1. family and parenting
2. motherhood
3. pregnancy

Volume 19
January/March 2013
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Medicinski žurnal 2013 Ⴠ19 (1)
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Contents
ORIGINAL ARTICLE
THE FETAL MAGNETIC RESONANCE IMAGING OF NEURAL AND THORACO -ABDOMINAL ANOMALIES ........................ 4
Sandra Vegar-Zubović, Spomenka Kristić,Lidija Lincender , Irmina Sefić-Pašić, Aladin Čarovac
OBSTETRIC CONDITIONS AS POSSIBLE PREDICTORS OF NEONATAL LESIONS OF PLEXUS BRACHIALIS .................. 9
Fatima Gavrankapetanović-Smailbegović, Muhamed Ardat, Lejla Imširija, Naima Imširija, Faruk Lazović, Mehmed Jamakosmanović
MALIGNANT LIP TUMOURS; SURVIVAL ANALYSIS ................................................................................................................. 14
Faris Fočo, Lejla Džananović, Zlatan Zvizdić, Edin Imamović, Irma Ramović, Semra Čavaljuga
THE SIGNIFICANCE OF IMPLEMENTATION OF DRG (DIAGNOSIS RELATED GROUPS) HEALTHCARE REFORMS
IN THE FIELD OF PHYSICAL MEDICINE AND REHABILITATION ............................................................................................ 20
Narcisa Vavra-Hadžiahmetović, Aldijana Kadić, Damir Čelik
AWARENESS OF PHYSICIANS ABOUT PATIENTS’ RIGHTS; PATIENT CONSENT FORM ..................................................... 25
Dragana Nikšić, Amela Džubur, Amira Kurspahić Mujčić
ADMISSION RATES OF PATIENTS WITH SCHIZOPHRENIA IN RELATION TO SEASONS
AND CLIMATIC FACTORS IN THE PERIOD OF TWO YEARS ................................................................................................................ 32
Ifeta Ličanin, Alem Ćesir, Saida Fišeković
HEART RHYTHM DISORDERS AS A CONTRIBUTING FACTOR TO ISCHEMIC STOKE ......................................................... 38
Jasminka Đelilović-Vranić, Azra Alajbegović, Mehmed Kulić, Amina Nakičević, Emina Ejubović, Merita Tirić-Čampara,
Edina Đozić, Ljubica Todorović, Salem Alajbegović
CORONARY ANGIOGRAPHY REVIEW OF ANATOMIC VARIATIONS OF THE CORONARY ARTERIES ............................... 43
Aida Hasanović, Belma Aščić-Buturović, Muhamed Spužić
PROFESSIONAL ARTICLE
PROGNOSTIC ASSESSMENT IN PATIENTS WITH DECOMPENSATED CIRRHOSIS .............................................................. 48
Dženela Prohić , Rusmir Mesihović, Nenad Vanis, Srđan Gornjaković, Amra Puhalović, Aida Saray
ETIOLOGY OF ANEMIA IN PATIENTS WITH GASTRIC LYMPHOMAS ...................................................................................... 54
Lejla Ibričević-Balić, Rusmir Mesihović, Alma Sofo-Hafzović, Nenad Vanis, Šefkija Balić, Semir Bešlija
CARDIOBORRELIOSIS IN BOSNIA AND HERZEGOVINA ........................................................................................................ 58
Sajma Dautović-Krkić, Alma Sijamija, Nedžad Hadžić, Hilmo Čaluk
REVIEW ARTICLE
ANTIMICROBIAL SAFETY OF FLUOROQUINOLONES: SPECIAL FOCUS ON NORFLOXACIN ........................................... 63
Anida Čaušević-Ramoševac, Lejla Zolić
CASE REPORT
SUPERIOR MESENTERIC ARTERY SYNDROME .................................................................................................................... 69
Zoran Roljić, Božina Radević, Novak Vasić, Milan Simatović, Jugoslav Đeri, Severin Dunović, Vladimir Keča, Jevrosima Roljić
PRIMARY CORRECTION OF BLADDER EXSTROPHY IN FEMALE NEWBORN ..................................................................... 63
Zlatan Zvizdić, Ibrahim Ulman, Adnan Hadžimuratović, Selma Vatrenjak-Vanis, Sadeta Begić-Kapetanović, Kenan Karavdić, Nusret Popović
INFORMATION
PFIZER NEFRO FORUM ............................................................................................................................................................... 75
Senija Rašić
UPUTSTVO AUTORIMA ........................................................................................................................................... 76
INSTRUCTIONS TO AUTHORS ......................................................................................................................... 78
Medicinski žurnal 2013 Ⴠ19 (1)
.
4
Sandra Vegar-Zubović, Spomenka Kristić, Lidija Lincender , Irmina Sefić-Pašić, Aladin Čarovac. 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-Zubović1*, Spomenka Kristić1, Lidija Lincender 2, Irmina Sefić-Pašić , Aladin Čarovac 1
1
Clinic of Radiology, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina;
Academy of Sciences and Arts of Bosnia and Herzegovina, 71000 Sarajevo, Bosnia and Herzegovina
2
* Corresponding author
ABSTRACT
SAŽETAK
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 – which is still the method of choice for screening.
Cilj ovog rada bio je procijeniti značaj MRI u dijagnostici fetalnih abnormalnosti, osobito u
slučajevima kada je nalaz ultrazvuka inkonkluzivan.
Jedanaest fetusa sa prethodno ultrazvučno
uočenim malformacijama je podvrgnuto MRI
pregledu. Fetalni MRI je rađen na aparatu jačine
1.5 T uz korištenje brzih T2 (HASTE) i T1 (TurboFLASH) sekvenci.
Deset pregleda je bilo adekvatne kvalitete za
analizu, dok jedan pregled nije bio dijagnostički
suficijentne kvalitete. Kod devet pacijenata nalaz
MRI je bio patološki, dok je kod jednog pacijenta
bio uredan. Ultrazvučno postavljene uputne dijagnoze su uključivale cistične promjene bubrega,
intraabdominalnu cistoidnu tumorsku formaciju,
distenziju želuca, anomalije centralnog nervnog
sistema. U 60% slučajeva uočena je podudarnost
ultrazvučnog i MRI nalaza, u 30% slučajeva nalaz
je bio oprečan, dok je u 10% slučajeva podudarnost nalaza dviju metoda bila djelomična. Rezultati ispitivanja su obrađeni upotrebom deskriptivne
statistike.
Zaključak: MRI je metoda koja daje važne informacije o fetalnim abnormalnostima, a komplementarna je sa fetalnim ultrazvukom koji je još
uvijek screening metoda izbora.
Key words: fetal MRI, fetal abnormalities, fetal
malformations
Ključne riječi: fetalni MRI, fetalne abnormanosti,
fetalne malformacije
Medicinski žurnal 2013 Ⴠ19 (1): 4 - 8
Sandra Vegar-Zubović, Spomenka Kristić, Lidija Lincender , Irmina Sefić-Pašić, Aladin Čarovac. 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 – 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 – 44), while the mean gestational
age of the fetuses was 33 weeks (a range of 27
– 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 mother’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 mother’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 – 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 žurnal 2013 Ⴠ19 (1): 4 - 8
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Sandra Vegar-Zubović, Spomenka Kristić, Lidija Lincender , Irmina Sefić-Pašić, Aladin Čarovac. 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 – 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 žurnal 2013 Ⴠ19 (1): 4 - 8
Sandra Vegar-Zubović, Spomenka Kristić, Lidija Lincender , Irmina Sefić-Pašić, Aladin Čarovac. 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 – 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 – in addition
to hydrocephalus – 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
– 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
– citing the discrepancy between the MRI and
ultrasound findings at 20 – 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 – 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 operator’s experience. The
MRI is an objective method, while ultrasound
is real-time method that highly depends of the
operator’s capacity and experience as well as the
patient’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 žurnal 2013 Ⴠ19 (1): 4 - 8
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Sandra Vegar-Zubović, Spomenka Kristić, Lidija Lincender , Irmina Sefić-Pašić, Aladin Čarovac. 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-Zubović Sandra, MD, PhD
Clinic of Radiology
Clinical Center University of Sarajevo
Bolnička 25, 71000 Sarajevo
Bosnia and Herzegovina
Phone: +387 61 202 880
Email: sandra.vegar@gmail.com
Naš prilog redukciji kardiovaskularnih bolesti !
Our contribution in reduction of cardiovascular diseases !
Medicinski žurnal 2013 Ⴠ19 (1): 4 - 8
Fatima Gavrankapetanović-Smailbegović, Muhamed Ardat, Lejla Imširija, Naima Imširija, Faruk Lazović, Mehmed Jamakosmanović.
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 MOGUĆI PREDIKTORI NEONATALNIH LEZIJA PLEKSUSA BRAHIJALISA
Fatima Gavrankapetanović-Smailbegović¹*, Muhamed Ardat¹, Lejla Imširija¹, Naima Imširija¹,
Faruk Lazović², Mehmed Jamakosmanović²
¹Clinic for Gynaecology and Obstetrics, Clinical Center University of Sarajevo, Patriotske lige 81, 71000 Sarajevo,
Bosnia and Herzegovina; ²Orhtopedic and Traumatology Clinic, Clinical Center University of Sarajevo,
Bolnička 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 baby’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
SAŽETAK
Tokom poroda možemo naići na poteškoće
koje mogu dovesti i do traume novorođenčeta.
Porođajna lezija brahijalnog spleta predstavlja
najčešći neurološki sindrom perifernog tipa nastao rođenjem, pa stoga zauzima važno mjesto u
polivalentnoj rehabilitaciji djece. Lezije mogu biti
različitog stepena, pa u literaturi nailazimo na
dvije forme, parezu i paralizu pleksus brahijalisa.
Različiti činioci mogu dovesti do povrede, ali niz
autora smatra da je sam tok poroda glavni uzrok oštećenja pleksus brahijalisa. Suština je, zapravo, da se u ovim slučajevima radilo o slaboj
opstetričkoj tehnici u najvećem broju opisanih
slučajeva. Povreda pleksusa može nastati i tokom spontanog poroda, iako je, najčešće direktan
uzrok trakcija sa abdukcijom glave bebe u odnosu
na rameni pojas. Sprovedena je retrospektivnoprospektivna, manipulativno, terapeutsko, kohortno kontrolirana, randomizirana studija Obrađeno
je Pacijentice su podijeljene u dvije skupine.
