Volume 19 January/March 2013 1 Recommendations of the European Society of Cardiology 2 Medical Journal www.kcus.ba Editor-in-Chief PUBLISHER Mirza DiliД‡ Institute for Research and Development Clinical Center University of Sarajevo 71000 Sarajevo, BolniДЌka 25 Bosnia and Herzegovina Editorial Board For publisher Damir AganoviД‡, MD, PhD general manager CCUS AIMS AND SCOPE . Medical Journal is the offical qarterly issued Journal of the Institute for Research and Development of the Clinical Center University of Sarajevo and has been published regularly since 1994. Journal is published on the languages of the people of Bosnia and Herzegovina i.e. Bosnian, Croatian and Serbian language as well . as in English. The Medical Journal aims to publish the highest quality material, both clinical and scientific, on all aspects of clinical medicine. 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CIRCULATION 500 copies Medicinski Еѕurnal 2013 бѓЂ19 (1) EBSCO publishing (USA). www.ebscohost.com 3 Contents ORIGINAL ARTICLE THE FETAL MAGNETIC RESONANCE IMAGING OF NEURAL AND THORACO -ABDOMINAL ANOMALIES ........................ 4 Sandra Vegar-ZuboviД‡, Spomenka KristiД‡,Lidija Lincender , Irmina SefiД‡-PaЕЎiД‡, Aladin ДЊarovac OBSTETRIC CONDITIONS AS POSSIBLE PREDICTORS OF NEONATAL LESIONS OF PLEXUS BRACHIALIS .................. 9 Fatima GavrankapetanoviД‡-SmailbegoviД‡, Muhamed Ardat, Lejla ImЕЎirija, Naima ImЕЎirija, Faruk LazoviД‡, Mehmed JamakosmanoviД‡ MALIGNANT LIP TUMOURS; SURVIVAL ANALYSIS ................................................................................................................. 14 Faris FoДЌo, Lejla DЕѕananoviД‡, Zlatan ZvizdiД‡, Edin ImamoviД‡, Irma RamoviД‡, Semra ДЊavaljuga THE SIGNIFICANCE OF IMPLEMENTATION OF DRG (DIAGNOSIS RELATED GROUPS) HEALTHCARE REFORMS IN THE FIELD OF PHYSICAL MEDICINE AND REHABILITATION ............................................................................................ 20 Narcisa Vavra-HadЕѕiahmetoviД‡, Aldijana KadiД‡, Damir ДЊelik AWARENESS OF PHYSICIANS ABOUT PATIENTSвЂ™ RIGHTS; PATIENT CONSENT FORM ..................................................... 25 Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡ ADMISSION RATES OF PATIENTS WITH SCHIZOPHRENIA IN RELATION TO SEASONS AND CLIMATIC FACTORS IN THE PERIOD OF TWO YEARS ................................................................................................................ 32 Ifeta LiДЌanin, Alem Д†esir, Saida FiЕЎekoviД‡ HEART RHYTHM DISORDERS AS A CONTRIBUTING FACTOR TO ISCHEMIC STOKE ......................................................... 38 Jasminka ДђeliloviД‡-VraniД‡, Azra AlajbegoviД‡, Mehmed KuliД‡, Amina NakiДЌeviД‡, Emina EjuboviД‡, Merita TiriД‡-ДЊampara, Edina ДђoziД‡, Ljubica TodoroviД‡, Salem AlajbegoviД‡ CORONARY ANGIOGRAPHY REVIEW OF ANATOMIC VARIATIONS OF THE CORONARY ARTERIES ............................... 43 Aida HasanoviД‡, Belma AЕЎДЌiД‡-ButuroviД‡, Muhamed SpuЕѕiД‡ PROFESSIONAL ARTICLE PROGNOSTIC ASSESSMENT IN PATIENTS WITH DECOMPENSATED CIRRHOSIS .............................................................. 48 DЕѕenela ProhiД‡ , Rusmir MesihoviД‡, Nenad Vanis, SrД‘an GornjakoviД‡, Amra PuhaloviД‡, Aida Saray ETIOLOGY OF ANEMIA IN PATIENTS WITH GASTRIC LYMPHOMAS ...................................................................................... 54 Lejla IbriДЌeviД‡-BaliД‡, Rusmir MesihoviД‡, Alma Sofo-HafzoviД‡, Nenad Vanis, Е efkija BaliД‡, Semir BeЕЎlija CARDIOBORRELIOSIS IN BOSNIA AND HERZEGOVINA ........................................................................................................ 58 Sajma DautoviД‡-KrkiД‡, Alma Sijamija, NedЕѕad HadЕѕiД‡, Hilmo ДЊaluk REVIEW ARTICLE ANTIMICROBIAL SAFETY OF FLUOROQUINOLONES: SPECIAL FOCUS ON NORFLOXACIN ........................................... 63 Anida ДЊauЕЎeviД‡-RamoЕЎevac, Lejla ZoliД‡ CASE REPORT SUPERIOR MESENTERIC ARTERY SYNDROME .................................................................................................................... 69 Zoran RoljiД‡, BoЕѕina RadeviД‡, Novak VasiД‡, Milan SimatoviД‡, Jugoslav Дђeri, Severin DunoviД‡, Vladimir KeДЌa, Jevrosima RoljiД‡ PRIMARY CORRECTION OF BLADDER EXSTROPHY IN FEMALE NEWBORN ..................................................................... 63 Zlatan ZvizdiД‡, Ibrahim Ulman, Adnan HadЕѕimuratoviД‡, Selma Vatrenjak-Vanis, Sadeta BegiД‡-KapetanoviД‡, Kenan KaravdiД‡, Nusret PopoviД‡ INFORMATION PFIZER NEFRO FORUM ............................................................................................................................................................... 75 Senija RaЕЎiД‡ UPUTSTVO AUTORIMA ........................................................................................................................................... 76 INSTRUCTIONS TO AUTHORS ......................................................................................................................... 78 Medicinski Еѕurnal 2013 бѓЂ19 (1) . 4 Sandra Vegar-ZuboviД‡, Spomenka KristiД‡, Lidija Lincender , Irmina SefiД‡-PaЕЎiД‡, Aladin ДЊarovac. The fetal magnetic resonance imaging of neural and thoraco-abdominal anomalies Original article THE FETAL MAGNETIC RESONANCE IMAGING OF NEURAL AND THORACOABDOMINAL ANOMALIES FETALNA MAGNETNA REZONANCA NEURALNIH I TORAKO-ABDOMINALNIH ANOMALIJA 1 Sandra Vegar-ZuboviД‡1*, Spomenka KristiД‡1, Lidija Lincender 2, Irmina SefiД‡-PaЕЎiД‡ , Aladin ДЊarovac 1 1 Clinic of Radiology, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina; Academy of Sciences and Arts of Bosnia and Herzegovina, 71000 Sarajevo, Bosnia and Herzegovina 2 * Corresponding author ABSTRACT SAЕЅETAK The aim of this study was to estimate the significance of MRI in the diagnostics of fetal abnormalities, especially in cases with inconclusive ultrasound results. The MRI was used on eleven fetuses with malformations previously detected by ultrasound. The fetal MRI was done on a machine of 1.5 T with the use of rapid T2 (HASTE) and T1 (TurboFLASH) sequences. Ten exams were sufficient for an adequate analysis, while one exam was not of a diagnostically adequate quality. In nine patients the MRI result was pathologic, while one was normal. The admission diagnosis of the ultrasound included cystic alternations in the kidneys, intra-abdominal cystic tumour formation, gastric distension and anomalies of the central nervous system. In 60% of cases the ultrasound findings coincide with those of the MRI, in 30% of cases the results were non coinciding, while in 10% of cases the results of the two methods were partially coinciding. The results were analyzed using descriptive statistic. Conclusion: The MRI supplies important information regarding fetal abnormalities and it is complementary to the ultrasound вЂ“ which is still the method of choice for screening. Cilj ovog rada bio je procijeniti znaДЌaj MRI u dijagnostici fetalnih abnormalnosti, osobito u sluДЌajevima kada je nalaz ultrazvuka inkonkluzivan. Jedanaest fetusa sa prethodno ultrazvuДЌno uoДЌenim malformacijama je podvrgnuto MRI pregledu. Fetalni MRI je raД‘en na aparatu jaДЌine 1.5 T uz koriЕЎtenje brzih T2 (HASTE) i T1 (TurboFLASH) sekvenci. Deset pregleda je bilo adekvatne kvalitete za analizu, dok jedan pregled nije bio dijagnostiДЌki suficijentne kvalitete. Kod devet pacijenata nalaz MRI je bio patoloЕЎki, dok je kod jednog pacijenta bio uredan. UltrazvuДЌno postavljene uputne dijagnoze su ukljuДЌivale cistiДЌne promjene bubrega, intraabdominalnu cistoidnu tumorsku formaciju, distenziju Еѕeluca, anomalije centralnog nervnog sistema. U 60% sluДЌajeva uoДЌena je podudarnost ultrazvuДЌnog i MRI nalaza, u 30% sluДЌajeva nalaz je bio opreДЌan, dok je u 10% sluДЌajeva podudarnost nalaza dviju metoda bila djelomiДЌna. Rezultati ispitivanja su obraД‘eni upotrebom deskriptivne statistike. ZakljuДЌak: MRI je metoda koja daje vaЕѕne informacije o fetalnim abnormalnostima, a komplementarna je sa fetalnim ultrazvukom koji je joЕЎ uvijek screening metoda izbora. Key words: fetal MRI, fetal abnormalities, fetal malformations KljuДЌne rijeДЌi: fetalni MRI, fetalne abnormanosti, fetalne malformacije Medicinski Еѕurnal 2013 бѓЂ19 (1): 4 - 8 Sandra Vegar-ZuboviД‡, Spomenka KristiД‡, Lidija Lincender , Irmina SefiД‡-PaЕЎiД‡, Aladin ДЊarovac. The fetal magnetic resonance imaging of neural and thoraco-abdominal anomalies INTRODUCTION Traditionally, the diagnostic method of choice for monitoring normal pregnancies and detecting pathologic pregnancies has been the fetal ultrasound. This method, which has greatly improved prenatal medicine, still bears certain restraints which can hinder, or altogether prevent, the detection of abnormal fetuses вЂ“ they include: the obesity of the mother, an inadequate position of the fetus, extensive scaring in the anterior abdomen wall, oligohydramnios, small FOW, as well as a limited visual image of the posterior cranial fossa after 33 weeks of gestation (1). The method which overcomes typical ultrasound obstacles is the fetal MRI. A notable improvement of the fetal MRI was the introduction of fast single-shot T2-weighted sequences which enable the elimination of artefacts caused by fetal movement (2). The MRI is a safe diagnostic method for both the mother and the unborn during second and third trimester; however, due to the possible risk of displacing organogenesis and abortions, it is not used during the first trimester. Since gadolinium passes through the placenta to the fetus, it is not approved for fetal MRI use (3). Indications for executing the fetal MRI are numerous and they include ultrasound verified pathological conditions of the fetus which require additional diagnostics, or inconclusive ultrasound diagnostics (4). Even if indications for the fetal MRI are mostly neurological, they have recently included more thoracic, abdominal, and genitourinary pathology (5,6,7,8). MATERIALS AND METHODS During a prospective nine-month study (from July 2011 to April 2012) conducted at Clinic of Radiology, Clinical Center University of Sarajevo, eleven pregnant women underwent fetal MRI examination due to suspicion of fetal malformation presence previously detected by ultrasound. The mean age of the mothers was 32.1 years of age (a range of 20 вЂ“ 44), while the mean gestational age of the fetuses was 33 weeks (a range of 27 вЂ“ 37 weeks). All patients gave a written consent for the examination. The MRI examinations were conducted on 1.5 T machine (Avanto, Siemens, Erlangen, Germany) with the use of external coils (surface coils) which were placed in the motherвЂ™s pelvis and centred above the gravid uterus. T2weighted sequence (HASTE) was used, while for obtaining T1-f weighted scans, the spoiled gradient sequence was utilized (recalled sequence -Turbo FLASH). The thickness of the layer was 5 mm. Due to the fact that sequences with short acquisition time that limit fetal movement were used, sedation of the patients was not necessary. All examinations took an average of 37 minutes. RESULTS In this study, eleven fetuses suspected of various organ malformations based on results of initial ultrasound were examined with the MRI. Ten examinations were of adequate quality and enabled analysis. In one case, which was done on suspicion of existing anomalies in the development of the heart, due to motherвЂ™s anxiety and artefacts of movement the obtained images were not diagnostically sufficient in quality and could therefore not serve as analysis of the heart. The findings of the MRI examination in nine patients were pathological вЂ“ the indications put forth by the ultrasound were justified. In one patient with ultrasound suspected presence of hydrocephalus, the MRI result was normal, hydrocephalus was ruled out. Ultrasound diagnosis, on which fetal MRIs were made, were varied and related to different organs. In Table 1 both the ultrasound and the MRI findings are displayed, while Figure 1 graphically shows the similarities and differences in the results of examinations done by these two methods. Table 1. Fetal ultrasound and MRI findings. Ultrasound findings MRI findings 1. Hydrocephalus Morphologically normal cerebral finding 2. Cystic dysplasia of kidneys Cystic dysplasia of kidneys with augmentation of longitudinal and transversal kidney diameters Cystic dysplasia of kidneys with augmentation of longitudinal and transversal kidney diameters Hydronephrosis of right kidney most probably as a consequence of ureteropelvic junction stenosis with preserve parenchyma width; normal finding of left kidney Multiple cysts with parenchyma width reduction and upper limit size of right kidney; normal finding of left kidney Intraperitoneal cyst with partially compressive character and benign characteristics Upper limits longitudinal diameter of stomach with normal finding regarding pylorus Cerebellar malformation type Chiari II 3. Cystic dysplasia of kidneys 4. Polycystic kidneys disease 5. Multicystic right kidney and smaller, spongy left kidney 6. Cystic tumours formation most probably of ovarian origin 7. Pathological gastric distension 8. Suspected posterior fossa malformation 9. Hydrocephalus 10. Hydrocephalus Hydrocephalus with aqueducts stenosis and dilatation of III and lateral ventricles Hydrocephalus with cerebral cortex atrophy Medicinski Еѕurnal 2013 бѓЂ19 (1): 4 - 8 5 6 Sandra Vegar-ZuboviД‡, Spomenka KristiД‡, Lidija Lincender , Irmina SefiД‡-PaЕЎiД‡, Aladin ДЊarovac. The fetal magnetic resonance imaging of neural and thoraco-abdominal anomalies Figure 1. Concordances and differences between ultrasound and MRI findings. Four exams were carried out to evaluate the cystic lesions of the kidney diagnosed by prenatal ultrasound. With two patients, the MRI confirmed the ultrasound diagnosis of the cystic dysplasia in both kidneys with an increase of their longitudinal and transverse diameters. With the third patient, suspected of polycystic kidney disease as discovered by the ultrasound, the MRI findings pointed to hydronephrosis on the right side most probably as a consequence of ureteropelvic junction stenosis along with an increased longitudinal diameter and preserved parenchymal width of the mentioned kidney, while the findings of the other kidney was normal (Figure 2). In fourth patient, whose ultrasound findings indicated a polycystic right kidney and a smaller, spongy left kidney, the MRI confirmed multiple cystic formations cortically on Ithe right side, along with a reduction in width of the parenchyma as well as upper size limit of the right kidney. The MRI finding of the left kidney was normal вЂ“ that is, the suspicion put forth by the ultrasound regarding the changes consistent with sponge kidney was dismissed.One fetal MRI was done for the evaluation of intraperitoneally localized cystic tumour, for which it was determined by the ultrasound to most likely be of ovarian origin. The fetal MRI facilitated a detailed spatial and tissue characterization: it was determined to be a question of an intraperitoneal thick wall cyst filled with clear, fluid contents. This cystic lesion did not have infiltrative but rather partially compressive character. In other words, the MRI examination concluded that it was a benign lesion, most likely a mesenteric cyst or an ovarian cyst (Figures 3 A,B). Figures 3 A,B. MRI of fetus with intraperitoneal cystic lesion. A Figure 2. MRI of fetus with hydronephrosis. B Coronal T2-weighted image shows hydronephro sis of right kidney most probably as a consequence of ureteropelvic junction stenosis since there is no evidence of ureter dilatation. The parenchyma width of the mentioned kidney is preserved. The finding regarding the other kidney is normal. Medicinski Еѕurnal 2013 бѓЂ19 (1): 4 - 8 Sandra Vegar-ZuboviД‡, Spomenka KristiД‡, Lidija Lincender , Irmina SefiД‡-PaЕЎiД‡, Aladin ДЊarovac. The fetal magnetic resonance imaging of neural and thoraco-abdominal anomalies Axial T2-weighted image (a) and coronal T2weighted image (b) showing intraperitoneal thick wall cyst filled with clear, fluid contents. Cystic lesions have partially compressive character and characteristics of benign lesion, most likely a mesenteric cyst or an ovarian cyst. In another case, the MRI was conducted because of ultrasonically verified pathological distension of the stomach. The MRI results determined an appropriate positioning of the stomach which longitudinal diameter reached upper limits, while the transverse diameter was within physiological limits according to the dimensions specified in the international chart of fetal organs dimensions. Also, among the MRI exams, pyloric narrowing was ruled out. Through our research, four fetal MRIs were performed on suspicion of central nervous system malformation. The MRI finding of a patient with ultrasound suspicion of having hydrocephalus, was normal. An ultrasonic indication for a fetal MRI in another patient was due to a malformation of the posterior cranial fossa вЂ“ closer analysis was hindered by the calcification in the cavalry. The MRI finding verified the ultrasonic suspicions; that is, it verified the malformation of the cerebellum type Chairi II. With other two patients the fetal MRI confirmed the ultrasonic evidence of hydrocephalus, but it also supplied additional information: one patient showed evidence of aqueduct stenosis based on third and lateral ventricles dilatation with a normal-sized fourth ventricle, while the other patient had вЂ“ in addition to hydrocephalus вЂ“ atrophy of the cerebral cortex. DISCUSSION Even if our research included a relatively small number of patients (n=11), the collected results confirmed the efficiency of this method in assessing fetal malformations. If we take into account that only one (9%) of the total number of examinations was inadequate for analysis, we can conclude that the fetal MRI is a non invasive method which patients undertake without major difficulties. This is the consequence of the technological development of MRI and the introduction of new rapid sequences вЂ“ which permits shorter examination periods. The average time of our examinations was 37 minutes (ranging from 34 to 48 min.), which is in accordance with the international time average of 30 minutes (4). From the total number of executed examinations (n=10), in six cases (60%) there was a concordance between both the MRI and the ultrasound findings; however, in all these cases the MRI was further able to provide additional clinical information which was not detected on the ultrasound. Our results matched those mentioned throughout international medical literature. Levine et al. demonstrated the concordance between MRI and ultrasound diagnosis of the central nervous system malformation in 60% of cases (9). Hill at al. in their research regarding MRI diagnosis of fetal abdominal abnormalities observed concordances in MRI and ultrasound diagnosis in 50% of cases (10). Similar results had Ferhataziz at al. researching the role of the fetal MRI in diagnosing genitourinary and gastrointestinal abnormalities (11). In three cases (30%), the findings of the fetal MRI opposed those of the ultrasound, which is in accordance with the existing medical literature вЂ“ citing the discrepancy between the MRI and ultrasound findings at 20 вЂ“ 40%, depending on the system under research (1,12). In our research in two cases fetal MRI findings were normal or in other words we excluded the presence of fetal malformations, while in one case the fetal MRI ruled out polycystic kidney disease and instead pointed out the unilateral hydronephrosis most probably as a consequence of ureteropelvic junction stenosis, in addition to normal finding of the other kidney. As long as we take into account the development of the polycystic kidney disease as ultimately leading to kidney failure, while the ureteropelvic junction stenosis is a surgically solvable anomaly which would, in accordance to the maintained cortical size of the mentioned kidney, have a good longterm prognosis вЂ“ the importance of the fetal MRI should come to fruition. In one case, the fetal MRI finding partially confirmed the ultrasound finding, while simultaneously partially refuting it. In Figure 1, the graphic image shows the relation between the ultrasound and MRI diagnosis. The discrepancy between the fetal MRI findings and that of the ultrasound could be explained by the objectivity of these two diagnostic methods and the dependence of operatorвЂ™s experience. The MRI is an objective method, while ultrasound is real-time method that highly depends of the operatorвЂ™s capacity and experience as well as the patientвЂ™s cooperation (2,4). In four cases (three cases of hydrocephalus and one case of ureteropelvic junction stenosis) the fetal MRI drew attention to the need of surgical intervention in order to correct congenital malformations which would prevent future complications. Medicinski Еѕurnal 2013 бѓЂ19 (1): 4 - 8 7 8 Sandra Vegar-ZuboviД‡, Spomenka KristiД‡, Lidija Lincender , Irmina SefiД‡-PaЕЎiД‡, Aladin ДЊarovac. The fetal magnetic resonance imaging of neural and thoraco-abdominal anomalies CONCLUSION The fetal MRI presents a safe, affable diagnostic method which provides a plethora of important clinical information regarding the presence and the type of fetal abnormalities. The fetal MRI is complementary with ultrasound: on one hand, the MRI supplements ultrasound by supplying additional information, while on the other hand the ultrasound is the preferred method for screening and formulating justified indication for conducting fetal MRI examination. Conflict of interest: none declared. REFERENCES 1. Coakley FV, Glenn OA, Qayyum A, Barkovich AJ, Goldstein R, Fillz RA. Fetal MRI: A Developing Technique for the Developing Patient. AJR Am J Roentgenol. 2004 Jan; 182(1): 243-252. 2. Prayer D (ed). Fetal MRI, Medical Radiology. Berlin Heidelberg: Springer-Verlag; 2011. pp. 1-16. 3. Shellock FG, Kanal E. Policies, Guidelines, and Recommendations for MR Imaging Safety and Pa tient Management. J Magn Reson Imaging. 1991 Jan-Feb; 1(1):97-101. 4.Levine D. Ultrasound versus Magnetic Resona nce Imaging in Fetal Evaluation. Top Magn Reson Imaging. 2001; 12:25-38. 5. Rao BG, Ramamurthy BS. Pictorial Essay: MRI of the Fetal Brain. Indian J Radiol Imaging. 2009; 19:69-74. 6. Kasprian G, Balassy C, Brugger PC, Prayer D. MRI of Normal and Pathological Fetal Lung Devel opment. Eur J Radiol. 2006; 57:261-270. 7. Brugger PC, Prayer D. Fetal Abdominal Magnetic Resonance Imaging. Eur J Radiol. 2006; 57:278293. 8. Cassart M, Massez A, Metens T, Rypens F, Lam bot MA, Hall M, Avni FE. V. Complementary Role of MRI After Sonography in Assessing Bilateral Urinary Tract Anomalies in the Fetus. AJR Am J Roentgenol. 2004; 182:689-695. 9. Levin D, Barnes PD, Madsen JR. Central Nervous System Abnormalities Assessed with Prenatal Magnetic Resonance Imaging. Obstet Gynecol. 1999; 94:1011-1019. 10. Hill JB, Joe BN, Qayyum A, Yeh BM, Goldstein R, Coakley FV. Supplemental Value of MRI in Fetal Abdominal Disease Detected on Prenatal Sonography: Preliminary Experience. AJR Am J Roentgenol. 2005; 184:993-998. 11. Ferhataziz N, Engels JE, Ramus RM, Zaretsky M, Twickler DM. Fetal MRI of Urine and Meconium by Gestational Age rdance between both the MRI and the ultrasound for the Diagnosis of Genitouri nary and Gastrointestinal Abnormalities. AJR Am J Roentgenol. 2005; 184:1891-1897. 12. Sohn YS, Kim MJ, Kwon JY, Kim YH, Park YW. The Usefulness of Fetal MRI for Prenatal Diagno sis. Yonsei Med J. 2007; 48(4):671-677. Address: Vegar-ZuboviД‡ Sandra, MD, PhD Clinic of Radiology Clinical Center University of Sarajevo BolniДЌka 25, 71000 Sarajevo Bosnia and Herzegovina Phone: +387 61 202 880 Email: [email protected] NaЕЎ prilog redukciji kardiovaskularnih bolesti ! Our contribution in reduction of cardiovascular diseases ! Medicinski Еѕurnal 2013 бѓЂ19 (1): 4 - 8 Fatima GavrankapetanoviД‡-SmailbegoviД‡, Muhamed Ardat, Lejla ImЕЎirija, Naima ImЕЎirija, Faruk LazoviД‡, Mehmed JamakosmanoviД‡. Obstetric conditions as possible predictors of neonatal lesions of plexus brachialis Original article OBSTETRIC CONDITIONS AS POSSIBLE PREDICTORS OF NEONATAL LESIONS OF PLEXUS BRACHIALIS OPSTETRICIJSKA STANJA KAO MOGUД†I PREDIKTORI NEONATALNIH LEZIJA PLEKSUSA BRAHIJALISA Fatima GavrankapetanoviД‡-SmailbegoviД‡В№*, Muhamed ArdatВ№, Lejla ImЕЎirijaВ№, Naima ImЕЎirijaВ№, Faruk LazoviД‡ВІ, Mehmed JamakosmanoviД‡ВІ В№Clinic for Gynaecology and Obstetrics, Clinical Center University of Sarajevo, Patriotske lige 81, 71000 Sarajevo, Bosnia and Herzegovina; ВІOrhtopedic and Traumatology Clinic, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT At the delivery we can encounter difficulties which can lead to trauma of a newborn. The birth lesions of the brachial plexus is the most common neurological disorder of the peripheral type developed at birth, and therefore occupies an important place in the polyvalent rehabilitation of children. The lesions may be of various degrees, so we find two forms in the literature, paresis and paralysis of plexus brachialis. Different factors can certainly lead to injuries, but many authors think that the very course of labor is the main cause of brachial plexus defects. The essence is, in fact, that in most described cases there was poor obstetric technique. Plexus injuries may occur during spontaneous labor, although the direct cause is often the traction with abduction of babyвЂ™s head in relation to the shoulder girdle. The study is a retrospective-prospective, manipulative, therapeutically, cohort, controlled, randomized. 190 patients were processed in the period of January 1, 2004 to June 1, 2009. Patients were divided into two groups. The study was conducted on 18,914 deliveries over a period of 5 years. The attention is particular directed on vaginal births in this period, 13.852, or 73.24%. Our main task was to record all injuries that occurred during the period between January 1, 2004 and June 1, 2009. The analysis of age distribution of parturient women showed that 23.33% of parturient women from the group with no injuries belonged to the age group of 30 to 40 years, and with the injury more than one third, 34.29%. Plexus brachialis injury that occurs during delivery is a serious disease, a disease that can have long-term consequences, and which degree is assessed also in years after its creation. It is necessary to provide qualitative and regular monitoring of pregnant women, regular ultrasound examinations, in order to follow the status of the fetus, and the determination of fetal presentation, but also the precise value of the biparietal parameter, as another of the risk factors and qualitative and accurate measurement of pelvic dimensions. Key words: brachial plexus, paresis, paralysis, delivery SAЕЅETAK Tokom poroda moЕѕemo naiД‡i na poteЕЎkoД‡e koje mogu dovesti i do traume novoroД‘enДЌeta. PoroД‘ajna lezija brahijalnog spleta predstavlja najДЌeЕЎД‡i neuroloЕЎki sindrom perifernog tipa nastao roД‘enjem, pa stoga zauzima vaЕѕno mjesto u polivalentnoj rehabilitaciji djece. Lezije mogu biti razliДЌitog stepena, pa u literaturi nailazimo na dvije forme, parezu i paralizu pleksus brahijalisa. RazliДЌiti ДЌinioci mogu dovesti do povrede, ali niz autora smatra da je sam tok poroda glavni uzrok oЕЎteД‡enja pleksus brahijalisa. SuЕЎtina je, zapravo, da se u ovim sluДЌajevima radilo o slaboj opstetriДЌkoj tehnici u najveД‡em broju opisanih sluДЌajeva. Povreda pleksusa moЕѕe nastati i tokom spontanog poroda, iako je, najДЌeЕЎД‡e direktan uzrok trakcija sa abdukcijom glave bebe u odnosu na rameni pojas. Sprovedena je retrospektivnoprospektivna, manipulativno, terapeutsko, kohortno kontrolirana, randomizirana studija ObraД‘eno je Pacijentice su podijeljene u dvije skupine. IstraЕѕivanje je provedeno na 18.914 poroda, tokom perioda od 5 godina. Analizom starosne distribucije porodilja, pokazalo se da je 23.33% Medicinski Еѕurnal 2013 бѓЂ19 (1): 9 - 13 9 10 Fatima GavrankapetanoviД‡-SmailbegoviД‡, Muhamed Ardat, Lejla ImЕЎirija, Naima ImЕЎirija, Faruk LazoviД‡, Mehmed JamakosmanoviД‡. Obstetric conditions as possible predictors of neonatal lesions of plexus brachialis porodilja iz grupe bez povrede spadalo u dobnu skupinu od 30 do 40 godina, a sa povredom viЕЎe od jedne treД‡ine, 34.29%. Povreda pleksus brahijalisa koje se javlja u toku poroda je teЕЎko oboljenje, koje moЕѕe ima dugogodiЕЎnje posljedice, i ДЌiji se stepen procjenjuje i godinama nakon nastanka. Neophodni kvalitativno i redovno praДЌenje trudnice, redovni ultrazvuДЌni pregledi, u cilju praД‡enja stanja fetusa, te odreД‘ivanja prezentacije ploda, ali i precizno odreД‘ivanje vrijednosti biparijetalnog parametra, takoД‘er potrebno je kvalitetno i precizno mjerenje dimenzija karlice. KljuДЌe rijeДЌi: pleksus brahijalis, pareza, paraliza, porod and repair on its own during the first weeks of the childвЂ™s life, in which the child fully recovers the lost function. A small part still has weakened function of limbs due to injury, which is primarily a result of dystocia consequences, and develops longterm effects that are present till the end of life, and which could probably be avoided (6,7). Besides all the above mentioned, the following factors may participate in the formation of paresis plexus brachialis: large weight of a child, maternal diabetes, if the second stage of delivery is longer than 60 minutes, assisted delivery (use of medium and low forceps, vacuum extraction), anamneses indicating the birth of a child with a paresis plexus brachialis, intrauterine torticollis (8). INTRODUCTION MATERIALS AND METHODS At the delivery we can encounter difficulties which can lead to trauma of a newborn. Today there are tries to predict the flow of delivery with all means available, and prevent the occurrence of these in juries. Taking into account the technical possibilities in the developed countries, we can say that the birth lesions of the brachial plexus is not a rare problem in everyday life, and that is the most common neurological disorder of the peripheral type developed at birth, and therefore occupies an important place in the polyvalent rehabilitation of children (1). The lesions may be of various degrees, so we find two forms in literature, pa resis and paralysis of plexus brachialis (2). Different factors can certainly lead to injuries, but many authors think that the very course of labor is the main cause of brachial plexus defects. The essence is, in fact, that in most described cases there was poor obstetric technique (3). Plexus injuries may occur during spontaneous labor, although the direct cause is often the traction with abduction of babyвЂ™s head in relation to the shoulder girdle. Experimental studies have shown that the isolated longitudinal traction is insufficient, but lateral flexion of neck is necessary to avoid injuries of the plexus (4). If there is a bone fracture as well, the traction force necessary to cause damage to the nerve structure is smaller. Damage may also occur due to clavicle fracture (10%), fracture of the humerus head (10%), cervical vertebral subluxation, distortion, subluxation or luxation of the shoulder joint, epiphyseolysis, paralysis nervus facialis, and bone fractures of the upper limb (5). The percentage of recovery in the first few weeks is a good indication that the final result could probably be a complete recovery. However, if there is no complete restitution ad integ rum until The study is a retrospective-prospective, manipulative, therapeutically, cohort, controlled, randomized study, analysis of parameters that are important for early identification and an attempt to prevent situations that can cause or be the cause of this type of injury. The study was done at the Clinic for Ginaecology and Obstetrics Clinical Center University of Sarajevo and Clinic for Orthopedics and Traumatology Clinical Center University of Sarajevo. 