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Use of colposcopy for detection of squamous intraepithelial lesions FEĐA OMERAGIĆ, AZUR TULUMOVIĆ, ERMINA ILJAZOVIĆ, AMELA ADŽAJLIĆ, ALIJA ŠUKO, LARISA MEŠIĆ ĐOGIC, VLADIMIR PERENDIJA .............................................................72-76 The evaluation of B-type Natriuretic Peptide and Troponin I in acute myocardial infarction and unstable angina NAFIJA SERDAREVIC, AZRA DURAK-NALBANTIC ............................................................................. 77-82 Prevalence of behavioral risk factors of non-communicable diseases among urban and rural population in the Federation of Bosnia and Herzegovina AIDA PILAV, AIDA RUDIĆ, SUADA BRANKOVIĆ, VILDANA DODER................................................... 83-89 Nurses’ knowledge and responsibility toward nutritional assessment for patients in intensive care units MAHMOUD AL KALALDEH, MAHMOUD SHAHEIN.......................................................................... 90-96 The effects of education and training on self-esteem of nurse leaders ANDREJA KVAS, JANKO SELJAK ..................................................................................................... 97-104 Influence of coffee consumption on bone mineral density in postmenopausal women with estrogen deficiency in menstrual history AMILA KAPETANOVIĆ, DIJANA AVDIĆ ........................................................................................... 105-109 Evaluation of the treatment efficacy of patients with multiple sclerosis using Barthel index and expanded disability status scale EDINA TANOVIĆ, DŽEVAD VRABAC, ALDIJANA KADIĆ, ADMIR RAMA, HARIS TANOVIĆ ................. 110-113 Adherence to oral anticoagulation therapy LANA LEKIĆ, ALEN LEKIĆ, ALDEN BEGIĆ ......................................................................................... 114-119 Knowledge, perception, practices and barriers of healthcare professionals in Bosnia and Herzegovina towards adverse drug reaction reporting and pharmacovigilance MAŠA AMRAIN, FAHIR BEČIĆ ......................................................................................................... 120-125 Mental foramen mimicking as periapical pathology - A case report ANUSHA RANGARE LAKSHMAN, SHAM KISHOR KANNEPADY, CHAITHRA KALKUR ....................................................................................................................... 126-129 Gastric antral vascular ectasia: A case report AMIR ĆEHAJIĆ, DENIS MAČKIĆ, ELVIRA DŽAMBASOVIĆ, FARUK ČUSTOVIĆ, AIDA MUJAKOVIĆ, NIJAZ TUCAKOVIĆ.............................................................. 130-133 Table of contents: RESEARCH ARTICLES CASE REPORTS
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Page 1: JHSCI-2014-v4-i2-september

Use of colposcopy for detection of squamous intraepithelial lesionsFEĐA OMERAGIĆ, AZUR TULUMOVIĆ, ERMINA ILJAZOVIĆ, AMELA ADŽAJLIĆ,ALIJA ŠUKO, LARISA MEŠIĆ ĐOGIC, VLADIMIR PERENDIJA .............................................................72-76

The evaluation of B-type Natriuretic Peptide and Troponin I in acutemyocardial infarction and unstable anginaNAFIJA SERDAREVIC, AZRA DURAK-NALBANTIC ............................................................................. 77-82

Prevalence of behavioral risk factors of non-communicable diseases amongurban and rural population in the Federation of Bosnia and HerzegovinaAIDA PILAV, AIDA RUDIĆ, SUADA BRANKOVIĆ, VILDANA DODER ................................................... 83-89

Nurses’ knowledge and responsibility toward nutritional assessmentfor patients in intensive care unitsMAHMOUD AL KALALDEH, MAHMOUD SHAHEIN .......................................................................... 90-96

The effects of education and training on self-esteem of nurse leadersANDREJA KVAS, JANKO SELJAK ..................................................................................................... 97-104

Infl uence of coffee consumption on bone mineral density inpostmenopausal women with estrogen defi ciency in menstrual historyAMILA KAPETANOVIĆ, DIJANA AVDIĆ ........................................................................................... 105-109

Evaluation of the treatment effi cacy of patients with multiple sclerosisusing Barthel index and expanded disability status scaleEDINA TANOVIĆ, DŽEVAD VRABAC, ALDIJANA KADIĆ, ADMIR RAMA, HARIS TANOVIĆ ................. 110-113

Adherence to oral anticoagulation therapyLANA LEKIĆ, ALEN LEKIĆ, ALDEN BEGIĆ ......................................................................................... 114-119

Knowledge, perception, practices and barriers of healthcareprofessionals in Bosnia and Herzegovina towards adverse drugreaction reporting and pharmacovigilanceMAŠA AMRAIN, FAHIR BEČIĆ ......................................................................................................... 120-125

Mental foramen mimicking as periapical pathology - A case reportANUSHA RANGARE LAKSHMAN, SHAM KISHOR KANNEPADY,CHAITHRA KALKUR ....................................................................................................................... 126-129

Gastric antral vascular ectasia: A case reportAMIR ĆEHAJIĆ, DENIS MAČKIĆ, ELVIRA DŽAMBASOVIĆ,FARUK ČUSTOVIĆ, AIDA MUJAKOVIĆ, NIJAZ TUCAKOVIĆ .............................................................. 130-133

Table of contents:

RESEARCH ARTICLES

CASE REPORTS

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An extremely rare case of testicular malign neoplasm; alveolar subtypeof rhabdomyosarcoma with long term follow-upTUMAY IPEKCI, YIGIT AKIN, BURAK HOSCAN, AHMET TUNCKIRAN ................................................ 134-135

LETTERS TO EDITOR

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http://www.jhsci.ba Feđa Omeragić, et al. Journal of Health Sciences 2014;4(2):72-76

Journal of Health Sciences

RESEARCH ARTICLE Open Access

Use of colposcopy for detection of squamous intraepithelial lesionsFeđa Omeragić1,2*, Azur Tulumović1,3, Ermina Iljazović1,4, Amela Adžajlić5, Alija Šuko6, Larisa Mešić Đogic7, Vladimir Perendija8

1Department of Gynecology and Obstetrics, University of Tuzla Medical Faculty, Tuzla, Bosnia and Herzegovina, 2Obstetrics and Gynecology Practice “Omeragić”, Tuzla, Bosnia and Herzegovina, 3Obstetrics and Gynecology Clinic, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina, 4Institute for Pathology, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina, 5Obstetrics and Gynecology Department, Health Centre Tuzla, Tuzla, Bosnia and Herzegovina, 6Obstetrics and Gynecology Department, Cantonal Hospital “Dr Safet Mujić”, Mostar, Bosnia and Herzegovina, 7Obstetrics and Gynecology Department, General Hospital, Tešanj, Bosnia and Herzegovina, 8Obstetrics and Gynecology Department, Clinical Centre, Banjaluka, Bosnia and Herzegovina

ABSTRACT

Introduction: Pap smear, the main tool of cervical cancer screening is not always available, but some patients are in urgent need for proper diagnostic. Aim of this article was to investigate accuracy of colpos-copy for detection of squamous intraepithelial lesions of low or high grade (LGSIL, HGSIL) and to promote colposcopy as useful tool for detection of patients in need for immediate further diagnostics.

Methods: Prospective multicentric study performed in B&H in 2012-2014 included 87 patients with colpo-scopic images related to squamous intraepithelial lesion (SIL) who formed experimental group: 56 patients with colposcopic images related to LGSIL and 31 patients related to HGSIL. Control group included 50 patients without colposcopic abnormalities. To test accuracy of colposcopy, PAP smear and histology were used. For statistical analysis χ2 was used.

Results: 94.5% patients in experimental group had abnormal PAP test: 64.3% correlated to LGSIL (χ2 = 60.48 P < 0.0001), while 64.5% correlated to HGSIL (χ2 = 54.23 P < 0.0001) Odds Ratio = 490; 95% CI = 42.024 to 5713.304). HGSIL was confi rmed in 27 (87%) cases by histology (CIN II/CIN III). There were no statistically signifi cant differences between colposcopic fi nding and histology results (Yates-corrected χ2 = 0.33 P = .5637).

Conclusions: This study showed high level of correlation between colposcopy and PAP results (63-64%) and to histology for HGSIL (87%). In absence of PAP test colposcopy could be used to select patients in need for biopsy.

Keywords: Papanicolaou test; cervical intraepithelial neoplasia; colposcopic surgical procedures

*Corresponding author: Feđa Omeragić, M. Tita 157, 75000 Tuzla, Bosnia and Herzegovina Phone: +387 35 262 622 E-mail: [email protected]

Submitted March 27 2014 / Accepted June 1 2014

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Feđa Omeragić, 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.

INTRODUCTIONSquamous intraepithelial lesion (SIL) starts at the cellular level as transformation and abnormal growth of squamous cells on the surface of the cer-vix. In  the cervical channel intraepithelial lesion

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starts as squamous metaplasia, which includes proliferation of undiff erentiated reserve cells, columnar cells and their transformation into the squamous cells. SIL begin as cellular change at low grade level (LGSIL) and during the time could advance to high grade lesion (HGSIL) and cervi-cal cancer. When detected, SIL can be successfully treated at any stage. It is well known and scien-tifi cally proven fact that cervical cancer screening program decreases incidence of cervical cancer by detecting early stages of intraepithelial changes (SIL) using PAP test as main tool (1). For the patients with abnormal PAP smear, colposcopy is usually the next step. However, what happens if the cervical cancer screening is not available and there is lack of information about disease prevention possibility? What happens if PAP control depends only on patients’ awareness of disease? In such cir-cumstances usually, incidence of inoperable cer-vical cancer is very high. Where does Bosnia and Herzegovina stand in this respect?Health system in Bosnia and Herzegovina does not provide cervical cancer screening at the any level (State level, Entity level, Cantonal level). System for education of patients does not exist. Even more, there is no cancer database. First offi cial reports about cancer incidence including cervical can-cer were published by Public Health Institute of Federation Bosnia and Herzegovina (PBIFB&H) in 2007. According to that Report cervical can-cer is second most common cancer in females in the Federation Bosnia and Herzegovina (FB&H). Furthermore in the period 1996  -2007 there were 20-25/100.000 newly detected cervical cancers in Tuzla Canton. Only 20.3% of those cases were in operable stages (2).If we do not have cervical cancer screening program and if we cannot provide a PAP test as frequently as needed (due to lack of means), could we use colpos-copy to select patients who are in need for a kind of “immediate” PAP smear or even biopsy?Th e aim of this article was to investigate accuracy of colposcopy for detection of squamous intraepi-thelial lesions (SIL) and to promote colposcopy as tool for detection of patients in need for immediate PAP smear in the health systems without screening program.

METHODSStudy designTh is was prospective multi-centric study that took a place in Obstetrics and Gynecology practice Omeragić, Tuzla, Health Centre of Tuzla, Health Centre Teašanj, Cantonal Hospitals of Mostar and Clinical Centre Banjaluka, during the period January 2012 to January 2014.

PatientsTh e patients in the study were selected in accor-dance to colposcopic criteria for squamous intraep-ithelial lesions.Experimental group marked as Group A was formed by 87 patients. Th ey were selected by means of col-poscopy which showed one or more coploscopic images (markers) related to squamous intraepithelial lesion (SIL).Colposcopic assessment of lesions was based on the following characteristics: location of the lesion related to Transformation zone (within or outside of the Transformation zone), reaction to 3-5% solu-tion of acetic acid, color intensity, surface and bor-ders, vascularization (inter-capillary distance), speed of emergence and time of duration.Group A was divided in two subgroups: A1 and A2. Subgroup A1 included 56 patients with colposcopic images that are clearly defi ned as characteristics of LGSIL. Subgroup A2 included 31 patients with col-poscopy images that are clearly defi ned as charac-teristics of HGSIL. Extensive lesion that was spread over the broad area of surface of the cervix, in the same time, was indication for biopsy.A group of 50  patients without any colposcopic changes related to SIL formed Control group marked as Group B.

To test accuracy of colposcopy1. PAP smear that was taken from all patients

including experimental and control group was analyzed. Results were interpreted using Bethesda system: BCC  -  Benign Cellular Changes, ASCUS-atypical squamous cells undetermined signifi cance, ASC H-  atypical squamous cell which does not exclude HGSIL, LGSIL-low grade squamous cell intraepithelial

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lesion, HGSIL-high grade squamous cell intraepithelial lesion (3).

2. Colposcopy directed biopsy was done in all patients from Subgroup A2. Histological results were analyzed as well.

Previous colposcopy and/or PAP smear were with-out any abnormality and were not taken 24 months prior to the beginning of the study. Cancers of any stage were not included in the study. Patients with unclear fi nding were not included in study.

Statistical analysisResults were analyzed by descriptive and analytical statistics. Chi  square test with or without Yates correction, Odds ratio, Fischer exact test were used. Th e level of signifi cance was defi ned as p<0.05. For statistical analysis software GrahPad Prism 6 for Windows, version 6 was used.

RESULTSExperimental group and control group were homog-enous. Th ere were:1. similar participation of nulliparous Group A 31

or 35%, Group B 16 or 32%,2. similar distribution within the age groups

20-50 year3. similar participation of those who previously

did not have PAP smear and colposcopy Group A 31 or 35% and Group B 19 or 38%.

In experimental group (Group  A) there were 87 patients with single or multiply markers for SIL. Out of all 82 (94.2%) had abnormal PAP test results including all varieties of Bethesda nomenclature.In control group (Group  B) out of all, 17  (34%) patients had abnormal PAP test. Diff erence is sta-tistically signifi cant (χ2 = 18.91 P < 0.0001: Odds Ratio = 3.027; 95% CI = 1.851 to 4.951) According to statistical analysis it means that patient with posi-tive colposcopic markers for SIL have 3 times higher chances to have abnormal PAP test (Figure 1).Out of all patients in experimental group there were 56  patients with colposcopic images defi ned as markers for LGSIL. Th ey formed Subgroup A1. Th ose patients had markers located within the trans-formation zone (100%). Aceto-white (AW) epithe-lium was the most frequently seen (53 or 94.6%)

as a single marker (50 or 89.3%) or associated with vascular changes, mosaic (M) or/and punctuation (P) (3 or 5.35%).When detected outside of Transformation zone (31  patients) more than one markers were seen most often. Aceto-white epithelium (AW) is most frequently seen, but only in two cases as a sin-gle marker (6.4%). Vascular changes (Mosaic, Punctuations) associated with AW epithelium were present in 29  (93.5%) cases. Th ese images (mark-ers) are defi ned as colposcopic criteria for HGSIL. Patients with such images formed Subgroup  A2 (Table 1). PAP smear was performed in all patients includ-ing control group. Distribution of PAP diagno-sis (Bethesda categories) per groups was shown in Table 2.Correlation between colposcopy and PAP diagnosis is shown of Figure 2.In control group there were 17 (34%) PAP results marked as abnormal. In 12  (24%) cases it was ASC-US, atypical cells were related to infl ammation or lack of hormonal activity, while only 8% had SIL.

FIGURE 1. PAP test results in experimental and control group.

FIGURE 2. Results of PAP test compared to colposcopy results.

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ASCUS was also seen in subgroups A1 (7.1%) and A2 (3.2%).Analysis of LGSIL and HGSIL results showed signifi cant diff erences compared to control group LGSIL (χ2 = 60.48 P < 0.0001); Odds Ratio = 141; 95% CI = 29.670 to 670.067), HGSIL (χ2 = 54.23 P < 0.0001 Odds Ratio = 490;95% CI = 42.024 to 5713.304) which means that chances for LGSIL or HGSIL in PAP test are very high if colposcopy result are positive too.All thirty-one (31) patients with extensive cervical tissue deterioration diagnosed by colposcopy as HGSIL (Subgroup  A2) had biopsy. Th e following correlation between colposcopy and histopathology diagnosis was noticed (Table 3).Th ere are no statistically signifi cant diff erences between colposcopic fi nding and histology results (Yates-corrected χ2 = 0.33 P =.5637) but there is a four times higher possibility that histology will show cervical intraepithelial lesion of medium grade (CIN II) and two times higher possibility that his-tology will show high grade dysplasia (CIN  III) [Odds Ratio = 2.086; 95% CI (logit method)=

0.627202 to 6.940587] if colposcopic images related to HGSIL are present [Odds Ratio = 4; 95% CI (logit method) = 0.362 to 44.112].

DISCUSSIONCorrelation between colposcopy and PAP, includ-ing all varieties of Bethesda nomenclature is high. Out of all 94.2% patient had both colposcopy and PAP results abnormal. According to statistical analyses patient with present colposcopic images (markers) for SIL have 3  times higher chances to have abnormal PAP test. Such results show that col-poscopy markers have high accuracy in detection of cellular pathology. High level of correlation is reported by other researches (3-6). PAP test results correlate with colposcopic staging, too: 64.3% for LGSIL (χ2 = 60.48 P < 0.0001), 64.5% for HGSIL (χ2 = 54.23 P < 0.0001). In literature similar results are shown. Parvin at all reported correlation in 76.1% patients. Koigi-Kamau R at all reported cor-relation in 59-65% cases (7-9).Biopsy or Loop excision of transformation zone (LETZ) was performed in 31  patients from sub-group A2/HGSIL. Medium and high grade intraep-ithelial dysplasia (CIN II/CIN III) were found by histology in 87% cases. Th ere are no statistically sig-nifi cant diff erences between colposcopic fi nding and histology results (Yates-corrected χ2 = 0.33 P = .5637). Correlation between colposcopic fi ndings and histol-ogy studied by many researchers showed high level of correlation. Savage EW at all reported accuracy of directed biopsies in 96% cases (10). Boelter WC 3rd at all found 96 - 98% correlation between the col-poscopic fi ndings, biopsies and cone specimens (11). Recent study by Boicea A at all showed correlation of 78.5% in the CIN I category, 84% in the CIN II cat-egory, 88.6% in the CIN III category (12).ASC-H was detected in 12% patients in Group A. However, ASC-H does not exclude LG or HG SIL (13-17). In the same time 34% abnormal PAP smear results in control group additionally confi rm hypothesis that the tissue architecture is not necessarily deteriorated from the beginning, partic-ularly in cases of HPV infection.Th ose patients were selected for intense fol-low-up. Same protocol were reported by other researchers (14,18,19).

TABLE 1. Frequency of the basic colposcopic images (markers)

AW EpitheliumN (%)

MosaicN (%)

PunctationN (%)

Total

*Subgroup A1 53 (94.6) 1 (1.78) 1 (1.78) 56**Subgroup A2 31 (100) 28 (90.3) 29 (83.5) 31*Colposcopic images related to LGSIL; **Colposcopic images related to HGSIL

TABLE 2. PAP test resultsGroups BCC

N (%)ASC-US

N (%)ASC-HN (%)

LGSILN (%)

HGSILN (%)

*Subgroup A1 4 (7.1) 6 (10.7) 8 (14.3) 36 (64.3) 2 (3.5)**Subgroup A2 1 (3.2) 2 (6.4) 3 (9.6) 4 (12.9) 20 (64.5)†Group B 33 (66) 12 (24) 1 (2) 3 (6) 1 (2)*Colposcopic images related to LGSIL; **Colposcopic images related to HGSIL; †No colposcopic abnormalities

TABLE 3. Results of histology - Subgroup A2*Lesion CIN I

N (%)CIN IIN (%)

CIN IIIN (%)

Patients 2 (6.4) 18 (58) 11 (35.4)*Subgroup A2, Colposcopic images related to HGSIL

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CONCLUSIONSColposcopy is useful method for detection of early stages of SIL. Th is study showed high level of cor-relation between colposcopy and both, PAP test and histology. In the absence of cancer screening pro-gram and regular frequency of PAP smear diagnos-tics or if PAP test is not available, it can be used as a non-invasive, inexpensive and accurate tool.

CONFLICT OF INTERESTTh e authors declare no confl ict of interest. No spe-cifi c funding was received for this study.

REFERENCES1. Massad LS, Einstein MH, Huh WK et al. 2012th Updated Consensus

Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis 2013;17(5):S1-S27 http://dx.doi.org/10.1097/LGT.0b013e318287d329.

2. Iljazović E, Kesić V. Patologija cervikalne epitelne neoplazije. Univerzitet u Tuzli. Grin, Gračanica; 2011.

3. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: termi-nology for reporting results of cervical cytology. JAMA. 2002;28(16):2114–9 http://dx.doi.org/10.1001/jama.287.16.2114.

4. Singer A, Monaghan J. M, QuekS.C., Deery A.R.S. Lower Genital Tract Precancer.Turin Italy: Bleckwell Science Ltd; 2000 http://dx.doi.org/10.1002/9780470760093.

5. González SJL, Pérez GC, Celorio AG, Chávez BJ, Ríos MFA. Cytologic correlation between the Bethesda system and colposcopy biopsy. Ginecol Obstet Mex.1998;66:330-4.

6. Cervical cancer in adolescents: screening, evaluation, and manage-ment. Committee Opinion No. 463. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2010;116:469–72 http://dx.doi.org/10.1097/AOG.0b013e3181eeb30f.

7. Parvin S, Kabir N, Lipe YS, Nasreen K, Nurul- Alam KM. Correlation of pap smear and colposcopic fi nding of cervix with histopatholgiocal report in a group of patient attending in a tertiary hospital. J Dhaka Medical College. 2013;22(1):39-44 http://dx.doi.org/10.3329/jdmc.v22i1.15604.

8. Koigi-Kamau R, Kabare LW, Machoki JM. Impact of colposcopy on man-agement outcomes of patients with abnormal cervical cytology. East Afr Med J. 2007;84(3):110-6.

9. Gadre SS, Gupta SG, Gadre AS. Descriptive analytical study looking for agreement between colposcopic cervical fi ndings and cervical exfoliative cytology. Int J Reprod Contracept Obstet Gynecol. 2013;2(3):402-405 http://dx.doi.org/10.5455/2320-1770.ijrcog20130928.

10. Savage EW. Correlation of colposcopically directed biopsy and conization with histologic diagnosis of cervical lesions. J Reprod Med.1975;15(6):211-3.

11. Boelter WC 3rd, Newman RL. The correlation between colpo-scopic grading, directed punch biopsy and conisation. Am J Obstet Gynecol.1975;122(8):945.

12. Boicea A, Pătraşcu A, Şurlin V, Iliescu D, Schenker M, Chiuţu L. Correlations between colposcopy and histologic results from colposcop-ically directed biopsy in cervical precancerous lesions Rom J Morphol Embryol. 2012;53(3):735–741.

13. Sherman ME, Castle PE, Solomon D. Cervical cytology of atypical squa-mous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H): characteristics and histologic outcomes. Cancer 2006;108:298–305 http://dx.doi.org/10.1002/cncr.21844.

14. Apgar BS, Kittendorf AL, Bettcher CM, Wong J, Kaufman AJ. Update on SCCP consensus guidelines for abnormal cervical screening tests and cervical histology. Am Fam Physician 2009;80:147-155.

15. American Society for Colposcopy and Cervical Pathology. Management of women with atypical squamous cells of undetermined signifi cance (ASC-US). Hagerstown (MD): ASCCP; 2007.

16. Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined signifi cance. JAMA 2002;287:2382 http://dx.doi.org/10.1001/jama.287.18.2382.

17. Darragh TM, Colgan TJ, Thomas Cox J, et al. The Lower Anogenital Squamous Terminology Standardization project for HPV-associated lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Int J Gynecol Pathol 2013;32:76 http://dx.doi.org/10.1097/PGP.0b013e31826916c7.

18. Waxman AG, Chelmow D, Darragh TM, et al. Revised terminology for cervi-cal histopathology and its implications for management of high-grade squa-mous intraepithelial lesions of the cervix. Obstet Gynecol. 2012;120:1465.

19. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC CancerBase No.10 Lyon, France: International Agency for Research on Cancer; 2010.[cited 2013 October 28]. Available from: http://globocan.iarc.fr.

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Journal of Health Sciences

RESEARCH ARTICLE Open Access

The evaluation of B-type Natriuretic Peptide and Troponin I in acute myocardial infarction and unstable anginaNafi ja Serdarevic1*, Azra Durak-Nalbantic2

1Institute for Clinical Chemistry and Biochemistry, Faculty of Health Sciences, University Clinical Centre Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina, 2Clinic for Hearth Disease and Rheumatism, University Clinical Centre Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina

ABSTRACT

Introduction: The diagnostic utility of B-type natriuretic peptide (BNP) has prompted interest in its use as an aid in the detection of early heart failure and assessment of diseases. The fi rst objective of this study was measurement of BNP and troponin I (TnI) blood levels in patients with acute myocardial infarction (AMI) and unstable angina. The second objective of this study was to fi nd a correlation between TnI and BNP in blood.