Istraživanje je provedeno na 18.914 poroda, tokom perioda od 5 godina. Analizom starosne
distribucije porodilja, pokazalo se da je 23.33%
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Fatima Gavrankapetanović-Smailbegović, Muhamed Ardat, Lejla Imširija, Naima Imširija, Faruk Lazović, Mehmed Jamakosmanović.
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 više od
jedne trećine, 34.29%. Povreda pleksus brahijalisa koje se javlja u toku poroda je teško oboljenje,
koje može ima dugogodišnje posljedice, i čiji se
stepen procjenjuje i godinama nakon nastanka.
Neophodni kvalitativno i redovno pračenje trudnice, redovni ultrazvučni pregledi, u cilju praćenja
stanja fetusa, te određivanja prezentacije ploda,
ali i precizno određivanje vrijednosti biparijetalnog parametra, također potrebno je kvalitetno i
precizno mjerenje dimenzija karlice.
Ključe riječi: pleksus brahijalis, pareza, paraliza, porod
and repair on its own during the first weeks of the
child’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 baby’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 child’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: mother’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 child’s life, then the chances for it to happen after are quite small. Many cases
of brachial plexus paralysis are of transient nature,
Medicinski žurnal 2013 Ⴠ19 (1): 9 - 13
Fatima Gavrankapetanović-Smailbegović, Muhamed Ardat, Lejla Imširija, Naima Imširija, Faruk Lazović, Mehmed Jamakosmanović.
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.
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Fatima Gavrankapetanović-Smailbegović, Muhamed Ardat, Lejla Imširija, Naima Imširija, Faruk Lazović, Mehmed Jamakosmanović.
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 žurnal 2013 Ⴠ19 (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 Gavrankapetanović-Smailbegović, Muhamed Ardat, Lejla Imširija, Naima Imširija, Faruk Lazović, Mehmed Jamakosmanović.
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.
Avery’s diseases of the newborn. Philadelphia: Elsavier Sounders; 2005. pp.1431-1433.
2. O’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, Düppe 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 Gavrankapetanović-Smailbegović, 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: fatima.smailbegovic@gmail.com
Medicinski žurnal 2013 Ⴠ19 (1): 9 - 13
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Faris Fočo, Lejla Džananović, Zlatan Zvizdić, Edin Imamović, Irma Ramović, Semra Čavaljuga. Malignant lip tumours ; survival analysis
Original article
MALIGNANT LIP TUMOURS; SURVIVAL ANALYSIS
MALIGNI TUMORI USANA; ANALIZA PREŽIVLJAVANJA
2
Faris Fočo1*, Lejla Džananović , Zlatan Zvizdić 3, Edin Imamović1, Irma Ramović1, Semra Čavaljuga2
1
Clinic for Maxillofacial Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo,
2
Bosnia and Herzegovina; Institute of Epidemiology and Biostatistics, Faculty of Medicine University
3
of Sarajevo, Čekaluša 90, 71000 Sarajevo, Bosnia and Herzegovina; Clinic for Paediatric Surgery,
Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina
*Corresponding author
ABSTRACT
SAŽETAK
This paper referred to malignant tumours of lips.
The objectives of this study were to present distribution of malignant diseases of lips according to
patients’ 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 patološke analize i predstavi analizu
petogodišnjeg preživljavanja ovih pacijenata, kao
i da ispita značaj rane dijagnoze i tretmana.
Sprovedena je desetogodišnja retrospektivna
klinička i observaciona studija na pacijentima
Klinike za maksilofacijalnu hirurgiju Kliničkog
centra Univerziteta u Sarajevu, koji su tretirani
zbog malignog tumora usana, u periodu januar
1998 – decembar 2007. Ukupno je tretiran 1.271
pacijent od kojih je njih 139 imalo tumor usana.
Rezultati ove studije pokazali su da je veći broj
tretiranih pacijenata muškog spola (odnos spolova 2,3 naprema 1 u korist muškaraca). Većina su
stariji pacijenti, a skoro ih polovina (49.64%) ima
60 i više godina. Histopatološka analiza tumora
pokazala je da je najčešći tip bio karcinom skvamoznih ćelija. Analiza preživljavanja pokazala je
petogodišnju stopu preživljavanja od 71,23%.
Ova studija ipak treba biti posmatrana kao pilot
studija. Preporučuje se sprovesti studiju slične
metodologije ali znatno obimniju – što se tiče broja pacijenata, detaljnijih anamnestičkih podataka i
dužeg perioda praćenja, u cilju razjašnjavanja korelacije svih demografskih podataka, riziko faktora,
terapije i tačnog vremena i stopa preživljavanja.
Key words: malignant lip tumours, survival,
survival analysis
Ključne riječi: maligni tumori usana, preživljavanje,
analiza preživljavanja
Medicinski žurnal 2013 Ⴠ19 (1): 14 - 19
Faris Fočo, Lejla Džananović, Zlatan Zvizdić, Edin Imamović, Irma Ramović, Semra Čavaljuga. 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 žurnal 2013 Ⴠ19 (1): 14 - 19
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Faris Fočo, Lejla Džananović, Zlatan Zvizdić, Edin Imamović, Irma Ramović, Semra Čavaljuga. 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.
Karapandžić, 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 žurnal 2013 Ⴠ19 (1): 14 - 19
Faris Fočo, Lejla Džananović, Zlatan Zvizdić, Edin Imamović, Irma Ramović, Semra Čavaljuga. 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 žurnal 2013 Ⴠ19 (1): 14 - 19
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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, Géraud 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 tumours’ 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-Sarobé 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 “V” and “W” excision (in 22 and 37 cases, respectively). Lopes and collaborators prefer “W”
and “Y” 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 Kayabaşoğlu G., prefer the method with local flaps. Reconstruction
by sec. Karapandžić, 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 žurnal 2013 Ⴠ19 (1): 14 - 19
survival without relapse was observed in about
98% cases (19, 21). Our study was conducted in
period 1998-2012, however patients’ 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 study’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. Dautović S, Tomić-Ćuk 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 Fočo, Lejla Džananović, Zlatan Zvizdić, Edin Imamović, Irma Ramović, Semra Čavaljuga. 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-Sarobé 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. Géraud 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, Oksüzler 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. Kayabaşoğlu 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 Fočo, MD, PhD
Clinic for Maxillofacial Surgery
Clinical Center University of Sarajevo
Hazima Šabanovića 1, 71000 Sarajevo
Bosnia and Herzegovina
Phone: +387 33 226661
Email: farisfoco@yahoo.com
Medicinski žurnal 2013 Ⴠ19 (1): 14 - 19
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Narcisa Vavra-Hadžiahmetović, Aldijana Kadić, Damir Čelik. 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
ZNAČAJ SPROVEDBE DRG (DIAGNOSIS RELATED GROUPS) REFORME U
ZDRAVSTVU ZA OBLAST FIZIKALNE MEDICINE I REHABILITACIJE
Narcisa Vavra-Hadžiahmetović*, Aldijana Kadić, Damir Čelik
Clinic for Physical Medicine and Rehabilitation, Clinical Center University of Sarajevo, Bolnička 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 žurnal 2013 Ⴠ19 (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
SAŽETAK
Projekat Reforme finansiranja sekundarne
zdravstvene zaštite u Bosni i Hercegovini finansiran je od strane Europske Unije, a opći cilj projekta je postavljanje temelja za sistem plaćanja
bolnica temeljen na rezultatima i budući razvoj
zdravstvenih informacijskih mogućnosti u bolnicama, te izrada čvrstih temelja za glavnu reformu
plaćanja bolnica. Cilj rada je prikazati prednosti i
nedostatke u primjeni DRG reforme na Klinici za
fizijatriju i bolnicama, te izrada čvrstih temelja
Narcisa Vavra-Hadžiahmetović, Aldijana Kadić, Damir Čelik. The significance of implementation of DRG (Diagnosis Related Groups) health care
reforms in the field of physical medicine and rehabilitation
za glavnu reformu plaćanja bolnica. Cilj rada je
prikazati prednosti i nedostatke u primjeni DRG
reforme na Klinici za fizijatriju i rehabilitaciju
Kliničkog 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 uključila 41 pacijenta hospitalizovanih na Klinici za fizijatriju i rehabilitaciju
KCUS. Kao izvor podataka korištena je medicinska dokumentacija. U studiju su uključene tri
grupe pacijenata sa: cerebrovaskularnim inzultom
(CVI) (n=19), diskus hernijom (HD) (n=17) i amputacijom potkoljenice (ABK) (n=15). Korištene su
mjere deskriptivne statistike: frekvencija i relativna
frekvencija (%). U grupi pacijenata sa CVI (n=19),
ranije dijagnostičko-terapeutske procedure (DTP)
koje su se šifrirale podrazumijevaju: pasivne
vježbe, hod uz pomagalo, balans, okupaciona terapija i galvanizacija. Prema DRG sistemu, ukupan
broj DTP je veći i podrazumijeva: biomehanička
procjena (19 ili 100%), aktivnosti svakodnevnog
života (ASŽ) (19 ili 100%), uzimanje krvi za dijagnostiku (16 ili 84,2%), terapija vježbanjem-rameni
zglob (4 ili 21,1%), terapija vježbanjem-mišići
grudnog koša i abdomena (1 ili 5,3%), terapija
vježbanjem-mišići leđa i vrata (2 ili 10,5%), terapija vježbanjem-mišići ruku (6 ili 31,6%), terapija vježbanjem-zglob lakta (3 ili 15,8%), terapija
vježbanjem-mišići šaka, ručnog zgloba i zglobova
prstiju ruke (1 ili 5,3%), terapija vježbanjem-zglob
kuka (2 ili 10,5%), terapija vježbanjem-mišići dna
zdjelice (3 ili 15,8%), terapija vježbanjem-mišići
nogu (6 ili 31,6%), terapija vježbanjem mišića stopala, skočnog zgloba i nožnih prstiju (4 ili 21,1%),
treniranje vještina u aktivnostima koje se odnose
na položaj tijela/pokretljivost/kretanje (21,1%), treniranje vještina u aktivnostima koje se odnose na
premještanje /kade, kreveta, stolice, poda, tuša,
toaleta, vozila/ (1 ili 5,3%), terapija vježbanjem respiratorni sistem /disanje/ (7 ili 36,8%), treniranje
vještina upotrebe pomoćnih ili adaptivnih naprava,
pomagala i opreme /stavljanje zavoja i bandaža,
trening pokretljivosti sa pomagalima/ (3 ili 15,8%),
terapija vježbanjem, cijelo tijelo /opća terapija
vježbanjem/ (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 /
hipertermička terapija/ (2 ili 10,5%), stimulacijska
terapija /EMS, FES, IFT, TENS/ (5 ili 26,3%), terapija vježbanjem, mišići lica/temporomandibularni
zglob (1 ili 5,3%), terapijska masaža ili manipulacija vezivnog ili mekog tkiva (1 ili 5,3%). U grupi pacijenata sa HD (n=17,) ranije DTP koje su šifrirane
podrazumijevaju: ASŽ, izometrijske vježbe, elektroprocedure, dok je prema DRG sistemu, ukupan
broj DTP je veći 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 šifrirane podrazumijevaju: bandažiranje, aktivne vježbe za bataljak uz otpor, vježbe hoda, dok
je prema DRG sistemu, ukupan broj DTP je veći i
podrazumijeva ukupno 10 DTP.