190 patients were processed in the period from January 1, 2004 to June 1, 2009. Patients were divided into two groups: examinee group (70 parturient woman whose infants were postpartaly diagnosed paresis or paralysis of plexus brachialis) and control group (120 parturient women, similar characteristics whose children were not diagnosed paresis or paralysis). For each of these groups, there were criteria based on which the parturient woman were involved in each of them. For the examinee group, the following criteria were set: fetus delivery, children born naturally and paresis or paralysis of plexus brachialis diagnosed by the childвЂ™s orthopedist. The following criteria were set for the control group for inclusion: children delivered, delivery finished in a natural way and parturient woman which were examined each even working day of the month. The following parameters were taken during data collection for this study, adjusted for both pre-defined groups: motherвЂ™s age, body height of mother, body weight of mother (before pregnancy, at the end of pregnancy, gained weight during pregnancy), and body mass index (BMI). BMI is the most widely used method of determining the degree of obesity. It relies primarily on sex and age, and is calculated by the number of kilograms divided by height in meters squared. the first two weeks of the childвЂ™s life, then the chances for it to happen after are quite small. Many cases of brachial plexus paralysis are of transient nature, Medicinski Еѕurnal 2013 бѓЂ19 (1): 9 - 13 Fatima GavrankapetanoviД‡-SmailbegoviД‡, Muhamed Ardat, Lejla ImЕЎirija, Naima ImЕЎirija, Faruk LazoviД‡, Mehmed JamakosmanoviД‡. Obstetric conditions as possible predictors of neonatal lesions of plexus brachialis RESULTS Distribution of the number of births, but also a way of completion, and the relationship of the number of deliveries completed vaginally and by Cesarean section, followed by analog were shown by Table 1. As can be seen, a total of 18,941 treated mothers, in most case of births were completed vaginally, n=13,852, which represents 73.24%. Among the 70 patients with injury, the youngest was 19 and the oldest 37 years old, while the age range for the group of patients in whom there was no injury was slightly higher, 21, compared with age range of 18 in the group of patients with njury (Table 4). Table 4. Arithmetic value and standard deviation for age value. Table 1. Distribution of the number of deliveries and the way of completion observed during 5 years. Young mothers are primarily watched in the two age groups where it was evident that the presence of 34.29% of mothers whose children were born with plexus brachialis paresis in group of 30 to 40 years, was slightly higher, compared to 23.33% in which children did not have injury (Table 2). The analysis showed that the average height of mothers was 170.12 cm in the group of pregnant women, and 169.14 cm in the group of mothers. The range in which the values were varied for the first group of 20, and 16 for the second, according to the present value of the standard deviation was larger for the first group of 4.749, and 2.908, for the second group (Table 5). Table 5. Arithmetic averages and standard deviations for body height. Table 2. Age distribution of mothers. In 55.88% of cases, the injury occurred in the mothers who have not previously given birth, and 38.24% in mothers with whom it was their second birth (Table 3). Table 3. Number of births and their relationship to the nature of injury. In Table 6 we can see that the maximum value of weight is given to mothers during pregnancy for the first group of 40 kg, and for the group without injuries of 34 kg. The average value, according to the range for the first group was 33, and 28 for the second. Mean range was 20.98, compared to 16.06 kg. Table 6. Arithmetic mean and standard deviation obtained weight during pregnancy. Medicinski Еѕurnal 2013 бѓЂ19 (1): 9 - 13 11 12 Fatima GavrankapetanoviД‡-SmailbegoviД‡, Muhamed Ardat, Lejla ImЕЎirija, Naima ImЕЎirija, Faruk LazoviД‡, Mehmed JamakosmanoviД‡. Obstetric conditions as possible predictors of neonatal lesions of plexus brachialis In Table 7 we can see that the maximum values of BMI, we received indirectly from the previously mentioned formula is as high as 30.52 for a group of patients with injury, and 28.36 in the group without injuries. The minimum amount for the first group of subjects was 19.05, compared to second group of 18.81. Table 7. Arithmetic mean and standard deviation of BMI before pregnancy. BMI at the end of pregnancy had a maximum val ue of 38.31 for the first group, while the second group was 34.72. The minimum amount for the first group was 22.49 and 23.03 for the second group. The standard deviation for the first group was3.398, and for the second group of 2.393 (Table 8). Table 8. Arithmetic mean and standard deviation of BMI at the end of pregnancy. Analysis of ultrasonic fetal interventricular includes analysis of biparietal diameter (BPD), femur length and sex of the child. The values in the BPD group without injuries have ranged from 15, and 11 mm in the group with injury. The mean value for the first group was 103.75 mm, with a standard deviation of 2.380, and without prejudice to and without injuries was of 102.09, with a standard deviation of 2.920 (Table 9). Table 9. Arithmetic averages and standard deviations for biparietal diameter in mm. Medicinski Еѕurnal 2013 бѓЂ19 (1): 9 - 13 DISCUSSION The study was conducted on 18,914 deliveries over a period of 5 years. The attention is particular directed on vaginal births in this period, 13.852, or 73.24%. Our main task was to record all injuries that occurred during the period between January 1, 2004 and June 1, 2009. During this period, we observed two groups of parturient woman, namely a group of 70 parturient women who received newborns with the plexus brachialis paresis, and a group of examinees by whom there was no violation, 120 randomly selected parturient woman, with previously established characteristics. It was significantly noted that the incidence of reporting these violations at the Clinic of Obstetrics and Gynecology, Clinical Center University of Sarajevo is in decline. In part, this phenomenon can be explained by increased number of caesarean section over a period of 5 years, with 921 in 2004 to 1109 in 2008 year. This represents an increase of 16.9%. During 2004 and 2005, the incidence of injury occurrence was 5.4, i.e. 5.6 cases per 1000 vaginal deliveries in average for both years, whereas in 2008 the incidence was 1.8 cases per 1000 births. If you look at the same table, one can see that in 2009 incidence was slightly higher, 2.5, but it should be taken into account that the data for this year relate to a period of the first five months. Anyway, for the observed period of 5 years the incidence was 3.7/1000 living children (9). For the monitoring period, we registered more than 70 plexus brachialis injuries, of which 70 occurred without the use of operating procedures, while others were excluded from the analysis due to use of operational procedures during childbirth, vacuum extraction and forceps (10). The analysis of the age distribution of parturient women showed that 23.33% of parturient women from the group with no injuries belonged to the age group of 30 to 40 years, and with the injury more than one third, 34.29% (11). This result can be explained by the fact that birth is physiologically more difficult in elderly (12). One of the possible reasons for this result should be sought in the fact that the cervix is of rigid structure in the elderly, and with its low maximum dilation a large resistance at delivery is created, and this delay conditions hard releasing of shoulders as the widest part of the child (13). The analysis of all the collected data showed that in the group with injuries, as much as 97.14% were occipital presentations, and only 2.86% pelvic (6). Therefore, we decided to monitor two cases that represent the pelvic presentation, comparing them with two descriptive cases of pelvic presentations that were recorded in the examinee group where infants had no injuries. Fatima GavrankapetanoviД‡-SmailbegoviД‡, Muhamed Ardat, Lejla ImЕЎirija, Naima ImЕЎirija, Faruk LazoviД‡, Mehmed JamakosmanoviД‡. Obstetric conditions as possible predictors of neonatal lesions of plexus brachialis So we first focused our analysis on 70 cases from the group with injuries, and their comparison with 120 cases without injury, but delivered with occipital presentation. CONCLUSIONS We conclude that the plexus brachialis injury that occurs during delivery is a serious disease, a disease that can have long-term consequences, and which degree is assessed also in years after its creation. It is necessary to provide qualitative and regular monitoring of pregnant women, and her consultations to prevent the formation of some previously mentioned risk factors, such as excessive weight gain, which can affect the outcome of better delivery, regular ultrasound examinations, in order to follow the status of the fetus, and the determination of fetal presentation, but also the precise value of the biparietal parameter, as another of the risk factors and qualitative and accurate measurement of pelvic dimensions may, only with other mentioned parameters, help the obstetrician in choosing ways to end the delivery, and to assess whether there is a real danger of injury. Conflict of interest: none declared. REFERENCES 1. Taeusch H, Ballard AR, Gleason AC, Avery ME. AveryвЂ™s diseases of the newborn. Philadelphia: Elsavier Sounders; 2005. pp.1431-1433. 2. OвЂ™Brien DF, Park TS, Noetzel MJ, Weatherly T. Management of birth brachial plexus palsy. Childs Nerv Syst. 2006 Feb;22(2):103-12. 3. Callahan LT, Caughey BA, Heffner JL. Blueprints obstetrics and gynecology. Massachusetts: Blackwell publishing; 2004. pp. 69-71. 4. Berghella V. Obstetric evidence based guidelines. London: Informa; 2007. pp. 157-182. 7. Vredeveld JW, Blaauw G, Slooff BA, Richards R, Rozeman SC. The findings in paediatric obstetric brachial palsy differ from those in older patients: a suggested explanation. Dev Med Child Neurol. 2000 Mar;42(3): 158-61. 8. Norwitz RE, Schorge OJ. Obstetrics and gynecology at a glance. Massachusetts: Blackwell publishing; 2001. pp.121-127. 5. Grossman JA, DiTaranto P, Price A, et al. Multidisciplinary management of brachial plexus birth injuries: 2004. The Miami experience. Semin Plast Surg. 2004;18(4):319-26. 6. Dahlin L, Erichs K, Andersson C, Thornquist C, Backman C, DГјppe H, et al. Incidence of early posterior shoulder distocia in brachial plexus birth palsy. J Brachial Plex Peripher Nerve Inj. 2007 Dec16;2:24. 9. Strombeck C, Krumlinde-Sundholm L, Forssberg H. Functional outcome at 5 years in children with obstetrical brachial plexus palsy with and without microsurgical reconstruction. Dev Med Child Neurol. 2000;42(3): 148-57. 10. Mercuri E, Dubowic V. Neuromuscular disorders. In: Levene IM, Chervenak AF, Whittle JM. Fetal and neonatal neurology and neurosurgery. Philadelphia: Elsavier Sounders; 2009. pp. 792-810. 11. Mollberg M, Wannergren M, Bager B, Ladfors L, Hagberg. Obstetric brachial plexus palsy: a prospective study on risk faktors related to manual assistence during the second stage of labor. Acta Obstet Gynecol Scand. 2007; 86(2):198-204. 12. Foad S, Mehlman C, Ying J. The Epidemiology of Neonatal Brachial Plexus Palsy in the United States. J Bone Joint Surg Am. 2008 Jun;90(6):1258-64. 13. Grossman JA, DiTaranto P, Price A, et al. Multidisciplinary management of brachial plexus birth injuries: 2004. The Miami experience. Semin Plast Surg. 2004;18(4):319-26. Address: Fatima GavrankapetanoviД‡-SmailbegoviД‡, MD, PhD Clinic for Gynaecology and Obstetrics Clinical Center Unversity of Sarajevo Patriotske lige 81, 71000 Sarajevo Bosnia and Herzegovina Phone:+387 33 250 316 Email: [email protected] Medicinski Еѕurnal 2013 бѓЂ19 (1): 9 - 13 13 14 Faris FoДЌo, Lejla DЕѕananoviД‡, Zlatan ZvizdiД‡, Edin ImamoviД‡, Irma RamoviД‡, Semra ДЊavaljuga. Malignant lip tumours ; survival analysis Original article MALIGNANT LIP TUMOURS; SURVIVAL ANALYSIS MALIGNI TUMORI USANA; ANALIZA PREЕЅIVLJAVANJA 2 Faris FoДЌo1*, Lejla DЕѕananoviД‡ , Zlatan ZvizdiД‡ 3, Edin ImamoviД‡1, Irma RamoviД‡1, Semra ДЊavaljuga2 1 Clinic for Maxillofacial Surgery, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, 2 Bosnia and Herzegovina; Institute of Epidemiology and Biostatistics, Faculty of Medicine University 3 of Sarajevo, ДЊekaluЕЎa 90, 71000 Sarajevo, Bosnia and Herzegovina; Clinic for Paediatric Surgery, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT SAЕЅETAK This paper referred to malignant tumours of lips. The objectives of this study were to present distribution of malignant diseases of lips according to patientsвЂ™ gender and age, localization of tumour, pathological analysis and to present a five-year survival analysis on these patients, as well as to assess the importance of early diagnosis and medical treatment. A ten-year retrospective clinical and observational follow-up study of patients treated at Clinic for Maxillofacial Surgery, Clinical Centre University of Sarajevo for malignant tumours of lips, in period from January 1998 to December 2007, was performed. Total of 1,271 patients were admitted for treatment, of which 139 patients had tumour of lips. Results showed that at our Clinic we treated more male patients with malignant lips tumours than female ones (gender ratio 2.3 men to 1 woman); mostly older patients, with almost half of them being at age 60 years or more. Regarding histopathology, tumours were predominantly squamous cell carcinoma type. Life-table analysis showed a five-year survival rate of 71.23%. Nevertheless, this study should be seen as the pilot study. One with similar methodology but more extensive - regarding number of patients, including more detailed anamnestic data and longer follow-up period - should be conducted, in order to clarify correlation of all demographic and risk factors, treatment data and exact survival times and rates. Rad se odnosi na analizu obolijevanja pacijenata od malignih tumora usana. Cilj ove studije bio je da prezentira distribuciju malignih tumora usana prema spolu i dobi pacijenata, lokalizaciji tumora, rezultatima patoloЕЎke analize i predstavi analizu petogodiЕЎnjeg preЕѕivljavanja ovih pacijenata, kao i da ispita znaДЌaj rane dijagnoze i tretmana. Sprovedena je desetogodiЕЎnja retrospektivna kliniДЌka i observaciona studija na pacijentima Klinike za maksilofacijalnu hirurgiju KliniДЌkog centra Univerziteta u Sarajevu, koji su tretirani zbog malignog tumora usana, u periodu januar 1998 вЂ“ decembar 2007. Ukupno je tretiran 1.271 pacijent od kojih je njih 139 imalo tumor usana. Rezultati ove studije pokazali su da je veД‡i broj tretiranih pacijenata muЕЎkog spola (odnos spolova 2,3 naprema 1 u korist muЕЎkaraca). VeД‡ina su stariji pacijenti, a skoro ih polovina (49.64%) ima 60 i viЕЎe godina. HistopatoloЕЎka analiza tumora pokazala je da je najДЌeЕЎД‡i tip bio karcinom skvamoznih Д‡elija. Analiza preЕѕivljavanja pokazala je petogodiЕЎnju stopu preЕѕivljavanja od 71,23%. Ova studija ipak treba biti posmatrana kao pilot studija. PreporuДЌuje se sprovesti studiju sliДЌne metodologije ali znatno obimniju вЂ“ ЕЎto se tiДЌe broja pacijenata, detaljnijih anamnestiДЌkih podataka i duЕѕeg perioda praД‡enja, u cilju razjaЕЎnjavanja korelacije svih demografskih podataka, riziko faktora, terapije i taДЌnog vremena i stopa preЕѕivljavanja. Key words: malignant lip tumours, survival, survival analysis KljuДЌne rijeДЌi: maligni tumori usana, preЕѕivljavanje, analiza preЕѕivljavanja Medicinski Еѕurnal 2013 бѓЂ19 (1): 14 - 19 Faris FoДЌo, Lejla DЕѕananoviД‡, Zlatan ZvizdiД‡, Edin ImamoviД‡, Irma RamoviД‡, Semra ДЊavaljuga. Malignant lip tumours ; survival analysis INTRODUCTION A tumour is abnormal matter whose growth outweighs the normal tissue growth and is not coordinated with it, and continues even after the stimulus causing it ceases as defined by Willis (1). This definition is not perfect, but somehow it gives instructions and guidelines for further research and understanding of the oncology issues. There are many aetiological factors that may cause tumorous formations in the area, i.e., their rosy parts. In literature there are some data about the direct relation between tumour lesion formation and gene mutation, smoking, some virus activity and sun rays (2-12). Tumours generally discussed in this paper are occurring at any site of the head or neck and at any age (13,14,15,16). Localization is very important in assessing the disease and degree of progress, since therapy depends on it (17,18,19,20). The main characteristics of malignant tumours of lips are that they grow uncontrollably, infiltrate and destroy tissue by spreading into immediate and remote sites, with frequent relapses and metastases (21). Literature cites that among tumours of head and neck, as many as about 27% develop on the lips (1,8,9,10,11,12,13,19,20). Therefore, the objectives of this paper were to: 1. Present data on histopathological verification, gender and age distribution of patients treated from malignant tumour of lips at Clinic for Maxillofacial Surgery, Clinical Center University of Sarajevo in a ten-year period (1998-2007) and compare them to the results available from other authors, Diagnosis of this disease was established on clinical examination and confirmed by histopathological verification. All operated patients had adequate pre-operative preparation, optimal operative treatment and postoperative therapy. A five-year follow-up for all patients was done and after that period, patients without relapse of the disease went for a once a year check-up. A five-year survival analysis of our patients was performed using life table analysis. In this study all patients of both gender and all ages are included, and the ones who accepted the suggested therapy. Patients who didn't accept the suggested treatment and with bad condition, from the a bove mentioned reasons are not included, and some of them were not be able to be operated or they were under irradiation and chemotherapy. RESULTS Table 1 presents the proportion of patients with malignant tumour of lips in total number of patients treated at Clinic for Maxillofacial Surgery, Clinical Center University of Sarajevo, in period from January 1998 to December 2007. It can be seen that 11% of treated patients had malignant tumour of lips. Table 1. Patients treated at Clinic for Maxillofacial Surgery, Clinical Center University of Sarajevo, in period from January 1998 to December 2007, according to diagnosis. 2. Perform a survival analysis on these patients, 3. Present factors which can help in early diagnosis in order to treat patients successfully. MATERIALS AND METHODS This study was performed as a retrospective clinical and observational ten-year follow-up.Data were collected from medical documentation of patients who were treated at Clinic for Maxillofacial Surgery, Clinical Center University of Sarajevo, for malignant tumours of head and neck, in period from January 1998 to December 2007. In total we included total of 1.271 patients who were admitted for treatment. Out of total number of patients we had 139 patients (10,93 %) with tumour of lips. Figure 1 and 2 presents distribution of patients treated for malignant tumours of lips (n=139) in the same period, by gender and age, respectively. Figure 1 shows that there were more male than female patients admitted for treatment of malignant tumours of lips. Figure 2 shows that almost half of patients were at 60 years of age or more. Medicinski Еѕurnal 2013 бѓЂ19 (1): 14 - 19 15 16 Faris FoДЌo, Lejla DЕѕananoviД‡, Zlatan ZvizdiД‡, Edin ImamoviД‡, Irma RamoviД‡, Semra ДЊavaljuga. Malignant lip tumours ; survival analysis Figure 1. Distribution of patients by gender. Figure 3. Different sizes of malignant tumour of lips in our patients. Figure 2. Distribution of patients by age. Table 3 and Table 4 present results of histopathological analysis of treated malignant tumours and their localization, respectively. It can be seen that over 80% of tumours were of squamous cell carcinoma type. Majority were localized on lower lip. Table 3. Results of histopathological analysis of malignant tumours. Table 2 presents distribution of patients by calendar year of first registration and treatment for malignant tumour of lips. Figure 3 shows these patients on hospital admission, with tumours of different sizes and lip localizations. Table 2. Patients treated by calendar year of first registration and treatment. Table 4. Location of malignant tumours. Figure 4 and Table 5 show structure of patients by operative method used in treatment of these tumours and type of surgical neck dissection performed, respectively. Figure 5 illustrates operative techniques used for lip tumours treatment. It can be seen that with almost 60% of patients we performed reconstruction of lips by sec. KarapandЕѕiД‡, sec. Dieffenbach or sec. BrunsSzymanowski. Regarding the type of performed neck dissection, on 36% of patients suprahyoid dissection was performed and on almost 22% radical neck dissection. Medicinski Еѕurnal 2013 бѓЂ19 (1): 14 - 19 Faris FoДЌo, Lejla DЕѕananoviД‡, Zlatan ZvizdiД‡, Edin ImamoviД‡, Irma RamoviД‡, Semra ДЊavaljuga. Malignant lip tumours ; survival analysis Figure 4. Structure of patients by operative method used in treatment of malignant tumours of lips. Figure 6 presents types of therapy used to treat patients. Type of therapy depended on local regional spreading of tumour, histopathological analysis and degree of radicality of operative procedure. Therapy was finished by radical operation as the method of the choice in 112 pa tients or 80.57%. The treatment was continued with postoperative irradiation in 19 patients or 13.66% and complemented by irradiation and chemotherapy in 8 patients. Figure 6. Type of therapy used in treatment of malignant tumours of lips. Table 5. Type of surgical neck dissection. Table 6. Life table analysis. Figure 5. The most often used operative methods. Figure 7. Survival curve for patients treated from 1998 to 2007 and followed until 2012. Medicinski Еѕurnal 2013 бѓЂ19 (1): 14 - 19 17 18 DISCUSSION From the above frequency data, during the study in a ten year period, it can be seen that out of 1,271 patients with malignant tumours of head and neck, 139 patients (16.72%) were treated because of malignant tumours of lips. Barna and collaborators, Brinca and collaborators, Moretti and collaborators and Unsal Tuna EE and collaborators presented that malignant tumours of lips appear in about 10.9% of cases of the total number of malignant tumours of maxillo-facial region (13,14,15,16). Among them about 81.3% are located on lower lip. Gender ratio of our patients was 2.3 men to 1 woman. Comparing our results to the results of Moore and collabo rators, Jadotte YT and collaborators, GГ©raud C and collaborators it can be stated that our results match their results (10,11,12). Same researches mention smoking as a lead etiologic factor in these tumoursвЂ™ development, as well as exposure to sun rays. This could not be confirmed in our study, as the study was not investigating risk factors for tumour development but survival after diagnosis and treatment. Older people, age over 60, were the most often group with malignant tumours on lips in our study. Papers of Mirbord and collaborators,Ben Slama L., Morris and collaborators, Gallagher R.P. and collaborators, Just-SarobГ© M. are about bad oral hygiene, bad habits, low standard of living and smoking (3,4,5,6,7). Regarding the fact that there had been an aggression against our country in the past period (1992-1995) and population passed through significant demographic changes among all others, it is not strange that this population is the most numerous. Many our patients came to the Clinic in advanced stage of the disease due to somehow unexplained reasons for us, but one would say it is lack of medical knowledge of our patients. The choice of operative treatment depended directly on the size of tumour. Small and medium size tumours were removed operatively by вЂњVвЂќ and вЂњWвЂќ excision (in 22 and 37 cases, respectively). Lopes and collaborators prefer вЂњWвЂќ and вЂњYвЂќ excision in relation to the use of flaps in cases when the corner, commissural of lips, is not affected by tumour (18). With large tumours when more than half of a lip was affected, reconstruction of lips was done by method of local flaps according to the authors. Brinca and collaborators, Moretti and collaborators, Unsal Tuna E.E. and collaborators and KayabaЕџoДџlu G., prefer the method with local flaps. Reconstruction by sec. KarapandЕѕiД‡, sec. Dieffenbach or sec. Bruns-Szymanowski we used Ion 80 patients or 57.55% (14,15,16,20). We can compare our results to data of McCombe and collaborators and Richards D. where in ten year follow-up period, Medicinski Еѕurnal 2013 бѓЂ19 (1): 14 - 19 survival without relapse was observed in about 98% cases (19, 21). Our study was conducted in period 1998-2012, however patientsвЂ™ enrolment was only until 2007, as we wanted to observe five-year survival rate for all enrolled patients. Life-table analysis showed that 71.23% of our patients survived from the beginning of treatment to the end of the fifth year. We did not have data on exact time of death for each patient, just the number of patients alive at the beginning of each year based follow-up interval, therefore the Kaplan-Meier method could not be applied in calculating survival. The last deceased patient was enrolled in 2005 and died in 2010. No deaths were reported in 2011 and 2012. To the best of our knowledge, all other patients are still alive, thus, if calculated, a ten-year survival rate would be the same as a five-year for this studyвЂ™s population. CONCLUSION Demographic frequency data collected in this study showed that at our Clinic, which is the only clinic for maxillo-facial surgery in the country, there are more male patients with malignant lips tumours than female ones, what is consistent with world literature data. These are also mostly older patients, with almost half of them being at age 60 years or more. Regarding histopathology, tumours were predominantly squamous cell car cinoma type. Survival rate of our patients proved to be consistent with results from other studies. Nevertheless, this study should be seen as the pilot study. One with similar methodology but more extensive - regarding number of patients, including more detailed anamnestic data and longer follow-up period - should be conducted, in order to clarify correlation of all demographic and risk factors, treatment data and exact sur vival times and rates. Conflict of interest: none declared. REFERENCES 1. DautoviД‡ S, TomiД‡-Д†uk I. Tumori maksilofacijalne regije. Sarajevo: Rail print; 1998. 2. Ostwald C, Gogacz P, Hillmann T, Schweder J,Gundlach K, Kundt G, et al. p53 mutational spectra are different between squamous-cell carcinomas of the lip and the oral cavity. Int J Cancer. 2000 Oct 1; 88(1):82-6. 3. Mirbod SM, Ahing SI. Tobacco-associated lesions of the oral cavity: Part II. Malignant lesions. J Can Dent Assoc. 2000 Jun;66(6):308-11. 4. Ben Slama L. Carcinoma of the lips. Rev Stomatol Chir Maxillofac. 2009 Nov;110(5):278-83. Faris FoДЌo, Lejla DЕѕananoviД‡, Zlatan ZvizdiД‡, Edin ImamoviД‡, Irma RamoviД‡, Semra ДЊavaljuga. Malignant lip tumours ; survival analysis 5. Morris RE. Mahmeed BE. Gjorgov AN. Jazzaf HG. Rashid BA.The epidemiology of lip, oral cavity and pharyngeal cancers in Kuwait 1979-1988. Br J Oral Maxillofac Surg. 2000 Aug;38(4):316-9. 6. Gallagher RP, Lee TK, Bajdik CD, Borugian M. Ultraviolet radiation. Chronic Dis Can. 2010;29 Suppl 1:51-68. 7. Just-SarobГ© M. Smoking and the skin. Actas Dermosifiliogr. 2008 Apr;99(3):173-84. 8. Pyle MA, Zak J, Bath M, Sawyer DR. Peri neural spread of squamous cell carcinoma of the lip: the importance of follow-up and collabora tion. Special Care in Dentistry. 1999 May-Jun; 19(3):118-22. 9. Burusapat C, Pitiseree A. Advanced squamous cell carcinoma involving both upper and lower lips and oral commissure with simultaneous re construction by local flap: a case report. J Med Case Rep. 2012 Jan ;6(1):23. doi: 10.1186/17521947-6-23. 10. Moore S, Johnson N, Pierce A, Wilson D. The epidemiology of lip cancer: a review of global incidence and aetiology. Oral Dis. 1999 Jul;5(3):185-95. 11. Jadotte YT, Schwartz RA. Solar cheilo sis: an ominous precursor part II. Therapeu tic perspectives. J Am Acad Dermatol. 2012 Feb;66(2):187-98. 12. GГ©raud C, Koenen W, Neumayr L, Doobe G, Schmieder A, Weiss C, et al. Lip cancer: retro spective analysis of 181 cases. J Dtsch Dermatol Ges. 2012 Feb;10(2):121-7. 13. Barna M, Gogalniceanu D, Voroneanu M, Mihai C. [Reconstructive plastic repair in cancer of the lips]. [Romanian]. Rev Med Chir Soc Med Nat Iasi. 1997 Jul-Dec;101(3-4):156-60. 14. Brinca A, Andrade P, Vieira R, Figueiredo A. Karapandzic flap and Bernard-Burrow-Webster flap for reconstruction of the lower lip. An Bras Dermatol. 2011 Jul-Aug;86(4 Suppl 1):S156-9. 15. Moretti A, Vitullo F, Augurio A, Pacella A, Croce A. Surgical management of lip cancer. Acta Otorhinolaryngol Ital. 2011 Feb;31(1):5-10. 16. Unsal Tuna EE, OksГјzler O, Ozbek C, Oz dem C. Functional and aesthetic results obtained by modified Bernard reconstruction technique af ter tumour excision in lower lip cancers. J Plast Reconstr Aesthet Surg. 2010 Jun;63(6):981-7. 17. Evans DM.The staggered ellipse. British Journal of Plastic Surgery. 2000 Apr; 53(3):240-2. 18. Lopez AC, Ruiz PC, Campo FJ. Gonzalez FD. Reconstruction of lower lip defects after tumor excision: an aesthetic and functional evaluation. Otolaryngology - Head & Neck Surgery. 2000 Sep;123(3):317-23. 19. McCombe D, MacGill K, Ainslie J, Beresford J, Matthews J. Squamous cell carcinoma of the lip: a retrospective review of the Peter MacCallum Cancer Institute experience 1979-88. Aust N Z J Surg. 2000 May;70(5):358-61. 20. KayabaЕџoДџlu G. Local flap reconstruction of resected non-melanoma malignant skin tumors: a case series of 57 patients. Kulak Burun Bogaz Ihtis Derg. 2012 Sep-Oct;22(5):259-266. 21. Richards D. Clinical recommendations for oral cancer screening. Evid Based Dent. 2010;11(4):101-2. Address: Ass.prof. Faris FoДЌo, MD, PhD Clinic for Maxillofacial Surgery Clinical Center University of Sarajevo Hazima Е abanoviД‡a 1, 71000 Sarajevo Bosnia and Herzegovina Phone: +387 33 226661 Email: [email protected] Medicinski Еѕurnal 2013 бѓЂ19 (1): 14 - 19 19 20 Narcisa Vavra-HadЕѕiahmetoviД‡, Aldijana KadiД‡, Damir ДЊelik. The significance of implementation of DRG (Diagnosis Related Groups) health care reforms in the field of physical medicine and rehabilitation Original article THE SIGNIFICANCE OF IMPLEMENTATION OF DRG (DIAGNOSIS RELATED GROUPS) HEALTHCARE REFORMS IN THE FIELD OF PHYSICAL MEDICINE AND REHABILITATION ZNAДЊAJ SPROVEDBE DRG (DIAGNOSIS RELATED GROUPS) REFORME U ZDRAVSTVU ZA OBLAST FIZIKALNE MEDICINE I REHABILITACIJE Narcisa Vavra-HadЕѕiahmetoviД‡*, Aldijana KadiД‡, Damir ДЊelik Clinic for Physical Medicine and Rehabilitation, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT The Project Financing of Secondary Health Care Reform in Bosnia and Herzegovina was financed by the European Union. The main objective is to establish hospital payment system based on the results and to develop health information system. Objective: To describe the advantages and disadvantages of the application of Diagnosis Related Groups (DRG) reform at the Clinic for Physical Medicine and Rehabilitation, Clinical Center University of Sarajevo (CCUS), compared to the previous period. A descriptive study was conducted in the period from April, the 1st 2012 until May, the 1st 2012, and included 41 patients hospitalized at Clinic for Physical Medicine and Rehabilitation, CCUS. Medical records are used as a source of data. There were three groups of patients with: cerebrovascular insult (CVI) (n=19), herniated disk (HD) (n=17) and lower leg amputation below the knee (ABK) (n=15). Measures of descriptive statistics were used: frequency and relative frequency (%).In the group of CVI patients (n=19), earlier diagnostic and therapeutic procedures (DTP) were: passive exercise, gait with the aids, balance, occupational therapy and galvanization. According to DRG system, the number of DTP is higher and represents: biomechanical evaluation (19 or 100.0%), activities daily living (ADL) (19 or 100.0%), blood collection for diagnosis (16 or 84.2%), exercise therapy-shoulder joint (4 or 21.1%), exercise therapy-the muscles thorax and abdomen (1 or 5.3%), exercise therapy-back muscles and neck (2 or 10.5%), exercise therapy-arm muscles (6 or 31.6%), exercise therapy elbow (3 or 15.8%), exercise therapy-hand muscles, wrist and phalangeal (1 or 5,3%), exercise therapy-hip joint (2 or 10,5%), exercise therapy-pelvic floor muscles (3 or 15.8%), exercise therapy-leg muscles (6 or 31.6%), exercise therapy- muscle foot, ankle and toes (4 or 21.1%), coaching skills in acMedicinski Еѕurnal 2013 бѓЂ19 (1): 20 - 24 tivities that relate to body posture (21.1%), coaching skills relating to the transfer (1 or 5.3%), exercise therapy-respiratory system /breathing/ (7 or 36.8%), coaching skills using aids and equipment (3 or 15.8%), exercise therapy -whole body (10 or 52.6%), the movable continuous electrocardiogram (ECG) (1 or 5.3%), holter mobile continuous ECG (1 or 5.3%), ultrasound of the heart (1 or 5.3%), treatment of warmth (2 or 10.5%), stimulation therapy / EMS, FES, IFT, TENS / (5 or 26.3%), exercise therapy-facial muscles (1 or 5.3%), massage therapy (1 or 5.3%). In the group of HD patients (n=17) earlier DTP were: ADL, isometric exercises, electro procedures. According to DRG system, the number of DTP is higher, accounting 10 DTP. In the group of ABK patients (n=5) earlier DTP were: bandage, active exercises stumped with the resistance, exercise walk. According to DRG system, the number of DTP is higher, accounting 10 DTP. Conclusion: The new encoding through a program DRG is a better option of encryption services and hence better collection incurred procedures, which lead to good monitoring of the effectiveness of hospitals and a better evaluation of the hospital sector as a whole. Key words: health care reform, Diagnosis Related Groups (DRG), rehabilitation SAЕЅETAK Projekat Reforme finansiranja sekundarne zdravstvene zaЕЎtite u Bosni i Hercegovini finansiran je od strane Europske Unije, a opД‡i cilj projekta je postavljanje temelja za sistem plaД‡anja bolnica temeljen na rezultatima i buduД‡i razvoj zdravstvenih informacijskih moguД‡nosti u bolnicama, te izrada ДЌvrstih temelja za glavnu reformu plaД‡anja bolnica. Cilj rada je prikazati prednosti i nedostatke u primjeni DRG reforme na Klinici za fizijatriju i bolnicama, te izrada ДЌvrstih temelja Narcisa Vavra-HadЕѕiahmetoviД‡, Aldijana KadiД‡, Damir ДЊelik. The significance of implementation of DRG (Diagnosis Related Groups) health care reforms in the field of physical medicine and rehabilitation za glavnu reformu plaД‡anja bolnica. Cilj rada je prikazati prednosti i nedostatke u primjeni DRG reforme na Klinici za fizijatriju i rehabilitaciju KliniДЌkog centara Univerziteta u Sarajevu (KCUS) u odnosu na raniji period. Sprovedena je deskriptivna studija u periodu od 01.04. do 01.05.2012. godine, koja je ukljuДЌila 41 pacijenta hospitalizovanih na Klinici za fizijatriju i rehabilitaciju KCUS. Kao izvor podataka koriЕЎtena je medicinska dokumentacija. U studiju su ukljuДЌene tri grupe pacijenata sa: cerebrovaskularnim inzultom (CVI) (n=19), diskus hernijom (HD) (n=17) i amputacijom potkoljenice (ABK) (n=15). KoriЕЎtene su mjere deskriptivne statistike: frekvencija i relativna frekvencija (%). U grupi pacijenata sa CVI (n=19), ranije dijagnostiДЌko-terapeutske procedure (DTP) koje su se ЕЎifrirale podrazumijevaju: pasivne vjeЕѕbe, hod uz pomagalo, balans, okupaciona terapija i galvanizacija. Prema DRG sistemu, ukupan broj DTP je veД‡i i podrazumijeva: biomehaniДЌka procjena (19 ili 100%), aktivnosti svakodnevnog Еѕivota (ASЕЅ) (19 ili 100%), uzimanje krvi za dijagnostiku (16 ili 84,2%), terapija vjeЕѕbanjem-rameni zglob (4 ili 21,1%), terapija vjeЕѕbanjem-miЕЎiД‡i grudnog koЕЎa i abdomena (1 ili 5,3%), terapija vjeЕѕbanjem-miЕЎiД‡i leД‘a i vrata (2 ili 10,5%), terapija vjeЕѕbanjem-miЕЎiД‡i ruku (6 ili 31,6%), terapija vjeЕѕbanjem-zglob lakta (3 ili 15,8%), terapija vjeЕѕbanjem-miЕЎiД‡i ЕЎaka, ruДЌnog zgloba i zglobova prstiju ruke (1 ili 5,3%), terapija vjeЕѕbanjem-zglob kuka (2 ili 10,5%), terapija vjeЕѕbanjem-miЕЎiД‡i dna zdjelice (3 ili 15,8%), terapija vjeЕѕbanjem-miЕЎiД‡i nogu (6 ili 31,6%), terapija vjeЕѕbanjem miЕЎiД‡a stopala, skoДЌnog zgloba i noЕѕnih prstiju (4 ili 21,1%), treniranje vjeЕЎtina u aktivnostima koje se odnose na poloЕѕaj tijela/pokretljivost/kretanje (21,1%), treniranje vjeЕЎtina u aktivnostima koje se odnose na premjeЕЎtanje /kade, kreveta, stolice, poda, tuЕЎa, toaleta, vozila/ (1 ili 5,3%), terapija vjeЕѕbanjem respiratorni sistem /disanje/ (7 ili 36,8%), treniranje vjeЕЎtina upotrebe pomoД‡nih ili adaptivnih naprava, pomagala i opreme /stavljanje zavoja i bandaЕѕa, trening pokretljivosti sa pomagalima/ (3 ili 15,8%), terapija vjeЕѕbanjem, cijelo tijelo /opД‡a terapija vjeЕѕbanjem/ (10 ili 52,6%), pokretno kontinuirano snimanje EKG- a (1 ili 5,3%), holter pokretno kontinuirano snimanje EKG- a (1 ili 5,3%), ultrazvuk srca /M-mode i 2-dimenzionalni ultrazvuk srca u realnom vremenu/ (1 ili 5,3%), terapija toplinom / hipertermiДЌka terapija/ (2 ili 10,5%), stimulacijska terapija /EMS, FES, IFT, TENS/ (5 ili 26,3%), terapija vjeЕѕbanjem, miЕЎiД‡i lica/temporomandibularni zglob (1 ili 5,3%), terapijska masaЕѕa ili manipulacija vezivnog ili mekog tkiva (1 ili 5,3%). U grupi pacijenata sa HD (n=17,) ranije DTP koje su ЕЎifrirane podrazumijevaju: ASЕЅ, izometrijske vjeЕѕbe, elektroprocedure, dok je prema DRG sistemu, ukupan broj DTP je veД‡i i podrazumijeva ukupno 10 DTP. U grupi pacijenata sa ABK (n=5), ranije DTP koje U grupi pacijenata sa ABK (n=5), ranije DTP koje su ЕЎifrirane podrazumijevaju: bandaЕѕiranje, aktivne vjeЕѕbe za bataljak uz otpor, vjeЕѕbe hoda, dok je prema DRG sistemu, ukupan broj DTP je veД‡i i podrazumijeva ukupno 10 DTP. ZakljuДЌak: Novo ЕЎifriranje kroz program DRG-a daje bolje moguД‡nosti ЕЎifriranja usluga a time i bolju naplatu uДЌinjenih procedura, ЕЎto vodi dobrom praД‡enju efektivnosti bolnica i boljem vrednovanju rada bolniДЌkog sektora u cjelini. KljuДЌne rijeДЌi: reforma u zdravstvu, Diagnosis Related Groups (DRG), rehabilitacija INTRODUCTION Project Financing Reform of secondary health care in Bosnia and Herzegovina which was financed by the European Union has the overall objective to lay the foundation for a system of paying hospitals based on the results and the future development of health information capabilities to hospitals, and the development of solid foundations for a major reform of hospital payment. DRG is based on a system developed by a team from Yale University in the United States called Diagnosis Related Groups (DRGs). There are different abbreviations for DRG. For example Norway, Sweden and Denmark use the abbreviation NordDRG. France, Portugal and Spain use modification of abbreviations used in the USA, called the HCFA. Great Britain has its own version, called HRG, which is not used in any other country. Classification according to diagnosis related groups belongs to the most widely applied classification, which has been evaluated and improved over the years, and there are many instruments in support of its application, as well as excellent comparative statistics. At the end of the sixties of the 20th century, the use of computer databases and advances in multivariate analytical techniques have alleviated some of the practical limitations of making classifications. The most important classifications were Diagnosis Related Groups (DRGs). The possibility of applying DRG classification as the basis of payment was realized soon. Specifically, patients in the same group of cases have similar costs of treatment so it is possible to apply a standard rate of payment. With payment based on DRGs are made and additional payments per day if the patient remains in the hospital after a predetermined number of days (вЂњtrim dayвЂќ) (1). From other sources, additional services such as education and research are paid. At about same time it has started to work in a few other countries. For example, Portugal has developed Medicinski Еѕurnal 2013 бѓЂ19 (1): 20 - 24 21 22 Narcisa Vavra-HadЕѕiahmetoviД‡, Aldijana KadiД‡, Damir ДЊelik. The significance of implementation of DRG (Diagnosis Related Groups) health care reforms in the field of physical medicine and rehabilitation a basic model of the 1989th year. Other countries have started late, but the application was quick. An example is Slovenia, where the hospital payment per case was introduced in 2003. Australian Refined Diagnosis Related Groups Version 5.1 (ARDRG v 5.1) used in FB&H was published in October 2004 and a total of 664 groups. Diagnostic Related Groups (DRG) is a grouping of treating acute episodes of stationary patients, the clinical use which is similar to those comparable levels