Methods: The concentrations of BNP and TnI in 150 blood levels were determined using CMIA (chemilu-minescent microparticle immunoassay) Architect and 2000 (Abbott diagnostics). The retrospective study included 100 patients who were hospitalized at the Department of Internal Medicine of the University Clinical Center Sarajevo and 50 healthy control. The reference blood range of BNP is 0-100 pg/mL and TnI is 0.00-0.4 ng/mL.

Results: In the patients with AMI the mean value of BNP is 764.48 ± 639.52 pg/mL and TnI is 2.50 ± 2.28 ng/mL. The patients with unstable angina have BNP 287.18 ± 593.20 pg/mL and TnI 0.10 ± 0.23 ng/mL. Our studies have shown that the correlation between BNP and TnI was statistically signifi cant for p < 0.05 using Student t test with correlation coeffi cient r = 0.36.

Conclusions: BNP and TnI levels can help to identify the patients with a high risk for cardiovascular diseases.

Keywords: BNP; TnI; acute myocardial infarction; unstable angina

INTRODUCTIONSince the discovery of the natriuretic peptides in the 1980s and their subsequent introduction into

clinical laboratory testing in the 2000s, assays of B-type Natriuretic peptides (BNP) have gained widespread acceptance as important tools for diagnosis and risk stratifi cation in the acute-care setting (1,2). BNP was fi rst isolated from porcine brain tissue, but heart has been determined to be the major source. It is synthesized and released in the blood in response to volume overload or condi-tions that cause ventricular stretch, to control fl uid and electrolyte homeostasis by interaction with

*Corresponding author: Assistant Professor Nafi ja Serdarevic, PhD.,Institute for Clinical Chemistry and Biochemistry, University Clinical Centre Sarajevo, Faculty of Health Sciences, Bolnička 25, 71000 Sarajevo, Bosnia and HerzegovinaE-mail: serdarevicnafi [email protected]

Submitted June 20 2014 / Accepted August 30 2014

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Nafi ja Serdarevic and Azra Durak-Nalbantic; 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.

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renin-angiotensin-aldosterone system. Pre-proBNP (134 amino acids) is synthesized in the cardiac myo-cytes and it is processed to a proBNP (108 amino acids) precursor molecule.BNP is realized from cardiac myocytes due to their stretching, volume overload and high fi lling pressure (3-5). It is a neurohormone produced in the ventricular myocardium in response to dilatation and pressure overload, and its plasma concentration cor-relates with the magnitude of pressure and/or volume overload. As markers of neurohormonal activation, BNP and NT-proBNP were subsequently studied within clinical trials of acute coronary syndrome (ACS) as adjuncts to risk stratifi cation and have been associated with short and long term mortality in (ACS) patients, even after adjusting for the pres-ence of congestive heart failure (6,7). Th e levels of BNP increase with decreasing functional capacities and elevated levels in the patients with heart failure (HF) indicate disease progression. BNP levels are very high in the patients with HF, but remain low in the patients with acute dyspnea due to other causes such as chronic obstructive pulmonary disease, asthma or obesity. Plasma BNP values increase with increasing age and are higher in women than in men (2).Unstable angina, for example is a common transi-tory phase of coronary ischemia, bordering on myo-cardial infarction (MI). It is a strong relationship with BNP and outcomes in ACS patients (8).It has been previously reported that 21% of ambu-latory patients with established chronic heart failure who are stable may have plasma BNP levels less than 100 pg/mL. All commercially available BNP assays incorporate the value 100 pg/mL as the diagnos-tic cut off (9). If BNP level is 100-500 pg/mL that requires further diagnostic evaluation (“grey zone”). If BNP is higher than 500 pg/mL there is probabil-ity of the hearth failure (10).Troponins I, T and C are structural proteins bound to the thin fi laments (actin) in striated muscle. A small amount (5-8%) of troponin exists free in the cytosol. Elevated levels of cTnI (above the values established for non-MI specimens) are detectable in serum within 4 to 6 hours after the onset of chest pain, reach peak concentration in approximately after 8 to 28 hours, and remain elevated for 3 to 10 days following MI. Cardiac troponin is the preferred biomarker for the

detection of myocardial injury based on improved sensitivity and superior tissue-specifi city compared to other available biomarkers of necrosis, including CK-MB, myoglobin, lactate dehydrogenase, and others. Th e high specifi city of cTnI measurements is benefi cial in identify cardiac injury for clinical condi-tions involving skeletal muscle injury resulting from surgery, trauma or muscular disease (11). Th e Joint European Society of Cardiology/American College of Cardiology/American Heart Association/World Heart Federation Task Force redefi nition of acute myocardial infarction (AMI) is predicated on the detection of increase or decrease of cardiac troponin (cTn), with at least 1 concentration above the 99th presence reference value in patients with evidence of myocardial ischemia. Blood samples for measurement of cTn are recommended to be drawn at presentation and 6-9 h later to optimize clinical sensitivity for rul-ing in AMI (12,13). Th e reference range for troponin I (TnI) in serum is 0.00-0.032 μg/mL.In our study we have measured BNP and TnI blood levels in the patients with ACS in a fi rst 12 hours and investigate correlation with peak value of TnI.

METHODS

PatientsOur research included patients (n  =  100) and 50 healthy control group in period from January till September 2011. Th e retrospective study included patients who were hospitalized at the Heart Disease Department at the University Clinical Center Sarajevo. In our study we included patients with acute myocardial infarction (AMI) and unstable angina. Th e clinical spectrum of ACS consists of ST elevated myocardial infarction (STEMI) and non-ST elevated myocardial infarction (NSTEMI)/or unstable angina (UA), which are classifi ed using electrocardiography (ECG) changes. Th e study included patients who had a level of BNP more than 100 pg/mL and level of TnI more than 0.032 μg/mL. Our research included determination of BNP and TnI in blood of patients in a fi rst 12 hours of ACS symptoms.Th e healthy control group included patients with-out AMI and unstable angina using electrocardi-ography (ECG), BNP level < 100 pg/mL and TnI level <0.032  μg/mL. Th e patients with history of

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pulmonary thromboembolism, acute and chronic renal failure, end stage renal disease, sepsis, liver cirrhosis, chronic obstructive lung disease, hyper-thyroidism and adult respiratory distress syndrome were excluded from the study. Th e research was done respecting ethical standards in the Helsinki Declaration.

Specimen preparationNa-EDTA plasma should be used for the Architect BNP assay. Samples should be collected in plastic collection tubes, because the BNP molecule has proven to be unstable in glass containers. Specimens containing blood cells or particle matters may give inconsistent results and must be clarifi ed by centrif-ugation prior to testing. Specimens with BNP assay value exceeding 5000.0 pg/mL are fl agged with the code “>5000.0 pg/mL ” and may be diluted using the Automated Dilution Protocol. Th e samples for determination of TnI should be collected in the tubes with gel. Th e TnI assay concentration greater than 50 ng/mL may be diluted using the Automated Dilution Protocol. Th e patients’ samples of blood were collected in Na-EDTA and gel Vacutainer test tubes (Becton Dickinson, Rutherford, NJ 07,070 U.S.) in volume of 3.5 mL.

AssaysAll immunoassays require the use of labeled material in order to measure the amount of antigen or anti-body. A label is a molecule that will react as a part of the assay, so that a change in signal can be measured in the blood after added reagent solution. CMIA is a noncompetitive sandwich assay technology to mea-sure analytes. Th e amount of signal is directly propor-tional to the amount of analyte present in the sample.

Chemiluminescent microparticle immunoassay – CMIAArchitect BNP or TnI assay is a two-step immuno-assay to determine the presence of BNP and TnI in human blood using CMIA technology. As a fi rst step, sample, assay diluent and anti-antibody-coated paramagnetic particles are combined. BNP or TnI present in the sample binds to the anti-coated micro-particles. After incubation and wash, anti-acridini-um-labeled conjugate is added in the second step.

Following another incubation and wash, pre-trigger and trigger solutions are then added to the reaction mixture. Th e pre-trigger solution (hydrogen peroxide) creates an acidic environment to prevent early release of energy (light emission), helps to keep microparticles from clumping and splits acridinium dye off the con-jugate bound to the microparticle complex (this action prepares the acridinium dye for the next step). Th e trigger solution (sodium hydroxide) dispenses to the reaction mixture. Th e acridinium undergoes an oxi-dative reaction when it is exposed to peroxide and an alkaline solution. Th is reaction causes the occurrence of chemiluminescent reaction. N-methylacridone forms and releases energy (light emission) as it returns to its ground state. Th e resulting chemiluminescent reaction is measured as relative light units (RLU). A  direct relationship exists between the amount of BNP in the sample and RLU detected by Architect System optics. Th e concentration of BNP or TnI will be read relative to a standard curve established with calibrators of known BNP and TnI concentration.

Statistical analysisTh e results were statistically analyzed using NCSS and statistical software SPSS version 12.0 software, determined by the average value (x–), standard devia-tion (SD) or median and interval. Th e date were not distributed normally we use Mann Whitney U-test. Pearson correlation test was used to assess associa-tion between measured parameters. P – Values less than <0.05 was considered as statistically signifi cant.

RESULTSTh e serum concentrations of BNP and TnI in the patients with AMI (acute myocardial infarction) and unstable angina are shown in Table 1. Th e study included 100 patients (53 men and 57 women), they were classifi ed depending on their diagnosis and healthy control group without ACS. Th e average age was 64 years for the AMI patients, and 61 years for the patients with unstable angina. Th e value of BNP and TnI was higher in the group with AMI than the group with unstable angina. Th e healthy control group had a lower concentration of BNP and TnI than the patient groups.Using Mann Whitney U test we made comparison of BNP and TnI levels among the groups including the

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TABLE 1. The mean concentration of biochemical parameters in groups with AMI, unstable angina and healthy control AMI group Unstable angina group Healthy control group P valueBNP (pg/mL) 764.48 287.18 18.74 p <0.001

SD 639.52 593.2 7.64SEM 90.44 83.44 1.08Median 585.25 98.1 19.1Interval 260-4441 18-2514 10-33.10

TnI (ng/mL) 2.5 0.1 0.01 p <0.001SD 2.28 0.23 0.024SEM 0.32 0.0033 0.0034Median 2.19 0.02 0Interval 0.31-7.07 0.00-1.10 0.00-0.09

patients with AMI, unstable angina and the healthy control group. According to Mann-Whitney U test for α = 5% the diff erence between concentrations of BNP in the patients with AMI and the patients with unstable angina were signifi cant. Th e same test for α = 5% has shown a signifi cant diff erence between concentrations of BNP in patients with AMI and healthy control group. Using Mann Whitney U test we made comparison between serum TnI concen-tration in the group of AMI patients and the healthy control group. Th e results between the groups were statistically signifi cant for P<0.05. Th e same test has shown a signifi cant diff erence between concen-trations of TnI in the patients with AMI and the patients with unstable angina for P<0.05.In our study we found a signifi cant correlation between the average concentrations of TnI and BNP with Pearson correlation coeffi cient (r = 0.36). Regression equation revealed a slope of 344.09 and a y axis intercept of 457.83. Th e results between average concentrations of TnI and BNP were sta-tistically signifi cant for P<0.05 using Student t test, the results are shown in Figure 1.

DISCUSSIONNatriuretic peptides elevations have shown the cor-relation with wall stress, and thus provided func-tional information. Th e level of plasma BNP depends on the equilibrium between myocardial secretion as compensatory response to injury or wall stress and an amount and activity of expressed guanylyl cyclase-type BNP receptors and also peripheral degradation rate of BNP through neutral endopeptidases. Th e

ischemia induced by increase in ventricular wall stress that induced release of BNP. Th e TnI elevations are seen in multiple chronic cardiac and noncardiac conditions, a rise or fall in serial measurement of TnI levels strongly supports an acutely evolving cardiac injury such as, most commonly, acute myo-cardial infarction (14). In our study we found sig-nifi cant elevated levels of plasma BNP and TnI in acute myocardial infarction. In our study we deter-mined the value of BNP 764.48 ± 639.52 pg/mL (260-4441 pg/mL) in the patients with AMI. Th e level of TnI in the group with AMI was 2.50 ± 2.28 ng/mL (0.31-7.07 ng/mL). Grybauskiene R. and al. (15) have got the mean concentration of TnI 0.499 ng/mL (0.07-2.89 ng/mL) and BNP level 758 pg/mL (206-2158 pg/mL). In our study patients with unstable angina had the concentration of BNP 287.18  ±  593.20 pg/mL (18-2514 pg/mL) and TnI level 0.10  ±  0.23 ng/mL (0.00-1.10 ng/mL) and healthy control group has concentration of BNP 18.74 ± 7.64 pg/mL (10-33.10 pg/mL) and TnI level 0.01 ± 0.024 ng/mL (0.00-0.09 ng/mL). It is a lower concentration of BNP and TnI than in the patients with AMI, the results are shown in Table  1. Th e other researchers have got results of BNP 70.2  ±  53.3 pg/mL in the patients with unstable angina (16). In the present study, we have shown signifi cantly higher BNP plasma level by patients with AMI in compare BNP level in healthy group results are shown in Table 1. Th e similarly results have got Morita and al. (17) and Richards and al.  (18). Patients with elevated plasma BNP levels (>80 pg/mL) had a signifi cantly higher incidence of new heart failure and all-cause

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mortality than those with a normal plasma BNP level (<or = 80 pg/mL) (19). In our study, patients with BNP level 80 pg/mL have stayed longer in the Department of Heart Diseases and had a higher incidence of new heart failure. Th e data of While HD and al. (14) have shown that BNP concentra-tion is increased during AMI and occurring after the fi rst AMI. BNP concentration in plasma during AMI is strongly related to the marker of myocar-dial necrosis refl ecting the extent of injured myocar-dium, and to degree of acute heart failure. During AMI BNP levels correlated strongly with TnI. In our study we have got good correlation of BNP and TnI in patients with AMI. In correlation between BNP and troponin we got correlation coeffi cient r = 0.36 with statistical signifi cance for p<0.05. Th e results are shown in Figure 1. Th e other researchers have got results of BNP and troponin correlation with correlation coeffi cient r = 0.273-0.70 (15, 19). Necrosis and apoptosis of myocytes in AMI are con-tributions of progressive left ventricle dysfunction. Th erefore we have done a correlation between BNP and TnI to contribute that BNP as TnI could be a marker of myocytes necrosis in patients with AMI. Th e results of Karcaiauskaite have shown a correla-tion coeffi cient r = 0.72 indicating strongly correla-tion between BNP and TnI. Th e reason why we got lower correlation coeffi cient is a fact that BNP gene transcription is increased both in infracted tissue

and it surrounding ischemic but viable myocardium whose extent diff ers (20). Studies have shown that BNP secretion and BNP mRNA expression are increased mainly in the borderline region between the infracted and non-infracted regions. Th e stimu-lus for this appears to be increased all stress directly related to the infarction. Th e clinical ischemia is result of extensive necrosis is associated with release of BNP. Ischemia itself rather than changes in wall stress secondary to ischemia might promote BNP release (21,22). Our study show that BNP can pre-dict high risk features in ACS such as more severe underlying atherosclerosis, left ventricular hyper-trophy and burden of ischemic insult. Th e patients with higher BNP have worse prognosis of AMI even with normal value of TnI. Th erefore BNP could be used as a marker of myocardial necrosis as well as marker of risk for myocardium ischemic viable.

CONCLUSIONIn our study BNP plasma levels are signifi cant higher in AMI in compared with unstable angina group and healthy control group. Plasma level BNP was elevated in patients with left ventricular (LV) dysfunction. Serial measurements of plasma BNP and TnI concentrations might be a useful tool for identifi cation of patients at risk of developing AMI and unstable angina. In patients with ACS BNP

FIGURE 1. Comparison of TnI and BNP in blood measured by Architect CMIA correlation coeffi cient r = 0.36.

Correlation between Troponin I and BNP

y = 344,09x + 457,83

R 2 = 0,1334

0

1000

2000

3000

4000

5000

6000

0 1 2 3 4 5

Serum concentration of Troponin I (ng/mL)

Pla

sma

BNP

con

cent

ratio

n (p

g/m

L)

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adds important prognostic information to clinical and laboratory variables as well as levels of troponin. Determination of BNP rise could be used for quick and easy estimation of infarction size. BNP together with TnI levels in acute phase of myocardial infarc-tion might be useful in predicting subsequent car-diac function.

CONFLICT OF INTERESTTh e authors declare that they have no competing interests.

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5. Kambayashi Y, Nakao K, Mukoyama M. Isolation and sequence deter-mination of human brain natriuretic peptide in human atrium. FEBS lett 1990;259(2):341-345. http://dx.doi.org/10.1016/0014-5793(90)80043-I.

6. De Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, et al. The prognostic value of B-type natriuretic peptide in patients with, acute coronary syndromes. N Engl J Med 2001;345:1014-21. http://dx.doi.org/10.1056/NEJMoa011053.

7. Omland T, Persson A, Ng L, O Brien R, Karlsson T, Herlitz J, et al. N-terminal pro-B-type natriuretic peptide and long – term mortality in acute coronary syndromes. Circulation 2002;106:2913-18. http://dx.doi.org/10.1161/01.CIR.0000041661.63285.AE.

8. Bassand JP, Hamm CW, Ardissino D. Guadelines for the diagnosis and Treatment of Non-ST-segment Evaluaton Acute Coronary Syndromes. Eur Heart J. 2007;28:1598-1660.

9. Wu A, Packer M, Smith A. Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure. A multisite study. Clin Chem. 2004;50:867-873. http://dx.doi.org/10.1373/clinchem.2003.026138.

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11. Hamm CW, Basssand JP, Angewall S. ESC Guidelines for the manage-ment of acute coronary syndromes in patients presenting without persistent ST evaluation. Eur Heart J 2011:32:2999-3054.

12. Mehta SR, Granger CB, Boden WE. TIMACS Investigatiors. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med. 2009;360 (21):2165-2175. http://dx.doi.org/10.1056/NEJMoa0807986.

13. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction rede-fi ned: a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefi nition of myo-cardial infarction. J Am Coll Cardiol. 2000; 36 (3):959-969. http://dx.doi.org/10.1016/S0735-1097(00)00804-4.

14. While HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wil CJ. Left ventricular end systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987;76:44-51. http://dx.doi.org/10.1161/01.CIR.76.1.44.

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16. Ogawa A, Seino Y, Yamashita T, Ogata K, Takano T. Difference in Elevation of N-Terminal Pro-BNP and Conventional Cardiac Markers between Patients with ST Elevation vs. Non-ST Elevation Acute Coronary Syn-drome. Circulation Journal 2006;70(11):1372-1378. http://dx.doi.org/10.1253/circj.70.1372.

17. Morita E, Yashue H, Yoshimura M, Ogawa H, Jougasaki M, Matsura T, et al. Increased plasma levels of BNP in patients with acute myocardial infarction. Circulation 1993;88: 82-91. http://dx.doi.org/10.1161/01.CIR.88.1.82.

18. Richards MA, Nicholls MG, Yandle TG, Ikram H, Espiner EA, Turner JG, et al. Neuroendokrine prediction of left ventricular function after acute myo-cardial infarction. Hearth 1999; 81:114-20.

19. Young E. Assessment of Extent of Myocardial Ischemia in Patients with Non-ST Evaluation Acute Coronary Syndrome using serum B-type natrium peptide level. Yonsei Med Journal. 2004:45(2):255-262.

20. Morrow AD, Cannon PC, Jesse LR, Newby LK, Ravkilde J, Storrow BA, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: characteristic and utilization of biochemical markers in acute coronary syndromes. Circulation 2007;115:356-75. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.182882.

21. Hama N, Itoh H, Shirakami G, Nakagawa O, Suga S, Ogawa Y, et al. Rapid ventricular induction of brain natriuretic peptide gene expression in exper-imental acute myocardial infarction. Circulation. 1995;92:1558-564. http://dx.doi.org/10.1161/01.CIR.92.6.1558.

22. D’Souza SP, Yellon DM, Martin C, Schulz R, Heush G, Onody A, et al. B-type natriuretic peptide limits infarct size in rat isolated hearts via KATP channel opening. Am J Physiol Heart Circ Physiol 2003;284:529-600.

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Journal of Health Sciences

RESEARCH ARTICLE Open Access

Prevalence of behavioral risk factors of non-communicable diseases among urban and rural population in the Federation of Bosnia and HerzegovinaAida Pilav1,2*, Aida Rudić2, Suada Branković2, Vildana Doder3

1Sector for Public Health, Monitoring and Evaluation, Federal Ministry of Health, Sarajevo, Bosnia and Herzegovina, 2Faculty of Health Studies, University Sarajevo, Sarajevo, Bosnia and Herzegovina, 3Sector for Project Implementation, Federal Ministry of Health, Sarajevo, Bosnia and Herzegovina

ABSTRACT

Introduction: The objective of the paper is to analyze and to assess prevalence of the major behavioral risk factors among adult population (25-64 years of age) in the rural and urban areas in the Federation of Bosnia and Herzegovina (FBIH).

Methods: Data were taken from cross-sectional population survey on the health status population in the FBIH. To ensure a sample representative for the adult population in the FBIH it was applied the two-stage stratifi ed systematic sample. The survey covered a total of 2735 adult population aged 25-64 years, of which 1087 in the urban areas and 1648 in rural areas.

Results: The prevalence of smoking among men in rural areas is signifi cantly higher than among men in urban areas (69% vs. 55%), while the prevalence of smoking among women is higher in urban than in rural areas (45% vs. 31%). There is no statistically signifi cant difference in prevalence of obesity and physical activity according to the age groups among men and women in the urban and rural areas. The frequency of changes in behavior related to acquiring healthy living habits in the rural areas is statistically signifi cant among men and women, while in the urban areas there is no statistical signifi cance among the sexes.

Conclusions:. The results indicate that there are no signifi cant differences in prevalence of factor risks in urban and rural areas. Prevalence of unhealthy lifestyles is high, and the results should be used to improve standard planning of health promotion-prevention programs.

Keywords: smoking; obesity; urban-rural differences

*Corresponding author: Aida Pilav, MD PhD, Sector for Public Health, Monitoring and Evaluation, Federal Ministry of Health, Titova 9, 71 000, Sarajevo, Bosnia and Herzegovina Telephone: +357 33 210 114, E-mail: [email protected]

Submitted May 20 2014 / Accepted August 24 2014

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Aida Pilav, 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.

INTRODUCTION

Th e health care systems of countries are facing chal-lenges of ensuring comprehensive protection aimed at reducing burden of diseases and early death from the non-communicable diseases (NCDs) through

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integrative approaches from health promotion and disease prevention to the management of NCDs at strategic level (1).Smoking, unhealthy eating habits and lack of phys-ical activity with consequent obesity are proven major risk factors for NCDs, especially diseases of the cardiovascular system (CVDs), as well as for subsequent events; hypertension, glucose intoler-ance and hyperlipidemia. Th ese risk factors are also indicators of major preventable health problems and their regular monitoring within the population makes a good basis for setting and implementing evidence-based preventive and promotional pro-grams (1,2).In the last decades the health care systems of coun-tries with clear and strong recommendations of the World Health Organization (WHO) implement activities to reduce prevalence of these risk factors that are proven to be preventable. Th ese are not activities of health care sector only, but also activ-ities of other government bodies, which represents the base of the new WHO European policy “Health 2020” (3,4).Th e increase in emergence of NCDs is recorded in the Federation of Bosnia and Herzegovina (FBIH) through the fi gures from the regular health-sta-tistical data, including mortality and morbidity data (5,6). Prevalence of the risk factors is assessed from periodic cross-sectional population surveys.Th e fi rst cross-sectional study population and risk factors for NCDs in a representative sample of the population in the FBIH was conducted in the autumn of 2002. Th e survey conducted in FBIH in 2002 was taken as a baseline survey, when signifi -cant prevalence of smoking habits, physical inactiv-ity and obesity, as critical risk factors for emergence of NCDs, was assessed among adult population in the FBIH (7).Ten years later, in 2012, a cross-sectional survey was conducted on the sample of adult population aimed at evaluating state of health of population and assessing prevalence of risk factors in the FBIH. Th e survey was conducted in line with internation-ally established standards and protocols (8-10).Th e paper shows analyses and assessment of prev-alence of main behavioral risk factors among adult population (25-64 years of age) in urban and rural

areas in the FBIH in order to examine possibilities of existence of diff erences, which is necessary for designing evidence-based population programs and interventions.