Zaključak: Novo šifriranje kroz program DRG-a
daje bolje mogućnosti šifriranja usluga a time i
bolju naplatu učinjenih procedura, što vodi dobrom praćenju efektivnosti bolnica i boljem vrednovanju rada bolničkog sektora u cjelini.
Ključne riječi: 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 (“trim
day”) (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 žurnal 2013 Ⴠ19 (1): 20 - 24
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Narcisa Vavra-Hadžiahmetović, Aldijana Kadić, Damir Čelik. 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 – 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 žurnal 2013 Ⴠ19 (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-Hadžiahmetović, Aldijana Kadić, Damir Čelik. 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
“Implementation of the DRGs impact on hospitals
and medical rehabilitation of geriatric patients in
Germany” 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), “The impact of
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Narcisa Vavra-Hadžiahmetović, Aldijana Kadić, Damir Čelik. 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 Germany” 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 žurnal 2013 Ⴠ19 (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 ‘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 ‘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-Hadžiahmetović, MD, PhD
Clinic for Physical Medicine and Rehabilitation
Clinical Center University of Sarajevo
Bolnička 25, 71000 Sarajevo
Bosnia and Herzegovina
Phone:+387 33 297 373
Email: paraplegijakcu@bih.net.ba
Dragana Nikšić, Amela Džubur, Amira Kurspahić Mujčić. Awareness of physicians about patients’ rights; patient consent form
Original article
AWARENESS OF PHYSICIANS ABOUT PATIENTS’ RIGHTS; PATIENT CONSENT
FORM
OBAVIJEŠTENOST LJEKARA O PRAVU PACIJENTA; INFORMIRANI PRISTANAK
PACIJENTA
Dragana Nikšić, Amela Džubur*, Amira Kurspahić Mujčić
Institute of Public Health, Faculty of Medicine, University of Sarajevo, Čekaluša 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 „authorized” 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 patient’s right
to informed medical consent and are there some
differences according to the institution of employment. The research represents a „cross-sectional
“study 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 „Dr. fra Mato Nikolić“ Nova
Bila, General Hospital Konjic) and primary health
care level (primary health care centers: Novi Grad
Sarajevo, Livno, Ljubuški, Orašje, Goražde 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
SAŽETAK
Informirani pristanak pacijenta je autonomna au torizacija medicinske intervencije-tretmana uz
znanje o mogućim posljedicama. To je promjena
tradicionalno-paternalističkog pristupa odnosa
doktor-pacijent. Glavna karakteristika te promjene
je što doktor postaje «opunomoćenik» pacijenta,
a pacijent subjekt odlučivanja o svom zdravlju i
životu. Cilj rada je utvrditi u kojoj mjeri su ljekari
specijalisti Federacije BiH koji su zaposleni na
različitim nivoima zdravstvene zaštite obaviješteni
o pravu pacijenta na informisani medicinski
pristanak kao i da li postoje razlike prema mjestu
zaposlenja. Istraživanje predstavlja « cross-sec tional» studiju odgovora doktora specijalista zaposlenih u kliničkim centrima, bolnicama i domovima zdravlja Federacije BiH. Na osnovu evidencije
zaposlenih ljekara u odabranim ustanovama randomiziranim uzorkovanjem dobiven je uzorak od
455 ispitanka (svaki četvrti doktor specijalista sa
liste evidencije ili 15,8% specijalista zaposlenih u
Federaciji BIH). Anketu je popunilo 357 doktora
što čini 78.5% stope odgovora. Istraživanje je provedeno u javnim zdravstvenim ustanovama tercijarnog nivoa zdravstvene zaštite (KCU Sarajevo,
Klinička bolnica Mostar, Univerzitetsko klinički
centar Tuzla), sekundarnog nivoa (Kantonalna
Medicinski žurnal 2013 Ⴠ19 (1): 25 - 31
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Dragana Nikšić, Amela Džubur, Amira Kurspahić Mujčić. Awareness of physicians about patients’ rights; patient consent form
bolnica Zenica, RMC Mostar, HB Nova Bila,
Opšta bolnica Konjic) i primarnog nivoa zdravstvene zaštite (domovi zdravlja: Novi Grad Sara jevo, Livno, Ljubuški, Orašje, Goražde i Cazin).
Ispitanici su u prosjeku znali odgovoriti na 50%
pitanja koja su se odnosila na općenito poznavanje informiranog pristanka. Prema zdravst venim ustanovama postoji signifikantna razlika
u stepenu općeg poznavanja informiranog pristanka. Ispitanici u bolnicama su imali značajno
veći broj tačnih odgovora u odnosu na ispitanike
iz drugih zdravstvenih ustanova.
Ključne riječi: obaviještenost, 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
„authorized" 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. Doctor’s knowlMedicinski žurnal 2013 Ⴠ19 (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 patient’s right
to informed medical consent and are there some
differences according to the institution of employment.
MATERIALS AND METHODS
The research represents a „cross-sectional“ 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 „Dr. fra Mato
Nikolić “Nova Bila, General Hospital Konjic) and
primary health care level (primary health care centers: Novi Grad Sarajevo, Livno, Ljubuški, Orašje,
Goražde 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 Nikšić, Amela Džubur, Amira Kurspahić Mujčić. Awareness of physicians about patients’ 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 „do
not know", defined as „no 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 patient’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 patient’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 „milder risks“ 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 žurnal 2013 Ⴠ19 (1): 25 - 31
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Dragana Nikšić, Amela Džubur, Amira Kurspahić Mujčić. Awareness of physicians about patients’ 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 žurnal 2013 Ⴠ19 (1): 25 - 31
,
Tabele 2. The answers to the doctor s place
of employment.
Dragana Nikšić, Amela Džubur, Amira Kurspahić Mujčić. Awareness of physicians about patients’ rights; patient consent form
DISCUSSION
In today’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 patient’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 patients’ 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
patient’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 žurnal 2013 Ⴠ19 (1): 25 - 31
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Dragana Nikšić, Amela Džubur, Amira Kurspahić Mujčić. Awareness of physicians about patients’ 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 patients’
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 special-
ist working in clinical centers involved in our
Medicinski žurnal 2013 Ⴠ19 (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 patient’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 patients’ 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 Nikšić, Amela Džubur, Amira Kurspahić Mujčić. Awareness of physicians about patients’ rights; patient consent form
5. McGuire AL, McCullough LB, Weller SC,
Whitney SN. Missed expectations? Physicians’
views of patients’ participation in medical deci sion making. Med Care. 2005; 43:466-70.
6. O’Leary KJ, Kulkarni N, Landler MP, Jeon
J, Hahn KJ, Englert KM, Williams MV. Hospi talized patients’ understanding of their plan of
care. Mayo Clin Proc. 2010; 85:47-52.
7. Jukić M, Kvolik S, Kardum G, Kozina S, Tomić
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 – his torical perspective and a clinician’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 doctors’
practices in South Africa. S Afr Med J. 1995
Dec;85(12):1273-8.
18. Zakon o pravima, obvezama i odgovornostima
pacijenata. Sarajevo: „Službene novine Federacije BiH“, broj 40/10.
19. Bencko V. Informed consent in the Czech
Republic. Sci Total Environ. 1996;184:77–81.
Address:
Prof. Dragana Nikšić, MD, PhD
Institute of Public Health
Faculty of Medicine, University of Sarajevo
Čekaluša 90, 71000 Sarajevo
Bosnia and Herzegovina
Phone: +387 33 226 478
Email: niksicd@gmail.com
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Ifeta Ličanin, Alem Ćesir, Saida Fišeković. 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 Ličanin*, Alem Ćesir, Saida Fišeković
*Psychiatric Clinic, Clinical Center University of Sarajevo, Bolnička 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.
Istraživanje je obavljeno na Psihijatrijskoj klinici
Kliničkog centra Univerziteta u Sarajevu. Randomizirano odabrani ispitanici (od 5-89 godina,
1316 muškog i 1039 ženskog spola) N=2355 su
intervjuisani korištenjem Strukturisanog Kliničkog
Uputnika (SCID) za postavljanje dijagnoze prema
DSM-IV. Studija je retrospektivno-prospektivna,
kliničko-epidemiološka. Analizirana je stopa prijema ispitanika sa shizofrenijom u toku određenih
godišnjih doba kao i korelacija uticaja godišnjih
doba na povećanu stopu prijema tih ispitanika na
Psihijatrijsku kliniku. Prikupljeni su i obrađeni relevantni podaci iz Federalnog hidrometeorološkog
zavoda u Sarajevu o klimatološkoj situaciji na
području Sarajevskog kantona za taj period. Rezultati i zaključci: Od ukupnog broja ispitanika koji
su primljeni na kliniku u periodu 2010/2011. godine,
među najfrekventnijim dijagnozama izdvojena je
šizofrenija (F20-F29). Nađeno je da postoji korelacija između određenih godišnjih doba i djelovanja
određenih vremenskih parametara na povećanu
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
SAŽETAK
Uticaj klime i klimatskih faktoria na ljudsko zdravlje
i duševne bolesti kod čovjeka i pogoršanje istih su
u fokusu istraživanja od davnina. Cilj samog rada
je ustanoviti da li godišnja doba i određeni vremenski faktori imaju uticaj na porast stope prijema
ispitanika sa šizofrenijom na liječenje.
