NCI 2014 / 2

ISSN 2148 - 4902

NORTHERN CLINICS OF ISTANBUL • İSTANBUL KUZEY KLİNİKLERİ

Vol. 1 • No. 2 • Year 2014

P WAVE DISPERSION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE AND ITS RELATIONSHIP WITH THE SEVERITY OF THE DISEASE • PATIENT SATISFACTION WITH

INDEXED IN TURKIYE CITATION INDEX.

OUTPATIENT HEALTH CARE SERVICES • EVALUATION AND PREVELANCE OF MAJOR CENTRAL NERVOUS SYSTEM MALFORMATIONS • ASSESMENT OF THE PATIENTS PRESENTING WITH SEVERE ANEMIA

TO THE EMERGENCY INTERNAL MEDICINE CLINIC • CLINICAL AND DEMOGRAPHIC CHARACTERISTICS AND FUNCTIONAL STATUS OF THE PATIENTS WITH FIBROMYALGIA SYNDROME • COMPARING

THE EFFECTIVENESS OF NEUTROPHILLYMPHOCYTE RATIO AS A MORTALITY PREDICTOR ON MIDDLE AND ADVANCED AGE CORONARY ARTERY BYPASS GRAFT PATIENTS • IMPACT OF STROKE ETIOLOGY ON

CLINICAL SYMPTOMS AND FUNCTIONAL STATUS • RELAPSING POLYCHONDRITIS AND OTOLOGIC FINDINGS • SUDDEN SENSORINEURAL HEARING LOSS IN A MULTIPLE SCLEROSIS CASE • ANNULAR

SARCOIDOSIS MIMICKING GRANULOMA ANNULARE: A CASE REPORT • USE OF ESWT IN AVASCULAR NECROSIS OF BILATERAL FEMORAL HEADS: CASE REPORT • SYNTHETIC CANNABINOIDS

NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ Editor-in-Chief

Vıce Editors

Bekir Durmus, M.D.

Banu Mesci, M.D. Berna Terzioglu Bebitoglu, M.D. Ender Onur, M.D. Levent Doganay, M.D. Tunc Eren, M.D.

Scientıfıc Commıttee Abdullah Aydin, M.D. Adem Ozkan, M.D. Ahmet Koc, M.D. Alattin Ozturk, M.D. Ali Ihsan Dokucu, M.D. Ali Riza Odabas, M.D. Aliye Yildirim Guzelant, M.D. Alper Sener, M.D. Asiye Kanbay, M.D. Atakan Yesil, M.D. Ates Kadioglu, M.D. Ayse Banu Sarifakioglu, M.D. Ayse Cikim Sertkaya, M.D. Ayse Serap Karadag, M.D. Ayten Kadanali, M.D. Bekir Atik, M.D. Beyhan Cengiz Ozyurt, M.D. Bilge Burcak Annagur, M.D. Birsen Yurugen, M.D. Bulent Gumusel, M.D. Canan Agalar, M.D. Cagri Ergin, M.D. Dervis Mansuri Yilmaz, M.D. Destina Yalcin, M.D. Didem Korular Tez, M.D. Dilaver Tas, M.D. Duygu Geler Kulcu, M.D. Ebru Zemheri, M.D. Elif Atici, M.D. Emek Kocaturk Goncu, M.D. Emin Evren Ozcan, M.D. Engin Emrem Bestepe, M.D. Eren Gozke, M.D. Eren Ozek, M.D. Eyup Gumus, M.D. Fahri Ovalı, M.D.

Fatih Saygılı, M.D. Fatma Eti Aslan, M.D. Ferruh Isman, M.D. Filiz Akyuz, M.D. Fugen Aker, M.D. Gencer Meryem, M.D. Gozde Kir Cinar, M.D. Gulendam Kocak, M.D. H. Muammer Karakas, M.D. Hale Akbaylar, M.D. Halil İbrahim Canter, M.D. Haluk Vahaboglu, M.D. Hamit Okur, M.D. Hanefi Ozbek, M.D. Haydar Sur, M.D. Hulya Apaydin, M.D. Huseyin Bayramlar, M.D. Ilgin Turkcuoglu, M.D. Ibrahim Akalin, M.D. Ibrahim Ikizceli, M.D. Ihsan Karaman, M.D. Ilhan Yargic, M.D. Ilknur Aktas, M.D. Kamil Ozdil, M.D. Kaya Saribeyoglu, M.D. Kemal Memisoglu, M.D. Kemal Nas, M.D. Kemalettin Koltka, M.D. Lutfullah Orhan, M.D. Mahmut Durmus, M.D. Medine Yazici Gulec, M.D. Mehmet Ali Ozcan, M.D. Mehmet Doganay, M.D. Mehmet Eren, M.D. Mehmet Kanbay, M.D. Mehmet Ruhi Onur, M.D.

Mehmet Selcuk, M.D. Mehmet Tayyap, M.D. Mehmet Tunca, M.D. Melek Celik, M.D. Metin Kapan, M.D. Muhammet Tekin, M.D. Murat Acar, M.D. Murat Tuncer, M.D. Mustafa Caliskan, M.D. Mustafa Girgin, M.D. Nilay Sahin, M.D. Onur S. Goksel, M.D. Orhan Alimoglu, M.D. Ozge Ecmel Onur, M.D. Ozlem Baysal, M.D. Ozlem Guneysel, M.D. Recep Alp, M.D. S. Tahir Eren, M.D. Sabahat Aksaray, M.D. Sait Naderi, M.D. Selcuk Mistik, M.D. Selcuk Peker, M.D. Serhat Citak, M.D. Seyhun Kursat, M.D. Sevki Erdem, M.D. Suayip Birinci, M.D. Sukran Kose, M.D. Tansu Kucuk, M.D. Tarik Sapci, M.D. Tuba Yavuzsen, M.D. Turhan Caskurlu, M.D. Umut Kefeli, M.D. Yasar Bukte, M.D. Yuksel Altintas, M.D. Yuksel Ersoy, M.D.

NORTHERN CLINICS OF ISTANBUL İSTANBUL KUZEY KLİNİKLERİ YEAR 2014 VOLUME 1 NUMBER 2

p-ISSN 2148 - 4902

Ownership and Accountability for Contents on behalf of the Istanbul Northern Anatolian Association of Public Hospitals

Kemal Memisoglu, M.D.

Publicatıon Manager

Bekir Durmus, M.D.

Publicatıon Coordinators

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Umut Elmas

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e-mail: bilgi@kuzeyklinikleri.com Issued by the Istanbul Northern Anatolian Association of Public Hospitals Indexed in Turkiye Citation Index.

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Northern Clinics of Istanbul (NCI) is a peer-reviewed journal published triannually by the Istanbul Northern Anatolian Association of Public Hospitals.

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CONTENTS Vol. 1 • No. 2 • Year 2014

VI IX

INSTRUCTIONS FOR THE AUTHORS EDITORIAL

ORIGINAL ARTICLES 65-70

P-wave dispersion and its relationship with the severity of the disease in patients with stable coronary artery diseasee

F. Akin, I. Firatli, F. Katkat, T. Gurmen, B. Ayca, M. Kalyoncuoglu, O. Abaci, M. Sari, M. Ersanli, S. Kucukoglu, Z. Yigit

71-77

Patient satisfaction with outpatient health care services: evaluation of the components of this service using regression analysis

F. Vural, S. Ciftci, Y. Cakiroglu, B. Vural

78-83

Evaluation and prevalence of major central nervous system malformations: a retrospective study

S. Tutus, S. Ozyurt, E. Yilmaz, G. Acmaz, M. A. Akin

84-88

Assesment of the patients presenting with severe anemia to the emergency internal medicine clinic

S. Akin, E. Ergin, S. Kazan, N. Keskin Tukel, D. Kilic Aydin, M. Tekce, M. Aliustaoglu

89-94

Clinical and demographic characteristics and functional status of the patients with fibromyalgia syndrome

N. Sahin, A. Atik, E. Dogan

95-100

Comparing the effecti̇ veness of neutrophil-lymphocyte ratio as a mortality predictor on mi̇ ddle and advanced age coronary artery bypass graft patients

D. Ay, B. Erdolu, G. Yumun, U. Aydin, A. Demir, O. Tiryakioglu, A. H. Vural

101-105 Impact of stroke etiology on clinical symptoms and functional status

O. G. Memetoglu, A. Taraktas, N. Bilgin Badur, F. Unlu Ozkan

CASE REPORTS 106-108 Relapsing polychondritis and otologic findings

S. Derin, A. Oran, F. Demirkuru, S. Ucar

109-113 Sudden sensorineural hearing loss in a multiple sclerosis case

M. Tekin, G. Ozbilen Acar, O. H. Cam, F. M. Hanege

114-116 Annular sarcoidosis mimicking granuloma annulare: a case report

Z. Turkoglu, B. Can, E. Zemheri, I. Zindanci, F. Topaloglu Demir, M. Kavala

117-120 Use of ESWT in avascular necrosis of bilateral femoral heads: case report

L. Ozgonenel, H. Yesil, M. Yesil

REVIEW 121-126 Synthetic cannabinoids

R. Bilici

INSTRUCTIONS FOR THE AUTHORS Northern Clinics of Istanbul

- NCI is a peer-reviewed open-access international journal published by the Istanbul Northern Anatolian Association of Public Hospitals. NCI printed three times a year. Free full-text articles in English are available at (www.kuzeyklinikleri.com). The NCI is indexed in Turkiye Citation Index. The journal publishes researches, interesting case reports, letters to the editor, review articles, editorial comments, medical news, guidelines. The journal accepts manuscripts written in Turkish, and English. Opinions presented in published articles by no means represent the official endorsement of the Istanbul Northern Anatolian Association of Public Hospitals.

Manuscripts should be prepared in accordance with the Uniform Requirements for Manuscripts Submitted to Biomedical Journals regularly updated by the International Committee of Medical Journal Editors, available at http:// www.icmje. org.

ARTICLE TYPES Northern Clinics of Istanbul accepts miscellaneous types of articles which will be briefly described below.

Research Articles: NCI accepts original clinical (conducted with healthy subjects or patients) or experimental (human, animal or in-vitro trials) research articles performed in all fields.

Case Reports: NCI publishes reports on interesting, instructive or rarely seen cases.

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Articles in press: Roten L, Derval N, Sacher F, Pascale P, Wilton SB, Scherr D, et al.

Ajmaline attenuates electrocardiogram characteristics of inferolateral early repolarization. Heart Rhythm 2011 Sep 19 [E-pub ahead of print], doi:10.1016/j.hrthm.2011.09.013.

2. Book: Brown AM. Physiology of the liver. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2003.

3. Chapter in book: Anderson JL, Muhlestein JB. The role of infection. In: Theroux P, editor. Acute

coronary syndromes: a companion to Braunwald’s Heart Disease. Philadelphia: W.B. Saunders; 2003. p. 88107.

4. Web page: Nainggolan L. New salt paper causes controversy. Heartwire.

May 3, 2011. Available at: http:// www.theheart.org/article/1220043. do. Accessed: June 12, 2011.

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EDITORIAL

Dear readers of Journal of Northern Clinics of Istanbul, No matter what they say, carrying on a project is as difficult, and as tedious as initiating it. Therefore, it is very exciting, and precious for us to come together with you again in our second issue of scientific publication of Association of PuÄąblic Hospitals of Northern Anatolian Region of Istanbul . Every published issue increases our hopes for the next issue, and we deeply feel the pride of regularly issuing a high quality scientific journal. I again want to communicate my gratitude to our Secretary General Assoc.

Prof. Kemal MEMISOGLU, PhD, MD who really supports us, and keeps our excitement, and motivation at a higher level during this arduous process filled with question marks.

In this issue we present to our readers 7 original articles, 4 case reports, and 1 invited review. In original articles, the relationship between P-wave dispersion in stable coronary artery disease, and severity of the disease; patient satisfaction in health care services in outpatient clinics; incidence of major central system anomalies; evaluation of the patients who presented to emergency services of internal medicine with severe anemia; clinical, demographic, and functional status of the patients with fibromyaqlgia syndrome; the effectiveness of neutrophil/lymphocyte ratio as a predictor of mortality following coronary bypass surgery; the impact of stroke etiology on clinical symptoms, and functional state of the patient have been scrutinized. In invited review, abuse of synthetic cannabinoids which we often encounter recently in the main news bulletin as a serious danger for young generation have been analyzed in detail.

In case presentations very interesting subjects which will attract the attention of the readers including a case of multiple sclerosis progressing with sudden hearing loss, relapsing polychonditis, audiological symptoms, a case of cutaneous sarcoidosis mimicking granuloma annulare, and effectiveness of ESWT in the management of bilateral femoral head necrosis have been discussed.

We congratulate our authors who contributed to the contents of this issue, and as an editorial board we express our gratitude to our referees who spared their valuable time to evaluate submitted manuscripts.

Hope to meet you in the next issue‌ Bekir Durmus, Assoc. Prof. M.D. Editor-in-Chief

Or覺g覺nal Article

CARDIOLOGY

North Clin Istanbul 2014;1(2):65-70 doi: 10.14744/nci.2014.25733

P-wave dispersion and its relationship with the severity of the disease in patients with stable coronary artery disease Fatih Akin1, Inci Firatli2, Fahrettin Katkat2, Tevfik Gurmen2, Burak Ayca2, Muhsin Kalyoncuoglu2, Okay Abaci2, Mustafa Sari2, Murat Ersanli2, Serdar Kucukoglu2, Zerrin Yigit2 Department of Cardiology, Mugla Sitki Kocman University School of Medicine, Mugla, Turkey;

1

Department of Cardiology, Istanbul University Institute of Cardiology, Istanbul, Turkey

2

ABSTRACT OBJECTIVE: P- wave dispersion (PD) is an indicator of inhomogeneous and discontinuous propagation of sinus impulses. In the present study we aimed to investigate the PD and its association with the severity of the disease. in patients with stable coronary artery disease.

METHODS: We prospectively analyzed 60 subjects with coronary artery disease (CAD) and 25 subjects with normal coronary angiograms (control group). The maximum and minimum P-wave duration and PD were measured from the 12-lead surface electrocardiograms. The CAD severity was assessed by the severity score (Gensini score) and the number of vessels involved (vessel score).

RESULTS: P max was longer in CAD group compared with the control group (p<0.001). PD was greater in the CAD group, compared with the control group (p<0.001). However, P min did not differ between the two groups. In bi-variate correlation, increased PD was correlated with presence of diabetes mellitus (r=0.316, p=0.014), smoking (r=0.348, p=0.006), left ventricular ejection fraction (r=-0.372, p=0.003), vessel score (r=0.848, p=0.001), and Gensini score (r=0.825, p=0.001). Multiple linear regression analysis showed that PD was independently associ竅ated with vessel score ((3=0.139, p=0.002) and Gensini score ((3=0.132, p=0.007).

CONCLUSION: PD was greater in patients with CAD than in controls and it was associated with CAD severity.

Key words: Coronary artery disease; gensini score; stable angina pectoris; P-wave dispersion.

P

wave dispersion (PD) may be defined as the difference between the longest and shortest P wave duration recorded from different multiple surface electrocardiographic leads [1, 2]. Prolonged P

wave duration and increased PD have been showed to be associated with an increased risk for atrial fibrillation (AF) which is characterized by inhomogeneous and discontinuous atrial conduction [3]. A

Received: July 11, 2014 Accepted: August 22, 2014 Online: December 08, 2014 Correspondence: Dr. Fatih AKIN. Mugla Sitki Kocman University School of Medicine, Mugla, Turkey.

Tel: +90 252 - 214 13 26 e-mail: fatih._akin@hotmail.com 穢 Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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growing evidence shows that people who are higher PD have higher risks for several cardiovascular-related conditions such as diabetes mellitus, obesity, hypertension, peripheral vascular disease, and myocardial infarction [4-7]. Furthermore, PD has been found to be to associated with an increase in carotid intima-media thickness and inflammatory markers such as C-reactive protein [8]. However, there are very few studies that have shown the relationship between stable coronary artery disease and P wave dispersion [9]. Therefore, in the present study we aimed to determine the association of PD with the severity of coronary artery disease (CAD) in patients with stable coronary artery disease.