METHODSData were taken from cross-sectional population surveys on the health status population in the FBIH. Population surveys were carried out by the Federal Ministry of Health (FMoH) and the Federal Public Health Institute (FPHI) in the period from November 2012 to January 2013, as a part of pri-mary health care reform process in the FBIH with purpose to measure performance in the health care system and public health.To ensure a sample representative for the adult population in the FBIH it was applied the two-stage stratifi ed systematic sample. Sample frame is a master sample of visiting sites and households from 2009, which was prepared by the Federal Institute of Statistics (FIS).Th e fi rst sampling stratums were visiting sites strati-fi ed by type of settlement - urban and rural, and by the cantons in the FBIH (ten cantons). Th e second sampling stratums were households. Th e visiting sites were selected by Lahiri method of sampling, which means the selection probabilities are not equal, but the probability of selection is proportional to the size of the primary unit, wherein the size of the primary unit is represented by the number of secondary sampling units, or households within the primary unit. Households were selected by system-atic method, which means that the choise probabil-ities were the same. Stratifi cation of units was made according to the type of settlement (urban/rural). Th e allocation of households was made proportion-ally to size of settlement types, taking care to include all cantons in the FBIH. In this population were not included collective households such as student hos-tels, residential colleges, nursing homes, prisons etc.Out of 1752 households that made the pattern in the FBIH, the survey was conducted in 1402 house-holds (RR 80%). From this number, 40% of house-holds were in urban areas and 60% in rural areas. Respondents were all adult members of the house-hold aged 18  years and older. For the purpose of comparison with the results of a cross-sectional

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survey that was conducted in the FBIH in 2002, the document analyzed the results of the adult population aged 25-64  years. Th e survey covered a total of 2735 adult population aged 25-64 years, of which 1087 in the urban areas and 1648 in rural areas.Th e study was conducted in accordance with the Helsinki Declaration, which defi nes the ethical prin-ciples of biomedical research on humans. All partici-pants were informed of the purpose of research, and were explained that use of data is needed solely for research purposes. Th e study included a standardized questionnaire and anthropometric measurements.Th e questionnaire included questions about behav-ioral risk factors (smoking, physical activity, nutri-tion habits), while anthropometric measurements included measurements of height, weight, blood pressure and biochemical analysis of capillary blood samples (blood sugar, cholesterol and triglycerides).Information on smoking was obtained from a set of questions that were set to respondents. Daily smokers were respondents who currently smoke or who have smoked in the previous month prior to the survey.Physical activity was estimated from a set of ques-tions about the frequency of physical activity in lei-sure time. Respondents who identifi ed themselves to exercise two or more times a week (issue related to the intensity of exercise that accelerates breathing or sweating), were all categorized as having moderate physical activity.Increased awareness of risk factors and the change in eating habits, were both estimated by set of ques-tions about habit changes in the past year.Physical measurements, among others things, included the measurements of height and weight. Height was measured by an stadiometer that was attached to the wall or to a special holder. Weight was measured in light clothing using digital scales. Obesity has been described in terms of BMI (body mass index) and was expressed in kg/m3.Fieldwork was carried out by ten trained teams.

Statistical analysisTh e data were analyzed using SPSS for Windows, version  17.0. Descriptive statistics was used to

represent the data – index of structure and relative relations. Statistical signifi cance was tested by χ2

test. Frequency of each observed variable relative to the place of residence (urban/rural), sex and age subgroup was examined by descriptive statistical analysis.

RESULTSSmokingIn the total sample in FBIH 37% of women and 63% of men are every day smokers. Prevalence of smokers among men in rural areas is signifi cantly higher than among men in urban areas (69% vs. 55%), while the prevalence of smoking among women is signifi cantly higher in urban than in rural areas (45% vs. 31%).Prevalence of daily cigarette smokers in urban areas is increased by the respondents’ age among both sexes, especially among women. In the group of respondents between 55-64 years of age the preva-lence is equal both among men and women (18%). Th ere is no statistically signifi cant diff erence in prevalence of smoking according to the age groups among respondents of both sexes in the urban areas (λ2=3.2 df=2 p=0.358) (Table 1).In the rural areas prevalence of smoking habits is higher among men and lower among women and it also increases with age of respondents of both sexes, especially among women. In the group of respondents between 45-54 years of age prevalence

TABLE 1. Prevalence of smoking according to age and sex, urban/rural differences

Urban areasDaily smokers

Rural areasDaily smokers

p value

N % N %Men 197 55 329 69 p<0.01Women 163 45 148 31 p<0.01Age (years)

Men 25-34 y 53 27 66 20 p>0.1Women 25-34 y 36 22 33 22 p>0.1Men 35-44 y 53 27 104 32 p>0.1Women 35-44 y 38 23 41 28 p>0.1Men 45-54 y 55 28 87 26 p>0.1Women 45-54 y 59 36 53 36 p>0.1Men 55-64 y 36 18 72 22 p>0.1Women 55-64 y 30 19 21 14 p>0.1

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is higher among women than among men (36% vs.26%). Th ere is no statistically signifi cant diff er-ence in prevalence of smoking according to the age groups among respondents of both sexes in the rural areas (λ2=6.91 df=2 p=0.075) (Table 1).

ObesityIn total 22% of respondents in the FBIH is obese (BMI >30 kg/m2). Prevalence of obesity in urban areas is 20%, while the prevalence of obesity in rural areas is 24%. In the urban areas prevalence of obesity is higher among men than among women (18% vs. 17%), while in the rural areas prevalence of obesity is higher among women than among men (37% vs. 28%). Th ere is no statistically sig-nifi cant diff erence in prevalence of obesity among men and women in the urban areas and rural areas (Table 2).Prevalence of obesity in the urban areas increases by the respondent’s age among both sexes. Th ere is no statistically signifi cant diff erence in prevalence of obesity according to the age groups among men and women in the urban areas (λ2=5.50 df=3 p=0.138) (Table 2).Prevalence of obesity in the rural areas increases by the respondent’s age among both sexes, and among both sexes aged between 35-54 years it grows much faster than in the urban areas. Prevalence of obesity is lower among both sexes between 55-64 years in the rural areas than among respondents in the urban areas. Th ere is no statistically signifi cant diff erence in prevalence of obesity according to the age groups among men and women in the rural areas (λ2=4.41 df=3 p=0.250) (Table 2).

Physical activityPhysical activity was measured as a physical activ-ity lasting 30 minutes where the respondent would be out of breath or sweat, but in diff erent intervals during seven days. 2-3 times a week as the recom-mended frequency of the physical activity. Total of 36% of respondents in the FBIH is physical inac-tive, while 14% of respondents is physically active 2-3  times a week, whereof 45% are women and 55% are men.Th e percent of physically active women and men aged between 25-34 years is the same in urban areas.

Generally, there is no signifi cant diff erence in the recommended physical activity among men and women in the urban areas (λ2=3.43 df=3 p=0.330) (Table 3). Th e percent of physically active women and men, especially in younger age groups, is the same in urban areas. Generally, there is no sig-nifi cant diff erence in the recommended physical activity among men and women in the rural areas (λ2=2.66 df=3 p=0.446) (Table 3).

Healthy behaviorsTh e respondents were asked whether, in the last

TABLE 2. Prevalence of obesity according to age and sex, urban/rural differences

Urban areasBMI>=30

Rural areasBMI>=30

p value

N % N %Men 111 18 166 28 p>0.01Women 105 17 220 37 p>0.01Age (years)

Men 25-34 y 14 13 13 8 p>0.01Women 25-34 y 8 8 20 9 p>0.01Men 35-44 y 20 18 46 28 p>0.01Women 35-44 y 10 9 42 19 p>0.01Men 45-54 y 31 28 54 32 p>0.01Women 45-54 y 37 35 83 38 p>0.01Men 55-64 y 46 41 53 32 p>0.01Women 55-64 y 50 48 75 34 p>0.01

TABLE 3. Physical activity according to age and sex, urban/rural differences

Urban areasPhysical activity

2–3 times a week

Rural areasPhysical activity

2–3 times a week

p value

N % N %Men 97 24 119 30 p=0.120Women 92 24 85 21 p=0.120Age (years)

Men 25-34 y 32 33 29 24 p>0.01Women 25-34 y 34 37 23 27 p>0.01Men 35-44 y 22 23 36 30 p>0.01Women 35-44 y 13 14 21 25 p>0.01Men 45-54 y 19 19 28 24 p>0.01Women 45-54 y 25 27 27 32 p>0.01Men 55-64 y 24 25 26 22 p>0.01Women 55-64 y 20 22 14 16 p>0.01

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12 month, they have changed their behavior related to the diet, increase in physical activity, giving up smoking and alcohol consumption.Th e changes in behavior are more frequent in the older age groups, between 45-64  years of age. Generally, the most frequently changed habits relate to increase in fruit and vegetable consump-tion, as well as reduction of fat intake, while the

reduction of smoking habits was recorded only in small percent.Th e frequency of changes in behavior related to acquiring healthy living habits in the rural areas is sta-tistically signifi cant among men and women, because women in rural areas change living habits rather more frequently than men, while in the urban areas there is no statistical signifi cance among the sexes (Figure 1).

FIGURE 1. Prevalence of changes in behavior according to the area, age and sex, urban/rural difference.

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DISCUSSIONTh e prevalence of risk factors for NCDs in the FBIH in the last decade was evaluated through a few isolated studies on risk factors and health behavior in diff erent samples of the population.Th e fi rst cross-sectional study population and risk factors for NCDs in a representative sample of the population in the FBIH was conducted in 2002. Th e prevalence of risk factors related to the health behav-ior of the population in the study from 2002 year was relatively high and there were signifi cant diff erences in the level of the main risk factors - smoking, physi-cal activity and obesity in urban and rural areas (11).Ten years later it was conducted a follow-up study in order to monitor trends in preventable risk factors and in getting real information about the profi le of risk factors for NVDs among the adult population in the FBIH. Great signifi cance of this research lies in representation of FBIH in both urban and rural areas, and the high response rate.Data from routine health statistics in the FBIH show a slight increase in circulatory system dis-eases, particularly CVDs, followed by malignant diseases. Th erefore, monitoring and control of risk factors are necessary measures to protect the health of the population. Conducting periodic surveys enables monitoring of trends and creation of evi-dences for development of public health activities and algorithms for clinical work within primary health care.Results of cross-sectional studies identify smoking as the most important risk factor in the occur-rence of NCDs among the adult population in the FBIH. Despite the existence of clear legislation in the FBIH regarding the limited use of tobacco products, the prevalence of smoking in the FBIH is still very high, what, among other things, speak in favor of an inconsistent implementation of the Law. Consistent implementation of the Law on the lim-ited use of tobacco products in the FBIH, promo-tion of non-smoking places and work environment free of tobacco smoke should be basic measures. In accordance with the practice in EU countries and in the region, part of the revenue from excise taxes on tobacco products would be redirected to funding for preventive and promotional programs related to reducing smoking prevalence, what would

treat causes and not consequences of the problem. As important actors in both prevention and pro-motional activities, apart from the health system, seems to be defi nitely local communities where peo-ple live. At the same time it is necessary to increase the knowledge and skills of healthcare workers in primary health care (PHC), especially for nurses, in treatments of smoking cessation, considering that the strengthening of PHC through continuous improvement of family medicine teams is a funda-mental commitment to the reform of the health sec-tor in the FBIH. Th ese treatments should become standard practice in teams of family medicine in PHC, given the very high prevalence of smoking in the FBIH, which is signifi cantly higher than in neighboring countries (12-13).Obesity is one of major public health challenges in the 21st  century. Th e prevalence of obesity from the 1980s nearly tripled in many countries of the European region, and consequently led to an increase in various physical disabilities and devel-opment of non-communicable diseases, especially diabetes mellitus. In the FBIH, the prevalence of obesity increases with age in both sexes. If we add this to an increasing prevalence of other risk factors in middle and old age, this creates an additional bur-den in the accumulation of unhealthy habits within the population. Enhancing public awareness about healthy eating and increasing knowledge about infl uences of obesity on health must be a method of everyday work in primary health care, in collab-oration with the local community. Increasing prev-alence of obesity in rural areas is signifi cant and this should be given special attention in the future.Prevalence of physical activity is insuffi cient and there is certainly a space for public health improve-ments. In recent population surveys conducted in Serbia, the prevalence of physical activity of the adult population was similar to those in the FBIH, indicating that the lack of physical activity in lei-sure time is almost culturally adopted a pattern of behavior in both the FBIH and the neighboring countries (14).It is especially necessary to improve awareness of population about the importance of physical activ-ity in all age groups. At the same time, it is necessary to create conditions for the massifi cation of physi-cal activity. Th e role of local communities in these

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activities is also necessary to be strengthened, as the creation of conditions for the implementation of physical activity in leisure time lies precisely within the places of residence of the population.Changing behavior related to the acquisition healthy habits in the last year prior to the survey was low in both men and women, and there are no signifi cant diff erences between urban and rural areas. Enhancing awareness of healthy habits is a long process and requires very lengthy preventive work. Th is is work that needs to be strengthened intensively in the coming period through individual and group counselings, work within the local com-munity, particularly through the work of nurses in primary health care. Th e advantage of the FBIH can be continuous strengthening of family medicine teams in PHC, and obtained matrix with several important indicators which should serve as proof for posting prevention programs and increasing awareness of the risk factors. Experiences in many countries show that a well-planned health interven-tion programs at the community level in order to promote health and health behavior changes have good results (15-16).Th e results of surveys showed no signifi cant diff er-ences in the prevalence of risk factors for NCDs in both urban and rural areas. Th e prevalence of unhealthy lifestyles in the FBIH is quite high and it is necessary to conduct vigorous public health action to reduce risk factors, as well as individual access to high-risk individuals.

CONCLUSIONSSocial responsibility for health in the local community includes the creation of preventive health programs and proposed measures for improv-ing and enhancing the health of the population. Th is is particularly important for rural areas, where the impacts of local communities can be signifi cant. Active involvement of all actors in the social system and the coordination of all government sectors, from the health sector to the education sector, the inspectorate, fi nance and other sectors, as well as active cooperation with non-governmental sectors in the implementation of the current legislation, can all create a favorable environment for reducing these risk factors. Intersectoral cooperation is the main

principle of the WHO European policy “Health 2020” and is refl ected in the approach “Health in all policies” and is necessary to follow in strategic and operational approaches in the FBIH.

ACKNOWLEDGEMENTSTh e survey was made as a part of the Health sector enhancement project in the Federation of Bosnia and Herzegovina, funded by the World Bank from the International Development Association (IDA) credit and authors would like to acknowledge.

REFERENCES1. World Health Report 2002: Reducing risks, promoting healthy life. Geneva:

World Health Organization; 2002.2. World Health Report 2003: Shaping the future. Geneva: World Health

Organization; 2003.3. Action plan for implementation of the European Strategy for the Prevention

and Control of Non-communicable Diseases 2012–2016. Copenhagen: World Health Organization Regional Offi ce for Europe; 2011.

4. Health 2020. A European policy framework and strategy for the 21st century. Copenhagen: World Health Organization Regional Offi ce for Europe; 2013.

5. Raljević E, Dilić M, Čerkez F. Prevencija kardivaskularnih bolesti. Udruženje kardiologa i angiologa BiH; 2003. p.171.

6. Zdravstveno stanje i organizacija zdravstvene zaštite u Federaciji Bosne i Hercegovine 2012. Zavod za javno zdravstvo Federacije Bosne i Hercegovine; 20 13.

7. Study of risk factors of non-communicable diseases in the Federation of Bosnia and Herzegovina 2002. Public Health Institute of the FBIH; 2002.

8. Survey protocol. [homepage on the Internet]. WHO MONICA Project; [cited 2011. Oct 15]. Available from: http://www.thl.fi /publications/monica/manual/index.htm

9. Protocol and Guidelines. Countrywide Integrated Non-communicable Diseases Intervention (CINDI) Programme. Copenhagen: World Health Organization Regional Offi ce for Europe; 1995.

10. European Health Interview Survey: Methodological manual. EUROSTAT 2010.

11. Pilav A, Jokić I, Nikšić D, Gusinac-Škopo A. Prevalence of behavioral risk factors among urban and rural population in the Federation of Bosnia and Herzegovina. Mat Soc Med. 2004; 16(1-2): 7-11.

12. Djikanovic B, Marinkovic J, Jankovic J, Vujanac V, Simic S. Gender dif-ferences in smoking experience and cessation: do wealth and education matter equally for women and men in Serbia? J Public Health. 2011; 33 (1): 31-38.

13. Samardžić S, Vuletić G, Tadijan D. Five-year cumulative incidence of smoking in adult croatian population: the CoHort Study. Coll. Antropol. 2012; 36 (1):99-103.

14. National Health Survey Serbia, 2006. Ministry of Health of the Republic of Serbia; 2007.

15. Puska P. Successful prevention of non-communicable disease: 25 year experiences with North Karelia Project in Finland. Public Health Medicine. 2002;4(1):5-7.

16. Nissinen A, Ximena B, Puska P. Community-based non-communicable dis-ease interventions: lessons from developed countries for developing ones. Bulletin of the World Health Organization. 2001;79:963-970.

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Journal of Health Sciences

RESEARCH ARTICLE Open Access

Nurses’ knowledge and responsibility toward nutritional assessment for patients in intensive care unitsMahmoud Al Kalaldeh1*, Mahmoud Shahin2

1Faculty of Nursing, Zarqa University, Zarqa, Jordan, 2Faculty of Nursing, Isra University, Amman, Jordan

ABSTRACT

Introduction: Nutritional assessment is a prerequisite for nutritional delivery. Patients in intensive care suffer from under-nutrition and nutritional failure due to poor assessment. Nursing ability to early detect nutritional failure is the key for minimizing imparities in practice and attaining nutritional goals. Aim of this article is to examine the ability of Jordanian ICU nurses to assess the nutritional status of critically ill patients, considering biophysical and biochemical measures.

Methods: This cross sectional study recruited nurses from different health sectors in Jordan. ICU nurses from the governmental sector (two hospitals) and private sectors (two hospitals) were surveyed using a self-administered questionnaire. Nurses’ knowledge and responsibility towards nutritional assessment were examined.

Results: A total of 220 nurses from both sectors have completed the questionnaire. Nurses were con-sistent in regard to knowledge, responsibility, and documentation of nutritional assessment. Nurses in the governmental hospitals inappropriately perceived the application of aspiration reduction measures. However, they scored higher in applying physical examination and anthropometric assessment. Although both nurses claimed higher use of biochemical measurements, biophysical measurements were less fre-quently used. Older nurses with longer clinical experience exhibited better adherence to biophysical mea-surement than younger nurses.

Conclusion: Nursing nutritional assessment is still suboptimal to attain nutritional goals. Assessment of body weight, history of nutrition intake, severity of illness, and function of gastrointestinal tract should be considered over measuring albumin and pre-albumin levels. A well-defi ned evidence-based protocol as well as a multidisciplinary nutritional team for nutritional assessment is the best to minimize episodes of under-nutrition.

Keywords: assessment; nutritional status; nurse

*Corresponding author: Mahmoud Al Kalaldeh, PhD RN MSN CNS,Faculty of Nursing, Zarqa University, Zarqa, JordanPhone: +962 5 3821100,E-mail: [email protected]

Submitted July 21 2014 / Accepted August 21 2014

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Mahmoud AL Kalaldeh and Mahmoud Shahin; 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 orig-inal work is properly cited.

INTRODUCTIONCritical illness is associated with many complications such as anorexia, hyper metabolism, malabsorption; atrophy of muscles, liver, kidney, gastrointestinal tract & heart; impaired cell mediated immunity,

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susceptibility to infections, poor wound healing, anemia, death (1,2). Enteral nutrition (EN) is the preferred nutritional method whenever is possible to feed critically ill patients (3,4). When gut is used for nutrition, bacterial translocation and septicemia are prevented.Malnutrition is a term used frequently in healthcare system which is the analogy of under-nutrition or inadequate energy intake less than the metabolic demands (5,6). Under-nutrition can also be resulted from abnormal digestion or absorption of protein and calories (5,6). It is also acknowledged that malnutrition in the critically ill is associated with impaired immune functions; impaired ventilator drive, and weakened respiratory muscles, leading to prolonged ventilator dependence and increased infectious morbidity and mortality (7,8).Proper nutritional assessment is strongly linked to successful nutritional plans for critically ill patients (4,9,10). Th e current focus on nutri-tion in critical care settings is that carefully select-ing patient’s parameters that would highly refl ect patient’s outcome (11-13). In order to design an appropriate and eff ective strategy for nutritional assessment in the intensive care, a crucial guidelines have to be applied systematically for all critically ill patients (14,15).Nurses in intensive care are in a key position to maintain patients’ nutritional status at an optimal level and closer to the nutritional goals (16,17). While most of the critical care nurses are responsi-ble for establishing nutritional access and initiating feeding, in some instances, they calculate the caloric needs according to the body requirements and mea-sure the daily calories delivered (16,17). However, imparity in nursing practices contributes to devel-oping serious defi ciencies and complications due lack of unifi ed guidelines (18,19). When adherence to evidence-based guidelines is assured, the discrep-ancy inherent in nursing practice can be curtailed and the eff ectiveness of nutritional practices are maintained (20,21).In Jordan, critical care nurses have no obvious role regarding nutritional care (22). While dietitians are available in the most of Jordanian hospitals, nurses often hold the responsibility for early detect-ing the sings of under-nutrition and assessing the

outcomes of the delivered feeding although lack of expertise and training is sometime evident (23,24). Unfortunately, a limited number of tools for nutri-tional assessment are available in the Jordanian hos-pitals; in addition to poor academic preparations that suffi ce this domain (22).Th e most recommended nutritional assessment tools are as follows: (a) biophysical assessment and anthropometric measurement which include body mass index (BMI), mid-arm muscle circumference, triceps skin fold thickness, in addition to measuring Gastric Residual Volume (GRV) and detecting tube placement for enteral fed patients (16,17). However, the ratio of subcutaneous layer to total body fat may vary from 20% to 70% in the normal individuals; so they are not recommended in extreme weight change due to the risk for overestimating body fat in malnourished patients (16). (b) Physical examina-tion which includes history of weight loss, alcohol abuse, dietary habits, skin, mouth, and neurologi-cal system monitoring (25,26). Body temperature is also a part of the physical examination (27,28). (c) Biochemical assessment includes serum albu-min, transferrin, transthyretin (prealbumin), reti-nol-binding protein, somatolin C and fi bronectin (29,30). However, changes in fl uid distribution may result in pseudo rise or fall in the value of albu-min level causing false medical interpretation (31). (d)  Dietary assessment which includes 24 hours recall, food records (diaries), diet history and food frequency questionnaires (32). Th ese methods may however be impractical for critically ill patients who are unable to communicate eff ectively with practi-tioners (18,33).Th e purpose of this study was to assess Jordanian nurses’ knowledge and responsibility of nutritional assessment in the critical care, considering biophys-ical and biochemical measures.

METHODSTh is descriptive cross sectional study employed nurses from four hospitals in Jordan; two govern-mental hospitals and two private hospitals. It is assumed that there are many diff erences between heath care sectors in Jordan in terms of medical pro-tocols and nursing practice (22). For that reason, nurses in diff erent heath care sectors may exhibit

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various level of adherence to nutritional assessment tools. Nurses working in any intensive care units and had at least one year of clinical experience and hold the bachelors or diploma degree in nursing was eligible for participation. Convenient sampling technique was used to select participants from each involved hospital. Th e estimation of sample size was based on the medium eff ect size, power of 0.80, and α of 0.05 (34). All selected hospitals are located in Amman, the capital of Jordan, and all are consid-ered as major and referral hospitals that operate well occupied intensive care units.Study instrument included a self-administered questionnaire developed to assess nurses’ ability to assess patients’ nutritional status while staying in the intensive care. Th is questionnaire consisted of fi ve demographic questions; six questions related to the attitudes towards nutritional assessment including aspiration-reduction measures; and fi ve questions related to using diff erent bio-physical and biochemical measures. Th e scoring system ranged from 1 (to a very small extent) to 5 (very great extent). A pilot study was carried out by 10 nurses from the same study target to test the clar-ity, applicability, and feasibility of the question-naire. Minor modifi cations were done after pilot-ing and those nurses participated in the pilot study were excluded from the study sample. Th e content validity was also assessed by a panel of experts in this fi eld, including a physician, a dietitian, and two expert nurses.Ethical approvals were anticipated from each hospital’s authority prior to data collection. A writ-ten permission (informed consent) for partici-pation was obtained from each participant after providing complete information about the study and its signifi cance. Anonymous participations and confi dentiality of data were also assured. Data were collected in collaboration with the head nurses of the unit in which they contributed in selecting the eligible participants, handing, and returning the completed questionnaires in a sealed envelope within one week.

Statistical analysisAfter returning all completed questionnaires, data were entered the statistical package for social

sciences (SPSS) software, version  17. Descriptive statistics including number, percent, mean, Standard Deviation (SD) were used and followed by comparing diff erences between study groups using Chi-square and Kruskal-Wallis test.

