Count 9 45 54% Extubation (h) 16.7 83.3 100.0

12.01+Count 5 41 46% Extubation (h) 10.9 89.1 100.0

TotalCount 14 86 100% Extubation (h) 14.0 86.0 100.0

Obstructive congenital heart disease: Aortic stenosis, coarctation of aorta, pulmonary stenosis. Non‑obstructive congenital heart disease: patent ductus arteriosus, atrial septal defect, ventricular septal defect, atrioventricular septal defect

TABLE 3. The frequency of certain types of CHD compared to the group of respondentsType of congenital heart anomalies

ASD sec

VSD PDA AVSD AS PS CoA ASD sec+ VSD

ASD sec+ PDA

VSD+ PS

ASD primum

ASD sec+ MR

ASAD primum+

CoA+ VSD

Extubation (h)<=12.00

N 10 14 16 1 1 1 6 1 1 0 2 0 0 1 54Extubation (%) 18.5 25.9 29.6 1.9 1.9 1.9 11.1 1.9 1.9 0.0 3.7 0.0 0.0 1.9 100.0

12.01+N 2 17 2 9 0 2 3 7 0 1 1 1 1 0 46Extubation (%) 4.3 37.0 4.3 19.6 0.0 4.3 6.5 15.2 0.0 2.2 2.2 2.2 2.2 0.0 100.0

TotalN 12 31 18 10 1 3 9 8 1 1 3 1 1 1 100Extubation (%) 12.0 31.0 18.0 10.0 1.0 3.0 9.0 8.0 1.0 1.0 3.0 1.0 1.0 1.0 100.0

ASD-atrial septal defect, VSD-ventricular septal defect, PDA-patent ductus arteriosus, AVSD-atrioventricular septal defect, AS-aortic stenosis, PS‑pulmonary stenosis, CoA‑coarctation of aorta, MR‑mitral regurgitation;

Early extubation in operating theatre is not routine, especially for neonate and infant period. In our study there were no detected extubation in operat-ing theatre. Barash and colleague (7) have published experience with early extubation in 197 patient’s age less than 3 years: 61% patients have been success-fully extubated in theatre. Schuller and colleagues reported on 209 consecutive children undergoing complex open-heart surgery with 88% of those older than 12 months extubated in the operating room (8). Heard et al. (9) published their experience on early extubation following surgery for CHD in 220 patients, of which 147 (67%) were extubated in the operating room, or within six hours in the ICU.A high-opioid anesthetic technique required pro-longed mechanical ventilation following surgery. By the introduction of improved and new anesthetic agents such as modern inhalational anesthetics, short acting opioids, hypnotics and sedatives with favorable pharmaco-dynamics and kinetic profiles “early extubation” approach has been achieved. Still, advantage of the extubation in operating room opposite from intensive care unit (ICU) is ques-tionable. Typically younger child, who underwent a complex surgery, requires a long time of the extra-corporeal circulation, requires prolonged mechani-cal ventilation.Heinle et al. (10) published their results about successful early extubation in 45% neonates and infants, with necessary for reintubation in 11% patients.In our study 46% patients extubated 12 hours after operation had median age 14 months with inter-quartile range 6-24 months. For each month of the age risk for prolonged ventilation is decreased for 4%. Significant pulmonary hypertension was con-sidered important risk factor of prolonged mechan-ical ventilation (11-14), that was confirmed by this study.Down syndrome is documented as factor which increases the risk for unsuccessful early extubation eight times [95% CI (1.6-43.15)]. Since airway obstruction is more likely in Down’s patients, it seems reasonable to carefully consider a fast-track-ing technique in this patient population, partic-ularly in younger patients after long time on CPB (cardiopulmonary bypass).

Study of the Neirotti et al (15) showed, as well as our research, that failure to thrive is one of the risk factor of prolonged ventilation [95%CI (1-18)].Congestive heart failure in preoperative period that emphasize Davis (16), in study 2004 confirmed our research, in contrast to prematurity. Time of extuba-tion and gender are independent factors and there is no published study that verify this relationship. In our study none of the patients did not have recent viral infection or anemia in preoperative period.Duration of the extracorporeal circulation has sta-tistically significant influence in prediction of extu-bation time, implied that prolongation ECC time increased risk for prolonged extubation for 2% and it is also marker (Figure 3) for prediction successful early extubation with cut off 45.5 minutes (sensi-tivity 71% and specificity 65%). Longer CPB time is also repeatedly reported to be associated with prolonged mechanical ventilation following CHD surgery (17).It was demonstrated that early extubation in chil-dren undergoing surgery for CHD has no nega-tive affect on postoperative control of the pain and it does not results with increased requirement for analgesics and it help for early mobilization of the patient (18,19).From all evaluated postoperative factors, significant influence had lung diseases, with odds ratio 35 times and blood transfusion (Odds 4 time), which also emphasize Szekely (20).Early extubation could result with mild respiratory acidosis, but contrary to results of the Kloth and Baum study (18), arterial blood gases analyses were in referral values during postoperative period.Mean value differences of the laboratory parameters in repeated measurements have not been statistically significant, in our study that could be explained as adequate postoperative treatment in intensive care unit.Generally, every patient is possible candidate for early extubation. Individual approach is recommended, considering all aspects, hemodynamic consequences of the congenital heart disease as well as extra car-diac characteristics of each patient. Early extuba-tion is not associated with increased reintubation or mortality. Implementation of a comprehensive early

extubation strategy for all children with congenital heart disease is associated with low morbidity rates and short length of stay. Although there are many benefits resulting from early extubation, it is import-ant to ensure that the practice is both successful and safe (21,22). The majority of children undergoing congenital heart surgery can be extubated in the operating room, but there is question of its benefit and drawback in comparison with extubation cou-ple hours after operation.This study included CHD with L-R shunt and obstructive anomalies, but it is necessary to expand research to complex CHD, in order to identify additional factors associated with early extubation concept.

CONCLUSIONSPatients with uncomplicated CHD, with short ECC time are appropriate candidates for early extubation, after assessment of preoperative, intraoperative and postoperative parameters.

CONFLICT OF INTERESTThe authors declare that they have no conflict of interest.

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2. Heard GG, Lamberti JJJ, Park SM, et al: Early extubation after repair of congenital heart disease. Crit Care Med.1985; 13:830‑2. http://dx.doi.org/10.1097/00003246‑198510000‑00010.

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5. Kanchi M. “Fast Tracking” Paediatric Cardiac Surgical Patients: Annals of Cardiac Anaesthesia. 2005;8:33‑8.

6. Laussan PC, Roth SJ. Fast tracking: Efficiently and safely moving patients through the intensive care unit. Progress in Pediatric Cardiology. 2003;18:149‑58. http://dx.doi.org/10.1016/j.ppedcard.2003.01.015.

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10. Venkataraman ST, Khan N, Brown A: Validation of predic‑tors of extubation success and failure in mechanically ventilated infants and children. Crit Care Med. 2000;28:2991‑6. http://dx.doi.org/10.1097/00003246‑200008000‑00051.

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16. Davis S, Worley S, Mee RB, Harrison AM. Factors associated with early extubation after cardiac surgery in young children. Pediatr Crit Care Med. 2004;5:63‑8. http://dx.doi.org/10.1097/01.PCC.0000102386.96434.46

17. Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, et al. Efficacy and safety of milrinone in preventing low cardiac output syn‑drome in infants and children after corrective surgery for congenital heart disease. Circulation. 2003;107:996‑1002. http://dx.doi.org/10.1161/01.CIR.0000051365.81920.28.

18. Kloth RL, Baum VC. Very early extubation in children after car‑diac surgery. Crit Care Med. 2002;30:787‑91. http://dx.doi.org/10.1097/00003246‑200204000‑00011.

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http://www�jhsci�ba Murthy EGK Talasila, et al� Journal of Health Sciences 2014;4(3):162-168

Effect of Costus igneus: The insulin plant, on pre-diabetes and diabetes in neonatal streptozotocin ratsMurthy EGK Talasila1*, Hemalatha Bavirisetti1, Jithendra Chimakurthy2, Mayuren Candasamy3

1Department of Pharmaceutics, Bapatla College of Pharmacy, Bapatla, Andhra Pradesh, India, 2Department of Pharmacology, Bapatla College of Pharmacy, Bapatla, Andhra Pradesh, India, 3Department of Life Sciences, International Medical University, Kualalumpur, Malaysia

ABSTRACT

Introduction: Pre-diabetes is a condition that persists for a considerable duration before progressing into type 2 diabetes mellitus (T2DM)� Development of resistance to insulin is the underlying cause of pre-dia-betes, preventive measures such as diagnosis, treatment and exercise will preclude its development into T2DM� The present study aims at studying the effect of pre-treatment and post-treatment with isolated fraction of Costus igneus on pre-diabetes and diabetes in neonatal streptozotocin (STZ) induced T2DM�

Methods: Neonatal rats were treated with STZ and differentiated for pre-treatment and post-treatment� Rats of pre-treated group were treated with isolated fraction of Costus igneus (CIF) from 4th week after STZ administration and after 12th week in non-treated rats of post-treatment group� The antihypergly-cemic was studied on 7th and 12th week after STZ treatment using oral glucose tolerance test and the hypoglycemic effect was studied on day 1, 7, 14 and 21 of treatment after 12th week of STZ treatment in both pre and post treated groups�

Results: Oral glucose tolerance test on 7th and 12th week had shown a protective effect against increase in blood glucose levels in pre-treated groups whereas, no such significant decrease was observed in non-treated groups� In the effect on hypoglycemia, a reduction in blood glucose levels was observed on treatment with CIF in both pre and post treated rats on 14th and 21st day�

Conclusions: Treatment with CIF in pre-diabetic stage could reduce the chances of progression into T2DM and is also beneficial in diabetic rats, which could be due to increase in the peripheral utilization of glucose and the insulin mimetic effect of Costus igneus�

Keywords: Prediabetes; Type 2 Diabetes mellitus; Costus igneus; streptozotocin; neonatal

INTRODUCTIONDevelopment of impaired glucose tolerance is an indication of pre-diabetes (1), which later cause

*Corresponding Author: Dr� T�E� Gopala Krishna Murthy, Department of Pharmaceutics, Bapatla college of Pharmacy, Bapatla, Guntur (Dt), AP, India - 552101, Phone: 08643 224144, Fax: 08643 221407� E-mail: bcp�principal@gmail�com�

Submitted July 14 2014 / Accepted September 15 2014

© 2014 Murthy EGK Talasila, et al�; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distribu-tion, and reproduction in any medium, provided the original work is properly cited�

a gradual increase in resistance to insulin (2) thus causing the risk of type 2 diabetes mellitus (T2DM) (3) if left unattended, making it the ini-tial avoidable indications of T2DM. The incidence of pre-diabetes is increasing at an alarming rate in the developing countries (4) and as 70% of these will turn into T2DM (5), identification and abo-lition of pre-diabetes preclude the occurrence of this otherwise impeccable disorder. The fact that

Murthy EGK Talasila, et al� Journal of Health Sciences 2014;4(3):162-168 http://www�jhsci�ba

obesity and physical inactivity are the most poten-tial causes leading to insulin resistance (6), the pre-cursor to pre-diabetes, can be explained by the role of adipose tissue in the synthesis of various medi-ators such as Non Esterified Fatty Acids (NEFA’s) and adipocytokines such as leptin, TNF-A, resistin andadiponectin (7), which are involved in the pathogenesis of insulin resistance and β-cell dys-function (8), the early steps involved in the course of development of whole body insulin resistance in T2DM (9).Drugs of herbal origin served a major role in the treatment of many ailments since centuries and still continue to be the mainstay in their treat-ment. Unfortunately, despite extensive research, no alternative drug therapy or herbal medicine has accrued adequate importance in the preven-tion of progression or treatment of T2DM (10), the most common disorder that affects majority of the population all over the world and considered to be one of the 10 leading causes of morbidity and mortality (11). Though number of plants and phytoconstituents with insulin secretagogue activ-ity were identified (12), they are of minimal use in conditions of hyperinsulinemia, the widely experi-enced characteristic of T2DM and primary cause of insulin resistance. Provided, very few plants such as Agrimony eupatoria, Helicteres isora and Ipomea batata, etc (13-15), have been mentioned to have an additional insulinomimetic activity along with their insulin secretory effects. Hence search for a potent insulinomimetic with considerable effect on insulin resistance is on, which could be a therapeu-tic breakthrough in the prevention and treatment of T2DM.Costus igneus or insulin plant is being used in the traditional folk medicine of various tribes in south East Asia, especially in southern parts of India for the treatment of symptoms such as unex-plained weight loss or gain, excessive thirst, hun-ger, insomnia, weakness or fatigue (16) together which can be characterized as the indicators of pre-diabetes and diabetes. Studies of various researches have reported the therapeutic efficacy of Costus igneus against T2DM (17). Hence the goal of our present study was to report the effect of isolated fractions of various extracts of Costus

igneus in neonatal streptozotocin (n5-STZ) model of T2DM in rats (18). The effect on pre-diabetes was studied using oral glucose tolerance test in rats during and after induction of T2DM in the pres-ence and absence of drug treatment. The effect on diabetes was studied after administration of drugs to rats which receive treatment before and after induction of diabetes.

METHODS

Animals and induction of T2DMAdult wistar albino rats of either sex (350 – 400 g) were procured from the animal house of Bapatla College of pharmacy (1032/ac/07/CPCSEA), Bapatla, India and were housed for breeding, at a constant temperature (22 ± 1°C), relative humid-ity (40-50%) and 12 – 12 h light/dark cycles were maintained. STZ 90 mg/kg (freshly prepared ace-tate buffer 0.1 M, pH 4.5) was administered intra-peritoneally to the neonatal rats (weighing 10-12 g) on day 5, postnatally (n5-STZ) (19) Buffer was administered accordingly to the neonatal rats which serve as control. These rats were separated from their mothers after 4 weeks and provided with standard pellet feed (Rayan’s Biotech, Hyderabad) and water ad libitum. Animals were acclimatized to laboratory conditions one week prior to initiation of experi-ments. The experimental protocol was approved by Institutional animal ethics committee (IAEC/IV-22/BCOP/2012). The handling and care of ani-mals was performed in accordance with CPCSEA guidelines for the use and care of experimental animals.

Plant materialFresh leaves of the plant Costus igneus were col-lected from ABS botanical gardens, karripatti, (Salem District of Tamilnadu) India. The leaves were identified and authenticated by the botanist Dr. A. Balasubramanian, Executive Director, ABS Botanical Conservation, Research and Training Centre, Salem, Tamilnadu. The voucher specimen AUT/BCP/025 was deposited in the department. The leaves were shade dried and powdered finely for extraction and isolation of various compounds.

Preparation of extract and isolation of the compoundsCostus igneus leaf powder (50 gm) was subjected to soxhlet extraction with petroleum ether for 12 hrs for defatting. The solvent was then evapo-rated and extract was dried using rotavac at a con-trolled temperature of 40-50°C. The resulting marc was subjected to soxhlet extraction with 300 ml of methanol for 24 hrs. The solvent was removed using rotavac apparatus and the resulting extract was sub-jected to extraction with various solvents as previ-ously described by Lui (20). The chloroform extract, which was found to be effective when studied for its effect on fasting blood glucose, was subjected to fractionation by preparative TLC, using 20 × 20 cm glass plates (0.5 mm) coated with silica gel G. The fractions were eluted with the chloroform and were screened for blood glucose lowering effect in normal rats and the biologically active Costus igneus fraction (CIF) was selected for the study.

Acute toxicity studiesAcute toxicity studies of the isolated fraction CIF was administered to male albino mice at doses of 5, 50, 500, 2000 mg/kg body weight orally, to 4 groups of (n=3) overnight fasted mice. They were observed for 24 hours for signs of toxicity and behavioral changes followed by observation for 7 days for mor-phological changes and mortality.

Grouping of animalsRats were divided into two sets, one for pre-treat-ment and other for post-treatment (i.e. non treated for 12 weeks after STZ administration) each con-taining five groups (n=10), of which treatment starts from 4th week of STZ administration in pre-treated groups and treatment starts after 12th week of STZ administration in post treated groups. Pre-treated set consists of five groups of which Group I served as control, group II served as negative control, group III and group IV were treated with CIF 20 and 40 mg/kg and group V rats were treated with pioglitaozone (PIO) 2.7 mg/kg. CIF and pioglita-zone were administered as suspension in 10% tween 20 (vehicle). Dilutions were made accordingly to administer 0.2 ml/100 g intragastric. Negative control group received vehicle alone. Post treated

rats were grouped into 5 groups (n=10), but do not receive any drug treatment till 12th week after STZ administration. All treatments were given intragastric.

Oral glucose tolerance test (OGTT)OGTT was performed in pre-treated and post treated groups on 7th and 12th week after STZ treat-ment. An additional 4 groups of normal rats of equal age were used to study the effects of these treat-ments on OGTT. The effect of CIF on glucose over-loaded hyperglycemia was studied in all the animals. Overnight fasted (12 h) normal rats were divided into 4 groups (n=6) of which Group I served as con-trol, Group II and Group III were treated with CIF 20 and 40 mg/kg orally administered, Group IV rats were treated with 2.7 mg/kg of pioglitazone intragas-tric. Group I to V of pre-treatedn 5-STZ rats were treated accordingly as discussed above, whereas post-treated n5-STZ rats did not receive any treatment. Zero hour blood glucose levels were determined by tail vein method. After 30 min of the drug treat-ment, the animals were fed with glucose (4 g/kg BW) orally and the blood glucose levels were determined after 0.5, 1, 2 and 3 hours after glucose administra-tion (21). Blood glucose levels were estimated using a glucometer (Accu-chekActiveTM Test meter).

Hypoglycemic effect in n5-STZ rats after chronic administrationAfter performing OGTT on 12 week after STZ administration, rats of both pre and post treated groups were used to study the effect on blood glucose levels. Rats with blood glucose levels >150 mg/dL were considered to be diabetic and are included in the study (n=6) (22). All the rats were treated with CIF and pioglitazone for 21 days as described pre-viously. They were used to study the effect of these treatments on hypoglycemia after treatment for 21 days. Fasting blood glucose levels were deter-mined using glucometer (Accu-chekActiveTM Test meter) by tail vein method on day 1, 7, 14 and 21, 30 min after drug administration (23).

Statistical analysisAll data were expressed as mean ± SEM. Statistical analysis was performed using one-way analysis of

variance (ANOVA) followed by Dunnett’s test. p<0.05 was considered to be significant.

RESULTS

Preparative TLC fractionThe percentage yield of chloroform extract was 6.52 and its TLC profile had shown the presence of two components with Rf value 0.48 and 0.61 respectively, which were separated using prepara-tive TLC. From 325 mg of chloroform extract, two fractions were obtained namely, CIF-1 (135 mg) and CIF-2 (154 mg). Both the fractions were pre-liminarily screened for their effect on blood glucose levels in normal rats and CIF-1 was found to have blood glucose lowering effect, hence was selected for the study.

Acute oral toxicity studiesAcute oral toxicity studies of CIF fraction of chlo-roform extract did not show any abnormal or toxic symptoms in mice treated with 5, 50, 500, 2000 mg/kg of the same and the LD50 value is above 2 g/kg.

Effect on oral glucose tolerance testIn normal ratsTreatment with CIF 20 mg/kg had shown a signif-icant decrease in the elevated blood glucose levels (p<0.01) and (p<0.001) at 2nd and 3rd h respectively and treatment with CIF 40 mg/kg had shown a sig-nificant decrease (p<0.001) at 2nd and 3rd h and the observed effects are similar to that of pioglitazone treatment (Figure 1).