MATERIALS AND METHODS Study population A total of 85 (30 women 55 men) consecutive patients routinely referred to coronary angiography for stable angina pectoris were included in the study after the following exclusions: any kind of rhythm abnormailities that could have interfered with P- wave analysis (AF, freguent atrial and ventriculer beats, pacemaker rhythm), acute coronary syndromes, valvular heart disease, serum electrolyte disturbances, abnormal thyroid function, pulmonary hypertension, cardiomyopathies, use of any antiarrhythmic drug, history of myocardial infarction, percutaneus coronary intervention, and cardiac surgery. Entry criteria included chest pain or other symptoms suggestive of myocardial ischemia whc clinically indicated coronary angiography. Detailed physical examination, electrocardiogram and echocardiogram were performed on all patients. The clinical risk factors for the patients such as age, gender, hypertension (HT), diabetes mellitus (DM), history of hyperlipidemia, and smoking status were noted.

Patients were divided into 4 groups based on their extent of angiographic coronary artery disease. Patients with normal coronary arteries were labeled as normal group (25 patients), 22 patients with signficant obstruction in 1 major epicardial artery were considered as having 1 vessel disease, 26 patients with significant obstruction in 2 major epicardial arteries were included in the 2 vessel disease

North Clin Istanbul â&#x20AC;&#x201C; NCI

group, finally 12 patients with significant obstruction in 3 major epicardial arteries were enrolled in the 3 vessel disease group. Hypertension was defined based on blood pressure 140/90 mm Hg or greater, and a history of antihypertensive drug use. DM was defined as fasting blood glucoseâ&#x2030;Ľ126 mg/dl on two occasions or being on treatment. The local ethics committee approved the study protocol. All demographic and clinical data were collected prospectively.

Electrocardiography A 12- lead surface electrocardiogram (ECG) was obtained from each patient while in supine position. Recordings were acquired at a paper speed of 50 mm/s, with 1 mV/cm standardization. Two in-vestigators without knowledge of the clinical status of the patients manually measured the maximum and minimum P-wave duration and PD. To improve accuracy we used calipers and magnifying lenses. ECG with measurable P- waves in over than 10-leads were included in the analysis. The onset of P-wave was defined as the junction between the end of the P-wave deflection and the ofset of the Pwave as the junction between the end of the P-wave deflection and the isoelectric line. We calculated P maximum (P max) and P minimum (P min) and their diferences were defined as PD. Echocardiographic measurement Echocardiographic measurements were performed by using a 2.5 mHz probe with Acuson Sequa echocardiographic device (Siemens, USA). LV dimensions were generally measured with 2D-guided M-mode from the parasternal projections, using a leading edge to leading edge convention. The left atrium and the left ventricle diameters, left ventricular ejection fraction (LVEF), and the presence of mitral insufficiency were evaluated.

Coronary Angiography Coronary angiography was performed using the standard Judkins technique through femoral artery access. The angiographic characteristics, which included lesion location and percentage stenosis, of all coronary lesions in the index coronary angiogram

Akin et al., P wave dispersion, coronary artery disease

67

were obtained by throughly reviewing the angiogram. Angiographic analysis was carried out by two experienced cardiologists who were blinded to the study protocol. The severity of CAD severity was assessed by using the vessel and Gensini score. Vessel score was the number of vessels with a significant stenosis (>%50). Scores ranged from 0 to 3, depending on the number of vessels involved [10]. We also used Gensini scoring system [11]. According to this method we defined narrowing of the lumen of coronary arteries as 1 for 1-25% stenosis, 2 for 26-50% stenosis, 4 for 51-75% stenosis, 8 for 76-90% stenosis, 16 for 91-99% stenosis and 32 for total occlusion.

Then the score is multiplied by a factor that shows the significance of the lesion’s location. The multiplication factor for the left main system lesion is 5.

It is 2.5 for proximal left anterior descending artery (LAD) and proximal circumflex artery (Cx) lesions, 1.5 for a mid-LAD lesion, and 1 for distal LAD, mid/distal CX and right coronary artery lesions.

The multiplication factor for any other branch is 0.5.

Statistical analyses SPSS-15.0 software (SPSS Inc., Chicago, IL) was

Table 1.

used for all statistical analyses. Baseline demographic data are presented as mean ± SD for continuous variables and frequancies for discrete variables. Comparison of parametric values between the 2 groups was performed by means of an independent samples t-test. Categorical variables were assessed by using chi-square test. Correlation between P wave measurements and angiographic, clinical, and echocardiographic variables were assessed by Pearson correlation coefficient. To ascertain the independent contribution to PD multiple linear regression analysis was made. A two- tailed value of p<0.05 was considered statistically significant.

RESULTS The clinical, echocardiographical and electrocardiographic characteristics of the cases in group 1 and group 2 are shown in Table 1. There was no difference in comparison of groups with regard to age, hypertension, diabetes and smoking. Male patients were more numerous in the CAD group. Pmax, PD and EF were also higher in the CAD group. We divided the study population into 4 subgroups according to vessel scores. P-wave measurements are given in Table

Baseline clinical, echocardiographical and electrocardiographic characteristics of the study population CAD group (n=60) n %

Control group (n=25)

p

Mean±SD n % Mean±SD

Age (years) 56.98±10.1 53.16±9.6 NS Male gender 44 73.3 11 44 0.01 Hypertension 35 58.3 12 48 NS Diabetes 25 41.6 11 44 NS Smoking 27 45 8 32 NS LAD (mm) 3.44±0.30 3.50±0.33 NS LVESD (mm) 2.66±0.88 2.68±0.10 NS LVEDD (mm) 5.24±0.23 5.18±0.26 NS LVEF 55±5.49 58.8±3.74 0.002 Pmax (ms) 102.22±10.47 84.28±6.36 <0.001 Pmin (ms) 54.72±9.53 53.76±7.24 NS PD (ms) 47.53±8.49 30.52±3.25 <0.001 CAD: coronary Artery Disease; LV: Left Ventricle; EDD: End-Diastolic Dimension; ESD: End-Systolic Dimension; EF: Ejection Fraction; LAD: Left Atrial Diameter; P max: P maximum; P min: P minimum; PD: P Dispersion; NS: Non-Significant.

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Table 2. Comparison of P wave measurements of the groups according to vessel score

Control Single vessel Double vessel Triple vessel

(Group 1) (Group 2) (Group 3) (Group 4) (n=25) (n=22) (n=26) (n=12) Pmax 84± 6 101±8 Pmin 53±7 57±9 PD 30±3 42±4

100±10 51±9 46±7

P1

P2

P3

110±10 <0.001 NS <0.013 54±9 NS NS NS 58±10 <0.001 0.039 0.001

P1: comparision of variables between group 1 and 2; P2: comparision of variables between group 2 and 3; P3: comparision of variables between group 2 and 4; P max: P maximum; P min: P minimum; PD: P Dispersion.

2. Although P max was significantly higher in Groups 2, 3 and 4, no difference was determined between Groups 1 and 2. PD was greater in all patient groups compared with the controls for all comparisons. The relationship between PD, and clinical, and echocardiographic characteristics in patients with CAD is shown in Table 3. In CAD group, PD was related to diabetes, smoking and EF (p=0.014, p=0.006, p=0.003) but not related to other clinical and echocardiographic characteristics (Table 3). Pmax and PD were related to vessel and Gensini scores in patients

Table 3. The relationship between P wave dispersion, and clinical and echocardiographic characteristics in patients with coronary artery disease

Age Gender Hypertension Diabetes Smoking LAD LVS LVD Mild MR LVEF

r p -0.004 0.974 0.052 0.695 0.017 0.895 0.316 0.014 0.348 0.006 -0.068 0.605 -0.102 0.440 -0.016 0.901 0.071 0.591 -0.372 0.003

LV: Left Ventricle; EDD: End-Diastolic Dimension; ESD: End-Systolic Dimension; EF: Ejection Fraction; LAD: Left Atrial Diameter; MR: Mitral Regurgitation

with CAD (Table 4). In multivariate logistic regression analysis, increased PD was found to be independently associated with vessel (β=4.139, p=0.002) and Gensini score (β=0.132, p=0.007).

DISCUSSION Our study showed, increased P wave duration and PD was related to the extent and severity of CAD in stable coronary artery disease patients. Similarly, increased PD has been observed to be associated with coronary artery disease severity [9].

AF is the most common cardiac rhythm abnor-

Table 4. The relationship between P wave measure-

ments and Gensini and vessel scores in patients with coronary artery disease

Pmax r p Pmin r p PD r p

Vessel score

Gensini score

0.668 0.001

0.615 0.001

-0.080 0.465

-0.128 0.249

0.848 0.001

0.825 0.001

P max: P maximum; P min: P minimum; PD: P wave dispersion

Akin et al., P wave dispersion, coronary artery disease

mality and its incidence was 0.6% in the Coronary Artery Surgery Study (CASS) registry [12]. It was demonstrated that atrial fibrillation is a predictor of survival. Interatrial conduction delays have been shown to be implicated in initiating and maintaining AF [13-15].

Another mechanism for increased PD may be the increase in collagen fiber deposition in the cardiac interstitium. It was reported that PD was associated with inhomogeneus and discontinuous propogation of sinus impulses [16]. Electrocardiographic markers of abnormal atrial conduction, such as PD, P maximum, and P minumum, may be influenced by myocardial ischemia. Atrial fibrosis due to myocardial ischemia may prolong PD [17-20]. Previous studies have demonstrated that atrial ischemia is implicated in the pathogenesis of AF [21, 22].

Dilaveris et al. reported that myocardial ischemia prolongs PD in 95 patients with documented CAD and Ă&#x2013;zmen et al. confirmed this feature in patients with angioplasty induced myocardial ischemia [23,24]. PD has also been found to be associated with carotid atherosclerosis [8]. In addition, it has been shown that P-wave dispersion is increased in coronary slow- flow phenomenon [25].

Ischemia- induced inhomogeneous and discontinuous atrial conduction may be related to increased P maximum and PD [26]. Reduced blood flow due to coronary atherosclerosis may contribute to the development of tissue injury and fibrosis [27]. Another explanation for this is that ischemia causes renin angiotensin system activation [28, 29].

The regional fibrosis in the atrial wall, due to chronic ischemia could cause different atrial conductions leading to increased PD in surface ECGs. Another pathophysiological explanation for increased P-wave duration and dispersion in CAD may be autonomic tone associated with CAD. TĂźkek et al.[30] reported that the autonomic tone changes may prolong PD. Increased serum catecholamine levels may cause atrial fibrosis and heterogeneus conduction properties.

It was reported that PD was significantly associated with LV diastolic dysfunction [31]. Ischemic left ventriculer dysfunction may increase left atrial

69

pressure, and might another fundamental causes of increased P wave duration and PD in patients with CAD compared to control subjects [32]. Atrial strain, which is a sugnificant factor in the pathophysiology of AF together with ischemia- induced hetergeneous atrial conduction, may results an increase in P wave duration and PD. Yilmaz et al. [9] found no significant association between P min and coronary artery disease severity. Similarly, in our study there was no significant association between P min and Gensini and vessel scores.

There were some limitations in our study. The major limitation of our study is the small number of patients included in the study. For evaluation of ECG results we did not use the high-resolution computer software program. Previous studies have found a low error of the measurement of PD on paper printed ECGs, contrarily other studies reported that manual PD measurement on paper printed ECGs obtained at a standard signal size may effect the accuracy and reproducibility of the results [33,34].

In conclusion, our results suggest that there is a considerable association between increased PD and the severity of CAD. Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Dilaveris PE, Gialafos EJ, Andrikopoulos GK, Richter DJ, Papanikolaou V, Poralis K, et al. Clinical and electrocardiographic predictors of recurrent atrial fibrillation. Pacing Clin Electrophysiol 2000;23:352-8.

2. Dilaveris PE, Gialafos EJ, Sideris SK, Theopistou AM, Andrikopoulos GK, Kyriakidis M, et al. Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J 1998;135:733-8.

3. Dilaveris PE, Gialafos JE. P-wave dispersion: a novel predictor of paroxysmal atrial fibrillation. Ann Noninvasive Electrocardiol 2001;6:159-65.

4. Yazici M, Ozdemir K, Altunkeser BB, Kayrak M, Duzenli MA, Vatankulu MA, et al. The effect of diabetes mellitus on the Pwave dispersion. Circ J 2007;71:880-3.

5. Liu T, Fu Z, Korantzopoulos P, Zhang X, Wang S, Li G. Effect of obesity on p-wave parameters in a Chinese population. Ann

70 Noninvasive Electrocardiol 2010;15:259-63.

6. Cagirci G, Cay S, Karakurt O, Eryasar N, Acikel S, Dogan M, et al. P-wave dispersion increases in prehypertension. Blood Press 2009;18:51-4.

7. Karabag T, Dogan SM, Aydin M, Sayin MR, Buyukuysal C, Gudul NE, et al. The value of P wave dispersion in predicting reperfusion and infarct related artery patency in acute anterior myocardial infarction. Clin Invest Med 2012;35:E12-9.

8. Ozuğuz U, Ergün G, Işık S, Gökay F, Tütüncü Y, Akbaba G, et al. Association between C-reactive protein, carotid intimamedia thickness and P-wave dispersion in obese premenopausal women: an observational study. Anadolu Kardiyol Derg 2012;12:40-6.

9. Yilmaz R, Demirbag R. P-wave dispersion in patients with stable coronary artery disease and its relationship with severity of the disease. J Electrocardiol 2005;38:279-84.

10. Sullivan DR, Marwick TH, Freedman SB. A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J 1990;119:1262-7.

11. Gensini GG. Coronary arteriogaphy. Mount Kisco, New York: Futura Publishing Co, 1975.

12. Cameron A, Schwartz MJ, Kronmal RA, Kosinski AS. Prevalence and significance of atrial fibrillation in coronary artery disease (CASS Registry). Am J Cardiol 1988;61:714-7.

13. Shimizu A, Centurion OA. Electrophysiological properties of the human atrium in atrial fibrillation. Cardiovasc Res 2002;54:302-14.

14. Centurión OA, Shimizu A, Isomoto S, Konoe A. Mechanisms for the genesis of paroxysmal atrial fibrillation in the Wolff Parkinson-White syndrome: intrinsic atrial muscle vulnerability vs. electrophysiological properties of the accessory pathway. Europace 2008;10:294-302.

15. Centurión OA. Clinical implications of the P wave duration and dispersion: relationship between atrial conduction defects and abnormally prolonged and fractionated atrial endocardial electrograms. Int J Cardiol 2009;134:6-8.

16. Spach MS, Dolber PC. Relating extracellular potentials and their derivatives to anisotropic propagation at a microscopic level in human cardiac muscle. Evidence for electrical uncoupling of side-to-side fiber connections with increasing age. Circ Res 1986;58:356-71.

17. Kostin S, Klein G, Szalay Z, Hein S, Bauer EP, Schaper J. Structural correlate of atrial fibrillation in human patients. Cardiovasc Res 2002;54:361-79.

18. Röcken C, Peters B, Juenemann G, Saeger W, Klein HU, Huth C, et al. Atrial amyloidosis: an arrhythmogenic substrate for persistent atrial fibrillation. Circulation 2002;106:2091-7.

19. Frustaci A, Chimenti C, Bellocci F, Morgante E, Russo MA, Maseri A. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997;96:1180-4.

20. Boldt A, Wetzel U, Lauschke J, Weigl J, Gummert J, Hindricks G, et al. Fibrosis in left atrial tissue of patients with atrial fibril-

North Clin Istanbul – NCI lation with and without underlying mitral valve disease. Heart 2004;90:400-5.

21. Ausma J, Wijffels M, Thoné F, Wouters L, Allessie M, Borgers M. Structural changes of atrial myocardium due to sustained atrial fibrillation in the goat. Circulation 1997;96:3157-63.

22. Brundel BJ, Henning RH, Kampinga HH, Van Gelder IC, Crijns HJ. Molecular mechanisms of remodeling in human atrial fibrillation. Cardiovasc Res 2002;54:315-24.

23. Dilaveris PE, Andrikopoulos GK, Metaxas G, Richter DJ, Avgeropoulou CK, Androulakis AM, et al. Effects of ischemia on P wave dispersion and maximum P wave duration during spontaneous anginal episodes. Pacing Clin Electrophysiol 1999;22:1640-7.

24. Ozmen F, Atalar E, Aytemir K, Ozer N, Açil T, Ovünç K, et al.

Effect of balloon-induced acute ischaemia on P wave dispersion during percutaneous transluminal coronary angioplasty. Europace 2001;3:299-303.

25. Turkmen M, Barutcu I, Esen AM, Karakaya O, Esen O, Basaran Y. Effect of slow coronary flow on P-wave duration and dispersion. Angiology 2007;58:408-12.