of hospital resources (664 AR-DRG- s). For successful encode we need: the main diagnosis (ICD-10), other diagnoses - complications and comorbidities (ICD-10), the procedure (ICD-10-AM), other procedures (ICD-10-AM), age, sex , weight at birth (infants only). For good clinical encryption the most important are: the definition of hospital treatment, the main diagnosis, additional diagnoses, diagnostic and therapeutic procedures (2, 3). The aim of this paper is to present the advantages and disadvantages in the application of DRG reforms KCUS вЂ“ Clinic of Physical Medicine and Rehabilitation in relation to the previous period. MATERIALS AND METHODS A descriptive study was conducted in the period from April, the 1st 2012 until May, the 1st 2012, and included 41 patients (out of 75 patients) hospitalized at Clinic for Physical Medicine and Rehabilitation Clinical Center University of Sarajevo. As a source of data we used medical records. There were three groups of patients with: cerebrovascular insult (CVI) (n=19), herniated disk (HD) (n=17) and lower leg amputation below the knee (ABK) (n=15). Measures of descriptive statistics were used: frequency and relative frequency (%). in activities that relate to body posture (21,1%), coaching skills relating to the transfer (1 or 5,3%), exercise therapy-respiratory system / breathing / (7 or 36,8%), coaching skills using aids and equipment (3 or 15,8%), exercise therapy -whole body (10 or 52,6%), the movable continuous ECG (1 or 5,3%), holter mobile continuous ECG (1 or 5,3%), ultrasound of the heart (1 or 5,3%), treatment of warmth (2 or 10,5%), stimulation therapy / EMS, FES, IFT, TENS / (5 or 26,3%), exercise therapyfacial muscles (1 or 5,3%), massage Therapy (1 or 5,3%) Table 1. The number and cost in convertible marks (KM) previously used therapeutic procedures in patients with stroke (n=19), Clinic for Physical Medicine and Rehabilitation, CCUS, 2011. According to DRG system, the number of DTP for group of CVI patients is higher, accounting 27 DTP. Table 2. The number and cost in KM. Therapeutic procedures according to the DRG in patients with stroke (n=19), Clinic for Physical Medicine and Rehabilitation,CCUS, 2012. RESULTS In the group of CVI patients (n=19) earlier diagnostic and therapeutic procedures (DTP), were (Table 1.): passive exercise, gait with the aids, balance, occupational therapy and galvanization. According to DRG system, the number of DTP is higher and representing (Table 2.): biomechanical evaluation (19 or 100%), activities daily liv ing (19 or 100%), blood collection for diagnosis (16 or 84,2%), exercise therapy-shoulder joint (4 or 21,1%), exercise therapy-the muscles thorax and abdomen (1 or 5,3%), exercise therapy-back muscles and neck (2 or 10,5%), exercise therapyarm muscles (6 or 31,6%), exercise therapy elbow (3 or 15,8%), exercise therapy-hand muscles, wrist and phalangeal (1 or 5,3%), exercise therapy-hip joint (2 or 10,5%), exercise therapy-pelvic floormuscles (3 or 15,8%), exercise therapy-leg muscles (6 or 31,6%), exercise therapy-muscle foot, ankle and toes (4 or 21,1%), coaching skills Medicinski Еѕurnal 2013 бѓЂ19 (1): 20 - 24 In the group of HD patients (n=17) earlier DTP were (Table 3): ADL, isometric exercises, electro procedures. According to DRG system, the number Narcisa Vavra-HadЕѕiahmetoviД‡, Aldijana KadiД‡, Damir ДЊelik. The significance of implementation of DRG (Diagnosis Related Groups) health care reforms in the field of physical medicine and rehabilitation (5 or 100%), score aids (5 or 100%), counseling or education-related aid and equipment (5 or 100%), exercise therapy-leg muscles (3 or 60%), stimulation therapy that is not classified in another place (3 or 60%), biomechanical evaluation (2 or 40%), blood collection for diagnosis (2 or 40%), stimulation therapy / EMS, FES, IFT, TENS / (2 or 40 %). Table 5. The number and cost in KM of previously used th. procedures for patients with amputation of the lower leg (n=5), Clinic for Physical Medicine and Rehabilitation, CCUS, 2011. Table 3. The number and cost in KM. Previously used therapeutic procedures in patients with discus hernia (n=17), Clinic for Physical Medicine and Rehabilitation, CCUS, 2011. According to DRG system, the number of DTP for group of ABK patients is higher, accounting 10 DTP. Table 6. The number and cost in KM th. procedures according to the DRG in patients with amputation (n=5), Clinic for Physical medicine and rehabilitation, CCUS, 2012. According to DRG system, the number of DTP for group of HD patients is higher, accounting 10 DTP. Table 4. The number and cost in KM of therapeutic procedures according to the DRG-discus hernia patients (n=17), Clinic for Physical Medicine and Rehabilitation, CCUS, 2012. DISCUSSION In a study conducted by Kleinow R, et a вЂњImplementation of the DRGs impact on hospitals and medical rehabilitation of geriatric patients in GermanyвЂќ came to a conclusion: 1. First Introduction of DRGs in Germany will result in changes in the quality of the rehabilitation sector; 2. Increasing of the number of patients; 3. Introduction of DRGs one hand will reduce the negative spillovers from other patients, hospital sectors on the other hand, will lead to improved efficiency of services (4).The REDIA study conducted by vo n Eiff W, et al (5), вЂњThe impact of Medicinski Еѕurnal 2013 бѓЂ19 (1): 20 - 24 23 24 Narcisa Vavra-HadЕѕiahmetoviД‡, Aldijana KadiД‡, Damir ДЊelik. The significance of implementation of DRG (Diagnosis Related Groups) health care reforms in the field of physical medicine and rehabilitation introducing DRG-acute medical and rehabilitation in GermanyвЂќ came to a conclusion: 1. Shorter stay in the acute sector; 2. Inclusion of patients in a rehabilitation program at an early stage of their recovery process. As the experience of other countries shows, the introduction and use of DRG's can have a significant impact on the process of rehabilitation. Institute of Hospital Management at Deutsche Rentenversicherung Bund and Deutsche Rentenversicherung Westfalen implemented research on possible health expenditures, which are redirected from acute care to rehabilitation as a result of the introduction of the DRG in Germany. Data were collected in the first two stages of 2003/04 and 2005/06 for a total of 1342 cardiac and orthopedic patients. Indication-specific compared two phases and showed significantly shorter stays in the acute sector, as well as shorter crossing times across sectors, resulting in the inclusion of patients in a rehabilitation program at an early stage of their recovery process (5). Analysis of the data obtained in CCUS - Clinic for Physical Medicine and Rehabilitation shows that the application of the DRG system could better show the analytical procedures to be implemented as part of rehabilitation programs. Comparing the fact that before DRG, and thus the bill, committed services for patients with CVI was the order of 4 procedures, and that with DRG method can be shown 27 procedures, gives a clear possibility of monitoring and recording the rehabilitation program. A similar situation occur when displaying data for a select group of patients with disc herniation and limb amputations, who were given the research period chosen as a representative group, which is also seen manifold increase in the potential shown by the procedures and the process of rehabilitation. But what is even more important when we talk about DRG classification is a better billing services option. We have to take special care that all procedures have to be encrypted, and given proper billing, what is feasible and accepted by the relevant structures. Past experiences show that necessary attention wasn't pay when it came to coding procedures of importance for rehabilitation of patients. Warning, according for rehabilitation programs and DRG classifications, is addressed by the experts, because the rehabilitation must be considered as a whole with all its attributes that makes it different from other branches of medicine (5). CONCLUSION Current phase of the DRG system is primarily focused on the development of a more precise description and definition of diagnostic and therapeutic procedures covered by the procedure code. It is a necessary prerequisite for a quality data base on which to base the assessment some diagnostic and therapeutic procedures in the later Medicinski Еѕurnal 2013 бѓЂ19 (1): 20 - 24 stages of the development and application of DRG systems, which will result in: 1. Better encryption capabilities to better service; 2. Better billing procedures incurred; 3.Good monitoring of the effectiveness of hospitals; 4.Better evaluation of the hospital sector as a whole. Conflict of interest: none declared. REFERENCES 1. Hydayat B. Lecture notes on вЂ�Diagnosis Related Groups (DRGs): Overview, Costing Methods and Empirical Evidences. Training on Health Care Financing and Payment Systems: Ensuring Efficient Universal Coverage. Sept 2001. Bali, Indonesia; 2011. 2. Clinical Research and Documentation Departments of 3M Health Information Systems. All Patient Refined DRGs (APR-DRGs). Version 20.0. Methodology Overview. Willingford, Connecticut and Murray, Utah; 2003. pp 85. 3. Pardede D. Lecture notes on вЂ�DRG/CBGs Paym ent by Jamkesmas: Experience and Challenges. Training on Health Care Financing and Payment Systems: Ensuring Efficient Universal Coverage. Sept, 2011. Bali, Indonesia; 2011. 4. Kleinow R, Hessel F, Wasem J. Impact of hospital diagnostic related groups on geriatric rehabilitation facilities. Z Gerontol Geriatr. 2002 Aug;35(4):355-60. 5. Von Eiff W, Meyer N, Klemann A, Greitemann B,Karoff M. Rehabilitation and Diagnosis Re lated Groups (REDIA Study): impact of DRG introduction in the acute sector on medical rehabilitation in German. Rehabilitation ( Stuttg). 2007 Apr;46(2):74-81. Address: Prof. Narcisa Vavra-HadЕѕiahmetoviД‡, MD, PhD Clinic for Physical Medicine and Rehabilitation Clinical Center University of Sarajevo BolniДЌka 25, 71000 Sarajevo Bosnia and Herzegovina Phone:+387 33 297 373 Email: [email protected] Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡. Awareness of physicians about patientsвЂ™ rights; patient consent form Original article AWARENESS OF PHYSICIANS ABOUT PATIENTSвЂ™ RIGHTS; PATIENT CONSENT FORM OBAVIJEЕ TENOST LJEKARA O PRAVU PACIJENTA; INFORMIRANI PRISTANAK PACIJENTA Dragana NikЕЎiД‡, Amela DЕѕubur*, Amira KurspahiД‡ MujДЌiД‡ Institute of Public Health, Faculty of Medicine, University of Sarajevo, ДЊekaluЕЎa 90, 71000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT Patient consent form is an autonomous authorization of a medical intervention - treatment with the knowledge of the possible consequences. This was a change from traditional paternalistic approach to doctor-patient relationships. The main feature of these changes is that the doctor is вЂћauthorizedвЂќ by the patient and the patient is an actor in decision making about its health and life. The goal is to establish the extent to which the doctors-specialists in Federation of Bosnia and Herzegovina who are employed at different levels of care are informed about the patientвЂ™s right to informed medical consent and are there some differences according to the institution of employment. The research represents a вЂћcross-sectional вЂњstudy of medical specialists answers employed in the clinical centers, hospitals and primary health care centers in Federation of Bosnia and Herzegovina. Based on the records of doctors employed in institutions randomized sampling produced a sample of 455 subjects (every fourth specialist doctor from the list of records, or 15.8% of specialists employed in the Federation of Bosnia and Herzegovina). Survey was answered by 357 doctors which makes response rate of 78.5%. The study was conducted in public health institutions of tertiary level health care (Clinical Center University of Sarajevo, Mostar University Hospital, University Clinical Centre Tuzla), secondary level (Cantonal Hospital Zenica, Regional Medical Center RMC Mostar, Croats Hospital вЂћDr. fra Mato NikoliД‡вЂњ Nova Bila, General Hospital Konjic) and primary health care level (primary health care centers: Novi Grad Sarajevo, Livno, LjubuЕЎki, OraЕЎje, GoraЕѕde and Cazin). Respondents were unable to answer on average to 50% of the questions that were related to the general knowledge on informed consent. According to health institutions there is a significant difference in the level of general knowledge about informed consent. Respondents in hospitals had a significantly higher number of correct responses compared to respondents from other health institutions. Key words: awareness, physicians, patient consent form SAЕЅETAK Informirani pristanak pacijenta je autonomna au torizacija medicinske intervencije-tretmana uz znanje o moguД‡im posljedicama. To je promjena tradicionalno-paternalistiДЌkog pristupa odnosa doktor-pacijent. Glavna karakteristika te promjene je ЕЎto doktor postaje В«opunomoД‡enikВ» pacijenta, a pacijent subjekt odluДЌivanja o svom zdravlju i Еѕivotu. Cilj rada je utvrditi u kojoj mjeri su ljekari specijalisti Federacije BiH koji su zaposleni na razliДЌitim nivoima zdravstvene zaЕЎtite obavijeЕЎteni o pravu pacijenta na informisani medicinski pristanak kao i da li postoje razlike prema mjestu zaposlenja. IstraЕѕivanje predstavlja В« cross-sec tionalВ» studiju odgovora doktora specijalista zaposlenih u kliniДЌkim centrima, bolnicama i domovima zdravlja Federacije BiH. Na osnovu evidencije zaposlenih ljekara u odabranim ustanovama randomiziranim uzorkovanjem dobiven je uzorak od 455 ispitanka (svaki ДЌetvrti doktor specijalista sa liste evidencije ili 15,8% specijalista zaposlenih u Federaciji BIH). Anketu je popunilo 357 doktora ЕЎto ДЌini 78.5% stope odgovora. IstraЕѕivanje je provedeno u javnim zdravstvenim ustanovama tercijarnog nivoa zdravstvene zaЕЎtite (KCU Sarajevo, KliniДЌka bolnica Mostar, Univerzitetsko kliniДЌki centar Tuzla), sekundarnog nivoa (Kantonalna Medicinski Еѕurnal 2013 бѓЂ19 (1): 25 - 31 25 26 Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡. Awareness of physicians about patientsвЂ™ rights; patient consent form bolnica Zenica, RMC Mostar, HB Nova Bila, OpЕЎta bolnica Konjic) i primarnog nivoa zdravstvene zaЕЎtite (domovi zdravlja: Novi Grad Sara jevo, Livno, LjubuЕЎki, OraЕЎje, GoraЕѕde i Cazin). Ispitanici su u prosjeku znali odgovoriti na 50% pitanja koja su se odnosila na opД‡enito poznavanje informiranog pristanka. Prema zdravst venim ustanovama postoji signifikantna razlika u stepenu opД‡eg poznavanja informiranog pristanka. Ispitanici u bolnicama su imali znaДЌajno veД‡i broj taДЌnih odgovora u odnosu na ispitanike iz drugih zdravstvenih ustanova. KljuДЌne rijeДЌi: obavijeЕЎtenost, doktori medicine, informirani pristanak pacijenta INTRODUCTION Patient consent form is an autonomous authorization of a medical intervention - treatment with the knowledge of the possible consequences. This was a change from traditional paternalistic approach to doctor-patient relationships. The main feature of these changes is that the doctor is вЂћauthorized" by the patient and the patient is an actor in decision making about its health and life (1,2,3). Patient consent form contains information and consent. These are two sides of the same coin: on the one hand, the doctor after soliciting consent interprets the information received by the patient as an important indicator of proper medical professional procedure, on the other hand, the agreement was conceived as a duty of the doctor in the maximum respect for the patient's right to independence and autonomy as a person (4,5,6,7). Patients' rights to informed consent in theory are based on the protection of physical integrity of each individual and the free expression of the will whether to undergo medical treatment or not. The concept of informed consent for medical procedures has its ethical, legal and clinical concepts.The basis of ethical dilemmas becomes in the new concept of doctor-patient relationship. In these relationships it should be especially considered the nature of the relationship, the establishment of a medical procedure, the benefit for the patient, the scope and quality of information and consent, as well as borderline cases (8,9,10). From clinical perspective, informed consent raises the possibility of cooperation between doctors and patients in terms of determining the disease and selecting appropriate treatment. DoctorвЂ™s knowlMedicinski Еѕurnal 2013 бѓЂ19 (1): 25 - 31 edge and attitudes about informed consent vary considerably in different countries and between different medical specialists (11). We undertook this study to compare the knowledge and practices for obtaining informed consent for medical procedures among three groups of experts (12,13). Goal The goal is to establish the extent to which the doctors-specialists in Federation of Bosnia and Herzegovina who are employed at different levels of care are informed about the patientвЂ™s right to informed medical consent and are there some differences according to the institution of employment. MATERIALS AND METHODS The research represents a вЂћcross-sectionalвЂњ study of medical specialists answers employed in the clinical centers, hospitals and primary health care centers in Federation of Bosnia and Herzegovina. Sample Based on the records of doctors employed in institutions randomized sampling produced a sample of 455 subjects (every fourth specialist doctor from the list of records, or 15.8% of specialists employed in the Federation of Bosnia and Herzegovina). Survey was answered by 357 doctors which makes response rate of 78.5%. The study was conducted in public health institutions of tertiary level health care (Clinical Center University of Sarajevo, Mostar University Hospi tal, University Clinical Center Tuzla), secondary level (Cantonal Hospital Zenica, Regional Medical Center RMC Mostar, Croats Hospital вЂћDr. fra Mato NikoliД‡ вЂњNova Bila, General Hospital Konjic) and primary health care level (primary health care centers: Novi Grad Sarajevo, Livno, LjubuЕЎki, OraЕЎje, GoraЕѕde and Cazin). Selection of health institutions was made with respect to the basic criterion that in each canton is included one public health facility, that includes all clinical centers, also that are represented county and the general hospitals, which was influenced by managers motivation to participate in the study. Choice of doctors was dependent on their free consent, length of service for longer than 1 year in a medical institution and that up to 20% of sample were specialists from clinics and hospitals and 10% doctors specialists in primary health care centers. The questionnaire was distributed to all Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡. Awareness of physicians about patientsвЂ™ rights; patient consent form physicians in the sample. The approval of the ethical committee of the clinical centers and the consent of the management of other institutions is obtained. Participation in the study was anonymous and voluntary. The questionnaire consisted of 8 questions about the knowledge of doctors. Ambiguity check was done by pilot study conducted with the participation of 30 doctors. The awareness of doctors was evaluated on the basis of the answers to the questions that are being asked as claims and response options as correct or incorrect. Respondents were left the option of вЂћdo not know", defined as вЂћno response". The questions were formulated according to guidelines for the assessment of basic knowledge about the medical consent (1,2). The differences in observed variables are estimated by chi-square test at level of statistical significance of p<0.05 RESULTS The sample consisted of 357 doctors- specialist, of which 165 employees at clinical centers, 87 employees in the cantonal and general hospitals and 105 in the primary health care centers. Of the total number of doctors, the highest percentage was employed in Clinical Center University of Sarajevo (CCUS) (22.4%) and Primary health care centers Sarajevo (PHC center) (17.6%). The highest percentage of respondents 152 (47.9%) was at age from 40-49 years, 0.3% were doctors younger than 30 years, with the duration of service of more than 15 years (51.6% - median 20 years). There was 0.3% of Physicians with less than 5 years of work experience. Understanding the concept of patient consent form Based on answers to the questions that were conceived in the form of assertions, doctors-specialists are partially aware of the process of informed consent (Table 1). On the question about the withdrawal of consent 80.1% of physicians gave the correct answer, knowing that the patient has the right to withdraw consent to any procedure at any time. 75.2% of doctors know the necessity of informing patients about the risks of undertaken procedures. Correct answer to the question on presented options gave 95% of physicians, because in addition to the proposed procedure to the patient all other options must be presented, including the option of non-performing any of the procedures and the advantages and differences of all the options presented to the patient so it had sufficient information to make an informed decision. A person who is competent for obtaining informed consent from the patient for only 41.2% of respondents is exclusively doctor and for 58.8% of respondents it can be anyone from the medical staff, if that person is able to present to the patient all the information that they need. There was no statistically significant difference in the frequency of the responses (p>0.05). Transfer of the authority informed consent from one doctor to another doctor is not allowed and the correct answer was given only 18.2% of doctors. The difference in the frequency of the responses was statistically significant (p <0.05). A patient who refuses to give written informed consent if it is not required by law (which is not required in our country) is not required to sign an informed refusal of the proposed procedure. However, the physician in this situation must note in the patientвЂ™s medical records the reasons for rejection if they are stated by the patient. On this question the correct answer was given by 63.8% of doctors. The doctor is still obliged to check whether the patient well-understood information that was presented, regardless of whether or not the patient has given informed consent to the procedure (There were 35.5% correct answers). Only 39.3% of respondents is aware that the general consent is not valid, but they also need to get the patientвЂ™s consent for any medical procedure presented (p<0.05). From eight offered questions the doctors accurately respond to an average of 4.65 questions (58.1% correct answers). Knowledge about concept of patient consent form according at the institution level Answers of doctors were viewed by the institution of employment (Table 2). The most correct answers were given by doctors employed in general and cantonal hospitals. The average number of correct responses from eight offered was 4.96 in hospitals (62.0%), 4.42 in primary health care centers (55.2%) and 4.52 at clinical centers (56.5%). Regardless of the institution of employment doctors-specialist know that the patient may withdraw consent to a medical procedure (p>0.05), mostly those employed in the clinical centers (82.2%). Specialists in clinical centers pay less attention to вЂћmilder risksвЂњ in relation to colleagues from other institutions, as only 68.8% said that patients should be informed about it (p<0.05). There is no difference in the knowledge of doctors according to the level of health care in terms of representing Medicinski Еѕurnal 2013 бѓЂ19 (1): 25 - 31 27 28 Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡. Awareness of physicians about patientsвЂ™ rights; patient consent form all of the options of medical procedures (p>0.05). Doctors in cantonal and general hospitals gave the highest number of correct answers (68.2%) believing that obtaining informed consent may be conducted by medical competent health professionals, not just a doctor. The differences in the responses according to the level of health care services are not statistically significant (p>0.05). Hospital doctors (30.7%) are bet ter informed than physicians in clinical centers (13.0%) that transfer of obtained informed con sent from the patient is not allowed (p<0.05). Specialists in clinical centers are most aware that the patient is not required to explain the reasons for rejecting the proposed medical pro cedures (70.5%) and the difference in frequency of responses obtained by level of health care services are statistically significant (p<0.05). Specialist working at primary health care cen ters have provided the highest percentage of correct answers about the need to test compre hension of medical information given to patient (44.8%), compared to specialist in clinical cen ters (27.3%) and the difference was statistically significant (p<0.05). Most doctors believe that received general medical consent imply consent to each specific procedure (65.2% of doc tors in clinical centers and 51.1% in hospitals), which is unacceptable (p<0.05). Table 1. Understanding of the concept of patient consent form. Medicinski Еѕurnal 2013 бѓЂ19 (1): 25 - 31 , Tabele 2. The answers to the doctor s place of employment. Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡. Awareness of physicians about patientsвЂ™ rights; patient consent form DISCUSSION In todayвЂ™s era of advanced information technologies (printed and electronic media), the patients and their family members are much more informed about medical issues and want to actively participate in decision-making, so this new reality must be taken into account in clinical practice. Patients today need to actively participate in medical decisions, since it has significant beneficial effects on overall treatment outcome and satisfaction (5). On the other hand, health care professionals have an obligation to provide to patientвЂ™s adequate information about the nature of his/her medical condition, the objectives of the proposed treatment, treatment alternatives and possible outcomes. Health care professionals need to recognize the informed consent not only as an obligation, but as a way to fairly and lawfully protect themselves against possible unjustified lawsuits to which, in case of not obtaining the consent, are extremely exposed (12,13). Taking into account all these facts, we carried out this study in order to determine the level of knowledge that doctors-specialists in FB&H have related to the obtaining medical informed consent from patients. Results showed that doctors mainly know the process of obtaining consent from patient, but there are a certain percentage of doctors who are not sufficiently familiar with this problem as showed by incorrect answers to most of the questions in this questionnaire. Medical informed consent is accepted as a cornerstone of medical practice in developed countries, but represents the challenge in developing countries. United States are considered to be the country of origin of informed medical consent. Initial aim was to ensure the dignity of the patient and ensure its independence during the decision-making process allowing the patient a choice of medical intervention (14,15). The first report on this topic appeared in the U.S. at the beginning of the 18th century, with an emphasis on problems and limitations in simple rights of patients when granting consent for medical intervention. A study conducted in Malaysia in 2007 was aimed at assessing the perception and practice of medical professionals regarding the use of informed medical consent. The results obtained from a survey of health professionals working in Malaysia and Kashmir hospitals were compared. In relation to doctors in Malaysia, doctors from Kashmir have shown a tendency of selective disclosure of medical information (p=0.051). The results of this study indicate that physicians have the practice of denial of information, if they believe in potentially harmful outcome (p<0.001) or it is requested by the relatives (p<0.023). The differences in the practice of doctors also exist in giving the information to females (p< 0.001) (16). Our research has confirmed that only 24.8% of respondents believe that it is necessary to always inform the patient regardless of the severity of risk and the difference in the frequency of the responses was statistically significant (p<0.05). The obtained data indicate the fact that we still need to additionally inform the health care professionals about when and to what extent they are required to inform patients about the further treatment. In our study, 5% of respondents believe that it is not required to present to a patient all treatment options and what is unacceptable, regardless of this small number of doctors who are incorrectly informed, so it is necessary to work on continuous education of physicians in order to improve their knowledge about patientsвЂ™ rights. Also is identified the failure in doctors knowledge when it comes to the person who can obtain medical informed consent, so almost half of the respondents considered that it can be taken by some other medical professional, besides doctor who is capable of that. Patient rights recognized a patientвЂ™s right to refuse treatment or procedure without explanation and this fact only known 36% of doctors. At every decision making the physician is obliged to check the understanding of it by patient, in our study we found that 36% of Medicinski Еѕurnal 2013 бѓЂ19 (1): 25 - 31 29 30 Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡. Awareness of physicians about patientsвЂ™ rights; patient consent form respondents do not know about this obligation of doctors. The research that was conducted at a Pediatric Clinic in Cape Town - South Africa on a sample of 254 health care professionals found that most physicians (79%) believe that it is their duty to ensure that patients and parents are fully informed about the diagnostic and therapeutical intervention. Many (62%) support the targeted standard for determining the type and amount of information that needs to be presented to parents of a sick child. Doctors disclose mostly the information required by law, except for information about alternative treatments and the existence of a serious risk. They almost never give information regarding medical costs of the treatment. Language, inadequate communication skills and lack of time were viewed as an obstacle in obtaining informed consent (17). Our study on the awareness of specialist-doc tors on informed consent for medical proce dures showed that the process was quite formal and inadequate when it comes to complying with legal and professional requirements. Although some of the respondents worked in teaching hospitals, where clinical trials are part of everyday work and education activities, we found no difference between their knowledge and attitudes in obtaining informed consent and those of their colleagues from non-academic hospitals and outpatient institutions. In FB&H, the Law on the rights, obligations and responsibilities of patients in FB&H - Chapter III, Article 10 and 11 regulates the rights of pa tients. Every health care institution shall inform their employees, especially doctors about their duty of informing physicians about patientsвЂ™ rights and the implementation of all procedures in obtaining medical informed consent (18). Study limitations include the fact that about 5% of respondents did not fill out all questions in questionnaire especially personal information in institutions with a small number of employees, because thereby they will reveal their identity. However, the response rate of 78.5% and the inclusion of a large number of health facilities increase the external validity of test results. In the U.S., the UK and Canada, doctors are thoroughly trained in the process of obtaining informed consent, primarily because of the possibility that patients seek compensation in the event of complications (12,19). That is not the case in the FB&H because only 34% of specialist working in clinical centers involved in our Medicinski Еѕurnal 2013 бѓЂ19 (1): 25 - 31 study was aware of the fact that the informed consent is a process for each procedure or treatment. In the FB&H general guidelines that determine which procedures require the patientвЂ™s written consent does not exist and there is no systematic education in this area. The law also does not define a common consent form, so it is left to health institutions to develop their own forms (18). Most doctors respect patient autonomy in their decisions and requirements at the time of the decision making. However there are still many doctors who have a paternalistic attitude toward their patients, as demonstrated by our results. CONCLUSIONS Respondents were unable to answer on average to 50% of the questions that were related to the general knowledge on informed consent. According to health institutions there is a significant difference in the level of general knowledge about informed consent. Respondents in hospitals had a significantly higher number of correct responses compared to respondents from other health institutions. Our study shows a serious problem in the legal protection of patientsвЂ™ rights in FB&H and calls for systematic training of doctors and other health professionals in this field. The fact is that the process of informed consent is more focused on informing patients than to obtain the necessary consents. Since the informed medical consent is ethical duty, the emphasis should not be on filling out forms but on the communication between doctor and patient and also on certain human values, principles and standards. Conflict of interest: none declared. REFERENCES 1. List, J. A. Informed Consent in Social Science. Science. 2008: 322(5902):672. 2. Jefford M, Moore R. Improvement of informed consent and the quality of consent documents. Lancet Oncol. 2008; 9:485-93. 3. Krist AH, Woolf SH, Johnson RE, Kerns JW. Patient education on prostate cancer screening and involvement in decision making. Ann Fam Med. 2007;5:112-9. 4. McKeown RE, Reininger BM, Martin M, Hoppmann RA. Shared decision making: views of firstyear residents and clinic patients. Acad Med. 2002; 77:438-45. Dragana NikЕЎiД‡, Amela DЕѕubur, Amira KurspahiД‡ MujДЌiД‡. Awareness of physicians about patientsвЂ™ rights; patient consent form 5. McGuire AL, McCullough LB, Weller SC, Whitney SN. Missed expectations? PhysiciansвЂ™ views of patientsвЂ™ participation in medical deci sion making. Med Care. 2005; 43:466-70. 6. OвЂ™Leary KJ, Kulkarni N, Landler MP, Jeon J, Hahn KJ, Englert KM, Williams MV. Hospi talized patientsвЂ™ understanding of their plan of care. Mayo Clin Proc. 2010; 85:47-52. 7. JukiД‡ M, Kvolik S, Kardum G, Kozina S, TomiД‡ Juraga A. Knowledge and practices of obtaining informed consent for medical procedures among specialist physicians: questionnaire study in 6 Croatian hospitals. Croat Med J. 2009; 50:567-4. 8. Habiba MA Examining consent within the patient-doctor-relationship. J Med Ethics. 2000:26:183-87. 9. King J. Informed consent: A review of empiri cal evidence. Institute of Medical Ethics, Bulle tin supp.1986: 3: 1-17. 10. Kour NW, Rauff A . Informed consent вЂ“ his torical perspective and a clinicianвЂ™s view. Singa pore Med J. 1992:33(1):44-46. 11. Nelson-Marten P, Rich RA. A historical perspective of informed consent in clinical practice and research. Oncology Nursing. 1999:15:81-8. 12. Paterick TJ, Carson GV, Allen MC, Paterick TE. Medical informed consent: general consid erations for physicians. Mayo Clin Proc. 2008 Mar;83(3):313-9. 13. Dalla-Vorgia P, Lascaratos J, Skiadas P, Garanis-Papadatos T. Is consent in medicine a concept only of modern times? J Med Ethics. 2011 Feb:27(1):59-61. 14. Cleary PD, Edgman-Levitan S, Roberts M, Moloney TW, McMullen W, Walker JD, Delban co TL. Patients evaluate their hospital care: a national survey. Health Affairs. 1991; 10:254-67. 15. Boisaubin EV. Observations of physician, patient and family perceptions of informed con sent in Houston, Texas. J Med Philos. 2004; 29:225-36. 16. Yousuf RM, Fauzi AR, How SH, Rasool AG, Rehana K. Awareness, knowledge and attitude toward informed consent among doctors in two different cultures in Asia: a cross-sectional comparative study in Malaysia and Kashmir, In dia. Singapore Med J. 2007 Jun; 48(6):559-65. 17. Henley L, Benatar SR, Robertson BA, En sink K. Informed consent--a survey of doctorsвЂ™ practices in South Africa. S Afr Med J. 1995 Dec;85(12):1273-8. 