In STZ treated ratsNo significant difference in the basal blood glucose levels were observed in the 7th week of pre-treated and non-treated rats. In OGTT at 7th week, the elevation in blood glucose levels after glucose over loading was more in non-treated rats than that observed in pretreated rats, though not significant. The decrease in the blood glucose levels was sig-nificant (p<0.01) in the 2nd and 3rd h CIF 20 and 40 mg/kg treated rats (Figure 2). No significant decrease in the blood glucose levels was observed

in non-treated rats. OGTT on 12th week after STZ treatment had shown a significant decrease in the blood glucose levels at 2nd and 3rd h of treatment with CIF 20 (p<0.05) and 40 mg/kg (p<0.01) in pre-treated rats. The increase in blood glucose levels after glucose administration was significant (p<0.01)(Figure 3) and no significant decrease in the blood glucose levels was observed in non-treated rats.

Effect on hyperglycemiaPretreatment with CIF 20 mg/kg and 40 mg/kg had shown a significant reduction in blood glucose

FIGURE 1. Effect of CIF on glucose overloaded hyperglycemia in normal rats (n=6). Blood glucose levels of CIF 20, 40 and piogl‑itazone treatments were compared with that of control group at respective time intervals **p<0.01. #p<0.001.

FIGURE 2. Effect on oral glucose tolerance test after 7th week of STZ administration in rats pretreated with CIF (n=10). Blood glucose levels of CIF 20, 40 and pioglitazone treatments were compared with that of negative control group at respective time intervals. *p<0.05, **p<0.01.

levels on 1st (p<0.05), 7th (p<0.05), 14th (p<0.01) and 21st day (p<0.001) when compared with that of blood glucose levels of negative control group whereas the reduction in blood glucose levels was significant only on 14th (p<0.05) and 21st (p<0.01) day, when compared with the blood glucose levels of day 1 (Table 1). Basal blood glucose levels were higher in post treated groups when compared with that of pre-treated rats in day 1. Post treatment with CIF 20 had shown a significant decrease in the blood glucose levels on 14th and 21st day (p<0.05) when compared with that of negative control group and 14th (p<0.05) and 21st (p<0.01) when compared with the basal blood glucose levels on day 1, and treatment with CIF 40 mg/kg had shown a signif-icant decrease on 7th (p<0.05), 14th (p<0.01) and 21st day (p<0.001), when compared with that of neg-ative control group and 7th (p<0.05), 14th (p<0.05)

and 21st day (p<0.001), when compared with the basal blood glucose levels on day 1 (Table 2).

DISCUSSIONInsulin resistance is the primary cause of develop-ment of T2DM, causing significant morbidity and mortality due to various micro and macro vascular changes affecting the quality of life of millions of people all over the world (24). Identification of indi-viduals susceptible to T2DM in their pre-diabetic stage and providing adequate treatment could cut the extent of damage caused. Costus igneus was stud-ied less in terms of its usefulness in the treatment of T2DM despite of its wide usage in many parts of south India. The present study has been designed to explore the possible role of isolated fraction of chloroform extract of Costus igneus on pre-diabetes and diabetes in pre and post treated n5-STZ rats. As n5-STZ rat model produces gradually develop-ing basal hyperglycemia, abnormal glucose toler-ance and mild hypoinsulinemia in the initial states of STZ induction up to 7th or 8th week, this could be due to the development of loss of sensitivity of β-cell towards glucose (25), though a compensatory increase in insulin levels to maintain the blood glu-cose levels occurs initially, there occurs a failure in such response, due to loss of beta cell sensitivity to glucose, which further inhibit insulin action, thus causing elevated blood glucose levels throughout the day leading to development of insulin resistance.The effect of CIF on normal glucose overloaded rats in oral glucose tolerance test (OGTT) exhib-its its potential in reducing the elevated blood glu-cose levels. OGTT itself has an ability to detect

FIGURE 3. Effect on oral glucose tolerance test after 12th week of STZ administration in rats pretreated with CIF (n=10). Blood glucose levels of CIF 20, 40 and pioglitazone treatments were compared with that of negative control group at respective time intervals. *p<0.05, **p<0.01.

TABLE 1. Effect of CIF on blood glucose levels in rats pretreated from 4th week after STZ administrationTreatment Blood glucose levels (mg/dL) at various intervals (days) after 12th week

1 7 14 21Control 64.3±4.9b# 68±5.2b# 60.5±7.1b# 62±7.1b#

Negative control 197.1±10.2 188.2±5.7 193.4±16.2 175.5±8.9CIF 20 mg/kg 163.4±12.1b* 130.6±10.4ansb* 124.3±11.3a*b** 103.8±9.3a**b#

CIF 40 mg/kg 154.4±10.3b* 112.1±7.9ansb** 103.2±7.8a*b# 92.4±14.2a**b#

PIO 2.7 mg/kg 158.3±6.8b* 118.7±6.8ansb** 100±10.2a*b# 82.3±9.6a**b#

Data represents mean±SEM of blood glucose levels in rats pretreated with CIF from 4th week to 21 days after 12th week of STZ administration. a=represents comparision of blood glucose levels on day 7, 14 and 21 with that of day 1. b=blood glucose levels of all the groups (n=6) were compared with that of negative control group using one way ANOVA followed by Dunnett’s test. *p<0.05; **p<0.01; #p<0.001, ns-non significant

the impaired glucose tolerance (26) an indicator of pre-diabetes. As every 1-5 % of individuals with impaired glucose tolerance, develop into T2DM every year and are at a risk of developing heart dis-eases (27). Neonatal STZ model of diabetes resemble both pre-diabetic and diabetic states of the human (28). In later stages after 7th or 8th week of age there occurs drastic destruction of β-cells accompanied with peripheral and hepatic resistance of cells against insulin due to prolonged hyperglycemic states (29), which resembles the condition of T2DM in humans. The reduction of blood glucose levels in pre-treated groups after glucose overloading at 7th week indicates the efficacy of CIF on peripheral utilization of glu-cose levels and could be due to increasing the insu-lin sensitivity as no such significant decrease in the blood glucose levels were observed in non-treated STZ rats. The effect of OGTT in pre-treated rats is similar to that of observed in normal rats. Whereas, in OGTT after 12 wk of induction pre-treated rats had shown a significant reduction in the blood glu-cose levels when compared with that of non-treated rats, but was less when compared with that of nor-mal rats. This could be due to the extent of destruc-tion of β-cellsleading to hypoinsulinemia, that might have occurred in the later stages of STZ induction in both pre-treated and non-treated groups (30). Protection against developing resistance to insulin at peripheral and hepatic tissues and increase in the sensitivity of β-cells towards glucose in pre-treated groups (31) could be responsible for the observed beneficial effect.Whereas, in the effect on hypoglycemia, the reduc-tion in blood glucose levels in the pre-treated groups was less than that observed in normal rats when

compared to the observed change in the OGTT per-formed at 7th week, which once again could be due to the destruction of β-cells in the adult rats. The elevation in the blood glucose levels on 12th week in both pre-treated and non-treated rats could be explained by the destructive phase of pancreatic β-cells after 8th week of STZ administration.In post treated rats, the basal blood glucose levels are higher than that observed in rats that receive CIF and pioglitazone from 4th week, this protective effect on pre-treatment could be explained by the fact that though there occurs a disruption of pancreatic β-cells, there exists insulin sensitivity, which is evi-dent with the low basal blood glucose levels in them. In conclusion, use of CIF as a prophylactic agent in individuals with basal hyperglycemic states could reduce the risk of developing into T2DM and is also of therapeutic value in the treatment of T2DM.

COMPETING INTERESTSThe authors declare that there is no conflict of interest.

ACKNOWLEDGEMENTSThe authors would like to thank All India Council for Technical Education (AICTE) for providing financial assistance under Research Promotion Scheme.

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TABLE 2. Effect of CIF on blood glucose levels in post treated rats during 21 days of treatment from 12th week after STZ administrationTreatment Blood glucose levels (mg/dL) at various intervals (days) after 12th week

1 7 14 21Control 71.5±4.3b# 68.2±6.1b# 66.1±4.2b# 72±6.8b#

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Zada Pajalic and Albert Westergren� Journal of Health Sciences 2014;4(3):169-175 http://www�jhsci�ba

A Network for Eating and Nutrition as a platform for cooperation over the organisational borders between healthcare sectors in SwedenZada Pajalic1, 2*, Albert Westergren2

1Faculty of Health Sciences, Department of Health, Nutrition and Management, Programme for Midwifery, Oslo, Norway and Kristianstad University, Sweden, 2The PRO-CARE Group, School of Health and Society, Kristianstad University, Kristianstad, Sweden, albert�westergren@hkr�se, Högskolan Kristianstad 291 88 Sweden

ABSTRACT

Introduction: Requirements to implement scientific knowledge can be implemented through networks in practice within the Swedish health and social care sectors have increased during the last decades� One of these networks was the Network for Eating and Nutrition that began in 2003� The aim of this study was to retrospectively evaluate how the Network for Eating and Nutrition has functioned during a period ten years and in what way it has affected work practice�

Methods: This is a descriptive qualitative study� Data sources for this study were meeting records col-lected over 10 years and two evaluation surveys (at five and 10 years)� Participants were members of the Network for Eating and Nutrition (n=12 at five years and n=10 at 10 years)� The manifest qualitative content analysis was used�

Results: The Network for Eating and Nutrition was seen as offering support for personal and organiza-tional knowledge development� Further aspects of support from the workplaces of the members and the significance for the work places were described� Further the Network for Eating and Nutrition reached out to care receivers by using specifically tailored education programmes and material� The Network for Eating and Nutrition results and recommendations were described as important references for the development of nutrition routines�

Conclusion: Networks between organisations with different professional backgrounds can form a basis for knowledge exchange both for focus on the specific topic but also on how to work with quality improvement, i�e� evidence based practice�

Keywords: network; research and development

*Corresponding Author: Dr� Zada Pajalic PhD Associated Professor Faculty of Health Sciences, Department of Health, Nutrition and Management, Programme for Midwifery, Oslo, Norway and Kristianstad University, Sweden� E-mail: zada�pajalic@hioa�no

Submitted: December 06 2014 / Accepted: December 15 2014

© 2014 Zada Pajalic and Albert Westergren; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited�

INTRODUCTIONHealth and care systems in countries with welfare programmes and systems are going through system changes due to increased pressure for cost control, efficiency and analysis of the effects of implementing scientific knowledge to practice (1, 2). One reason

http://www�jhsci�ba Zada Pajalic and Albert Westergren� Journal of Health Sciences 2014;4(3):169-175

for this is ongoing demographical change, i.e., the increase of the aging population and age related needs for the health and care system’s service (3). To deal with these complex needs, that now reach over organisational boundaries, networks have emerged as a solution to link across the boundaries (4).Networks in the Swedish health and social care fos-ter innovation and new ways of working by involv-ing the whole health community in knowledge sharing and development of practice (5). These networks were initiated as a solution to deal with complex problems over organisational borders and to support practitioners in incorporating evidence based knowledge (6). Networks are interacting and non-linear systems that in practice create the sharing of knowledge and organisational culture minimise organisational barriers and support devel-opment in the practice. The knowledge develop-ment is a process formed through dialogue in both directions among practitioners and social and care consumers (1,7).The networks in the public sector are complex, as common mechanisms for the delivery of public services and the advantage of these networks is that many of the members in the networks are employed by the organisations that build the networks. The effectiveness of these networks depends on their focus on community-level goals, not only their focus on client and public goals (8-10). Further, networks can be important contexts in which to set agendas that imply sustained, creative and system-atic ways to work that are based on evidence based knowledge (11). As an important form of multi-or-ganisational governance the networks enhance learning, efficient use of resources, increased capac-ity to plan for, and address complex problems, greater competitiveness and better service for clients and consumers (9).Networks have been described as one for imple-mentation of innovative methods for dealing with complex issues in the social care and service sector. Collaboration through a network structures and establishes an innovative response towards dealing with outcomes and processes based on new ways of working. The involvement of policy makers in these networks can maximize the benefits of unique mechanisms. Networks provide a way of dealing

with problems and provides solutions by bringing systemic change in traditional methods of knowl-edge development and intervention (6). The net-work is a construction of critical knowledge mass by the involvement of heterogenic knowledge that can enable improvement of health and care services (12).This study provides new information about a net-work entitled, Network for Eating and Nutrition (NEN), for use as a platform for cooperation over the organisational borders in healthcare sectors in Sweden. The study will, hopefully, give a better understanding of the NEN’s influence on work practice and contribute towards gaining new knowl-edge that can highlight the networks benefits on practice, nationally and internationally, by gaining insights into how the NEN has functioned during the ten years it has been in operation.The aim of this study was to retrospectively evaluate how the Network for Eating and Nutrition (NEN) has functioned during a period of ten years and in what way it has affected work practices.

METHODS

ContextThe NEN began in 2003 and includes members from six municipal primary care centres, two hos-pitals and one university in the north east of the Swedish province of Scania. In connection with the start-up of the network, members had the oppor-tunity to design the network’s work form, i.e. goals for the network and common ethical values and to primarily draw upon organisational differences and common problems. Common problems became the basis for further work guided by the approved ethical values. In 2004, joint guidelines were drawn up and developed regarding how to detect those at risk for malnutrition, which in 2005, contributed as input to the first large scale point prevalence study in Sweden on eating and nutrition (13). This study was followed up by two further studies in 2007 and 2009 that showed some improvement in nutritional care following an educational intervention (14-16). One indicator of success appeared to be due to the relatively fast feedback to each unit that had the ability to compare its performance with their own community or hospital (14).

ParticipantsToday the NEN has 24 members. At different times, a total of 22 members took part in a survey about their experiences of being a member of the NEN. The first survey was made after five years of NEN operation, where 12 members participated (average age was 50 years) and in the second survey that was made after 10 years where 10 members participated (average age was 42.5 years). Due to the fact that participation in these two surveys was anonymous, it is not possible to state to what extent it was the same persons who had participated in both surveys. The professions represented in the survey after five years were: six registered nurses, one head of unit, three dieticians, and two university lecturers, and their average length of membership in NEN was 3.5 years. In the survey taken after 10 years the fol-lowing professions participated: one head of a diet unit, two university lecturers, four dieticians and three registered nurses and their average length of membership in NEN was 6.2 years.

Data collection methodsData for the present study was taken from meeting records collected over 10 years (n=20, about 250 pages) and evaluations of the network after 5 and 10 years were performed as surveys with open ques-tions. The surveys were sent to all NEN members.Questions included in the 5 and 10 year surveys were focused on followed:Age, profession and working place?For how long have you been a member of NEN?Describe your general experiences of being a mem-ber of NEN?Do you experience support from your workplace regarding your membership in NEN and atten-dance to the NEN meetings?What is your reflection of being a member in NEN from the perspective of your profession?What significance has NEN for your work?Do you have suggestions for new working forms and if yes specify?Does NEN have any significance for how you work - if yes specify how? - if no specify why?Do your colleagues know about your activity and

membership in NEN, its existence, and working forms (if yes specify - if no describe why not)Do you consider that NEN work reaches out to care receivers? (If yes specify- if no describe why not)Is there something more in relation to NEN that we didn’t ask about that you want to highlight?The written text from the meeting records and sur-veys was analysed by using manifest qualitative anal-ysis (17). The analyse process began with reading all the answers to get an overall impression of content, in the next step the text was structured into groups and then the groups into categories.

Ethical considerationsThe present study was performed in accordance with the Helsinki Declaration and The Swedish Research Council directives (18, 19). All participants in the study received detailed information about the study and confirmation of their right to cancel their par-ticipation at any time without any consequences for them. Formal approval was not needed for this type of study, in accordance with Swedish law (20). All participants gave their informed consent following oral and written information regarding the aim and procedures of the study. No personal information that would allow any data to be linked to individual participants was recorded.

RESULTS

The NEN as support for personal knowledge developmentThe majority of participants described their mem-bership in NEN as positive. They described NEN as a good platform for increasing and supporting individual knowledge development. As an example, they described that it was enriching to gain insight into how other colleagues work with nutrition at hospitals, municipalities and in primary care set-tings. Further they highlighted that it was valuable to get news of developments in nutrition and to be updated in all types of research and development as all members were willing to share their experi-ences with each other. The NEN was described as a network with various perspectives and possibili-ties to create guidelines, target documents or other

solutions that were positive for patients, care units and food production kitchens. Many of the partic-ipants described their membership as giving them a feeling of being involved in something important and that membership could give them influence at various levels from organisational to individual. One of the participants expressed it as: “I learn new things the whole time through this network, together with good colleagues who are passionate about nutrition”.

The NEN as a support for organisational knowledge developmentFrom a professional perspective many experi-enced that it was especially positive to meet other professionals and to unite in a common quest for the patients or care receivers best. The nurse was described as having a central role in this work but needed help from others including support from another professional’s competence. Involvement in the NEN was described as offering a broader under-standing of the possibilities of other professionals and the complexities to be found within various working places. The exchange of experience was described as invaluable and it was noted that if all professions had attended NEN network meetings they could become excellent spreaders of knowledge within their own working places. One participant described it as:”My membership in the NEN gives me support and offers suggestions for proposals for proce-dures that I can present to the patient responsible doctor as we do not have a dietician in our municipality”. Further the participants described membership as an important forum offering the possibility to high-light nutrition from the patient’s perspective as well as overall nutrition routines. The importance of wide representation by many professions was high-lighted and as well as the co-operation with profes-sionals from the university. One of the participants described the NEN meetings as follows: ”I think that it is positive that we have a short round where everyone talks briefly about what is going on regarding nutrition and eating at their own workplace and gives informa-tion about actual news. In addition, I think that it is positive that the network uses information letters that are distributed with meal boxes”. It was also described as important that all organisations are represented, i.e. municipalities, hospitals, primary health care and the university. The members emphasised that

there are some professionals missing in the mem-bership of the NEN: for example, public home care officers, medically responsible nurses, and unit man-agers and that their perspective is missing. Further many of the participants agreed that the NEN has come a long way and managed to achieve a wider composition and is seen as an inspiration source for the whole country to form similar networks. One of participants expressed it as: “I believe that the NEN should be a player who actively participates in the design of nutrition work and be an obvious referral body for nutritional issues”.

Workplace support to NEN members and its significance for the working placeSeveral participants expressed that they have the support of their managers. However one of them expressed that her manager considered that her membership was not consistent with a district nurse’s area of responsibility. Support from the man-agers for NEN members was described as a confir-mation that nutrition was important, as also when the NEN is used as a reference for the development of nutrition routines. Some of the participants expressed that they have support from their manage-ment but that it is not always easy because they have an enormous work load. One of them expressed it as: “In contrast, my participation is questioned by col-leagues since a whole afternoon disappears each time there is a meeting”. One of the participants described that the education material produced by NEN was useful: “The NEN’s documents are on our web-page”. Some participants described that they often use the part of NEN’s handbook related to eating and nutrition to find various alternatives or sugges-tions for how to help their care receivers towards better nutrition. Further, membership in the NEN offers knowledge that can be used in education and in research. To gain insight into how others work with nutrition through membership of the NEN is inspiring for both the members and other organisa-tions. One of the participants expressed it as: “It is good to be able to coordinate different professions who all think that nutrition is important and simultane-ously obtain both municipal and county points of view on issues”. Further, participants described how they followed the NEN’s recommendations and used the information materials they produced. One of the

participants described how they had implemented all the education material developed by the NEN at her workplace.