26. Lammers WJ, Kirchhof C, Bonke FI, Allessie MA. Vulnerability of rabbit atrium to reentry by hypoxia. Role of inhomogeneity in conduction and wavelength. Am J Physiol 1992;262:H47-55.

27. Anderson KR, Sutton MG, Lie JT. Histopathological types of cardiac fibrosis in myocardial disease. J Pathol 1979;128:79-85.

28. Michelucci A, Bagliani G, Colella A, Pieragnoli P, Porciani MC, Gensini G, et al. P wave assessment: state of the art update. Card Electrophysiol Rev 2002;6:215-20.

29. Cha YM, Dzeja PP, Shen WK, Jahangir A, Hart CY, Terzic A, et al. Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability. Am J Physiol Heart Circ Physiol 2003;284:H1313-20.

30. Tükek T, Akkaya V, Demirel S, Sözen AB, Kudat H, Atilgan D, et al. Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. Am J Cardiol 2000;85:896-9, A10.

31. Gunduz H, Binak E, Arinc H, Akdemir R, Ozhan H, Tamer A, et al. The relationship between P wave dispersion and diastolic dysfunction. Tex Heart Inst J 2005;32:163-7.

32. Chen YJ, Chen SA, Tai CT, Yu WC, Feng AN, Ding YA, et al.

Electrophysiologic characteristics of a dilated atrium in patients with paroxysmal atrial fibrillation and atrial flutter. J Interv Card Electrophysiol 1998;2:181-6.

33. Aytemir K, Ozer N, Atalar E, Sade E, Aksöyek S, Ovünç K, et al. P wave dispersion on 12-lead electrocardiography in patients with paroxysmal atrial fibrillation. Pacing Clin Electrophysiol 2000;23:1109-12.

34. Magnani JW, Mazzini MJ, Sullivan LM, Williamson M, Ellinor PT, Benjamin EJ. P-wave indices, distribution and quality control assessment (from the Framingham Heart Study). Ann Noninvasive Electrocardiol 2010;15:77-84.

Orıgınal Article

HEALTH SERVICES

North Clin Istanbul 2014;1(2):71-77 doi: 10.14744/nci.2014.30074

Patient satisfaction with outpatient health care services: evaluation of the components of this service using regression analysis Fisun Vural1, Seval Ciftci2, Yigit Cakiroglu3, Birol Vural3 Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey;

1

Golcuk Necati Celik Public Hospital, Kocaeli, Turkey;

2

Kocaeli University Faculty of Medicine, Kocaeli, Turkey;

3

ABSTRACT OBJECTIVE: In health care services, patient’s expectations, and satisfaction levels are important markers of the services provided. The aim of this study is to determine patient satisfaction level, and its influential factors in patients receiving treatment on an ambulatory basis who applied to a state hospital.

METHODS: In this cross-sectional study a total of 210 patients were face-to-face interviewed, and patient satisfaction questionnaire survey was performed. Socioeconomic characteristics, physical conditions of the hospital, pecularities of the health care providers, and satisfaction from health care services received were questioned independently. Regression analysis was performed to investigate factors effective on patient satisfaction.

RESULTS: A significant correlation was not found between sociodemographic factors, and patient satisfaction (p<0.05). Favourable patient acceptance of the health care services received is effected by the duration of the waiting period. Communication skills of the health care professionals have been found to be the fundamental factors effective on the preference or recommendation of a certain health care institute once more (p<0.005).

CONCLUSION: Empowering the communication skills of health care professionals, and decreasing the waiting period were found to be necessary in order to increase the satisfaction levels of ambulatory patients Key words: Communication; health care professional; patient satisfaction.

R

apid developments in medicine and technology increased expectations of the individuals for medical services. The integration of technological innovations with health care services has brought with them the concept of providing health care services

of good quality [1]. Fulfillment of the community’s expectations and requirements, in brief, satisfaction of the receivers of the health care services is an indispensable component of institutional success. As an indicator of offering services of high quality, patient

Received: September 11, 2014 Accepted: November 12, 2014 Online: December 08, 2014 Correspondence: Dr. Fisun VURAL. Haydarpasa Numune Egitim ve Arastirma Hastanesi, Tibbiye Cad., No: 40 Uskudar, Istanbul, Turkey.

Tel: +90 216 - 542 32 32 e-mail: fisunvural@yahoo.com.tr © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

72

satisfaction has a significant place in the management of health care services [1]. Health care institutions are complex organizations that harbour many professional health workers from auxillary personnel to highly educated staff [2]. In this complex structure, personal characteristics of the patients, many other factors related to service providers, and institutions affect satisfaction levels of the patients [3-5]. The aim of this study is to determine satisfaction levels of the patients who applied to a state hospital to receive ambulatory health care services, and investigate relevant influential factors.

MATERIALS AND METHODS This research is a cross-sectional and descriptive study performed between July and December 2012 in Kocaeli Gölcük Necati Çelik State Hospital. Approval for the study was obtained from the Ethics Committee of Kocaeli University. A questionnaire survey was conducted after approval received from the Chief Medical Officer. The survey includes items similar to those employed in ambulatory patient satisfaction questionnaire issued by Turkish Ministry of Health and Social Welfare ( July 2011).

Responses to questions were evaluated using threepoint Likert scale as “yes, no, and somewhat”.

The study was performed on 210 volunteered patients who complied with the inclusion criteria, among 300 patients who applied to the Information Bureau of the Chief Medical Officer. The patients who did not complete bureaucratic procedures or applied to the outpatient clinic after working hours, and patients scheduled for operation, hospitalization or postoperative care and referred to another health care institution excluded from the study.

People with examination priorities such as emergency department patients, pregnant and puerperal women, elderlies (>65 years) or very young (<16 years) patients, psychiatric and, dialysis patients were also excluded.

The questionnaire consisted of 4 primary domains, and 20 items and a survey study realized with face-to-face interviews.

1. Descriptive characteristics of the patients asked (patient’s age, gender, educational level, pro-

North Clin Istanbul – NCI

fession, social security coverage).

2. The section related to the health care professionals (attitudes, and behaviours of the physician, and the staff, attention to personal intimacy, sufficient time reserved for physical examination, and informing the patient).

3. Questions related to physical conditions and bureaucratic procedures of the institution (comfort of the patient registration /admission office, waiting time for one’s turn for registration –examination / analysis, cleanliness of the place).

4. Thoughts about the hospital (advisability, preferring the same institution once more and quality of the health care service).

To investigate participants’ preference, recommendations for health care institute, favourable acceptance of the service, factors related to institutional and health care providers were questioned separately. Institutional factors were comfortability of the waiting area of registration/admission office, general cleanliness of the outpatient clinics, shorter waiting period for one’s turn for examinations/analyses. Factors related to health care providers were examining physician’s sparing time for informing the patients about their disease(s), rapport between examining doctor and the staff, and respecting a patient intimacy.

Statistical analysis For the statistical evaluation of data, we used SPSS 14.0 (Statistical Package for Social Sciences) for Windows 97 program. The p- value <0.05 was accepted as the level of statistical significance, and all analyses bidirectionally evaluated within 95% confidence interval. In addition to descriptive statistical methods, the relationship between parametric/nonparametric variables was analyzed using Pearson/ Spearman correlation coefficients. Besides, components of the health care services were evaluated using regression analysis (use of linear or logistic regression analysis whether data were parametric or nonparametric). Internal consistency and reliability of the satisfaction questionnaire were analysed, and the result was expressed with Cronbach’s alpha coefficient. Calculation of Satisfaction Coefficient

Vural et al., Patient satisfaction with outpatient health care services

performed in compliance with 2012 Application Guideline of Questionnaire reported by Turkish Republic Ministry of Health Directorate of Department of Performance Management and Quality Development Calculation of coefficient was based on the following formula: Ambulatory Patient: (Total score /number of participants) x 100/ 36.

RESULTS Internal consistency, and reliability of the satisfaction questionnaire were analyzed, and Cronbachâ&#x20AC;&#x2122;s alpha coefficient was found to be 0.80. Starting from this data, we can say that our questionnaire survey is reliable. Study participants (n=210) consisted of female (48.6%), and male (51.4%) patients.

They were mostly (77.1%) married, and 50.4% of them aged less than 35 years. Vast majority of them were housewives and workers. Nearly all of them (97.1%) did not consult to the hospital for the first time. Satisfaction rate of the ambulatory patients estimated as 96.31 percent. Table 1 shows the sociodemographic characteristics of the patients. The correlation between sociodemographic factors, favourable acceptance of health care services, preference, and the advisability of an institution was not detected (p>0.05).

I. Preference for the same institution once more: Nearly all (93.3%) participants preferred the same organization for the second time. Factors related to the institution and health care personnel were associated with preference for the institution for the second time (Table 2). Regression analysis of these factors revealed that health care staff is as an independent and significant factor for preference of hospital [health care personnel (p=0.000 CI: 0.241 -0.472) and physician (p=0.001 CI: -0.33â&#x20AC;&#x201C;0.08)] (Table 3).

II. Recommending an individual institution: Majority of the (92.9%) patients found the institution worthy of recommendation. Many factors related to an institution, and health care personnel were found to correlate with preference for the institution for the second time. Table 2 shows the results. The correlated factors were entered into regression analysis to find associates of advisability.

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Table 1.

Sociodemographic characteristics of the patients participating in the study

Gender Female Male Marital status Married Single Age (years) 16-35 36-55 56-65 >66 Education Illiterate Literate Primary school Secondary school University Profession Unemployed Retired Tradesman Officer Worker Housewife Student Social security coverage Yes None

n

%

102 108

48.6 51.4

162 48

77.1 22.9

106 67 25 12

50.4 31.9 11.9 5.8

2 10 99 75 24

0.95 4.75 47.2 35.7 11.4

6 33 16 9 66 68 12

2.9 15.7 7.6 4.3 31.4 32.4 5.7

189 21

90 10

Any correlation was not detected between sociodemographic factors, global satisfaction with health care services, preferring, and recommending a medical institution (p>0.05).

Communication skills of the physician (p=0.000 CI: 0.14-0.43), and health care personnel (p=0.037 CI: -0.32-0.01) were the independent factors that significantly predicted advisability of institution.

Table 3 presents the details of the analysis.

III. Global approval of health care services: Nearly all (94%) patients favorably evaluated health care services provided which was found to be related to many factors. Table 2 presents the results. In regres-

74

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Table 2. Factors related to recommending or preferring the same medical institution once more and generally favourable thoughts about the services provided

Recommendation* Preference for* Favourable opinions

the second time about the service provided Comfortable waiting area in the registration, and admission office Shorter waiting period for analyses/ examinations General cleanliness of outpatient clinics Physician’s sparing some time for informing patients Communication between the patient and the examining physician Communication of the health care personnel Respecting privacy of the patients

0.413

0.511

0.187**

0.349 0.310 0.455* 0.391 0.300 0.387 ** 0.299

0.243

0.358

0.399 0.468 0.406

0.198 0.628 0.468

0.328 0.637 0.343

r: correlation coefficient; *: p<0.0001; **:p <0.01.

sion analysis, shorter waiting period for analytical procedures (p=0.000 CI: 0.084 -0.16), and comfortable waiting area in the registration and admission office (p=0,02 CI: 0.0009-0.11) were the independent variables. Table 3 shows the regression analysis.

In conclusion, patients’ evaluation of outpatient health care services “as favourable “ has been directly associated with waiting period before the procedures of registration and analysis. The primary factor influencing patients’preference for a certain institution for the second time, or its advisability has been related to communication skills of the health care personnel. Favourable evaluation of health care services, their preference for the second time or their advisability are interrelated factors. If the services of an individual institution are usually approved by the patients, then it is more frequently preferred, and recommended (p<0.05).

DISCUSSION Patient satisfaction constitutes an important component of the quality of health care services. Since health care services can not be ‘reserved for future use’ and they are influenced by many factors, it is

hard to measure the quality of service. The presence of many influential factors such as conditions related to patients, medical staff, and institution complicate measurement of the quality of the service [6].

Determination of the patients’ satisfaction level is a must for providing services of higher quality, orientation, and management of health care systems [7].

In recent years, interest in patient satisfaction both in private, and public health care institutions is gaining momentum, and studies on measurement tools of patient satisfaction are becoming more prevalent [1]. Although an exact cut-off value for patient satisfaction used in relevant studies is not available, satisfaction rates over 70% have been asserted to reflect favourable satisfaction levels [8]. In our study, a 96.31% patient satisfaction rate was detected for the previous six months. Therefore, we can say that our patients are very much satisfied with health care services of this hospital. These higher levels of patient satisfaction might be at least partially attributed to the fact that Gölcük Necati Çelik State Hospital is the only hospital in our region without any competing health care institution.

Various factors affect patient satisfaction. These have indicated as factors related to patients, health

Vural et al., Patient satisfaction with outpatient health care services

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Table 3. Regression analysis results of the factors related to preferring, and recommending a certain health care institute, and generally favourable thoughts about the services provided

Reasons for preferring the same institute Communication skills of the examining physician Communication skills of the other health care personnel Comfortable waiting area in the registration, and admission office Shorter waiting period for analyses/examinations General cleanliness of the outpatient clinics Physician’s sparing some time for informing patients Respecting privacy of the patients Reasons for recommending a health care institution Communication skills of the examining physician Communication skills of the other health care personnel Comfortable waiting area in the registration, and admission office Shorter waiting period for analyses/examinations General cleanliness of the outpatient clinics Physician’s sparing some time for informing patients Respecting privacy of the patients Favourable acceptance of the health care services provided Comfortable waitinmg area in the registration, and admission office Shorter waiting period for analyses/examinations General cleanliness of the outpatient clinics Physician’s sparing some time for informing patients Communication skills of the examining physician Communication skills of the other health care personnel Respecting patients’ privacy

care providers, and institutions [3, 4, 5]. Patientrelated factors cited in the literature demonstrate variations [3, 8-13]. Konca et al., Çelikkalp et al. did not detect any significant correlation between sociodemographic factors and satisfaction levels [9, 10]. In other relevant studies Hekkert et al., Quintana et al., Ercan et al. revealed the presence of a correlation between sociodemographic factors and satisfaction scale scores [11-13]. However, in our study, a significant correlation was not detected between the satisfaction rates of the ambulatory patients and personal characteristics of the patients (p>0.05). We think that the reason for arriving at different conclusions as cited in the literature is related to the diverse sociocultural characteristics of the study sites.

p value

CI (95% confidence interval)

0.001 0.000 0.280 0.380 0.268 0.567 0.124

-0,33_-0.08 0.24 -0.47 0.2-0.64 0.86-1.67 0.93-1.89 0.96-2.5 0.23-0.46

0.000 0.037 0.290 0.512 0.122 0.321 0.486

0.14-0.43 -0.32 -0.01 -0.44-1.5 1.5-3.8 0.3-4.2 0.8-2.2 0.21-0.41

0.02 0.000 0.188 0. 798 0.865 0.122 0.129

0.0009-0.11 0,084 -0,16 -1.2_-2.5 2.6-6.4 2.5-4.8 1.2-3.4 1.9-6.7

Previous studies acknowledged that a patient satisfied with the health care services both prefer and advise the same service [9, 13, 14]. The prevalence rates of patients’ preference for the same institution they were satisfied with varied in the Turkish medical literature. Önsüz et al. 76.7%, Aytar, and Yeşildal et al. 93.4%, and Konca et al. 99% [3, 9, 15]. In our study, 93.3% of our patients preferred the same institution for the second time. In the literature, communication skills of medical personnel have been reported as the most important factor influencing patient satisfaction [4, 16-18]. Communication induces establishment of confidence among individuals [19, 20].

Professional approach of the medical staff, their affection, and interest to patients increase patient’s

76

compliance to treatment and participation in medical decisions [21]. Attitudes and behaviors of the personnel, rather than a technical, and clinical characteristics of the hospital have been indicated as important factors in patients’ repetitive preferences of the same hospital [22]. Also in our study, attitudes, and behaviours of the physicians, and health care personnel were found to be the most important factors for the preference of the same institution. Previous studies were done by Tükel et al. and Önsüz et al. in different settings. They found that most of the patients were recommending their health care service to others (88.6 and 70.7%, respectively) [3, 7]. In our research, the rate of advisability was much higher (92.9%). Another study performed in Izmir, physical conditions of the hospital were found to be the least important service quality dimension [23].

As a consequence, recommending or preferring an individual institution for the second time is related to the communication skills of the health care staff.