RESULTSParticipants’ demographicsA total of two hundred and twenty intensive care nurse participated in the study and returned the completed questionnaires. As shown in Table  1, the majority of the study participants were female accounting 65% while 34% were male. Regarding the ages, around 38% were aged less than 25 years old and the second majority age group was between 25-45 years old. About the half of the sample had a clinical experience of less than fi ve years and very few had an experience of more than 20 years. While the majority of participants (71.4%) hold the bach-elor degree of nursing, the vast majority (82.3%) claimed no previous clinical training received with the respect of nutritional assessment (Table 1).

TABLE 1. Participants’ demographicsVariable Category Governmental

n (%)Private n (%)

Total n (%)

Gender Male 46 (35.7) 31 (34.1) 77 (35)Female 83 (64.3) 60 (65.9) 143 (65)Total 129 (100) 91 (100) 220 (100)

Age <25 51 (39.6) 33 (36.3) 84 (38.1)25-35 33 (25.5) 25 (27.5) 58 (26.4)36-45 29 (22.5) 25 (27.5) 54 (24.6)>45 16 (12.4) 8 (8.7) 24 (10.9)Total 129 (100) 91 (100) 220 (100)

Years of experience

<1 36 (27.9) 26 (28.5) 62 (28.2)1-5 28 (21.7) 17 (18.7) 45 (20.5)6-10 24 (18.6) 15 (16.5) 39 (17.7)11-15 24 (18.6) 16 (17.6) 40 (18.2)16-20 12 (9.3) 9 (9.9) 21 (9.5)>20 5 (3.9) 8 (8.8) 13 (5.9)Total 129 (100) 91 (100) 220 (100)

Level of Education

Diploma 45 (34.9) 18 (19.8) 63 (28.6)Bachelor 84 (65.1) 73 (80.2) 157 (71.4)Total 129 (100) 91 (100) 220 (100)

Attending Nutrition Course

Yes 13 (10.1) 26 (28.6) 39 (17.7)No 116 (89.9) 65 (71.4) 181 (82.3)Total 129 (100) 91 (100) 220 (100)

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Attitudes to nutritional assessmentAs shown in Table  2, the nurses showed a con-sistent adherence to the use of nutritional assess-ment in the ordinary nursing process. Th ere were no any signifi cant diff erences between nurses from both groups in relation to the importance of assess-ment in acquiring knowledge, having responsibil-ity, and documenting nutritional changes. Scores were mainly above the midpoint of 2.5, indicating that nurses perceived the importance of assessment through their nursing process. Regarding some nutritional assessment tools, nurses in the private sectors claimed measuring gastric aspirate more frequently than nurses in governmental sectors. Similarly, detecting tube placement was also scored higher among nurses in the private sectors than governmental nurses. In addition, nurses in the pri-vate hospitals claimed using other aspiration reduc-tion measures such as degree of head of the bed, controlling feeding rates, and using of promotility agents more frequently than nurses in the govern-mental hospitals.

Adherence to various nutrition assessment toolsTh is section shows nurses’ attitudes towards adher-ence to various nutritional assessment tasks while providing EN care for critically ill patients. Th ere were a statistical signifi cant diff erences between governmental and private sector nurses in regard to adherence to these nutritional assessment provi-sions. Nurses in the governmental hospitals scored signifi cantly higher in undertaking assessment using physical examination, anthropometric assessment, and dietary assessment than nurses working in the private sector. However, both groups had equally showed the extent of using biomedical assessment

and screening for nutritional risks as main tools for assessing the nutritional status (Table 3).

Variations in nutritional assessment between demographic groupsWhile no signifi cant diff erences between male and female nurses in regard to the adherence to nutri-tional assessment, older nurses with longer clini-cal experience scored higher in applying a nutri-tional assessment using biophysical measurements (x²  =  24.261, df=3, p=0.043). However, younger nurses with shorter clinical experience scored higher in having a nutritional assessment using biochemical measurements (x²=35.171, df=3, p<0.001). Although bachelor and diploma degree holders did not diff er signifi cantly in term of nutritional assessment, nurses who received previous nutritional training were more likely to adhere to diff erent assessment measures than those who did not (x²=76.184, df=1, p<0.001).

DISCUSSIONIt was evident that nurses well perceived the knowl-edge and responsibility for nutritional assessment and claimed competency in undertaking nutri-tional assessment while examining the eff ectiveness of delivered feeding. Th is premise is supported by other researchers who reinforced the importance of nutritional assessment as the fi rst step of nutritional care (14,35,36).Aspiration is the most common dangerous side eff ect resulting from EN. Aspiration-reduction mea-sures can be applied individually; however, most of them are combined into one protocol especially in patients with mechanical ventilation. For instance, Bowman et al. (2005) established and implemented a new ‘evidence-based feeding protocol’ and an

TABLE 2. Attitude to nutritional assessmentGovernmental (n=129) Private (n=91) Total (n=220) Kruskal-Wallis test

M SD M SD M SD χ² test p-valueKnowledge of assessment 2.79 1.28 3.22 1.22 2.97 1.21 5.782 0.056Responsibility of assessment 2.87 1.19 3.26 1.11 3.03 1.13 5.696 0.058Documentation of assessment 3.13 1.32 3.00 1.08 3.01 1.17 1.598 0.450Measuring gastric aspirates 3.14 1.36 4.05 1.29 3.70 1.33 25.909 <0.001Detecting tube placement 3.88 1.31 4.31 0.93 4.00 1.14 10.176 0.006Other aspiration reduction measures 3.06 1.19 3.59 0.99 3.27 1.14 9.249 0.010Scores range from 1 (to a very small extent) to 5 (very great extent) * M: Mean, * SD: Standard deviation

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‘aspiration reduction algorithm’ for enteral fed, mechanically ventilated patients in the ICUs. Also, Metheny et al. (2010) evaluated the eff ectiveness of using ‘Aspiration Risk-Reduction Protocol’ (ARRP) for enteral fed patients with mechanical ventilation. Th e importance of controlling GRVs was adequately perceived by nurses as a protective measure to pre-vent higher GRV limits (28, 37). Th is conforms to the evidence-based recommendations that measur-ing GRV is an essential element in EN and should be maintained under the universal threshold of 200-500 ml (10). It is also accepted to defi ne GRV as the cutoff point of 30% of the last given feeding amount which is remaining in the stomach (38,39). However, previous studies addressed that GRVs should not be taken into account for all potential risks for pulmonary aspiration, the evidence showed that many other factors should be considered along with GRVs to reduce the risk of aspiration such as trauma, head injury, using of sedation, and mental instability (40). A  number of other recommenda-tions are helpful to accomplish nutritional goals such as avoiding inappropriate feeding cessation, using prokinetic agents with EN, keeping the head of the bed elevated at 35-45°, increasing feeding rate in a constant manner and using pre-prepared feed-ing packs (10,41,42).Studies stressed on the regular checking for tube position which is strongly associated with low complication incidences. Feeding tube should be checked regularly before each feeding administration or at least every day using a reliable indicator such as radiographic confi rmation (X-ray) which is still con-sidered as a ‘gold standard’ (43-45). Measuring pH of gastric aspirate is another reliable indicator for tube placement. However, studies have confi rmed that radiography is superior to other technique despite

the risk of radiation exposure, but if not available, pH method can be applied (10,38,46-50).Th e use of bio-physiological and bio-chemical parameters such as body weight, abdominal girth, bowel exam, skin integrity, and urine and stool anal-ysis in addition to serum protein level in the blood were assessed in this study. Th e nurses showed a higher reliance on the bio-chemical indicator than bio-physical measurement. Previous studies revealed that not all patients in intensive care have a regular nutritional assessment and the essential aspects of nutritional documentation are missing(23,51). Also, it is unlikely to have entire screening tool for evalu-ating nutritional outcomes (52, 53). Evidence-based guidelines stressed on investigating weight, history of nutrition intake, severity of illness, and function of gastrointestinal tract prior to admission instead of measuring albumin and pre-albumin (10,54). Th e frequent assessment of BMI should also be mea-sured by dividing weight in kilograms by the square of the height in meters (Normal range 19-25) (55). In general, all studies confi rmed the signifi cance of using evidence-based guidelines for nutritional assessment as the majority of nurses showed incon-sistency in having the systematic tools for measuring nutritional outcomes (52).Although the study recruited sample from two heath care sectors in Jordan, involving the other heath sec-tors such as the military heath sector would enhance the external validity of the study. In addition, including other hospitals from diff erent geograph-ical location, away from the capital, would provide further understanding about the phenomenon and enhance generalizability.Nurses require understanding factors associated with under-nutrition and hypo-caloric feeding through undertaking such nutritional assessment

TABLE 3. Adherence to nutritional assessmentGovernmental

Mean (SD) (n=129)Private

Mean (SD) (n=91)Kruskal-Wallis test

χ² test p-valuePhysical examination 2.28 (1.03) 1.48 (0.87) 22.43 <0.001Anthropometric assessment 2.56 (1.35) 1.74 (1.08) 19.65 <0.001Dietary assessment 4.31 (0.93) 3.79 (1.09) 24.09 <0.001Biochemical assessment 3.51 (1.33) 3.69 (1.09) 5.54 0.590Screening for nutritional risks 3.27 (1.64) 3.46 (1.23) 8.17 0.360Scores range from 1 (to a very small extent) to 5 (very great extent)

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measures that assist to early detecting the risk for these episodes. Th e application of bio-physical mea-surements in the intensive care is still defi cient so further insight about the usefulness of these mea-sures should practically be applied.Future researchers are invited to conduct other extensive research works that involve more aspects about nutritional care. Investigating the role of multidisciplinary work is also a priority to provide further understanding about the role of physicians and dietitians in assessing patients’ nutritional status while being in the intensive care.

CONCLUSIONNursing nutritional assessment is still subopti-mal to promote patients’ successful nutrition. Th e impact of nutritional assessment on determining the patients’ status and detecting some complications such as aspiration pneumonia is well-known, but nurses need to underpin their practice with some evidence-based guidelines to manage these issues eff ectively.Th is study provides overview to the body of knowl-edge about the role of intensive care nurses in maintaining optimal nutritional therapy In Jordan. Awareness about the current feature of nutritional assessment sheds the light on the future develop-ment strategies. In eventual, nurses’ practitioners would emphasize of the role of training to improve their professional competency in the light of nutri-tional delivery in the critically ill.

CONFLICT OF INTERESTTh e authors declare that they have no competing interests.

ACKNOWLEDGMENTAuthors are indebted to all nurses participated in this study including nursing staff , head nurses, and nurse managers.

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RESEARCH ARTICLE Open Access

The effects of education and training on self-esteem of nurse leadersAndreja Kvas1, Janko Seljak2*

1Faculty of Health Sciences, University of Ljubljana, Ljubljana, Slovenia, 2Faculty of Administration, University of Ljubljana, Ljubljana, Slovenia

ABSTRACT

Introduction: A successful leader must have high self-esteem. The main aims of this study were to iden-tify changes in the self-esteem of nurse leaders in Slovenia from 2001 to 2011 and to determine homo-geneous groups of leaders with similar personal characteristics.

Methods: The study used a version of a personal characteristics questionnaire with 16 self-descriptive statements. Two surveys were conducted among nurse leaders in Slovenian public hospitals, one in 2001 and the other in 2011. Relationships between variables were analysed using chi-square tests for categor-ical variables and the one-way analysis of variance for quantifi able variables. Factor analysis was used to determine groups of leaders with similar personal characteristics.

Results: A total of 327 nurse leaders participated in the survey in 2001 and 296 fi lled in questionnaires in 2011. The analysis showed that the level of self-assessment of personal characteristics among nurse leaders in Slovenian public hospitals was signifi cantly higher in 2011 than in 2001, and that differences among individual leaders decreased in most areas. Based on the assessments of personal characteristics, four groups of nurse leaders were established: task-oriented, knowledge and creativity oriented, rela-tionship oriented and extroverted nurse leaders. In the 2011 data, the groups of personal characteristics were much more clearly defi ned. These groups were established in accordance with leadership theory and research from other fi elds.

Conclusions: The positive effects of better education and training are visible in nurse leaders in terms of both their higher self-esteem and in the establishment of more homogeneous groups of leaders.

Keywords: education; nursing; leadership; self-esteem; Slovenia

INTRODUCTIONOnly a leader with high self-esteem can be a good leader as high self-esteem is the foundation on which

*Corresponding Author: Seljak Janko, Faculty of Administration, University of Ljubljana, Gosarjeva Ulica 5, 1000 Ljubljana,Slovenia, Phone: +386 41 998 499,E-mail: [email protected]

Submitted July 09 2014 / Accepted September 02 2014

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Andreja Kvas and Janko Seljak; 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.

he or she builds positive relationships with colleagues and superiors and is able to infl uence them. Th e leaders who are capable of appropriately motivating their co-workers to achieve targets are key elements of the excellence, effi ciency and eff ectiveness of every organization (1-3). Increasing attention is therefore being paid to leadership in nursing (4).Leadership styles have signifi cantly changed over the past 25 years, and nurse leaders must also adapt

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accordingly. Th e autocratic style of leadership, which prevailed in nursing in the past, needs to be replaced with more democratic leadership styles: transfor-mational, sharing, authentic, servant, etc. (5,6). In addition to high integrity, all these leadership styles call for leaders with high self-esteem as only such leaders are capable of sharing leadership with their subordinates and patients. Because only secure lead-ers, which have a strong sense of self-worth are able to give themselves away (7).Defi ning self-esteem is beyond the scope of this article. Our study used the concept of self-esteem in its broadest sense: ‘Positive self-concept can be equated with a positive self-evaluation, self-re-spect, self-esteem, self-acceptance, while a negative self-concept becomes synonymous with a negative self-evaluation, self-hatred, inferiority and a lack of feelings of personal worthiness and self-accep-tance’ (8). In this way, concepts like ‘self-concept’, ‘self-perception’, ‘self-attitude’ and ‘self-esteem’ become synonymous and, if considered attitudes toward self, can be seen to exist on a positive—negative continuum, or scale (9).Leaders with low self-esteem who doubt their abilities, knowledge and views do not get respect and appreciation and are not satisfi ed with them-selves (10). Insecure leaders are dangerous – to themselves, their followers, and the organizations they lead – because a leadership position amplifi es personal fl aws (11). If a leader cannot rely on his or her own abilities, he or she will doubt others’ abili-ties, and in turn cause mistrust in them as well (12).Individuals’ self-esteem is shaped gradually through their psychological development and interaction with their environment from early childhood, through adolescence and maturity (13). An indi-vidual’s self-esteem is the basis for the develop-ment of professional self-confi dence and the two infl uence each other throughout one’s professional career (14). Th erefore, the creation of a professional group of self-confi dent and balanced leaders is a process infl uenced by many factors the results of which only become apparent over a longer period of time. However, appropriate education and training are key factors in this process.Th e development of professions has been most pronounced within the health care system (15). An

important characteristic of professionalism is the integrity of systematic and generalized knowledge which must be used by professionals to solve dif-ferent problems (16,17). Th e basis for the nursing profession and nurses’ knowledge is a good edu-cational system that must be supplemented with continuing education following graduation and should be provided by professional associations and health care organisations (18). Th e signifi -cance of continuing education and development after graduation has been emphasized since the beginning of the nursing profession (19), includ-ing among others, within international nursing organisations (20).Th e health care system in Slovenia employs 16.783 nurses, or 36.6% of all employees in health care (21). Th e fi eld of education in nursing in Slovenia has changed signifi cantly since 2000. In 2000 Slovenia had two nursing colleges with 974 students, while in 2010 there were three faculties and three nurs-ing colleges with 2.435 students (bachelor of sci-ence in nursing, master of nursing) (21,22). Th e higher number of colleges and faculties also resulted in an increased scope of research into leadership in nursing.Leadership training programmes within profes-sional organisations have also undergone signif-icant changes resulting in a greater awareness of the importance of good leadership. In 2000, the Professional Group of Nurses in Management was established as part of the Nurses and Midwives Association of Slovenia (23). Its aim is to provide nursing leaders with modern knowledge, attitudes and skills relating to the management of organisa-tions and human resources. Nurse leaders now have more opportunities to meet and exchange leadership experiences and ideas. Such meetings are intended both for training and for shaping and reinforcing their professional self-confi dence and the homoge-neity of their professional group.Th ese changes will undoubtedly lead to signifi cant improvement in leaders’ self-esteem. We were inter-ested in (research questions):• whether there were signifi cant changes in the

self-assessment of personal characteristics between 2001 and 2011 that would indicate changes in leaders’ self-esteem?

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• whether it was possible to determine homo-geneous groups of leaders with similar charac-teristics based on self-assessments of personal characteristics?

METHODSStudy designTh is study was part of a larger research project enti-tled ‘Leaders in Nursing’ conducted between the autumn of 2010 and the spring of 2011. Th e authors of the study had previously obtained approval from the Management Board of the Nurses and Midwives Association of Slovenia and the managements of individual hospitals. Th e survey was conducted at the 15 largest Slovenian public hospitals: two university medical centers, six general hospitals, and seven specialized hospitals. Th ese institutions employ 87% of all hospital nurses in Slovenia. Th e participating institutions employ 526 nurse leaders, 296 of whom (56% the sample) answered the ques-tionnaire (Table 1).A comparative study (13) entitled ‘Nurses in Slovenia’ was conducted on a representative sam-ple of nurses in 2001. A  sample of 2,450 nurses in Slovenia was established based on the National Register of Nurses and Midwives. A total of 1,067 nurses (44% of the sample) participated in the sur-vey. A secondary data analysis was used to include in Sample 2 only 327 nurse leaders who were employed in public hospitals in 2001.Statistically signifi cant diff erences between the sam-ples were recorded at the leadership level (χ2=7.32, p=0.039). Th e larger share of team leaders in the 2011 sample was the consequence of a reorganisa-tion of nursing care in hospitals aimed at increasing the importance of team work.Th e greatest changes in the population of nurses in Slovenia occurred in the area of formal educa-tion. Th e diff erence is even more pronounced in the group of nurse leaders, which is also refl ected in the sample (statistically signifi cant diff erences at χ2=287.0, p=0.0001). In 2001, 17.5 % of nurse leaders had at least a university education, while in 2011 their share rose to 85.2%.In terms of gender (χ2=0.22; p=0.638) and age (χ2=3.1, p=0.379), there were no statistically signifi -cant diff erences between the samples.

Measurement instrumentTo enable direct comparison, in 2011 the study used the same group of statements that were used in 2001 and other studies of the population of nurses in Slovenia (13, 24). Th e study focused on personal characteristics relating to:• leaders’ self-image (self-satisfaction and person-

al-self (25), personal self-esteem (26), self-im-age and self-values (27), self-mastery (28), agreeableness/neuroticism/conscientiousness (29,30) – item number 1-9 (Table 2),

• leaders’ opinion about their relationships with others: social self (25), social self-esteem (26), interpersonal values (27), people skills (28), extraversion/openness (29, 30) – item number 10-16 (Table 2).

TABLE 1. Demographic data on the sample of nurse leadersSample 1 –

nurse leaders in 2011

Sample 2 – nurse leaders in

2001Number % Number %

Leadership levelHead nurse and heads of departments

19 6.4 30 9.2

Ward head nurses and nurses supervising several teams

111 37.5 149 45.6

Team leader nurse 166 56.1 148 45.3Gender

Female 273 92.2 302 92.4Male 23 7.8 22 6.7N/A 0 0.0 3 0.9

EducationSecondary school 6 2.0 95 29.1Professional college degree

38 12.8 172 52.6

University degree 216 73.0 45 13.8Specialisation, master’s degree, doctorate

36 12.2 12 3.7

N/A 0 0.0 3 0.9Age

Under 30 40 13.5 60 18.330 to 40 93 31.4 102 31.241 to 50 101 34.1 110 33.6Over 50 59 19.9 55 16.8N/A 3 1.0 0 0.0Total 296 100.0 327 100.0

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Th e study used a version of a personal characteristics questionnaire with 16 self-descriptive statements (Table 2). Th e statements were formulated so that they expressed positive self-esteem. Th e respondents used a three-grade scale to answer the following question: “To what degree, in your opinion, are you…” (1 - Not at all, 2 - Moderately, 3 – Very).

Statistical analysisTh e data was analysed using SPSS 19.0. Descriptive statistics were used to describe the sample. Internal consistency was examined using the Cronbach’s alpha. Factor analysis was used to determine groups of leaders with similar personal characteristics. In the factor analysis, principal component analysis with varimax rotations was used to examine which factors of the scale comprised coherent groups of items (31,32). Th e Kaiser-Meyer-Olkin (KMO) test and Bartlett’s test of sphericity was applied to measure sampling adequacy (33). Relationships between variables were analysed using chi-square

tests for categorical variables and the one-way anal-ysis of variance for quantifi able variables (ANOVA). A signifi cance level of alpha = 0.05 was used for all statistical tests.

Reliability and validity of measurement instrumentFirst, we verifi ed the degree of reliability of the mea-surement instrument. Cronbach’s Alpha was 0.79 in 2011 and 0.81 in 2001. Th e value indicated a high level of reliability of the measuring instrument. A similar degree of reliability was produced by the questionnaire in studies on nursing students and nurses conducted in previous years (13,24).Factor Analysis was applied to determine the con-struct validity of the measurement instrument. Th e KMO measure of sampling adequacy was 0.822 in 2001 and 0.793 in 2011 and indicated that factor analysis was appropriate. Bartlett’s test was signifi -cant (p-value less than 0.005). Th is indicates good construct validity.

TABLE 2. Comparison of assessment results between years and groups of nurse leadersItem no.

To what degree, in your opinion, are you…

Mean Std. deviation Index - mean (2001=100)

Index - std. deviation

(2001=100)

Differences between groups according to the F-test (ANOVA)Year Year

2011 2001 2011 2001 Leadership level Education Age GenderA B C D E F G H I J K L1 Reliable 2.92 2.80 0.26 0.41 104.3 64.12 Diligent 2.83 2.56 0.40 0.53 110.5 76.0 **3 Responsible 2.94 2.82 0.24 0.39 104.1 61.8 **4 Practical 2.83 2.58 0.39 0.53 109.5 72.9 * *5 Independent 2.83 2.62 0.38 0.50 108.1 75.6 **6 Intelligent 2.47 2.15 0.51 0.39 114.8 130.07 Educated 2.40 2.13 0.49 0.37 112.9 132.0 */** * **8 Reasonable 2.81 2.57 0.39 0.51 109.3 77.79 Creative 2.58 2.25 0.50 0.49 114.9 101.510 Understanding 2.82 2.68 0.39 0.48 105.0 80.6 *11 Sociable 2.57 2.34 0.52 0.55 109.6 94.1 **12 Willing to put your

ideas into practice2.40 2.11 0.50 0.53 113.7 95.2

13 Interested in social issues

2.49 2.15 0.53 0.55 115.7 97.7 ** */**

14 Critical 2.64 2.52 0.49 0.55 105.1 90.1 *15 Articulate 2.43 2.16 0.51 0.50 112.4 101.2 *16 Interested in new

fi elds of study2.62 2.43 0.52 0.59 107.8 88.3 *

* - Year 2011: difference between groups is signifi cant at p<0.05. ** - Year 2001: difference between groups is signifi cant at p<0.05

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Ethical considerationTh e study was approved by the Honorary Court of Arbitration of the Nurses and Midwives Association of Slovenia. Participants were assured that there was no risk from participating in the study and that their responses would be treated confi dentially.

RESULTSChanges in the self-esteem of nurse leadersTh e average ratings of the detected personal char-acteristics increased in 2011 as compared to 2001 in all areas (Table 2). Nurse leaders in 2011 were signifi cantly more interested in social issues, and they saw themselves as more creative and intelli-gent and more willing to put their ideas into prac-tice. Th e results of the analysis clearly show that the self-esteem of the observed leaders increased signifi cantly.Th e order of importance of individual personal characteristics did not change in any signifi cant way. Most nurse leaders in both years believed they were responsible, reliable and, at least, suffi -ciently educated and willing to put their ideas into practice.A comparison of standard deviations in 2001 and 2011 shows in which areas the diff erences between nurse leaders increased and in which they decreased. Th e variability of assessment results decreased, which indicates a higher homogeneity of the observed group. Th e greatest decreases were recorded in the areas of responsibility (38.2%) and reliability (35.9%) (Colum H in Table  2). Diff erences between the results of the self-assess-ments of personal characteristics among nurse lead-ers increased in the areas of education (32.0 %) and intelligence (30.0%).We examined whether the self-assessments of per-sonal characteristics had been infl uenced by the level of leadership, gender, education or age. Statistically signifi cant diff erences were evident in the following areas (year 2011):• Nurse leaders at the highest leadership levels

said they were more practical and educated, but less understanding.