Medicinski žurnal 2013 Ⴠ19 (1): 32 - 37
Ključne riječi: klima, klimatski faktori, meteoropatija, duševna oboljenja, shizofrenija
INTRODUCTION
Ifeta Ličanin, Alem Ćesir, Saida Fišeković. 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 “pushed” to from and has been par ticularly linked with affective disorders and their
tragic consequences –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 „stressful 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
• Determine the total number of patients admitted
to hospital during the period 2010-2011.
• Determine whether there is an increased
incidence of schizophrenia in certain seasons
during the 2010-2011.
• Determine whether there are some specific
weather parameters which affect the increased
incidence of schizophrenia.
Medicinski žurnal 2013 Ⴠ19 (1): 32 - 37
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Ifeta Ličanin, Alem Ćesir, Saida Fišeković. 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 žurnal 2013 Ⴠ19 (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 Ličanin, Alem Ćesir, Saida Fišeković. 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
൹-34
൹-37
ൻ-18
1
൹-30 1
1
Medicinski žurnal 2013 Ⴠ19 (1): 32 - 37
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Ifeta Ličanin, Alem Ćesir, Saida Fišeković. 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 žurnal 2013 Ⴠ19 (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 Ličanin, Alem Ćesir, Saida Fišeković. 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 today’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 body’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 Ličanin, MD, PhD
Psychiatric Clinics,
Clinical Center University of Sarajevo,
Bolnička 25, 71000 Sarajevo
Bosnia and Herzegovina
Phone; +387 33 297 228
Email: licaninifeta@hotmail.com
Conflict of interest: none declared.
Medicinski žurnal 2013 Ⴠ19 (1): 32 - 37
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Jasminka Đelilović-Vranić, Azra Alajbegović, Mehmed Kulić, Amina Nakičević, Emina Ejubović, Merita Tirić-Čampara, Edina Đozić, Ljubica Todorović,
Salem Alajbegović. Heart rhythm disorders as a contributing factor to ischemic stoke
Original article
HEART RHYTHM DISORDERS AS A CONTRIBUTING FACTOR TO ISCHEMIC
STROKE
POREMEĆAJI SRČANOG RITMA KAO ETIOLOŠKI FAKTOR U NASTANKU
ISHEMIČNOG MOŽDANOG UDARA
1*
1
1
Jasminka Đelilović-Vranić , Azra Alajbegović , Mehmed Kulić 2, Amina Nakičević ,
1
1
1
Emina Ejubović , Merita Tirić-Čampara , Edina Đozić 1, Ljubica Todorović , Salem Alajbegović 3
1
Neurology Clinic, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina
Hearth Center Sarajevo, Clinical Center University of Sarajevo, Bolnička 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 žurnal 2013 Ⴠ19 (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
SAŽETAK
Moždani udar - cerebrovaskulatrni inzult je bolest koja
ima tendenciju rasta u svijetu, a posebno u zemljama u razvoju gdje spadamo i mi. Čest uzrok nasatnka
ishemičnog moždanog udara je poremećaj srčanog ritma.Cilj rada je utvrditi postojanje poremećaja srčanog
ritma kod oboljelih od moždanog udara. Sprovedeno
je retrospektivno istraživanje je u regionu Sarajevo,
u toku jednogodišnjeg perioda (juli 2011-juli 2012.),
gdje su registrovani svi oboljeli od ishemičnog moždanog
udara. Svim pacijentima su uz anamnezu i neurol
oški pregled urađeni CT mozga radi potvrde ishemič
nog inzulta, te EKG i kardiološki nalaz radi utvrđivanja
poremećaja srčane frekvencije uz laboratorijske nalaze. U toku jednogodišnjeg perioda (juli 2011-juli 2012)
ukupno je liječeno 961 pacijenata od ishemičnog moždanog udara. Od toga je 71% pacijenta sa trombotičnim, a
29% sa embolijskim moždanim udarom. Muškarci su
činili 48,4% ispitanika, a žene 51,6% sa rasponom
životne dobi od 37 do 79 godina. Najčešći riziko faktori su bili hipertenzija kod 83,7% pacijenata, diabetes
mellitus kod 34,4% pacijenata, a poremećaj srčanog
ritma je zabilježen kod 22,7% pacijenata, pri čemu
Jasminka Đelilović-Vranić, Azra Alajbegović, Mehmed Kulić, Amina Nakičević, Emina Ejubović, Merita Tirić-Čampara, Edina Đozić, Ljubica Todorović,
Salem Alajbegović. Heart rhythm disorders as a contributing factor to ischemic stoke
je sinusnu tahikardiju imalo 18% pacijenta, SVES
22% pacijenata , a čak 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 zabilježena kod 15,15%.
Umrlo je 35% pacijenata, a preživjelo 65%, i to
u grupi sa fibrilacijom atrija smrtnost je iznosila
31,2 %.Zaključak: Poremećaji srčanog ritma se
mogu javiti u bilo kojoj dobi, ali produženje ljudskog vijeka ima za posljedicu učestalije poremećaje
srčanog ritma, što povećava rizik obolijevanja
od moždanog udara. Poremećaji srčanog ritma
povećavaju rizik recidiva embolijskog moždanog
udara. Pravovremenim otkrivanjem poremećaja
srčanog ritma i adekvatnim liječenjem moguće je
spriječiti nastanak moždanog udara, a time i bitno
smanjiti broj invalidnih osoba te troškove liječenja
svesti na manji nivo, a život u trećoj dobi učiniti
kvalitetnijim.
Ključne riječi: poremećaji srčanog ritma, ishemični moždani 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 žurnal 2013 Ⴠ19 (1): 38 - 42
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Jasminka Đelilović-Vranić, Azra Alajbegović, Mehmed Kulić, Amina Nakičević, Emina Ejubović, Merita Tirić-Čampara, Edina Đozić, Ljubica Todorović,
Salem Alajbegović. 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 žurnal 2013 Ⴠ19 (1): 38 - 42
Jasminka Đelilović-Vranić, Azra Alajbegović, Mehmed Kulić, Amina Nakičević, Emina Ejubović, Merita Tirić-Čampara, Edina Đozić, Ljubica Todorović,
Salem Alajbegović. 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 Terént, 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 hyper-
tension, 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 Bošnjak-Pašić and
Marijana Bosnar-Puretić 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 „cardiac" 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 žurnal 2013 Ⴠ19 (1): 38 - 42
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Jasminka Đelilović-Vranić, Azra Alajbegović, Mehmed Kulić, Amina Nakičević, Emina Ejubović, Merita Tirić-Čampara, Edina Đozić, Ljubica Todorović,
Salem Alajbegović. 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): 319–329.
2. Demarin V, Trkanjec Z, Šerić V. Moždani udar.
Hrvatsko društvo za prevenciju moždanog 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): 488–502.
Medicinski žurnal 2013 Ⴠ19 (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. O’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, Bošnjak-Pašić M, Bosnar-Puretić
M. Moždani udar-vodeći uzrok invaliditeta. Hrvatsko društvo za prevenciju moždanog udara Hrvatska.
2011; 3(3):212-218.
10. Santamarina E, Alvarez Sabín 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 Đelilović-Vranić, MD, PhD
Neurology Clinic,
Clinical Center of University of Sarajevo
Bolnička 25,
71000 Sarajevo
Bosnia and Herzegovina
Phone: +387 33 297 236
Email: jasminka000@bih.net.ba
Aida Hasanović, Belma Aščić-Buturović, Muhamed Spužić. 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 Hasanović , Belma Aščić-Buturović 2, Muhamed Spužić 3
1
Department of Anatomy, Faculty of Medicine, University of Sarajevo, Čekaluša 90, 71 000 Sarajevo, Bosnia
2
and Herzegovina; Clinic for Endocrinology, Diabetes and Metabolism disorders, Clinical Center University of
3
Sarajevo, Bolnička 25, 71 000 Sarajevo, Bosnia and Herzegovina; Heart Center, Clinical Center University of
Sarajevo, Bolnička 25, 71 000 Sarajevo, Bosnia and Herzegovina
* Corresponding author
ABSTRACT
SAŽETAK
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 istraživanja je bio prikazati različite tipove varijacija koronarnih arterija na angiogramima ispitivanih pacijenata, utvrditi njihovu incidencu i klinički
značaj. Retrospektivno istraživanje obuhvatilo je
670 pacijenata sa ishemičnom bolesti srca, kojima
je u periodu od 01. 04.2011. – 01.04. 2012.godine
urađena koronarna angiografija u Centru za srce
Kliničkog centra Univerziteta u Sarajevu. Varijacije koronarnih arterija su otkrivene u 10 slučajeva
(incidenca 1.5%). Kod 2 pacijenta (0,3%), uočene
su varijacije polazišta koronarnih arterija (1 pacijent sa anomalijom polazišta koronarne arterije
iz suprotnog sinusa Valsalvae i 1 pacijent sa
ektopičnim polazištem desne koronarne arterije
iz lijevog sinusa Valsavlae.Varijacije broja (jedna
koronarna arterija) uočene su kod 1 pacijenta
(0,1%), varijacije pravca pružanja (mišićni most)
kod 4 pacijenta (0,6%), dok su varijacije završetka
koronarnih arterija (koronarne fistule) uočene kod
3 pacijenta (0,4%). Statistička analiza upotrebom
Kolmogorow-Smirnow testa pokazala je da ne
postoje statistički značajne razlike u zastupljenosti
varijacija koronarnih arterija među grupama. Varijacije koronarnih arterija imaju nisku učestalost
javljanja u općoj populaciji i rijetko se otkrivaju koronarnom angiografijom. Najčešće varijacije kod
naših ispitanika bile su varijacije pravca pružanja
(miokardni most) sa 0,6%, a najmanje zastupljene su varijacije broja su varijacije broja (jedna
koronarna arterija) sa 0,1%. Varijacije koronarnih
arterija, u većini slučajeva nisu prouzrokovale
simptome, te su slučajno otkrivene pri koronarnoj
angiografiji. Neke varijacije mogu biti udružene
sa ozbiljnim posljedicama kao što su angina pektoris, infarkt miokarda, sinkopa, srčane aritmije
ili iznenadna smrt.
Key words: coronary arteries, variations, coronary
angiography
Ključne riječi: koronarne arterije, varijacije, koronarna angiografija
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Aida Hasanović, Belma Aščić-Buturović, Muhamed Spužić. 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, 17–65 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 žurnal 2013 Ⴠ19 (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 Hasanović, Belma Aščić-Buturović, Muhamed Spužić. 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
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Aida Hasanović, Belma Aščić-Buturović, Muhamed Spužić. 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 into”benign” (asymptomatic) and “potentially
serious”. 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 žurnal 2013 Ⴠ19 (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. Hasanović A, Dilberović F, Ovčina F. Anatomical-clinical investigations of variations of the
human coronary arteries. Bosn J Basic Med Sci.