These outcomes indicate the importance of medical personnel in providing improved quality of healthcare systems. When we analyzed perceptions, and expectations of the patients, health care service quality, preference, and the advisability were found to be intermingled, and integrated factors. Professional approach and attitudes of the healthcare providers and their ways of transferring their knowledge and skills to those needed, play a significant role in patient satisfaction. When we evaluated components of the service, shorter waiting period ensures more proper evaluation of the service offered while preference and the advisability of the institute are also related to communication skills of the medical staff.

Limitation of this study is its cross-sectional design, and so its outcomes can not be generalized.

Since patient satisfaction questionnaire of the study performed has a higher internal consistency, and reliability, we can be sure of reliability of the present study. Apart from other satisfaction surveys, the present study analyzed the components of the health care services and detected deficiencies and patients’ expectancies. In this respect, we think that the present study will shed light on future studies on patients’ satisfaction.

Studies concerning patient satisfaction provide

North Clin Istanbul – NCI

feedback for offering a high-quality health care and determination of institutional targets. According to the results of the present study, we think that increasing communication skills and decreasing the number of the patients on the waiting list will increase patients’ satisfaction with health care services. The present study has revealed that patient satisfaction surveys should not be evaluated only by the satisfaction scores, but at the same time it should be analyzed based on the components of the service offered. In our study, the only element which is useful on advisability, and preference of an institute was found to be the professional attitudes and communication skills of health care personnel independent from other factors. In conclusion, we think that reinforcing communication skills of the medical staff with in-service training provided by the institutions, and satisfaction of the medical professionals for efficient working are essential.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Aslantekin F. Sağlık hizmetlerinde kalite deneyimi: Dr. Ekrem Hayri Üstündağ Kadın Hastalıkları ve Doğum Hastanesi Örneği. Fırat Sağlık Hizmetleri Dergisi 2007;2:55-71.

2. Kanber NA, Gürlek Ö, Çiçek H, Gözlükaya A. Bir Sağlık Kurumunda Sağlık Çalışanlarının Memnuniyeti. Sağlıkta Performans ve Kalite Dergisi 2010;2:114-27.

3. Önsüz M, Toğuzoğlu A, Cöbek U, Ertürk S, Yılmaz F, Birol S. İstanbul’da Bir Tıp Fakültesi Hastanesinde Yatan Hastaların Memnuniyet Düzeyi. Marmara Medical Journal 2008;21:33-49.

4. Yılmaz M. Sağlık bakım kalitesinin bir ölçütü: hasta memnuniyeti C. Ü. Hemşirelik Yüksekokulu Dergisi 2001;5:69-74.

5. Özer A, Çakıl E. Sağlık hizmetlerinde hasta memnuniyetini etkileyen faktörler. Tıp Araştırmaları Dergisi 2007:5:140-3.

6. Pala T, Saatlı G, Eser E. Hastanede yatan hastaların hastane hizmetleri ve hastane çalışanlarından memnuniyeti ve bunu oluşturan bileşenler. 8. Ulusal Halk Sağlığı Kongresi Bildiriler Kitabı, Diyarbakır; 2003:538-41.

7. Tükel B, Acuner A, Önder Ö, Üzgül A. Ankara Üniversitesi İbn–i Sina Hastanesi’nde yatan hasta memnuniyeti (genel cerrahi anabilim dalı örneği). Ankara Üniversitesi Tıp Fakültesi Mecmuası 2004;57:205-14.

8. Şahin T, Bakıcı H, Bilban S, Dinçer Ş, Yurtçu M, Günel E.

Vural et al., Patient satisfaction with outpatient health care services

Meram Tıp Fakültesi Çocuk Cerrahisi Servisinde yatan hasta yakınlarının memnuniyetinin araştırılması. Genel Tıp Dergisi 2005;15:137-42.

9. Konca G, İlhan NM, Bunin MA. “Yatarak Tedavi Gören Hastaların Hastane Çalışanları ve Hastane Hizmetlerinden Beklentileri ve Beklentilerine ilişkin Memnuniyet Durumlarının Değerlendirilmesi”. Gazi Tıp Dergisi 2006;17:160-70.

10. Çelikkalp Ü, Temel M, Saraçoğlu G, Demir M. Bir Üniversite Hastanesinde Yatan Hastaların Hizmet Memnuniyeti. Fırat Sağlık Hizmetleri Dergisi 2011;6:1-14.

11. Hekkert KD, Cihangir S, Kleefstra SM, van den Berg B, Kool RB. Patient satisfaction revisited: a multilevel approach. Soc Sci Med 2009;69:68-75.

12. Quintana JM, González N, Bilbao A, Aizpuru F, Escobar A, Esteban C, et al. Predictors of patient satisfaction with hospital health care. BMC Health Serv Res 2006;6:102.

13. Ercan İ, Ediz B, Kan İ. “Sağlık Kurumlarında Teknik Olmayan Boyut için Hizmet Memnuniyetini Ölçebilmek Amacıyla Geliştirilen Ölçek”. Uludag Üniversitesi Tıp Fakültesi Dergisi 2004;30:151-7.

14. Argan M, Argan TM. “Bursa İlindeki Özel Hastanelerde Poliklinik Hizmeti Alan Hastaların Kalite Algılamaları ve Memnuniyeti Üzerine Bir Araştırma”, Modern Hastane Yönetimi Dergisi 2004;3:46-57.

15. Aytar G, Yeşildal N. Yatan Hasta Memnuniyeti. Düzce Tıp

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Fakültesi Dergisi 2004;3:10-4.

16. Avis M, Bond M, Arthur A. Satisfying solutions? A review of some unresolved issues in the measurement of patient satisfaction. J Adv Nurs 1995;22:316-22.

17. Avis M, Bond M, Arthur A. Exploring patient satisfaction with out-patient services. J Nurs Manag 1995;3:59-65.

18. Meredith P. Patient satisfaction with communication in general surgery: problems of measurement and improvement. Soc Sci Med 1993;37:591-602.

19. Williams OA. Patient knowledge of operative care. J R Soc Med 1993;86:328-31.

20. Uz HM, Özbakır D, Ergin C. Birinci basamak sağlık hizmetlerinde hasta memnuniyeti: bir saha çalışması, Sağlık Hizmetlerinde Toplam Kalite Yönetimi ve Performans Ölçümü, Ankara Haberal Eğitim Vakfı 1997;113-8.

21. Alcan Z. Bayınndır Tıp Merkezi hemşirelik hizmetleri müdürlüğü hasta memnuniyet anket sonuçları. Çoruh M (ed).

Sağlık hizmetlerinde toplam kalite yönetimi ve performans ölçümü, Ankara Haberal Eğitim Vakfı 1997;133-8.

22. Kavuncubaşı Ş. Hastane ve sağlık kurumları yönetimi. Siyasal kitabevi. Ankara 2000;291-304.

23. Devebakan N, Yağcı K. Sağlık işletmelerinin algılanan hizmet kalitesi düzeylerinin karşılaştırmasında SERVQUAL yöntemi.

Sağlık ve hastane yönetimi 2. Ulusal Kongresi bildiriler kitabı Ankara 2005;543-53.

Or覺g覺nal Article

RADIOLOGY

North Clin Istanbul 2014;1(2):78-83 doi: 10.14744/nci.2014.84803

Evaluation and prevalence of major central nervous system malformations: a retrospective study Sadan Tutus1, Sezin Ozyurt2, Ebru Yilmaz3, Gokhan Acmaz2, Mustafa Ali Akin4 1

Department of Radiology, Kayseri Education and Research Hospital, Kayseri, Turkey;

Department of Gynecology and Obstetric, Kayseri Education and Research Hospital, Kayseri, Turkey

2

Department of Radiology, Istanbul Taksim Education and Research Hospital, Istanbul, Turkey;

3

Department of Children, Kayseri Education and Research Hospital, Kayseri, Turkey

4

ABSTRACT OBJECTIVE: Central nervous system (CNS) anomalies are the most common abnormalities of all malformations and can be diagnosed on routine prenatal ultrasonography (US). We aimed to find out fetal CNS anomaly rate in our clinic which is the referral center in the region.

METHODS: This is a retrospective study of 15000 pregnant women who were scanned for routine obstetric follow-up from January 2012 to July 2013 in our referral center. We diagnosed CNS anomalies in 41 fetuses by using high resolution ultrasound unit with 3.5 MHz transabdominal and 6 MHz transvaginal transducers.

RESULTS: CNS anomalies included 12 Chiari malformations, 2 Dandy-Walker malformations (DWM), 1 variant of Dandy-Walker syndrome (DWS), 3 iniencephalies, 15 anencephalies, 1 alobar holoprosencephaly, 2 isolated hydrocephalies, 3 hydrocephalies with cerebellar hypoplasia, 1 occipital encephalocele, 1 lumbosacral myelomeningocele accompanied with microcephaly. There were some associated anomalies in the groups that included club-foot deformities in 6 cases, ventricular septal defect (VSD) in 2 cases, polycystic kidney in 2 cases, scoliosis in 1 case, hypoplasic left ventricle in 1 case; alone atrium, single umbilical artery, echogenic focus, hydronephrosis and cleft lip and palate in the same case, and omphalocele in one.

CONCLUSION: Prognosis and early detection of CNS abnormalities have become an important issue because the most serious complications of major CNS anomalies are disability and getting bedridden and this situation is inevitably related to health economy. On the other hand prognosis of the fetus and family counseling is another important issue. Parents should decide whether to continue their pregnancies or not.

Key words: Anencephaly; Chiari; fetal anomaly; prenatal ultrasonography.

Presented at the 34th National Radiology Congress (November 6-10, 2013, Antalya, Turkey).

Received: August 31, 2014 Accepted: November 12, 2014 Online: December 08, 2014, ????

Correspondence: Dr. Sadan TUTUS. Kayseri Egitim Arastirma Hastanesi, Radyoloji Klinigi, Kayseri, Turkey.

Tel: +90 352 - 336 88 84 e-mail: tutusa@yahoo.com 穢 Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Tutus et al., Evaluation and prevelance of major central nervous system malformations

C

entral nervous system (CNS) anomalies are the most common abnormalities of all malformations and can be diagnosed on routine prenatal ultrasonography (US). Thanks to recent advances in ultrasound technology including the development of high-resolution transducers, improvements in color Doppler signal processing and new scanning techniques, structural and vascular abnormalities in the fetuses can be visualized [1]. Ultrasound examination is used as the first choice modality to detect fetal CNS malformations. It has been established in several studies that accuracy of US detection varies from 92% to 99.7% for CNS abnormalities [2]. Routine anomaly scan has become a part of current obstetric follow up. CNS malformations were defined as any abnormality visualized on head and spine evaluation. Goetzinger et al showed that some of the CNS abnormalities could be associated with chromosomal abnormalities [1]. For this reason, common CNS abnormalities such as choroid plexus cysts and ventriculomegaly were not included in this study because they may not be considered as malformations.

Prognosis and early detection of CNS abnormalities have become an important issue because the most serious complications of major CNS anomalies are disability and getting bedridden and inevitably, this situation is related to health economy. On the other hand prognosis of the fetus and family counseling is another important issue. Parents should decide whether to continue pregnancy or not.

The aim of this study was to determine CNS anomaly rate in our clinic.

Table 1.

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MATERIALS AND METHODS This is a retrospective study of 15000 pregnant women who were scanned for routine obstetric follow-up from January 2012 to July 2013 in our referral center. In our department, anomaly scanning is performed by expert radiologists between 11 and 14 weeks and between 20 and 24 weeks of gestation and additionally, in the third trimester if it is clinically required. We diagnosed CNS anomalies in 42 fetuses by using high resolution ultrasound unit with 3.5 MHz transabdominal and 6 MHz transvaginal transducers (Toshiba Xzario Shimuishigami, Otawara-Shi, Tochigi, Japan). Each ultrasound scan took approximately 20 minutes. Fetusesâ&#x20AC;&#x2122; brains and spinal canals were all scanned in axial, coronal and sagittal sections through transventricular, transcerebellar, transthalamic and spinal canal planes.

Major structural abnormalities like anencephaly, and holoprosencephaly were diagnosed in the first trimester and terminated with the approval. By considering this issue, we classified the cases with CNS abnormalities into two main groups. The first group contained the fatal abnormalities which were diagnosed in the first trimester and then terminated (Table 1). In the second group, the fetuses with mild abnormalities were followed up until their birth when the parents decided to give birth (Table 2). In the first group, however, postmortem findings and ultrasound images were compared. In the second group, cranial ultrasound or cranial magnetic resonance imaging (MRI) findings after birth were compared with the pediatriciansâ&#x20AC;&#x2122; feedback and the

Table 2. Mild abnormalities in the second group

Fatal abnormalities in the first group

Abnormalities Number

Abnormality Number

Anencephaly 15

Chiari malformations

12

Iniencephaly 3

Dandy-Walker syndrome

2

Alobar holoprosencephaly

1

Variant of Dandy-Walker syndrome

1

Hydrocephaly with cerebellar hypoplasia

3

Isolated hydrocephaly

2

Occipital encephalocele

1

Lumbosacral myelomeningocele accompany with microcephaly 1

80

North Clin Istanbul – NCI

comparison of prenatal USG findings and postnatal physical examination findings were compared.

Other fetal structural abnormalities evaluated routinely included cardiac, genitourinary, musculoskeletal systems anomalies. Maternal age, and drugs used were not taken into consideration.

Our research is a retrospective scanning study.

We aimed to find out fetal CNS anomaly rate in our clinic which is the referral center in the region.

RESULTS In the current study, in sonographic examination of 15000 pregnant women, CNS anomalies were detected in 41 fetuses and some fetuses had more than one anomaly. The mothers’ age ranged between 18 and 39 years. Major CNS anomalies were as follows: Chiari malformations, 12; Dandy-Walker Syndrome, 2; variant of Dandy-Walker Syndrome, 1; iniencephaly, 3; anencephaly, 15; alobar holoprosencephaly, 1; isolated hydrocephaly, 2; hydrocephaly with cerebellar hypoplasia, 3; occipital encephalocele, 1; lumbosacral myelomeningocele accompany with microcephaly, 1.

Nineteen of the 23 cases in Group 1 were terminated with the parents’ approval. These cases were 14 anencephalies (Figure 1), 1 alobar holoprosencephaly, 3 iniencephalies, 1 hydrocephaly with cerebellar hypoplasia. In 4 of the 23 cases, parents did not accept the termination of their pregnancy. Two of these 4 cases were hydrocephaly with cerebellar hypoplasia (Figure 2), and they were in utero ex in the 20th and 22th weeks of gestation. The other two of the 4 cases were occipital encephaloceles and anencephalies. Two cases were born at term but died soon.

Eleven of the 18 cases in Group 2 were born at term and operated by a neurosurgeon. These cases had Chiari malformations (n=7/12) (Figure 3), Dandy-Walker syndrome (1/2), isolated hydrocephaly (2/2)lum-bosacral myelomeningocele accompanied with microcephaly (n=1). The two of the other three cases in Group 2 had Dandy-Walker syndrome (n=1), and variant of Dandy-Walker Syndrome (n=1) that were born at term without being operated and then followed up. Five of the

Figure 1. Fetus with anencephaly.

Figure 2. 18

weeks fetus with hydrocephaly and cerebellar hypoplasia available.

Figure 3. Chiari malformation in the fetus, there is seen apparent neural tube defects.

12 Chiari malformations were terminated with the parents’ approval. Among these cases, there were four cases with relative marriage. Two of them were Chiari malformation, one of them was isolated hydrocephaly and one of them was anencephaly.

Tutus et al., Evaluation and prevelance of major central nervous system malformations

There were some associated anomalies in the groups that included club-foot deformity in six cases; ventricular septal defect (VSD) in two cases; polycystic kidney in two cases; scoliosis in one cases; hypoplasia left ventricule, in one case; alone atrium, single umbilical artery, echogenic focus, hydronephrosis and cleft lip and palate in the same case, and omphalocele in one case.

Polycystic kidney was seen in one anencephaly case and in one Dandy-Walker case. Six clup foot was seen in four Chiari cases, one with L-S meningomyelocele accompanied with microcephaly and one with iniencephaly case. VSD was seen in two fetuses in one anencephaly and in the other one alobar holoprosencephaly. Only one fetus with scoliosis had Chiari malformation. One Chiari case had left hearth hypoplasia. The only case with alobar holoprosencephaly had echogenic focus, single atrium, VSD, cleft lift-palate, hydronephrose and single umblical artery. Six meningocele, one scolosis and four clup foot deformity cases were seen out of twelve Chiari cases. One of the three fetuses with iniencephaly had omphalocele and clup foot deformity. One anencephaly case had policlistic kidney, hydronephrose and anhydramnios Lumbosacral meningomyelocele accompanied with microcephaly had interhemispheric cyst.