The NEN reaches out to care receiversThe representativeness of all the professions involved in nutrition was highlighted and their involvement was described as important for dissemination of knowledge into the workplace. Further, knowledge was disseminated through education programmes, information material and decision-making. One participant highlighted the importance of the large surveys of nutrition and nutritional care that have been conducted in cooperation with the univer-sity. The university was described as an important partner for the network, and the surveys as being important for the work on quality improvements. The workplaces with good nutrition routines should be highlighted as being good models and public home care officers, as well as unit managers, should be an asset for the NEN. Furthermore, one of the participants suggested that all members of the NEN should attend nutrition conferences and also work more in project form with focus on reconnecting the results of projects and surveys. The NEN can be used as a platform for discussions regarding how the various workplaces can implement national guide-lines and regulations from the Swedish National Board of Health and Welfare (Socialstyrelsen) and the National Food Agency (Livsmedelsverket) with other advice about nutrition.

DISCUSSIONThe present study showed that the NEN was seen as: support for individual and organisational knowl-edge development, that the public health care and social organisation supports the NEN and that it is an important reference for the development of nutrition routines. Further the NEN reaches out to care receivers through specifically tailored education programmes and material. This is in line with results from Tsai’s (2001) in which the author argues that networks produce more innovations and enjoy bet-ter performance that provides access to new knowl-edge. However this also depends on motivation, absorptive capacity and the ability to successfully use new knowledge, and the networks position.

A network’s position can represent various oppor-tunities to have access to new external information and this information is necessary to generate new ideas for organisational development. Interaction between absorptive capacity and the position of a network can have significantly positive effects on practice, as indicated in this study. This position can promote social learning that links an organisation and its members and enables them to work collec-tively (21). Correspondingly the networks were fur-ther described by Wasko & Faraj (2005) as social constructions based on common interests that make it possible to focus on problems of practice and exchanges of ideas with others. Further they found that NEN network members are ready to add their knowledge when they recognize that it improves their professional status when they have experience to share and when they are organisationally rooted in the network (22).A network is the key for the transmission of evi-dence into practice and was described as import-ant for its own and its organisational knowledge development. Clinicians as members in a network combine different types of information taken from research to develop their practice. They interact with colleagues and patients and other sources of tacit knowledge. They use networking as a part of their professional development by using and deriv-ing knowledge collectively (23). Heaney and Israel (2002) highlighted the point that networks have a powerful influence on the health and care sector in various ways including facilitation and exchange and support to all involved (24). For knowledge development it is important to highlight links between the culture in an organisation and its own knowledge.Questions arise, for instance, is knowledge worth managing? What is the relation between an individ-ual’s and an organisations’ knowledge? How effec-tive can an organisation be at creating, sharing and applying knowledge and how should new knowl-edge be created, legitimised and distributed? (25). For example, multilevel organisations for regional innovation need, in an interactive way, to position specific local “sticky” knowledge resources as well as external world-class “ubiquitous” knowledge related to strength effectiveness and successful high quality practice development (26). Networks encourage the

sharing of knowledge by face-to-face interaction for transferring tacit knowledge. Further there is need to share knowledge across organisational bound-aries and communities (27). Nicolini et al (2008) highlighted that knowledge development in clini-cal practice needs to understand the patients’ role and assumptions in health care as well as using both researchers and practitioners knowledge as linear transfer. To achieve this, tailored policies of a char-acteristic professional and local nature of knowledge in the health and care sectors are required (28).The cooperation with the University and the involvement of researchers in the network was described as a strength. Cooke (2005) highlighted the importance of building research capacity, achieved and shaped by the following principles: development of skills and confidence, support for linkages and partnerships, ensuring research close to practice, developing appropriate distribution, investing in infrastructure and building elements of sustainability and continuity. Each principle should operate at an individual, team and organ-isational level. This may contribute to establishing knowledge that is research capacity building effec-tive in the health and care sector (29). Networks between organisations, and with different profes-sional backgrounds, can form a basis for knowl-edge exchange and knowledge development both with focus on the specific topic but also on how to work with quality improvement, i.e. evidence based practice. The members inspire others in the NEN network by giving examples from their own prac-tice. Furthermore, the network has the acceptance and power to influence the organisation at large through guidelines and recommendations.

CONCLUSIONThe NEN is important for knowledge development at individual and organisational levels in the Swedish health and care sector. The present study and results from other studies highlight the importance of sup-port from the side of the involved organisations managements, i.e. new knowledge from the NEN should be an important reference for the develop-ment of nutrition routines through tailored educa-tion programmes and materials and the making of policies.

COMPETING INTERESTSThe authors declare that they have no competing interests or financial interests.

ACKNOWLEDGEMENTThe publications fee and language review for the study was supported by the Faculty of Health Sciences, Department of Health, Nutrition and Management, Programme for Midwifery, Oslo, Norway. Further, the study was supported by the Swedish Research Council, The Kamprad Family Foundation for Entrepreneurship and Charity, and the Vårdal Foundation. The authors wish to thank all of the participating respondents in the NEN for their cooperation.

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http://www�jhsci�ba Bećir Heljić, et al� Journal of Health Sciences 2014;4(3):176-180

The role of natural supplement of apple vinegar and syrup in the management of type 2 diabetes mellitusBećir Heljić1*, Zelija Velija-Ašimi1, Azra Bureković1, Vanja Karlović1, Azra Avdagić2, Murisa Ćemalović2

1Clinic for Endocrinology, Diabetes and Metabolism Diseases, University Clinical Centre of Sarajevo, Bosnia and Herzegovina,2The Public Institution Health Centre of Sarajevo Canton, Bosnia and Herzegovina

ABSTRACT

Introduction: The increased risk of coronary artery disease in diabetics could be explained by the lipopro-tein irregularities associated with diabetes mellitus� The primary aim of this study is to examine the role of apple vinegar and syrup in the management of type 2 diabetes mellitus�

Methods: The interventional study included 500 participants (195 men and 305 women) with dyslipid-emia and prediabetes or type 2 diabetes mellitus, aged 50-70 years, living in Sarajevo area� Patients were recruited from 5 outpatient diabetes counselling departments and treated with natural apple vinegar and syrup supplementation over a period of five weeks� The patients have been evaluated before treatment and 5 weeks after the treatment� During the study, dosage of drugs for diabetes or prediabetes was not changed�

Results: After 5 weeks of supplementation with apple vinegar and syrup waist circumference (p=0�016), total cholesterol (p=0�01), low density lipoprotein (LDL) cholesterol (p=0�008) and triglycerides (p=0�019) were significantly reduced, as well as blood pressure (-14%)� Study results show decrease of mean fasting blood levels of glucose, but statistically not significant (p=0�058)� The body mass index also decreased insignificantly (p=0�089)� The high density lipoprotein cholesterol level was not increased significantly after supplementation (p=0�26)�

Conclusion: According to our results, apple vinegar has important role in reduction of total cholesterol levels, triglycerides, LDL cholesterol and waist circumference in patients with type 2 diabetes� Also, it has positive effect on blood pressure�

Keywords: Natural products; apple vinegar; dyslipidemia; type 2 diabetes mellitus

*Corresponding Author: Bećir Heljić, Clinic for Endocrinology, Diabetes and Metabolism Diseases, Clinical Centre University of Sarajevo, Bolnička 25, 71 000 Sarajevo, Bosnia and Herzegovina, Phone: +38733298383, Fax: +38733258480� E-mail: heljicbecir@hotmail�com

Submitted October 20 2014 / Accepted December 15 2014

INTRODUCTIONCoronary artery disease is the most common cause of death in patients with diabetes. The increased risk of coronary artery disease in diabetics could be explained by the lipoprotein irregularities associated with diabetes mellitus (1). The most common lipid

© 2014 Bećir Heljić; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distri-bution, and reproduction in any medium, provided the original work is properly cited�

Bećir Heljić, et al� Journal of Health Sciences 2014;4(3):176-180 http://www�jhsci�ba

abnormalities in diabetics are hypertriglyceridemia and low levels of high-density lipoprotein (HDL). In type 1 diabetes mellitus, these abnormalities can usually be reversed with glycemic control. In type 2 diabetes mellitus (T2DM), although lipid values improve, abnormalities commonly persist even after optimal glycemic control has been achieved (1). The lipoprotein abnormalities are related to the severity of the insulin resistance. A study that measured insu-lin sensitivity using euglycemic clamp in patients with and without T2DM found that greater insulin resistance was associated with larger very low den-sity lipoprotein (VLDL) particle size, smaller low density lipoprotein (LDL) particle size, and smaller HDL particle size (2).Annual screening for dyslipidemia is recommended in patients with diabetes mellitus. Such screen-ing should include measurements of total choles-terol, HDL, low-density lipoprotein (LDL) and triglyceride levels. An acceptable LDL level is less than 3.35 mmol/l; triglycerides should be less than 2.25 mmol/l. In patients with clinically evident vascular disease, LDL levels should be less than 2.60 mmol/l, and triglycerides should be less than 1.70 mmol/l. Whether these lower values should be the target for all patients with diabetes, regard-less of whether they manifest vascular disease, has been a matter of debate. An HDL level greater than 1.15 mmol/l is recommended (3).Primary lines to lowering the levels of lipids in sub-jects with diabetes mellitus should include glycemic control, diet, exercises and weight loss. If the goals for lipid levels have not been reached after 3 to 6 months of diet, exercise and improved glycemic control including drug therapy should be started (4). Effective treatment includes a combination of pharmacologic and non-pharmacologic therapy.Currently, the accessibility of multiple lipid-low-ering drugs and supplements make available new opportunities for patients to succeed target lipid levels. However, the variety of therapeutic options poses a challenge in the ordering of drug therapy. Most people with diabetes mellitus are candi-dates for statin therapy, and often need treatment with multiple agents to achieve therapeutic goals. Nevertheless, drug therapy for dyslipidemia must be personalized (5).