2003;3(4): 23-25.
4. Hasanović A. Doprinos istraživanju varijacija
srčanih arterija čovjeka 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. Koşar P, Ergun E, Öztürk C, Koşar U. Anatomic
variations and anomalies of the coronary arteries:
64-slice CT angiographic appearance. Diagn Interv Radiol. 2009;15:275–283.
Aida Hasanović, Belma Aščić-Buturović, Muhamed Spužić. 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. Mædica 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. Hasanović A, Junuzović A, Spužić M,
Kudumović 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 Hasanović, MD, PhD
Department of Anatomy
Faculty of Medicine, University of Sarajevo
Čekaluša 90, 71 000 Sarajevo
Bosnia and Herzegovina
Phone: +387 33 665 949
Email: aidah@utic.net.ba
Nova centralna zgrada Kliničkog Centra Univerziteta u Sarajevu
New Central building of the Clinical Center University of Sarajevo
Medicinski žurnal 2013 Ⴠ19 (1): 43 - 47
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48
Dženela Prohić, Rusmir Mesihović, Nenad Vanis, Srđan Gornjaković, Amra Puhalović, Aida Saray. Prognostic assessment in patients with
decompensated cirrhosis
Professional article
PROGNOSTIC ASSESSMENT IN PATIENTS WITH DECOMPENSATED CIRRHOSIS
PROGNOSTIČNE PROCJENE KOD PACIJENATA SA DEKOMPENZIRANOM CIROZOM
1,2
Dženela Prohić* , Rusmir Mesihović , Nenad Vanis , Srđan Gornjaković , Amra Puhalović ,
1
Aida Saray
1
1
1
1
1
Clinic for Gastroenterohepatology, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo,
2
Bosnia and Herzegovina; Department of Medicine, Universitetssykehuset Nord Nodge, Norway
*Corresponding author
ABSTRACT
SAŽETAK
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 prognostičkih skorova kreiran
je u cilju procijene mortaliteta kod pacijenata sa
dekomepnziranom cirozom. The Model for the
End Stage Liver Disease (MELD) je široko prih vraćen i korišten u odnosu na ostale, osobito tradi cionalni Child Pugh (CP) skor u procijeni preživljenja pacijenata sa dekompenziranom jetrenom cirozom. Serumska vrijednost kreatinina smatra se
signifikantnim parametrom preživljenja kod ove
grupe pacijenata. Cilj ovog istraživanja 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 praćena je u periodu od
6 mjeseci. CP, kreatinin modificirani CP i MELD
skor su izračunati. Kreatinin modificirani CP skor
je izračunat koristeći serum kreatinin kao šestu
kategoričku varijablu dodatu tradicionalnom CP
skoru uz dodatnih 0-3 boda. Izračunali smo i usporedili tačnost (c- index) sva tri skora u procijeni šestomjesečnog mortaliteta. Rezultati: Area
ispod ROC krivulje pokazala je da sva tri skora
imaju signifikatnu prediktivnu tačnost, kreatinin
modificirani CP skor je pokazao bolju prognostičku
tačnost uspoređen sa tradicionalnim CP skorom
(CP c-statistika: 0,761 vs. kreatinin modificirani
CP 0,846). MELD skor je pokazao najjaču prog nostičku snagu (vrijednost c statistike:0,872). Sva
tri skora statistički koreliraju međusobno sa najja čom korealcijskom vrijednosti između tradicionalnog CP i kreatinin modificiranog CPskora (r 95,1%)
Zaključak: MELD skor posjeduje jaču prediktivnu
tačnost uspoređeno 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 žurnal 2013 Ⴠ19 (1): 48 - 53
Dženela Prohić, Rusmir Mesihović, Nenad Vanis, Srđan Gornjaković, Amra Puhalović, Aida Saray. Prognostic assessment in patients with
decompensated cirrhosis
Dodavanjem serumske vrijednosti kreatinina vrijednostima CP skora unapređuje se prognosticka jačina tradicionalnog CP skora.
Ključne riječi: 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).
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Dženela Prohić, Rusmir Mesihović, Nenad Vanis, Srđan Gornjaković, Amra Puhalović, 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 žurnal 2013 Ⴠ19 (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 – 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).
Dženela Prohić, Rusmir Mesihović, Nenad Vanis, Srđan Gornjaković, Amra Puhalović, 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-mak-
ing 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
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Dženela Prohić, Rusmir Mesihović, Nenad Vanis, Srđan Gornjaković, Amra Puhalović, 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 Resić, 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? J Hepatol. 2004 Aug;41(2):344-50.
3. Child CG3, Turcotte JG. Surgery and por tal hypertension. In: Child CG3, ed. The Liv er and Portal Hypertension. Philadelphia:
W.B.Saunders;1964. pp.1-85.
4. Pugh RNH,Murray-Lyon M, Dawson JL, Pi etroni MC, Williams R. Transection of the oe sophagus for bleeding oesophageal varices. Br
J Surg. 1973; 60(8): 646-9.
Medicinski žurnal 2013 Ⴠ19 (1): 48 - 53
5. Forman LM,Lucey MR. Predicting the prognosis of chronic liver disease: an evolution from
Child to MELD. Hepatology. 2001 Feb; 33(2):
473-5.
6. Conn HO.A peak at the Child-Turcotte clas sification.Hepatology. 1981 Nov-Dec;1(6): 673-6.
7. Reuben A.Child comes of age. Hepatology.
2002 Jan; 35(1): 244-5.
8. Villeneuve JP,Infante-Rivard C, Ampelas M,
Pomier-Layrargues G, Huet PM, Marleau D.
Prognostic value of the aminopyrine breath test
in cirrhotic patients. Hepatology. 1986 Sep-Oct;
6(5):928-31.
9. Adler M, Verset D, Bouhdid H, Bourgeois N,
Gulbis B, Le Moine O, et al. Prognostic evalua tion of patients with parenchymal cirrhosis. Proposal of a new simple score. J Hepatol.1997 Mar;
26(3):642-49.
10. Kamath PS, Wiesner RH, Malinchoc M, Kre mers W, Therneau TM, Kosberg CL, et al. A
model to predict survival in patients with endstage liver disease.Hepatology.2001 Feb; 33(2):
464-70.
11. Malinchoc M, Kamath P S, Gordon FD, Peine
CJ, Rank J, ter Borg PC. A model to predict poor
survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000
Apr; 31(4): 864–71.
12. Salerno F, Merli M, Cazzaniga M,Valeriano
V, Rossi P, Lovaria A, et al. MELD score is better
than Child–Pugh score in predicting 3-month sur vival of patients undergoing transjugular intrahe patic portosystemic shunt. J Hepatol. 2002 Apr;
36(4): 494–500.
13. Everson G T. MELD: the answer or just more
questions? Gastroenterology. 2003 Jan; 124(1): 251–4.
14. Sanyal A J, Genning C, Rajender Reddy K,
Wong F, Kowdley KV, Benner K,et al. The North
American study for the treatment of refractory
ascites. Gastroenterology. 2003 May; 124(3):
634–41.
15. Giannini E, Botta F, Fumagalli A, Malfatti F,
Testa E, Chiarbonello B, et al. Can inclusion of
serum creatinine values improve the Child- Turcotte-Pugh score and challenge the prognostic
yield of the model for end-stage liver disease score
in the short-term prognostic assessment of cirrhotic
patients? Liver Int. 2004 Oct; 24(5): 465–70.
16. Wiesner R, Edwards E, Freeman R,Harper A,
Kim R, Kamath P, et al. Model for end-stage liver
disease (MELD) and allocation of donor livers. Gas troenterology. 2003 Jan; 124(1): 91–6.
17. Llovet J M, Planas R, Morillas R, Quer JC,
Cabré E, Boix J, et al. Short-term prognosis of
cirrhotics with spontaneous bacterial peritonitis:
multivariate study. Am J Gastroenterol. 1993 Mar;
88(3):388–92.
18. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy – definition, nomenclature, diagnosis, and quantification:
final report of the working party at the 11th World
Congresses of Gastroenterology, Vienna, 1998.
Dženela Prohić, Rusmir Mesihović, Nenad Vanis, Srđan Gornjaković, Amra Puhalović, Aida Saray. Prognostic assessment in patients with
decompensated cirrhosis
19. Fernandez-Esparrach G, Sanchez-Fueyo A,
Gines P, Uriz J, Quinto L,Ventura PJ, et al. A prognostic model for predicting survival in cirrhosis with
ascites. J Hepatol. 2001 Jan;34(1):46–52.
20. Mansour A, Watson W, Shayani V, Pickleman
J. Abdominal operations in patients with cirrhosis:
still a major surgical challenge. Surgery. 1997 Oct
;122(4):730–5 [discussion 735–736].
21. Merkel C, Bolognesi M, Sacerdoti D, Bombonato
G, Bellini B, Bighin R, et al. The hemodynamic response to medical treatment of portal hypertension
as a predictor of clinical effectiveness in the primary
prophylaxis of variceal bleeding in cirrhosis. Hepatol ogy. 2000 Nov ;32(5):930–4.
22. Gluud C, Henriksen JH, Nielsen G. Prognostic indicators in alcoholic cirrhotic men. Hepatology. 1988
Mar-Apr;8(2):222–7.
23. Planas R, Balleste B, Alvarez MA, Rivera M, Montoliu S, Galeras JA, et al. Natural history of decompensated hepatitis C virus-related cirrhosis.A study
of 200 patients.J Hepatol. 2004 May;40(5):823–830.
24. Wiesner, RH, McDiarmid, SV, Kamath, PS, Malinchoc M, Kremers WK, et al. MELD and PELD: application of survival models to liver allocation. Liver
Transpl. 2001 Jul; 7(7):567-80.
25. Dunn W, Jamil LH, Brown LS, Wiesnes RH, Kim
WR, Menon KV, et al. MELD accurately predicts mortality in patients with alocholic hepatitis. Hepatology.
2005 Feb; 41(2):353-8.
26. Ahmad J, Downey KK, Akoad M, Cacciarelli TV.
Impact of the MELD scoreom waiting time and disease severity in liver transplantation in United States
28. Botta F, Giannini E, Romagnoli P, Fasoli A,
Malfatti F, Chiarbonello B, et al. MELD scoring
system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a Europeanstudy. Gut. 2003
Jan; 52)1):134–9.