DISCUSSION CNS malformations are the most common congenital abnormalities. Neural tube defects are the most frequent CNS malformations and the ratio is about 1â&#x20AC;&#x201C;2 cases out of 1000 births. The incidence of anencephaly case depends on geographical distribution and it might be between one out of a hundred births and one out of a thousand births [3]. In our study, there were 41 central nervous system malformations on ultrasound in 15000 pregnant women.

The incidence in our study was 0.28%. Similarly, Onkar et al. reported that the incidence of central nervous system malformations on ultrasound was 0.31% [4]. In their study there was a high correlation between autopsy and postnatal examination findings with ultrasound findings. The sum of the Occipital encephalocele, L-S meningomiyelocele

81

and Chiari 2 cases in our clinic were found meaningful by the frequency of neural tube defects. In addition to that, the incidence of the anencephaly case is also meaningful. The incidence of hidrocephaly cases without neural tube defect is 1 out of 2000 [5]. In our clinic, in 5 cases seen out of 15000 patients the incidence of alobar holoprosencephaly was 1 out of 10000, however, it was reported as 1 out of 250 and generally seen as sporadic [6]. No underlying reason was determined in our case as well Dandy-Walker malformation is a rare abnormality of the CNS with a reported incidence of 1 in 25,00-35,00 live births and a slight female predominance [7]. Also iniencephaly is a very rare anomaly.

According to us, the reason why we have relatively more cases in our clinic for those two anomalies are due to its being a referral center. The incidence of intracranial abnormalities with an intact neural tube is uncertain as probably most of these escape detection at birth and only become manifest in later life. Early diagnosis of fetal malformations has been a goal in fetal medicine for a long time [8].

The assessment of fetal anatomy has always been part of this early scan and in recent years signiďŹ cant improvements have been seen in ultrasound technology [9, 10]. The first trimester ultrasound examination can detect the majority of anencephalies [11]. In our research, all of the anencephalies (15 cases) and iniencephalies (3 cases) were detected at the first trimester. Cyr et al. [12] described the sonographic appearance of the fetal rhombencephalon in 25 fetuses aged between 8 and 10 gestational weeks.

Blaas et al. [13, 14] were able to demonstrate the development of the fetal brain from 7 to 12 weeks.

Since the beginning of these studies, improvements in ultrasound equipment with increasingly widespread availability have allowed the investigation of the fetal brain in a much larger population, during the routine ďŹ rst-trimester scanning [12-14].

Detailed screening of CNS has become available through high-resolution vaginal ultrasound probes and the development of a variety of 3-dimensional (3D) ultrasound modalities. Since three dimensional and doppler ultrasound scan have not clearly demonstrated their superiority over the routine two dimensional ultrasound imaging, prenatal ultraso-

82

nography has been based on two dimensional techniques. The early development of the central nervous system (CNS), as described by embryologists and anatomists in modern embryological textbooks, is compared with sonoanatomic descriptions from two-dimensional (2D) and three-dimensional (3D) ultrasound studies, week by week in the first trimester [15] color and power Doppler ultrasound scan may be used mainly to identify and cerebral vessels and 3D ultrasound can help detect the lesions with complex anatomy [15].

Structures that should be noted in the routine examination of central nervous system include the head shape, lateral ventricles, cerebellum, cisterna magna, cavum septi pellucidum, corpus collosum and spine. The parameters affecting ultrasound examination are gestational age, fetal position, obesity and amnion fluid index.

MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation [16]. In recent years fetal MRI has emerged as a promising new technique that may add important information in selected cases mainly after 20-22 weeks [17]. We reinforced our diagnosis with two fetal MRI cases with caudal regression syndrome and cerebellar hypoplasia with hydrocephaly. MRI can provide additional information that cannot be obtained by US and is invaluable in CNS anomaly evaluation, airway management, and planning for postnatal intervention [18].

In the current study, we performed standard two dimensional imaging and established major CNS anomalies like anencephaly, iniencephaly etc. at first trimester. Most cases were detected at the first or the second trimester. CNS malformations are major anomalies. Therefore, we tried to draw attention to early diagnosis because therapeutic abortion of the major CNS anomalies is of great importance to the health economy.

In conclusion, the most common CNS anomalies in our clinic are Chiari malformation and anencephaly. Half of the cases (25 cases) were terminated with the parents’ approval and most of the cases

North Clin Istanbul – NCI

were detected at the first trimester. From our experience, using standard two dimensional ultrasound to determine CNS anomalies is an adequate choice and the investigation of the fetal CNS during the first trimester scanning has become widespread with the improvements in ultrasound equipment.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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2. Blaas HG, Eik-Nes SH. Sonoembryology and early prenatal diagnosis of neural anomalies. Prenat Diagn 2009;29:312-25.

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6. Blaas HG, Eriksson AG, Salvesen KA, Isaksen CV, Christensen B, Møllerløkken G, et al. Brains and faces in holoprosencephaly: pre- and postnatal description of 30 cases. Ultrasound Obstet Gynecol 2002;19:24-38.

7. Lavanya T, Cohen M, Gandhi SV, Farrell T, Whitby EH. A case of a Dandy-Walker variant: the importance of a multidisciplinary team approach using complementary techniques to obtain accurate diagnostic information. Br J Radiol 2008;81:e242-5.

8. Cullen MT, Green J, Whetham J, Salafia C, Gabrielli S, Hobbins JC. Transvaginal ultrasonographic detection of congenital anomalies in the first trimester. Am J Obstet Gynecol 1990;163:46676.

9. Markov D, Pavlova E, Atanassova D, Markov P, Ivanov S. First trimester prenatal diagnosis of structural fetal anomalies with three dimensional ultrasound--possibilities and limitations. [Article in Bulgarian] Akush Ginekol (Sofiia) 2010;49:4-10. [Abstract] 10. Economides DL, Braithwaite JM. First trimester ultrasonographic diagnosis of fetal structural abnormalities in a low risk population. Br J Obstet Gynaecol 1998;105:53-7.

11. Carroll SG, Porter H, Abdel-Fattah S, Kyle PM, Soothill PW. Correlation of prenatal ultrasound diagnosis and pathologic findings in fetal brain abnormalities. Ultrasound Obstet Gynecol

Tutus et al., Evaluation and prevelance of major central nervous system malformations

2000;16:149-53.

12. Cyr DR, Mack LA, Nyberg DA, Shepard TH, Shuman WP. Fetal rhombencephalon: normal US findings. Radiology 1988;166:691-2.

13. Blaas HG, Eik-Nes SH, Kiserud T, Hellevik LR. Early development of the forebrain and midbrain: a longitudinal ultrasound study from 7 to 12 weeks of gestation. Ultrasound Obstet Gynecol 1994;4:183-92.

14. Blaas HG, Eik-Nes SH, Kiserud T, Hellevik LR. Early development of the hindbrain: a longitudinal ultrasound study from 7 to 12 weeks of gestation. Ultrasound Obstet Gynecol 1995;5:151-60.

15. International Society of Ultrasound in Obstetrics & Gynecol-

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ogy Education Committee. Sonographic examination of the fetal central nervous system: guidelines for performing the ‘basic examination’ and the ‘fetal neurosonogram’. Ultrasound Obstet Gynecol 2007;29:109-16.

16. Saleem SN. Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development. J Child Neurol 2013;28:890-908.

17. Levine D, Barnes PD, Robertson RR, Wong G, Mehta TS. Fast MR imaging of fetal central nervous system abnormalities. Radiology 2003;229:51-61.

18. Hibbeln JF, Shors SM, Byrd SE. MRI: is there a role in obstetrics? Clin Obstet Gynecol 2012;55:352-66.

Orıgınal Article

INTERNAL MEDICINE

North Clin Istanbul 2014;1(2):84-88 doi: 10.14744/nci.2014.10820

Assesment of the patients presenting with severe anemia to the emergency internal medicine clinic Seydahmet Akin1, Ercan Ergin2, Sinan Kazan1, Nurgul Keskin Tukel3, Didem Kilic Aydin1, Mustafa Tekce1, Mehmet Aliustaoglu1 Department of Internal Medicine, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Istanbul, Turkey;

1

Department of Internal Medicine, Savastepe State Hospital, Balıkesir, Turkey;

2

Department of Internal Medicine, Batman State Hospital, Batman, Turkey

3

ABSTRACT OBJECTIVE: Etiological evaluation of the patients who were hospitalized with the diagnosis of severe anemia (Hb<7 gr/dl) in the emergency internal medicine clinic between January and July, 2013.

METHODS: In this study, 112 patients who were hospitalized in Dr. Lutfi Kirdar Kartal Education and Research Hospital emergency internal medicine clinic with severe anemia between January and July 2013 were retrospectively analyzed. Patients’ initial complaints, underlying causes of their anemia and prognosis of the patients were evaluated.

RESULTS: The etiology of anemia was iron deficiency in 60 (53.6%), chronic kidney failure in 16 (14.2%), hematologic malignancies in 12 (10.7%), liver cirrhosis in 12 (10.7%) and other non-malignant hematologic disorders in 4 (3.6%) patients.

CONCLUSION: The most common cause of anemia in patients who apply to emergency internal medicine clinic with severe anemia is iron deficiency. The most common complaints on admission are subjective ones such as weakness, fatigue and lassitude. Chronic disease anemia does not cause severe anemia as much as iron deficiency.

Key words: Anemia, chronic disease, iron deficiency.

Received: June 24, 2014 Accepted: November 11, 2014 Online: December 08, 2014 Correspondence: Seydahmet AKIN. Dr. Lutfi Kirdar Kartal Egitim ve Arastirma Hastanesi, Ic Hastaliklari Klinigi, Cevizli, Kartal, Istanbul, Turkey.

Tel: +90 216 - 441 39 00 / 1624 e-mail: seydahmeta@hotmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Akin et al., Assesment of the patients presenting with severe anemia to the emergency internal medicine clinic

A

nemia refers to decreased erythrocyte count in circulation or decreased hemoglobin content of the blood. Anemia is a finding rather than a disease.

The correct diagnosis in a patient with anemia must include the cause of anemia (ie. iron deficiency anemia, and hemolytic anemia etc.), otherwise only a finding is detected, but not the disease [1, 2]. Hemoglobin and hematocrit values differ with sex and age and also show diurnal variations. The highest levels are seen in the morning whereas the lowest ones are seen in the evening in the same person. But difference between the highest, and the lowest values is not so wide, it rarely exceeds 1 gr/dl and most of the time it is less than this. The reason of this daily variation is probably the fluctuations in plasma volume.

When evaluating an anemic patient and response to treatment, diurnal variations in hemoglobin levels should be taken into account [3]. Epidemiologic studies point out that frequency of anemia increases with age. According to National Health and Nutritional Examination Survey III, anemia is present in 10% of Americans that are older than 65 years of age. After age 85, this ratio can reach 25% in females and 20% in males [4]. It is stated that the incidence of anemia is between 8.3-16.3% in Asian countries [5, 6]. In a study of Choi et al. among 1254 patients older than 60 years of age in 3 cities, incidence of anemia was found to be 13.6% [6]. Studies in our country also demonstrate variations in the incidence rates of anemia in different age groups (31.5, 16.9, and 7.9% in patients older than 50, 60, and 65 years of age, respectively) [7, 8, 9]. This ratio is 21% in elderly patients who had consulted to internal medicine outpatient clinic [10]. Frequently encountered causes of anemia include malignancies of prostate, genitourinary, and gastrointestinal systems. In spite of the fact that evidence about the effects of hemoglobin levels on health are rapidly accumulating, it is still controversial if these effects are due to anemia or anemia is just an innocent bystander [11].

Studies have shown that anemia increases mortality in elderly patients by causing cardiovascular and neurological complications [12, 13]. Anemia also increases mortality by adversely effecting physical performance and requiring hospitalization due to motion limitation and falls [14, 15]. In studies in-

85

vestigating the effect of anemia of any etiology on mortality, it has been shown that mortality rates are significantly higher in anemic patients compared to non- anemic ones during long- term follow- up [12, 13, 14, 15, 16]. Emergency services are used for the situations that emerge suddenly, with acute onset requiring urgent help from a physician. Due to increased rate of elderly in the population, the number of patients in the emergency services has increased.

In our study, we evaluated patients who were hospitalized with severe anemia in emergency internal medicine service from etiologic, symptomatological and prognostic perspectives.

MATERIALS AND METHODS A hundred and twelve patients who were hospitalized in emergency internal medicine services for severe anemia (Hb<7g%) between January and July 2013 were included in this cross-sectional study.

Patientsâ&#x20AC;&#x2122; initial complaints, etiologic factors for anemia and prognosis were evaluated. Patients under 18 years of age were excluded from the study. Patients with evidence of active bleeding (gastrointestinal bleeding , intracranial bleeding, hematuria, etc.) at admission were not included in the study.

RESULTS Total of 112 patients (52 males, 46.3% and 60 females, 53.7%) were included in the study (Figure 1, Table 1). Mean age of the patients was 62.7Âą13.6 years and mean hemoglobin level was 6.5Âą3.63 gr/

Female (53.7%)

Figure 1. Gender distribution.

Male (46.3%)

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North Clin Istanbul – NCI

Forgetfulness (3.6%)

Benign hematologic states (3.6%)

Hair loss (7.1%)

Liver cirrhosis (3.6%)

Pica (7.1%)

B12 deficiency (3.6%)

Weight loss (17.9%)

Non-hematologic malignancy (10.7%)

Lassitude (64.3%)

Hematologic malignancy (10.7%) Chronic kidney disease (14.2%) Iron deficiency (53.6%)

0

20

40

60

80

0

Figure 2. Complaints in admission.

40

60

Figure 3. Anemia etiology.

dl. Patients presented with fatigue, weakness and lassitude (n=72; 64.3%), weight loss and night sweats (n=20; 17.9%) pica signs such as craving for ice and soil, hair loss (n=8; 7.1%) and amnesia (n=4; 3.6%) (Figure 2). The etiologies of anemia included iron deficiency in 60 (53.6%), chronic kidney fail-

Table 1.

20

ure in 16 (14.2%), hematologic malignancies in 12 (10.7%), hematologic malignancies in 12 (10.7%), non-hematologic malignancies in 12 (10.7%), liver cirrhosis in 4 (3.6%), B12 deficiency in 4 (3.6%) and other non-malignant hematologic disorders in 4 (3.6%) patients (Figure 3, Table 2).

Gender and age distribution of the patients

Gender distribution Mean age of the patients (years)

Male Female 46.3% (n=52) 60.7±11.7

53.7% (n=60) 63.9±12.4

Table 2. Some laboratory parametres in various forms of anemia

Iron

deficiency

Chronic Hematologic kidney malignancy disease

Non Vit. B12 Liver hematologic deficiency cirrhosis malignancy

Benign hematologic disease states

HB (gr/dL) 6.2 6.9 6.4 6.1 6.8 6.4 6.9 MCV (fl) 59 62 101 74 112 82 88 WBC (/mm³) 7480 9200 3200 2100 3500 4590 6500 PLT (/mm³) 225000 185000 64000 74000 56000 110000 35000 FERRITIN (ng/mL) 5.3 7.4 125 95 105 135 124 Vit. B12 (pg/mL) 350 240 900 1010 35 395 712 Folate (ng/mL) 8.2 6.5 14 8 5 6 12 Hb: Hemoglobin; MCV: Mean corpuscular volume; WBC: White blood cell counts; PLT: Platelets.

Akin et al., Assesment of the patients presenting with severe anemia to the emergency internal medicine clinic

DISCUSSION Most patients apply to physicians with known symptoms of anemia. But sometimes prominent symptoms are related to disease that anemia stem from.

It is not rare that patients see doctors with different complaints and coincidentally iron deficiency is found. Although weakness, fatigue, lassitude, palpitation, headache, dyspnea and pallor are mostly seen reasons for seeing a doctor, they are nonspecific and can be seen in pathologies other than anemia. In our study, weakness, fatigue and lassitude were mostly seen complaints with a frequency of 64.3%. In 20 patients (17.9%) night sweats and weight loss were more prominent. Pica syndrome which is seen in iron, cupper or zinc deficiency was present in only 8 (7.1%) patients. In a study of Young et al., pica syndrome was found to be strongly related to iron deficiency and seen in 40% of the patients with iron deficiency [17]. Accordingly, it could be expected to see more pica syndrome patients among iron deficient patients in our study. Pica syndrome which is defined as consumption of uneatable objects is not one of the reasons for emergency service visit. That is why its incidence may seem lower than expected.