• Nurse leaders with the highest education said they were more educated, practical and more

interested in new areas of work, but less inter-ested in social issues.

• Older nurse leaders assessed they were more critical and more interested in social issues, but less articulate.

• No diff erences between genders were apparent in any of the areas.

Th e diff erences between the genders were greater in 2001: the women said they were more educated, responsible and diligent, but less independent and sociable than men.Statistically signifi cant diff erences between the results of the self-assessments of personal character-istics between groups defi ned according to the level of leadership, gender, education and age were evi-dent only in a small number of areas. Th erefore, dif-ferences between these groups cannot be seen as the reason for such a pronounced increase in self-esteem between 2001 and 2011.

Homogeneous groups of nurse leaders with similar characteristicsBy using factor analysis we were able to defi ne groups of personal characteristics, and each of these groups was characteristic of one of the groups of nurse leaders. Th e Principal Component Analysis (PCA) method was applied to the extraction of components. According to Kaiser criterion, only the factors that have eigenvalues greater than one are retained. Four factors were extracted that accounted for 49.5% (2011) and 50.4% (2001) of total vari-ability. Varimax rotation was applied in order to optimize the loading factor of each item on the extracted components.In the 2011 data, we defi ned four groups of nurse leaders. Th e fi rst group comprised leaders who believed they were reliable, responsible, practical and independent. Th is group was oriented towards the management of tasks, work, procedures, but less so towards the leadership of people. Th ey are believed to be conscientious and precise.Th e second group comprised leaders who believed they were intelligent, educated, creative and rea-sonable. Th ese leaders are defi ned by knowledge, on which they also base their actions. Th ey are supposed to be characteristically self-restrained and emotionally stable.

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Th e third group comprised leaders who believed they were understanding and sociable. Th eir pri-mary leadership style is people-oriented and inclu-sive. Th ey are open and kind to people around them. Th eir actions are defi ned by empathy.Th e fourth group comprised leaders who were will-ing to put their ideas into practice, interested in social issues and critical, as well as interested in new areas of work and articulate. Leaders in this group are characteristically outward-oriented and tend to shape and infl uence relationships with other people. Th eir actions are supposedly defi ned by their extro-verted nature.Th e results of the factor analysis for 2001 data paint a slightly diff erent picture (Table 3). Here, four fac-tors stand out as well. Th e fi rst factor, which could arguably be linked to extraverted nature and intel-ligence, clearly stands out. Th e groups of character-istics defi ned on the basis of the remaining factors would be diffi cult to relate to the personal charac-teristics of a leader. In the 2011 data, the groups of characteristics were much more clearly defi ned and in accordance with the theory of leadership in other fi elds.

DISCUSSIONTh e analysis shows that the self-assessments of personal characteristics, on the basis of which the self-esteem of a group of nurse leaders was eval-uated, improved between 2001 and 2011 (fi rst research question). In both observed periods (2001 and 2011) the highest ratings were assigned to per-sonal characteristics related to the nature of work in nursing (reliability and responsibility). Other research also shows personal characteristics related to work be the most important for workers in nurs-ing care (34,35).Th e greatest increase was recorded in characteris-tics indicating leaders’ high self-esteem: the share of nurse leaders who believed they were intelligent, creative and interested in social issues increased from 2001 to 2011. Diff erences between assessment results were smaller than in 2001. Th is is indic-ative of the creation of a more homogenous and successful group of leaders as a solid and realistic self-image is one of the key characteristics of a good leader (36). Professional identity, which is shaped by the educational process (37) can only be pre-served through appropriate organized continuing

TABLE 3. Rotated component matrixTo what degree, in your opinion, are you…

Component – 2011a Component – 2001a

1 2 3 4 1 2 3 4Reliable 0.74 0.55Diligent 0.63 0.74 Responsible 0.61 0.58Practical 0.56 0.40 Independent 0.55 0.48Intelligent 0.84 0.63 Educated 0.77 0.46 Reasonable 0.38 0.49 Creative 0.37 0.61 Understanding 0.71 0.64 Sociable 0.64 0.74 Willing to put your ideas into practice 0.70 0.70 Interested in social issues 0.58 0.51 Critical 0.50 0.76Interested in new fi elds of study 0.44 0.55 Articulate 0.41 0.75 Total variance explained 49.5% 50.4%Cronbach’s Alpha 0.79 0.81aExtraction Method: Principal Component Analysis; Rotation Method: Varimax with Kaiser Normalization

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education programs (38). A  nurse’s career path from graduation to the highest leadership position takes 10-15 years (39). Th e positive dimensions of improved self-esteem and better training and educa-tion will only start to show results after a few years, which needs to be confi rmed through additional research.By using the factor analysis of the 2011 data, we defi ned four groups of nurse leaders with similar personal characteristics (second research question). Th e data shows three groups that are most often defi ned as positive for leadership in the Big Five model (10,40,41): extraversion (fourth factor), con-scientiousness (fi rst factor) and openness (third fac-tor). Other studies also confi rm that those factors are most directly linked to leadership (29,30,40).Th e main limitation of our study was that it included only nurse leaders in hospitals. Th erefore, a similar method should be employed to study the self-es-teem of all nurses and compare it to that of nurse leaders. Furthermore, the study does not answer the question whether the higher self-esteem of leaders resulted in better leadership in health care. Studies in other areas show that high self-esteem has a posi-tive impact on the quality of leadership, but there are many other factors infl uencing leadership (10,11).

CONCLUSIONSOur analysis shows that in the period between the two studies (2001 and 2011) a group of leaders with high self-esteem was formed within the nursing profession in Slovenia. Th is was undoubtedly partly due to the activities of professional associations and the expansion of the network of colleges and faculties. Th ere were 3,209 nurses with a univer-sity degree, specialisation and masters’ or doctoral degrees in Slovenia in 2001 compared to 5,576 in 2011  (21,22). Since 2005, increasing numbers of nurses have been coming out of faculties with a university education and are gradually assuming important leadership positions in health care organ-isations. Better support from professional organisa-tions, leadership and management oriented training and higher formal education have all contributed to the higher self-esteem of nurse leaders. Clearly, the key part of responsibility now falls on health care organisations, which need to ensure that this

potential is realised in the form of a higher quality of nursing care.

COMPETING INTERESTSTh ere was no funding source. Th e authors declare that there is no confl ict of interest.

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Journal of Health Sciences

RESEARCH ARTICLE Open Access

ABSTRACT

Introduction: Complex etiology of osteoporosis include genetic, hormonal, environmental and nutritional factors. The aim of this study was to examine infl uence of coffee consumption on bone mineral density in postmenopausal women with estrogen defi ciency in menstrual history.

Methods: This prospective study included 100 postmenopausal women, aged 50-65 years living in Sarajevo area, with estrogen defi ciency in their menstrual history. The controlled clinical trials were con-ducted. Two groups were formed (based on bone mineral density values). The examination group included 50 women who had osteoporosis, while the control group included 50 women without osteoporosis (osteopenia, normal bone mineral density). The lumbar spine and proximal femur bone mineral density was measured by Dual–Energy X–ray Absorptiometry using Hologic QDR-4000 scanner. Coffee drinking habits were assessed for each subject.

Results: The average daily intake of coffee in women with estrogen defi ciency in menstrual history was at 267.6 ml in the examination group and in the control group 111.6 ml. The difference in the average daily intake of coffee between the two groups was statistically signifi cant (p < 0.001). There was registered signifi cant correlation between intake of coffee and bone mineral density in examination (p < 0.01) and in control group (p < 0.05).

Conclusion: This study indicates that coffee consumption is a risk factor for osteoporosis in postmeno-pausal women, aged 50-65 years living in Sarajevo area, with estrogen defi ciency in their menstrual his-tory. It was shown that the effects of coffee on bone mineral density are dose-dependent.

Keywords: coffee consumption; osteoporosis

INTRODUCTIONTh e female reproductive system plays a major role in regulating the acquisition and loss of bone by the skeleton from menarche through senescence  (1). Longer exposure to estrogen, either through nat-ural menstruation or postmenopausal Estrogen Replacement Th erapy, have protective eff ects

Infl uence of coffee consumption on bone mineral density in postmenopausal women with estrogen defi ciency in menstrual historyAmila Kapetanović1*, Dijana Avdić2

1Medical Rehabilitation Center Fojnica, Fojnica, Bosnia and Herzegovina, 2Clinic for orthopedics and traumatology, University Clinical Center of Sarajevo, Sarajevo, Bosnia and Herzegovina

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Amila Kapetanović and Dijana Avdić; 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.

*Corresponding author: Amila Kapetanović,Medical Rehabilitation Center Fojnica, Fojnica, Bosnia and Herzegovina E-mail [email protected]

Submitted August 3 2014 / Accepted September 9 2014

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on bone mineral density (2). Th e loss of ovarian function, whether premature or not, lead to an increased risk of bone mineral loss and developing of osteoporosis because of the lengthened time of exposure to reduced estrogen (3).Osteoporosis has a complex etiology and is con-sidered as a multifactorial polygenic disease in which genetic determinants are modulated by hor-monal, environmental, and nutritional factors (4). Determination of osteoporosis risk factors related to habits (lifestyle) is important for both, preven-tion as well as disease treatment, as these factors can be modifi ed. Caff eine for years is under discus-sion, whether has positive whether adverse impact on health (5). Opinions about impact of coff ee consumption on bone metabolism are still con-troversial. Study of Hasling C. et al. found that a coff ee intake in excess of 1000 ml could induce an extra calcium loss of 1.6 mmol calcium/d, whereas intakes of 1-2 cups of coff ee per day would have lit-tle impact on calcium balance in postmenopausal osteoporotic women, age 48 to 77 years, with post-menopausal crush fracture (6). Barger-Lux MJet Heaney RP analyzed data from 560 calcium balance studies carried out on women aged from 34.8 to 69.3  years. Th e authors found a caff eine relation-ship such that for every 177.5  ml serving of caf-feine-containing coff ee, calcium balance was more negative by 0.114 mmol/day (4.6  mg/day). Th ere was no evidence that the putative caff eine eff ect is confi ned to, or is greater among, subjects with low calcium intakes or those who are older or estro-gen-deprived  (7). Heaney RP found no evidence that caff eine has any harmful eff ect on bone sta-tus or on the calcium economy in individuals who ingest the currently recommended daily allowances of calcium  (8). Study of Lacerda et al. examining eff ects of coff ee on bone metabolism of mousses, indicated that coff ee consumption has an eff ect on metabolism of calcium (including increased level of calcium in urine and plasma, decreased bone mineral density and lower bone volume) (9). Study of Sakamoto et al haven’t found that coff ee stim-ulates loss of bone tissue in mousses (10). Th at intakes of caff eine in amounts >300 mg/d acceler-ate bone loss at the spine in elderly postmenopausal women and that women with the genetic variant of vitamin D receptor appear to be at a greater risk

for this deleterious eff ect of caff eine on bone was indicated in the study of Rapuri PB et al. (11). Direct negative eff ects of caff eine on osteoblastic cells (deleterious eff ect on the osteoblasts viability) was suggested in the study of Tsuang YH et al. (12). Goto et al. have found that plasma concentration sex hormone-binding globulin (SHBG) that binds estrogen (lower bioavailability of sex hormones) was higher in women who consumed four or more cups than women who did not consume coff ee (13). Th e results of Wedick NM et al. study do not indicate a consistent eff ect of caff einated coff ee consumption on SHBG in men or women (14).Th e data about the eff ects of coff ee on bone are inconsistent. Th e aim of this study was to examine infl uence of coff ee consumption on bone mineral density in postmenopausal women with estrogen defi ciency in menstrual history.

METHODSStudy designTh is prospective study included 100 postmeno-pausal women, aged 50-65 years living in Sarajevo area, with estrogen defi ciency in their menstrual history. Th e controled clinical trials were con-ducted. Two groups were formed (based on bone mineral density values, according to the WHO criteria). Th e examination group included 50 women who had osteoporosis, while the con-trol group included 50 women without osteopo-rosis (osteopenia, normal bone mineral density). Th e lumbar spine and proximal femur bone min-eral density was measured by Dual–Energy X–ray Absorptiometry using Hologic QDR-4000 scan-ner. Coff ee drinking habits were assessed for each subject.Th e women who met the following criteria were included in the study: postmenopausal women with estrogen defi ciency in menstrual history (fewer than 30  years menstruation, menopause before age of 45  years), women aged 50-65  years, women who live in the Sarajevo area, women with osteoporosis, women without osteoporosis (osteopenia or normal bone mineral density), women who do not use hor-mone replacement therapy. Th e exclusion criteria were postmenopausal women without estrogen defi -ciency in menstrual history, women younger than

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50 and older than 65  years, women who do not live in the Sarajevo area, women who are not post-menopausal, women who use hormone replacement therapy, women who have a disease that can cause osteoporosis, women who use drugs that may cause osteoporosis.

Statistical analysisStatistical signifi cance between examination and control group in intake of coff ee was tested by Student’s t-test. Th e coeffi cient of linear correlation between intake of coff ee and bone mineral density was calculated. P values less than 0.05 was consid-ered as statistically signifi cant. Data is presented in graphical and tabular forms.

RESULTSTh e average age of women with estrogen defi ciency in their menstrual history in the examination group was 58.48  years, and in the control group was 57.30  years (Figure  1). Th ere was no statistically signifi cant diff erences between these two groups, t = 1.169.Th e average daily intake of coff ee in women with estrogen defi ciency in menstrual history was 267.6  ml in the examination group and in the control group 111.6 ml (Figure 2). Th e diff erence in the average daily intake of coff ee between the two groups was statistically signifi cant, t = 8.697; p < 0.001.Th e coeffi cient of linear correlation between T scores and the average daily intake of coff ee among women with estrogen defi ciency in menstrual history in the examination group was statistically signifi cant, r = − 0.491; p < 0.01. Th e coeffi cient of linear cor-relation between T scores (Table  1) and the daily intake of coff ee among women with estrogen defi -ciency in menstrual history in the control group was statistically signifi cant, r = − 0.356; p < 0.05.

DISCUSSIONTh e peak bone mass in the young can be increased and the rate of bone loss in the elderly possibly be reduced by dietary manipulation, which would be important and benefi cial in the prevention of oste-oporosis (15).

Coff ee, a beverage used worldwide, includes a wide array of components that can have potential implication on health (16). Results of the studies on infl uence of coff ee consumption on calcium metabolism, bone mineral density and fracture risk are contradicting. (6-8, 17–22). Potential of coff ee intake as an osteoporosis risk factor is under debate  (16). Lloyd T. et al. found no association between dietary caff eine intake and total body or femoral neck bone density or bone mass and found no associations between caff eine consumption and longitudinal changes in total body or femoral neck bone measurements (with and without statistical adjustment for calcium intake) (17). In the study of Choi EJ et al. coff ee consumption showed no

0

10

20

30

40

50

60

70

8058.48

57.3

Age

(yea

rs)

EXAMINATION GROUP CONTROL GROUP

FIGURE 1. The average age of women with estrogen defi ciency in menstrual history t = 1.169; no statistically signifi cant.

0

50

100

150

200

250

300 267.6

111.6

Aver

age

daily

inta

ke o

f co

ffee(

ml)

EXAMINATION GROUP CONTROL GROUP

FIGURE 2. The average daily intake of coffee in women with estrogen defi ciency in menstrual history, p < 0.001.

TABLE 1. The coeffi cient of linear correlation between T scores and the daily intake of coffee among women with estrogen defi ciency in menstrual historyParameters Examination group Control groupCoeffi cient of linear correlation

r = −0.491p < 0.01

r = −0.356p < 0.05

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signifi cant association with bone mineral density of either femoral neck or lumbar spine in Korean premenopausal women (18). Ilich JZ et al. found that caff eine is negatively associated with bone mineral density of diff erent skeletal sites in elderly women (19). Hallström H. et al. studied the rela-tion between coff ee intake and bone mineral den-sity, taking into account, genotypes for cytochrome P450 1A2 (CYP1A2) associated with metabolism of caff eine. Men consuming 4 cups of coff ee or more per day had 4% lower bone mineral density at the proximal femur compared with low or non-con-sumers of coff ee. Th is diff erence was not present in women. High consumers of coff ee with C/C geno-type, rapid metabolism of caff eine, had lower bone mineral density than slow metabolizers (T/T and C/T genotypes). Calcium intake did not modify the relation between coff ee and bone mineral den-sity  (20). In their study Tavani A. et al. found no association between hip fractures among women and consumption of regular or decaff einated coff ee, tea, and cola (21). Hallstrom H. et al. found that a high coff ee consumption signifi cantly increased the risk of osteoporotic fractures. Th e results of the study indicate that a daily intake of 330 mg of caf-feine, equivalent to 4 cups (600  ml) of coff ee, or more, may be associated with a modestly increased risk of osteoporotic fractures, especially in women with a low intake of calcium (22).Data from animal studies are also inconsis-tent (9,10). In animal studies the infl uence of indi-vidual constituents of coff ee on bone tissue was examined (23,24). Th e aim of Folwarczna J. et al.

study was to investigate the eff ects of trigonelline, an alkaloid present in coff ee, on bone mechanical properties of rats with normal estrogen level and estrogen defi ciency. Administration of trigonelline did not aff ect the bone turnover markers, bone min-eralization and mechanical properties of the tibial metaphysis, femoral diaphysis, and femoral neck in non-ovariectomized rats, but it worsened the min-eralization and mechanical properties of cancellous bone in ovariectomized rats (estrogen-defi cient rats) (23). Th e results of Folwarczna J. et al. study showed that caff eine has favorably aff ected on the skeletal system of ovariectomized rats, slightly inhib-iting the development of bone changes induced by estrogen defi ciency. Study found no signifi cant

caff eine eff ects on the bone in non-ovariectomized rats (normal estrogen levels) (24).In this study infl uence of coff ee consumption on bone mineral density in postmenopausal women, aged 50-65 years living in Sarajevo area with estro-gen defi ciency in their menstrual history was exam-ined. Th e diff erence in the average daily intake of coff ee between the group of women with osteopo-rosis and group of women without osteoporosis was statistically signifi cant (p < 0.001). Th e coeffi cient of linear correlation between T scores and the aver-age daily intake of coff ee was statistically signifi -cant in both, group of women with osteoporosis (p < 0.01) and group of women without osteopo-rosis (p < 0.05). Results of this study showed that intake of coff ee has an impact on bone mineral den-sity in postmenopausal women, aged 50-65  years living in the Sarajevo area, with estrogen defi ciency in their menstrual history. Th e eff ect of coff ee on bone mineral density was dose-dependent. Th e average amount of consumed coff ee in women with osteoporosis was 267.7 ml, and in women without osteoporosis 116.6 ml.

CONCLUSIONTh is study indicates that coff ee consumption is a risk factor for osteoporosis in postmenopausal women, aged 50-65  years living in Sarajevo area, with estrogen defi ciency in their menstrual his-tory. It was shown that the eff ects of coff ee on bone mineral density are dose-dependent. Based on the results of this research, it recommended that daily consumption of coff ee be limited in order to pre-serve bone health of postmenopausal women with estrogen defi ciency in their menstrual history (the average amount of consumed coff ee in women with-out osteoporosis was 116.6 ml).

CONFLICT OF INTERESTTh e authors declare that they have no competing interests.

REFERENCES1. Clarke BL, Khosla S. Female reproductive system and bone. Estrogen

increase bone formation and decrease loss of bone mass. Arch Biochem Biophys. 2010 Nov 1;503(1):118-28. http://dx.doi.org/10.1016/j.abb.2010.07.006.

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2. Nguyen TV, Jones G, Sambrook PN, White CP, Kelly PJ, Eisman JA. Effects of estrogen exposure and reproductive factors on bone mineral density and osteoporotic fractures. J Clin Endocrinol Metab. 1995 Sep;80(9):2709-14.

3. Kurtoglu-Aksoy N, Akhan SE, Bastu E, Gungor-Ugurlucan F, Telci A, Iyibozkurt AC, Topuz S. Implications of premature ovarian failure on bone turnover markers and bone mineral density. Clin Exp Obstet Gynecol. 2014;41(2):149-53.

4. Gennari L, Merlotti D, De Paola V, Calabrò A, Becherini L, Martini G, Nuti R. Estrogen Receptor Gene Polymorphisms and the Genetics of Osteoporosis: A HuGE Review Am. J. Epidemiol. (2005)161 (4): 307-320. http//dx.doi.org/10.1093/aje/kwi055.

5. Wierzejska R. Caffeine - common ingredient in a diet and its infl uence on human health. Rocz Panstw Zakl Hig. 2012;63(2):141-7.

6. Hasling C, Søndergaard K, Charles P, Mosekilde L. Calcium metabolism in postmenopausal osteoporotic women is determined by dietary calcium and coffee intake. J Nutr. 1992 May;122(5):1119-26.

7. Barger-Lux MJ, Heaney RP. Caffeine and the calcium economy revisited. Osteoporos Int. 1995 Mar;5(2):97-102. http://dx.doi.org/10.1007/BF01623310.

8. Heaney RP. Effects of caffeine on bone and the calcium economy. Food Chem Toxicol. 2002 Sep;40(9):1263-70. http://dx.doi.org/10.1016/S0278-6915(02)00094-7.

9. Lacerda SA, Matuoka RI, Macedo RM, Petenusci SO, Campos AA, Brentegani LG. Bone quality associated with daily intake of coffee: a bio-chemical, radiographic and histometric study. Braz Dent J. 2010;21(3):199-204. http//dx.doi.org/10.1590/S0103-64402010000300004.

10. Sakamoto W, Nishihira J, Fujie K, Iizuka T, Handa H, Ozaki M, Yukawa S. Effect of coffee consumption on bone metabolism. Bone. 2001 Mar;28(3):332-6. http//dx.doi.org/10.1016/S8756-3282(00)00444-0.

11. Rapuri PB, Gallagher JC, Kinyamu HK, Ryschon KL. Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr. 2001 Nov;74(5):694-700.

12. Tsuang YH, Sun JS, Chen LT, Sun SC, Chen SC. Direct effects of caffeine on osteoblastic cells metabolism the possible causal effect of caffeine on the formation of osteoporosis. J Orthop Surg Res. 2006 Oct 7;1:7. http://dx.doi.org/10.1186/1749-799X-1-7.

13. Goto A, Song Y, Chen BH, Manson JE, Buring JE, Liu S. Coffee and caffeine consumption in relation to sex hormone-binding globulin and risk of type 2 diabetes in postmenopausal women. Diabetes. 2011 Jan;60(1):269-75. http://dx.doi.org/10.2337/db10-1193.

14. Wedick NM, Mantzoros CS, Ding EL, Brennan AM, Rosner B, Rimm EB, Hu FB, van Dam RM. The effects of caffeinated and decaffeinated cof-fee on sex hormone-binding globulin and endogenous sex hormone lev-els: a randomized controlled trial. Nutr J. 2012 Oct 19;1186. http//dx.doi.org/10.1186/1475-2891-11-86.

15. Wang P, Zhang H. Review of dietary risk factors for osteoporosis. Wei Sheng Yan Jiu. 2003 Jan;32(1):81-3.

16. Cano-Marquina A, Tarín JJ, Cano A. The impact of coffee on health. Maturitas. 2013 May;75(1):7-21. http://dx.doi.org/10.1016/j.maturitas.2013.02.002.

17. Lloyd T, Rollings N, Eggli DF, Kieselhorst K, Chinchilli VM. Dietary caf-feine intake and bone status of postmenopausal women Am J Clin Nutr. 1997 Jun;65(6):1826-30.

18. Choi EJ, Kim KH, Koh YJ, Lee JS, Lee DR, Park SM. Coffee consumption and bone mineral density in korean premenopausal women. Korean J Fam Med. 2014 Jan;35(1):11-8. http://dx.doi.org/10.4082/kjfm.2014.35.1.11.

19. Ilich JZ, Brownbill RA, Tamborini L, Crncevic-Orlic Z. To drink or not to drink: how are alcohol, caffeine and past smoking related to bone mineral density in elderly women? J Am Coll Nutr. 2002 Dec;21(6):536-44. http://dx.doi.org/10.1080/07315724.2002.10719252.

20. Hallström H, Melhus H, Glynn A, Lind L, Syvänen AC, Michaëlsson K. Coffee consumption and CYP1A2 genotype in relation to bone mineral density of the proximal femur in elderly men and women: a cohort study. Nutr Metab (Lond). 2010 Feb 22;7:12. http://dx.doi.org/10.1186/1743-7075-7-12.