18. Zakon o pravima, obvezama i odgovornostima pacijenata. Sarajevo: вЂћSluЕѕbene novine Federacije BiHвЂњ, broj 40/10. 19. Bencko V. Informed consent in the Czech Republic. Sci Total Environ. 1996;184:77вЂ“81. Address: Prof. Dragana NikЕЎiД‡, MD, PhD Institute of Public Health Faculty of Medicine, University of Sarajevo ДЊekaluЕЎa 90, 71000 Sarajevo Bosnia and Herzegovina Phone: +387 33 226 478 Email: [email protected] NaЕЎ prilog redukciji kardiovaskularnih bolesti ! Our contribution in reduction of cardiovascular diseases ! Medicinski Еѕurnal 2013 бѓЂ19 (1): 25 - 31 31 32 Ifeta LiДЌanin, Alem Д†esir, Saida FiЕЎekoviД‡. Admission rates of patients with schizophrenia in relation to seasons and climatic factors in the period of two years Original article ADMISSION RATES OF PATIENTS WITH SCHIZOPHRENIA IN RELATION TO SEASONS AND CLIMATIC FACTORS IN THE PERIOD OF TWO YEARS STOPA PRIJEMA PACIJENATA SA SHIZOFRENIJOM U RELACIJI SA SEZONSKIM I KLIMATSKIM FAKTORIMA U PERIODU OD DVIJE GODINE Ifeta LiДЌanin*, Alem Д†esir, Saida FiЕЎekoviД‡ *Psychiatric Clinic, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT Climate and its impact on human health and mental illness have been in the focus of the research for ages. The aim of the research is to study the role of environmental influences on schizophrenia admissions to the Psychiatric Clinic in correlation to seasons and climate. The research was conducted in Psychiatric Clinic Clinical Center University of Sarajevo. Randomly selected subjects (aged 5-89 years, 1316 males and 1039 females) N=2355, were interviewed by the Structural Clinical Interview (SCID) which generated DSM-IV. In this retrospective-prospective, clinical-epidemiological study subjects with schizophrenia were analyzed in correlation with seasons and climate factors. Certain data were taken from Federal Hydrometeorological Institute in Sarajevo of the climatic situation for period of the study. Results and conclusions: Of the total number of subjects who were admitted to the Clinic in the period of 2010/2011shizophrenia (F 20-F29) was one of the most common diagnoses. Correlation between certain seasons and the effects of the certain weather parameters at an increased admission rate of subjects with the schizophrenia was found. IstraЕѕivanje je obavljeno na Psihijatrijskoj klinici KliniДЌkog centra Univerziteta u Sarajevu. Randomizirano odabrani ispitanici (od 5-89 godina, 1316 muЕЎkog i 1039 Еѕenskog spola) N=2355 su intervjuisani koriЕЎtenjem Strukturisanog KliniДЌkog Uputnika (SCID) za postavljanje dijagnoze prema DSM-IV. Studija je retrospektivno-prospektivna, kliniДЌko-epidemioloЕЎka. Analizirana je stopa prijema ispitanika sa shizofrenijom u toku odreД‘enih godiЕЎnjih doba kao i korelacija uticaja godiЕЎnjih doba na poveД‡anu stopu prijema tih ispitanika na Psihijatrijsku kliniku. Prikupljeni su i obraД‘eni relevantni podaci iz Federalnog hidrometeoroloЕЎkog zavoda u Sarajevu o klimatoloЕЎkoj situaciji na podruДЌju Sarajevskog kantona za taj period. Rezultati i zakljuДЌci: Od ukupnog broja ispitanika koji su primljeni na kliniku u periodu 2010/2011. godine, meД‘u najfrekventnijim dijagnozama izdvojena je ЕЎizofrenija (F20-F29). NaД‘eno je da postoji korelacija izmeД‘u odreД‘enih godiЕЎnjih doba i djelovanja odreД‘enih vremenskih parametara na poveД‡anu stopu prijema ispitanika sa shizofrenojom. Key words: climate, climatic factors, meteropathy mental illness, schizophrenia Since ancient times there is a belief that weather and seasons affect human mood and consequently, that some psychiatric conditions have a certain period in a year when their clinical manifestations are more frequently expressed. The effect of weather on mood and health is well known from the time of ancient Greece. In ancient times, be fore any clinical studies, it was believed that most suicides occur in the fall and winter, when there are less light which in humans leads to mood changes (1,2). The human body is very sensitive SAЕЅETAK Uticaj klime i klimatskih faktoria na ljudsko zdravlje i duЕЎevne bolesti kod ДЌovjeka i pogorЕЎanje istih su u fokusu istraЕѕivanja od davnina. Cilj samog rada je ustanoviti da li godiЕЎnja doba i odreД‘eni vremenski faktori imaju uticaj na porast stope prijema ispitanika sa ЕЎizofrenijom na lijeДЌenje. Medicinski Еѕurnal 2013 бѓЂ19 (1): 32 - 37 KljuДЌne rijeДЌi: klima, klimatski faktori, meteoropatija, duЕЎevna oboljenja, shizofrenija INTRODUCTION Ifeta LiДЌanin, Alem Д†esir, Saida FiЕЎekoviД‡. Admission rates of patients with schizophrenia in relation to seasons and climatic factors in the period of two years to changes in temperature, humidity, wind, air pressure, insolation, precipitation, positive or negative ionization of the air, particularly when these factors increase or decrease (3). With the increasing number of publications and more rigorous studies, it became clear that the period of spring and early summer period have the most frequent occurrence of suicide (4,5). From the cooperation between meteorologists and doctors originated a specific subset of weather prognosis -bio-prognosis. The term meteropathy in recent times is increasingly used. Meteropathy is de fined as a group of symptoms and reactions that are manifested when there is a change of one or more meteorological factors (3). Meteropathy term have roots from the Greek word Meteoron (celestial phenomenon) and Pathos (disease) (3). In person suffering from meteropathy the emergence of health problems or a deteriora tion of basic disease regularly is associated with weather changes. Usually it is a case of middleaged women, the elderly and chronically ill, or in total every third inhabitant of our planet (5,6). Meteropathy problems are most pronounced in case of sudden temperature changes, sudden changes in atmospheric pressure or a sudden increase in air moisture. Additional factors are increased concentrations of pollen in the air and the winds. Usually one to two days before the weather changes in susceptible people the problems that we describe as meteropathy occur. In addition to the physical health the weather conditions affect mood, behavior and general bodily condition of every human. In a population of sensitive people, the weather has the ability to produce a certain discomfort accompanied with increased aggressiveness, irritability, anxiety (linked directly with the increasing number of accidents and suicides, and probably increases in crime rate). It is widely believed that weather conditions affect human mood and many people believe that they are happier when the days are longer with sunny intervals then when the days are shorter, darker and rainy (5). Season of certain psychological disorders is a theory that has for long been вЂњpushedвЂќ to from and has been par ticularly linked with affective disorders and their tragic consequences вЂ“suicides (5,6). The fact that certain physiological and psychopathological processes are significantly altered during certain times of year or season suggests a direct exposure to climatic variables. However, it can also be an expression of autonomous biorhythm and the question of whether climatic conditions and climatic variables have an impact on the mental state (6). The term climate is considered as a set of meteorological phenomena and factors in a given period of time which constitute the state of the atmosphere over some part of the Earth's surface. Besides the weather, there is a biological and geographical term of climate (7). Contemporary definitions define climate as a dynamic system in which have influence to one another the atmosphere, oceans, lithosphere, ice and snow cover and biosphere including human impact (7,8). The elements of climate that are taken into account in determining climate are insolation, air temperature, air pressure, wind direction and speed, humidity, precipitation, cloudiness, snow cover and are changing under the influence of climatic factors or modifiers. Based on the collected data and the values the climate is divided into several so-called climate zones and our country is divided into three zones: north temperate-continental, continental in the central part and south-mediterranean climate. Some weather parameters in a certain way alter the functions of the human organism and are considered as вЂћstressful weather". Strong ionized wind known as the foehn and warm fronts are the two most common climatic stress factors (8,9). Mental illness in itself is a sort of complication, and the effect of weather conditions on the deterioration of these symptoms is an additional problem. Almost all people react in certain ways to adverse weather conditions. Few feel good during extremely high or extremely low temperatures or sudden changes in air pressure. The term meteorology stress has been used in recent years, and under it are all situations where the body's equilibrium of homeostatic mechanisms is disturbed in certain ways. According to another definition meteorological stress represents significant distortion of the body homeostatic mechanisms due to the influence of changes in either isolated or combined weather components (7,8). Goals вЂў Determine the total number of patients admitted to hospital during the period 2010-2011. вЂў Determine whether there is an increased incidence of schizophrenia in certain seasons during the 2010-2011. вЂў Determine whether there are some specific weather parameters which affect the increased incidence of schizophrenia. Medicinski Еѕurnal 2013 бѓЂ19 (1): 32 - 37 33 34 Ifeta LiДЌanin, Alem Д†esir, Saida FiЕЎekoviД‡. Admission rates of patients with schizophrenia in relation to seasons and climatic factors in the period of two years MATERIALS AND METHODS This study was conducted in the period from January 1st 2010 until December 31st 2011 at the Psychiatric Clinic, Clinical Center University of Sarajevo University and included respondents selected randomly. The study included a total of 2355 respondents, aged from 5 to 89 years, 1316 males and 1039 females. During 2010 there were 669 (58%) male respondents and in 2011 - 647 or 54%. There were 486 (42%) female respondents in 2010, and in 2011 - 553 (46%). Within the total number of respondents in the study period (N-2355), the most frequent age was 51-60 years (35%), followed by 41-51 years (29%). Respondents aged 31-40 years were represented by 14%, and 19-30 years 8%. Over 60 years of age there were 7% of respondents, while there were also 4% of children under 14 years. The least represented group was respondents aged 15 to 18 years with 2%. Of the total respondents 38% were unemployed, 36% were employed and 18% retired. The least number included students with 7%. As the survey instrument Structured psychiatric interview was used and the diagnosis was made according to ICD-10 classification system. Conducted study was of clinical type and includes a retrospective-prospective research based on observation and analysis of the variables present, the processing of diagnostic entities and their grouping. The comparison of schizophrenia incidence is made in certain months of the year in order to find possible correlation between this disorder and the seasons, and correlation of certain weather parameters (temperature, humidity, barometric pressure, and precipitation) and increased admission rates of patients with schizophrenia at the Psychiatric Clinic. Also the data from the Federal Hydrometeorological Institute in Sarajevo were collected on the values of climatic parameters for 2010 and 2011 that were relevant to the research (air temperature, atmospheric pressure, humidity and rainfall values - for the same period, and the total climatological analysis for that period). Data from the same Institute about the analysis of the climatological situation in that year and cited observations were collected. RESULTS Statistical analysis of data obtained during the investigation was performed by using StigmaStat 3.5 and Microsoft Office Excel 2007. The data are, after the statistical analysis, presented in tables Medicinski Еѕurnal 2013 бѓЂ19 (1): 32 - 37 and charts and included the number of patients with certain diagnosis and admission in certain seasons and months of the year. Statistical significance between the groups was tested by Chisquare and Kolmogorov-Smirnov test, depending on the type of data. Table 1. The total number of patients admitted to hospital during the 2010-2011 by diagnoses. From Table 1 it is evident that the most commonly diagnosed during 2010 and also 2011 are diagnosis from group F40-F48 with 33% in 2010 and 29% in 2011. The second most common diagnoses were from group F20-F29 with 29% during 2010 and 28% during 2011. The third most common diagnoses were F30-F39 with 23% during 2010 and 22% during 2011. Diagnosis F10-F19 is the fourth most common with 5% during 2010 and 4% during 2011. All the other diagnoses are shown in the Table. Tentamen suicidii for 2010 was recorded in 0.1% of the total number of respondents and for 2011 a significant increase to 1% was observed. Analysis by chi-square test confirmed the above differences and indicates statistical significance at p <0.05. Table 2. Presentation of the most common diagnosis seasons during 2010. Table 2 shows that the diagnosis F10-F19 was mostly present in the fall with 42%, then the summer with 24%, spring 22% and winter with 12%. With the diagnosis F20-F29 most of the respondents was admitted in the spring 27%, then in the summer and fall with 25% and 23% during the winter. With the diagnosis F30-F39 most of the patients were admitted in spring 28%, then winter 27%, fall 25% and summer 20%. In case of diagnosis F40-F48 the most respondents were adm- Ifeta LiДЌanin, Alem Д†esir, Saida FiЕЎekoviД‡. Admission rates of patients with schizophrenia in relation to seasons and climatic factors in the period of two years itted in the winter 29%, then fall 28%, 23% during the spring and summer 20%. Most of the respondents have attempted Tentamen suicidii in the spring and same during the winter - 50%. Chisquare test revealed statistically significant differences in the prevalence of certain diagnostic groups according to the seasons of 2010 at confidence level of 99% or p <0.01. Table 5. Presentation of weather parameters with the mean monthly values and the increase/ decrease in the number of patients for the SCH and other diagnoses in certain months of 2010. Table 3. Presentation of the most common diag nosis seasons during 2011. Table 3 shows that most patients with diagnoses F10-F19 were admitted in the spring with 30%. With diagnosis F20-F29 most patients were admitted in the summer or 27%. With di agnosis F30-F39 most patients were admitted in the winter or 28%. With diagnosis F40-F48 most patients were treated during the winter 32%. In case of Tentamen suicidii most respondents attempted suicide in the winter or 40%. Chi-square test revealed statistically significant differences in the prevalence of certain diagnostic groups according to the seasons of 20110 at the confidence level of 99% or p <0.01. Table 5 shows the weather parameters, which influence has been studied in the course of this research with their values for all months in 2010 and the increase in admissions with diagnoses F20-F29 in the months of January and May and decrease in November. Table 6. Display of weather parameters with the mean monthly values and the increase / de crease the number of subjects in SCH for some months, 2011. Table 4. Number of patients per month who were admitted to the Clinic in 2010/2011 with diagno ses F20-F29. Table 4 shows that most patients with diagno ses F20-F29 was treated in January 2010, June 2010 and November 2011 or 10%. In January 2010 there was 7%, June 2011 also 7% and 8% in November. There were no statistically signifi cant differences in the number of patients who were treated by months of 2010 and 2011 with the diagnosis from the group F20-F29 (p>0.05). Table 6 shows the weather parameters, which influence was studied in the course of this research and their values for all months in 2011, as well as an increase or decrease of the number of admissions during the months where significant changes were observed. The increase in diagnoses F20-F29 was recorded in September and November and a decrease was recorded in December. Table 7. Correlation of climatic factors and admission rates. IX X XI XII 15 .0 126. 4 8.7 8 1.1 9.5 1 39.4 1.5 1 12.7 71 7 9 69 75 9 42.6 9 42.7 936. 3 938. 0 аµ№-34 аµ№-37 аµ»-18 1 аµ№-30 1 1 Medicinski Еѕurnal 2013 бѓЂ19 (1): 32 - 37 35 36 Ifeta LiДЌanin, Alem Д†esir, Saida FiЕЎekoviД‡. Admission rates of patients with schizophrenia in relation to seasons and climatic factors in the period of two years Statistical analysis by Spearman rank correlation coefficient shows that in the case of diagnostic group F20-F20 there is strong statistically significant correlation by months (more hospitalizations in the second half of the year), and the temperature which indicates that increase in temperature leads to more frequent hospitalization of persons with schizophrenia. DISCUSSION The above results in this study conducted at the Psychiatric Clinic, Clinical Center University of Sarajevo show that study covers a total of 2355 respondents, of whom 1039 are women and 1316 men. During this study data were taken from the Federal Hydrometeorological Institute in Sarajevo with the values of climatic parameters for 2010 and 2011 year that was relevant to the survey and also were taken from the same Institute information about the climatological analysis of the situation in that year, and referred to the observations. Respondents are processed and sorted into groups according to the diagnoses under which they were admitted to the clinic. Analyzing and processing the collected data it became obvious that the frequency of admission at the Clinic during the two years was mostly patients with diagnoses F40-F48- Neurotic and somatoform disorders caused by stress. In the second place were diagnosis F20-F29 (Schizophrenia, schizophrenia like disorders and mad states). Most patients with diagnoses F40-F48-Neurotic and somatoform disorders, and disorders caused by stress during the 2010 were admitted during the winter 29%, fall 28%, 23% during the spring and 20% during the summer. During 2011 the majority of patients were admitted during the winter 32%, 26% during fall, spring 24% and summer 18%. Data for both years coincide. In the literature the authors come to a conclusion similar to us that these dis orders occur independently of climatic factors (2). This study specifically analyzes the F20-F29 (Schizophrenia, schizophrenia like disorders and mad states) that is second in frequency. In both years the number of respondents is the same-338. During the 2010 most respondents 27% were admitted in spring, equally during summer and autumn with 25% and 23% during winter. Most of the respondents during 2011 were admitted in June. Temperatures were above average for that month and for the whole year, with increased rainfall, while humidity and air pressure values were within the limits of normal. In November, 32 respondents were admitted. Medicinski Еѕurnal 2013 бѓЂ19 (1): 32 - 37 The temperature was higher than the average for that month and the values of pressure, rainfall and humidity were within normal. The least number of patients were in February. It was reported that the temperature during this month was higher than average and precipitation, humidity and air pressure were within normal values. We can therefore conclude that the months in which there was increase in temperature were for those months in which we admitted most patients to Psychiatric Clinic with multiple diagnoses F20-F29 in both years and that their number decreased during the months in which temperature was lower. These results coincide with the results of relevant literature that in the summer months there is increased rate of hospitalized patients suffering from schizophrenia. The data of the study are indicative that the current high temperatures can cause psychotic exacerbation in patients with schizophrenia and an increase in hospitalizations (6). Also, the authors reached research results, as in our study that the summer season is with the highest prevalence of schizophrenia (10,11). When we talk about a possible deviation of some our results from those from studies in the literature it should be taken into account that no one has taken the relevant studies in Bosnia and Herzegovina or of this part of the European continent, with the different climatic conditions and where people are exposed to different climatic factors and elements. It should also be taken into consideration whether the respondents were admitted to the Clinic for other reasons, or whether the worsening of their underlying disease was caused by some specific condition or situation, also are they in a period of ill health stay in open spaces or indoors, and whether they were generally exposed to the weather, because there are in fact some studies conducted in psychiatric asylums where patients a part of a day spent outdoors. As for research directly related suicide attempts, the sample was too small to be able to make some important conclusions so we need to continue research in this field. Statistical analysis confirmed the hypothesis that the admission rate in patients with schizophrenia during the 2010 and 2011 is in correlation with the climatic elements and weather conditions and tends to increase with climate change in certain parameters and that the admission rate of subjects during the 2010/2011 increase in certain seasons. Specifically, as can be seen from Table 7 statistical analysis by Spearman rank correlation Ifeta LiДЌanin, Alem Д†esir, Saida FiЕЎekoviД‡. Admission rates of patients with schizophrenia in relation to seasons and climatic factors in the period of two years coefficient indicates that the climate and climatic factors have a statistically significant impact on admission rates of patients with schizophrenia (and other diagnostic groups, except for F10-F19). One explanation of the correlation in this study, which explains higher frequency of meteropathy is todayвЂ™s modern lifestyle, which is further away from nature. Scientists believe that life is mainly carried out in sealed, air-conditioned spaces which often reduce the ability of our bodyвЂ™s natural adaptation to different environmental conditions. The human body is accustomed to closed spaces, which are often overheated in winter and cooled in summer so that self-regulation mechanisms are no longer able to optimally respond to sudden weather changes (3). CONCLUSIONS 1. The total number of patients admitted to the Psychiatric Clinic during the period 2010/2011 was 2355, of which 1039 (44%) were females and 1316 or 56% males. 2. In relation to the age most of the respondents were 51-60 years old or 35%, and the least number of respondents was in a group of 15-18 years or 2%. Most are unemployed or 38% and there were 7% of pupils/students. 3. Schizophrenia is one of the most common illnesses that occurred in the period 2010/2011 and at the second place by its frequency (F40-F48, F20-F29). 4. Data analysis showed that there is an increased incidence of admissions due to schizophrenia (F20-F29) during the spring and summer. Statistical analysis by Spearman rank correlation coefficient indicates that the climate and climatic factors have a statistically significant impact on admission rates of subjects with schizophrenia. Comparing the results we obtained by analyzing the data of other studies conducted in literature we obtained partial matching results. REFERENCES 1. Rapley C. The health impacts of climate change. Br Med J. 2012 Mar 19; 344:e1026. 2. Jaap JA. Denissen et al. The effects of Weather on Daily Mood. A Multilevel Approach. Humboldt University Berlin; 2008. pp 662-667. 3. Sung TI, Chen MJ, Lin CY, Lung SC, Su HJ. Relationship between mean daily ambient temperature range and hospital admissions for schizophrenia: Results from a national cohort of psychiatric inpatients. Sci Total Environ. 2011 Dec; 410-411:41-6. 4. Rocchi MB, Sisti D, Cascia MT, Preti A. Seasonality and suicide in Italy: Amplitude is positively related to suicide rates. J Affect Disord. 2007 Jun; 100(1-3):129-36. 5. Marion SA, Agbayewa MO, Wiggins S. The effect of season and weather on Suicide rates in the elderly in British Columbia. Can.J Public Health. 1999 Nov-Dec; 90(6): 418-22. 6. Shiloh R, Shapira A, Potchter O, Hermesh H, Popper M, Weizman A. Effects of climate on admission rates of schizophrenia patients to psychiatric hospitals. Eur Psychiatry. 2005 Jan; 20(1):61-4. 7.Gupta S, Murray RM. The relationship of environmental temperature to the incidence and outcome of schizophrenia.Br J Psychiatry. 1992 Jun; 160:788-92. 8. C. W. Thornthwaite. An Approach toward a Rational Classification of Climate. Geographical Review. 1948 Jan; 38(1):55-94 (Published by: American Geographical Society) 9. Salib E, Sharp N. Relative humidity and affective disorders. Int J Psychiatry Clin Pract. 2002; pp 53-147. 10. Aviv A, Bromberg G, Baruch Y, Shapira Y, Blass DM. The role of environmental influences on schizophrenia admissions in Israel. Int J Soc Psychiatry. 2011 Jan; 57(1):57-68. 11. Amr M, Volpe FM. Seasonal influences on admissions for mood disorders and schizophrenia in a teaching psychiatric hospital in Egypt. J Affect Disord. 2012 Mar; 137(1-3):56-60. Address: Ifeta LiДЌanin, MD, PhD Psychiatric Clinics, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo Bosnia and Herzegovina Phone; +387 33 297 228 Email: [email protected] Conflict of interest: none declared. Medicinski Еѕurnal 2013 бѓЂ19 (1): 32 - 37 37 38 Jasminka ДђeliloviД‡-VraniД‡, Azra AlajbegoviД‡, Mehmed KuliД‡, Amina NakiДЌeviД‡, Emina EjuboviД‡, Merita TiriД‡-ДЊampara, Edina ДђoziД‡, Ljubica TodoroviД‡, Salem AlajbegoviД‡. Heart rhythm disorders as a contributing factor to ischemic stoke Original article HEART RHYTHM DISORDERS AS A CONTRIBUTING FACTOR TO ISCHEMIC STROKE POREMEД†AJI SRДЊANOG RITMA KAO ETIOLOЕ KI FAKTOR U NASTANKU ISHEMIДЊNOG MOЕЅDANOG UDARA 1* 1 1 Jasminka ДђeliloviД‡-VraniД‡ , Azra AlajbegoviД‡ , Mehmed KuliД‡ 2, Amina NakiДЌeviД‡ , 1 1 1 Emina EjuboviД‡ , Merita TiriД‡-ДЊampara , Edina ДђoziД‡ 1, Ljubica TodoroviД‡ , Salem AlajbegoviД‡ 3 1 Neurology Clinic, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina Hearth Center Sarajevo, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo 3 Bosnia and Herzegovina; Internal Department, Cantonal Hospital, Crkvica 67, 72 000 Zenica, Bosnia and Herzegovina 2 *Corresponding author ABSTRACT Stroke-cerebrovascular insult is a disease that has an increasing tendency in the world, especially in developing countries such as ours. Common cause of ischemic stroke is a heart rhythm disorder. The aim is to determine the existence of heart rhythm disturbances in patients with ischemic stroke. The study was conducted as a retrospective in Sarajevo region, during the one-year period (July 2011-July 2012) where all patients with ischemic stroke were registered. In each respondent medical history was taken and a neurological examination was performed, with CT of the brain to confirm ischemic stroke, ECG and cardiology examination in order to determine heart rate disorders and laboratory findings.During the one-year period (July 2011-July 2012) a total of 961 patients with ischemic strokewere treated. Out of these, 71% of patients were with thrombotic and 29% with embolic stroke. Men accounted for 48.4% and women for 51.6% with age range from 37-79 years. The most common risk factors were hypertension in 83.7% of patients, diabetes mellitus in 34.4% of patients, heart rhythm disorder was noted in 22.7% of patients with a sinus tachycardia in 18% of patients, SVES 22% of patients and 38% had atrial fibrillation, and 22% had a block of one of the branches. The hyperlipidemia was detected in 19.6% of patients from the group up to 50 years; atrial fibrillation was recorded in 15.15%. 35% of patients died and 65% survived, while in the group with atrial fibrillation the mortality was 31.2%. Conclusion: Cardiac rhythm disorders can occur at any age, but the extension of life expectancy resulted in frequent disturbances in heart rhythm, which increases the risk of stroke. Heart rhythm disturbances increase the risk of recurrence of Medicinski Еѕurnal 2013 бѓЂ19 (1): 38 - 42 embolic stroke. Timely detection of cardiac arrhythmias and appropriate treatment can help to prevent the onset of stroke and thus significantly reduce the number of disabled persons and the cost of treatment making the life in the third age better. Key words: cardiac rhythm disorders, ischemic stroke SAЕЅETAK MoЕѕdani udar - cerebrovaskulatrni inzult je bolest koja ima tendenciju rasta u svijetu, a posebno u zemljama u razvoju gdje spadamo i mi. ДЊest uzrok nasatnka ishemiДЌnog moЕѕdanog udara je poremeД‡aj srДЌanog ritma.Cilj rada je utvrditi postojanje poremeД‡aja srДЌanog ritma kod oboljelih od moЕѕdanog udara. Sprovedeno je retrospektivno istraЕѕivanje je u regionu Sarajevo, u toku jednogodiЕЎnjeg perioda (juli 2011-juli 2012.), gdje su registrovani svi oboljeli od ishemiДЌnog moЕѕdanog udara. Svim pacijentima su uz anamnezu i neurol oЕЎki pregled uraД‘eni CT mozga radi potvrde ishemiДЌ nog inzulta, te EKG i kardioloЕЎki nalaz radi utvrД‘ivanja poremeД‡aja srДЌane frekvencije uz laboratorijske nalaze. U toku jednogodiЕЎnjeg perioda (juli 2011-juli 2012) ukupno je lijeДЌeno 961 pacijenata od ishemiДЌnog moЕѕdanog udara. Od toga je 71% pacijenta sa trombotiДЌnim, a 29% sa embolijskim moЕѕdanim udarom. MuЕЎkarci su ДЌinili 48,4% ispitanika, a Еѕene 51,6% sa rasponom Еѕivotne dobi od 37 do 79 godina. NajДЌeЕЎД‡i riziko faktori su bili hipertenzija kod 83,7% pacijenata, diabetes mellitus kod 34,4% pacijenata, a poremeД‡aj srДЌanog ritma je zabiljeЕѕen kod 22,7% pacijenata, pri ДЌemu Jasminka ДђeliloviД‡-VraniД‡, Azra AlajbegoviД‡, Mehmed KuliД‡, Amina NakiДЌeviД‡, Emina EjuboviД‡, Merita TiriД‡-ДЊampara, Edina ДђoziД‡, Ljubica TodoroviД‡, Salem AlajbegoviД‡. Heart rhythm disorders as a contributing factor to ischemic stoke je sinusnu tahikardiju imalo 18% pacijenta, SVES 22% pacijenata , a ДЌak 38% je imalo fibrilaciju atrija, 22% je imalo blok jedne od grana, a hiperlipidemija je otkrivena kod 19,6%. U grupi do 50 godina, fibrilacija atrija je zabiljeЕѕena kod 15,15%. Umrlo je 35% pacijenata, a preЕѕivjelo 65%, i to u grupi sa fibrilacijom atrija smrtnost je iznosila 31,2 %.ZakljuДЌak: PoremeД‡aji srДЌanog ritma se mogu javiti u bilo kojoj dobi, ali produЕѕenje ljudskog vijeka ima za posljedicu uДЌestalije poremeД‡aje srДЌanog ritma, ЕЎto poveД‡ava rizik obolijevanja od moЕѕdanog udara. PoremeД‡aji srДЌanog ritma poveД‡avaju rizik recidiva embolijskog moЕѕdanog udara. Pravovremenim otkrivanjem poremeД‡aja srДЌanog ritma i adekvatnim lijeДЌenjem moguД‡e je sprijeДЌiti nastanak moЕѕdanog udara, a time i bitno smanjiti broj invalidnih osoba te troЕЎkove lijeДЌenja svesti na manji nivo, a Еѕivot u treД‡oj dobi uДЌiniti kvalitetnijim. KljuДЌne rijeДЌi: poremeД‡aji srДЌanog ritma, ishemiДЌni moЕѕdani udar INTRODUCTION A stroke is a condition of acute disorder of cerebral circulation with transient or permanent dysfunction of the brain whether is the case of ischemic, which accounts for 80%, or hemorrhagic stroke, which occurs in about 20% cases. It is a disease that, despite diagnostic and therapeutic advances, has an increasing trend in the world. Unchangeable risk factors of stroke are: age, sex, genetic predisposition, while a group of variable factors include: hypertension, arrhythmia, diabetes mellitus, hyperlipidemia. Bad habits, particularly smoking, alcohol consumption, physical inactivity, obesity, and lately more and more stress, especially chronic, which enhances platelet aggregation, activates the renin angiotensin system and increases the production of angiotensin II which leads to an increase in blood pressure significantly contribute to stroke onset (1,2). Separate cause of stroke is disturbances in heart rhythm. When the heart beats very fast or very slow, or at irregular rhythm, its pump function is reduced and cannot pumped out enough blood to all parts of the body. This has the effect of brain parenchyma ischemia and if that state lasts long enough can cause a stroke. Arrhythmia can be caused by: disorders in the impulse creation (sinus tachycardia, sinus bradycardia, extrasistole, supraventricular tachycardia, atrial flutter, atrial In the group of patients fibrillation, ventricular tachycardia) and the disorders in terms of impulse conduction (SA and AV block) or a combination of these two disorders. Cerebral embolism of cardiac origin occurs in 1520% cases of ischemic stroke. The consequences are the same: non rheumatic fibrillation (45%), followed by acute myocardial infarction (15%), post infarction left ventricular aneurysm (10%), rheumatic heart defect (10%), valvular prosthesis, while in case of others 10% is due to other cardiovascular disorders, primarily cardiac arrhythmia. In patients with chronic stable atrial fibrillation, the risk of stroke increases fivefold and in case when the atrial fibrillation is caused by rheumatic heart disease, the risk of brain embolism is increased up to 17 times (3,4). Clinical state is featured by abrupt onset of neurologic deficits, usually without consciences disorder. Patients are in average about 10 years younger than those with atherosclerotic CVI and have in the history data on heart disease. According to data, 15-20% of all ischemic strokes has cardiogenic genesis. Studies have shown a significantly higher incidence of stroke in patients with cardio vascular diseases. With regard to age, the incidence of stroke was doubled in the presence of ischemic heart disease, tripled in the presence of hypertension, four times higher in the case of congenital heart disease and five times higher in the presence of atrial fibrillation. It was found that atrial fibrillation is responsible for 15% of all ischemic strokes. The significance of this risk factor increases with age, so in persons at age of 80-90 years it is treated as an independent risk factor for the occurrence of embolism (4,5). Goal Determine the presence of heart rhythm disturbances in patients with ischemic stroke. MATERIALS AND METHODS The study was conducted as a retrospective in the Sarajevo region, during the one-year period (July 2011-July 2012). The study included all patients with ischemic stroke. A medical history was taken from each respondent and a neurological examination was performed, with CT of the brain to confirm ischemic stroke, also ECG and cardiology examination in order to determine heart rate disorders and laboratory findings. Medicinski Еѕurnal 2013 бѓЂ19 (1): 38 - 42 39 40 Jasminka ДђeliloviД‡-VraniД‡, Azra AlajbegoviД‡, Mehmed KuliД‡, Amina NakiДЌeviД‡, Emina EjuboviД‡, Merita TiriД‡-ДЊampara, Edina ДђoziД‡, Ljubica TodoroviД‡, Salem AlajbegoviД‡. Heart rhythm disorders as a contributing factor to ischemic stoke RESULTS During the one-year period a total of 961 patients were treated because of ischemic stroke at age from 37-79 years of life. Thrombotic stroke was present in 71.1% and embolic in 28.9% of patients. Figure 4. Risk factors. Figure1. Distribution of patients by age groups. By age groups,13% of patients were in the group up to 50 years,43% in the group of 50-65 years, and older than 65 years 44% of patients. Analyzing risk factors individually, we have come to a result that hypertension was present in 83.7%, smoking in 56%, diabetes mellitus in 34.4%, abnormal heart rhythm in 22.7% of patients, whereas dyslipidemia was present in 19.6%. Figure 5. Cause of hearth rhythm disorders. Figure 2. Distribution of patients by gender. Of the total number of patients, males accounted for 48.4% of patients and women for 51.6%. Figure 3. Distribution of patients by type of stroke. In the group of patients with heart rhythm disorders (which was present in 22.7% of cases), atrial fibrillation was present in 38% of patients; SVES in 22% of patients, 22% had a block of one of the branches, while sinus tachycardia was present in 18% of patients. In the group of patients under the age of 50 years, atrial fibrillation was noticed in 15.15% of patients. In all 961 patients, the diagnosis was confirmed by CT, in 21.6% of cases with a relapse of ischemic stroke and in 18% of cases in patients with atrial fibrillation. Majority of patients, 91% had two or more associated