It is thought that a research with patients from internal medicine outpatient clinics will yield results comparable to those reported in the literature. In a study by Joosten et al., etiologic factors for anemia in elderly population were as follows: chronic disease anemia (34%), iron deficiency anemia (15%), vitamin B12 and folate deficiency anemia (5.6%), idiopathic anemia (17%), post hemorrhagic anemia (7.3%), chronic leukemia or lymphoma (5.1%) and myelodysplastic syndrome and acute leukemia (5.6%) [18]. In our study, iron deficiency was the leading cause of anemia in 60 patients (53.6%). The other detected etiologies were chronic kidney failure (14.2%), hematologic malignancies (10.7%), liver cirrhosis (10.7%) and nonmalignant hematologic pathologies (3.6%). The reason of this difference is probably due to the fact that we only included patients with hemoglobin levels under 7 gr/dl in our study. Anemia is not severe in chronic disease anemia as reported by various studies in the literature.

But in a study of Chernetsky et al., the leading cause

87

of anemia was chronic diseases (65%), followed by chronic liver disease (13.2%), nutritional deficiency (iron, vitamin B12, folate) (4%) and idiopathic etiologies (15.9%) [19]. As a similar result, chronic kidney failure was found to be the second leading cause of anemia with a rate of 14.2% in our study.

A significant correlation between anemia and nutritional deficiency has been also revealed [20, 21].

Iron deficiency anemia is characterized by decreased iron storage, low serum iron transferrin saturation, hemoglobin and hematocrit levels. Iron deficiency may develop because of several different factors such as low iron intake from diet, malabsorption, chronic blood loss, usage for erythropoiesis in fetus or by lactating, hemoglobinuria with intravascular hemolysis or combinations of these factors [22]. It is caused by uncompensated iron needs in increased demand or pathologic conditions that effects iron balance negatively. Choi et al. reported that increased age, decreased albumin, increased creatinine and decreased body mass index are independent risk factors for anemia in elderly population [23]. In our study, the most common etiologic factor in patients hospitalized with severe anemia was found to be iron deficiency anemia. As seen in the literature, in our study, nutritional deficiency of iron plays the main role in iron deficiency. But results of our study were found to be different than most sources in the literature. The main reason of this difference is thought to be that only patients with severe anemia were included in our study. Etiologic factors vary between anemia in outpatient clinic patients and severe anemia that requires blood transfusion. In fact, chronic disease anemia which is seen frequently in normal population rarely causes severe anemia. This study only shows the frequency of severe anemia in emergency internal medicine service and does not reflect the actual rate in population. Moreover, because the study is cross- sectional, it provides limited information about anemia patients. But despite this limitation, this study has a critical importance in that it shows frequent symptoms and reasons of severe anemia in patients that are hospitalized in an emergency internal medicine service, and emphasizes that further examination may be needed in severe anemia patients. Furthermore, larger studies about

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anemia prevalence and incidence should be done not only in patients visiting outpatient clinics with mild complaints, but also in asymptomatic patients in general population.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Lux SE. Introduction to anemias. In: Handin RI, Lux SE, Stossel TP, editors. Blood principles & Practice of Hematology. Philadelphia: Lippincott Co; 1995. p. 1383-98.

2. Atamer T. Anemik hastaya yaklaşım. Büyük öztürk K (ed). İç hastalıkları. Nobel Tıp Kitabevleri: İstanbul; 1992. p. 427-34.

3. Bessman JD, Johnson RK. Erythrocyte volume distribution in normal and abnormal subjects. Blood 1975;46:369-79.

4. Gunter EW, Lewis BG, Koncikowski SM. Laboratory procedures used fort he third national health and nutrition examination survey (NHANES III) 1988-1994. Atlanta: GA 30341-3724; National Centers of Disease Control and Prevention: 1996.

5. Bang SM, Lee JO, Kim YJ, Lee KW, Lim S, Kim JH, et al. Anemia and activities of daily living in the Korean urban elderly population: results from the Korean Longitudinal Study on Health and Aging (KLoSHA). Ann Hematol 2013;92:59-65.

6. Choi CW, Lee J, Park KH, Yoon SY, Choi IK, Oh SC, et al.

Prevalence and characteristics of anemia in the elderly: crosssectional study of three urban Korean population samples. Am J Hematol 2004;77:26-30.

7. Özdemir L, Koçoglu G, Sümer H, Nur N, Polat H, Aker A, ve ark. Sivas ili merkezinde yaşlı nüfusta bazı kronik hastalıkların prevalansı ve risk faktörleri. CÜ Tıp Fakültesi Dergisi 2005;27:89-94.

8. Kisioglu AN, Uskun E, Ozturk M. Socio-demographical examinations on disability prevalence and rehabilitation status in southwest of Turkey. Disabil Rehabil 2003;25:1381-5.

9. Çetin İ, Bulut Y, Yıldırım B, Ozturk B, Yenisehirli G, Etikan I, Ozdemır M, et al. The investigation of some hematological values and anemia prevalence in adult population of Tokat province. International Journal of Hematology and Oncology 2009;19:166-74.

North Clin Istanbul – NCI 10. Çelebi H, Vardı Ş, Tahtacı M, Tamer A, Balaban Y, Kanat M, ve ark. İzzet Baysal Tıp Fakültesi İç Hastalıkları polikliniğine başvuran 50 yaş üstü bireylerde kronik hastalık sıklığı. AİBÜ İzzet Baysal Tıp Dergisi 2009;4:38-42.

11. Nissenson AR, Goodnough LT, Dubois RW. Anemia: not just an innocent bystander? Arch Intern Med 2003;163:1400-4.

12. Izaks GJ, Westendorp RG, Knook DL. The definition of anemia in older persons. JAMA 1999;281:1714-7.

13. Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med 2006;119:327-34.

14. Penninx BW, Pahor M, Cesari M, Corsi AM, Woodman RC, Bandinelli S, et al. Anemia is associated with disability and decreased physical performance and muscle strength in the elderly.

J Am Geriatr Soc 2004;52:719-24.

15. Chaves PH, Ashar B, Guralnik JM, Fried LP. Looking at the relationship between hemoglobin concentration and prevalent mobility difficulty in older women. Should the criteria currently used to define anemia in older people be reevaluated? J Am Geriatr Soc 2002;50:1257-64.

16. Chalmers KA, Knuiman MW, Divitini ML, Bruce DG, Olynyk JK, Milward EA. Long-term mortality risks associated with mild anaemia in older persons: the Busselton Health Study. Age Ageing 2012;41:759-64.

17. Young SL, Khalfan SS, Farag TH, Kavle JA, Ali SM, Hajji H, et al. Association of pica with anemia and gastrointestinal distress among pregnant women in Zanzibar, Tanzania. Am J Trop Med Hyg 2010;83:144-51.

18. Joosten E, Pelemans W, Hiele M, Noyen J, Verhaeghe R, Boogaerts MA. Prevalence and causes of anaemia in a geriatric hospitalized population. Gerontology 1992;38:111-7.

19. Chernetsky A, Sofer O, Rafael C, Ben-Israel J. Prevalence and etiology of anemia in an institutionalized geriatric population.

[Article in Hebrew] Harefuah 2002;141:591-4, 667. [Abstract] 20. Smith DL. Anemia in the elderly. Am Fam Physician 2000;62:1565-72.

21. Woodman R, Ferrucci L, Guralnik J. Anemia in older adults.

Curr Opin Hematol 2005;12:123-8.

22. Foirbanks VF, Beutler E. Iron Defiency. In: Ernest Beutler, editor. Williams Hematology 5th edition. Mc Grow-Hill: USA; 1995. p. 490-506.

23. Choi CW, Lee J, Park KH, Yoon SY, Choi IK, Oh SC, et al.

Prevalence and characteristics of anemia in the elderly: crosssectional study of three urban Korean population samples. Am J Hematol 2004;77:26-30.

Or覺g覺nal Article

PM&R

North Clin Istanbul 2014;1(2):89-94 doi: 10.14744/nci.2014.07108

Clinical and demographic characteristics and functional status of the patients with fibromyalgia syndrome Nilay Sahin1, Aziz Atik2, Erdal Dogan3 Department of Physical Medicine and Rehabilitation, Balikesir University Faculty of Medicine, Balikesir, Turkey;

1

Department of Orthopedics and Traumatology, Balikesir University Faculty of Medicine, Balikesir, Turkey;

2

Department of Physical Medicine and Rehabilitation, Malatya Goverment Hospital, Malatya, Turkey

3

ABSTRACT OBJECTIVE: To investigate the clinical and demographic characteristics and functional status of the patients with fibromyalgia syndrome (FMS).

METHODS: Ninety-four patients with the diagnosis of FMS were included in the study. All patients were evaluated with short form 36 for quality of life (SF-36), pain, depression, benign joint hypermobility syndrome (BJHS), myofacial pain syndrome (MPS), and demogrophic characteristics. End-point measurements were SF-36 for quality of life, visual analogue scale, Beck Depression Index, anamnesis, and physical examination.

RESULTS: The majority of the patients were women who were suffering from generalised pain with a median age of 40.4. Mostly depression and sleep disorders were accompanying the syndrome. Physical examination revealed MPS and BJHS in most of the patients.

CONCLUSION: BJHS and MPS must also be investigated in patients with the diagnosis of FMS. Key words: Depression; fibromyalgia; joint hypermobility; myofacial pain; pain; sleep disorder.

F

ibromyalgia syndrome (FMS) is a syndrome with a complex symptomatology which does not demonstrate apparent morphological characteristics [1]. Since central sensitivity involves in the pathogenesis of FMS, occasionally physicians can find it difficult to establish a diagnosis of FMS. FMS is the second most frequently established diagnosis made by the physicians specialized in the musculoskeletal

system diseases. Each one of 10 patients is diagnosed as FMS among musculoskeletal physicians.

Its incidence in the population has been reported as 8-15 percent. It is seen 4-8 times more frequently in women than men. FMS can be seen within age range of 18, and 55 years, however it is more prevalent among women of the childbearing age.

Clinical symptoms are more frequently associ-

Received: July 18, 2014 Accepted: November 23, 2014 Online: December 08, 2014??? ??, ????

Correspondence: Dr. Nilay SAHIN. Balikesir Universitesi Tip Fakultesi, Fiziksel Tip ve Rehabilitasyon Anabilim Dali, Balikesir, Turkey.

Tel: +90 266 - 612 14 61 e-mail:nilaysahin@gmail.com 穢 Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

90

North Clin Istanbul – NCI

Table 1.

Myofacial pain syndrome (MPS) diagnostic

criteria

Table 2. Beighton criterias

Major Criteria

Major Criteria

1.

2.

3.

4

5.

1. Beighton scores ≥4/9 (+) 2. presence of arthralgia in ≥4 joints lasting for more than 3 months

Localized spontaneous pain Spontaneous pain or alteration of perception along the pathway of the trigger point Palpable taut band of the involved muscle group Hypersensitivity of one tender point along the taut band Restricted range of motion

Mi̇ nor Criteria 1. When pressed on the trigger point, emergence of spontaneously perceived pain, and altered sensations 2. Emergence of local twitchings of local muscle fibers when trigger point pricked or palpated 3. Alleviation of pain when the involved muscle is stretched or an analgesic was injected into the trigger point.

For the establishment of the diagnosis of MPS, 5 major, and at least one minor criteria should be detected.

Mi̇ nor Criteria 1.

2.

3.

4.

5.

6.

7.

8.

Beighton score 1,2 or 3/9 (if aged 50+ then 0,1,2 or 3 /9) Arthralgia detected in one of three affected joints or back pain or spondylosis, spondylolisthesis Dislocation/sublocation of more than one joint ≥3 soft tissue pathologies (bursitis, tenosynovitis, epicondylitis) Marfanoid appearance, and habitus (tallness, long arms, upper/lower extremity <0.89, arachnodactyly Cutaneous strias, hyperextensibility, thin skin, abnormal scarring Ophthalmological signs: Prolapsus of the eyelid or myopia or antimongoloid slant Varicose veins or hernia or uterine /rectal prolapsus

For the establishment of diagnosis presence of 2 major or 1 major + 2 minor or 4 minor criteria or in 1st degree relatives 2 minor criteria should be revealed.

ated with pain. Pain is generalized or regional, and it is described on the right or left side of the body, below or above the waist or along the axial skeleton.

Pain persisting for at least 3 months is observed.

However at the beginning, complaints of pain are related to only one region. Because of presence of neuroendocrine dysfunction playing a role in the pathology of FMS, myofacial pain syndrome, restless leg syndrome, migraine, irritable bowel syndrome, and chronic fatigue syndrome can accompany the clinical picture. Indeed, these syndromes are associated with similar pathogenetic mechanisms [2, 3].

Symptoms seen in most of the patients are associated with these syndromes.

Psychological problems are also widely observed in FMS patients. Especially symptoms of depression or anxiety are encountered among them [4].

In the majority of the patients, sleep disorders can be seen. Therefore, complaints of fatigueness develop, and especially morning fatigueness be-

Beighton Criteria

Right Left

90o dorsiflexion of the metocarpal joint 1 Passive apposition of the thumb to the flexor aspect of the forearm 1 Ability to hyperextend the arm more than 10˚ 1 Ability to hyperextend the knee more than 10˚ 1 Touching the palm of the hand on the ground while the foot, and the knee in extension 1 Total 9

1 1 1 1

1

For the establishment of diagnosis at least 4/9 (+) criteria should be present. Since this scoring system evaluated some certain regions of the body, and it did not demonstrate the degree of hypermobility, its routine use had been severely criticized, and it was revised in 1998 so as to construct Beighton criteria.

Sahin et al., Clinical and demographic characteristics and functional status of the patients with fibromyalgia syndrome

91

Table 3. Demographic data, and other concomitant conditions Parametres (n:94) Age BMI Gender (female) Marital status (married) Education (university) Profession (housewife)

Concomitant conditions

40.4 MPS 75.2% 24.4 BJHS 78.9% 89.5% Sleep disorder 71.3% 68% Depression 63.5% 48% 38.8%

comes predominant. Patients frequently complain of problems in falling asleep, especially sound sleep, and frequent arousals from their sleep at night [5].

The aim of this study is to analyze potentially concomitant diseases, clinical, demographic findings, and functional state of the patients in order not to overlook FMS in the differential diagnosis.

MATERIAL AND METHOD A total of 94 volunteered patients who met inclusion criteria of the study and diagnosed as FMS, and consulted to the outpatient clinic because of widespread bodily pains, and complaints of poorly localized chronic pain enrolled in the study. Patients with complaints of radicular pain, neurological deficit, discal herniation, fractures, infection, malignancy, serious systemic disease, and pains secondary to established diagnosis of psychotic disorders were not included in the study. From every study population informed consent forms were obtained.

General demographic information of the patients were obtained, and then sleep disorder was interrogated. Depressive state of the patients was evaluated using Beckâ&#x20AC;&#x2122;s depression scale (BDS) [6].

Pain perception of the patients was questioned, and scored between 0, and 10 points using visual analogue scale (VAS). For the evaluation of general health state, physical function, physical strength, pain, general health, energy (vitality), social function, emotional power, and mental health, short form-36 (SF-36) was used [7]. As a chronic pain

syndrome, presence of myofacial pain syndrome (MPS) (Table 1) was inquired, and benign joint hypermobility syndrome (BJHS) was evaluated using Beighton diagnostic criteria (Table 2).

RESULTS For statistical analysis, SPSS (Statistical Package for Social Science) Windows statistics program version 11.0. was used. As statistical methods frequencies, and descriptive methods were employed.

Age range of the patients varied between 16, and 75 years (median, 40.4 years), and mean body mass index (BMI) was 24.44 kg/m2. Study group consisted of female (89.5%), and male (10.5%) individuals. Most of the patients were married (68%), and university graduates (48%). MPS, and BJHS were detected in 75.2, and 78.9% of the patients with diagnosis of FMS. Sleep disorders were detected in 71.3% of the patients, and using BDS, depression was disclosed in 63.5% of the patients (Table 3). Mobility VAS scores ranged between 4, and 9 points (median, 6.55 pts), and resting VAS scores varied between 0, and 9 points (median 5.98 pts) (Table 4). Mostly, lower physical role, pain, and energy scores were detected in SF-36 health screening of the patients (Table 5).