29. Llado L, Figueras J, Memba R, Xiol X, Baliellas C, Vázquez S, et al. Is MELD really the definitive score for liver allocation? Liver Transpl. 2002
Sep;8(9):795–8.
30. Angermayr B, Koening F, Cejna M, Karnel F,
Gschwantler M, Ferenci P. Creatinine-modified
Child-Pugh score (CPSC) compared with MELDscore to predict survival in patients undergoing
TIPS. Hepatology. 2002; 36: 860A.
31. Cardenas A, Gines P, Uriz J, Bessa X, Salmerón JM, Mas A, et al. Renal failure after upper gastrointestinal bleeding in cirrhosis: incidence, clinical
course, predictive factors, and short-term progno sis. Hepatology. 2001 Oct; 34(4 Pt 1):671–6.
32. Fraley DS, Burr R, Bernardini J, Angus D,
Kramer DJ, Johnson JP. Impact of acute renal
failure on mortality in end-stage liver disease with
or without transplantation. Kidney Int. 1998 Aug;
54(3):518–24.
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): 999–1006.
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:
Dženela Prohić, MD
Clinic for Gastroenterohepatology
Clinical Center University of Sarajevo
Bolnička 25, 71000 Sarajevo
Bosnia and Herzegovina
Email: Dzanela.Prohic@unn.no
Medicinski žurnal 2013 Ⴠ19 (1): 48 - 53
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Lejla Ibričević-Balić, Rusmir Mesihović, Alma Sofo-Hafizović, Nenad Vanis, Šefkija Balić, Semir Bešlija. Etiology of anemia in patients with gastric
lymphomas
Professional article
ETIOLOGY OF ANEMIA IN PATIENTS WITH GASTRIC LYMPHOMAS
ETIOLOGIJA ANEMIJE KOD PACIJENATA SA LIMFOMIMA ŽELUCA
1*
2
1
2
Lejla Ibričević-Balić , Rusmir Mesihović , Alma Sofo-Hafizović , Nenad Vanis ,
4
3
Šefkija Balić , Semir Bešlija
2
1
Clinic of Hematology, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, B&H; Clinic
for Gastroenterohepatology, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, B&H;
3
Clinic for Endocrinology, Diabetes and Metabolism Diseases, Clinical Center University of Sarajevo,
4
Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina; Clinic for Oncology, Clinical Center University
of Sarajevo, Bolnička 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
SAŽETAK
Cilj rada je procjeniti razvoj anemije hronične
bolesti kod pacijenata sa limfomima želuca. Anemija se kod pacijenata sa malignim ne Hočkinovim
limfomima može razviti iz više razloga, kao anemija hronične bolesti, u sklopu infiltracije limfomskim stanicama koštane srži te kao sideropenična
anemija. Analizirana je grupa od 40 pacijenata
liječen ih radi limfoma želuca. U grupi bolesnika sa
MALT limfomom želuca evidentirana je statistički
signifikantna razlika u stepenu anemije u odnosu
na grupupa cijenata sa difuznim velikostaničnim B
limfomom želuca. Obzirom na tip anemije utvrdjeno je da je anemija kod MALT limfoma bila mikrocitna sideropenična usljed nedostatka serumskog
željeza, u odnosu na anemiju kod pacijenata sa
DLBCL koji su imali normocitnu anemiju koja odgovara
Medicinski žurnal 2013 Ⴠ19 (1): 54 - 57
odgovara anemiji hronične bolesti. Zaključak: Kod
pacijenata sa lim fomima želuca razvoj anemije
je multifaktorijalan, a terapijski modalitet može ovisiti
o tipu limfoma kao i uzroku anemije.
Ključne riječi: MALT limfom, DLBCL limfom, anemija hronične 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 Ibričević-Balić, Rusmir Mesihović, Alma Sofo-Hafizović, Nenad Vanis, Šefkija Balić, Semir Bešlija. 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 (ECOGุ2)
advanced Ann Arbor stage (III-IV)
involvement of extranodal sites ุ2
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 žurnal 2013 Ⴠ19 (1): 54 - 57
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56
Lejla Ibričević-Balić, Rusmir Mesihović, Alma Sofo-Hafizović, Nenad Vanis, Šefkija Balić, Semir Bešlija. 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 žurnal 2013 Ⴠ19 (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 Ibričević-Balić, Rusmir Mesihović, Alma Sofo-Hafizović, Nenad Vanis, Šefkija Balić, Semir Bešlija. 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 Ibričević-Balić, MD
Clinic of Hematology
Clinical Center University of Sarajevo
Bolnička 25, 71000 Sarajevo
Bosnia and Herzegovina
Phone: +387 33 297 240
Email:lejla99@hotmail.com
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58
Sajma Dautovic-Krkić, Alma Sijamija, Nedžad Hadžić, Hilmo Čaluk. Cardioborreliosis in Bosnia and Herzegovina
Professional article
CARDIOBORRELIOSIS IN BOSNIA AND HERZEGOVINA
KARDIOBORELIOZA U BOSNI I HERCEGOVINI
Sajma Dautovic-Krkić¹*, Alma Sijamija², Nedžad Hadžić², Hilmo Čaluk²
1
Sajma Krkić-Dautović , Koševo 22, 71000 Sarajevo, Bosnia and Herzegovina;
²Cantonal 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
SAŽETAK
Lyme boreliosis je zoonoza uzrokovana boreli jama genusa Borrelia burgdorferi sensu lato
koja ima 14 genospecijesa. Iako se bolest često
manifestira kliničkom slikom kožnog Erythema
migrans, ona može predstavljati multisistemski
poremećaj sa zahvaćanjem zglobova, nervnog
sistema, srca, rjeđe bubrega, jetre, kože ili bilo
kog drugog organa. Boreliozni miokarditis se javlja
u 2-10% slučajeva. Na temelju kliničke slike nije
moguće procijeniti etiologiju miokarditisa, a kad
se posumnja na Lyma miocarditis teško je procijeniti radi li se o ranoj diseminaciji i lokaliziranoj
infekciji (stadij 1) ili je već došlo do diseminacije
(stadij 2). U ovom radu smo prezentirali tri slučaja
kardioborelioze hospitalizirana sa kliničkim manMedicinski žurnal 2013 Ⴠ19 (1): 58 - 62
ifestacijama akutnog karditisa, pankarditisa i
poremećaja ritma, AV bloka II i III stepena.
Ključne riječi: 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-Krkić, Alma Sijamija, Nedžad Hadžić, Hilmo Čaluk. 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 žurnal 2013 Ⴠ19 (1): 58 - 62
60
Sajma Dautovic-Krkić, Alma Sijamija, Nedžad Hadžić, Hilmo Čaluk. 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 žurnal 2013 Ⴠ19 (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-Krkić, Alma Sijamija, Nedžad Hadžić, Hilmo Čaluk. 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. Cardioborreliosis is treated
with antimicrobial treatment. A multicenter, ran domized study by several authors (for 72-232 -246
patients) found equal effectiveness of treatment:
REFERENCES
1. Lipschütz B. Über eine seltene Erythemform(erythema
chronicum migrans). Arch Dermatol Syph. 1913;118:349-56.
2. Hollstrom E. Penicillin treatment of erythema chroni cum migrans and lyme arthritis Afselius. Acta Derm Venerol. 1958;38:285-9.
3. Margos G, Gatewood AG, Aanensen DM, Hanincová
K, Terekhova D, Vollmer SA, et al. MLST of housekeep ing genes captures geographic population structure and
suggests a European origin of Borrelia burgdorferi. Proc
Natl Acad Sci U S A. 2008 Jun 24;105 (25):8730-5.
4. Steere AC. Lyme disease. N Engl J Med.
1989;321(9):586-96.
Medicinski žurnal 2013 Ⴠ19 (1): 58 - 62
61
62
Sajma Dautovic-Krkić, Alma Sijamija, Nedžad Hadžić, Hilmo Čaluk. Cardioborreliosis in Bosnia and Herzegovina
5. Steere A, Malawista C, Snydman DR, Shope RE,
Andiman WA, Ross MR, Steele FM. Lyme arthritis:an
epidemic of oligoarthritis in children and adults in
three Connecticut communites. Arthritis Rheum. 1977
Jan-Feb;20 (1):7-17.
6. Burgdorfer W, Barbour AG ,Hayes SF, Benach JL,
Grunwaldt E, Davis JP. Lyme disease:a tick borne spirochetosis? Science. 1982 Jun; 216(4552):1317-9.
7. Benach JL, Bosler EM, Hanrahan JP, Coleman JL,
Habicht GS, Bast TF, et al. Spirochetes isolated from
the blood of two patients with Lyme disease. N Engl J
Med. 1983;308 (13):733-40.
8. Afzelius A. Verhandlungen der Dermatologischen Gesellschaft zu Stockholm. Arch Dermtol Syph.
1910;101:100-2.
9. Dautovi- Krkić S, Čavaljuga S, Ferhatovic M, Mostarac N,Gojak R, Hadžović M, Hadžić A. Lajmska
borelioza u Bosni i Hercegovini: klinička, laboeratorijska i epidemiološka istraživanja. Med Arh. 2008; 62
(2); 107-110.
10. Hass A, Treib J. Neurologic manifestation classification of borreliosis. Infection. 1996;24:467-9.
11. Pelliccia A, Fagard R, Bjørnstad HH, Anastassakis A, Arbustini E, Assanelli D, et al. Recommendations for competitive sportsparticipation in athletes with cardiovascular disease. Eur Heart J. 2005
Jul;26(14):1422-45.
12. LoGiudice K, Ostfeld R, Schmidt K, Keesing F.
The ecology of infectious disease:effects of host diver
sity and community composition on Lyme disease risk.
Proc Natl Acad Sci USA. 2003 Nov; 100 (2):567-71.
13. Kahl O, Gern L, Gray JS, Guy EC, Jongejan F,
Kirstein F, et al. Detection of borrelia burgdorferi sensu loto in ticks :immunofluorescence assay versus polimerase chain reaction. Zentbl Bacteriol. 1998 Mar;
287(3):205-10.
14. Levine JF, Wilson ML, Spielman A. Mice as reservoirs of the Lyme disease spirochete. Am J Trop Med
Hyg. 1985;34:336-60.