For more than 2000 years, vinegar has been used to flavor and preserve foods, heal wounds, clean surfaces, fight infections, and manage diabetes. However, many recent studies have reported that vinegar reduces the glucose answer to a carbohydrate load in healthy adults and in people with diabetes (6). Vinegar can be made from practically any fermentable carbohydrate source, as well as wine, apples, molasses, dates, pears, coconut, grapes, melons, honey, beer, maple syrup, potatoes, beets, grains. Vinegar’s use can be consid-ered safe by default. Yet there are rare reports about adverse reactions to vinegar ingestion (6).The effect of vinegar on glucose was first reported by Ebihara and Nakajima (7) in 1988. In healthy adults, the insulin response was reduced for 20% after the ingestion of 50 g sucrose in combination with 60 mL strawberry vinegar (7). Several years later, Brighenti and colleagues (8) demonstrated that 20 mL white vinegar as a salad dressing ingredient reduces the glycemic answer by over 30% in healthy people (p<0.05). As well, additional placebo-con-trolled studies have documented antiglycemic effects of 20 g vinegar in healthy adults (9,10).Apple vinegar might help lower blood sugar levels in people with diabetes by changing how foods get absorbed from the gut (11). In the past decade, there has been an increase in the use of natural products in type 2 diabetes mellitus (12). According to our knowledge, few studies have been done with apple vinegar in people with diabetes mellitus. Therefore, we designed pilot study, first in our country to investigate the effect of apple vinegar and syrup by brand product called Cardio Fit in participants with diabetes. The aim of this study was to examine the role of apple vinegar and syrup supplements in the management of type 2 diabetes mellitus.

METHODSStudy designThe interventional study included 500 participants (195 men and 305 women) with dyslipidemia and prediabetes or type 2 diabetes mellitus, age 50-70 years, living in Sarajevo area. Patients were recruited from April to July 2013, from five differ-ent outpatient diabetes counselling departments.The inclusion criteria were: participants with dys-lipidemia and prediabetes or T2DM according

to ADA criteria (13) on oral antidiabetic therapy. Patients with prediabetes used metformin, whereas patients with diabetes used metformin or combina-tion of metformin and sulfonil-urea products. Total of 29% of the patients have never used statins for treatment of dyslipidemia, and 71% of patients have been using them occasionally, but ceased the usage during the study. Most of the participants had T2DM (n=485), while the number of subjects with prediabetes was 15 (3%) which is statistically insignificant, so that the subjects were not divided into two groups. The exclusion criteria were: alco-hol consumption, liver diseases, chronic renal failure and hypothyroidism.The patients were treated with natural apple vine-gar supplementation (Cardio Fit, BioBrand, Bosnia and Herzegovina) over a period of five weeks. The patients have been thoroughly evaluated before treatment, and 5 weeks after the treatment. The study was performed according to the principles outlined in the Declaration of Helsinki and in accordance with ethical recommendations of the local Ethics Committee. The study was approved by the Ethics committee of the Medical Chamber.Before and after the treatment, all the patients were measured fasting blood levels of glucose (FBG), total cholesterol, triglyceride, LDL-C (low density lipo-protein cholesterol), HDL-C (high density lipopro-tein cholesterol), AST (aspartate transaminase), ALT (alanine transaminase), creatinine, blood pressure, ECG, waist circumference and body mass index (BMI). Glycosylated hemoglobin (HbA1c) was mea-sured only at the beginning because the short period since the last measurement. BMI was calculated as weight in kilograms divided by the square of height in meters (kg/m2). During the study, dosage of drugs for diabetes or prediabetes was not changed. All patients with prediabetes were taking metformin, whereas 33% of diabetics were taking only metformin and 67% diabetics were taking combination of oral antidi-abetics: metformin and glimepiride or glibenclamide.The patients were familiarized with the usage of Apple vinegar and syrup preparation and received the complete dosage. Each patient was taking 40 ml of apple syrup and 20 ml apple vinegar, daily. Doses are standardized by using plastic cups that were included in the supplement package.

Four patients experienced side effects related to their gastrointestinal tracts (vomiting and nausea) and decided against further consumption of the prepa-ration (0.8%), eight patients had minor gastroin-testinal difficulties and continued to consume half of the recommended dosage of the preparation for 3-5 days after which the difficulties ended and they continued using the full dosage of the preparation. Fourteen patients (2.8%) out of the total number of patients, did not show up for the control check-up after 5 weeks of consuming the preparation due to unknown reasons.

Statistical analysesNormal distribution was investigated using Shapiro-Wilk test. Data were expressed as means (SD) or absolute numbers (percentages) according to type of variables and normality of distributions. Statistical analysis of laboratory parameters was carried out by Student’s T. The cut-off for statistical significance was 0.05.

RESULTSClinical data of the patients included in the study are shown in Table 1.The patients have been thoroughly evaluated before treatment, and 5 weeks after treatment with supple-ments. After 5 weeks of treatment with Apple vin-egar and syrup the waist circumference (p=0.016), total cholesterol (p=0.01), LDL cholesterol (p=0.008) and triglycerides (p=0.019), significantly reduced as well as blood pressure (-14%). Reduction of waist circumference is shown in Figure 1, reduc-tion of triglycerides is shown in Figure 2, while the effect of Apple vinegar and syrup on blood pressure is shown in Figure 3.Study results show decrease of mean FBG, but sta-tistically not significant (p=0.058). The BMI also decreases insignificantly (p=0.089). The HDL level was not significantly elevated after the supplemen-tation (p=0.26).

DISCUSSIONMany studies have investigated the antiglycemic and antilipidemic effects of natural products in diabe-tes mellitus. Some of them have proved the positive

Bećir Heljić, et al� Journal of Health Sciences 2014;4(3):176-180 http://www�jhsci�ba

effect of these natural products on lipid and glucose level in diabetics (14-16).On the other hand, based on the published infor-mation, there is little evidence to support the use of herbal products for the treatment of T2DM. Some agents may be useful as adjunctive therapy (12).This research examines the scientific evidence for uses of apple vinegar, focusing particularly on the recent investigations supporting vinegar’s role as antilipidemic agent. The hypoglycemic and hypolipidemic proper-ties have been reported for vinegar, but some cases of discrepant effects were also observed. Mahmodi et al. showed hypoglycaemic effect of apple vinegar (17).In comparison with these results, the effectiveness of Apple vinegar and syrup on glycemic control in our study was not significantly registered. Partial expla-nation for this difference could be the short dura-tion of the study.According to our results, it is important to empha-size the influence of Apple vinegar and syrup on a significant reduction of total cholesterol levels, tri-glycerides and LDL cholesterol. Mahmoodi et al.

did not find lipid changes in diabetics after vinegar supplementation (17).Also, it is necessary to emphasize the reduction of BMI and a pronounced reduction in waist

FIGURE 1. The effects of apple vinegar and syrup on waist circumference in patients with type 2 diabetes mellitus (p=0.016)

FIGURE 2. The effects of apple vinegar and syrup on triglycerides in patients with type 2 diabetes mellitus (p=0.019)

FIGURE 3. The effects of apple vinegar and syrup on blood pres‑sure in patients with type 2 diabetes mellitus (p<0.05)

TABLE 1. Clinical and laboratory characteristics of the study populationParameters Descriptive statistics T P

Before treatment

After 5 weeks of treatment

+Number n (%) 500 (100) 486 (97,2)*Age (y) 59.89±9.9 58.45±7,6+Sex M/F (n/%)

195/305 (39/61)

195/291 (40/60)

+Blood pressure (mmHg)

150/90 130/80 (−14%)

*HbA1c (%) 8,64±1,77*BMI (kg/m2) 29.43±1.41 26.95±1.12 1.7 0.089*Waist (cm) 102.65±6.36 95.47±3.54 2.4 0.016*FBG (mmol/l) 6.36±2.11 5.91±1.72 1.9 0.058*Total Cholesterol (mmol/l)

6.95±0.99 6.49±0.35 2.56 0.010

*HDL (mmol/l) 1.05±0.47 1.11±0.21 1.11 0.260*LDL (mmol/l) 3.75±2.22 3.27±0.95 2.64 0.008*Triglycerides (mmol/l)

3.71±0.67 2.17±0.77 2.35 0.019

Data in descriptive statistics were expressed as *means (SD) and, +absolute numbers (%). Laboratory parameters were analyzed by Student’s T test for paired samples (T). P=significance

circumference, which show a statistically significant reduction. This reduction of visceral fat can be explained by an adequate response of insulin after meal, which is shown in study of Ostman et al (18).A significant reduction of 14% in blood pressure was registered in comparison to prior registered values of all patients. Kondo and colleagues (19) reported a significant reduction in systolic blood pressure. These observed reductions in systolic blood pressure were associated with reductions in both plasma renin activ-ity and plasma aldosterone concentrations reductions in renin activity and aldosterone concentrations.Apple vinegar preparation did not have any reported harmful metabolic effects apart from (0.8%) insig-nificant gastrointestinal difficulties in 4 patients for which we are unsure whether they were other coin-cidental gastrointestinal and alimentary disorders. Inflammation of the oropharynx and second-degree caustic injury of the oesophagus after vinegar con-sumption occur rarely (20).Future investigations are needed to delineate the mechanism by which apple vinegar alters lipids and glucose metabolism, especially in subjects with diabetes mellitus. Furthermore, future controlled studies need to follow-up patients over a longer period of time.

CONCLUSIONAccording to our results, apple vinegar has import-ant role in reduction of total cholesterol levels, tri-glycerides, LDL cholesterol and waist circumference in patients with type 2 diabetes. Also, it has positive effect on blood pressure.

COMPETING INTERESTSThe authors declare that they have no competing interests.