DISCUSSION FMS is seen 4 to 8-fold more frequently in women, than men [8]. FMS can be seen at every age, however it is especially more prevalent in women of the

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North Clin Istanbul – NCI

Table 4. Evaluation of pain using VAS Parametres (n:94)

0-10

mean±SD

VAS (mobility) VAS (resting)

4-9 0-9

6.55±1.614 5.98±3.651

Table 5. Evaluation of general health state using SF-36 SF-36 subgroups (n:94) Physical function Physical role Pain General health Energy Social Emotional Mental

minimum

maximum

15.00 .00 12.00 5.00 .00 12.50 .00 16.00

childbearing age. It is generally seen within the age range of 18, and 55 years. In various studies, median age of the patients was reported as 31 (27-46 yrs) years [9, 10, 11]. In our study, age range was 16-75 (mean, 40.4 yrs) years which was similar to those found in other studies.

Goldman observed joint laxity in patients with FMS, and fibrositis [12]. Hudson N. et al. encountered soft - tissue rheumatic disorders (FMS, bursitis, and tendinitis) in 67% of BJHS patients, and 25% of the control group, and demonstrated a statistically significant increase in soft- tissue disorders in BJHS [13]. In our study, detection of BJHS in 78.9% of FMS patients supports the outcomes of other studies.

Granges et al. encountered MPS in 68.3% of their 60 FMS patients [14]. However Gerwin et al.made diagnoses of FMS (n=18/96) and MPS (n=25/96) in 18.7%, and 26% of the patients who consulted to their outpatient clinics, respectively.

Since MPS was detected in most (75.2%) of our

mean±SD

100.00 69.687±21.128 100.00 38.437±37.724 90.00 35.812±17.535 92.00 49.859±22.057 85.00 38.812±20.908 100.00 62.812±22.587 100.00 51.666±40.007 100.00 52.100±18.046

patients, our results were deemed to be comparable with the results of other studies [15].

Sleep disorders can be seen in patients because of generalized pain which also worsens quality of life of the patients. MPS, and FMS are associated with sleep disorders, and interventions aiming at increasing sleep quality, also alleviate patients’ pain [16]. Still in our study, a close correlation was observed between MPS, and sleep disorders.

Previous studies also demonstrated lower quality of life in patients with FMS [17]. In a study where functional state, and quality of life of FMS patients were compared with healthy controls, quality of life scores of FMS patients were found to be significantly lower than those of the healthy controls [18].

In our study, in all SF-36 subgroups which evaluated disability, poor scores were obtained especially in physical role, energy, and pain subgroups similar to those seen in other studies.

Frequently depression accompanies FMS [19, 20]. Various studies demonstrated the presence of

Sahin et al., Clinical and demographic characteristics and functional status of the patients with fibromyalgia syndrome

neuroendocrine dysfunction in FMS [21]. Neuroendocrine dysfunction aggravates stress, adverse psychosocial factors, and pain. In these patients, higher rates of depression, and somatization symptoms relative to those without history of generalized pain were encountered. Depressive symptoms were detected in 63.5% of our patients.

In FMS chronic, moderate-severe episodes of pain are observed [21]. Similarly in our study, based on VAS scores, moderate pain which aggravated with movements was detected.

Kohl et al. investigated mental reconstruction of hot-cold tolerance, and depth of pain, and could not detect any difference between FMS patients, and control subjects as for process of cognitive reconstruction of hot-cold tolerance [22]. Flodin et al. reported that interaction, and communication between cerebral regions involving in the perception of painful stimuli, and sensorimotor regions is disrupted which resulted in defective regulation of painful stimuli [23].

Kleinman et al. investigated sleep disorders in FMS patients, and strongly evidenced that sleep disorders are seen in FMS patients. They also reported that most of the disorders seen in these patients triggered insomnia, and problems in falling asleep which worsened symptoms because of inadequate resting periods [24]. We also found a significant correlation between FMS, and sleep disorders.

Gonzalez et al. investigated the association between personal dispositions, previous traumatic events, and psychopathologies and onset of FMS, and found that personal characteristics were very closely linked with FMS, and contrary to common assumptions, previous traumatic events did not exert a strong impact on the onset of the disease [25].

In our study, personal disposition of the women in their chldbearing age was associated with the onset of FMS. Cassisi et al. emphasized the association between FMS, and central nervous system anomalies, MPS, BJHS, and temporomandibular joint disorders, and indicated the necessity of a multidisciplinary approach so as to relieve symptoms of pain, and restricted mobility suffered by these patients [26].

93

Fitzcharles et al. reported that FMS patients with low socioeconomic status experienced worse functional disability, and more severe symptoms compared with other FSM patients despite the same levels of pain, anxiety, and depression due to the differences in the perception of the disease state [27].

We also revealed the necessity of investigating additional pathologies, and supportive treatment in addition to pharmacological, and non-pharmacological treatment modalities applied for FMS patients.

CONCLUSION In this study, we have observed that most of the patients with FMS are middle-aged women with complaints of generalized pain, and sleep disorders.

This study has also revealed that these patients suffer from painful episodes while resting being more severe with movements. In some patients presence of depression was detected. In patients with established diagnosis of FMS, criteria of MPS, and BJHS should be absolutely evaluated. Moreover, it has been detected that majority of the patients experience considerable decreases especially in physical role, energy (vitality), and pain scores which necessitate multidisciplinary approach to the treatment of FMS patients.

Clinical message In patients with established diagnosis of FMS, concomitant pathologies as MPS, and BJHS should be also investigated.

It should not be forgotten that patients with diagnosis of FMS require multidisciplinary approach.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Imbierowicz K, Egle UT. Childhood adversities in patients with fibromyalgia and somatoform pain disorder. Eur J Pain 2003;7:113-9.

2. Yunus MB. Fibromyalgia syndrome: clinical features and spec-

94 trum. J Musculoskelet Pain 1994;2:5-21.

3. Yunus MB. Suffering, science and sabotage. J Musculoskelet Pain 2004;12:3-18.

4. Matarán-Peñarrocha GA, Castro-Sánchez AM, García GC, Moreno-Lorenzo C, Carreño TP, Zafra MD. Evid Based Complement Alternat Med 2009. [Epub ahead of print].

5. Schneider MJ, Brady DM, Perle SM. Commentary: differential diagnosis of fibromyalgia syndrome: proposal of a model and algorithm for patients presenting with the primary symptom of chronic widespread pain. J Manipulative Physiol Ther 2006;29:493-501.

6. Hisli N. “Validity and reliability of the Beck depression inventory in university students.” J Psychol (Psikoloji Dergisi) 1989;7:3-13.

7. Kocyigit H, et al. “Validity and reliability of Turkish version of Short form 36: A study of a patients with romatoid disorder.”

Journal of Drug and Therapy (in Turkish) 1999;12:102-6.

8. İnanıcı F. Fibromiyalji ve Miyofasiyal Ağrı Sendromları. Türkiye Klinikleri J Med Sci 2005;1:11-8.

9. Baysal Ö, Altay Z, Öner T, Dilek Y, Ünal S, Kaya B. Fibromiyaljili hastalarda venlafaksin ve amitriptilinin karşılaştırılması.

Hipokrat Lokomotor 2005;6:36.

10. Karakoç M, Nas K, Çevik R, Erdoğan F, Saraç AY, Coşut S. Fibromiyaljili Hastalarda Amitriptilin ve Lazer Tedavilerinin Etkinliklerinin Karşılaştırılması. Türkiye Fiziksel Tıp ve Rehabilitasyon Dergisi 2001;3:47.

11. Buskila D, Neumann L, Alhoashle A, Abu-Shakra M. Fibromyalgia syndrome in men. Semin Arthritis Rheum 2000;30:47-51.

12. Goldman JA. Hypermobility and deconditioning: important links to fibromyalgia/fibrositis. South Med J 1991;84:1192-6.

13. Hudson N, Starr MR, Esdaile JM, Fitzcharles MA. Diagnostic associations with hypermobility in rheumatology patients. Br J Rheumatol 1995;34:1157-61.

14. Granges G, Littlejohn G. Pressure pain threshold in pain-free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. Arthritis Rheum 1993;36:642-6.

15. Gerwin RD. Classification, epidemiology, and natural history of myofascial pain syndrome. Curr Pain Headache Rep

North Clin Istanbul – NCI 2001;5:412-20.

16. Moldofsky HK. Disordered sleep in fibromyalgia and related myofascial facial pain conditions. Dent Clin North Am 2001;45:701-13.

17. Marques AP, Ferreira EA, Matsutani LA, Pereira CA, Assumpção A. Quantifying pain threshold and quality of life of fibromyalgia patients. Clin Rheumatol 2005;24:266-71.

18. Çiğdem B, Yesim SA, Yesim K. Primer fibromiyalji sendromlu hastalarda yasam kalitesi: Ege Fiz Tıp Reh Der 1999;5:241-5.

19. Montesó Curto MP, Ferré i Grau C, Martínez Quintana V. Fibromyalgia: beyond the depression. [Article in Spanish] Rev Enferm 2010;33:20-6. [Abstract] 20. Normand E, Potvin S, Gaumond I, Cloutier G, Corbin JF, Marchand S. Pain inhibition is deficient in chronic widespread pain but normal in major depressive disorder. J Clin Psychiatry 2011;72:219-24.

21. Berker E, Dinçer N. Chronic pain and rehabilitation. Agri 2005;17:10-6.

22. Kohl A, Rief W, Glombiewski JA. Do fibromyalgia patients benefit from cognitive restructuring and acceptance? An experimental study. J Behav Ther Exp Psychiatry 2014;45:467-74.

23. Flodin P, Martinsen S, Löfgren M, Bileviciute-Ljungar I, Kosek E, Fransson P. Fibromyalgia is associated with decreased connectivity between pain- and sensorimotor brain areas. Brain Connect 2014;4:587-94.

24. Kleinman L, Mannix S, Arnold LM, Burbridge C, Howard K, McQuarrie K, et al. Assessment of sleep in patients with fibromyalgia: qualitative development of the fibromyalgia sleep diary.

Health Qual Life Outcomes 2014;12:111.

25. Gonzalez B, Baptista TM, Branco JC, Novo RF. Fibromyalgia characterization in a psychosocial approach. Psychol Health Med 2014:1-6.

26. Cassisi G, Sarzi-Puttini P, Casale R, Cazzola M, Boccassini L, Atzeni F, et al. Pain in fibromyalgia and related conditions. Reumatismo 2014;66:72-86.

27. Fitzcharles MA, Rampakakis E, Ste-Marie PA, Sampalis JS, Shir Y. The association of socioeconomic status and symptom severity in persons with fibromyalgia. J Rheumatol 2014;41:1398-404.

Orıgınal Article

CARDIOVASCULAR SURGERY

North Clin Istanbul 2014;1(2):95-100 doi: 10.14744/nci.2014.75047

Comparing the effecti̇ veness of neutrophillymphocyte ratio as a mortality predictor on mi̇ ddle and advanced age coronary artery bypass graft patients Derih Ay1, Burak Erdolu1, Gunduz Yumun2, Ufuk Aydin1, Ahmet Demir3, Osman Tiryakioglu4, Ahmet Hakan Vural1 Department of Cardiovascular Surgery, Bursa Yuksek Ihtisas Education and Research Hospital, Bursa, Turkey;

1

Department of Cardiovascular Surgery, Namik Kemal Univercity, Medical Faculty, Tekirdag, Turkey;

2

Department of Cardiovascular Surgery, Yalova State Hospital, Yalova, Turkey;

3

Department of Cardiovascular Surgery, Bahcesehir Univercity, Medical Faculty, Medical Park Hospital, Bursa, Turkey

4

ABSTRACT OBJECTIVE: In this study, the effect of neutrophil-lymphocyte ratio (NLR), which is a recently developed inflammatory parameter, as an early stage mortality predictive marker on coronary artery bypass (CABG) patients of various age groups was examined.

METHODS: Seventy eight patients under the age of 45 (Group 1) and 80 patients who were older than 45 (Group 2) randomly chosen from the patients who underwent isolated CABG surgery, were examined. The preoperative characteristics and NLRs were noted. The primary end point of the study was determined as all-cause in- hospital mortality.

RESULTS: Mortality was observed in 2 patients in Group 1 and 11 patients in Group 2. The threshold value of NLR was 2,47 in the Receiver Operating Characteristic (ROC) curve in Group 1 and there wasn’t any significant correlation between preoperative NLR and mortality rates in the patients whose NLRs were above this curve. The threshold value was determined as 4.07 in Group 2 and there was a significant relation between preoperative NLR and mortality (p<0,01). No relation was found between NLR and mortality when all the examined patients were considered (p>0.05).

CONCLUSION: NLR that can be easily calculated, can be used as a mortality predictor in the patients of advanced age who will undergo isolated CABG procedure.

Key words: Biological markers; coronary artery disease; inflammation; prognosis.

Received: August 20, 2014 Accepted: October 21, 2014 Online: December 08, 2014?? ??, ????

Correspondence: Dr. Derih AY. Prof. Tezok Cad., Duacinari 16300, Bursa, Turkey.

Tel: +90 224 - 360 50 50 e-mail: ayderih@hotmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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A

lthough coronary artery bypass grafting (CABG) surgery is a surgical procedure described for coronary artery disease, still unpredicted mortality, and morbidity have been observed [1]. EuroSCORE is frequently accepted, and used risk assessment model in cardiac surgery [2]. Because of concerns about under-, or overestimation of the risk, more reliable markers, and scoring systems are needed.

In many studies inflammation markers, and their relationship with cardiovascular risks have been indicated [3]. White blood cell count (WBC) has been demonstrated as a predictor of mortality after CABG [4, 5]. However subtypes of WBC, and their ratios have been demonstrated as more valu-

Table 1.

able predictors than WBC [6, 7]. Neutrophil /lymphocyte ratio (NLR) can be estimated easily from differential cell counts. Although NLR is a marker of inflammatory conditions, it also enables combined evaluation of neutrophilia, and lymphopenia which have worse cardiovascular prognosis [8, 9].

We investigated NLR which is an early-phase post-CABG mortality predictor in various age groups.

MATERIALS AND METHODS After approval of our hospital’s scientific publication rating committee, 158 patients who had under-

Preoperative, and operative data Group 1

Group 2

Clinical characteristics N 78 80 Gender (F/M) 28(35.8%)/50(64.2%) 30(37.5%)/50(62.5%) Age (mean)years 39.4±4.1 63.9±9.2 EF 48.7±10.9 48.6±13.1 Euroscore 1.2±1.4 3.4±2.3 Smoking 40(51.2%) 33(41.5%) Hypertension 38(48.7%) 35(43.7%) Diabetes mellitus 27(34.7%) 18(22.5%) CVD 2(2.5%) 4(5%) Hyperlipidemia 27(34.7%) 20(25%) COPD (Moderate -Advanced) 10(12.8%) 13(16.3%) Laboratory Urea 23.2±10.7 37.5±12.9 Creatinine 0.9±0.6 2.3±1.3 WBC 9.2±2.5 9.7±10.6 Neutrophil 5.8±2.1 6.2±5.2 Lymphocyte 2.4±0.7 1.9±0.8 N/L ratio (mean ) 2.47 4.07 Operatif Duration of CPB (min) 70.3±44.9 93.6±34.6 Duration of CC (min) 52.9±37.6 67.1±26.7 CABG (number of grafts) 2.3±0.9 3.0±0.8 Mortality (1 month) 2 11

P

NS NS 0.001 NS 0.001 0.490 0.748 0.122 0.317 0.395 0.523 0.001 NS NS NS 0.001 0.001 0.001 0.007 0.001 0.001

EF: Ejection Fraction; CVD: Cardiovascular Disease; COPD: Chronic Obstructive Pulmonary Disease; WBC: Total White Blood Cell Count; CPB: Cardiopulmonary Bypass; CC: Cross-Clamping; CABG: Coronary Artery Bypass Grafting; NS: Not Significant P<0.05 significant.