21. Tavani A, Negri E, La Vecchia C. Coffee intake and risk of hip fracture in women in northern Italy. Prev Med. 1995 Jul;24(4):396-400. http://dx.doi.org/10.1006/pmed.1995.1064.

22. Hallström H, Wolk A, Glynn A, Michaëlsson K. Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women. Osteoporos Int. 2006;17(7):1055-64. http://dx.doi.org/10.1007/s00198-006-0109-y.

23. Folwarczna J, Zych M, Nowińska B, Pytlik M, Janas A. Unfavorable effect of trigonelline, an alkaloid present in coffee and fenugreek, on bone mechanical properties in estrogen-defi cient rats. Mol Nutr Food Res. 2014 Jul;58(7):1457-64. http://dx.doi.org/10.1002/mnfr.201300936.

24. Folwarczna J, Pytlik M, Zych M, Cegieła U, Kaczmarczyk-Sedlak I, Nowińska B, Sliwiński L. Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats. Mol Nutr Food Res. 2013 Oct;57(10):1772-84.

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Journal of Health Sciences

RESEARCH ARTICLE Open Access

Evaluation of the treatment effi cacy of patients with multiple sclerosis using Barthel index and expanded disability status scaleEdina Tanović1*, Dževad Vrabac1, Aldijana Kadić1, Admir Rama2, Haris Tanović3

1Clinic for Abdominal Surgery, University Clinical Center Sarajevo, Bosnia and Hercegovina, 2Turkish Clinic Bahceci, Sarajevo, Bosnia and Hercegovina, 3Clinic for Physical Medicine and Rehabilitation, University Clinical Center Sarajevo, Bosnia and Hercegovina

ABSTRACT

Introduction: Multiple sclerosis (MS) is a chronic, autoimmune and progressive multifocal demyelinating disease of the central nervous system. The aim of this study was to evaluate rehabilitation of patients with multiple sclerosis using BI (Barthel index) and EDSS (Expanded Disability Status Scale).

Methods: A clinical observational study was made at the clinic for physical medicine and rehabilitation in Sarajevo. We analyzed 49 patients with MS in relation of gender, age and level of disability at admission and discharge, patient disability were estimated using EDSS scale. The ability of patients in their activities of daily living were also analyzed according to the BI at admission and discharge.

Results: Of the total number of patients (n=49) there were 15 men and 34 women. The average age of female patient was 42.38±13.48 and male patient 46.06±9.56. EDSS values were signifi cantly different at the beginning and at the end of the therapy (p=0.001) as was the value of BI (p=0.001).

Conclusion: MS patients, after the rehabilitation in hospital conditions show signifi cant recovery and a reduced level of disability; they show higher independence in activities but rehabilitation demands individual approach and adjustment with what patients are currently capable of achieving.

Keywords: rehabilitation; MS (Multiple Sclerosis); EDSS (Expanded Disability Status Scale); BI (Barthel Index)

*Corresponding author: Prof. Dr Edina Tanović,Clinic for Physical medicine and rehabilitation,University Clinical Center Sarajevo,Bolnička 25, 71000 Sarajevo,Bosnia & HerzegovinaE-mail: [email protected]

Submitted August 03, 2014 / Accepted September 08, 2014

© 2014 Edina Tanović, 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.

INTRODUCTIONMultiple sclerosis (MS) is a chronic, demyelinating and progressive multi-focal disease which aff ects

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

the auto-immunity of the central nervous system. When a certain part of the myelin sheath is infl amed and damaged, transfer of impulses through neurons is disturbed, slow or intermittent (1-3). Clinical symptoms of MS include nystagmus, tremors and dysarthria, eye disorder, movement disorders, sen-sibility problems with the coordination and balance of movement, problems with urination and defeca-tion, sexual dysfunction, disturbances in cognition, fatigue, pain etc. (4,5).

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Symptomatic treatment includes a full range of pro-cedures that aim to alleviate the existing symptoms, in order to maintain active mobility for as long as possible and reduce the degree of disability of these patients (6,7).Th e plan of rehabilitation of these patients is made to the status of disability by EDSS scale. Th e minimum value of the EDSS scale is 0 (normal neurological examination result) and the highest 10 (death due to complications of MS).Activities of daily living were assessed by the Barthel Index with the lowest value of 0 (total dependence on others for care and assistance) to 20 (indepen-dent in activities of daily living) (8,9).MS is often diagnosed in people between the ages of 25 and 50, but rarely in children and persons above age of 60. Women are 2 to 3 times more prone than man in contracting MS (6,7).Th e aim of this study was to evaluate rehabilitation of patients with multiple sclerosis using BI (Barthel index) and EDSS (Expanded Disability Status Scale).

METHODSA clinical observational study was made at the Clinic for physiology and rehabilitation, University Clinical center Sarajevo. Th e study included 49 patients with MS of both genders aged between 18 and 65 who were diagnosed with MS and who have undergone the recommended physical therapy as per the protocol. Th e study excluded patients who have not undergone physical therapy as per the protocol or had their treatment continued at the Neurological clinic in Sarajevo due to the worsen-ing of the underlying disease. Level of disability of patients at admission and discharge in accordance with the EDSS (Expanded Disability Status Scale) is used as a measure of disease progression. Th is scale ranges from 0 to 10, with lower scores indicating

lower level of disability. We have also analyzed the abilities of the patients in their activities of daily liv-ing according to the Barthel index at admission and discharge. Th is scale ranges from 0 to 20. A patient is fully dependent when the sum of point was 0-4, 5-12 shows high level of dependence, 13-18 shows moderate level, 19 shows low level and 20 shows total independence.

Statistical analysisAll the analytical data are presented in tables with an absolute number of cases, the arithmetic mean, standard deviation and range of value χ2  -  square test. We also used ANOVA and Wilcoxon nonpara-metric test. All the tests with p<0.05 were consid-ered statistically signifi cant.

RESULTSOf the total number of patients (n=49) there were 15 men and 34 women. Th e average age was 43.51±12.43, the average age of female patients was 42.38±13.48 years, and the average age of male patients was 46.06±9.56 years (Table 1).By using a nonparametric Wilcoxon test, there was a statistically signifi cant diff erence in the EDSS value before and after therapy (Table 2). Th e EDSS value before therapy was 6.04±1.52 (required regular or occasional assistance to walk up to 100 m with or without rest), whereas after therapy, the value fell to 5.46±1.51 (mobile without aid or rest, but with restrictions in daily activities), Z=-0.514; p=0.001.By analyzing activities of daily living of the patients-before and after the therapy-based on the Barthel index and by implementing the Wilcoxon test, we have established a statistically signifi cant diff erence in the clinical status. Before the therapy and after reception, based on the Barthel index, the patients were classifi ed in the heavily dependent cat-egory (12.89±5.52), while after therapy their clinical

TABLE 1. Gender and age of patientsN Mean SD SE 95% CI for mean Minimum Maximum

Lower bound Upper boundFemale 34 42.38 13.48 2.31 37.67 47.08 18.00 66.00Male 15 46.06 9.56 2.46 40.76 51.36 28.00 65.00Total 49 43.51 12.43 1.77 39.98 47.08 18.00 66.00

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condition improved and they were classifi ed, accord-ing to the Barthel index, with moderate dependence (14.48± 5.37), Z=-4.843; p=0.001 (Table 3).

DISCUSSIONMultiple sclerosis (MS) is a chronic disease of the central nervous system. It was named after lesions where histopathological samples of brain tissue appear as indurated areas-plaques (6). Th ese plaques are “disseminated” in diff erent areas of the cen-tral nervous system and appear at irregular inter-vals. With the development of neuro-radiological techniques, especially MRI (magnetic resonance imaging) of the brain, the number of diagnosed and newly diagnosed patients with MS has dramatically increased. It was found that in patients with MS, typically only one clinical manifestation of the dis-ease occurs for each new 8 to 10 new lesions in the brain, that were confi rmed by MRI (7).Clinical features of patients with MS is actually very diverse with diff erent symptoms that vary in severity. Th ese patients, after diagnosis and neuro-logical therapy, register for the rehabilitation mainly because of the problems with their motor skills and their inability to control their sphincters (8,9).Study results show statistically signifi cant diff erence in the gender representation of the respondents, and in the examined sample women dominated (p=0.007). Th ese fi gures correspond to data from the literature; female patients suff er from MS, 2 to 3 times more than men.

Analysis of the age structure of patients shows that the average age was 43.51±12.43, the average age of female patients was 42.38±13.48 years, and for male patients, it was 46.06±9.56 years. Th is data indicates that there is no statistically signifi cant diff erence in age structure of the respondents in relation to their gender (p=0.344). Research conducted earlier show that the average age of patients with MS in reha-bilitation was lower. We think that reason for this diff erence is better diagnosis and the earlier involve-ment of patients in the rehabilitation process, but it is also possible that other studies involved younger patients (10,11).Th e assessment of the degree of disability is shown through EDSS and used as a measure of the pro-gression of the disease and severity of neurological disorder in these patients (12). During the process of rehabilitation, patients tried to increase their mobility by kinesiotherapy (13). Also, all patients underwent occupational therapy to gain compe-tence in day to day activities. Th e analysis of the EDSS values before and after the therapy showed statistically signifi cant diff erences. Th e EDSS value before therapy was V6.04±1.52 which means that patients needed permanent or temporary orthope-dic aid such as the use of canes, crutches or walk-ing frame to walk up to 100 m, with or without rest; while after the therapy, the value dropped to 5.46±1.51, which means that the patient is mobile without assistance or rest, but is limited in daily activities (p=0.001). Our research shows that patients with a greater degree of disability were registered for the rehabilitation then what other studies have shown (14,15). Research conducted in France and England have shown that inpatient rehabilitations is carried out for small disabilities and in the earlier phases of the disease when they expect the eff ects of the treatment to be better (16-18).By analyzing the activities of daily living accord-ing to the Barthel index, signifi cant statistical diff erence in clinical conditions was established (p=0.001) before and after physical therapy. Upon reception, the patients were classifi ed as being heav-ily dependent (12.89±5.52), while after the treat-ment, their clinical condition improved and they were, according to the Barthel index, classifi ed as being moderately dependent (14.48±5.37). Th ese

TABLE 2. EDSS scale values at admission and dischargeN Mean Std. deviation Minimum Maximum

EDSS at admission

49 6.0408 1.52697 3.00 9.00

EDSS at discharge

49 5.4694 1.51523 3.00 9.00

Z=-0.514; p=0.001

TABLE 3. Barthel index value at admission and dischargeN Mean Std. deviation Minimum Maximum

BI at admission

49 12.89 5.52 3.00 20.00

BI at discharge

49 14.48 5.37 4.00 20.00

Z=-4.834; p=0.001

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data confi rm that physical therapy (kinesiotherapy and occupational therapy) is of great importance in enabling patients in carrying out day to day activi-ties. Research done in the last three years also gives similar results. It is recommended that the evalua-tion of diff erent possibilities and aspects of physi-cal therapy should be tailored to each patient and to respect current possibilities of these patients in each therapeutic procedure (19,20). An important prognostic factor is the movement in the Barthel index at the beginning, during and after physical therapy which will, if stagnant, show that the best clinical recovery in day to day life activities has been reached (20).

CONCLUSIONPatients with the MS, after rehabilitation in hospital conditions, show signifi cant recovery and reduced degrees of disability. In activities of daily living they were more independent, but the rehabilitation demands an individual approach and adaptation to the current capacities of the patients.

CONFLICT OF INTERESTTh e authors declare no confl ict of interest.

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13. Robinet E, Favre A, Zaaraoui W, Guye M, Asquinazi P, Bardot P, Pelletier J, Ranjeva JP, Audoin B. Physical rehabilitation in associated with structural and functional brain plasticity in patients with multiple sclerosis. Europ J of Phys and Rehabil Med 2014;50(1) 111.

14. Gallien P, Nicolas B, Durufl e A, Robineau S, Petrilli S, Autret K, Houdakor J, Le Meur C. Physical training and muscle strengthening im multiple sclero-sis. Europ J of Phys and Rehabil Med 2014;50(1) 112.

15. Thoumie P. Balance in multiple sclerosis. Evaluation and rehabilitation. Europ J of Phys and Rehabil Med 2014;50(1) 112.

16. Allart E, Benoit A, Thevenon A, Tiffreau V, Outteryck O, Zephir H, Lacour A, Vermersch P, Blanchard A. Characteristics of walking fatigability in Mutiple Sclerosis. Europ J of Phys and Rehabil Med 2014;50(1) 112-3.

17. Rasova K. Describing availability and characteristics of ohysical therapy in Multiple Sclerosis across Europe: a qualitative study. Europ J of Phys and Rehabil Med 2014;50(1) 115.

18. Loiseau K, Valentini F, Robain G. Management of urinary dysfunction in multiple sclerosis patients: our experience vs United-Kingdom consensus. J Neurol Neurosurg Psychiatry 2009;80:470-477.

19. Norbert M, Lemaire-Desreumaux S, Guyot MA, Donze C, Weissland T. Contribution of the adapted physical activities for the improvement of the quality of life at the persons affected by multiple sclerosis. American Journal od Prevetive Medicine 2013;44:76-84.

20. Layadi K, Chu O. Multiple sclerosis, a multidimensional disability. Europ J of Phys and Rehabil Med 2014;50(1) 117.

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Journal of Health Sciences

RESEARCH ARTICLE Open Access

Adherence to oral anticoagulation therapyLana Lekić1*, Alen Lekić2, Alden Begić3

1Boehringer Ingelheim RCV GmbH&Co.KG, Representative Offi ce, Grbavička 4, 71000 Sarajevo, Bosnia and Herzegovina, 2Sanofi -aventis Groupe, Representative Offi ce in Bosnia and Herzegovina, Fra Anđela Zvizdovića 1/VIII, 71000 Sarajevo, Bosnia and Herzegovina, 3Clinic for Vascular Diseases, Clinical Center of Sarajevo University, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina

ABSTRACT

Introduction: Warfarin is the most frequently prescribed anticoagulant. Clinical treatment is demanding because of the narrow therapeutic range and considerable differences between the patients. The aim of this survey is to establish adherence to warfarin in subjects who have been prescribed warfarin as a long-term therapy.

Methods: The survey included 30 subjects, and was conducted at local pharmacy store. Statistical processing was carried out using the SPSS (ver. 21.) software. Used for qualitative variables was the Chi-square test, and for quantitative ones the ANOVA test. Data were provided in the form of tables and charts. Level of signifi cance was p=0.05.

Results: The survey included 30 subjects, 14 men and 16 women. Of the total number of polled subjects, 15 were informed by a health care professional about the specifi cities of warfarin use, 7 said they were not informed, while 8 said they did not know. Most compliant in terms of regularly taking their medicines were pensioners, followed by the unemployed, χ2=13.231; p<0.05. The number of subjects within the expected therapeutic INR range was 22 (p<0.05).

Conclusion: Strict compliance with the warfarin regimen is important in order to increase its effective-ness, extend the time and strengthen the intensity of anticoagulant action in the body. That is why the target groups of patients, who use warfarin, need additional information before and during therapy, in order to avoid side effects, and at the same time maintain therapeutic effi cacy of the medicine through-out the treatment.

Keywords: adherence; compliance; anticoagulation therapy

*Corresponding Author: Lana Lekić, mr sci pharm specBoehringer Ingelheim RCV GmbH&Co.KG, Representative Offi ceGrbavička 4, 71000 Sarajevo, Bosnia and HerzegovinaPhone: +387 62 205950E-mail: [email protected]

Submitted August 12, 2014 / Accepted September 11, 2014

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Lana Lekić, 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.

INTRODUCTIONWarfarin is the most frequently prescribed anti-coagulant; it is prescribed to more than 2 million

new patients every year. Warfarin is often used as a permanent therapy for prevention of embo-lism in patients with atrial fi brillation, heart valve disease, and for primary and secondary preven-tion of venous thromboembolism (1). Warfarin is also used to prevent thromboembolic attacks in patients with acute myocardial infarction and angina pectoris, in patients with biological heart valves, and after certain orthopedic surgeries. Clinical treatment is demanding because of the

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narrow therapeutic range and considerable dif-ferences between the patients. In the absence of data obtained by genetic research or clinical infor-mation to predict the necessary dose of warfarin for each individual patient (2), initial prescribed doses may be too low, which increases the risk of thrombosis, or too high, which leads to the risk of excessive anticoagulation and heavy bleeding. In the United States, there are annually up to 800 adverse events related to the use of warfarin that are encompassed by the reporting rule (3). Th e risk of serious warfarin-related side-eff ects, its narrow therapeutic range and large inter-individual dosing diff erences require a preparation of algorithms in order to be able to predict, as closely as possible, the dose necessary at the initial stage(s) of treatment. Because proper administration of therapy remains a clinically signifi cant problem despite years of research (4), a new assessment of basic issues, such as the terms used in the fi eld, may be necessary to be able to identify innovative strategies of clinical interventions and investigations (5). Adherence is defi ned as: “the extent to which patients fol-low the instructions they are given for prescribed treatments” (6). Adherence to warfarin treatment, as well to that of other medicines (7), is essential for a good health condition of elderly patients and is thus a critical health care component. Non-compliance with the recommendations for the therapy at old age has been proven to increase the likelihood of therapeutic failure (8) and is respon-sible for unnecessary complications leading to increased health protection costs, early functional disability and premature death (9). Poor adherence to therapy was reported in all age groups. However, a larger prevalence of cognitive and functional dis-orders in elderly persons increases the risk of poor adherence. Multiple concomitant diseases and a complex medical treatment may further compro-mise warfarin adherence. Age-related changes in pharmacokinetics and pharmacodynamics render this population even more sensitive to the prob-lems caused by poor adherence to therapy (10).Th e aim of the study was to determine the adher-ence to warfarin in patient’s whom warfarin is a long-term therapy and to evaluate the factors that directly or indirectly reduce or increase the level of adherence.

METHODSTh e survey included 30 subjects, who were under-going an anticoagulant therapy. Th e survey was con-ducted at local pharmacy store in Sarajevo in 2013. Th e main inclusion criterion was continuous war-farin therapy through at least 12  months. Within the group of subjects who met inclusion criteria, 30  patients were randomly chosen. Th e subjects were polled, and the answers received were statisti-cally processed. Modifi ed Morisky questionnaire on chronic therapy adherence has been used. Subjects have had 4 measurements of INR values during the therapy course.

Statistical analysisStatistical processing was carried out using the SPSS (ver. 21.) software. Used for qualitative variables was the Chi-square test, and for quantitative ones the ANOVA test. Data were provided in the form of tables and charts. Level of signifi cance was p=0.05.

RESULTSTh e survey included 30 subjects, 14 men and 16 women. An analysis of average age of the subjects, by applying the ANOVA test, did not fi nd a statis-tically signifi cant diff erence (Table 1). Th e average age of male subjects was 55.14±16.96  years, and that of female subjects 54.43±15.48 years, F=0.014; p=0.906.An analysis of marital status of the subjects included in the survey found that the majority of the subjects were married (n=22), while three subjects from each group have never been married or have the status of a widow(er). One of the subjects was divorced (Figure 1).Figure  2 shows INR values during measurement. Established with the use of the Chi-square test, there was a statistically signifi cant diff erence in the frequency of fi ndings within the expected thera-peutic range (p<0.05). On fi rst measurement, in 12 subjects the INR values were within the expected therapeutic range, on the second measurement 14, on the third measurement 17, and fi nally on the ultimate, fourth, measurement the number of subjects whose results were within the expected INR therapeutic range was 22.

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Of the total number of polled subjects, 15 were informed by a health care professional about the specifi cities of warfarin use, 7 said they were not informed, while 8 said they did not know (Table 2).Answers to the question about the frequency of forgetting to take the medicine have produced statistically signifi cant diff erence (Table  3). Most compliant in terms of regularly taking their medi-cines were pensioners, followed by the unemployed, χ2=13.231; p<0.05.Over the past two weeks, the frequency of forgetting to take medicine was the lowest in pensioners and the unemployed (Table 4), while those employed and students tend to forget to take their medicines more often, so there is a statistically signifi cant diff erence

in relation to the employment status, χ2=14.948; p<0.05.Based on the answers to the question on adherence, the subjects mostly said they did not forget to take medicines while traveling; also they never stop using medicines without prior consultation with the rel-evant doctor. When asked whether they feel under pressure because daily administration of medicines might be impractical, they mostly said they never felt that way, while 5 subjects said they sometimes do feel under pressure (Table 5).

DISCUSSIONCoumarine derivatives (warfarin and acenocouma-rol) are vitamin K antagonists (VKA) and are used for long-term treatment of patients with venous thrombo-embolism (VTE). Warfarin therapy usually starts within 24-72 hours of the onset of parenteral heparin treatment. Th e usual initial dose is 5-10 mg, while lower doses are recommended to elderly patients, or those with lower body weight, or underweight patients. Warfarin doses and their monitoring have been adjusted to the INR (inter-national normalized ratio) values (11). Th e survey polled 30  patients on warfarin. Th e average age of the subjects was 55. Most of the subjects were married. While measuring INR values during the treatment statistically signifi cant diff erence in terms of the number of subjects with referent

3

22

13

10

5

10

15

20

25

never married marrıed dıvorced widower widower livingwith the Partner

FIGURE 1. Marital status of subjects.

TABLE 1. Age and gender of subjectsN Mean SD Std.

Error95% confi dence interval for mean Minimum Maximum

Lower bound Upper boundMale 14 55.14 16.96 4.53 45.3473 64.9384 23.00 75.00Female 16 54.43 15.48 3.87 46.1848 62.6902 30.00 75.00Total 30 54.76 15.91 2.90 48.8247 60.7086 23.00 75.00

FIGURE 2. INR values during measurement period.

1214

17

22

12 1311

763 2 1

0

5

10

15

20

25

I measurement II measurement III measurement IV measurement

the anticipated therapeutic rangebelow the targeted therapeutic valueabove the target therapeutic value

TABLE 2. Level of information concerning the specifi cities of warfarin use, provided by health care professional

Frequency Percent Valid percent

Cumulative percent

Answer Yes 15 50.0 50.0 50.0No 7 23.3 23.3 73.3Do not know

8 26.7 26.7 100.0

Total 30 100.0 100.0

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values during 4 measurements was discovered. On fi rst measurement, the fi gure was 12, and after the fourth measurement the number of subjects within the expected therapeutic INR range was 22 (p<0.05) (Chart 2). Randomized clinical studies during which the patients indicated for anticoag-ulant therapy were randomly prescribed warfarin or some other alternative anticoagulant were rather helpful by showing the risk of warfarin-related non-compliance (5,12), independently from the potentially confounding factors aff ecting the valid-ity of observational studies. When it comes to patients who were prescribed warfarin or an alter-native medicine, it is necessary to analyze addi-tional factors aff ecting the treatment outcome due to non-compliance or improper drug administra-tion (6,8). In such studies, regular INR testing was carried out mostly on randomized patients using warfarin. In these studies, both the side-eff ects and the monitoring may be factors aff ecting poor adherence (13). Some trials have shown that sub-jects using oral anticoagulants tend to discontinue their therapy more often, while some have shown no diff erence in terms of non-compliance with the prescribed therapy in relation to placebo (13). In the polled group, only 50% of the subjects were informed by a health care professional about the specifi cities of warfarin administration. Th e

frequency of forgetting to take medicines was most often reported in those employed, while pen-sioners were most regular in taking their therapy. Th e subjects polled mostly said they did not for-get to take warfarin even when they traveled. Of the total number of subjects (n=30), 28 said they never stopped taking warfarin without consulting a physician, despite good clinical picture of primary disease for which warfarin has been administered. Most of the subjects never feel pressure on account of the medicine administration regimen, while 5  subjects said they sometimes felt pressure, and 4  subjects feel pressure more often. Unemployed subjects are the ones who have most diffi culties remembering to take warfarin. A study conducted in Japan analyzed warfarin adherence in subjects who took therapy for atrial fi brillation (14). Of the total number of subjects (n=330), as many as 52% did not know the therapeutic signifi cance of war-farin. A questionnaire found that only 51% of the subjects had a basic preliminary knowledge of war-farin, atrial fi brillation and heart attack (14).

CONCLUSIONStrict compliance with the warfarin regimen is important in order to increase its eff ectiveness, extend the time and strengthen the intensity of anticoagulant action in the body. Th at is why the target groups of patients, who use warfarin, need additional information before and during therapy, and a quality interaction between the health care professional and the patient, in order to avoid side eff ects, and at the same time maintain therapeutic effi cacy of the medicine throughout the treatment. Adherence to warfarin can be successfully mon-itored by determining the value of INR, however adherence itself is directly aff ected by patient’s knowledge on warfarin’s mode of action, patient’s

TABLE 3. Frequency of forgetting to take medicineEmployment status Total

Unemployed Employed Student PensionerI never forget to take medicine 9 5 0 11 25I forget to take medicine once a week 2 2 0 0 4I forget to take medicine 2 to 3 times a week 0 0 1 0 1Total 11 7 1 11 30

TABLE 4. Frequency of forgetting to take medicine over the past two weeks

Employment status TotalUnemployed Employed Student Pensioner

Not once 11 5 0 11 27Once or twice

0 2 0 0 2

3 to 5 times 0 0 1 0 1Total 11 7 1 11 30

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daily and professional activities as well as form of the drug and therapy regimen.