risk factors which increase the risk of stroke. DISCUSSION During the one-year period due to ischemic stroke was treated a total of 961 patients.Stroke is showing an increasing tendency in the world in general and particularly in developing countries like ours Medicinski Еѕurnal 2013 бѓЂ19 (1): 38 - 42 Jasminka ДђeliloviД‡-VraniД‡, Azra AlajbegoviД‡, Mehmed KuliД‡, Amina NakiДЌeviД‡, Emina EjuboviД‡, Merita TiriД‡-ДЊampara, Edina ДђoziД‡, Ljubica TodoroviД‡, Salem AlajbegoviД‡. Heart rhythm disorders as a contributing factor to ischemic stoke Bruce Ovbiagele and Mai N. Nguyen-Huynh in their study reported that the stroke is the fourth leading cause of death and the leading cause of disability in the United States (1,2). Of the total of 961 patients with ischemic stroke, 684 patients (71.1%) had thrombotic and 277 patients (28.9%) embolic stroke. William David Freeman and Maria I. Aguilar in their study have shown that about 20% of all ischemic strokes belong to the category of embolic stroke (3,4). Group of authors from Japan have come to the conclusion that ulcerated atherosclerotic plaque in aortal arc can be the cause of embolic stroke. Their study showed that 10.6% of stroke patients had ulcerated plaque just as a source of emboli that led to stroke (5). Probable reasons for variation of data in this study in relation to the data presented by the authors mentioned lies in the standard of living in our region, during and after the was events and an unhealthy lifestyle. In our study, men are presented by 48.4% and women by 51.6%. In a study carried out by Peter Appelros, Birgitta Stegmayr and Andreas TerГ©nt, which was a systematic review of 98 articles around the world on the topic of gender differences among patients with stroke, it was concluded that stroke occurs more frequently among male patients, compared to female patients (6). The data obtained in this study partially deviate from the data presented by the authors in their review study. However, we should bear in mind that the aforementioned data are related to stroke in general, not just the ischemic type and that despite this the deviation is not too large. Patients involved in the study were in the age range from 39-79 years. Chih-Ying Wu, Hung-Ming Wu, Jianni-Der Lee and Hsu-HueiWeng from School of Medicine in Taiwan in their study published in 2010 showed that 60.5% of patients with ischemic stroke were in the age group of 50-75 years, 26.4% had more than 75 years and 13.2% had less than 50 years of age (7). Although age is one of the leading risk factors for stroke overall, including the ischemic type, it is evident that the age of patients, unfortunately, moves toward younger age groups. The data that were obtained in our study show that the youngest patient was 39 years old. The reasons for this probably lie in the stress that people are constantly exposed to, an unhealthy lifestyle and poor general care for health. One of the main questions, with regard to the frequency and consequences of ischemic stroke, refer to factors that can contribute to the development of the stroke. Our research has shown that the most common risk factors is hypertension, which was observed in 83.7% of patients, smoking in 56%, diabetes mellitus was recorded in 34.4% of patients, a heart rhythm disorder in 22.7% of patients and hyperlipidemia in 19, 6% of patients. O'Donnell MJ, Xavier D, Liu L et al. in their study, which is a review of research from 22 countries, have come up with data that hypertension is the leading risk factor for the ischemic stroke, while diabetes mellitus is the sixth by the frequency among risk factors (8). Data from our study fully coincide with the results of the survey study of those authors, where hypertension is by far the leading risk factor. Diabetes mellitus as a risk factor had a total of 34.4% of patients which places it at the second place among the high risk factors. Vida Demarin, Marija BoЕЎnjak-PaЕЎiД‡ and Marijana Bosnar-PuretiД‡ in their study presented the fact that diabetes mellitus is a major risk factor for cerebrovascular disease and progression of atherosclerosis. Out of five people who have experienced a stroke, one in its medical history has records of previous diabetes (9). Data from our study indicate that diabetes is even more significant risk factor than stated above mentioned authors. In the group of patients with heart rhythm disorder (which was present in 22.7% of cases), atrial fibrillation was present in 38% of patients; SVES in 22% of patients, 22% had a block of one of the branches, while sinus tachycardia was present in 18% of patients. In the group of patients under the age of 50 years, atrial fibrillation was observed in 15.15% of patients. William David Freeman and Maria I. Aguilar stated that atrial fibrillation is by far the most common cause of cardio embolic stroke. However, they listed also other вЂћcardiac" causes of stroke, such as acute myocardial infarction, ventricular thrombi (20%), structural heart defects, cardiac tumors (15%) and valvular disease (15%) (4,10). Santamarina E, Alvarez Sabin J in their study concluded that atrial fibrillation is by far the most common form of cardiac arrhythmia, which acts as a risk factor for ischemic stroke (10). Hyperlipidemia is a very important factor in the development of atherosclerosis and cerebrovascular disease and in our study was present in 19.6% of cases, so our research is correlated with the studies of other authors. P. Laloux, L. and J. Galanti Jamarta in their research showed that hyperlipidemia, diabetes and hypertension are one of the leading risk factor for the occurrence of ischemic stroke (11). Mortality of patients in our study was 25%, while 75% of patients survive a stroke. In the group of patients with atrial fibrillation, the mortality was 21.2%. Medicinski Еѕurnal 2013 бѓЂ19 (1): 38 - 42 41 42 Jasminka ДђeliloviД‡-VraniД‡, Azra AlajbegoviД‡, Mehmed KuliД‡, Amina NakiДЌeviД‡, Emina EjuboviД‡, Merita TiriД‡-ДЊampara, Edina ДђoziД‡, Ljubica TodoroviД‡, Salem AlajbegoviД‡. Heart rhythm disorders as a contributing factor to ischemic stoke Mortality was higher in case of cardio embolic CVI (67% of total mortality). The explanation for this is found in association with existing cardiac comorbidity, such as myocardial infarction, atrial fibrillation, etc. These data differ from the results for the general population of patients with ischemic stroke, where cardio embolic stroke mortality is represented with 40% of total mortality (12). CONCLUSIONS Heart rhythm disturbances can occur at any age, but the extension of life expectancy has resulted in more frequent disturbances in heart rhythm, which increases the risk of stroke. Heart rhythm disturbances increase the risk of recurrence of embolic stroke. Timely detection of cardiac arrhythmias and appropriate treatment can help to prevent the stroke and thus significantly reduce the number of disabled persons, also the cost of treatment and improve quality of life in the elderly. Conflict of interest: none declared. REFERENCES 1. Ovbiagele B, Nguyen-Huynh MN. Stroke Epidemiology: Advancing Our Understanding of Disease Mechanism and Therapy. Neurotherapeutics. 2011 July; 8(3): 319вЂ“329. 2. Demarin V, Trkanjec Z, Е eriД‡ V. MoЕѕdani udar. Hrvatsko druЕЎtvo za prevenciju moЕѕdanog udara Hrvatska. 2010; 1(3):32-36. 3. Andersen KK, Olsen TS, Dehlendorff C, Kam mersgaard LP. Hemorrhagic and Ischemic Strokes Compared Stroke Severity, Mortality, and Risk Factors. Stroke. 2009; 40:2068-2072. 4. Freeman WD, Aguilar MI. Prevention of Cardioembolic Stroke. Neurotherapeutics. 2011 July; 8(3): 488вЂ“502. Medicinski Еѕurnal 2013 бѓЂ19 (1): 38 - 42 5. Yoshimura S, Toyoda K, Kuwashiro T, Koga M, Otsubo R, Konaka K,Naganuma M, MatsuokaH, Naritomi H, Minematsu K. Ulcerated plaques in the aortic arch contribute to symptomatic multiple brain infarction. J NeurolNeurosurg Psychiatry. 2010; 81:1306-1311. 6. Appelros P, Stegmayr B, Terent A. Sex Differences in Stroke Epidemiology-A Systematic Review. Stroke. 2009; 40:1082-1090. 7. Wu CY, Wu HM, Lee JD, Weng HH. Stroke risk factors and subtypes in different age groups: A hospital-based study. Neurology India. 2010; 58 (6): 863-868. 8. OвЂ™Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et all. Risk factors for ischaemic and intracerebralhaemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet. 2010 Jul 10:376(9735):112-23. 9. Demarin V, BoЕЎnjak-PaЕЎiД‡ M, Bosnar-PuretiД‡ M. MoЕѕdani udar-vodeД‡i uzrok invaliditeta. Hrvatsko druЕЎtvo za prevenciju moЕѕdanog udara Hrvatska. 2011; 3(3):212-218. 10. Santamarina E, Alvarez SabГn J. Social impact of stroke due to atrial fibrillation. Neurologia. 2012 Mar; 27 (Suppl 1):10-4. 11. Laloux P, Galanti L, Jamart J. Lipids in ischemic stroke subtypes. Acta Neurol Belg. 2004; 104: 13-19. 12. Ingall T. Stroke - incidence, mortality, morbidity and risk. J Insur Med. 2004;36(2):143-52. Address: Jasminka ДђeliloviД‡-VraniД‡, MD, PhD Neurology Clinic, Clinical Center of University of Sarajevo BolniДЌka 25, 71000 Sarajevo Bosnia and Herzegovina Phone: +387 33 297 236 Email: [email protected] Aida HasanoviД‡, Belma AЕЎДЌiД‡-ButuroviД‡, Muhamed SpuЕѕiД‡. Coronary angiography review of anatomic variations of the coronary arteries Original article CORONARY ANGIOGRAPHY REVIEW OF ANATOMIC VARIATIONS OF THE CORONARY ARTERIES PREGLED ANATOMSKIH VARIJACIJA KORONARNIH ARTERIJA METODOM KORONARNE ANGIOGRAFIJE 1* Aida HasanoviД‡ , Belma AЕЎДЌiД‡-ButuroviД‡ 2, Muhamed SpuЕѕiД‡ 3 1 Department of Anatomy, Faculty of Medicine, University of Sarajevo, ДЊekaluЕЎa 90, 71 000 Sarajevo, Bosnia 2 and Herzegovina; Clinic for Endocrinology, Diabetes and Metabolism disorders, Clinical Center University of 3 Sarajevo, BolniДЌka 25, 71 000 Sarajevo, Bosnia and Herzegovina; Heart Center, Clinical Center University of Sarajevo, BolniДЌka 25, 71 000 Sarajevo, Bosnia and Herzegovina * Corresponding author ABSTRACT SAЕЅETAK The aim of this study was to present the different types of coronary artery variations on coronary angiograms, to determine the incidence of the coronary artery variations and to elucidate their clinical significance. The retrospective study included 670 patients with ischemic heart disease who underwent coronary angiography in Heart Center of the Clinical Center University of Sarajevo in period from April 1, 2011 to April 1, 2012. Coronary artery variations were found in 10 patients (1.5% incidence). Variation of origin were observed in 2 patients (0,3%). Out of these 2 patients, 1 had anomalous origin of the coronary artery from the opposite sinus of Valsalvae and 1 had ectopic origin of the right coronary artery from left sinus of Valsalva. Variation of number (single coronary artery) were established in 1 patient (0,1%), variations of distribution (muscular bridge) in 4 patients (0,6%) and variations of termination (coronary artery fistulae) in 3 patients (0,4%). There were no statistically significant differences in the prevalence of coronary artery variations between groups. Coronary artery variations have low incidence in the general population, and rarely are discovered at coronary angiography. The most common coronary variations were variations of distribution (muscular bridge) in 0,6% of patients, and the least represented were variations of number (single coronary artery) in 0,1% patients. The majorities of coronary artery variations are asymptomatic and found incidentally at the time of catheterization. Other anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias or sudden death. Cilj istraЕѕivanja je bio prikazati razliДЌite tipove varijacija koronarnih arterija na angiogramima ispitivanih pacijenata, utvrditi njihovu incidencu i kliniДЌki znaДЌaj. Retrospektivno istraЕѕivanje obuhvatilo je 670 pacijenata sa ishemiДЌnom bolesti srca, kojima je u periodu od 01. 04.2011. вЂ“ 01.04. 2012.godine uraД‘ena koronarna angiografija u Centru za srce KliniДЌkog centra Univerziteta u Sarajevu. Varijacije koronarnih arterija su otkrivene u 10 sluДЌajeva (incidenca 1.5%). Kod 2 pacijenta (0,3%), uoДЌene su varijacije polaziЕЎta koronarnih arterija (1 pacijent sa anomalijom polaziЕЎta koronarne arterije iz suprotnog sinusa Valsalvae i 1 pacijent sa ektopiДЌnim polaziЕЎtem desne koronarne arterije iz lijevog sinusa Valsavlae.Varijacije broja (jedna koronarna arterija) uoДЌene su kod 1 pacijenta (0,1%), varijacije pravca pruЕѕanja (miЕЎiД‡ni most) kod 4 pacijenta (0,6%), dok su varijacije zavrЕЎetka koronarnih arterija (koronarne fistule) uoДЌene kod 3 pacijenta (0,4%). StatistiДЌka analiza upotrebom Kolmogorow-Smirnow testa pokazala je da ne postoje statistiДЌki znaДЌajne razlike u zastupljenosti varijacija koronarnih arterija meД‘u grupama. Varijacije koronarnih arterija imaju nisku uДЌestalost javljanja u opД‡oj populaciji i rijetko se otkrivaju koronarnom angiografijom. NajДЌeЕЎД‡e varijacije kod naЕЎih ispitanika bile su varijacije pravca pruЕѕanja (miokardni most) sa 0,6%, a najmanje zastupljene su varijacije broja su varijacije broja (jedna koronarna arterija) sa 0,1%. Varijacije koronarnih arterija, u veД‡ini sluДЌajeva nisu prouzrokovale simptome, te su sluДЌajno otkrivene pri koronarnoj angiografiji. Neke varijacije mogu biti udruЕѕene sa ozbiljnim posljedicama kao ЕЎto su angina pektoris, infarkt miokarda, sinkopa, srДЌane aritmije ili iznenadna smrt. Key words: coronary arteries, variations, coronary angiography KljuДЌne rijeДЌi: koronarne arterije, varijacije, koronarna angiografija Medicinski Еѕurnal 2013 бѓЂ19 (1): 43 - 47 43 44 Aida HasanoviД‡, Belma AЕЎДЌiД‡-ButuroviД‡, Muhamed SpuЕѕiД‡. Coronary angiography review of anatomic variations of the coronary arteries INTRODUCTION RESULTS The term coronary artery variations refer to a wide range of congenital abnormalities involving the origin, number, course and termination of coronary arteries. These abnormalities occur in about 1% of the general population (1,2). Isolated congenital coronary artery variations have been described in approximately 1% of patients who undergo coronary angiography and approximately 0.3% of patients at autopsy. Although coronary variations are far less common than atherosclerosis, their impact on premature cardiac morbidity and mortality in young individuals needs to be emphasized. While some of these anomalies are benign and have no clinical sequelae, others are associated with myocardial ischemia, ventricular dysfunction, and sudden death (3,4,5). Accurate recognition and documentation of coronary artery anomalies at the time of coronary angiography are essential to determine the significance of such findings and to avoid therapeutic complications. The incidence of various coronary anomalies and associated clinical, angiographic and hemodynamic findings has been cited in several internationally published clinical series (6-14). To compare our experience with previously reported studies, we have reviewed angiographic and clinical findings of 670 patients with coronary artery disease. The coronary angiograms of 670 patients were reviewed and 10 adult patients were identified with coronary artery variations (1,5%). Out of these 670 patients variation of number (single coronary artery) was discovered in one case (0,1%) (Figure 1). Variation of origin were observed in 2 patients (0,3%). Out of 2 patients in 1 patient was identified anomalous origin of the coronary artery from the opposite sinus of Valsalvae (Figure 2) and 1 patient had ectopic origin of the circumflex coronary artery from the right coronary artery. Variations of distribution were found in 4 patients (0,6%), all of them had muscular bridge (Figure 3). The variations of termination were identified in 3 adults (0,4%), in all cases coronary artery fistulae. The most frequent variations were established in men and elderly patients aged 50-65 years. Table 1. Coronary artery variations. MATERIALS AND METHODS Coronary angiograms of 670 adult patients with coronary artery disease (410 males, 260 females; age range, 17вЂ“65 years) who underwent coronary angiography in Heart Centre of the Clinical Center University of Sarajevo in period from April 1, 2011 to April 1, 2012, were retrospectively reviewed to identify the coronary anatomy and determine anatomic variantions. Clinical characteristics of each patient had been recorded at the time of catheterization. We classified the variations as variations in number, origin, distribution and termination of coronary arteries. Statistical analysis The statistical analysis of the results was performed using Kolmogorow-Smirnow test and the differences in the prevalence of coronary artery variations between groups were considered significant on the level p<0,05. Medicinski Еѕurnal 2013 бѓЂ19 (1): 43 - 47 Figure 1.Variation in coronary artery number A single coronary artery -Left coronary artery Right coronary artery origin of the left antrior descending artery of the left coronary artery. Aida HasanoviД‡, Belma AЕЎДЌiД‡-ButuroviД‡, Muhamed SpuЕѕiД‡. Coronary angiography review of anatomic variations of the coronary arteries Figure 2. Anomalous origin of the coronary from the opposite sinus of Valsalva. B There were no statistically significant differences in the prevalence of coronary artery variations between groups. The highest incidence of myocardial bridges we found on the left anterior descending branch, although myocardial bridges were established on the circumflex branch of the left coronary artery (CX), and at the end on the right coronary artery (RCA). Right coronary artery was dominant in all patients with myocardial bridges. Figure 3. Systolic narrowing typical of myocardial bridging on the left anterior descending branch (A) and changes in diastole (B) are indirect signs of myocardial bridges. A DISCUSSION Coronary artery variations represent marked deviations from the normal pattern. Most variations are discovered as incidental findings during coronary angiography or at autopsy. However, some variations present symptoms or potentially serious sequelae that require surgical treatment. The clinician should suspect the presence of coronary artery anomaly in young person who experiences exertional syncope, myocardial infarction, exercise-induced arrhythmias, or cardiac arrest. The incidence of coronary artery variations in our review is 1,5%, which compare well with the incidence from other studies of patients referred for coronary angiography (1,2). In our study, as in others coronary artery anomalies appear to be more common in men than in women (8 males, 2 females) (3,4,5). These variations included variations of origin, number, distribution and termination. Single coronary artery is a rare anomaly, occurring in one of our patients (0,1%). Fiss et al reported that a single coronary artery occurred in 0.024% of people. It is usually benign, but may be associated with congenital heart disease, such as transposition of the Great Arteries, tetrology of Fallot, truncus arteriosus, and coronary artery fistula (1). The majority of patients younger than 20 years of age are presented with an associated abnormality with most frequent transposition of the great vessels or coronary artery fistula-while older patients Medicinski Еѕurnal 2013 бѓЂ19 (1): 43 - 47 45 46 Aida HasanoviД‡, Belma AЕЎДЌiД‡-ButuroviД‡, Muhamed SpuЕѕiД‡. Coronary angiography review of anatomic variations of the coronary arteries have a low incidence of associated anomalies. In the absence of significant coronary atherosclerosis, a single coronary artery may be a benign finding unassociated with functional or anatomic evidence of ischemia (6,7). Variation of origin were observed in 2 of 10 patients with variations (0,3%). Anomalous origin of the coronary artery from the opposite sinus of Valsalvae was found in 1 patient (0.1 %) of the study population, and ectopic origin of the circumflex coronary artery from the right coronary artery (0,1%) which is smaller than reported by Altaii et al, (0,6%) (8). Coronary artery fistula was identified in 3 patients (0,4%) of our study population. Coronary artery fistulas as abnormal communications between a coronary artery and another vascular structure are seen in approximately 0.1% to 0.2% of all patients who undergo selective coronary angiography. More often, the fistula is formed with a right sided (venous) structure. Minor fistulas are not uncommon and are of little clinical significance. Approximately one-half of the patients with large fistulas develop complications, which include congestive heart failure, sub-acute bacterial endocarditis, myocardial ischemia, and rupture of an aneurysmal fistula (9,10,11). Variations of distribution were found in 4 patients (0,6%), all of them had muscular bridge. On arteriograms, the bridged portion of the vessel can be visualized during systole, when the bridging fibers contract and distort the vessel lumen. Myocardial bridging has been associated with angina, myocardial infarction, and sudden death (12,13). Ironically, the bridged segment is rarely affected by atheroscle rosis and can easily go unrecognized on arteriography as what otherwise appears to be a normal coronary artery. There were no statistically significant differences in the prevalence of coronary artery variations between groups. Anatomically, coronary variations included variations of origin, number, distribution and termination. Clinically, anomalies may be arbitrarily divided intoвЂќbenignвЂќ (asymptomatic) and вЂњpotentially seriousвЂќ. Potentially serious anomalies (ectopic coronary origin from the pulmonary artery, ectopic origin of the left coronary artery from the right sinus of Valsavla and others) would have been detected earlier in life or resulted in sudden death (14). Coronary artery variations require accurate recog nition, and at times, surgical correction. Medicinski Еѕurnal 2013 бѓЂ19 (1): 43 - 47 CONCLUSIONS Coronary artery variations have low incidence in the general population, and rarely are discovered at coronary angiography. Coronary artery variations were found in 10 patients (1.5% incidence). The most common coronary variations were variations of distribution (muscular bridge) in 4 patients (0,6%), and the least represented were variations of number (single coronary artery) in 1 patient ( 0,1%). The most frequently variations were established in men and elderly patients aged 50-65 years.The majority of coronary artery variations is asymptomatic and found incidentally at coronary angiography in patients who undergo the procedure for evaluation of coronary artery stenosis. Other anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias or sudden death. Coronary artery variations require accurate recognition in order to ensure appropriate management. Conflict of interest: none declared. REFERENCES 1. David MF. Normal coronary anatomy and anatomic variations. Applied Radiology Journal. 2007; 36 (1): 14-26. 2. Khan MQ, Nuri MH, Irfan M, Raza A, Abbas S. Coronary artery anomalies; an afic/nihd experience. Profess Med J. 2008 Jun; 15(2): 247-254. 3. HasanoviД‡ A, DilberoviД‡ F, OvДЌina F. Anatomical-clinical investigations of variations of the human coronary arteries. Bosn J Basic Med Sci. 2003;3(4): 23-25. 4. HasanoviД‡ A. Doprinos istraЕѕivanju varijacija srДЌanih arterija ДЌovjeka disekcijom i metodom koronarne angiografije. Veterinaria. 2000; 49 (3-4): 389-396. 5. Karahan ST, Surucu HS, Karaoz E. Chronic degenerative changes in the myocardium supplied by bridged coronary arteries in eight post mortem samples. Jpn Circ J. 1988 Sep; 62(9):691-4. 6. Bhimalli S, Dixita D, Siddibhavi M, Spirol VS. A study of variations in coronaryarterial system in cadaveric human heart. World Journal of Science and Technology. 2011;1(5): 30-35. 7. KoЕџar P, Ergun E, Г–ztГјrk C, KoЕџar U. Anatomic variations and anomalies of the coronary arteries: 64-slice CT angiographic appearance. Diagn Interv Radiol. 2009;15:275вЂ“283. Aida HasanoviД‡, Belma AЕЎДЌiД‡-ButuroviД‡, Muhamed SpuЕѕiД‡. Coronary angiography review of anatomic variations of the coronary arteries 8. Altaii FG, Youssef M, Takla M. Angiographic coronary artery study: Anatomy, Variation and Anomalies. Kasr El Aini Journal of Surgery. 2010; 11 (1):71-76. 9. Muresian H. Coronary arterial anomalies and variations. MГ¦dica J Clin Med. 2006;1(1): 38-48. 10. Trejo Gutierrez JF, Cecena L. Coronary arteriovenous fistula. Study of 14 cases. Arch Inst Cardiol Mex. 1985; 55 (2): 153-64. 11. Hunh G, Fassbender D, Gleichmann U. Congenital arteriovenous fistula of the coronary arteries in adults, 12 personal cases, review of the literature, discussion of treatment possibilities. Z Kardiol. 1989 Jul; 78 (7): 435-40. 12. Somanath HS, Reddy KN, Gupta SK. Myocardial bridge (MB): an angiographic curiosity?. Indian Heart J. 1989; 41 (5): 296-300. 13. HasanoviД‡ A, JunuzoviД‡ A, SpuЕѕiД‡ M, KudumoviД‡ A. Angiographic evaluation of myocardial bridges in relation to myocardial ischemia. HealthMED 2010; 4(2): 398-403. 14. Yamanaka O, Hobbs RE. Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. Cathet Cardiovasc Diag. 1990; 21:28-40. Address: Prof. Aida HasanoviД‡, MD, PhD Department of Anatomy Faculty of Medicine, University of Sarajevo ДЊekaluЕЎa 90, 71 000 Sarajevo Bosnia and Herzegovina Phone: +387 33 665 949 Email: [email protected] Nova centralna zgrada KliniДЌkog Centra Univerziteta u Sarajevu New Central building of the Clinical Center University of Sarajevo Medicinski Еѕurnal 2013 бѓЂ19 (1): 43 - 47 47 48 DЕѕenela ProhiД‡, Rusmir MesihoviД‡, Nenad Vanis, SrД‘an GornjakoviД‡, Amra PuhaloviД‡, Aida Saray. Prognostic assessment in patients with decompensated cirrhosis Professional article PROGNOSTIC ASSESSMENT IN PATIENTS WITH DECOMPENSATED CIRRHOSIS PROGNOSTIДЊNE PROCJENE KOD PACIJENATA SA DEKOMPENZIRANOM CIROZOM 1,2 DЕѕenela ProhiД‡* , Rusmir MesihoviД‡ , Nenad Vanis , SrД‘an GornjakoviД‡ , Amra PuhaloviД‡ , 1 Aida Saray 1 1 1 1 1 Clinic for Gastroenterohepatology, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, 2 Bosnia and Herzegovina; Department of Medicine, Universitetssykehuset Nord Nodge, Norway *Corresponding author ABSTRACT SAЕЅETAK Many prognostic liver scores have been devised to predict mortality of patients with decompensated cirrhosis. Today, the Model of End stage Liver Disease (MELD) has gained wide acceptance over the traditional Child Pugh (CP) score in predicting survival in patients with decompensated liver cirrhosis. The serum creatinine level is significant parameter of survival in patients with decompensated liver cirrhosis. The aim of this study was to evaluate and compare the predictive power of the CP, the creatinine modified CP score and MELD score in patients with decompensated liver cirrhosis. 80 patients with decompensated liver cirrhosis were followed up for a 6 months. CP, creatinine modified CP and MELD score were calculated. Creatinine modified CP score was calculated using creatinine as a sixth categorical variable added to CP score and adding additional 0-3 points. We calculated and compared the accuracy (cindex) of the three scores in predicting 6-months mortality Results: Areas under the receiver operating curves showed all three scores having significant predictive diagnostic accuracy, the creatinine modified CP score showed better prognostic accuracy compared to the traditional CP score (CP c-statistics: 0,761 vs. the creatinine modified CP 0,846). However, the MELD proved to have the best diagnostic accuracy (c statistics:0,872). All three scores statistically correlated with highest correlation between the traditional CP and the creatinine CP scores ( r 95,1%) Conclusion:The MELD score has better predictive accuracy compared to the traditional CP and creatinine modified CP score in predicting mortality in patients with decompensated liver cirrhosis. Adding serum creatinine values to the CP score improves the prognostic strength of the traditional CP score. Veliki broj jetrenih prognostiДЌkih skorova kreiran je u cilju procijene mortaliteta kod pacijenata sa dekomepnziranom cirozom. The Model for the End Stage Liver Disease (MELD) je ЕЎiroko prih vraД‡en i koriЕЎten u odnosu na ostale, osobito tradi cionalni Child Pugh (CP) skor u procijeni preЕѕivljenja pacijenata sa dekompenziranom jetrenom cirozom. Serumska vrijednost kreatinina smatra se signifikantnim parametrom preЕѕivljenja kod ove grupe pacijenata. Cilj ovog istraЕѕivanja je evaluacija i usporedba prediktivne snage CP skora, kreatinin modificiranog CP skora i MELD skora kod pacijenata sa dekomepnziranom jetrenom cirozom Grupa od 80 pacijenata sa dekompenziranom jetrenom cirozom praД‡ena je u periodu od 6 mjeseci. CP, kreatinin modificirani CP i MELD skor su izraДЌunati. Kreatinin modificirani CP skor je izraДЌunat koristeД‡i serum kreatinin kao ЕЎestu kategoriДЌku varijablu dodatu tradicionalnom CP skoru uz dodatnih 0-3 boda. IzraДЌunali smo i usporedili taДЌnost (c- index) sva tri skora u procijeni ЕЎestomjeseДЌnog mortaliteta. Rezultati: Area ispod ROC krivulje pokazala je da sva tri skora imaju signifikatnu prediktivnu taДЌnost, kreatinin modificirani CP skor je pokazao bolju prognostiДЌku taДЌnost usporeД‘en sa tradicionalnim CP skorom (CP c-statistika: 0,761 vs. kreatinin modificirani CP 0,846). MELD skor je pokazao najjaДЌu prog nostiДЌku snagu (vrijednost c statistike:0,872). Sva tri skora statistiДЌki koreliraju meД‘usobno sa najja ДЌom korealcijskom vrijednosti izmeД‘u tradicionalnog CP i kreatinin modificiranog CPskora (r 95,1%) ZakljuДЌak: MELD skor posjeduje jaДЌu prediktivnu taДЌnost usporeД‘eno sa tradicionalnim CP i kreat inin modificiranim CP skorom u procjeni mortalite ta kod pacijenata sa dekompenziranom jetrenom cirozom. Key words: Child Pugh, MELD, creatinine, decompensated liver cirrhosis, mortality Medicinski Еѕurnal 2013 бѓЂ19 (1): 48 - 53 DЕѕenela ProhiД‡, Rusmir MesihoviД‡, Nenad Vanis, SrД‘an GornjakoviД‡, Amra PuhaloviД‡, Aida Saray. Prognostic assessment in patients with decompensated cirrhosis Dodavanjem serumske vrijednosti kreatinina vrijednostima CP skora unapreД‘uje se prognosticka jaДЌina tradicionalnog CP skora. KljuДЌne rijeДЌi: Child Pugh skore, MELD, kreatinin, dekompenzirana jetrena ciroza, mortalitet INTRODUCTION Cirrhosis represents a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and the formation of regenerative nodules. It is generally considered to be irreversible in its advanced stages at which point the only option may be liver transplantation. It means that cirrhosis belongs to the group of severe conditions for which survival remains the principal end-point of the treatment. The course and outcome of chronic liver disease may be dif ficult to predict. Many factors need to be considered: the specific diagnosis, the stage, the dis ease activity, the likely rate of progression and the occurrence of decompensation and complications. It is a challenging issue for physicians to elaborate reliable tools for predicting outcome (1). The main objective of the prognostic scores in cirrhotic patients is to estimate the probability of the death within a given time interval (2). The Child-Pugh (CP) classification (3,4) have been by far the most widely applied prognostic score in patients with decompensated cirrhosis mainly due to its simplicity for use as bedside test in daily clinical practice (5,6,7). The determination of CP score, which may range from 5-15, is based on the presence and severity of ascites and hepatic encephalopathy, the prolongation of protrombine time, and the levels of serum bilirubin and albumin. According to their CP scores, patients are classified into three classes (Child class A; B and C with scores 5-6, 7-9, and 1015 respectively) (4). During the last two decades, due to the difficulties and interobserver variability for the subjective parameters in the CP classification led to development several scoring systems or prognostic instruments for predicting survival in patients with decompensated cirrhosis (8,9). The model for end-stage liver disease (MELD), published in 2000, is a mathematical model, which is calculated from 3 objective biochemical variables (serum bilirubin and creatinine levels and international normalised ration (INR) for prothormbine score) (10). The model for end-stage liver disease (MELD), published in 2000, is a mathematical model, which is calculated from 3 objective biochemical variables (serum bilirubin and creatinine levels and international normalised ration (INR) for prothormbine score) (10). The MELD score has been shown to predict 3-mon th survival in patients undergoing tranasjugular intrahepatic portosystemic shunt (TIPSS), and to be able to assess prognosis of patients with liver cirrhosis in the short as well as in the long term (11,12,13). Since February 2002, patients are prioritized for receiving organs for liver transplantation based on their MELD score. The advantage of the MELD score over the CP classification is based upon clinically relevant issues. The main benefits of the MELD are the absence of subjective criteria, the lack of "floor and ceiling effect", it is a continuous progressive score which increases with worsening of its parameters. Nevertheless, the fact that inclusion of the renal function seems to be the only important difference as compared with the traditional CP classification and the use of the MELD may not be easy to apply since it requires a mathematical calculation to compute the score, and provide a result, which is a continuous variable graded an a large scale rather than categorising the patients into few classes (14,15). The renal function is a significant independent parameter determining the prognosis of patients with decompensated liver cirrhosis both during the natural course of the disease as well as during acute complications (5,16,17). Keeping the above consideration in mind, the aim of this study was to evaluate whether the traditional CP can be improved by adding serum creatinine values, and to assess whether the creatinine modified CP score can challenge the short-term prognostic ability of the MELD score. MATERIALS AND METHODS Patient population Eighty patients with decompensated liver cirrhosis who visited our Clinic from 2009 -2011 were evaluated and had follow- up of 6 months. The outcome was assessed as the 6-month mortality. The diagnosis of decompensated cirrhosis was based on clinical, laboratory, previous histological and radiological signs of cirrhosis with at least one sign of liver decompensation. Patients with hepatocellular carcinoma, sepsis or evidence of organic renal failure were excluded from analysis. All patients underwent routine physical examination and biochemical assessment. Hepatic encephalopathy was diagnosed and graded on the basis of clinical criteria (18). Ascites evaluation was performed ultrasonographically. The CP score was calculated according to the modified CT score (3,4). The creatinine modified CP score was calculated according to modification by Giannini et al. (15). Medicinski Еѕurnal 2013 бѓЂ19 (1): 48 - 53 49 50 DЕѕenela ProhiД‡, Rusmir MesihoviД‡, Nenad Vanis, SrД‘an GornjakoviД‡, Amra PuhaloviД‡, Aida Saray. Prognostic assessment in patients with decompensated cirrhosis We assessed the mean creatinine serum level and standard deviation of the 80 patients included into this study. We assigned a score of 1 to patients with serum creatinine levels < standard deviation (SD), a score of 2 to patients with serum creatinine levels between the mean and the mean +1SD, and a score of 3 to patients with serum creatinine levels above the mean +1SD. Then we calculated each patient modified creatinine CP score by adding creatinine score to their traditional CP value. The MELD score was calculated in all patients according to the UNOS modified formula: Table 1. Baseline demographic, clinical and biochemical characteristics. 