15. Gray JS. The development and seasonal activity
of the ticks Ixodes ricinus:a vector for Lyme borreliosis. Rev Med Vet Entomol. 1991;79:323-33.
16. Kušljugić Z, Baraković F, Arslanagić 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 žurnal 2013 Ⴠ19 (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. Bolanča-Bumber S, Šitum M, Balić 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. Dautović-Krkić S. Borelioza: U: Dautović-Krkić
S, ured. Infektologija. Sarajevo-Tuzla: Medicinski
fakultet; Asocijacija infektologa u Bosni i Hercegovini;
2011. str. 227-229.
Address:
Prof. Sajma Dautović-Krkić, MD, PhD
„Private outpatient clinic”
Koševo 22,
71000 Sarajevo,
Bosnia and Herzegovina
Phone: +387 70 255 055
Email:sajmadautovic@gmail.com
Anida Čaušević-Ramoševac, Lejla Zolić. 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 Čaušević-Ramoševac*, Lejla Zolić
Bosnalijek, Pharmaceutical and Chemical Company, Jukićeva 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 “sensitive” 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
SAŽETAK
Praćenje sigurnosti i podnošljivosti lijeka je od
izrazitog značaja, zbog čega su tokom posljednjih
godina neželjeni efekti koji su povezani s određenim lijekovima i skupinama lijekova privukli izrazitu pažnju zdravstvenih radnika. Savršen izvor
podataka za individualnu kvantifikaciju procjene
rizika lijeka ne postoji. Međutim, podaci dobiveni iz
pretkliničkih testiranja, faza 1-3 ispitivanja, kao i iz
postmarketinškog praćenja mogu biti od velike koristi za procjenu rizika povezanu s određenim lijekom ili skupinom lijekova. Fluorokinoloni se nalaze
na tržistu duže od 25 godina i predstavljaju sigurne antibiotike. Dobro se podnose i imaju sigurnosni profil sličan drugim antimikrobnim lijekovima.
Najčešće prijavljeni neželjeni efekti povezani s primjenom fluorokinolona uključuju gastrointestinalni
sistem (mučnina i proljev) i centralni nervni sistem
(CNS) (glavobolja i vrtoglavica). Ispred navedeni
neželjeni efekti su uglavnom blagog karaktera i ne
zahtijevaju prekid terapije. Manje česti i potencijalno ozbiljni neželjeni efekti povezani s ispred navedenom skupinom lijekova pak uključuju i CNS
(npr. generalizovani napadi), jetru (npr. hepatitis,
akutno zatajenje jetre), bubrege (npr. akutni intersticijalni nefritis, zatajenje bubrega), imuni sistem
(reakcije hipersenzitivnosti), kožu (npr. toksična
epidermalna nekroliza, Stevens-Johnsonov sindrom, fototoksičnost), mišićno-koštani sistem (npr,
artritis, perforacija tetiva) i kardiovaskularni sistem
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Anida Čaušević-Ramoševac, Lejla Zolić. Antimicrobial safety of fluoroquinolones: special focus on norfloxacin
(npr. QTc prolongacija, torsades de pointes). Rijetki neželjeni efekti, koji se mogu pripisati isključivo
pojedinim članovima skupine kinolona (npr. torsades de pointes, hepatotoksičnost), pak, imaju
veću vjerovatnoću nastanka u odabranih “osjetljivih” osoba. Ovaj pregled će se dotaći nedavno
objavljene literature o sigurnosti fluorokinolona i
zasnovan je na opsežnom pretraživanju različitih
baza podataka, prvenstveno Medline-a i MICROMEDEX-a.
Ključne riječi: fluorokinoloni, norfloksacin, sigurnost lijekova, neželjeni 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;
• Uncomplicated gonorrhea;
• Infectious diarrhea, including traveler’s diarrhea.
Evaluation of safety and antimicrobial profile on
basis of molecular structure of fluoroquinolones
Medicinski žurnal 2013 Ⴠ19 (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 Čaušević-Ramoševac, Lejla Zolić. 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 – 2.2%
Nausea – 1.1%
Dyspepsia –
0.3%
Abdominal pain
– 0.2%
Others(< 0.1%):
diarrhea,
anorexia,
dysphagia,
tongue
enlargement)
CNS all – 1.5%
Dizzines – 0.5%
Headache – 0.3%
Others(< 0.1%):
depression,
euphoria,
hallucinations,
insomnia,
somnolence, dry
mouth.
Dermatological
all – 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 – 4.2% Nausea – 2.6%
Dizziness –
Headache –
2.6%
2.8%
Headache –
Dizziness –
2.0%
1.7%
Abdominal
Asthenia –
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 – 3.9%
CNS all – 4.4%
Dermatological
all – 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:
• 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];
• 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].
• 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.
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Anida Čaušević-Ramoševac, Lejla Zolić. 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 – 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 žurnal 2013 Ⴠ19 (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 – 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 – 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 “specific” 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 Čaušević-Ramoševac, Lejla Zolić. 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 “contribution”
of age to the safety profile of these drugs – 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 – 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 – 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
workers’ 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 žurnal 2013 Ⴠ19 (1): 63 - 68
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68
Anida Čaušević-Ramoševac, Lejla Zolić. 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. Utinorâ. 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):27–31.
5. Bruno MJ. Magnification endoscopy, high
resolution endoscopy and chromoscopy. Gut.
2003;52(suppl 4):iv7–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):568–77.
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):1094–8.
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):310–6.
Medicinski žurnal 2013 Ⴠ19 (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. Noroxinâ. 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 Čaušević-Ramoševac, MA.Pharm.
Regulatory Affairs Department
Bosnalijek, Pharmaceutical and
Chemical Company
Jukićeva 53, 71 000 Sarajevo,
Bosnia and Herzegovina
Phone: +387 33 254 578
Email: anida.c@bosnalijek.ba
Zoran Roljić, Božina Radević, Novak Vasić, Milan Simatović, Jugoslav Đeri, Severin Dunović, Vladimir Keča, Jevrosima Roljić.
Superior mesenteric artery syndrome
Case report
SUPERIOR MESENTERIC ARTERY SYNDROME
SINDROM GORNJE MEZENTERIČNE ARTERIJE
Zoran Roljić*, Božina Radević, Novak Vasić, Milan Simatović, Jugoslav Đeri, Severin Dunović,
Vladimir Keča, Jevrosima Roljić
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
SAŽETAK
Sindrom gornje mezenterične arterije predstavlja
skup gastrointestinalnih i opštih poremećaja zbog
visoke crijevne opstrukcije kompresijom horizontalnog dijela duodenuma gornjom mezenteričnom
arterijom i aortom. Dijagnoza je teška. Uporedo sa
medikamentoznom, hirurška 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 slučajeva hirurškog liječenja.
Javlja se u 0,013% do 0,78 % radioloških nalaza
kod ispitanika sa gastrointestinalnim tegobama.
Bolesnica sa tegobama hronične, visoke crijevne
opstrukcije i angiografskim nalazom kompresije
horizontalnog duodenuma gornjom mezenteričnom arterijom i aortom, liječena je medikamentozno i hirurški, resekcijom Treitz ligamenta,
mobilizacijom, derotacijom i distalnom transpozicijom duodenojejunalnog spoja u području
veće aortomezenterične distance. U postoperativnom toku došlo je do značajnog poboljšanja.
Ključne riječi: gornja mezenterična arterija, dijagnostika, hirurško liječenje.
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
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Zoran Roljić, Božina Radević, Novak Vasić, Milan Simatović, Jugoslav Đeri, Severin Dunović, Vladimir Keča, Jevrosima Roljić.
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 žurnal 2013 Ⴠ19 (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 Roljić, Božina Radević, Novak Vasić, Milan Simatović, Jugoslav Đeri, Severin Dunović, Vladimir Keča, Jevrosima Roljić.
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, Creţan C, Rusănescu 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. Jiménez JC, Quinones-Baldrich WJ. Mesenteric Vascular Disease : General Considerations.
7th ed. Cronenwett: Rutherford’s Vascular Surgery; 2010. Chapter 147.
8. Berard X, Cau J, Déglise 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 Roljić, 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: roljicas@spinter.net
Naš prilog redukciji kardiovaskularnih bolesti !
Our contribution in reduction of cardiovascular diseases !
Medicinski žurnal 2013 Ⴠ19 (1): 69 - 71
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Zlatan Zvizdić, Ibrahim Ulman, Adnan Hadžimuratović, Selma Vatrenjak-Vanis, Sadeta Begić-Kapetanović, Kenan Karavdić, Nusret Popović. Primary
correction of bladder exstrophy in female newborn
Case report
PRIMARY CORRECTION OF BLADDER EXSTROPHY IN FEMALE NEWBORN
PRIMARNA KOREKCIJA EKSTROFIJE MOKRAĆNOG MJEHURA ŽENSKOG
NOVOROĐENČETA
1*
2
1
3
Zlatan Zvizdić , Ibrahim Ulman , Adnan Hadžimuratović , Selma Vatrenjak-Vanis , Sadeta
1
1
1
Begić-Kapetanović , Kenan Karavdić , Nusret Popović
1
Clinic of Pediatric Surgery, Clinical Center University of Sarajevo, Bolnička 25, 71000 Sarajevo, Bosnia and
3
2
Herzegovina; Department of Pediatric Surgery, Ege University Faculty of Medicine, 35100 İzmir, Turkey; Clinic for
Anaesthesiology and Reanimation, Clinical Center University of Sarajevo, Bolnička 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
SAŽETAK
Ekstrofija mokraćnog mjehura je ekstremno rijetka kongenitalna anomalija koja pripada širokom
spektrumu epispadija-ekstrofičnom kompleksu
sa zabilježenom incidencom od 1:10000-200000
živorođenih i sa ukupno većom zastupljenošću
muškog spola. Mi izvještavamo o slučaju tri dana
starog ženskog novorođenčeta sa klasičnom
ekstrofijom mokraćnog mjehura tretiranog primarnom korekcijom.