COMPETING INTERESTSLana Lekić works as a medical representative for 1Boehringer Ingelheim RCV GmbH&Co.KG. Alen Lekić works as a medical representative for Sanofi Aventis groupe.

REFERENCES1. Hylek EM, Skates SJ, Sheehan MA, Singer DE. An analysis of the lowest

effective intensity of prophylactic anticoagulation for patients with non-rheumatic atrial fi brillation. N Engl J Med 1996;335:540-6. http://dx.doi.org/10.1056/NEJM199608223350802.

2. Redman AR, Zheng J, Shamsi SA, Huo J, Kelly EJ, Ho RJY, et al. Variant CYP2C9 alleles and warfarin concentrations in patients receiv-ing low-dose versus average-dose warfarin therapy. Clin Appl Thromb Haemost 2008;14:29-37. http://dx.doi.org/10.1177/1076029607304403.

3. Božina N, Bradamante V, Lovrić M. Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxic-ity, and cancer risk. Arh Hig Rada Toksikol 2009;60:217-42. http://dx.doi.org/10.2478/10004-1254-60-2009-1885.

4. García-Martín E, Martínez C, Ladero JM, Agúndez JA. Interethnic and

TABLE 5. Answers to questions on complianceEmployment status Total

Unemployed Employed Student PensionerWhen you travel, do you forget to take your medicines with you?I do not travel 5 4 1 6 16Never 6 3 0 5 14χ2=1.197; p=0.754When you feel your health is under control, do you sometimes stop taking medicines on your own, without consulting a doctor?I never do it alone 11 6 0 11 28I sometimes do it alone 0 1 0 0 1I always do it alone 0 0 1 0 1χ2=11.727; p=0.068Taking medicines every day is impractical for many people. Do you feel under pressure because you need to follow recommendations for your treatment?I never feel that way 8 5 0 7 20I sometimes feel that way 1 2 0 2 5I often feel that way 2 0 0 2 4I always feel that way 0 0 1 0 1χ2=12.006; p=0.213How often do you have diffi culties remembering to take your medicine?Never 8 6 0 10 24Sometimes 3 1 0 1 5Often 0 0 1 0 1χ2=0.249; p=0.168

intraethnic variability of CYP2C8 and CYP2C9 polymorphisms in healthy individuals. Mol Diagn Ther 2006;10:29-40. http://dx.doi.org/10.1007/BF03256440.

5. Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest. 2008;133(6 Suppl):454S–545S.

6. Fanikos J, Stapinski C, Koo S, Kucher N, Tsilimingras K, Goldhaber SZ. Medication errors associated with anticoagulant therapy in the hos-pital. Am J Cardiol. 2004;94(4):532–535. http://dx.doi.org/10.1016/j.amjcard.2004.04.075.

7. Brandolese R, Scordo MG, Spina E, Gusella M, Padrini R. Severe phenyt-oin intoxication in a subject homozygous for CYP2C9*3. Clin Pharmacol Ther 2001;70:391-4.

8. The 5 million lives campaign. http://www.ihi.org/IHI/Programs/Campaign/Updated 2009. Accessed December 1, 2009.

9. Rollason V, Samer C, Piguet V, Dayer P, Desmeules J. Pharmacogenetics of analgesics: toward the individualization of prescription. Pharmacogenomics 2008;9:905-33. http://dx.doi.org/10.2217/14622416.9.7.905.

10. Urquhart BL, Tirona RG, Kim RB. Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interin-dividual variability in response to drugs. J Clin Pharmacol 2007;47:566-78. http://dx.doi.org/10.1177/0091270007299930.

11. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic therapy in atrial fi brillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest. 2008;133(6 Suppl):546S–592S.

12. Salem DN, O’Gara PT, Madias C, Pauker SG, American College of Chest

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Physicians Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)Chest. 2008;133(6 Suppl):593S–629S.

13. Stafford RS, Singer DE. National patterns of warfarin use in atrial fi brilla-tion. Arch Intern Med. 1996; 156 (22):2537–2541.

14. Nobuyuki A, Hiroko A, Rieko M, Makiko A, Sadako F. Patıents’ knowledge of atrıal fıbrıllatıon and warfarın: adherence and complıance to war-farın and frequency dıstrıbutıon of ınternatıonal normalızed ratıo values durıng warfarın takıng free to vıew. Anzai-Furuya Clinic, Oyama, Japan Chest. 2009; 136 (4_Meeting Abstracts):99S.

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Journal of Health Sciences

ORIGINAL ARTICLE Open Access

Knowledge, perception, practices and barriers of healthcare professionals in Bosnia and Herzegovina towards adverse drug reaction reportingMaša Amrain1*, Fahir Bečić2

1Boehringer Ingelheim BH d.o.o., Regulatory Affairs Department, Sarajevo, Bosnia and Herzegovina, 2 Department of Pharmacology, University of Sarajevo Faculty of Pharmacy, Sarajevo, Bosnia and Herzegovina

ABSTRACT

Introduction: Pharmacovigilance is an arm of patient care. No one wants to harm patients, but unfortunately any medicine will sometimes do just this. Underreporting of adverse drug reactions by healthcare professionals is a major problem in many countries. In order to determine whether our phar-macovigilance system could be improved, and identify reasons for under-reporting, a study to investigate the role of health care professionals in adverse drug reaction (ADR) reporting was performed.

Methods: A pretested questionnaire comprising of 20 questions was designed for assessment of knowl-edge, perceptions, practice and barriers toward ADR reporting on a random sample of 1000 healthcare professionals in Bosnia and Herzegovina.

Results: Of the 1000 respondents, 870 (87%) completed the questionnaire. The survey showed that 62.9% health care professionals would report ADR to the Agency for Medicinal Products and Medical Device of Bosnia and Herzegovina (ALMBIH). Most of surveyed respondents has a positive perception towards ADR reporting, and believes that this is part of their professional and legal obligation, and they also recognize the importance of reporting adverse drug reactions. Only small percent (15.4%) of surveyed health care professionals reported adverse drug reaction.

Conclusions: The knowledge of ADRs and how to report them is inadequate among health care pro-fessionals. Perception toward ADR reporting was positive, but it is not refl ected in the actual practice of ADRs, probably because of little experience and knowledge regarding pharmacovigilance. Interventions such as education and training, focusing on the aims of pharmacovigilance, completing the ADR form and clarifying the reporting criteria are strongly recommended.

Keywords: knowledge; health care professionals; adverse drug reaction (ADR); pharmacovigilance; Bosnia and Herzegovina

*Corresponding author: Maša Amrain,Boehringer Ingelheim BH d.o.o.,Regulatory Affairs department Sarajevo,Bosnia and Herzegovina,Phone:+38762849727,E-mail: [email protected]

Submitted August 3 2014 / Accepted September 20 2014

© 2014 Maša Amrain and Fahir Bečić; 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.

INTRODUCTIONAny drug/medicine during its normal therapeu-tic use has a potential to produce adverse drug reaction(s) (ADRs). ADRs contribute to a signif-icant number of morbidity and mortality all over the world (1). It has been estimated that around

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2.9-5.6% of all hospital admissions are due to ADRs and as many as 35% of hospitalized patients experi-ence an ADR during their hospitalization (2). Th e economic burden of ADRs is also considerable; for example in the United States, annual total cost of $47.4 billion for 8.7 million drug related admis-sions were reported (3).Many developed countries have strong and effi cient pharmacovigilance systems. Good pharmacovigi-lance system will identify the risks and the risk fac-tors in the shortest possible time so that harm can be avoided or minimized (4). Th ese systems among other use spontaneous reporting to collect and ana-lyze adverse events associated with the use of drugs. Th ough this process is not perfect, it can provide evidence that can be used to establish regulatory action to protect public health, and in addition it is fast and cost-effi cient method.Several studies (5) have indicated a variety of obsta-cles to the spontaneous reporting of ADRs, such as lack of time (6,7) diff erent care priorities (7), uncer-tainty about the drug causing the ADR (7-10), diffi culty in accessing reporting forms (6), lack of awareness of the requirements for reporting (7,10) and lack of understanding of the purpose of sponta-neous reporting systems (6).Physicians, pharmacists, dentists and nurses are in a position to play a major key role in pharmacovig-ilance programs (11,12) but underreporting is very common, with an estimated median underreporting rate (defi ned as percentage of ADRs detected from intensive data collection that were not reported to relevant spontaneous reporting systems) of 94% (5).Pharmacovigilance is still in its infancy in Bosnia and Herzegovina (BiH) and there exists very limited knowledge about this discipline. In the period after the war, until the establishment of the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina (ALMBIH) there were two regional centers where health care professionals (HCP) were able to report ADR. In the Federation of Bosnia and Herzegovina (FBiH), this was a Center for Medicine at the Institute of Pharmacology, Faculty of Medicine in Sarajevo, while in the Republic of Srpska (RS) this was Drug Agency RS.Th e ALMBIH was established in accordance with the Medicinal Products and Medical Devices Act

of Bosnia and Herzegovina as the competent body responsible for the fi eld of medicinal products and medical devices manufactured and used in BiH. It began operating on May 1  2009. (13). ADR reporting in BiH is closely linked to economic problems in the local healthcare system, which is still being developed. Th e level of ADR reporting is inadequate despite the fact that information on the safety of medicinal products is of vital importance and despite the fact that reporting on adverse eff ects to the ALMBiH is a legal obligation. Th is obligation is defi ned in the Book of rules on the manner of reporting, collecting and following adverse eff ects of the medicinal product, in Article 11 (14) “medicinal product manufacturers, health care institutions and health care professionals (medicinal doctors, dentists, pharmacists, health technicians, nurses) are under the obligation to report to the Agency any suspicion about the adverse eff ects of a medicinal product”.Th e objective of this study was to gain insight into the perceptions, practices and barriers of HCP in BiH with respect to the reporting of ADRs and pharmacovigilance.

METHODSKnowledge, perceptions, practices and barriers of healthcare professionals about terms related to phar-macovigilance and reporting of adverse drug reac-tions have been tested with the help of a structured questionnaire that was distributed in person (the response to the survey was either obtained at the same time or collected at a later time) or via e-mail. A random sample of healthcare professionals (doctors of diff erent specialties, pharmacist, dentists, techni-cians and nurses) were randomly selected from dif-ferent hospitals and health centers, distributed over all regions of BiH. As there is no common database of HCP in BiH there is no guarantee they represent country profi le. Th e questionnaire included issues addressed in previous studies examining the same problem (6-8,15-20), but was modifi ed by taking into account local features and simplifi ed to exclude non relevant questions. A  draft questionnaire was pretested by administering it to 6 healthcare profes-sionals, which consisted of three pharmacists, two physicians and two dentists. Based on their com-ments and suggestions a fi nal questionnaire was

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prepared for conducting the survey. Th e fi nal ver-sion consisted of fi ve sections containing 20 ques-tions. Among these questions, 5 items were related to the demographical and professional profi les, 3 to the knowledge, 3 to the perception, 2 were related to practice aspects and the remaining 7 items were related to the barriers. Except questions related to demographical and professional profi le, questions were worded as a series of statements and the health-care professionals were asked to indicate their agree-ment or disagreement on a 4-point Likert scale from ‘strongly agree’ to ‘strongly disagree’.Th is questionnaire survey was conducted during January 2012 to September 2012.

Statistical analysisTh e collected data were entered into the Excel table and then analyzed using the IBM Statistical Package for Social Sciences (SPSS) version 20.0.

RESULTSA total of 1000 questionnaires were distributed/sent and 870 were returned completed, so all anal-yses were therefore made based on the 870 fi lled in questionnaires. Th e demographic and professional details of the respondents are shown in Table 1.

Most respondents were in Sarajevo (36.9%), Tuzla (22.8%) and Banja Luka (21.5%). Th e remaining 18.8% of respondents were interviewed in other cities.Th e majority of respondents (84. 6%, i.e.  736 respondents) provided a negative response to the question “Have you ever reported an adverse drug reaction?” and only 15.4% (133 respondents) gave a positive response. 17.1% of them were physicians, 25.2% pharmacists, 6.6% dentists, 10.7% nurses and 13.8% technicians.62.9% of respondents recognize the Agency for Medicinal Products and Medical Devices of Bosnia and Herzegovina  as the institution to which ADR of a medicinal product are to be reported. A further question we used to establish how informed the respondents are on the issue pharmacovigilance was whether they agreed with the assertion that ADR reporting forms are available. Pharmacists in many cases (43.4%) claimed that the reporting forms are available, while not even a fi fth of the respondents from the other categories agreed that this was the case.Asked about their experience in fi lling out the ADR reporting form, 46.6 % of the respondents from our sample stated that they do not have enough experience.Almost three quarters (79.1%) of respondents report ADR only if they are certain that it is linked to a specifi c medicinal product, 80.5% of respon-dents would consult with a physician/pharmacist/dentist before reporting an ADR and only 4.1% do not share such a view.It was found out from the result that almost all health providers agree towards the fact that report-ing about ADR is part of their ethical (83.2%) and legal (82.2%) duty and that the science of pharma-covigilance is important (92.6%).Several factors were reported that negatively aff ected health care professionals’ willingness to report. Table  2 lists factors that may act as deterrents to reporting by HCP.

DISCUSSIONTh is is the fi rst survey, which we are aware of, to explore healthcare professionals knowledge, attitude,

TABLE 1. Demographic and professional details of HCPRespondents

Number %nw 870 100.0

Sex Male 243 27.9Female 627 72.1

Profession Doctor 258 29.7Pharmacist 143 16.4Dentist 61 7.0Nurse 234 26.9Technician 174 20.0

Work experience 0-5 year 181 20.86-10 year 186 21.411-20 year 206 23.721-30 year 201 23.1More than 30 year 95 10.9

Entity FBiH 644 74.0RS 225 25.9Brčko district 1 0.1

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perceptions and their barriers towards ADR report-ing and pharmacovigilance in BiH. Th e survey response rate was good (87%).Although the majority of healthcare professionals correctly responded to whom they should report adverse reactions, it needs to be noted that almost a third gave a wrong answer to this question. Th is is a relatively high percentage of healthcare profes-sionals who failed to provide a correct answer. Th is also indicates that although more than 4 years have passed since the establishment of ALMBIH, not enough publicity has been given to this. Results of the survey in one of Istanbul’s districts show that only 6.7% of pharmacists would send their reports to the national pharmacovigilance center (TUFAM), i.e. the correct address (21).It has transpired that the unavailability of ADR reporting forms is signifi cantly impacting the informedness of healthcare professionals, despite the fact that the forms are also on the ALMBIH web-site, as well as in the Register of Medicinal Products. Th e Rhode Island survey (22) provided similar results with 38% of physicians stating that they do not know where to fi nd the forms and that this is why they were not reporting adverse reactions.Asked about their experience in fi lling in the ADR reporting form, just under 50% of healthcare pro-fessionals included in the survey stated that they do not have enough experience.Th e majority of healthcare professional in our sur-vey have never reported an adverse reactions.

Th e percentage of reported adverse reactions is very low when compared to the number of adverse reactions reported by physicians in Great Britain (23), the Netherlands (24), Spain (25) and China (26). Diff erences in the number of reported ADRs can be attributed to the priority, care and commitment to pharmacovigilance on the part of the national governments of those countries. Regulatory bodies in BiH should also adopt such an approach. It is evident that pharmacovigilance activities in BiH are not adequately presented or advertised.Questions concerning perception focused on the general perception of healthcare professionals regarding the standard aspects of ADR reporting. Th e survey has shown that healthcare profession-als have a positive attitude towards ADR report-ing. Th e vast majority consider reporting a part of their professional obligations, as well as an integral part of the code of ethics. Th ese results are largely similar to the results of surveys carried out among pharmacists working in pharmacies in cities in the Netherlands (27) and Great Britain (28).Although the majority of healthcare profession-als covered by the survey expressed a proper and positive attitude towards ADR reporting, actual hands-on experience in reporting is still lacking. Similar responses were obtained through three surveys conducted in India (29-31) where both the knowledge and a positive attitude exist, but adverse reactions are still not being reported.Even though the Book of Rules on Adverse Eff ects (14) stipulates that all adverse eff ects are to be reported, even when a link has not been estab-lished, healthcare professionals have stressed that they must be certain that a link between a medic-inal product and an adverse eff ect does exist. Th is is in line with the conclusions from earlier surveys conducted among pharmacists and physicians in other countries (10,32,33) who expressed concern over showing a lack of knowledge because they are uncertain whether a medicinal product has caused an adverse reaction or not. Th is problem needs to be approached carefully and educational programs need to be organized to alleviate the anxiety of healthcare professionals and strengthen their confi dence in reporting adverse reactions.

TABLE 2. Barriers to spontaneous reporting of ADRsBarriers Level of agreement (percentage)

Agree Partially Agree

Partially disagree

Disagree

Reporting form too complicated

19.9 31.3 10.8 37.0

Reporting ADRs is time consuming

20.2 29.5 10.6 38.6

Diffi cult to admit harm to patient

26.6 27.7 9.2 36.4

Fear of liability 10.6 14.9 12.3 62.1Insuffi cient clinical knowledge

13.1 19.2 10.3 57.2

Patient confi dence 11.3 26.4 14.4 47.5No motivation 9.2 18.4 11.4 60.9

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A large percentage of healthcare professionals have indicated that they would consult a colleague (physician/pharmacist/dentist) before reporting an adverse eff ect even though they are not under an obligation to do so. Th is could indicate a lack of confi dence in their own knowledge, and perhaps even fear of legal consequences. Similar results came out of previous surveys (27,28). Colleagues should not be consulted in relation to reporting an adverse eff ect because that could be an obstacle to reporting and lead to a situation where the person reporting the adverse eff ect is dependent on someone else’s opinion.It is widely accepted that reporting on adverse eff ects is linked to a high degree of side eff ects not being reported, however, it is diffi cult to assess the scope of this problem. It is estimated that 90-95% of adverse eff ects go unreported (34). To identify the reasons for underreporting, several studies were conducted where diff erent authors investigated the knowledge, attitudes and practices of healthcare professionals toward the ADR reporting. According to the fi ndings of the studies (1,5,26,32) health-care professionals mentioned diff erent factors that have contributed towards their underreporting: lack of awareness of the requirement for reporting, lack of resources for surveillance and reporting, time-consuming reporting process, well-known reactions, an uncertain association, what is similar to our results. Of all obstacles mentioned in the survey, respondents have identifi ed two as being the dominant reasons for the failure to report adverse eff ects, including lack of experience in fi lling out the ADR reporting forms (71.4%) and unavailability of ADR reporting forms (72.7%). Other reasons men-tioned in the survey include: the ADR reporting form is too complicated (51.6%), reporting requires a lot of time (50.2%), reporting could show a lack of knowledge (32.3%), reporting requires the use of my own resources and I am not motivated to do that (27.6%), fear of responsibility (25.6%) and the position that one case that goes unreported does not make a diff erence (18.1%).According to responses provided by healthcare pro-fessionals covered by the survey, non-reporting of adverse eff ects in BiH appears to be linked with a lack of knowledge concerning the ADR reporting process and not with the personal and professional

characteristics reported in other surveys. Th e ADR reporting rate can therefore be increased by over-coming the abovementioned obstacles as has been confi rmed by certain studies. Some of these obsta-cles can be addressed by proper management and the promotion of a pharmacovigilance program, and with relevant guidelines that would be available to all. Also there is an urgent need for postgraduate educa-tional programs to emphasize the role and responsi-bility of the HCP in pharmacovigilance practices, to underline the importance of pharmacovigilance and ADR reporting. In conclusion, it is necessary to off er continuous educational programs until we reach the point that voluntary reporting of ADRs become cus-tomary and habitual among all HCP.Th e limitation of this study is the fact that sur-veyed HCP as well as related institutions and cit-ies, which are randomly selected, do not represent HPC in all BiH. Another limitation of this study is the answer reliability  -  inherent problem with surveys and interviews, and whether the responses of HCP are truly representative. Th ird limitation of study is small number of questions in the survey which evaluated knowledge and perception of PV. Although this study has certain limitations and it would be inappropriate to plan interventions based on the fi ndings of this study alone, however, it does provide an insight into the possible interventions that could be planned in future.

CONCLUSIONUnder-reporting of adverse reactions is a phenome-non present in all parts of the world, this has been confi rmed by surveys already conducted, and it can be attributed to all healthcare professionals.Th e results of this survey have shown that even though the majority of healthcare professionals have never reported an ADR, although they do have a positive perspective towards pharmacovigilance. Th e results suggest that ADR under-reporting is a result of unfamiliarity with the existing reporting system. Regulatory bodies need to improve the management and promotion of the reporting system in BiH in order to address the issue of healthcare professionals lacking the necessary knowledge on ways to report. It could take a while before healthcare profession-als accept ADR reporting as part of their everyday

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practice, but on the long run, this is defi nitely worth the eff ort.

COMPETING INTERESTSTh e authors declare no confl ict of interest.

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9. Hasford J, Goettler M, Munter KH, Muller-Oerlinghausen B. Physicians’ knowledge and attitudes regarding the spontaneous reporting system for adverse drug reactions. J Clin Epidemiol 2002; 55: 945-50 http://dx.doi.org/10.1016/S0895-4356(02)00450-X.

10. Williams D, Feely J. Underreporting of adverse drug reactions: attitudes of Irish doctors. Ir J Med Sci 1999;168:257-61 http://dx.doi.org/10.1007/BF02944353.

11. Ahmad SR. Adverse drug event monitoring at the Food and Drug Administration: your report can make a difference. J Gen Intern Med 2003; 18:57-60. http://dx.doi.org/10.1046/j.1525-1497.2003.20130.x.

12. Wysowski DK, Swartz L. Adverse drug event surveillance and drug with-drawals in the United States, 1969-2002: the importance of reporting suspected reactions. Arch Intern Med. 2005;165:1363-69. http://dx.doi.org/10.1001/archinte.165.12.1363.

13. Medicinal products and medical devices act. Offi cial Gazette of BiH 58/08. 14. Book of rules on the manner of reporting, collecting and following adverse

effects of the medicinal products. Offi cial Gazette of BiH 58/12. 15. McGettigan P, Feely J. ADR reporting: opinions and attitudes of medical

practitioners in Ireland. Pharmacoepidemiol Drug Saf 1995;4:355-8 http://dx.doi.org/10.1002/pds.2630040607.

16. Cosentino M, Leoni O, Oria C, et al. Hospital-based sur-vey of doctors’ attitudes to adverse drug reactions and per-ception of drug-related risk for adverse reaction occurrence. Pharmacoepidemiol Drug Saf 1999;8:S27-35 http://dx.doi.org/10.1002/(SICI)1099-1557(199904)8:1+<S27:AID-PDS407>3.3.CO;2-H.

17. Figueiras A, Tato F, Fontainas J, et al. Physicians’ attitudes towards vol-untary reporting of adverse drug events. J Eval Clin Pract 2001;7:347-54 http://dx.doi.org/10.1046/j.1365-2753.2001.00295.x.

18. Vallano A, Cereza G, Pedro´ s C, et al. Obstacles and solutions for sponta-neous reporting of adverse drug reactions in the hospital. Br J Clin Pharmacol 2005;60:653-8 http://dx.doi.org/10.1111/j.1365-2125.2005.02504.x.

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Journal of Health Sciences

CASE REPORT Open Access

Mental foramen mimicking as periapical pathology - A case reportAnusha Rangare Lakshman1*, Sham Kishor Kannepady2, Chaithra Kalkur1

1Department of Oral Medicine and Radiology, Century International Institute of Dental Science and Research Centre, Poinachi, Kasaragod – 671541, Kerala, India, 2School of Dentistry, International Medical University, Kuala Lumpur, Malaysia

ABSTRACT

The radiographic recognition of any disease requires a thorough knowledge of the radiographic appear-ance of normal structure. Intelligent diagnosis mandates an appreciation of the wide range of variation in the appearance of normal anatomical structures. The mental foramen is usually the anterior limit of the inferior dental canal that is apparent on radiographs. It opens on the facial aspect of the mandible in the region of the premolars. It can pose diagnostic dilemma radiographically because of its anatomical variation which can mimic as a periapical pathosis. Hereby we are reporting a rare case of superimposed mental foramen over the apex of right mandibular second premolar mimicking as periapical pathology.