3.78 loge (bilirubin (mg/dl))111.2 loge (INR.)19.57 loge (creatinine (mg/dl))16.4. Statistical analysis All statistical analyses were conducted with SPSS for Windows version 11.5.18 SPSS inc. Chicago, IL).The chi-square test was used for categorical data and the Mann Whitney U ranked sum test for continuous data. Correlations between variables was assessed using Pearson`s correlation coefficient. To compare the accuracy of the three scores as predictors of mortality in follow up period, the concordance c statistics (area under the receiver operating cures (ROC) was calculated. This statistics may vary from 0-1, with 1 indicating perfect discrimination and 0,5 indicating what is experienced by chance alone. A p values< 0,05 was considered statistically significant. All data are expressed as number (%) or mean (SD), (range). Table 2. CP, creatinine modified CP and MELD of study population. Table 3.CP, creatinine modified CP and MELD scores of the patients according to 6 months prognosis. RESULTS Table 1shows baseline characteristics of 80 patients with decompensated cirrhosis. They were predominantly male (62%). Patients with virus related cirrhosis and alcoholic cirrhosis were to main diseaseetiologies. During this period none of the patients underwent OLT. CP divided patients into three classes, A, B and C, 11,3%, 51,5% and 37,5% respectively with significantly different mortality rates (Table 2 and Table 3.) Table 3 shows patients who died within study period had significantly higher CP, the creatinine modified CP and the MELD scores compared to survived group (p <0,000).The 6 months mortality was 36%. Medicinski Еѕurnal 2013 бѓЂ19 (1): 48 - 53 All values are expressed as median (inter-quartile range). The Mann-Whitney U-test was used for statistical analysis, MELD model for the end stage liver disease. The accuracies of the three scores for 6 months mortality were compared. The creatinine-modified CP score showed a marginal better prognostic accuracy as compared with the traditional CP score (CP vs. creatinine вЂ“ modified CP, c statistics and 95% confidence intrevall CI(0,761 (0,64-0,87) vs. 0,846 95% confidence interval CI (0,75-0,94), while the MELD score showed a significantly higher prognostic value (c statistics 0,872 and 95%confidence interval CI (0,79-0,95) (Table 4, Figure1). DЕѕenela ProhiД‡, Rusmir MesihoviД‡, Nenad Vanis, SrД‘an GornjakoviД‡, Amra PuhaloviД‡, Aida Saray. Prognostic assessment in patients with decompensated cirrhosis Table 4. Sensitivity and specificity for all three tests used. Figure 1. ROC curve for Child Pugh (CP), creatinine modified Child Pugh (CP) score and the Model for End stage Liver Disease (MELD) scores. All three scores correlate with statistically significant correlation coefficients (p value <0,005), which means that they correlate in between (Table 5). Table 5.Matrix of correlations for all scores (all patients). CP score CP score Creatinine modified CP score MELD score r p r p r p 1 .00 0 0 0 0 .951 .0 .617 .0 Creatinine-modified CP score 0 .951 0 .0 1.0 0 0.756 0.0 1 MELD score 0.61 7 0.0 .756 0.0 .0 We have strongest correlation between the CP and the creatinine modified CP score, which amounts 95,1%. Correlation between MELD and Child Pugh scores is minimal, 61,7, % but still significant. DISCUSSION Prognosis is an essential part of the baseline assessment of any disease. It is not only the basis for the information that a physician provides to the patient, but is also the basis for any decision-making process. Establishment of prognostic factors is the key towards evaluating clinical interventions and treatment in any disease. The most commonly used prognostic model in patients with cirrhosis is the CP score. It has been reference for more than 30 years for assessing the prognosis of cirrhosis. It prognostic value has been validated in the settings of ascites, liver surgery, ruptured oesophageal varices, alcoholic cirrhosis, decompensated HCVrelated cirrhosis (19,20,21,22,23). MELD score comes as the most serious challenger for replacing the CP score and overcoming its limitations.The principal advantages of the MELD score are that it is based on variables selected by statistical analysis rather than clinical judgement, the variables are objective and unlikely to be influenced by external factors, each variable is weighted according its proper influence on prognosis and the score is continuous which helps scoring individuals more precisely among large populations (1,10,11). The MELD scoring system has been widely applied in recent years and shown to predict mortality across a broad spectrum of liver diseases in most studies (24,25,26). The utilisation of the MELD has been demonstrated to have an equal or better ability in short or intermediate term outcome prediction in comparison with CP score (16,27). An European series of cirrhotic patients showed that the MELD is useful in assessing both 6-month and 1-year survival (28). An American series of cirrhotic patients on OLT waiting lists and classified UNOS 2A or 2B, showed that the MELD score predicted the 3-month survival of patients better than the CTP (25). However, other researchers did not obtain the same results (29,30). In this study, the aim was to evaluate the 6 months mortality of patients with decompensated cirrhosis and to compare prognostic accuracy and correlation of the CP, the creatinine modified CP and the MELD score in series of patients with decompensated cirrhosis hospitalised at our department. The creatinin modified CP we used in our study was introduced by Giannini et al for several reasons (15). The development of renal failure in cirrhotics is the most important predictor factor of survival and it is possible that the perceived superiority of MELD to CP in chronic liver disease is related to using serum creatinine as variable (15,16,17,31,32) We hypothesised that including serum creatinine values in the traditional CP score would increase the prognostic accuracy of the score and challenged the prognostic strength of MELD. Our data support thesis that MELD score is significantly superior to CP score in predicting survival in patients with decompensated liver disease. The c-statistics for predictionof 6 months mor tality by the MELD score was found to be 0,872 Medicinski Еѕurnal 2013 бѓЂ19 (1): 48 - 53 51 52 DЕѕenela ProhiД‡, Rusmir MesihoviД‡, Nenad Vanis, SrД‘an GornjakoviД‡, Amra PuhaloviД‡, Aida Saray. Prognostic assessment in patients with decompensated cirrhosis comparing to c statistics of CP score 0,761 and creatinine modified CP score 0,846, which is compatible with previousfindings in studies of the patients with decompensated cirrhosis (15,28). Area under the curve indicates excellent diagnostic accuracy for all three scores. All three scores were shown to be predictive. The inclusion of creatinine as categorical parameter in traditional CP score was found to improve the predictive accuracy of CP score but still inferior to prognostic accuracy of MELD score. Correlation between all three testwere statistically significant. Notably, it showed highest correlation between the traditional CP and the creatinine modified CP score, which is expected since the creatinine modified CP is based on the CP score. This finding implicates that results we achieve with both tests significantly correlate with each other. CONCLUSION In conclusion, both MELD and CP scores can accurately predict 6 months mortality in patients with decompensated cirrhosis, while MELD appears to have slight higher statistical significance. Thus, our results demonstrate that use of the MELD score is preferred compared to CP score, inpopulations of wide spectrum of cirrhot icpatients with various degrees of liver disease outside of transplantation settings. Thecreati nine modified CP score seem to deserve further evaluation, since it is simpler than and of simi lar predictive accuracy with MELD score and have higher predictive accuracy than the old CP score. Conflict of interest: none declared. Acknowledgement:Professor Emina ResiД‡, Ph.D., for help with statistics. REFERENCES 1. Durand F, Valla D. Assessment of the prog nosis of cirrhosis: Child-Pugh versus MELD. J Hepatol. 2005; 42 Suppl.(1): S100-7. 2. Christensen E. Prognostic models including the Child-Pugh, MELD and Mayo risk scoreswhere are we and where should we go? 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Kidney Int. 1998 Aug; 54(3):518вЂ“24. 33. Christensen E, Krintel J J, Hansen S M, Johansen JK, Juhl E. Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis.Survival and prognostic factors. Scand J Gastroenterol. 1989 Oct; 24(8): 999вЂ“1006. veterans. Liver Transpl. 2007 Nov;13(11):1564-9. 27. Wang YW, Huo IT, Yang YY, Hou MC, Lee PC, Lin HC, et al.Correlation and comparison of the Model for End-Stage Liver disease, portal pressure, and serum sodium for outcome prediction in patients with liver cirrhosis. J Clin Gastroenterol. 2007 Aug;41(7):706-12. Address: DЕѕenela ProhiД‡, MD Clinic for Gastroenterohepatology Clinical Center University of Sarajevo BolniДЌka 25, 71000 Sarajevo Bosnia and Herzegovina Email: [email protected] Medicinski Еѕurnal 2013 бѓЂ19 (1): 48 - 53 53 54 Lejla IbriДЌeviД‡-BaliД‡, Rusmir MesihoviД‡, Alma Sofo-HafizoviД‡, Nenad Vanis, Е efkija BaliД‡, Semir BeЕЎlija. Etiology of anemia in patients with gastric lymphomas Professional article ETIOLOGY OF ANEMIA IN PATIENTS WITH GASTRIC LYMPHOMAS ETIOLOGIJA ANEMIJE KOD PACIJENATA SA LIMFOMIMA ЕЅELUCA 1* 2 1 2 Lejla IbriДЌeviД‡-BaliД‡ , Rusmir MesihoviД‡ , Alma Sofo-HafizoviД‡ , Nenad Vanis , 4 3 Е efkija BaliД‡ , Semir BeЕЎlija 2 1 Clinic of Hematology, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, B&H; Clinic for Gastroenterohepatology, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, B&H; 3 Clinic for Endocrinology, Diabetes and Metabolism Diseases, Clinical Center University of Sarajevo, 4 BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina; Clinic for Oncology, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT Aim of the study was to evaluate type of anemia in patients with gastric lymphoma. Anemia in patients with gastric lymphoma can be caused by iron deficiency, infiltration of bone marrow with malignant cells of lymphoma or effect of chronic disease. Group of 40 patients with gastric lymphoma (MALT, DLBCL lymphoma and other type) was analyzed. There was statistically significant difference between grades of anemia in patients with MALT lymphoma comparing to patents with DLBCL lymphoma. Conclusion: Anemia in patients with gastric lymphoma is multifactorial due to iron deficiency, presence of chronic disease and infiltration of bone marrow. Key words: gastric lymphoma, MALT lymphoma, DLBCL lymphoma, anemia of chronic disease SAЕЅETAK Cilj rada je procjeniti razvoj anemije hroniДЌne bolesti kod pacijenata sa limfomima Еѕeluca. Anemija se kod pacijenata sa malignim ne HoДЌkinovim limfomima moЕѕe razviti iz viЕЎe razloga, kao anemija hroniДЌne bolesti, u sklopu infiltracije limfomskim stanicama koЕЎtane srЕѕi te kao sideropeniДЌna anemija. Analizirana je grupa od 40 pacijenata lijeДЌen ih radi limfoma Еѕeluca. U grupi bolesnika sa MALT limfomom Еѕeluca evidentirana je statistiДЌki signifikantna razlika u stepenu anemije u odnosu na grupupa cijenata sa difuznim velikostaniДЌnim B limfomom Еѕeluca. Obzirom na tip anemije utvrdjeno je da je anemija kod MALT limfoma bila mikrocitna sideropeniДЌna usljed nedostatka serumskog Еѕeljeza, u odnosu na anemiju kod pacijenata sa DLBCL koji su imali normocitnu anemiju koja odgovara Medicinski Еѕurnal 2013 бѓЂ19 (1): 54 - 57 odgovara anemiji hroniДЌne bolesti. ZakljuДЌak: Kod pacijenata sa lim fomima Еѕeluca razvoj anemije je multifaktorijalan, a terapijski modalitet moЕѕe ovisiti o tipu limfoma kao i uzroku anemije. KljuДЌne rijeДЌi: MALT limfom, DLBCL limfom, anemija hroniДЌne bolesti INTRODUCTION Lymphomas present large heterogenic group of clonal proliferative diseases with different clinical presentation and pathologic and biologic characteristics (1). They are clonal tumors composed of mature and immature B, T and NK cells in different staged of differentiation according to World Health Organization WHO (1). Incidence of non-Hodgkin lymphoma is higher in men. Lymphomas can be aggressive or indolent depending of their type (2). Mature B lymphomas present more that 80% of all non-Hodgkin B lymphomas. MALT lymphoma is mucosa associated lymphatic tissue lymphoma which is composed of heterogenic group of small B cells including marginal zone cells, cells resembling monocytes, small lymphocytes, scattered immunoblasts and centroblasts. MALT lymphoma is indolent in clinical course (1). 50% of MALT lymphomas are lymphomas of gastrointestinal tract and almost half of them are gastric lymphomas. They mainly occur in organs without organized lymphatic tissue. Means age is 61 years. Bone marrow is infiltrated in 15-30% cases and it depends of primary site of tumor. Clinical presenta- Lejla IbriДЌeviД‡-BaliД‡, Rusmir MesihoviД‡, Alma Sofo-HafizoviД‡, Nenad Vanis, Е efkija BaliД‡, Semir BeЕЎlija. Etiology of anemia in patients with gastric lymphomas presented with dyspepsia, nausea, flatulaton and vomiting which is associated with gastritis caused by H.pylori infection. GI tract bleeding and obstruction is rare. B symptoms (weight loss, night sweats, fever and repeated infections) are not common (3). Diffuse large B cell lymphoma DLBCL is lymphoma composed of large B lymphatic cells with nucleoli large as/or larger then macrophage nucleoli or double size of normal lymphocytes (1). This is most common type of lymphoma. It presents as nodal and extranodal mass. Most common site of extranodal tumor is GI tract, mainly stomach. Prognosis and treatment of gastric lymphomas depend of its type and stage. MALT lymphomas are indolent and their progression is slow (4). Infiltration of bone marrow in stage IV does not contribute to outcome. DLBCL lymphomas are aggressive tumors and their prognosis is determined according to international prognostic index - IPI index for aggressive lymphomas: IPI index Unfavorable factors: age>60 years poor performance status (ECOGаёё2) advanced Ann Arbor stage (III-IV) involvement of extranodal sites аёё2 high LDH IPI index is adjusted for patients less than 60 years Prognostic models which calculate risk of death use level of hemoglobin or anemia as a part of prognostic criteria, which stresses out role of anemia in this group of patients.Anemia is manifested in about 40% of cases of lymphoma (5). It is found most commonly in advanced stages of the disease as well as in cases with B symptoms. Usually it is normocytic normochromic anemia with hemoglobin of 100-120 g/L. Anemia is defined as reduction of complete red blood cell mass or hemoglobin level in peripheral blood. Anemia is the most common comorbidity in patient with chronic diseases as well as patients with malignant diseases. It affects overall status and impairs patient in everyday activities. They are divided according to pathophysiological processes, but in clinical practice most common ones are microcytic anemias due to iron deficiency, normocytic anemia in chronic and inflammatory disease, macrocytic anemia with vitamin deficiency or anemias due to bone marrow infiltration with tumor cells (5,6,7). Iron deficiency is caused largely due to GI and gynecologic bleeding or inadequate intake. Bleeding from GI tract can be clinically insignificant but over long period of time can cause significant anemia. Normocytic anemia is mainly caused with impaired iron metabolism. Iron metabolism is closely regulated by efficient system of iron conservation and recycling by which only a part of daily requirements is replaced by duodenal uptake. Anemia of chronic disease or anemia of inflammation is characterized by normocytic or microcytic iron-refractory anemia, low serum iron and relatively preserved bone marrow depoes of iron. Pathogenic mechanism of this anemia if not well understood but is believed to be caused by shortened life span of erythrocytes and inadequate erythropoiesis due to effect of cytokines produced in inflammation process. Anemia in lymphomas can be caused also by infiltration of lymphatic cells in bone marrow. In some type of lymphomas it is considered as prognostic marker. Treatment of anemia with gastric lymphoma can be challenging process due to its multifactorial nature, since iron overload by therapeutic agents or erythrocyte transfusion can cause hemosiderosis with its significant side effects and can influence outcome of treatment. In this study we speculated that anemia presented in patients with gastric lymphomas is mainly caused by iron deficiency. MATERIALS AND METHODS Patient study It was single-center observational retrospective study. 40 patients which were treated at Clinic of Hematology and Clinic of Gastroenterohepatology with histological diagnosis of gastric lymphoma from 2002 and 2009 were analyzed. Medicinski Еѕurnal 2013 бѓЂ19 (1): 54 - 57 55 56 Lejla IbriДЌeviД‡-BaliД‡, Rusmir MesihoviД‡, Alma Sofo-HafizoviД‡, Nenad Vanis, Е efkija BaliД‡, Semir BeЕЎlija. Etiology of anemia in patients with gastric lymphomas Methods Data were collected from medical reports. Patents were assessed according to pathohistologic diagnosis as patients with MALT, DLBCL lymphoma or other type of lymphoma. Standard analysis of hematologic parameters such as leukocyte level, red blood cell count, hemoglobin level, mean corpuscular volume MCV, serum iron level, lactate dehydrogenase LDH, beta2microglobuline and albumin were analyzed and compared. Staging of lymphoma was done according to algorithm at Clinic of Hematology which included abdominal ultrasound (UZ), computerized tomography of abdomen and chest (CT), endoscopic ultrasound of stomach (EUS) and bone barrow biopsy. Stage of disease was determined with Ann Arbor classification modified by Musshoff and Radaszkiewics. Figure 2. Distribution of patients according to stage of disease. Table 1. Descriptive statistics of biohumorals parameters according to type of lymphoma DLBCL and MALT. Statistical analysis Correlation of clinical and biohumoral parameters was analyzed with variance analysis ANOVA and Student T-test for the data which had normal distribution, and Kruskal-Wallis and Mann-Whitney without normal distribution. Computer program SPSS Statistics 17.0 was used, p< 0,05 value was considered statistically significant. RESULTS Total number of 40 patients was evaluated, 21 male 52%, 19 female 48% in age from 31 to 78 (Figure 1). Figure 1. Distribution of patients according to sex. Out of 40 patients, 1 had Hodgkin lymphoma and 39 had non Hodgkin lymphoma from which 17 with DLBCL lymphoma, 15 MALT, 2 follicular lymphoma grade I, 1 anaplastic DLBCL, 1 mantle cell lymphoma and 1 Burkitt lymphoma. Stage of the disease was assessed according to Ann Arbor classification. There were 35 % patients in first stage, stage II 25%, stage III 25% and stage IV 15% (Figure 2). Medicinski Еѕurnal 2013 бѓЂ19 (1): 54 - 57 Patients with MALT type of lymphoma had lower levels of serum iron comparing to group of patients with DLBC lymphoma, with significance of p=0.010. Hemoglobin levels difference in these two groups did not have statistical significance. Patients with MALT lymphoma had lower level of ferritin in contrast to patients with DLBCL lymphoma with statistical significance of p=0.02. Table 2. Descriptive statistics according to the type of lymphoma in advanced and low stage of disease. There was no statistical significance in Hgb levels in IV stage of MALT and DLBCL, p=0.10. Lejla IbriДЌeviД‡-BaliД‡, Rusmir MesihoviД‡, Alma Sofo-HafizoviД‡, Nenad Vanis, Е efkija BaliД‡, Semir BeЕЎlija. Etiology of anemia in patients with gastric lymphomas DISCUSSION Gastric lymphoma is relatively rare disease. According to histologic type most common type is MALT, then DLBCL lymphoma and other types of B cell lymphoma in lower percent. In this study there were 48 % female patents and 52% male with average age of 54.5 years. These data are in accordance with similar published data (8). This study found that 65 % of patients with gastric lymphoma were in advanced stage II, III i IV while 35% were in stage I. Staging was performed by Ann Arbor staging system. Radere etal. found similar results in their study of newly diagnosed gastric lymphomas where 43 % patients were in advanced stage of disease. These results are compatible, most probably since both the studies used same method, Ann Arbbor staging system in diagnostic procedure. Anemia in group of patient with MALT lymphoma comparing to the DLBCL group was more expressed, with statistical significant difference. Zucca et al. noted microcytic sideropenica anemia, iron deficiency and in some cases only microcytosis without anemia (9,11 ). Their results correlate with results from this study. Difference in iron levels in these two groups may be related due to indolent nature of the MALT lymphoma. B symptoms only occur in later time. Slow progression of disease may cause occult hemorrhage from GI tract which lasts longer period of time. Other cause is probably anemia of chronic disease. It is specific due characteristic disturbance of iron metabolism, where release of iron from tissues to blood is blocked, mainly from RES system (reticuloendothelial system) (9, 10). Sub clinical form of hemolysis might be present due to shortened life span of red blood cells as well as relative renal impairment. It is usually caused by inhibition of production of erythrocytes in adequate numbers to compensate their increased destruction. Serum level of ferritin so far was used to distinguish more accurately iron deficiency anemia from anemia of chronic disease. But it can also be misleading since ferritin is protein of inflammatory faze (10, 11). Lower serum iron levels may also be caused by reduced uptake due to loss of appetite. Unlike MALT lymphoma MALT, DLBCL Low iron levels in serum may also be caused by reduced absorption due to loss of appetite (12). Unlike MALT lymphoma, DLBCL lymphoma is aggressive disease whose constitutional symptoms occur earlier, therefore they are diagnosed earlier and there is not enough time for anemia of chronic disease to develop or gastrointestinal bleeding lasts for shorter period of time. Analysis of subgroup of patients in IV clinical stage with infiltration of bone marrow with lymphoma did not show statistically significant difference in hemoglobin levels or anemia. It is possible to conclude that different level of anemia in MALT and DLBCL lymphoma patents most probably is not affected by type of lymphoma. CONCLUSION Anemia in gastric lymphoma is multifactorial and therapeutical approaches are different. Treatment of anemia will depend of predominant cause and it should be treated with great care. Anemia is essential as part of prognostic model of risk factors of death, since MALT lymphoma is indolent lymphoma in clinical course while DLBCL lymphoma is aggressive type of disease. Development of anemia in this group of patients if not completely understood and further studies should be conducted in illuminating this problem. Conflict of interest: none declared. REFERENCES 1. Swerdlow S, C ampo E, Harris NL,et al .WHO Classification of Tumors of Haematopoetic and Lymphoid Tissues. 4th ed. Lyon: IARC 2008. pp.158, 163-4, 214-7, 233-7. 2. Young N, Gerson S, Hugh K. Clinical hemathol ogy. Amsterdam: Elsevier Inc., 2006; pp. 505-510, 517-518. 3. Bacon C, Ming-Ding D, Dogan A, Mucosa-associated lymphoid tissue (MALT) lymphoma; a practical guide for pathologist. J Clin Pathol. 2007;60:361-372. 4. Fusaroli P, Buscarini E, Peyre S, Federici T, Parente F, De Angelis C, et al., Interobserver agree ment in stageing gastric lymphoma by EUS. Gastro intest Endosc. 2002 May; 55(6):662-8. 5. Hoepffner N, Lahme T, Gilly J, Menzel J, Koch P, Foerster EC. Value of endosonography in diagnostic staging primary gastric lymphoma (MALT type). Med Klin (Munich). 2003 Jun 15; 98(6):313-7. 6. Nakamura S, Matsumoto T, Suekane H, Takeshita M, Hizawa K, Kawasaki M, et al. Predictive value of endoscopic ultrasonography for regression of gas tric low grade and high grade MALT lymphomas after eradication of Helicobacter pylori. Gut. 2001; 48: 454-460. 7. Ruskone-Fourmestraux A, Lavergne A, Aergerter PH, Megraud F, Palazzo L, deMascarel A, et al. Pre dictive factors for regression of gastrtic MALT lym phoma after anti-Helicobacter pylori treatment, the Grouped Etude des Lymphomas Digestifs (GELD). Gut. 2001; 48: 297-303 8. Boot H. Diagnosis and staging in gastrointestinal lymphoma. Best Pract Res Gastroenterol. 2010 Feb; 24(1):3-12. Address: Lejla IbriДЌeviД‡-BaliД‡, MD Clinic of Hematology Clinical Center University of Sarajevo BolniДЌka 25, 71000 Sarajevo Bosnia and Herzegovina Phone: +387 33 297 240 Email:[email protected] Medicinski Еѕurnal 2013 бѓЂ19 (1): 54 - 57 57 58 Sajma Dautovic-KrkiД‡, Alma Sijamija, NedЕѕad HadЕѕiД‡, Hilmo ДЊaluk. Cardioborreliosis in Bosnia and Herzegovina Professional article CARDIOBORRELIOSIS IN BOSNIA AND HERZEGOVINA KARDIOBORELIOZA U BOSNI I HERCEGOVINI Sajma Dautovic-KrkiД‡В№*, Alma SijamijaВІ, NedЕѕad HadЕѕiД‡ВІ, Hilmo ДЊalukВІ 1 Sajma KrkiД‡-DautoviД‡ , KoЕЎevo 22, 71000 Sarajevo, Bosnia and Herzegovina; ВІCantonal Hospital Travnik-Internal Department, 72270 Travnik, Bosnia and Herzegovina *Corresponding author ABSTRACT Lyme borreliosis is a zoonotic disease caused by borrelia genus Borrelia burgdorferi sensu lato, which has 14 genospecies. Although the disease is often manifested with clinical signs of erythema migrans, it can present a multisystem disorder with abstraction joints, nervous system, heart, rarely, kidney, liver, skin or any other organ, myocarditis occurs in 2-10% of cases. Based on the clinical presentation it is not possible to assess the etiology of myocarditis, and when the suspect Lyme myocarditis is difficult to estimate if dissemination (stage 2) already occurred. In this paper we present three cases of cardioboreliosis hospitalized with clinical manifestations of acute carditis and arrhythmias, AV block II and grade III. This is the first case report of Lyme myocarditis in Bosnia and Herzegovina literature. Keywords: myocarditis, Lyme disease, cardioborreliosis SAЕЅETAK Lyme boreliosis je zoonoza uzrokovana boreli jama genusa Borrelia burgdorferi sensu lato koja ima 14 genospecijesa. Iako se bolest ДЌesto manifestira kliniДЌkom slikom koЕѕnog Erythema migrans, ona moЕѕe predstavljati multisistemski poremeД‡aj sa zahvaД‡anjem zglobova, nervnog sistema, srca, rjeД‘e bubrega, jetre, koЕѕe ili bilo kog drugog organa. Boreliozni miokarditis se javlja u 2-10% sluДЌajeva. Na temelju kliniДЌke slike nije moguД‡e procijeniti etiologiju miokarditisa, a kad se posumnja na Lyma miocarditis teЕЎko je procijeniti radi li se o ranoj diseminaciji i lokaliziranoj infekciji (stadij 1) ili je veД‡ doЕЎlo do diseminacije (stadij 2). U ovom radu smo prezentirali tri sluДЌaja kardioborelioze hospitalizirana sa kliniДЌkim manMedicinski Еѕurnal 2013 бѓЂ19 (1): 58 - 62 ifestacijama akutnog karditisa, pankarditisa i poremeД‡aja ritma, AV bloka II i III stepena. KljuДЌne rijeДЌi: miokarditis, Lajmska bolest, kardioborelioza INTRODUCTION Lyme borreliosis is a zoonotic disease caused by borrelia genus Borrelia burgdorferi sensu lato, which has 14 genospecies, some of which are pathogens: B.burgdorferi (sensu stricto), and B.afzelii B.garini, transferred to humans by forest ticks. Lyme borreliosis can present as early and as late infections (1,2,3). Although the disease often manifests itself early as an erythema migrans at the site of a tick bite (stage I) after infection generalization it may represent a multisystem disorder (stage II). Joints are most frequently affected (migratory arthralgia, pain in muscles, bones, tendons, bursae, brief arthritis), nervous system (mono-and polyneuritis, paresis of the facial nerve, radiculo neuritis, lymphocytic meningitis) heart (AV block I, II, III degree and pankarditis), significantly less kid ney, liver, eye, skin, and lymph glands. (3,4,5,6, 7,8,9). Late Lyme borreliosis-persistent infection, is the third stage, manifested by severe rheuma tological symptoms (prolonged attacks of arthritis, chronic arthritis, periostitis), symptoms related to skin (Acrodermatitis atroficans) and neurological manifestations (chronic encephalomyelitis, spastic paraparesis, mental disorders) (9,10,11). The dis ease occurs seasonally throughout the world, from early spring to late fall, usually in people who often reside in nature, professionally or recreationally (9, 10,11,12,13,14). In about 10% of patients infect ed with the spirochete Borrelia burgdorferi cardiac symptoms, transient character will usually occur. Cardioborelliosis may manifest primarily as AV Sajma Dautovic-KrkiД‡, Alma Sijamija, NedЕѕad HadЕѕiД‡, Hilmo ДЊaluk. Cardioborreliosis in Bosnia and Herzegovina conduction disturbances, and very rare as myocarditis and pancarditis, which represents the second stage of Lyme borreliosis. Myocarditis is defined as myocardial inflammation caused by infectious and non-infectious causes. Histological basis is myocyte degeneration and necrosis, not ischemic in origin, associated with inflammatory infiltration (16,17). Damage is caused by weakening of the myocardium contractility, usually of both ventricles and dilatation occurs reducing the stroke volume of the heart. If the process affects conduction system of heart arrhythmias and conduction disorders which causes further deterioration of the hemodynamics of the heart. Etiologic diagnosis requires extensive bacteriological, parasitological and serological tests. ECG changes are not specific. They are manifested in the form of dislocation of ST segment, T wave inversion and different atrial and ventricular arrhythmias and atrio-ventricular (AV) block. Complete AV block occurs in 15% of patients, associated with syncope, usually transitory in character. X-ray of lungs and heart usually shows normal heart size, but dilatation can be detected and, with signs stasis in the lungs, and pericarditis. Ultrasonography detects signs of systolic and diastolic dysfunction of both ventricles, dilatation of ventricular cavities, abnormal myocardial contractility and focal or diffuse inflammation of the affected area. Endomyocardial biopsy and histopathological analysis is still considered the gold standard. Etiological therapy is required, increased physical activity, which increases cardiac work, exacerbates myocardial inflammation and increases morbidity and mortality (17). It is recommended to use antipyretics but not salicylates and NSAIDs, because of increase of myocardial injury in the first two weeks of illness. Myocarditis in most cases leaves no permanent damage because there is complete healing and restoring of ventricular function. Borrelia can be isolated from the blood of patients of Borrelia myocarditis (6, 7). The disease can be confirmed by evidence of the existence of specific antibodies to Borrelia (18,19). Microbiological diagnosis is based on serological tests, usually immunofluorescence (IFA), enzyme linked immuno assay (ELISA) and immunoblot (WB), and polymerase chain reaction (PCR) in diagnosing Lyme arthritis (9,18,19). Cardioborreliosis treatment with antibiotics is useful for all stages of the disease, but is most successful in the first stage, if it is recognized. The goal of treatment of early stage Lyme disease 59 is reduced signs and symptoms of erythema migrans, and to remove or reduce the risk of late manifestations of disease. In this sense, different treatments have been attempted, so the experience is different from author to author (20, 21, 22, 23, 24, 25, 26, 27). The aim was the presentation of three cases of cardioborreliosis in different areas of Bosnia and Herzegovina. Case No. 1: 17 years old female patient, student, was sent to the Infectious Diseases Clinic because of loss of consciousness during the training course. The patient was previously reviewed by an internist who found subfebrility, catarrhal angina, and bradycardia. At examination patient gives data dizziness, heart palpitations. The day before the patient complained on sore throat. She was afebrile, conscious, bradycardic 42/min, RR 100/80, with inflamed throat, normal auscultator findings on lung, normal neurological findings and all other findings were normal. In laboratory findings mild leukocytosis (12,3), with 72% neutrophils, other basic laboratory tests (done on urea, creatinine, fibrinogen, and transaminase) were normal. ECG showed third degree block, frequency 38/min. Hospitalization was refused by patient, and agreed to the outpatient monitoring and treatment with amoxicillin with clavulonic acid. At control after 2 weeks patient was in good general condition and was submitted to the control of internal medicine and ECG. On next appointment patient remembered a tick bite one month before the crisis of consciousness. Redness of annular shape that spreads to the chest at the spot of the bite did not bother her, had no itching, and disappeared after three weeks without treatment. ELISA and Western blot tests were done and found positive results. Type Value Borrelia burgdorferi IgM 1628 Borrelia burgdorferi IgG 492U/m l B. burgdorferi (WB) IgM 16 points Evaluation Positive Positive Positive Subsequent doxycycline therapy was performed, patient was followed for another 2 months, and clinical findings and ECG findings were normal. Case No. 2: Patient F.D., male, 30 years old, from Travnik, was hospitalized on the fifth day of disease due to epigastric pain, feeling short of breath, difficult breathing, rapid fatigue, general weakness, malaise. Findings on admission: conscious, oriented, normal breathing sounds with single whistles. ECG on admission: second degree AV block type Wenckebach, ventr. fr. 43/min. Control ECG the following day: AV block second degree Mobitz II ventr. fr.33/min. Medicinski Еѕurnal 2013 бѓЂ19 (1): 58 - 62 60 Sajma Dautovic-KrkiД‡, Alma Sijamija, NedЕѕad HadЕѕiД‡, Hilmo ДЊaluk. Cardioborreliosis in Bosnia and Herzegovina Figure 1. ECG on admission Control ECG recordings show repeatedly AV block of the second degree which, AV block of the first degree and ECG at discharge: normogram, sinus rhythm, PQ interval of 0.20 sec.The third day of hospitalization 24 hour ECG Holter monitoring was done: AV block I and II degree Wenckebach type was registered, the average chamber frequency 47/min. The highest frequency was 84/min during increased physical activity. The lowest frequency was 28/min. 19 individual VES were registered. There were 163 episodes of bradycardia, frequency <50/min. in total duration of 17.6 h. 3224 prolongation of RR intervals> 2.1 sec. The longest RR interval was 3.4 sec. Significant dislocation of ST segment is not registered. During patient monitoring no subjective complaints were noted. Laboratory findings: SE 20/50; RBC ll, 5g/dl; PLT 132; WBC 10.2;AST 18 IU; ALT 38 IU L; CRP 16.0 mg / L; Rheuma factor <40 IU / ml, waler Rose negative. At the control testing all findings were normal. Echocardiography: a little wider cavitary dimensions of both atria, increased left ventricular cavitary dimensions. Preserved ejection fraction, 64.65%. Valves without significant morphological changes. Mitral and tricuspidal regurgitation of second degree, secondary, without hemodynamic repercussion. No pulmonary hypertension. Pericardium without pathological fluids. Echocardiographic signs of marked dilatation of the left ventricle and both atria. Given the transient nature of AV block and the course of disease, infective carditis was suspected. Subsequently information about a tick bite a month before coming to the hospital was obtain, and a description of skin lesions on the right thigh by type of erythema migrans. Medicinski Еѕurnal 2013 бѓЂ19 (1): 58 - 62 We performed a serological analysis of Borrelia at the Institute of Microbiology, University Clinical Center Sarajevo. The results are summarized as follows. Search Type: ELISA Type Value Evaluation Borrelia burgdorferi IgM 1817 from the positive Borrelia burgdorferi IgG 353 U / ml positive B. burgdorferi IgM (WB) 20 points positive Mycoplasma pneumoniae: IgM is negative findings, IgG (15.6 NTU) is positive. Serology of Coxiella burnetii and Brucella was repeatedly negative. Case No. 3: Patient S.M. (30 years old) admitted to the intensive care unit with internal departments because of the crisis of consciousness, dizziness, vertigo, headache, fever, ECG verified third degree AV block, and ECHO verified small pericardial effusion. From social and epidemiological data: living in the countryside, had a tick bite 20 days prior to admission, rash of the type of erythema migrans at the site of bites on the left thigh. On admission: conscious, oriented, communicative, sub-febrile. Bradicardia was noted, TA 130/80 mmHg, pulse: 36/min. Laboratory findings: ESR: 25/50, RBC 4.36, MCV 87.9, HCT 38.4, HGB 12, 8, PLT 251, WBC 10.8; GRA 79.2% (H) 17.9 Ly (L), AST / ALT 24/60 U / L, Other findings were within reference values. ECG: at the reception: complete AV block / stage III with a ventricular freq. 36/min. Upon admittance antibiotic therapy with amoxicillin and doxycycline was started with analgesics, antipyretics, salicylates at a later stage, with clinical improvement after three days: transient AV block character. Serology testing con firmed previously suspected M.Lyme. Figure 2. ECG on admission Sajma Dautovic-KrkiД‡, Alma Sijamija, NedЕѕad HadЕѕiД‡, Hilmo ДЊaluk. Cardioborreliosis in Bosnia and Herzegovina Serological tests: Search type: ELISA Type Value Evaluation Borrelia burgdorferi IgM 1261 from the positive Borrelia burgdorfer IgG 730 U / ml positive 14 points 21 points positive positive Borrelia burgdorferi (WB) IgM Borrelia burgdorferi (WB)IgG Serologic response to ECHO and Coxackie viruses showed earlier contact and had no significance for the present illness. The third day of hospitalization 24 hour ECG Holter monitoring was performed: basic sinus rhythm, the average chamber frequency 70/min. The highest frequency (fr.) was 138/min (8:13). The lowest frequency was 45/min. (03:21). There was a VES, an episode of SVT in the total duration of 2.2 second. Registered tachy cardia: 48 episodes, fr.