ACKNOWLEDGEMENTSThe author wishes to thank all subjects who partici-pated in the study.

REFERENCES1. O’Brien T, Nguyen TT, Zimmerman BR. Hyperlipidemia and Diabetes

Mellitus. Mayo Clinic Proceedings, 1998;73(10),969–976. http://dx.doi.org/10.4065/73.10.969.

2. Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 2003;52:453. http://dx.doi.org/10.2337/diabetes.52.2.453.

3. AACE Lipid and Atherosclerosis Guidelines. Endocr Pract. 2012;18(suppl 1).

4. American Diabetes Association. Standards of Medical Care in Diabetes—2013. Diabetes Care, 2013; 36, S4-S10. http://dx.doi.org/10.2337/dc13‑S004.

5. Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009; 5(3):150‑9. http://dx.doi.org/10.1038/ncpendmet1066.

6. Johnston CS, Gaas CA. Vinegar: Medicinal Uses and Antiglycemic Effect. MedGenMed. 2006; 8(2): 61.

7. Ebihara K, Nakajima A. Effect of acetic acid and vinegar on blood glu‑cose and insulin responses to orally administered sucrose and starch. Agric Biol Chem. 1988;52:1311–1312. http://dx.doi.org/10.1271/bbb1961.52.1311.

8. Brighenti F, Castellani G, Benini L, et al. Effect of neutralized and native vinegar on blood glucose and acetate responses to a mixed meal in healthy subjects. Eur J Clin Nutr. 1995;49:242–247.

9. Johnston CS, Buller AJ. Vinegar and peanut products as comple‑mentary foods to reduce postprandial glycemia. J Am Diet Assoc. 2005;105:1939–1942. http://dx.doi.org/10.1016/j.jada.2005.07.012.

10. Leeman M, Ostman E, Bjorck I. Vinegar dressing and cold storage of pota‑toes lowers postprandial glycaemic and insulinaemic responses in healthy subjects. Eur J Clin Nutr. 2005;59:1266–1271. http://dx.doi.org/10.1038/sj.ejcn.1602238.

11. Web MD. Apple cider vinegar uses & effectiveness (cited 2014 Oct 18). Available from: http://www.webmd.com/vitamins‑supplements.

12. Mansukhani R, Volino L, Varghese R. Natural Products for the Treatment of Type 2 Diabetes Mellitus. Pharmacology & Pharmacy, 2014; 5, 487-503. http://dx.doi.org/10.4236/pp.2014.55059.

13. American Diabetes Association. Standards of medical care in diabe‑tes–2013. Diabetes Care. 2013; 36 (Suppl 1): S11-S66. http://dx.doi.org/10.2337/dc13‑S011.

14. Jung HL, Kang HY. Effects of Korean red ginseng supplementation on mus‑cle glucose uptake in high-fat fed rats. Chin J Nat Med. 2013;11(5):494-9.

15. Wang Q, Jiang C, Fang S, Wang J, Ji Y, Shang X, Ni Y, Yin Z, Zhang J. Antihyperglycemic, antihyperlipidemic and antioxidant effects of ethanol and aqueous extracts of Cyclocarya paliurus leaves in type 2 diabetic rats. J Ethnopharmacol. 2013;150(3):1119-27. http://dx.doi.org/10.1016/j.jep.2013.10.040.

16. Kianbakht S, Dabaghian FH. Improved glycemic control and lipid pro‑file in hyperlipidemic type 2 diabetic patients consuming Salvia offi‑cinalis L. leaf extract: a randomized placebo. Controlled clinical trial. Complement Ther Med. 2013;21(5):441‑6. http://dx.doi.org/10.1016/j.ctim.2013.07.004.

17. Mahmoodi M, Hosseini‑zijoud SM, Hassanshahi G, Nabati S, Modarresi M, Mehrabian M, et al. “The effect of white vinegar on some blood biochemical factors in type 2 diabetic patients.” Journal of Diabetes and Endocrinology. 2013;4(1):1‑5.

18. Ostman E, Granfeldt Y, Persson L, Bjorck I. Vinegar supplementation lowers glucose and insulin responses and increases satiety after a bread meal in healthy subjects. Eur J Clin Nutr. 2005;59:983–988. http://dx.doi.org/10.1038/sj.ejcn.1602197

19. Kondo S, Tayama K, Tsukamoto Y, Ikeda K, Yamori Y. Antihypertensive effects of acetic acid and vinegar on spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2001;65:2690–2694. http://dx.doi.org/10.1271/bbb.65.2690.

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Senka Dinarević et al� Journal of Health Sciences 2014;4(3):181-185 http://www�jhsci�ba

PROFESSIONAL ARTICLE Open Access

Modern treatment of patent ductus arteriosus – Single center experienceSenka Dinarević, Almira Kadić*, Zijo Begić, Mirza Halimić, Emina Vukas

Pediatric clinic, University clinical centre Sarajevo, Patriotske lige 81, Sarajevo, Bosnia and Herzegovina

ABSTRACT

Introduction: Transcatheter closure is a treatment choice for the most children with patent ductus arteri-osus (PDA)� The closure of the ductus is indicated in any child or adolescent with developed symptoms of significant L-R shunt� The aim of this article is to present our results in 5 years treatment of patients with PDA and their outcome�

Methods: From 2009 to 2014, 30 patients underwent a transcatheter closure of PDA at Centre for Heart and Pediatric clinic of Clinical University Centre of Sarajevo� Aortic angiogram was performed to evaluate the size, position, and shape of the duct for selection of appropriate occluder device type and size� All procedures were performed by local team of cardiologists from the Department of Cardiology, Pediatric clinic, with invasive cardiologists team from Sweden and Austria� Echocardiography was repeated at intervals of 24 hours, then 1 month, 3 months, and 1 year after the procedure to assess the outcome�

Results: Thirty patients underwent transcatheter closure of PDA during the study period� PDA of ≤ 2�0 mm was present in 8 patients and they underwent PDA closure with coils, while 22 patients had PDA diameter ≥ 2 mm, and they were treated by Amplatzer duct occluder (ADO)� Only in 2 (6�2%) patients complica-tions have been observed� The length of hospital stay after the treatment was two to three days�

Conclusion: Transcatheter closure of PDA is a modern, safe and efficient method that ensures a faster recovery of the patients, shortens the length of hospitalization�

Keywords: PDA; Transcatheter closure; occluder device; coil; ADO

INTRODUCTIONPatent Ductus Arteriosus (PDA) is a common form of congenital heart disease. Knowledge of the pathophysiology, clinical implications and manage-ment of patent ductus arteriosus (PDA) is a very

*Corresponding Author: Almira Kadić, Pediatric Clinic, University clinical centre Sarajevo, Patriotske lige 81, 71000 Sarajevo, Bosnia and Herzegovina, Tel: +39761260052, E-mail: almira�kadic@yahoo�com

Submitted September 25 2014 / Accepted December 20 2014

© 2014 Senka Dinarević et al; licensee University of Sarajevo - Faculty of Health Studies� This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons�org/licenses/by/2�0), which permits unrestricted use, distri-bution, and reproduction in any medium, provided the original work is properly cited�

important task for pediatricians-cardiologists and adult cardiologists. In the last three decades tran-scatheter closure of PDA has largely replaced surgi-cal ligation (1).PDA represents vascular structure that connects the proximal part of the descending aorta to the main pulmonary artery (MPA), localized to the left branch of the pulmonary artery (LPA). PDA appears in certain syndromes such as: Down syn-drome, Wolf-Hirschhorn syndrome, Carpenter syn-drome, Holt-Oram syndrome (2).

http://www�jhsci�ba Senka Dinarević et al� Journal of Health Sciences 2014;4(3):181-185

The incidence of PDA in term newborns is 1/2000 births, representing 5% to 10% of all congenital heart anomalies, and sex distribution is 2:1 in favor of females (3). Hemodynamic repercussions depend on ductal resistance, which are affected by the size and appearance of the duct, the pressure gradient (PG) between the aorta and pulmonary artery. Most patients are asymptomatic. If there is a larger left-right shunt (L-R shunt), there is intolerance to effort. A significant PDA that is not closed, may lead to sequelae such as congestive heart failure, pulmonary hypertension, pulmo-nary vascular obstructive disease, recurrent chest infection, ductal aneurism and an increased risk of infective endocarditis. (4-6). Echocardiography is a noninvasive diagnostic method that provides the information about hemodynamics of PDA. Transcatheter closure is the method of choice for the most children with patent ductus. The closure of the ductus is indicated in any child or adoles-cent with developed symptoms of significant L-R shunt. Asymptomatic patients with significant L-R shunt, through PDA and enlargement of the left heart cavities, are definitely in a group of patients for PDA closure, in order to prevent the develop-ment of complications (7).In patients with a small shunt - “silent” ductus, the closing should be consider due to later complica-tions. However, considering that this is a safe, effec-tive method with minimal morbidity, it is recom-mended to close the PDA at any age (8,9).Contraindications for transcatheter closure of PDA are: age of the child is less than 6 months; the pres-ence of blood clots in the heart and blood vessels, or general disorder of coagulation system; body weight less than 6 kg; presence of infection; increased pres-sure in the pulmonary artery (PA) (10).Common complications of transcatheter closure of PDA include: bleeding, arrhythmia, residual shunt, left pulmonary artery (LPA) obstruction, protrusion of the device into the aorta, embolization of the device (11,13).In this study, we are reporting our experience during past five years with PDA closure using detachable coils and Amplatzer duct occluder (ADO) and out-come of the patients.