Keywords: mental foramen; periapical radiolucency; mandibular premolars

*Corresponding author: Anusha Rangare Lakshman, Department of Oral Medicine and Radiology, Century International Institute of Dental Science and Research Centre, Poinachi, Kasaragod – 671541, Kerala, India E-mail: [email protected]

Submitted July 23 2014 / Accepted September 1 2014

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Anusha Rangare Lakshman, 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, distribution, and reproduction in any medium, provided the original work is properly cited.

lower right second premolar, which was suggestive of periapical pathology.

CASE REPORTA 30  year old male patient reported to the Department of Oral Medicine and Radiology with the complaint of tooth decay in the lower right back tooth jaw region since six months. It was associated with dull, intermittent, non-radiating type of pain. Medical, family and dental histories were non-con-tributory. On intra oral examination, deep class  II cavity with respect to right second premolar, fi rst and second molar was observed. Provisional diagno-sis of chronic irreversible pulpitis was considered for right mandibular fi rst and second molar and deep dental caries with respect to right mandibular sec-ond premolar.Periapical radiograph of right mandibular poste-rior region revealed diff use coronal radiolucency

INTRODUCTION

Many articles have been reported about various conditions that may mimic periapical infl ammatory lesion such as carcinoma (1), odontogenic cyst (2) and periapical cemental dysplasia (3) etc. Film pro-cessing errors has also been reported to mimic the appearance of periapical infection (4), while normal anatomies such as the mental foramen or incisive foramina are familiar as radiolucencies that may overlie teeth and cause diagnostic confusion. Th is case report enlightens an anatomical variation of mental foramen (MF) manifesting as well defi ned periapical radiolucency in relation to the roots of

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involving pulp with no periapical changes noticed with respect to mandibular molars. Th e mandibu-lar second premolar revealed diff use coronal radio-lucency approximating the pulp with intact lamina dura in the periapical region. Hazy periapical radio-lucency (Figure 1) noticed at the apex of mandib-ular second premolar with poor defi ned borders mimicking as periapical pathology. To rule out, a second radiograph (Figure 2) was taken at diff erent angulation which revealed the same fi nding but the radiolucency had moved mesially with an intact the lamina dura around the tooth, hence we arrived at a provisional diagnosis of mental foramen which was mimicking as periapical pathology. We also noticed

increased in the width of root at the apical one third of the second premolar suggestive of hypercemen-tosis. Th e patient was referred to the Department of Conservative Dentistry and Endodontics for the further treatment.

DISCUSSIONTh e MF is an opening on the anterolateral surface of the mandible, which is generally seen to be oval or circular in shape from where the mental neu-rovascular bundle exits. After passing through the mandibular foramen, the inferior alveolar nerve and artery, exit at the mental foramen as the men-tal nerves and vessels which innervate the lower teeth, lip, gingiva and soft tissues of chin area. Th e foramen opens directed posteriorly, outward and upwards. Th ere are variations in the posi-tion of mental foramen. Frequent position is in between and below the apices of fi rst and second premolars (5).Th e mental nerve is a somatic aff erent sensory nerve and corresponds to the terminal branch of the mandibular nerve, which is the third division of the trigeminal nerve. In the premolar region, the inferior alveolar nerve, a branch of the mandibular nerve, usually splits into two branches, the mental nerve and the incisive nerve. Th e incisive nerve runs intra-osseously along with veins and innervates the anterior mandibular teeth (incisors, canines, and premolars) (6). Th e mental nerve emerges at the mental foramen and divides into four branches: angular (innervations of the angle of the mouth region), medial and lateral inferior labial (skin of the lower lip, oral mucosa, and gingiva as far posterior as the second premolar), and mental branch (skin of the mental region) (7).It is usually the anterior limit of the inferior dental canal that is apparent on radiographs. Its image is quite variable and it may be identifi ed only about half the time because the opening of the mental canal is directed superiorly and posteriorly. Because of this, the usual view of the premolars is not pro-jected through the long axis of the canal opening. Th is circumstance is responsible for the variable appearance of the mental foramen (8).Mental foramen variations are often encountered, ranging from diff erence in position of foramen

FIGURE 1. Intraoral periapical radiograph showing the poor- defi ned periapical radiolucency at the apex of mandibular second premolar with intact lamina dura around the root, mimicking as periapical pathology.

FIGURE 2. The second radiograph of mandibular premolar region from different angulation showed slight mesial shift in the periapi-cal radiolucency with intact lamina dura.

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on anterolateral surface of mandible or presence of accessory foramina or even complete absence in some rare cases. Th e location of mental fora-men also changes along with the age changes (9). Usually the MF is seen to be closer to the alveo-lar ridge in children before tooth eruption; as the teeth starts to erupt the MF starts descending to the midway between the upper margin and lower border and in adults with the teeth present for long time, the MF moves is somewhat closer to the inferior border comparatively. In old age even-tually with the loss of teeth and bone resorption of the edentulous ridge the MF moves relatively up towards the alveolar ridge. In extreme cases of resorption, the MF and the adjacent part of the mandibular canal are open at the alveolar margin. According to the degree of resorption, in severe cases, the mental nerve and the fi nal part of the inferior alveolar nerve may be found directly under the oral mucosa (10).Radiographically, this foramen appears as small, ovoid or round radiolucent area located in the api-cal region of the mandibular premolars (11). Th e absence of a MF (12) and the presence of multiple MF (13) are rarely reported. Th e presence of more than one MF, referred to as accessory mental foram-ina, has been noted on dissection, surgical fi ndings, conventional radiographs, spiral computed tomog-raphy (CT), and cone beam CT.When it is projected over one of the premolar api-ces, it may mimics periapical disease as seen in our case. In such cases, evidence of the mandibular canal extending to the suspected radiolucency or a lamina dura traceable around the root apex would suggest the true nature of the radiolucency. In the case pre-sented here, there was intact lamina dura around the root. However, the lamina dura superimposed on the radiolucent foramen may be of too low a den-sity to be recognized in the image (‘burn out’) (14). Nevertheless, a second radiograph from another angle is likely to show the lamina dura clearly, as well as some shift in position of the radiolucent foramen relative to the apex (8). Similarly, the sec-ond radiograph was taken in the present case which showed intact lamina dura with slight mesial shift in the periapical radiolucency. Th us, confi rming our diagnosis of mental foramen mimicking as periapi-cal pathology.

However, radiography is not a perfect diagnostic tool, partly because radiographs are two-dimen-sional representations of three-dimensional struc-tures, and partly because particular clinical and biological features may not be refl ected in radio-graphic changes. Th e presence of a lesion may not be directly evident and its real extent and the spatial relationships to important anatomical landmarks are not always easily visualized. Th e diagnosis and man-agement of periapical pathosis requires a thorough clinical and radiographic examination. As chronic apical periodontitis often develops without subjec-tive symptoms, the radiological diagnosis is partic-ularly important and should not be confused with the variations of the normal anatomical landmarks.

CONCLUSIONA basic knowledge of the variations of the normal anatomical landmarks of jaw bones is mandatory for all the dental physicians, so that we can avoid misdi-agnosing as any periapical pathology. In this paper, we have highlighted about the variations of mental foramen which was mimicking as periapical pathol-ogy. As the routine dental intraoral radiographs are the two dimensional representation of the three dimensional object, the newer radiographic methods has to be implemented to overcome this limitation.

CONFLICT OF INTERESTTh e authors declare that they have no competing interests.

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10. Gershenson A, Nathan H, Luchansky E. Mental Foramen and Mental Nerve: Changes with Age. Acta Anatomica 1986;126:21–28. http://dx.doi.org/10.1159/000146181.

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third edition, Elsevier. pp 385.12. de Freitas V, Madeira MC, Toledo Filho JL, Chagas CF. Absence of the men-

tal foramen in dry human mandibles. Acta Anat (Basel) 1979;104:353-355. http://dx.doi.org/10.1159/000145083.

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14. Sisko Huumonen & Dag Ørstavik. Radiological aspects of api-cal periodontitis. Endodontic Topics 2002;1:3–25. http://dx.doi.org/10.1034/j.1601-1546.2002.10102.x

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Journal of Health Sciences

CASE REPORT Open Access

Gastric antral vascular ectasia: a case reportAmir Ćehajić*, Denis Mačkić, Elvira Džambasović, Faruk Čustović, Aida Mujaković, Nijaz Tucaković

Department of Internal Medicine, General Hospital “Prim. dr Abdulah Nakaš”, Sarajevo, Bosnia and Herzegovina

ABSTRACT

Gastric antral vascular ectasia (GAVE) is a vascular gastric malformation which represents a rare cause of upper gastrointestinal system bleeding, mostly in elderly. It is usually presented with a signifi cant anemia and it is diagnosed with an endoscopic examination of the upper gastrointestinal system. The disease is often associated with other chronic illnesses such as liver cirrhosis, scleroderma, diabetes mellitus and arterial hypertension. It is treated symptomatically in terms of anemia correction with blood transfusions and iron supplements, proton pump inhibitors, beta-blockers and endoscopic procedures such as argon plasma coagulation which currently represents the treatment of choice in Sy. GAVE cases. We report a case of a 76 years old female patient who was admitted to the hospital because of general weakness, exhaustion and abdominal pain. Laboratory analysis of blood went in favor of anemia. Proximal endos-copy showed no changes on the esophagus, the stomach had a normal volume with pale mucosa and signs of antral vascular ectasia which is presented typically as a “watermelon” stomach due to the longi-tudinal creases oriented toward pylorus. The patient was treated symptomatically in terms of anemia cor-rection with blood transfusions and iron supplements, proton pump inhibitors, beta-blockers. Five months later control proximal endoscopy fi ndings were identical to those found in the previous hospitalization.

Keywords: endoscopy; GAVE; gastric antral vascular ectasia; gastrointestinal bleeding

INTRODUCTIONGastric antral vascular ectasia, scientifi cally identifi ed also as Sy. GAVE is a rare and usually undiagnosed cause of the occult gastrointestinal bleeding, mostly in elderly. Proximal endoscopy usually reveals lon-gitudinal creases oriented towards pylorus. It is also known as a “watermelon stomach” due to the lon-gitudinal “stripes”. It is histologically characterized with dilated and thrombosed capillaries as well as

*Corresponding author: Amir Ćehajić, MD,Department of Internal Medicine, General Hospital“Prim.dr. Abdulah Nakaš”, Kranjčevičeva 12, 71 000, SarajevoBosnia and Herzegovina, Phone: 387 33 285 100,E-mail: [email protected]

Submitted July 23 2014 / Accepted September 6 2014

© 2014 Amir Ćehajić, 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.

with fi bro muscular hyperplasia of lamina propria. Th e treatment includes conservative procedures such as blood transfusions and endoscopic therapy with argon plasma coagulation. Recent reports sug-gest that Endoscopic Band Ligation (EBL) is a regu-lar and effi cient alternative treatment.A study by Irish authors reported an overall treatment of 23 Sy. GAVE cases. Eight patients were treated with EBL, with a mean number of 2.5 treatments. Six (75%) of those eight patients had previously failed APC (argon plasma coagulation treatment) despite having a mean of 4.7 sessions. Band ligation was not associated with any compli-cations. EBL treatment resulted with the signifi cant improvement of endoscopic fi nding and the need

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for blood transfusions was periodical (1). Antral vascular ectasia is considered as a cause of nonvari-ceal upper gastrointestinal system bleeding in 4% of cases (2).Th e disease can be presented with occult bleeding which demands blood transfusions or as acute gas-trointestinal bleeding. It is often associated with a signifi cant mortality and morbidity rate and fol-lowing comorbidities: scleroderma, diabetes melli-tus and arterial hypertension. Sy. GAVE may also be developed as a complication after haematopoetic stem cell transplantation or after per oral or intra-venous application of busulfan (3). An average of 30% of Sy GAVE cases is associated with liver cir-rhosis (4). Th e treatment of the syndrome is divided into three categories: pharmacological, endoscopic and surgical. A few studies compared the effi ciency and complications of endoscopic and medicamen-tous treatment of Sy. GAVE. Current evidence of endoscopic Sy. GAVE treatment are insuffi cient. Sy. GAVE diagnosis is often based on endoscopic examination according to its characteristical appear-ance, thus it can be easily misinterpreted with mild to severe form of gastritis. Radiofrequency abla-tion represents an alternative therapeutic option for Sy. GAVE. It is considered a secure and eff ec-tive method (5). Among the most frequent illnesses associated with Sy GAVE is a chronic renal insuffi -ciency (6).

CASE REPORTA female patient, 76 years old, was admitted to the Department of Internal Medicine, General hospital “Prim.dr. Abdulah Nakaš”, Sarajevo in December,

2012. Th e symptoms on the day of the admission were general weakness, exhaustion and abdominal pain. Laboratory fi ndings on the admission reported signs of anemia: RBC 3.71  ×  1012, Hemoglobin 87.4 g/L, Hematocrit 0.28, MCV 74.8 fL, MCH 23.6 pg, MCHC 315 g/L, Reticulocytes 8 × 103/E. Plt 103 × 109/L, WBC 4.1 × 109/L. Serum iron level 3.7 umol/L, TIBC 66.0 umol/L, UIBC 62.3 umol/L. Th e abdominal ultrasound showed signs of chronic calculous cholecystitis, with a bended gallbladder and a slightly larger spleen  -  craniocaudal diame-ter of 15.5  cm. Proximal endoscopy  -  showed no changes on the esophagus, the stomach had a nor-mal volume with pale mucosa and antral vascular ectasia – typical watermelon fi nding (Figure  1). Duodenal bulb showed no changes, D1 and D2 were neat.During hospitalization, the patient was treated with deplasmatized erythrocytes transfusions (a  total of 300 ml), parenteral iron supplements, primarily intravenously administered proton pump inhibitors followed with peroral administra-tion of the same. Th e patient was discharged with a recommendation of per oral use of proton pump inhibitors in a single dose of 40 mg per day with non-selective beta blockers, Propranolol in a single dose of 40 mg per day. On April, 2013 the patient was readmitted to the Department because of severe anemia signs: RBC 2.54 ×  10*12, Hemoglobin 51.0 g/L, Hematocrit 0.17 I, MCV 65.7 fL, MCH 20.1 pg, MCHC 305 g/L, Plt 171 × 10*9/L, WBC 5.6 × 10*9/L, RDW 18%. Follow up proximal endoscopy fi ndings were identical to those found in previous hospitalization – antral vascular ectasia was still present (Figure 2).

FIGURE 1. Endoscopic image of GAVE. Typical endoscopic appearance of “watermelon” stomach after the fi rst exam.

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DISCUSSIONGastric antral vascular ectasia represents a vascu-lar malformation of gastrointestinal system and a rare cause of upper gastrointestinal tract bleed-ing. Hemorrhage within Sy GAVE may be pro-found as well as occult with signs of mild, mod-erate or severe anemia. Th e disease may be treated conservatively by anemia correction with blood transfusion and iron supplements as well as with proton pump inhibitors and beta blockers. Well-designed controlled randomized studies will be necessary to prove the effi cacy and complications of conservative and endoscopic treatment of Sy. GAVE (7). According to some authors capsule endoscopy is superior in GAVE syndrome cases, compared to classic endoscopic examination. Th e diagnosis may be established with an endoscopic examination only, although it may be misdiag-nosed with moderate to severe form of gastritis. Classic endoscopic examination is considered to be physiological without need for air insuffl ations and consequent vascular compression and there-fore misdiagnosis of the same (8). Current model of invasive treatment is proximal endoscopy with argon plasma coagulation. Proximal endoscopy with APC is in general more acceptable way of treatment for Sy. GAVE patients, although many of them continue to bleed and demand contin-uous blood transfusions after the treatment and show a low level of endoscopic improvement. Endoscopic band ligation (EBL) according to mentioned studies proved to be a safe and eff ec-tive treatment of GAVE. Radiofrequency ablation may serve as an alternative therapeutic method. Endoscopic laser photocoagulation or diathermia

are proved to be effi cient in stopping hemorrhage. Antrectomia represents the fi nal and only defi ni-tive therapeutic solution specially in patients with severe symptoms such as severe anemia and recur-rent profuse bleeding (9).

CONCLUSIONGastric antral vascular ectasia or Sy. GAVE rep-resents a group of vascular gastric malformations and is a rare cause of upper gastrointestinal system bleeding. Th e diagnosis is set throughout a proximal endoscopy exclusively. It may be treated conserva-tively with proton pump inhibitors and beta block-ers or using invasive methods such as argon plasma coagulation, radiofrequency ablation or endoscopic band ligation.

CONFLICT OF INTERESTTh e authors declare that they have no competing interests.

REFERENCES1. Keohane J, Berro W, Harewood GC, Murray FE, Patchett SE. Band

ligation of gastric antral vascular ectasia is a safe and effective endo-scopic treatment. Dig Endosc. 2013 Jul;25(4):392-6. http://dx.doi.org/10.1111/j.1443-1661.2012.01410.x

2. Liu F, Ji F, Du Y. Gastric antral vascular ectasia (GAVE) in two non-cirrhotic patients involved large area of stomach: Case report and literature review. J Interv Gastroenterol. 2013 Jul;3(3):107-110. http://dx.doi.org/10.7178/jig.113.

3. Fukuda K, Kurita N, Sakamoto T, Nishikkii H, Okoshi Y, Sugano M, Chiba S. Post-transplant gastric antral vascular ectasia after intra-venous busulfan regimen. Int J Hematol. 2013 Jul;98(1):135-8. http://dx.doi.org/10.1007/s12185-013-1342-8.

4. Kar P, Mitra S, Resnick JM, Torbey CF. Gastric antral vascular ectasia: Case report and review of the literature. Clin Med Res. 2013 Jun;11(2):80-5. http://dx.doi.org/10.3121/cmr.2012.1036.

FIGURE 2. Control endoscopic image – GAVE still present - Four months after the fi rst exam – the same fi ndings still persisting.

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5. McGorisk T, Krishnan K, Keefer L, Komanduir S. Radiofrequency abla-tion for refractory gastric antral vascular ectasia. Gastroinest Endosc. 2013 Oct;78(4):584-8. http://dx.doi.org/10.1016/j.gie.2013.04.173.

6. Pisharam JK; Ramaswami A, Chong VH, Tan J. Watermelon stomach: A rare cause of anemia in patients with end-stage renal disease. Clin Nephrol. 2014 Jan;81(1):58-62. http://dx.doi.org/10.5414/CN107527.

7. Swanson E, Mahgoub A, Macdonald R, Shaukat A. Clin Gastroenterol Hepatol. 2013 Sep 5 S 1542-3565(13)01289-5.

8. Ohira T, Hokama A, Kinjo N, Nakamoto M, Kobashigawa C, Kise Y et al. Detection of active bleeding from gastric antral vascular ectasia by capsule endoscopy. World J Gastrointest Endosc. 2013 Mar 16;5(3):138-40. http://dx.doi.org/10.4253/wjge.v5.i3.138.

9. Sciume C, Geraci G, Pisello F, Facella T, Pinto G, Fernandez P. et al. Ectasia vascolare gastrica antrale (GAVE) o “Watermelon Stomach Syndrome”: Report di 3 casi ed indicazioni cliniche e terapeutiche. Ann. Ital. Chir. 2003; 74(4):477-484.

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Journal of Health Sciences

LETTER TO EDITOR Open Access

An extremely rare case of testicular malign neoplasm; alveolar subtype of rhabdomyosarcoma with long term follow-up

Dear Editor,We would like to draw readers attention to tes-tis tumours, notably rare ones in this letter. Yue et al. recently reported rare tumours in testis (1). However, subtypes of testicular tumours with their incidences are well-defi ned in published literature, some rare types of them could be reported by pathol-ogy (2). Overcome these issues, we would like to affi x an extremely case of paratesicular alveolar rhab-domyosarcome. A handful of cases were published in literature and also most of them were including childhood series. A 23-year-old man was admitted to our urology outpatient clinic with main symp-toms of right scrotum. In detailed physical examina-tions, there was a nodular mass with 6 cm diameter in upper part of right testis. Ultrasonography (US) revealed 6 × 5 × 4 cm and computed tomography (CT) showed an 11 × 9 mm parailiac lymph node. Radical orchiectomy was performed and pathology reported paratesticular alveolar rhabdoyosarcoma (Figure  1). He has no metastasis after 6  cycles of chemotherapy with vincristine, actinomycin, and cyclophosphamide. However, rare tumour can occur in testis, early diagnosis and adequate treatments can provide long-term survival without metastasis.Paratesticular and testicular tumours usually occur in childhood and most of these have benign charac-teristics (3). Th ey are originated from mesenchymal tissue of testis and spermatic cord. Besides these, paratesticular tumours may be felt like arising from testis during physical examinations, US is useful

UNIVERSITY OF SARAJEVO FACULTY OF HEALTH STUDIES

© 2014 Tumay Ipekci, 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.

for diff erential diagnosis. Nevertheless, the exact diagnosis can be made by histopathology examina-tions. Th ere were hyperchromatic nucleuses and spindle cytoplasmic cells with haematoxylin–eosin (Figure  1). Additionally actin, desmin, and myo-globulin were positive (Figure 1). Alveolar subtype was reported by pathology, in the present case.Sarcomas consist of 1% of all malign tumours, and they are originated from embryonic tissues. Th e common sites of sarcomas are skeletal system. However, paratesticular rhabdomyosarcom is an extremely rare. Specifi cally, embryonic subtype of rhabdomyosarcoma were reported in literature (4). Subtypes can be diagnosed by pathology examina-tions. Alveolar subtype of rhabdomyosarcoma is an extremely entity for paratesticular tumours, as in our case. Th e main clinical sign of this tumour is painless scrotal mass. Weakness and tiredness with palpable lymph nodes in inguinal and abdominal area may come into question, in advanced stages. Radical orchiectomy, chemotherapy, and radio-therapy are the main parts of treatment. Our case had clinical stage 1 tumour with intermediate risk (5). Th us, he underwent chemotherapy for 6  cycles, after operation. He did not need radio-therapy. Chest x-ray, abdominal and pelvic CT has been used for follow-up. He has been in follow-up period for 7 years and he had no metastasis.Diff erential diagnosis is an important entity for testicular and paratesticular masses. Surgery with adjuvant therapy options are used for contemporary

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treatment. Long-survival can be provided by suit-able treatment options with close follow-up.

Tumay Ipekci1, Yigit Akin2*, Burak Hoscan1, Ahmet Tunckiran1

1Department of Urology, Baskent University Alanya Research Hospital, Alanya, Antalya, Turkey, 2Department of Urology,

Harran University School of Medicine, Sanliurfa, Turkey

*Corresponding author: Yigit Akin, M.D. Assistant Professor of Urology, Department of Urology, Harran University School of Medicine, 63100, Sanliurfa, Turkey. Tel: +90-506-533 49 99,

Fax: +90-414-318 30 05. E-mail: [email protected]

Submitted 2 September 2014 / Accepted 12 September 2014

REFERENCES1. Yue X, Wang JZ, Tian Y, Wang KJ. Paratesticular desmoplastic small round

cell tumor with metastasis: A report of two cases. Kaohsiung J Med Sci 2014;30:104-5. http://dx.doi.org/10.1016/j.kjms.2013.01.018.

2. Emerson RE, Cheng L. Premalignancy of the testis and paratestis. Pathology 2013;45:264-72. http://dx.doi.org/10.1097/PAT.0b013e32835f3e1a.

3. Khoubehi B, Mishra V, Ali M, Motiwala H, Karim O. Adult para-testicular tumors. BJU Int 2002;90:707-15. http://dx.doi.org/10.1046/j.1464-410X.2002.02992.x.

4. Kizer WS, Dykes TE, Brent EL, Chatham JR, Schwartz BF. Paratesticular spindle cell rhabdomyosarcoma in an adult. J Urol 2001; 166: 606-7. http://dx.doi.org/10.1016/S0022-5347(05)65997-6.

5. Mondaini N, Palli D, Saieva C, Nesi G, Franchi A, Ponchietti R et al. Clinical characteristics and overall survival in genitourinary sarcomas treated with curative intent: a multicenter study. Eur Urol 2005;47:468-73. http://dx.doi.org/10.1016/j.eururo.2004.09.013.

FIGURE 1. Histopathologic features of paratesticular alveolar subtype rhabdomyosarcoma (a) Tumour cells are seen with hyperchro-matic nucleus and spindle eosinophilic cytoplasm. Alveolar subtype of rhabdomyosarcoma were presented with desquamated small, round, and poorly differentiated cells (HE.x10), (b) Tumour cells were positive with actin (x10), (c) Tumour cells were positive with desmin (x10), (d) Tumour cells were positive with myoglobulin (x10).

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