> 100/min. for a total of 44.6 min.te 28 episodes of bradycardia, fr. <50/ min. in total duration of 19.5 min. During 24 hour monitoring registered a first degree AV block with a PQ interval of 0.40 sec.i two episodes sinus pauses> 2.1 sec. type second degree AV block (Mobitz II). Significant ST segment dislocation is not registered. The patient was discharged in good clinical condition. ECG at discharge: normogram, sinus rhythm, fr.59/minute. PQ interval 0.24 sec. Echocardiography: Cavitary dimensions of the heart showed normal values. Parameters of systolic and diastolic function of normal. EF 67.48%. Pericardium showed a smaller pericardial effusion without hemodynamic repercussion. Systolic separation of 12 mm, diastolic separation of 2 mm. Mitral and tricuspidal mild degree regurgitation. At the first control after one month, improvement of all parameters in comparison with findings at admission was registered. amoxicillin with probenecid, cefuroxinom / cefuroxim axetil and doxycycline during 21 days, while azithromycin therapy for 7 days less efficient than the previous (21,22,23). Oral doxycycline treat ment of early disseminated phases of Lyme is as effective as a treatment of intravenous ceftriaxone during 14 days (21). All three patients presented (one treated at the outpatient clinic in Sarajevo and two hospitalized at an internal department of Travnik) on admission were in the second stage of Lyme borreliosis. Patient treated for syncope and sore throat at all had conduction disturbances and AV block caused by borreliosis lesion. Amoxicillin therapy was conducted for 10 days, then with doxicyclin two weeks. The other two patients had the clinical manifestation of acute carditis; pancarditis disorder and conduct, along with AV block II or III level. They were treated with antibiotic therapy: Ceftriaxone 2xl g iv Doxycycline and 2x100 mg tablets, along with symptomatic therapy. The recovery was very good, and cardiac disturbances were resolved. After discharge at the first control, both our patients had normal clinical and ultrasound findings. CONCLUSION - Lyme disease occurs in Bosnia and Herzegovina in various clinical forms. - Cardio borreliosis occurs rarely, but it is diagnosed. - It is necessary to think of cardioborreliosis in all patients with cardiac symptoms unexplained etiology. - Early treatment with antibiotics according to the recommended protocols leads to complete healing of Lyme myocarditis. DISCUSSION Conflict of interest: none declared. Infective myocarditis starts with general symptoms, fever, fatigue, arthralgias, but palpitations and syncopa can be presenting symptoms. Miocarditis can be asymptomatic during the course of infectious diseases, and in more then half of patients disease is undiagnosed. For diagnosis beside clinical presentation and data about tick bites serological confirmation is needed except for typical early skin lesions (18,19,20). However, even erythema migrans may not be pathognomonic for Lyme borreliosis, where there is no microbiological evidence of infection. 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KuЕЎljugiД‡ Z, BarakoviД‡ F, ArslanagiД‡ A, Gerc V i sar. Kardiologija. Tuzla: PrintCom; 2006. str. 395-437. 17. Cooper LT Jr. Giant Cell Myocarditis.In: Crawford HM (ed). Valvular heart disease. New York: Mc GrawHill; 2003; pp.196. (Lange medical Books). 18. Wilske B, Preac-Mursic V. Microbiological diag nosis of Lyme borreliosis. In: Webwr K, Burgdorfer W. Aspects of Lyme borreliosis. Berlin: Springer; 1993. pp. 267-300. Medicinski Еѕurnal 2013 бѓЂ19 (1): 58 - 62 19. Mwlchers W, Meis J, Rosa P, Claas E, Nohlmans L, Koopman R, et al. Amplification of Borrelia burgdorferi DNA in skin biopsies from patients with Lyme disease. J Clin Microbiol. 1991Nov; 29(11):2401-6. 20. BolanДЌa-Bumber S, Е itum M, BaliД‡ Winter A. First isolation of Borrelia burgdorferi sensu loto in Croatia. Acta Dermatovenerolog Croat. 1997;5-95-9. 21. Dattwyler RJ, Volkman DJ, Conaty SM, Platkin SP, Luft BJ. Amoxicillin plus probanecid versus doxycyclin for treatment of erythema migrans borreliosis. Lancet. 1990 Dec; 336 (8728):1404-6. 22. Luger SW, Paparone P, Wormser GP, Nadelman RB, Grunwaldt E, Gomez G, et al. Comparison of cefuroxime axetil and doxycyclin in the treatment of patient s with early Lyme disease associated with erythema migrans. Antibicrob Agents Chemother. 1995 Mart; 39(3):661-7. 23. Nadelman RB, Luger SW, Frank E, Wisniewski M, Collins JJ, Wormser GP. Comparison of cefuroxim axetil and doxycyclin in the treatment of Lyme dis ease. Ann Intern Med. 1992 Aug; 117(4):273-80. 24. Dattwyler RJ, Luft BJ, Kunkel MJ, Finkel MF, Wormser GP, Rush TJ, et al. Cefrtriakson compared with doxycyclin for the treatment of acute diseminated Lyme disease. N Engl J Med. 1997 Jul 31;337(5):289-94. 25. Nowakowski J, Mckenna D, Nadelman RB, Cooper D, Bittker S, Holmgren D, et al. Failure of treatment with cephalexin for Lyme disease. Arch Fam Med. 2000 Jun; 9(6):563-7. 26. Agger WA, Callister SM, Jobe DA. In vitro susceptibilites of Borrelia burgdorferi to 5 oral cephalosporins and cephtriaxone. Antimicrob Agents Chemother. 1992 Aug ;36 (8):1788-90. 27. DautoviД‡-KrkiД‡ S. Borelioza: U: DautoviД‡-KrkiД‡ S, ured. Infektologija. Sarajevo-Tuzla: Medicinski fakultet; Asocijacija infektologa u Bosni i Hercegovini; 2011. str. 227-229. Address: Prof. Sajma DautoviД‡-KrkiД‡, MD, PhD вЂћPrivate outpatient clinicвЂќ KoЕЎevo 22, 71000 Sarajevo, Bosnia and Herzegovina Phone: +387 70 255 055 Email:[email protected] Anida ДЊauЕЎeviД‡-RamoЕЎevac, Lejla ZoliД‡. Antimicrobial safety of fluoroquinolones: special focus on norfloxacin Review article ANTIMICROBIAL SAFETY OF FLUOROQUINOLONES: SPECIAL FOCUS ON NORFLOXACIN ANTIMIKROBNA SIGURNOST FLUOROKINOLONA: POSEBAN OSVRT NA NORFLOKSACIN Anida ДЊauЕЎeviД‡-RamoЕЎevac*, Lejla ZoliД‡ Bosnalijek, Pharmaceutical and Chemical Company, JukiД‡eva 53, 71 000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT Monitoring of drug safety and tolerability is of great importance, which is why in recent years, adverse effects associated with certain medications and drugs have attracted distinct groups of health care workers. A perfect source of data for individual quantification of risk assessment does not exist. However, the data obtained from preclinical testing, phase 1-3 trials, and post-marketing experience can be of great use to assess the risk associated with a particular drug or group of drugs. Fluoroquinolones (FQs) have been on the market for more than 25 years and are considered as safe antibiotics. They are well tolerated and have a safety profile similar to other antimicrobial drugs. The most commonly reported adverse effects associated with the use of fluoroquinolones include gastrointestinal system (nausea and diarrhea) and central nervous system (CNS) (headaches and dizziness). The listed adverse effects are generally mild in character and do not require discontinuation of therapy. Less common and potentially serious adverse effects associated with the mentioned group of antimicrobials include the CNS (e.g., generalized seizures), liver (e.g. hepatitis, acute liver failure), kidney (e.g., acute interstitial nephritis, renal failure), immune system (hypersensitivity reactions), skin (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, phototoxity), musculoskeletal system (e.g., arthritis, tendon rupture) and cardiovascular system (e.g. QTc prolongation, torsades de pointes). Rare adverse effects that can be associated only with some members of the group of quinolones (e.g., torsades de pointes, hepatotoxicity), in turn, have a higher probability of occurrence in certain вЂњsensitiveвЂќ individuals. This review will focus on the recently published literature on safety of fluoroquinolones and is based on a detailed search of several databases, primarily Medline and MICROMEDEX. Key words: fluoroquinolones, drug safety, adverse effects, norfloxacin SAЕЅETAK PraД‡enje sigurnosti i podnoЕЎljivosti lijeka je od izrazitog znaДЌaja, zbog ДЌega su tokom posljednjih godina neЕѕeljeni efekti koji su povezani s odreД‘enim lijekovima i skupinama lijekova privukli izrazitu paЕѕnju zdravstvenih radnika. SavrЕЎen izvor podataka za individualnu kvantifikaciju procjene rizika lijeka ne postoji. MeД‘utim, podaci dobiveni iz pretkliniДЌkih testiranja, faza 1-3 ispitivanja, kao i iz postmarketinЕЎkog praД‡enja mogu biti od velike koristi za procjenu rizika povezanu s odreД‘enim lijekom ili skupinom lijekova. Fluorokinoloni se nalaze na trЕѕistu duЕѕe od 25 godina i predstavljaju sigurne antibiotike. Dobro se podnose i imaju sigurnosni profil sliДЌan drugim antimikrobnim lijekovima. NajДЌeЕЎД‡e prijavljeni neЕѕeljeni efekti povezani s primjenom fluorokinolona ukljuДЌuju gastrointestinalni sistem (muДЌnina i proljev) i centralni nervni sistem (CNS) (glavobolja i vrtoglavica). Ispred navedeni neЕѕeljeni efekti su uglavnom blagog karaktera i ne zahtijevaju prekid terapije. Manje ДЌesti i potencijalno ozbiljni neЕѕeljeni efekti povezani s ispred navedenom skupinom lijekova pak ukljuДЌuju i CNS (npr. generalizovani napadi), jetru (npr. hepatitis, akutno zatajenje jetre), bubrege (npr. akutni intersticijalni nefritis, zatajenje bubrega), imuni sistem (reakcije hipersenzitivnosti), koЕѕu (npr. toksiДЌna epidermalna nekroliza, Stevens-Johnsonov sindrom, fototoksiДЌnost), miЕЎiД‡no-koЕЎtani sistem (npr, artritis, perforacija tetiva) i kardiovaskularni sistem Medicinski Еѕurnal 2013 бѓЂ19 (1): 63 - 68 63 64 Anida ДЊauЕЎeviД‡-RamoЕЎevac, Lejla ZoliД‡. Antimicrobial safety of fluoroquinolones: special focus on norfloxacin (npr. QTc prolongacija, torsades de pointes). Rijetki neЕѕeljeni efekti, koji se mogu pripisati iskljuДЌivo pojedinim ДЌlanovima skupine kinolona (npr. torsades de pointes, hepatotoksiДЌnost), pak, imaju veД‡u vjerovatnoД‡u nastanka u odabranih вЂњosjetljivihвЂќ osoba. Ovaj pregled Д‡e se dotaД‡i nedavno objavljene literature o sigurnosti fluorokinolona i zasnovan je na opseЕѕnom pretraЕѕivanju razliДЌitih baza podataka, prvenstveno Medline-a i MICROMEDEX-a. KljuДЌne rijeДЌi: fluorokinoloni, norfloksacin, sigurnost lijekova, neЕѕeljeni efekti INTRODUCTION Fluoroquinolones (FQs), derivatives of nalidixic acid, are antibiotics with a broad spectrum of activity. First quinolone, nalidixic acid, was introduced in 1962. Since then, structural modifications have resulted in the emergence of fluoroquinolone of second, third and fourth generation, which have improved activity against gram-positive organisms. In the past decade, fluoroquinolones have become important drugs in the treatment of many infections of various organs and degrees of severity. Antimicrobial activity and pharmacological properties of fluoroquinolones indicate their potential clinical application in the treatment of infections of the urinary system and gonorrhea, as well as in infections of other body parts. Generally, fluoroquinolones could be used in the treatment of bacterial infections in patients in whom other drugs such as beta-lactams or aminoglycosides are contraindicated, and in the treatment of infections caused by multi-resistant bacteria. After more than twenty years of application, norfloxacin (NFLX) is still considered an effective representative of the quinolone group. Norfloxacin is a significant oral antimicrobial agent with a broad spectrum of bacterial activity that includes many bacteria that are resistant to other agents. It is indicated in the treatment of (1) Upper and lower, complicated and un complicated, acute and chronic urinary tract infections caused by bacteria sensitive to norfloxacin. These infections include cystitis, pyelitis, chronic prostatitis, and infections that are associated with urological surgical operations, neurogenic bladder or nephrolithiasis; вЂў Uncomplicated gonorrhea; вЂў Infectious diarrhea, including travelerвЂ™s diarrhea. Evaluation of safety and antimicrobial profile on basis of molecular structure of fluoroquinolones Medicinski Еѕurnal 2013 бѓЂ19 (1): 63 - 68 All quinolones derive from quinine. However, the chemical structure differs between members of certain generations. The current classification of fluoroquinolones includes first, second, third and fourth generation of these antibiotics. The first modification in the quinolone molecule was the introduction of floure at position 6 and piperazine ring at position 7, which resulted in better antimicrobial spectrum compared to that of nalidixic acid (2, 3). Adding a cyclopropyl to the fluoroquinolone fundamental molecule has also enhanced their bio logical application while modifications obtained by introducing a group of piperazine to the third and fourth generation of fluoroquinolones improved their activity against streptococci. Increased activity against anaerobic microorganisms evolved as a result of changes, such as addition of a 8-methoxy group to gatifloxacin. Correlation between the structure of quinolones and their antimicrobial activity is well established. As there is a correlation between the structure of quinolones and their activity, there are also associations between their structure and the reported adverse effects (3). Therefore, potential adverse reactions to fluoroqui nolones could be predicted on the basis of their molecular structure. The presence of substitution groups at certain positions of fluoroquinolone molecules is responsible for their adverse effects (4, 5). At position C-1, most fluoroquinolones contain ethyl, cyclopropyl and 2,4-difluorophenyl groups. While cyclopropyl boosts clastogenicity and interacts with theophylline, 2,4-difluorophenyl group does not cause adverse reactions. The positions C-3 and C-4 are responsible for the mechanisms of metal halation, while the groups at position C-5 affect phototoxity and genotoxicity (6). Position C-7 is the most important since groups at this position are responsible for neurological and psychiatric adverse reactions, mostly seizures. This position and groups located at this position affect the inhibition of binding of gamma-aminobutyric acid (GABA) to its receptor (7, 8). Substituted pyrrolidine at this position 7 is responsible for the cytotoxicity, while position C-8 is the most important position for phototoxity and genotoxicity (6) (Figure 1). Figure 1. Structure - adverse reaction relationship. Anida ДЊauЕЎeviД‡-RamoЕЎevac, Lejla ZoliД‡. Antimicrobial safety of fluoroquinolones: special focus on norfloxacin Safety / tolerability of norfloxacin in clinical trials; Considering the large number of clinical studies and extensive clinical use world-wide, safety/tolerability profile of NFLX has been well established. To a great extent, safety/tolerability aspects of NFLX are common to FQs in general, but there are also drug-specific differences. Incidence of adverse events of norfloxacin in clinical trials (9,10,11). The first systematic overview of safety/tolerability of NFLX in clinical trials was provided by Holmes et al. in 1985 (9). Since that time, several other overviews have been published with up-dated information. The latest review providing this kind of information is that by Ball et al. (10). Safety/tolerability data from clinical trials are also comprehensively presented in the currently approved FDA monograph on Noroxin (11). These sources were used for the purpose of this report (Table 1). Table 1. Incidence of adverse events in clinical trials with NFLX as reported in respective reviews. Holmes et al. 1985 (9) 1162 patients; 2x400 mg NFLX for 3-10 days in treatment of UTI Gastrointestinal all вЂ“ 2.2% Nausea вЂ“ 1.1% Dyspepsia вЂ“ 0.3% Abdominal pain вЂ“ 0.2% Others(< 0.1%): diarrhea, anorexia, dysphagia, tongue enlargement) CNS all вЂ“ 1.5% Dizzines вЂ“ 0.5% Headache вЂ“ 0.3% Others(< 0.1%): depression, euphoria, hallucinations, insomnia, somnolence, dry mouth. Dermatological all вЂ“ 0.5% Erythema 0.17% Pruritus - 0.17% Rash - 0.26% Noroxin FDA monograph 2007 (11) 82he althy 52he althy subjectsand subjects and 228 patients 1980 patients with gonorrhea: with UTI: NFLX (2x200 NFLX 1x800 mg or 2x400 mg) from 3 days to several weeks Nausea вЂ“ 4.2% Nausea вЂ“ 2.6% Dizziness вЂ“ Headache вЂ“ 2.6% 2.8% Headache вЂ“ Dizziness вЂ“ 2.0% 1.7% Abdominal Asthenia вЂ“ pain- 1.6% 1.3% Others Others (<1.0%): (<1.0%): anorexia, abdominal diarrhea, pain, back hyperhidrosis, pain, sthenia, constipation, constipation, diarrhea, dry flatulence, mouth, dyspepsia, dyspepsia, vomiting. flatulence, loose stools, pruritus, rash, somnolence, vomiting, anorexia, anxiety, blurred vision, depression etc. Ball et al. 1999 (10) All data on clinical NFLX trials available from publications and regulatory agencies (No. of patients not repo rted) Gastrointestinal all вЂ“ 3.9% CNS all вЂ“ 4.4% Dermatological all вЂ“ 0.5% Adverse events (AEs) recorded in >1.0% following the recommended daily dose of NFLX (from 3 days to up to several weeks) were related to: вЂў Gastro-intestinal system: from 2.0% to around 4.0% overall, with prevailing nausea (1.1% to around 4.0%), followed by abdominal pain (from 0.2% to 1.6%) and all other gastro-intestinal adverse events seen in far less than 1.0% of patients]; вЂў Central nervous system (CNS) from 1.5% to 4.4% overall, with prevailing headache (from 0.3% to 2.8%) and dizziness (from <0.1% to 1.7%) and all other CNS adverse events in far less than 1.0% of patients]. вЂў Dermatological adverse events were rare (<0.5% overall) and no cases of phototoxicity were observed. Specific toxicities of FQs (including NFLX ) Based on clinical trial data, post-marketing observations and non-clinical toxicology data, FQs including NFLX have a potential of causing severe and serious adverse effects affecting specific organs and organ systems: CNS (e.g., generalized seizures), liver (e.g., hepatitis, acute liver failure) kidney (e.g., acute interstitial nephritis, renal failure), immune system (hypersensitivity reactions), skin (e.g., TEN, Stevens-Johnson syndrome, phototoxicity),musculoskeletal system (e.g., ar thritis, tendon ruptures) and cardiovascular system (e.g., QTc prolongation, torsades de pointes). These specific toxicities of FQs, including NFLX, have been extensively reviewed over the years (10,12,13,14,15,16, 17). CNS. CNS-related ad verse event associated with the use of FQs vary from trivial (e.g., dizziness) to serious (e.g., generalized convulsions). Overall incidence of CNS-related adverse events in NFLX clinical trials varies between 1.5% and 4.4%. The prevailing were dizziness (0.5% to 2.6%) and headache (0.3% to 2.0%). In the postmarketing surveillance study, headache and dizziness were each reported at a rate of 1 event /1000 patients during the 1st week of treatment and at a rate of around 0.3 events/1000 patients in subsequent 5 weeks. Considering all FQs, incidence of CNS-related adverse events associated with NFLX is lower than that associated with fleroxacin, trovafloxacin and grepafloxacin and apparently higher than with sparfloxacin, ciprofloxacin, enoxacin, ofloxacin, pefloxacin and levofloxacin. Medicinski Еѕurnal 2013 бѓЂ19 (1): 63 - 68 65 66 Anida ДЊauЕЎeviД‡-RamoЕЎevac, Lejla ZoliД‡. Antimicrobial safety of fluoroquinolones: special focus on norfloxacin CNS. CNS-stimulatory effects (epileptogenic) of FQs are related to their structural characteristics. It is thought to be related to enhanced NMDA transmission and inhibition of GABA-A receptors. Compounds with unsubstituted piperazinyl ring at R7 side-chain, like NFLX, ciprofloxacin and enoxacin, have higher affinity for GABA-A in vitro than other FQs. Studies in mice indicate that enoxacin is the most potent in inducing seizures, followed by norfloxacin, ciprofloxacin, ofloxacin and levofloxacin. However, no non-clinical model has been developed that would validly predict epileptogenic potential in humans. Such events have been sporadically reported with all FQs including NFLX, but incidence rate is (low) unknown. Most of the cases have been associated with predisposing statesepilepsy, cerebral trauma or anoxia, metabolic imbalance or concomitant treatment with interacting agents (e.g. theophylline or NSAIDs). Liver. Hepatic toxicity is not specific for NFLX and is particularly related to specific FQ compounds (e.g., temafloxacin). Overall, in clinical trials with NFLX consistently around 0.3-1.5% patients were reported with higher-than-normal values in liver function tests (but not excessive, and transient), and no signs of hepatotoxicity were seen in nonclinical toxicology testing. In the post-marketing surveillance study there were overall 4 liver-related events (2 hepatitis, 1 lab test abnormal , 1 jaundice unspecified) in a cohort of 11110 patients prescribed NFLX at typical dose and for urinary tract infection that were observed for 6 months (a total of >333000 patient-weeks). Kidney. Clinical observations and non-clinical studies indicate the potential of FQs to cause renal damage вЂ“ the underlying mechanism is proposed to include formation of crystals (FQ-protein com plexes), especially in very alkaline urine, triggering events leading to nephropathy. However, other mechanisms are likely to be involved as renal-related events that have been de scribed as associated with FQs use include allergic interstitial nephritis, interstitial nephritis, granulo matous interstitial nephritis, acute renal failure, acute tubular necrosis and crystaluria. Incidence of patients with elevation in serum creatinine associated with the use of NFLX in clinical trials has been reported to be around 0.5%. However, considering that NFLX has been almost exclusively used for urinary tract infections, this finding is not very informative form the drug toxicity standpoint. A search of the Medline database for the period between 1985 and 1999 identified 43 reports on FQassociated nephropathy/nephrotoxicity, 41 of which were associated with ciprofloxacin and 2 with NFLX Medicinski Еѕurnal 2013 бѓЂ19 (1): 63 - 68 - 1 75-year old women using NFLX 2x400 mg for urinary tract infection and 1 68-year old women using NFLX 2x400 mg for pyelonephritis вЂ“ both with acute interstitial nephritis proven by biopsy (14). Immune system. Considering all FQs, parenteral and oral, incidence rate of anaphylactic or anaphylactoid reactions has been estimated to be between 0.5 and 1 case /100000 expositions. There are no estimates specifically for oral NFLX. Hypersensitivity reactions to one FQ are considered to be indicative for potential reaction to other FQs. By far the most common hypersensitivity reactions to FQs include skin manifestations вЂ“ rush, eryhtema, urticaria, pruritus. In NFLX clinical trials, rush, urticaria and pruritus were each recorded in around 0.2% of patients. In the post-marketing surveillance study, the report rate for skin rush associated with NFLX was 0.9/1000 patients in week 1 one of treatment and 0.3/1000 over the subsequent 5 weeks. For the overall cohort of 11100 patients observed for 6 months, there were 4 reports on skin reactions in 4 patients, and 1 case of angioneurotic edema, and 1 patient had urticaria which re-occurred at reexposure. Skin. Sporadic severe skin diseases have been described associated with the use of practically all FQs (e.g., TEN, exfoliative dermatitis, StevensJohnsons syndrome). The incidence rates are unknown, but these are clearly rare events. Apart for dermatological manifestations of hypersensitivity reactions, skin-effects вЂњspecificвЂќ for FQs are photosensitivity reactions. Non-clinical studies indicate that compounds with a halogen substituent at position X8 have the greatest potential for phototoxicity. The approximate order or phototoxic potential is: lomefloxacin, fleroxacin> sparfloxacin > enoxacin > pefloxacin > ciprofloxacin, grepafloxacin > norfloxacin, ofloxacin, levofloxacin, trovafloxacin. However, it is recommended that patients are not exposed to direct sunlight or use sun-screens during treatment. Musculoskeletal system. Non-clinical data show that FQs (including NFLX) have a potential of chondrotoxicity resulting in irreversible damage to the cartilage and arthritis/arthropathy, and also that they may affect the epiphiseal growth-plate resulting in inhibited growth of the long bones. No such cases have been observed in clinical use of FQs, even in children, and data on acquisition of developmental milestones related to musculoskeletal system in children born to women using FQs during pregnancy (NFLY or ciprofloxacin) have not indicated any reason for concern in this respect. The discrepancy between non-clinical and clinical data is likely due to the fact that doses producing these effects in animals are by far in excess Anida ДЊauЕЎeviД‡-RamoЕЎevac, Lejla ZoliД‡. Antimicrobial safety of fluoroquinolones: special focus on norfloxacin of therapeutic doses in humans. Incidence of patients complaining of arthralgia in FQ clinical trials (including NFLX) has been estimated at <1.0%, but the background of this adverse event does not included chondro- or bone toxicity. Cases of tendinitis, tendosynovitis or even tendon rupture have been reported associated with the use of all FQs. Non-clinical data also show the potential of FQs (including NFLX) to cause tendon damage. However, there were no cases reported in NFLX clinical trials. In the post-marketing surveillance study on 11100 using NFLX, 2 cases of tendinitis and 1 case of tendon rupture were observed within 2 months since initiation of treatment. In similarly large cohorts of patients treated with cefixim or azithromycin (nonFQs), there were 3 cases of tendinitis and 2 cases of tendosynovitis. Cardiovascular system. Some of the FQs are known to prolong QTc interval, but this is not a property of NFLX. Sporadically, patients in NFLX clinical trials or general use (see above) have reported adverse events like palpitation, tachycardia, syncope, however no temporal relationship has been established between the use of NFLX and these events as assessed by analyzing treatment and treatment-free periods. Safety/toxicity in special populations Elderly. Older age per se does not affect bioavailability of NFLX (see Pharmacokinetics), however more pronounced decline in renal function (i.e., creatinine clearance <30 mL/min/1.73m3) is not uncommon in the elderly and this is likely to lead to greater bioavailability. Therefore, NFLX dose need to be adjusted in patients with impaired renal function. Analysis of data on elderly patients treated with FQs in clinical trials or general practice have not indicated any particular specific вЂњcontributionвЂќ of age to the safety profile of these drugs вЂ“ apart from the fact that the elderly are more likely to suffer from conditions that may precipitate safety/tolerability problems: using multiple drugs (increasing interaction potential), cardiovascular disease (increasing the risk of cardiovascular complications), renal disease (bioavailability), neuropsychiatric conditions and similar (16,17). HIV-infected вЂ“ generally, adverse events seen in FQ-treated HIV-infected patients are by type identical to those in non-HIV infected patients, but their incidence appears to be higher (17). There are no specific data for NFLX. Neutropenic вЂ“ generally, neutropenic patients receiving FQs for prophylaxys do not seem to differ from non-neutropenic patients regarding the type, incidence and severity of Aes. However, neutropenic patients receiving FQs for treatment of infections suffer more frequent AEs, likely due to the fact that the doses used are higher and duration of treatment longer than in the rest of the population (17). CONCLUSIONS Fluoroquinolones, derivatives of nalidixic acid, are antibiotics with a broad spectrum of activity. In the past decade, fluoroquinolones have become important drugs for the treatment of many infections of various organ systems and various degrees of such infections. Norfloxacin is a valuable oral antimicrobial agent with a wide range of bacterial activity which includes many strains of bacteria resistant to other agents. After more than twenty years of application, norfloxacin is still considered an effective representative of the quinolone group. It is indicated in the treatment of urinary tract infections and gonorrhea, and in the treatment of infections of other parts of body. Certain safety/ tolerability aspects of norfloxacin and fluoroquinolone antibiotics in general became apparent only during the extensive clinical use and prompted further non-clinical investigations aimed at assessing underlying mechanisms. Consequently, non-clinical pharmacology and toxicology aspects of norfloxacin have been extensively investigated in appropriate studies that are in line with the current standards and should be considered well elucidated and established. Accordingly, it was found that there is a link between the structure of fluoroquinolones and their described adverse effects. Analysis of many clinical studies, and post-marketing experience demonstrated a low incidence of adverse effects due to fluoroquinolones. However, these adverse effects included almost all organ systems, most commonly the gastrointestinal system and the CNS. Minimal differences in adverse effects exist between individual fluoroquinolones and are equally present in both sexes. Special focus should be aimed on the serious adverse effects affecting specific organs and organ systems. Among them are: CNS (eg., generalized seizures), liver (e.g., hepatitis, acute liver failure) kidney (e.g., acute interstitial nephritis, renal failure), immune system (hypersensitivity reactions), skin (e.g., TEN, Stevens-Johnson syndrome, phototoxicity), musculoskeletal system (e.g., arthritis, tendon ruptures) and cardiovascular system (e.g., QTc prolongation, torsades de pointes). Since fluoroquinolones are widely used antimicrobial drugs, it should be noted that by health care workersвЂ™ analysis of reported adverse events that occur in the everyday practice, the safety profile of the drug can be better understood, which will allow the prescribed medication to be used in the best way possible. Based on this knowledge, indicaMedicinski Еѕurnal 2013 бѓЂ19 (1): 63 - 68 67 68 Anida ДЊauЕЎeviД‡-RamoЕЎevac, Lejla ZoliД‡. Antimicrobial safety of fluoroquinolones: special focus on norfloxacin tions, dosage, contraindications and precautions for the medication can be added, which will provide a safer and more effective use of medicines. REFERENCES 1. UtinorГў. Summary of product characteristics. Approved by MHRA 2009. www.medicines.org.uk 2. Domagala JM. Structure-activity and structure-side-effect relationships for the quinolone antibacterials. J Antimicrob Chemother. 1994 Apr;33(4):685-706. 3. Tillotson GS. Quinolones: structure-activity relationships and future predictions. J Med Microbiol. 1996 May;44(5):320-4. 4. Shimizu S, Tada M, Kawai K. Early gastric cancer: its surveillance and natural course. Endoscopy. 1995 Jan;27(1):27вЂ“31. 5. Bruno MJ. Magnification endoscopy, high resolution endoscopy and chromoscopy. Gut. 2003;52(suppl 4):iv7вЂ“iv11. 6. Gono K, Obi T, Yamaguchi M et al. Appearance of enhanced tissue features in narrow-band endoscopic immaging. J Biomed Opt. 2004 MayJun;9(3):568вЂ“77. 7. Machida H, Sano Y, Hamamoto Y Muto M, Kozu T, Tajiri H, Yoshida S. Narrow-band immaging in the diagnosis of colorectal mucosal lesions: a pilot study. Endsocopy. 2004 Dec; 36(12):1094вЂ“8. 8. East JE, Suzuki N, Saunders BP. Comparison of magnified pit pattern interpretation with narrow band immaging versus chromoendoscopyfor diminutive colonic polyps: a pilot study. Gastrointest Endosc. 2007 Aug; 66(2):310вЂ“6. Medicinski Еѕurnal 2013 бѓЂ19 (1): 63 - 68 9. Holmes B, Brogden RN, Richards DM. Norfloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1985 Dec;30(6): 482-513. 10. Ball P, Mandell L, Niki Y, Tilloston G. Compara tive tolerability of the newer fluoroquinolone anti bacterials. Drug Saf. 1999 Nov; 21(5):407-421. 11. NoroxinГў. FDA Professional Monographs 2007. Available: www.fda.gov/cder/foi/ label/2001/ 19384s39lbl.pdf 12. Fish DN. Fluoroquinolone adverse effects and drug interactions. Pharmacotherapy. 2001; 21(10 Pt 2):2525-2535. 13. Mandell I, Tillostson G. Safety of fluoroquino lones: an update. Can J Infect Dis. 2002; 13:54-61. 14. Lomaestro BM. Fluoroquinolone-induced renal filure. Drug Saf. 2000; 22:479-485. 15. Bertino J, Fish D. The safety profile of fluoroqui nolones. Clin Ther. 2000; 22:798-817. 16. Stahlmann R, Lode H. Fluoroquinolones in the elderly. Safety considerations. Drugs Aging. 2003; 20:289-302. 17. Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis. 1999;28:352-364. Address: Anida ДЊauЕЎeviД‡-RamoЕЎevac, MA.Pharm. Regulatory Affairs Department Bosnalijek, Pharmaceutical and Chemical Company JukiД‡eva 53, 71 000 Sarajevo, Bosnia and Herzegovina Phone: +387 33 254 578 Email: [email protected] Zoran RoljiД‡, BoЕѕina RadeviД‡, Novak VasiД‡, Milan SimatoviД‡, Jugoslav Дђeri, Severin DunoviД‡, Vladimir KeДЌa, Jevrosima RoljiД‡. Superior mesenteric artery syndrome Case report SUPERIOR MESENTERIC ARTERY SYNDROME SINDROM GORNJE MEZENTERIДЊNE ARTERIJE Zoran RoljiД‡*, BoЕѕina RadeviД‡, Novak VasiД‡, Milan SimatoviД‡, Jugoslav Дђeri, Severin DunoviД‡, Vladimir KeДЌa, Jevrosima RoljiД‡ Department of Vascular Surgery, Clinical Center of Banja Luka, Dvanaest beba 1, 78000 Banja Luka, RS, Bosnia and Herzegovina * Corresponding author ABSTRACT Superior mesenteric artery syndrome is a set of general and gastrointestinal disorders of intestinal obstruction due to high compression of the horizontal part of the duodenum by the superior mesenteric artery and aorta. Diagnosis is difficult. Along with conservative treatment, surgical treatment is the gastrojejunal or duodenal and jejunal anastomosis, or resection of the ligamentum Treitz, as well as relaxation, mobilization and rotation of the duodenal and jejunal transition, with or without duodenal and jejunal anastomosis. The literature describes a small number of cases with surgical treatment. The prevalence is 0,013% to about 0,78% of all radiographic findings in patients with gastrointestinal complaints. We had a female patient with chronical, high intestinal obstruction, and angiographic findings of the horizontal compression of the duodenum of the superior mesenteric artery and aorta, and she was treated with medications and surgery, resection of the ligament of Treitz, mobilization, transposition and dista rotation of the duodenal and jejuna circuit. There was a significant improvement in the postoperative period. Key words: superior mesenteric artery, diagnosis, surgical treatment SAЕЅETAK Sindrom gornje mezenteriДЌne arterije predstavlja skup gastrointestinalnih i opЕЎtih poremeД‡aja zbog visoke crijevne opstrukcije kompresijom horizontalnog dijela duodenuma gornjom mezenteriДЌnom arterijom i aortom. Dijagnoza je teЕЎka. Uporedo sa medikamentoznom, hirurЕЎka terapija je gastrojejuno ili duodenojejuno anastomoza, ili resekcija ligamentum Treitz, relaksacija, mobilizacija i dero- tacija duodenojejunalnog spoja sa jejunoduodenalnom anastomozom ili bez nje. U literaturi je opisan vrlo mali broj sluДЌajeva hirurЕЎkog lijeДЌenja. Javlja se u 0,013% do 0,78 % radioloЕЎkih nalaza kod ispitanika sa gastrointestinalnim tegobama. Bolesnica sa tegobama hroniДЌne, visoke crijevne opstrukcije i angiografskim nalazom kompresije horizontalnog duodenuma gornjom mezenteriДЌnom arterijom i aortom, lijeДЌena je medikamentozno i hirurЕЎki, resekcijom Treitz ligamenta, mobilizacijom, derotacijom i distalnom transpozicijom duodenojejunalnog spoja u podruДЌju veД‡e aortomezenteriДЌne distance. U postoperativnom toku doЕЎlo je do znaДЌajnog poboljЕЎanja. KljuДЌne rijeДЌi: gornja mezenteriДЌna arterija, dijagnostika, hirurЕЎko lijeДЌenje. INTRODUCTION The syndrome of the superior mesenteric artery caused major problems after eating. These are pains in the form of pierced and tension in the region of the stomach immediately after eating, rapid saturation, belching, vomiting, fear of eating and weight loss. Some symptoms are similar or identical to the symptoms of other diseases, and diagnosis is very difficult. It is difficult to distinguish from myopatic and neuropathic forms of chronic intestinal syndromes of pseudo-obstruction (1,2). Superior mesenteric artery arises from the aorta at the level of lumbar vertebra and usually at an angle of 35 to 58 degrees with aortomesenteric distance 10 to 20 mm. Such apposition is supported by most of fat and partly lymphoid tissues which surround it. Rarely mesenteric artery arises from the aorta at an angle of 6 to 20 degrees and Medicinski Еѕurnal 2013 бѓЂ19 (1): 69 - 71 69 70 Zoran RoljiД‡, BoЕѕina RadeviД‡, Novak VasiД‡, Milan SimatoviД‡, Jugoslav Дђeri, Severin DunoviД‡, Vladimir KeДЌa, Jevrosima RoljiД‡. Superior mesenteric artery syndrome the aortomesenteric distance of 5 to 10 mm, where the third portion of duodenum pressed to the aorta and cause varying degrees of obstruction. These patients are candidates for this disorder. It has a chronic course with intermittent exacerbation, as a risk factor for the asthenic constitution, high insertion of the duodenum with the Treitz ligament and a low starting point of the superior mesenteric artery (3). MATERIALS AND METHODS Patient aged 38 years had a long-standing pain in the stomach and a feeling of fullness immediately after eating, with nausea, belching and vomiting, loss of appetite and body weight. The patient was treated for gastritis and duodenal ulcers. We underwent the endoscopic, radiological, MSCT study of the gastrointestinal tract. Duodenal ulcer, gastritis, duodenal dilatation and slow duodenal and jejuna passages were found. The patient was treated for duodenal ulcer and gastritis, but the problems still did not stop. MR angiography of the abdomen showed dilatation of the second horizontal portion of the duodenum, which in the terminal part compressed mesenteric artery and aorta. Findings of MSCT angiography of the abdomen showed targeted benchmarks and flow of the superior mesenteric artery was almost identical, aortomesenteric angle was 14 degrees and aortomesenteric distance was of 6 mm. At this level the horizontal duodenum was compressed and narrowed but a proximal part was dilated. With the clinical diagnosis of this and other findings the idea of the superior mesenteric artery syndrome and surgical treatment is justified. After surgical exploration, resection of the Treitz's ligament was performed, mobilization of the duodenojejunal junction, rotation and transposition of the duodenum distal to the area of aortomesenteric greater distance. Operation and postoperative period was coursed orderly and patient's overall condition was improved (4). DISCUSSION Superior mesenteric artery syndrome is a very serious gastrointestinal disease resulting from the pressure on the superior mesenteric artery and aorta on the final part of the horizontal duodenum. This disease was first described by Rokitanskyin (1861) after an autopsy, and Wilkiein (1927) first published a series of 75 patients. It occurs in 0.013% to 0.78% of all radiological findings in patients with gastrointestinal disturbances. About 25 to 45% of these patients have a peptic ulcer and almost 50% have hyperchloremia. Symptoms begin with pain immediately after eating, fear of eating, continued loss of appetite, catabolism with malnutrition, dehydration, electrolyte imbalance, acute gastric and intestinal perforation, Medicinski Еѕurnal 2013 бѓЂ19 (1): 69 - 71 gastrointestinal bleeding, shock and hipovolemic . sudden cardiovascular collapse (5). Retroperitoneal tumors are predisposed, slow absorption, cachexia, excessive relaxation of the anterior abdominal wall, marked lumbal lordosis. Aneurysm of the abdominal aorta, renal artery and superior mesenteric arteries rarely cause the syndrome. Acute symptoms of the syndrome can cause spinal cord trauma with prolonged immobilization and position on the back, and surgical correction of scoliosis and left nephrectomy. The above procedure with extension of the superior mesenteris arterie and aortomesenteric distance have a similar effect, weight loss and retroperitoneal adipose tissue that surrounds this artery making the buffer distance from the aorta. The clinical picture is not specific, so the diagnosis needs several imaging methods. The clinical picture is not specific, so the diagnosis needs several methods (6). X-ray and hypotonic duodenography showed dilatation of the duodenum and distinct break in the passage height projections of the superior mesenteric artery, endoscopy, which determines dilation of the duodenum and stomach and duodenal retro peristaltic wave. Manometry proved the limpness of the peristaltic duodenal waves in the form of chronic myopatic pseudo obstructive syndrome, irregularity of postprandial motility of the stomach and duodenum in the form of neuropathic chronic intestinal pseudo-obstructive syndrome and increased amplitude of propulsive contractions of the duodenum and retrogrades in the superior mesenteric artery syndrome as a sign of mechanical obstruction. MSCT angiography of the abdomen with showing the organs and the abdominal aorta and its branches, measurements of the aortomesenteric distance and angle, illuminates the clinical picture and help us in the final diagnosis of superior mesenteric artery syndrome (7). The diagnosis is usually late, and the patient was already psychologically and physically exhausted and often in metabolic imbalance. After correction of metabolic imbalances and improve overall physical and mental condition perform the surgery. This procedure was performed for the resection of Treitz's ligament, mobilization of the duodenal and jejuna segment rotation and distal transposition. This procedure can be obtained by duodenal and jejuna Rou en Y anastomosis (8). We had a female patient with obstructive disorder of the gastrointestinal tract and her clinical condition was serious. We did a resection of the ligament, mobilization, and distal transposition detorsio of jejunal and duodenal segment in the greater aortomesenteric distance. The patient feels better. Analyzing the local status, especially the dilated duodenum, we would recommend that the above mentioned procedure adds duodenal and jejunal anastomosis (9). Zoran RoljiД‡, BoЕѕina RadeviД‡, Novak VasiД‡, Milan SimatoviД‡, Jugoslav Дђeri, Severin DunoviД‡, Vladimir KeДЌa, Jevrosima RoljiД‡. Superior mesenteric artery syndrome CONCLUSION Data from the literature and our own experience re commend that patients with clinical signs of obstruc tive gastrointestinal tract disorders need diagnostic procedures in order to exclude superior mesenteric artery syndrome. Modern diagnostic methods are sufficient to prove the cause of the disease. Accurate diagnosis and on time treatment excludes long-term suffering patients and their psychological and physi cal devastation. Conflict of interest:none declared. REFERENCES 1. Mikkelsen WP. Intestinal angina: its surgical significance. Am J Surg. 1957; 94:262-2267. 2. Bond JH, Prentiss RA, Levitt MD. The effects of feeding on blood flow to the stomach, small bowel, and colon of the conscious dog. J Lab Clin Med. 1979; 93:594-599. 3. Ciurea M, Ion D, CreЕЈan C, RusДѓnescu M. The duodenal compression syndrome (DCS) due to an aorto-mesenteric shunt associated with primary intestinal malrotation. Chirurgia (Bucur). 1998 JulAug; 93(4):255-60. 4. Roayaie S, Jossart G, Gitlitz D, Lamparello P, Hollier L, Gagner M. Laparoscopic release of celiac artery compression syndrome facilitated by laparoscopic ultrasound scanning to confirm restoration of flow. J Vasc Surg. 2000;32:814e7. 5. Moyes LH, McCarter DH, Vass DG, Orr DJ. Intraoperative retrograde mesenteric angioplasty for acute occlusive mesenteric ischaemia: a case series. Eur J Vasc Endovasc Surg. 2008 Aug;36(2):203-6. 6. Grotemeyer D, Duran M, Iskandar F, Blondin D, Nguyen K, Sandmann W. Median arcuate ligament syndrome: vascular surgical therapy and follow-up of 18 patients. Langenbecks Arch Surg. 2009 Nov;394 (6):1085-92. 7. JimГ©nez JC, Quinones-Baldrich WJ. Mesenteric Vascular Disease : General Considerations. 7th ed. Cronenwett: RutherfordвЂ™s Vascular Surgery; 2010. Chapter 147. 8. Berard X, Cau J, DГ©glise S, Trombert D, SaintLebes B, Midy D, Corpataux JM, Ricco JB. Laparoscopic surgery for coeliac artery compression syndrome: current management and technical aspects. Eur J Vasc Endovasc Surg. 2012 Jan;43(1):38-42. 9. Tshomba Y, Coppi G, Marone EM, Bertoglio L, Kahlberg A, Carlucci M, Chiesa R. Diagnostic laparoscopy for early detection of acute mesenteric ischaemia in patients with aortic dissection. Eur J Vasc Endovasc Surg. 2012 Jun;43(6):690-7. Address: Zoran RoljiД‡, MD Department of Vascular Surgery Clinical Center of Banja Luka 78000 Banja Luka, RS Dvanaest beba 1 Bosnia and Herzegovina Phone: +387 65 673 135 Email: [email protected] NaЕЎ prilog redukciji kardiovaskularnih bolesti ! Our contribution in reduction of cardiovascular diseases ! Medicinski Еѕurnal 2013 бѓЂ19 (1): 69 - 71 71 72 Zlatan ZvizdiД‡, Ibrahim Ulman, Adnan HadЕѕimuratoviД‡, Selma Vatrenjak-Vanis, Sadeta BegiД‡-KapetanoviД‡, Kenan KaravdiД‡, Nusret PopoviД‡. Primary correction of bladder exstrophy in female newborn Case report PRIMARY CORRECTION OF BLADDER EXSTROPHY IN FEMALE NEWBORN PRIMARNA KOREKCIJA EKSTROFIJE MOKRAД†NOG MJEHURA ЕЅENSKOG NOVOROДђENДЊETA 1* 2 1 3 Zlatan ZvizdiД‡ , Ibrahim Ulman , Adnan HadЕѕimuratoviД‡ , Selma Vatrenjak-Vanis , Sadeta 1 1 1 BegiД‡-KapetanoviД‡ , Kenan KaravdiД‡ , Nusret PopoviД‡ 1 Clinic of Pediatric Surgery, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and 3 2 Herzegovina; Department of Pediatric Surgery, Ege University Faculty of Medicine, 35100 Д°zmir, Turkey; Clinic for Anaesthesiology and Reanimation, Clinical Center University of Sarajevo, BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina *Corresponding author ABSTRACT Bladder exstrophy is an extremely rare congenital anomaly that belongs to the wide spectrum of the epispadias-exstrophy complex with a reported incidence of 1 in 10,000 to 200,000 live births and with an overall greater proportion of affected males. We report a case of 3-day-old female newborn with classical bladder exstrophy managed by primary correction. Key words: bladder extrophy, female, manage ment SAЕЅETAK Ekstrofija mokraД‡nog mjehura je ekstremno rijetka kongenitalna anomalija koja pripada ЕЎirokom spektrumu epispadija-ekstrofiДЌnom kompleksu sa zabiljeЕѕenom incidencom od 1:10000-200000 ЕѕivoroД‘enih i sa ukupno veД‡om zastupljenoЕЎД‡u muЕЎkog spola. Mi izvjeЕЎtavamo o sluДЌaju tri dana starog Еѕenskog novoroД‘enДЌeta sa klasiДЌnom ekstrofijom mokraД‡nog mjehura tretiranog primarnom korekcijom. KljuДЌne rijeДЌi: ekstrofija mokraД‡nog mjehura, Еѕenski spol, tretman INTRODUCTION The first description of bladder exstrophy was noted on Assyrian tablets nearly 4000 years ago. Schenck von Grafenberg was the first to describe exstrophy of the bladder, in his report published in 1597, while the term вЂ�exstrophyвЂ™ was first used by Chaussier in 1780. The first case of successful closure and continence in a female patient with bladder exstrophy was not reported until 1942 by Young in the USA. Michon subsequently reported successful reconstruction in a male patient 6 years later (1). Medicinski Еѕurnal 2013 бѓЂ19 (1): 72 - 74 Bladder exstrophy also known as ectopia vesica is an extremely rare congenital anomaly that belongs to the wide spectrum of the epispadias-exstrophy complex (EEC) with a reported prevalence of classic bladder exstrophy (CEB) of 3.3 per 100,000 births (range 1:10,000 вЂ“ 1: 200,000) (1). It is rarer in females with a male-female sex ratio of between 1.5 to 6:1 (2). This anomaly involves urinary bladder wall, lower anterior abdominal wall, pubic bones and external genitalia. Bladder exstrophy usually occurs sporadically, but there are some cases that are inherited in an autosomal dominant fashion (3). On the basis of a survey of 2500 indexed cases, familiar occurrence was found to be 1 in 275 (4). Bladder exstrophy is rarely associated with other congenital anomalies, like rectal prolapse, spinal anomalies or undescended testes (5,6). Bladder exstrophy is classified according to the presence or absence of associated congenital cloacal anomalies into simple or complex (simple bladder exstrophy means without cloacal anomaly and complex bladder exstrophy means with cloacal anomaly) (6). CASE REPORT A 1-day-old female baby was referred to our institution for definitive treatment of classic bladder exstrophy by the regional hospital. Baby was born by full term normal vaginal delivery to a 25-yearold mother. An Apgar score 1/5 was >7, whereas birth weight was 3390 grams. Family history was showed no case of bladder exstrophy cases. The gross examination showed a classic bladder exstrophy which consisted of open bladder plate and urethra with bifid clitoris and with divergent labia superiorly (Figure 1.). The vagina and anus were displaced anteriorly while the umbilical cord was Zlatan ZvizdiД‡, Ibrahim Ulman, Adnan HadЕѕimuratoviД‡, Selma Vatrenjak-Vanis, Sadeta BegiД‡-KapetanoviД‡, Kenan KaravdiД‡, Nusret PopoviД‡. Primary correction of bladder exstrophy in female newborn separated from the superior margin of the blad der exstrophy but displaced inferiorly. On the exstrophic bladder surface, hamartomatous polyps were visible (Figure 1). There was a significant pubic diastasis, which was confirmed by preoperative plane roentgenogram, demonstrating 3.5 cm separation of the pubic bones. No other se vere congenital anomalies were detected during the preoperative evaluation. Following the preoperative evaluation and resuscitation, the patient was taken to the operating room in the third day of age. Figure 1. Female newborn with classical bladder exstrophy and visible hamartomatous polyps on the exstrophic bladder surface (black arrows). Surgical treatment consisted of complete pri mary repair of bladder exstrophy. Following complete mobilization of the bladder, the bladder was closed anteriorly in the midline and the urethra tu bularized over a 10-Fr sound. The traction suture was initially placed anterior to the vagina, which was fully mobilized, as the neourethra was tubularized. The vagina was then repositioned to cre ate a more caudal angle of entry. Pubic approxi mation without ancillary osteotomy was done by interrupted sutures through the pubic bones. The newly closed bladder and urethra were covered by reapproximation of the rectus fascia and skin, with externalization of a suprapubic cystostomy and ureteral catheters (Figure 2). Figure 2. Postoperative appearance of the anterior abdominal wall and external genitalia. Postoperatively, the patient was maintained on antibiotic prophylaxis and was put on oral feeds after 24 h. The patient was discharged home on the fifteenth postoperative day after removal of the suprapubic catheter and ureteral catheters, in good condition. DISCUSSION The exstrophy-episapadias complex represents a wide spectrum of congenital anomalies that includes classic bladder exstrophy, epispadies, cloacal exstrophy, and several variants. In the base of all of these anomalies lies the same embryological defect (7). Central rupture of the cloacal membrane after complete separation of the genitourinary and gastrointestinal tracts results in classic bladder exstrophy which is in female patients characterized by open bladder plate and urethra with bifid clitoris and with divergent labia superiorly. The vagina and anus uniformly displaced anteriorly while the pubic symphysis widely separated. Surgical reconstruction of exstrophy-epispadias complex remains one of the great challenges for pediatric surgeons and pediatric urologist. The main objectives of the management of these patients are continence, protection of the kidneys and the cosmetic appearance of functional genitalia. The surgical treatment of bladder exstrophy can be achieved in a single or multiple stages. For approximately 30 years, staged reconstruction was the gold standard for bladder exstrophy. Thanks to the works of Mitchell and GradyвЂ™s (8,9,10) in the last two decades the concept of complete primary repair of bladder exstrophy which combines the goals of staged reconstruction into a single operation was introduced: bladder closure, epispadias repair in males and achievement of urinary continence, all without a formal bladder-neck reconstruction. Major potential benefits of this approach include the earlier creation of bladder outlet resistance, theoretically leading to normal cycling and improved bladder capacity and functionality as the patient grows. In accordance with this, our management consisted of complete primary repair of bladder exstrophy without pelvic osteotomy and with excision of hamartomatous polyps which are otherwise visible on the exstrophic bladder surface in about 50% of the cases (11). CONCLUSION The treatment of bladder exstrophy is surgical reconstruction, which could be done as a single or multi-staged approach. Primary repair of bladder exstrophy have resulted in acceptable function and cosmesis for the majority of patients with classic bladder exstrophy. Also, reduces the cost and decrease the morbidity associated with multiple Medicinski Еѕurnal 2013 бѓЂ19 (1): 72 - 74 73 74 Zlatan ZvizdiД‡, Ibrahim Ulman, Adnan HadЕѕimuratoviД‡, Selma Vatrenjak-Vanis, Sadeta BegiД‡-KapetanoviД‡, Kenan KaravdiД‡, Nusret PopoviД‡. Primary correction of bladder exstrophy in female newborn operative procedures. Long term follow-up is recommended to evaluate renal function, bladder compliance and external genitalia appearance. Conflict of interest: none declared. REFERENCES 1. Buyukunal CS, Gearhart JP. A short history of bladder exstrophy. Semin Pediatr Surg. 2011; 20(2):62-65. 2. Ebert AK, Reutter H, Ludwig M, RГ¶sch WH. The exstrophy-epispadias complex. Orphanet J Rare Dis. 2009 Oct; 4:23. doi: 10.1186/1750-1172-4-23. 3. Froster UG, Heinritz W, Bennek J, Horn LC, Faber R. Another case of autosomal dominant exstrophy of the bladder. Prenat Diagn 2004; 24(5):375-377. 4. Ludwig M, Ching B, Reutter H, Boyadjiev SA. Bladder exstrophy-epispadias complex. Birth Defects Res A Clin Mol Teratol. 2009 Jun; 85(6):509 522. 5. Jayachandran D, Bythell M, Platt MW, Rankin J. Register based study of bladder exstrophy-epispadias complex: prevalence, associated anomalies, prenatal diagnosis and survival. J Urol. 2011; 186(5):2056-2060. 6. Purves JT, Baird AD, Gearhart JP. The Modern Staged Repair of Bladder Exstrophy in the- Fe male: A Contemporary Study. J Pediatr Urol. 2008; 4(2): 150-153. 7. Muecke EC. The role of the cloacal membrane in exstrophy: The first successful experimental study. J Urol. 1964 Dec;92:659-667. 8. Mitchell M, BГ¤gli D. Complete penile disassem bly for epispadias repair: the Mitchell technique. J Urol. 1996 Jan;155(1):300-303. 9. Grady R, Mitchell M. Newborn exstrophy closure and epispadias repair. World J Urol. 1998; 16(3):200-204. 10. Grady R, Mitchell M. Complete primary repair of exstrophy. J Urol. 1999 Oct; 162(4):1415-1420. 11. Novack TE, Lakshmanan Y, Frimberger D, Epstein JI, Gearhart JP. Polyps in the exstrophic bladder. A cause for concern? J Urol. 2005 Oct; 174(4 Pt2):1522-1526. Address: Zlatan ZvizdiД‡, M.D, MA Clinic of Pediatric Surgery Clinical Center University of Sarajevo BolniДЌka 25, 71000 Sarajevo, Bosnia and Herzegovina Phone: +387 33 297 142 Email: [email protected] Nova centralna zgrada KliniДЌkog Centra Univerziteta u Sarajevu New Central building of the Clinical Center University of Sarajevo Medicinski Еѕurnal 2013 бѓЂ19 (1): 72 - 74 Prof. Senija RaЕЎiД‡, MD, PhD Pfizer Nefro Foruma 75 IZVJEЕ TAJ SA PFIZER NEFRO FORUMA, Sarajevo, mart 2013. U Sarajevu je od 22.03. do 24.03. 2013. godine u hotelu Bristol odrЕѕan PFIZER NEFRO FORUM, na kojem su uДЌestvovali nefrolozi iz Bosne i Hercegovine i Hrvatske na kojem su mlaД‘i lijeДЌnici iz ove dvije drЕѕave prikazali reprezentativne sluДЌajeve iz kliniДЌke prakse. Rad Foruma je pratio i ocjenjivao Еѕiri sastavljen od eminentnih i iskusnih nauДЌnih radnika iz oblasti nefrologije i dijalize. Na ovom struДЌnom druЕѕenju prikazani su interesantni sluДЌajevi iz nefroloЕЎke prakse, koji su konstruktivno prodiskutovani, aiskustvo steДЌeno kroz ovaj vid saradnje je od izuzetne vaЕѕnosti za svakodnevni kliniДЌki rad. Na kraju prvog NEFRO FORUMA, ДЌiji pokrovitelj je bila farmaceutska kompanija Pfizer iz Hrvatske i Bosne i Hercegovine, dodijeljene su nagrade za najbolje ocijenjene prikaze sluДЌajeva iz kliniДЌke prakse. Prvu nagradu (odlazak na Evropski kongres nefrologa u Atini 2014. godine) dobio je dr.mr.sc.Nihad Kukavica sa Klinike za hemodijalizu KCUS. Drugu nagradu (odlazak na Summer Nephrology School u BudimpeЕЎtu 2013/14. godine) dobila je dr. Amira Srna sa Klinike za nefrologiju KCUS. TreД‡u nagradu (odlazak na Hrvatski kongres za hipertenzije 2013. godine) dobila je dr. Martina PavletiД‡-PeЕЎiД‡ iz KliniДЌko-bolniДЌkog centra Rijeka, dok su ДЌetvrtu nagradu (knjiga Gerijatrija i farmakoterapija u gerijatriji) dobili dr. Damir RebiД‡ sa Klinike za nefrologiju KCUS i dr.sc.Karmela Altabas iz Bolnice Sveti duh u Zagrebu. Osvojene tri nagrade od strane mladih lijeДЌnika koji se bave nefrologijom i dijalizom iz KCU Sarajevo su joЕЎ jedna potvrda kvalitete i afirmacije nefroloЕЎke sluЕѕbe iz KCU Sarajevo i na meД‘unarodnom planu. REPORT FROM PFIZER NEPHROPATHY FORUM, Sarajevo, March 2013. PFIZER nephropathy forum was held in Sarajevo at the Bristol Hotel, from 22.03. to 24.03. 2013, with the participation of nephrologists from Bosnia and Herzegovina and Croatia. Attending physicians from these two countries showed representative cases from clinical practice. The Forum was monitored and evaluated by a jury of eminent and experienced scientists in the field of nephrology and dialysis. At this professional gathering, interesting cases in nephrology practices were shown and constructively discussed. Experience gained through this kind of cooperation was rated as of great importance for routine clinical practice. At the end of nephropathy forum, sponsored by Pfizer pharmaceutical company from Croatia and Bosnia and Herzegovina, the awards were presented to the highest rated illustrative cases in clinical practice. The first prize (going to the European Congress of Nephrologists in Athens in year 2014), received dr.mr.sc.Nihad Kukavica, from Clinic for hemodialysis, Clinical Center University of Sarajevo. Second prize (going to the Summer Nephrology School in Budapest 2013/14), received dr. Amira Srna from Department of Nephrology, Clinical Center University of Sarajevo. Third prize (going to the Croatian Congress of Hypertension 2013.), received dr. Martina PavletiД‡PeЕЎiД‡, from Clinical Hospital Center Rijeka, while the fourth prize (Geriatrics book and Pharmacotherapy in geriatrics book), received dr. Damir RebiД‡ from Department of Nephrology, Clinical Center University of Sarajevo and dr.sc. Karmela Altabas from Sveti duh Hospital in Zagreb. Three awards won by the young doctors from Clinical Center in Sarajevo, working in the field of nephrology and dialysis, is yet another confirmation of the quality and affirmation of nephrology services provided by the Clinical Center University of Sarajevo at the international level. Prof. Senija RaЕЎiД‡, MD, PhD Clinic for Nephrology Clinical Center University of Sarajevo 71000 Sarajevo, Bosnia and Herzegovina Medicinski Еѕurnal 2013 бѓЂ19 (1) 76 UPUTSTVA AUTORIMA MEDICINSKOG ЕЅURNALA UPUTSTVA AUTORIMA ДЊasopis вЂњMedicinski ЕѕurnalвЂќ objavljuje originalne nauДЌne radove, struДЌne, pregledne i edukativne radove, prikaze sluДЌajeva, recenzije, saopД‡enja, struДЌne obavijesti i drugo iz podruДЌja svih medicinskih disciplina. Radovi se piЕЎu in-exstenso na engleskom jeziku, uz saЕѕetak i naslov rada koji se uz engleski piЕЎe joЕЎ i na naЕЎem jeziku. Autori su odgovorni za sve navode i stavove u njihovim radovima. Ukoliko je rad pisalo viЕЎe autora, potrebno je navesti taДЌnu adresu (uz telefonski broj i e-mail adresu) onog autora s kojim Д‡e uredniЕЎtvo saraД‘ivati pri ureД‘enju teksta za objavljivanje. Ukoliko su u radu prikazana istraЕѕivanja na ljudima, mora se navesti da su provedena u skladu s naДЌelima medicinske deontologije i Deklaracije iz Helsinkija. Ukoliko su u radu prikazana istraЕѕivanja na Еѕivotinjama, mora se navesti da su provedena u skladu s etiДЌkim naДЌelima. Prilikom navoД‘enja mjernih jedinica, treba poЕЎtovati pravila navedena u SI sistemu. Radovi se ЕЎalju Redakciji na adresu: вЂњMEDICINSKI ЕЅURNALвЂќ Institut za nauДЌnoistraЕѕivaДЌki rad i razvoj KliniДЌkog centra Univerziteta u Sarajevu BolniДЌka 25 71000 Sarajevo Bosna i Hercegovina Email: [email protected] POPRATNO PISMO Uz svoj rad, autori su duЕѕni Redakciji В«Medicinskog ЕѕurnalaВ» dostaviti popratno pismo, koje sadrЕѕava vlastoruДЌno potpisanu izjavu svih autora: 1. da navedeni rad nije objavljen ili primljen za objavljivanje u nekom drugom ДЌasopisu 2. da je istraЕѕivanje odobrio EtiДЌki komitet, 3. da prihvaД‡eni rad postaje vlasniЕЎtvo В«Medicinskog ЕѕurnalaВ». OPSEG I OBLIK RUKOPISA Radovi ne smiju biti duЕѕi od deset stranica na raДЌunaru, ubrajajuД‡i slike, grafikone, tabele i literaturu. CD zapis teksta je obavezan (Microsoft Word). Prored: 1,5: lijeva margina: 2,5 cm; desna margina: 2,5 cm; gornja i donja margina: 2,5 cm. Grafikone, tabele, slike i crteЕѕe unijeti/staviti u tekst rada, tamo gdje im je mjesto, bez obzira u kojem programu su raД‘ene. Cijeli rad mora biti napisan na engleskom jeziku. Apstrakti na engleskom i jezicima naroda BiH. Rad se dostavlja na CD-u, uz dva ЕЎtampana primjerka, ili e-mailom. CD se ne vraД‡a. RAD SADRЕЅI: NASLOV RADA NA NAЕ EM JEZIKU NASLOV RADA NA ENGLESKOM JEZIKU Ime i prezime autora i koautora Naziv i puna adresa institucije u kojoj je autor-koautor/i zaposlen/i (jednako za sve autore), na naЕЎem i na engleskom jeziku, te na kraju rada navedena adresa kontakt-autora. SaЕѕetak na naЕЎem jeziku i njegov obavezan korektan prevod na engleskom вЂ“ Abstract od oko 200 rijeДЌi, s najznaДЌajnijim ДЌinjenicama i podacima iz kojih se moЕѕe dobiti uvid u kompletan rad. KljuДЌne rijeДЌi - Key words (na naЕЎem jeziku i na engleskom): do pet rijeДЌi; navode se ispod SaЕѕetka, odnosno Abstracta. Medicinski Еѕurnal 2013 бѓЂ19 (1) 77 SADRЕЅAJ SadrЕѕaj rada mora biti sistematiДЌno i strukturno pripremljen i podijeljen u poglavlja i to: - UVOD MATERIJAL I METODE REZULTATI DISKUSIJA ZAKLJUДЊAK LITERATURA UVOD Uvod je kratak, koncizan dio rada i u njemu se navodi svrha rada u odnosu na druge objavljene radove sa istom tematikom. Potrebno je navesti glavni problem, cilj istraЕѕivanja i/ili glavnu hipotezu koja se provjerava. MATERIJAL I METODE Potrebno je da sadrЕѕi opis originalnih ili modifikaciju poznatih metoda. Ukoliko se radi o ranije opisanoj metodi dovoljno je dati reference u literaturi. U kliniДЌko-epidemioloЕЎkim studijama opisuju se: uzorak, protokol i tip kliniДЌkog istraЕѕivanja, mjesto i vrijeme istraЕѕivanja. Potrebno je opisati glavne karakteristike istraЕѕivanja (npr. randomizacija, dvostruko slijepi pokus, unakrsno testiranje, testiranje s placebom itd.), standardne vrijednosti za testove, vremenski odnos (prospektivna, retrospektivna studija), izbor i broj ispitanika вЂ“ kriterije za ukljuДЌivanje i iskljuДЌivanje u istraЕѕivanje. REZULTATI Navode se glavni rezultati istraЕѕivanja i nivo njihove statistiДЌke znaДЌajnosti. Rezultati se prikazuju tabelarno, grafiДЌki, slikom i direktno se unose u tekst gdje im je mjesto, s rednim brojem i konciznim naslovom. Tabela treba imati najmanje dva stupca s obrazloЕѕenjem ЕЎto prikazuje; slika ДЌista i kontrastna, a grafikon jasan, s vidljivim tekstom i obrazloЕѕenjem. DISKUSIJA PiЕЎe se koncizno i odnosi se prvenstveno na vlastite rezultate, a potom se nastavlja uporeД‘ivanje vlastitih rezultata s rezultatima drugih autora, pri ДЌemu se citiranje literature navodi po vaЕѕeД‡im Vankuverskim pravilima. Diskusija se zavrЕЎava potvrdom zadatog cilja ili hipoteze, odnosno njihovim negiranjem. ZAKLJUДЊAK Treba da bude kratak, da sadrЕѕi najbitnije ДЌinjenice do kojih se doЕЎlo u radu tokom istraЕѕivanja i njihovu eventualnu kliniДЌku primjenu, kao i potrebne dodatne studije za potpuniju aplikaciju. Obavezno navesti i afirmativne i negirajuД‡e zakljuДЌke. LITERATURA Literatura se obavezno citira po Vankuverskim pravilima. Svaku tvrdnju, saznanje ili misao treba potvrditi referencom. Reference u tekstu treba oznaДЌiti po redoslijedu unoЕЎenja arapskim brojevima u zagradi na kraju reДЌenice. Ukoliko se kasnije u tekstu pozivamo na istu referencu, navodimo broj koji je referenca dobila prilikom prvog unoЕЎenja/pominjanja u tekstu. Literatura se popisuje na kraju rada, rednim brojevima pod kojim su reference unesene u tekst (ulazni broj reference), a naslov ДЌasopisa se skraД‡uje po pravilima koje odreД‘uje Index Medicus. Ukoliko je citirani rad napisalo viЕЎe autora, navodi se prvih ЕЎest i doda В«et al.В». Vrlo je vaЕѕno ispravno oblikovati reference prema uputama koje se mogu preuzeti na adresama Natuinal Library of Medicine Citing Medicine http://www.ncb.nlm.nih.gov/books/bv.fcg?rid=citmed.TOC&depth=2, ili International Committee of Medical Journal Editors Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Sample References http://www.nlm.nih.gov/bsd/uniform_requirements.html Medicinski Еѕurnal 2013 бѓЂ19 (1) 78 INSTRUCTIONS TO AUTHORS Journal вЂњMedical JournalвЂќ publishes original research articles, professional, review and educative articles, case reports, criticism, reports, professional news, in the fields of all medical disciplines. Articles are written in-extenso in English, with the abstract and the title in English and Bosnian/Croatian/Serbian language. Authors take responsibility for all the statements and attitudes in their articles. If article was written by several authors, it is necessary to provide full contact details (telephone numbers and email addresses) of the corresponding author for the cooperation during preparation of the text to be published. Authors should indicate whether the procedures carried out on humans were in accordance with the ethical standards of medical deontology and Declaration of Helsinki. Articles that contain results of animal studies will only be accepted for publication if it is made clear that ethics standard were applied. Measurements should be expressed in units, according to the rules of the SI System. Manuscript submission should be sent to Editorial Board and addressed to: вЂњMEDICINSKI ЕЅURNALвЂќ Institut za nauДЌnoistraЕѕivaДЌki rad i razvoj KliniДЌkog centra Univerziteta u Sarajevu BolniДЌka 25 71000 Sarajevo Bosna i Hercegovina Email: [email protected]; [email protected] COVER LETTER Apart from the manuscript, the authors should enclose a cover letter, with the signed statements of all authors, to the Editorial Board of вЂњMedical JournalвЂќ stating that: 1. the work has not been published or accepted for publication previously in another journal, 2. the work is in accordance with the ethical committee standards, 3. the work, accepted for publication, becomes ownership of В«Medical JournalВ». PREPARATION OF MANUSCRIPT Works should be no longer than 10 computer pages, including figures, graphs, tables and references. The work may be submitted as CD disk (Microsoft Word). Spacing: 1,5: left margin: 4 cm; right margin: 2,5 cm; top and bottom margin: 4 cm. Graphs, tables, figures and drawings should be incorporated in the text precisely in the text where these will be published, regardless of the program in which they are prepared. The work could be submitted in English language in extenso. The manuscript should be submitted on CD disc, together with two printed copies, or by e-mail, CD disks will not be returned to the authors. ARTICLE CONTAINS: TITLE OF THE ARTICLE IN BOSNIAN/SERBIAN/CROATIAN (B/S/C) LANGUAGE TITLE OF THE ARTICLE IN ENGLISH LANGUAGE First name and last name of author and co-authors Name and address of institution in which author/co-authors are employed (same for all authors) in B/S/C and English language as well as the address of corresponding author at the end of the paper. Summary in B/S/C language with the precise translation in English. Abstract of approximately 200 words should concisely describe the contents of the article. Key words (in B/S/C and in English language): up to five words should be listed below Summary, or Abstract. Medicinski Еѕurnal 2013 бѓЂ19 (1) 79 ARTICLE BODY The main body of the article should be systematically ordered under the following headings: - INTRODUCTION - MATERIALS AND METHODS - RESULTS - DISCUSSION - CONCLUSION - REFERENCES INTRODUCTION Introduction is a concise, short part of the article, and it contains purpose of the article relating to other published articles with the same topic. It is necessary to quote the main problem, aim of investigation, and/or main hypothesis which is investigated. MATERIALS AND METHODS This part should contain description of original or modification of known methods. If there is a method that has previously been described, it would be sufficient to include it in the reference list. In clinical and epidemiological studies the following should be described: sample, protocol and type of clinical investigation, place and period of investigation. Main characteristics of investigation should be described (randomization, double-blind test, cross test, placebo test), standard values for tests, time framework (prospective, retrospective study), selection and number of patients вЂ“ criteria for inclusion and exclusion from the study. RESULTS Main results of investigation and level of its statistical significance should be quoted. Results should be presented in tables, graphs, figures, and directly incorporated in the text, at the exact place, with ordinal number and concise heading. Table should have at least two columns and explanation; figures clean and contrasted, graphs clear, with visible text and explanation. DISCUSSION Discussion is concise and refers to own results, in comparison with the other authorsвЂ™ results. Citation of references should follow Vancouver rules. Discussion should be concluded by the confirmation of the stated aim or hypothesis, or by its negation. CONCLUSION Conclusion should be concise and should contain most important facts, which were obtained during investigation and its eventual clinical application, as well as the additional studies for the completed application. Affirmative and negative conclusions should be stated. REFERENCES References should follow the format of the requirements of Vancouver rules. Every statement, knowledge and idea should be confirmed by reference. Each reference in the text is given its own superscript in Arabic number in parenthesis at the end of the sentence according to the order of entering. Every further referring to the same reference, number of the first referring in the text should be stated. References are to be placed at the end of the article, and are to be numbered by ordinal numbers in the order of entering in the text (entering reference number). JournalвЂ™s title is abbreviated using Index Medicus abbreviations. The names of the first six authors of each reference item should be provided, followed by В«et al.В». It is very important to properly design references according to instructions that be downloaded from addresses National Library of Medicine Citing Medicine http://www.ncbi.nlm.nih.gov/ books/bv.fcg?rid=citmed.TOC&depth=2, or International Committee of Medical Journal Editors Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Sample References http:/www.nlm.nih.gov/bsd/uniform_requirements.html Medicinski Еѕurnal 2013 бѓЂ19 (1) 80 ISSN (print) 1512-5866 ISSN (online) 2232-853X MEDICINSKI ЕЅURNAL je upisan u evidenciju javnih glasila u Ministarstvu obrazovanja, nauke, kulture i sporta pod rednim brojem 440, od 10.08.1994. godine. Upis u evidenciju javnih glasila izvrЕЎen je u skladu sa Zakonom o javnom informisanju (вЂќSl. List SRBiHвЂќ , br 21/90 ) ) Papir koriЕЎten za ЕЎtampu / Paper used for pressing: Korica / Binding - FABRIA Bianco 240 g/m2 / gsm Strenice / Pages - Fabria Bianco 100 g/m2 / gsm ACID FREE ECF FREE ELEMENTARY CHLORINE NEUTRAL pH Medicinski Еѕurnal 2013 бѓЂ19 (1) NAЕ DOPRINOS REDUKCIJI KARDIOVASKULARNIH BOLESTI U BOSNI I HERCEGOVINI