METHODS

Study designAll patients who had undergone transcatheter clo-sure of PDA between 2009 and 2014 on Pediatric clinic and Center for Heart, University Clinical Center Sarajevo, were included in this retrospective study. 30 patients underwent transcatheter closure of PDA. All procedures were performed by local team of cardiologists from the Department of Cardiology, Pediatric clinic with a team from Sweden and Austria.The exclusion criteria included those who have been found to be not suitable for device closure after reviewing. We excluded one patient with presence of Pulmonary arterial hypertension and one that was unsuccessful.All patients had clinical evaluation and echocardio-graphic confirmation of the diagnosis. A complete diagnostic evaluation and assessment of hemody-namics (evaluation of pulmonary vascular resis-tance, type of shunt) before transcatheter closure is of a crucial importance.This was followed by an aortic angiography to eval-uate the anatomy (size, position and shape) of the ductus arteriosus for appropriate device choice for closure: type and size (Table 1). It is very important to determine the minimum and maximum diameter (aortic ampulla), the length and shape of the ductus before performing closing procedure.Size is determined by minimal ductal diameter on angiographic view.Before starting the procedure the patient must be under general anesthesia along with monitoring of vital parameters. Devices used for occlusion were detachable coils and ADOs. Detachable coils (14) were used for patients with small PDAs of ≤2.5 mm at the narrowest diameter (Figure 1A). ADOs were used for PDAs that were >2.5 mm (Figure 1B).

TABLE 1. Classification of PDA based on sizeType Description Silent PDA Less than 1.5 mm and no murmurVery small PDA ≤ 1.5 mm with audible murmurSmall PDA 1.5‑3 mm and murmurModerate PDA 3‑5 mm and murmurLarge PDA >5 mm and murmur

Protocol of PDA closure implies that patients are undergoing right and left heart catheterization, using 4Fr or 5Fr sheath, placed in the femoral artery and 6Fr sheath in the femoral vein. Heparin is administered during the procedure. After select-ing occluders (≥ 1-2 mm larger than the minimum size of a PDA), it was connected with the catheter system and submerged in sterile water to avoid the presence of air drawn into the delivery system.The coil are delivered into the main pulmonary artery. The guide wire is fixed in position and the catheter is slowly withdrawn over the wire into the descending aorta, thus extruding the remaining coil into the aortic end of the ductal ampulla.If the position is adequate, occluder is released. A second aortic angiogram was performed after device deployment. After the procedure, it is rec-ommended the next two doses of antibiotics and aspirin therapy at a dose of 2-3 mg/kg/day, which is given the next 4-6 months. Patients than had fol-low-up in Pediatric Cardiology Clinic 24 hours after procedure (vital signs, x-ray and echocardiography). Further monitoring means repeated echocardiogra-phy after 1 month, 3 months and 1 year, when eval-uation of: residual shunt, moving occluders, throm-bus, aortic or pulmonary stenosis, is performed.

RESULTSThirty patients underwent transcatheter closure of PDA during the study period. Of these, 17 (57%) were girls and 13 (43%) were boys (Figure 2).Age structure ranged of the treated patients from 1 year to 10 years. (Figure 3).Eight patients had PDA of ≤ 2.0 mm at the narrow-est diameter and they underwent PDA closure with coils and 22 patients with PDA diameter ≥ 2 mm, had their PDAs closed with ADOs (Figure 4).

After the procedure, patients with closed PDA were treated at the Department of Cardiology, Pediatric Clinic, University Clinical Center in Sarajevo. The length of hospitalization after procedure is two days (28 patients) and three days in only 2 patients.Only in 2 (6.2%) patients complications have been observed. In one patient, we detected transient myo-cardial ischemia. Device embolization occurred in one case, which is successfully retrieved back. There

FIGURE 1. Gianturco coil (cylindrical shape) (A) and Amplatzer duct occluder (B)

FIGURE 2. Sex structure of the treated patients

FIGURE 3. Age structure of the treated patients

FIGURE 4. The type of occlude used

http://www�jhsci�ba Senka Dinarević et al� Journal of Health Sciences 2014;4(3):181-185

were no significant residual PDA shunt during patients short postprocedure follow up period.

DISCUSSIONPDA closure is indicated for several reasons: pre-venting the development of bacterial endocarditis, hypertensive pulmonary disease, aneurysm forma-tion, and congestive heart failure.In the majority of the world’s cardiac centers, tran-scatheter closure of PDA is considered to be a stan-dard type of treatment (1). Even though there is no clear consensus, the advantages of transcatheter clo-sure is preferred because of the high success rates, shorter hospital stay, less blood loss, low rates of morbidity, without opening the patient’s chest. This mode of treatment is particularly suitable in cases of cardiac and respiratory diseases in which the risk of surgery is increased (15).A retrospective cohort study of nine representative publications, included in the meta-analysis from around the world, correlate benefit of different ways of treatment of PDA through a series of morpholog-ical and hemodynamic parameter (16). There was no significant difference in primary success rate and post procedure complications. The residual shunt was more frequent in the group of catheterized patients, while remarkable reduction in length of hospitalization was in catheterized patients (16 -18).Liddy et al. (19) in their retrospective study demon-strated a small percentage of residual shunt follow-ing patients after transcatheter closure, 1, 3 and 6 months (6.8, 1.7 and 1.1%). Arodiwe et al. (10) compared the success the closure of the PDA, the development of complications, using different types of occluders. Correlation analysis demonstrated that success of intervention largely depends on several factors: the experience of cardiologists, duct size, age and body weight. Diameter and morphology of the ductus had affected the selection of occluder type and success. Development of complications was similar in both groups (coil and ADO).Our study of 30 patients showed that the transcath-eter closure of PDA has a great success, with a low complication rate. Follow up of all patients with implanted occluders requires a serious approach of well-trained cardiologist, who will on time recognize

any deviations in the positions and changing of hemodynamics.

CONCLUSIONIn our five years experience in the treatment of PDA by transcatheter closure, this method demonstrated fast patient recovery, shorter length of hospitaliza-tion and no residual shunt on follow up.

CONFLICT OF INTERESTSThe authors declare no conflict of interest.

REFERENCES1. Gray DT, Fyler DC, Walker AM, et al. Clinical outcomes and costs of

transcatheter as compared with surgical closure of patent ductus arte‑riosus. N Engl J Med. 1993;329:1517–1523. http://dx.doi.org/10.1056/NEJM199311183292101.

2. Nora JJ. Multifactorial inheritance hypothesis for the etiology of congenital heart diseases: the genetic‑environmental interaction. Circulation. 1968; 38: 604–617. http://dx.doi.org/10.1161/01.CIR.38.3.604.

3. Lloyd TR, Beekman RH III. Clinically silent patent ductus arteriosus. Am Heart J. 1994; 127: 1664–1665 http://dx.doi.org/10.1016/0002-8703.

4. Dyamenahalli U, Smallhorn JF, Geva T, Fouron JC, Cairns P, Jutras L, Hughes V, Rabinovich M, Mason CA, Hornberger LK. Isolated ductus arteriosus aneurysm in the fetus and infant: a multi‑institutional expe‑rience. J Am Coll Cardiol. 2000; 36: 262–269. http://dx.doi.org/10.1016/S0735‑1097(00)00707‑5.

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7. Fisher RG, Moodie DS, Sterba R, Gill CC. Patent ductus arterio‑sus in adults—long term follow-up: nonsurgical vs surgical treat‑ment. J Am Coll Cardiol. 1986; 8: 280–284. http://dx.doi.org/10.1016/S0735‑1097(86)80040‑7.

8. Verin VE, Saveliev VS, Kolody SM, Prokubovski VI. Results of transcatheter closure of the patent ductus arteriosus with the Botalloocluder. J Am Coll Cardiol 1993;22:1509 –14. http://dx.doi.org/10.1016/0735‑1097(93)90564‑H.

9. Moore JW, George L, Kirkpatrick SE, et al. Percutaneous closure of the small patent ductus arteriosus using occluding spring coils. J Am Coll Cardiol 1994;23:759–65. http://dx.doi.org/10.1016/0735‑1097(94)90765‑X.

10. O. Arodiwe, D. K. Adiele, J. M. Chinawa, V. Gouthami, K. S. Murthy, E. O. Obidike, et al.; Clinical Study of Trans-catheter Closure of Patent Ductus Arteriosus with Occluder Devices among Children Aged 9 Months to 18 Years International Journal of TROPICAL DISEASE & Health4(1): 31-44, 2014.

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occlusion for patent ductus arteriosus: a matched cohort study of out‑comes and cost; Surg Endosc 2008; 22:1643. http://dx.doi.org/10.1007/s00464‑007‑9674‑1.

14. U.S. Food and Drug Administration Medical Devices. Devices/Products and Medical Procedures/Device Approvals and Clearances/default.htm (Accessed on January 20, 2014).

15. Sheridan BJ, Ward CJ, Anderson BW, et al. Transcatheter closure of the patent ductus arteriosus: an intention‑to‑treat analysis. Heart Lung Circ. 2013;22:428–432. http://dx.doi.org/10.1016/j.hlc.2012.12.007.

16. Hawkins JA, Minich LL, Tani LY, et al. Cost and efficacy of surgical ligation versus transcatheter coil occlusion of patent ductus arteriosus. J Thorac

Cardiovasc Surg. 1996;112:1634–1639. http://dx.doi.org/10.1016/S0022‑5223.

17. Li T, Pan GT, Yang Y. The comparison between percutaneous transcath‑eter Amplatzer occluder and surgical closure in patent ductus arteriosus patients. Clin Med. 2003;23:23.

18. Ruan J, Deng XH, Chen J, et al. Comparison between Amplatzer duct occluder and surgical closure on patent ductus arteriosus. Guangxi Med J. 2006;28:2.

19. Liddy S, Oslizlok P, Walsh KP. Comparison of the results of transcatheter closure of patent ductus arteriosus with newer amplatzer devices. Catheter Cardiovasc Interv. 2013;82:253–259 http://dx.doi.org/10.1002/ccd.24768.

jhsci-2014-4-3

university of ljubljana

university of osijek

universityof sarajevo

trnava university of

department of microbiology

department of pathology

department of radiotherapy

department of pediatrics

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