Ključne riječi: ekstrofija mokraćnog mjehura,
ženski 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 ‘exstrophy’ 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 žurnal 2013 Ⴠ19 (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 – 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 Zvizdić, Ibrahim Ulman, Adnan Hadžimuratović, Selma Vatrenjak-Vanis, Sadeta Begić-Kapetanović, Kenan Karavdić, Nusret Popović. 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 Grady’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 žurnal 2013 Ⴠ19 (1): 72 - 74
73
74
Zlatan Zvizdić, Ibrahim Ulman, Adnan Hadžimuratović, Selma Vatrenjak-Vanis, Sadeta Begić-Kapetanović, Kenan Karavdić, Nusret Popović. 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, Rösch 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, Bägli 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 Zvizdić, M.D, MA
Clinic of Pediatric Surgery
Clinical Center University of Sarajevo
Bolnička 25, 71000 Sarajevo,
Bosnia and Herzegovina
Phone: +387 33 297 142
Email: zlatanzvizdic@yahoo.com
Nova centralna zgrada Kliničkog Centra Univerziteta u Sarajevu
New Central building of the Clinical Center University of Sarajevo
Medicinski žurnal 2013 Ⴠ19 (1): 72 - 74
Prof. Senija Rašić, MD, PhD Pfizer Nefro Foruma
75
IZVJEŠTAJ SA PFIZER NEFRO FORUMA, Sarajevo, mart 2013.
U Sarajevu je od 22.03. do 24.03. 2013. godine u hotelu Bristol održan PFIZER NEFRO FORUM, na
kojem su učestvovali nefrolozi iz Bosne i Hercegovine i Hrvatske na kojem su mlađi liječnici iz ove dvije
države prikazali reprezentativne slučajeve iz kliničke prakse. Rad Foruma je pratio i ocjenjivao žiri
sastavljen od eminentnih i iskusnih naučnih radnika iz oblasti nefrologije i dijalize. Na ovom stručnom
druženju prikazani su interesantni slučajevi iz nefrološke prakse, koji su konstruktivno prodiskutovani,
aiskustvo stečeno kroz ovaj vid saradnje je od izuzetne važnosti za svakodnevni klinički rad.
Na kraju prvog NEFRO FORUMA, čiji pokrovitelj je bila farmaceutska kompanija Pfizer iz Hrvatske i
Bosne i Hercegovine, dodijeljene su nagrade za najbolje ocijenjene prikaze slučajeva iz kliničke
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 Budimpeštu 2013/14. godine) dobila je dr.
Amira Srna sa Klinike za nefrologiju KCUS.
Treću nagradu (odlazak na Hrvatski kongres za hipertenzije 2013. godine) dobila je dr. Martina
Pavletić-Pešić iz Kliničko-bolničkog centra Rijeka, dok su četvrtu nagradu (knjiga Gerijatrija i
farmakoterapija u gerijatriji) dobili dr. Damir Rebić sa Klinike za nefrologiju KCUS i dr.sc.Karmela
Altabas iz Bolnice Sveti duh u Zagrebu.
Osvojene tri nagrade od strane mladih liječnika koji se bave nefrologijom i dijalizom iz KCU Sarajevo
su još jedna potvrda kvalitete i afirmacije nefrološke službe iz KCU Sarajevo i na međunarodnom
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 PavletićPešić, from Clinical Hospital Center Rijeka, while the fourth prize (Geriatrics book and
Pharmacotherapy in geriatrics book), received dr. Damir Rebić 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 Rašić, MD, PhD
Clinic for Nephrology
Clinical Center University of Sarajevo
71000 Sarajevo,
Bosnia and Herzegovina
Medicinski žurnal 2013 Ⴠ19 (1)
76
UPUTSTVA AUTORIMA MEDICINSKOG ŽURNALA
UPUTSTVA AUTORIMA
Časopis “Medicinski žurnal” objavljuje originalne naučne radove, stručne, pregledne i edukativne radove, prikaze slučajeva, recenzije, saopćenja, stručne obavijesti i drugo iz područja svih medicinskih
disciplina. Radovi se pišu in-exstenso na engleskom jeziku, uz sažetak i naslov rada koji se uz engleski piše još i na našem jeziku. Autori su odgovorni za sve navode i stavove u njihovim radovima.
Ukoliko je rad pisalo više autora, potrebno je navesti tačnu adresu (uz telefonski broj i e-mail adresu)
onog autora s kojim će uredništvo sarađivati pri uređenju teksta za objavljivanje.
Ukoliko su u radu prikazana istraživanja na ljudima, mora se navesti da su provedena u skladu s
načelima medicinske deontologije i Deklaracije iz Helsinkija.
Ukoliko su u radu prikazana istraživanja na životinjama, mora se navesti da su provedena u skladu s
etičkim načelima. Prilikom navođenja mjernih jedinica, treba poštovati pravila navedena u SI sistemu.
Radovi se šalju Redakciji na adresu:
“MEDICINSKI ŽURNAL”
Institut za naučnoistraživački rad i razvoj Kliničkog centra Univerziteta u Sarajevu
Bolnička 25
71000 Sarajevo
Bosna i Hercegovina
Email: institutnir@bih.net.ba
POPRATNO PISMO
Uz svoj rad, autori su dužni Redakciji «Medicinskog žurnala» dostaviti popratno pismo, koje sadržava
vlastoručno potpisanu izjavu svih autora:
1. da navedeni rad nije objavljen ili primljen za objavljivanje u nekom drugom časopisu
2. da je istraživanje odobrio Etički komitet,
3. da prihvaćeni rad postaje vlasništvo «Medicinskog žurnala».
OPSEG I OBLIK RUKOPISA
Radovi ne smiju biti duži od deset stranica na računaru, ubrajajući 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 crteže unijeti/staviti u tekst rada, tamo gdje im je mjesto, bez obzira u kojem
programu su rađene. Cijeli rad mora biti napisan na engleskom jeziku. Apstrakti na engleskom i jezicima
naroda BiH.
Rad se dostavlja na CD-u, uz dva štampana primjerka, ili e-mailom. CD se ne vraća.
RAD SADRŽI:
NASLOV RADA NA NAŠEM 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 našem
i na engleskom jeziku, te na kraju rada navedena adresa kontakt-autora.
Sažetak na našem jeziku i njegov obavezan korektan prevod na engleskom – Abstract od oko 200
riječi, s najznačajnijim činjenicama i podacima iz kojih se može dobiti uvid u kompletan rad.
Ključne riječi - Key words (na našem jeziku i na engleskom): do pet riječi; navode se ispod Sažetka,
odnosno Abstracta.
Medicinski žurnal 2013 Ⴠ19 (1)
77
SADRŽAJ
Sadržaj rada mora biti sistematično i strukturno pripremljen i podijeljen u poglavlja i to:
-
UVOD
MATERIJAL I METODE
REZULTATI
DISKUSIJA
ZAKLJUČAK
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 istraživanja i/ili glavnu hipotezu koja se
provjerava.
MATERIJAL I METODE
Potrebno je da sadrži opis originalnih ili modifikaciju poznatih metoda. Ukoliko se radi o ranije opisanoj
metodi dovoljno je dati reference u literaturi. U kliničko-epidemiološkim studijama opisuju se: uzorak,
protokol i tip kliničkog istraživanja, mjesto i vrijeme istraživanja. Potrebno je opisati glavne karakteristike
istraživanja (npr. randomizacija, dvostruko slijepi pokus, unakrsno testiranje, testiranje s placebom itd.),
standardne vrijednosti za testove, vremenski odnos (prospektivna, retrospektivna studija), izbor i broj
ispitanika – kriterije za uključivanje i isključivanje u istraživanje.
REZULTATI
Navode se glavni rezultati istraživanja i nivo njihove statističke značajnosti. Rezultati se prikazuju tabelarno, grafički, slikom i direktno se unose u tekst gdje im je mjesto, s rednim brojem i konciznim naslovom. Tabela treba imati najmanje dva stupca s obrazloženjem što prikazuje; slika čista i kontrastna,
a grafikon jasan, s vidljivim tekstom i obrazloženjem.
DISKUSIJA
Piše se koncizno i odnosi se prvenstveno na vlastite rezultate, a potom se nastavlja upoređivanje vlastitih rezultata s rezultatima drugih autora, pri čemu se citiranje literature navodi po važećim Vankuverskim pravilima. Diskusija se završava potvrdom zadatog cilja ili hipoteze, odnosno njihovim negiranjem.
ZAKLJUČAK
Treba da bude kratak, da sadrži najbitnije činjenice do kojih se došlo u radu tokom istraživanja i njihovu
eventualnu kliničku primjenu, kao i potrebne dodatne studije za potpuniju aplikaciju. Obavezno navesti
i afirmativne i negirajuće zaključke.
LITERATURA
Literatura se obavezno citira po Vankuverskim pravilima.
Svaku tvrdnju, saznanje ili misao treba potvrditi referencom. Reference u tekstu treba označiti po redoslijedu unošenja arapskim brojevima u zagradi na kraju rečenice. Ukoliko se kasnije u tekstu pozivamo na istu referencu, navodimo broj koji je referenca dobila prilikom prvog unošenja/pominjanja u
tekstu. Literatura se popisuje na kraju rada, rednim brojevima pod kojim su reference unesene u tekst
(ulazni broj reference), a naslov časopisa se skraćuje po pravilima koje određuje Index Medicus. Ukoliko
je citirani rad napisalo više autora, navodi se prvih šest i doda «et al.».
Vrlo je važno 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 žurnal 2013 Ⴠ19 (1)
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INSTRUCTIONS TO AUTHORS
Journal “Medical Journal” 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:
“MEDICINSKI ŽURNAL”
Institut za naučnoistraživački rad i razvoj Kliničkog centra Univerziteta u Sarajevu
Bolnička 25
71000 Sarajevo
Bosna i Hercegovina
Email: institutnir@bih.net.ba; bibliotekanir@kcus.ba
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 “Medical Journal” stating that:
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2. the work is in accordance with the ethical committee standards,
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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).
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Graphs, tables, figures and drawings should be incorporated in the text precisely in the text where these
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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
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Abstract.
Medicinski žurnal 2013 Ⴠ19 (1)
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ARTICLE BODY
The main body of the article should be systematically ordered under the following headings:
- INTRODUCTION
- MATERIALS AND METHODS
- RESULTS
- DISCUSSION
- CONCLUSION
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to other published articles with the same topic. It is necessary to quote the main problem, aim
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MATERIALS AND METHODS
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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 – 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
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DISCUSSION
Discussion is concise and refers to own results, in comparison with the other authors’ results.
Citation of references should follow Vancouver rules. Discussion should be concluded by the
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Conclusion should be concise and should contain most important facts, which were obtained
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REFERENCES
References should follow the format of the requirements of Vancouver rules.
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Uniform Requirements for Manuscripts Submitted to Biomedical Journals:
Sample References http:/www.nlm.nih.gov/bsd/uniform_requirements.html
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