Ay et al., Comparing the effecti̇ veness of neutrophil -lymphocyte ratio as a mortality predictor

97

Table 2. Preoperative, and operative data of the patients with decreased, and increased NLR values

Increased N/L Decreased N/L P

51 107 Age (mean) 50.4±15.2 52.5±13.7 NS EF 49.1±10.7 48.4±12.6 NS EuroSCORE 2.5±2.5 2.2±2.0 NS Urea 31.0±14.9 30.1±13.3 NS Creatinine 1.1±0.8 1.9±1.3 NS WBC 10.5±3.8 9.0±4.6 NS Neutrophil 7.9±3.2 5.1±4.0 0.0001 Lymphocyte 1.7±0.7 2.4±0.8 0.0001 CPB 74.7±40.9 85.7±41.6 NS CC 52.8±28.9 63.6±34.6 NS CABG 2.5±0.9 2.8±0.9 NS Mortality 7 6 NS P<0.05 significant; NS: Not Significant.

gone isolated on-pump CABG operation between 2011, and 2014 by the same surgical team were retrospectively evaluated. The patients were divided into 2 groups as 78 patients of ≤45 years of age (Group 1), and 80 randomly selected patients aged over 45 years (Group 2). Routine biochemical, and hematological values of the patients were recorded.

Their pulmonary functions, medications used, presence of diabetes mellitus, and concomitant diseases were investigated, and together with their cardiac data EuroSCORE values were calculated (Table 1).

Preoperative demographic characteristics, total white blood cell count,neutrophil ratios, lymphocyte ratios, NLR, cross-clamping, and cardiopulmonary bypass times were recorded (Table 2). Primary endpoint was observation of all-cause in-patient mortality. Mean NLR values were calculated separately for each group (Table 3).

Statistical analysis The patients included in the study were analyzed in two separate groups, and 4 subgroups, and values were expressed as mean±standard deviation.

Parametric data were evaluated with t-test, and

non-parametric data using chi-square test. In the evaluation of characteristics effective on mortality, Pearson’s two-way correlation test was used.

P<0.05 was accepted as statistically significant.

RESULTS Estimated threshold NLR values were 2.47 for Group 1, and 4.07 for Group 2. In Group 1, a significant correlation was not detected between mortality rates, and NLR values in patients whose NLR values were above threshold values (p<0.05).

In Group 2, a significant correlation was detected between mortality rates, and NLR values in patients whose NLR values were above threshold values (p<0.01). When all patients included in the study were evaluated, a significant correlation was not found between NLR values, and mortality rates (p<0.05). In addition, a statistically significant correlation existed between EuroSCORE scale scores, and mortality rates. Higher mortality rates were detected in patients with higher EuroSCORE scale scores (p=0.0001). However any relation of this association with NLR values was not observed. (p>0.05). Only in the group with higher EuroS-

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North Clin Istanbul – NCI

Table 3. Variables effective on mortality Variables

Deceased (13)

Inotropic use IABP Prolonged ventilation Duration of CPB EuroScore NLR Lymphocyte Age (years)

Living (145)

P

13 77 0.001 6 8 0.001 6 11 0.004 104(20-207) 81(0-262) 0.041 5(3-9) 2(0-9) 0.001 4.28(2-14) 2.33(1-21) 0.001 1.6(1-3) 2.1(0-5) 0.001 62.6±14 50.8±13.8 0.004

IABP: Intraaortic Balloon Pump; CPB: Cardiopulmonary Bypass; NLR: Neutrophil/Lymphocyte Ratio.

CORE scale scores left ventricular ejection fraction (EF) was effective on mortality (p=0.0001). However age, NLR, and even lower EF values had no effect on mortality rates (Table 2). Difference detected between creatinine levels of both two group were not statistically significant. This difference in creatinine levels might trigger inflammatory processes with resultant higher NLR values. However as stated above this difference was not statistically significant.

Exclusion criteria Patients who underwent off-pump surgery, concurrent valvular surgery, urgently operated cases, those with acute or chronic infections, known malignancies, and hematological problems were not included in the study.

DISCUSSION The main purpose of developing EuroSCORE system was to measure the quality of cardiac surgical procedures [10]. However following its introduction into medical practice, inadequacities of the EuroSCORE system have been reported [11]. Later on, another scoring system by The Society of Thoracic Surgeons (STS) was described, and published [12]. STS scoring system which is more detailed relative to the EuroSCORE system has demon-

strated its superiority over EuroSCORE in many cardiac surgery groups [13-15]. However clinical application of STS scoring system is very difficult.

Therefore, in our clinic we are using EuroSCORE system for risk assessments. In our survey, we have detected higher EuroSCORE values in patients with increased risk of mortality. However higher mortality rates have been evaluated independent from increases in NLRs. The primary purpose of using risk scoring systems, and biopredictors is to predict unwanted intraoperative conditions. In addition to EuroSCORE systems, new markers have been defined.

Total white blood cell count was the first biopredictor found to be correlated with mortality. Bagger et al. performed a study on 2058 patients, and determined WBC as a predictor of post-CABG 30-day mortality [4]. Besides, Newall et al. in their series consisting of 3024 patients, detected a correlation between preoperative WBC, and perioperative myocardial injury, and 1-year mortality [5]. Despite the outcomes of such a large series, it is known that white blood cell count is a nonspecific marker which can increase due to various conditions. For this reason, it is not reliable to use this marker by itself.

Contrary to these studies, Gibson et al. analyzed specific cell counts, and ratios in a study population of 1938 patients, and couldn’t find a correlation between WBC, and mortality rates [8].

Ay et al., Comparing the effecti̇ veness of neutrophil -lymphocyte ratio as a mortality predictor

Recently, NLR has become prominent as a biomarker. As an indicator of inflammatory state, combination of netrophilia, and lymphopenia has been associated with poor cardiovascular prognosis [16].

Increase in the number of neutrophils is an indicator of active inflammatory process, while decrease in the number of lymphocytes is an indicator of inadequacy of the active inflammatory process. Correlation between lymphopenia, and progression of atherosclerosis, and major cardiac complications has been demonstrated [17,18]. Neutrophils induce formation of reactive oxygen radicals, and inflammatory mediators in myocardium during CPB [19]. In large series, it is possible to correlate preoperative NLR, and post-CABG mortality rates. Gibson et al. pioneered this assumption. A correlation between preoperative NLR derived from WBC and mortality rates exists which is independent from well-known personal factors, and EuroSCORE values [8]. In a study performed by Ünal et al., a correlation was detected between preoperative NLR, and post-CABG mortality rates [20]. However in our study among young patient group an association between NLR, and mortality was not detected, however a correlation was found between NLR, and mortality in the elder patient group. When all patients were considered, a correlation was not detected between NLR, and mortality rates.

Limitations of the study: A single-centered investigation was performed on a small patient group which can be considered as an important limitation of our study. Apart from many clinical parametres we evaluated, unknown factors as inflammatory responses induced by cardiac injury during clinical course, and cardiopulmonary bypass might effect accuracy of our outcomes.

CONCLUSION We think that, as an easily calculable post-CABG biopredictor of mortality with low cost, NLR together with EuroSCORE scoring system can be used in the elder population. In our study, higher NLO value has been demonstrated as a marker of mortality. However for quantitative determination of the risk of mortality based on NLR values, larg-

99

er-scale studies should be conducted.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Møller CH, Penninga L, Wetterslev J, Steinbrüchel DA, Gluud C. Off-pump versus on-pump coronary artery bypass grafting for ischaemic heart disease. Cochrane Database Syst Rev 2012;3:CD007224.

2. Siregar S, Groenwold RH, de Heer F, Bots ML, van der Graaf Y, van Herwerden LA. Performance of the original EuroSCORE. Eur J Cardiothorac Surg 2012;41:746-54.

3. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.

4. Bagger JP, Zindrou D, Taylor KM. Leukocyte count: a risk factor for coronary artery bypass graft mortality. Am J Med 2003;115:660-3.

5. Newall N, Grayson AD, Oo AY, Palmer ND, Dihmis WC, Rashid A, et al. Preoperative white blood cell count is independently associated with higher perioperative cardiac enzyme release and increased 1-year mortality after coronary artery bypass grafting. Ann Thorac Surg 2006;81:583-9.

6. Grau AJ, Boddy AW, Dukovic DA, Buggle F, Lichy C, Brandt T, et al. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke 2004;35:1147-52.

7. Horne BD, Anderson JL, John JM, Weaver A, Bair TL, Jensen KR, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 2005;45:1638-43.

8. Gibson PH, Cuthbertson BH, Croal BL, Rae D, El-Shafei H, Gibson G, et al. Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 2010;105:186-91.

9. Madjid M, Awan I, Willerson JT, Casscells SW. Leukocyte count and coronary heart disease: implications for risk assessment. J Am Coll Cardiol 2004;44:1945-56.

10. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9-13.

11. Gogbashian A, Sedrakyan A, Treasure T. EuroSCORE: a systematic review of international performance. Eur J Cardiothorac Surg 2004;25:695-700.

12. The Society of Thoracic Surgeons. Executive Summary: Society of Thoracic Surgeons Spring 2007 report. Chicago, IL: The Society of Thoracic Surgeons; 2007.

100 13. Metzler B, Winkler B. SYNTAX, STS and EuroSCORE - how good are they for risk estimation in atherosclerotic heart disease?

Thromb Haemost 2012;108:1065-71.

14. Wendt D, Osswald BR, Kayser K, Thielmann M, Tossios P, Massoudy P, et al. Society of Thoracic Surgeons score is superior to the EuroSCORE determining mortality in high risk patients undergoing isolated aortic valve replacement. Ann Thorac Surg 2009;88:468-75.

15. Kunt AG, Kurtcephe M, Hidiroglu M, Cetin L, Kucuker A, Bakuy V, et al. Comparison of original EuroSCORE, EuroSCORE II and STS risk models in a Turkish cardiac surgical cohort. Interact Cardiovasc Thorac Surg 2013;16:625-9.

16. Gibson PH, Cuthbertson BH, Croal BL, Rae D, El-Shafei H, Gibson G, et al. Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 2010;105:186-91.

North Clin Istanbul – NCI 17. Major AS, Fazio S, Linton MF. B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol 2002;22:1892-8.

18. Núñez J, Sanchis J, Bodí V, Núñez E, Mainar L, Heatta AM, et al. Relationship between low lymphocyte count and major cardiac events in patients with acute chest pain, a non-diagnostic electrocardiogram and normal troponin levels. Atherosclerosis 2009;206:251-7.

19. Zahler S, Massoudy P, Hartl H, Hähnel C, Meisner H, Becker BF. Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass. Cardiovasc Res 1999;41:722-30.

20. Ünal EU, Durukan AB, Özen A, Kubat E, Kocabeyoglu SS, Yurdakok O, et al. Nutrophil / lymphocyte ratio as a mortality predictor following coronary artery bypass graft surgery. Turk Gogus Kalp Damar 2013;21:588-93.

Orıgınal Article

PM&R

North Clin Istanbul 2014;1(2):101-105 doi: 10.14744/nci.2014.40327

Impact of stroke etiology on clinical symptoms and functional status Ozge Gulsum Memetoglu, Aslihan Taraktas, Naciye Bilgin Badur, Feyza Unlu Ozkan Department of Physical Medicine and Rehabilitation, Fatih Sultan Mehmet Training and Research Hospital, Istanbul, Turkey

ABSTRACT OBJECTIVE: The aim of this study is to investigate the differences between hemorrhagic and ischemic stroke patients in terms of clinical and functional features.

METHODS: Medical records of the patients with stroke were analyzed retrospectively. The patients’ demographic characteristics, stroke etiology, time interval after the event, comorbid illness and functional status were recorded.

RESULTS: The stroke etiology was ischemia for 60 (36 male/24 female) (75%) patients, and haemorrhage for 20 (10 male/10 female) (25%) patients. Patients with ischemic stroke were classified as Group 1, and patients with hemorrhagic stroke were classified as Group 2. The mean age for Group 1 was 62.2±13.2, and 55.8±17.1 years for Group 2 (p=0.592). In Group 1, 33 (55%) patients, and in Group 2, 11 (55%) patients were primary school graduates (p=0.984). Localization of the lesion was in the right side for 33 (55%) patients in Group 1, and for 15 (75%) patients in Group 2 (p=0.372). The mean time interval after event for Group 1 was 7 months (0-211 days), and for Group 2 it was 14.5 (1-420 days) months (p=0.592). FIM score for Group 1 was 71.9±28.0, and 68.1±21.0 for Group 2 (p=0.575). The mean Brunnstrom score for upper extremity was 3.5 for Group 1, 3 for Group 2, (p=0.866), and for lower extremity, it was 3.5 for Group 1, and 3 for Group 2 (p=0.143). Spasticity was present in 45 (75%) patients in Group 1, and in 12 (60%) patients in Group 2 (p=0.311). In Group 1 51 (85%) of the patients and 18 (95%) patients had a history of comorbid disease (p=0.554).

CONCLUSION: Etiology of stroke is thought to be not effective on the patient’s clinical and functional status.

Key words: Hemorrhage, ischemia, stroke

C

erebrovascular diseases have been defined by National Institute of Neurological Disorders and Stroke (NINDS) as permanent, and transient involvement of certain cerebral region as a result of ischemia or bleeding and/or primary pathological damage of one or more than one blood vessels sup-

plying brain tissue [1]. Stroke ranks third among causes of mortality after heart disease, and cancer in developed countries. At the same time it ranks on top of the neurological diseases which cause mortality, and disability in adults [2]. Although geographic, racial, and ethnic differences are detect-

Received: August 10, 2014 Accepted: August 11, 2014 Online: December 08, 2014 Correspondence: Dr. Ozge Gulsum MEMETOGLU. Fatih Sultan Mehmet Egitim ve Arastirma Hastanesi, Fiziksel Tip ve Rehabilitasyon Bolumu, Istanbul, Turkey.

Tel: +90 216 - 578 30 00 e-mail: ozgeilleez@hotmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

102

ed, studies performed within the last two decades have demonstrated the incidence, and prevalence of stroke ranging between 1-3/1000, and 6/1000, respectively [3, 4]. The incidence of stroke increases markedly with age, and for every decade after 55 years of age it rises twofold. It is more frequently seen in men rather than women [5]. Nearly 80% of the stroke patients require rehabilitation therapy [6]. Many factors including risk factors, concomitant diseases, location of the lesion, duration of rehabilitation, and severity of the lesion are effective on the outcomes of functional development, and rehabilitation therapy [7, 8].

In the literature studies performed on the outcomes of stroke patients, demographic information including gender, educational level, comorbid diseases, location, and extent of the lesion (if dominant hemisphere is involved), time elapsed after the incident, and history of the transient ischemic attack have been investigated [6, 8-12]. In our literature review, we have not encountered any study investigating whether etiological factors effect functional level of stroke patients. If the stroke etiology effects clinical findings and functional status independent from other factors, acceptance of the patients into rehabilitation services and schedule of rehabilitation programs can be determined according to the etiology of the patients’ diseases.

Therefore, with this study we aimed to investigate if any difference exists between hemorrhagic, and ischemic stroke patients as for clinical findings, and functional levels.

MATERIALS AND METHODS Medical files of 80 stroke patients who consulted to Fatih Sultan Mehmet Training and Research Hospital were retrospectively investigated.

Demographic information including gender, educational level, etiological factors for stroke, date of the incident, time elapsed after the incident, comorbid diseases, and functional status of the patients were recorded. For the evaluation of the functional state, functional independence measure (FIM) scale, and for the evaluation of functional motor recovery of upper, lower extremities, and hand, Brunnstrom

North Clin Istanbul – NCI

staging was used. Spasticity was indicated with the terms ‘present or absent’.

Statistical analysis was performed using SPSS 16.0 package program. Quantitative data were expressed as mean±standard deviation or median (minimum-maximum), and qualitative data as numerical values (numbers, and percentages). In intergroup comparisons qualitative data were evaluated using chi-square test, and quantitative data with Mann-Whitney U test.

RESULTS Sixty (75%) ischemic, and 20 (25%) hemorrhagic stroke patients were investigated. Patients were classified as cases with ischemic (Group 1), and hemorrhagic (Group 2) stroke patients. Mean ages of the patients were 62.2±13.2 years in Group 1, and, 55.8±17.1 years in Group 2 (p=0.592). Male patients constituted 60% (n=36), and 50% (n=50) of the total patient population in Groups 1, and 2, respectively (p=0.726). Primary school graduates in Groups 1 (n=33; 55%), and 2 (n=11; 55%) were also indicated (p=0.984). Right-sided lesions were detected in a total of 48 patients (Group 1, n=33; 55 %55, and Group 2, n=15; 75%) (p=0.372).

Median (range) duration of time elapsed after the incident was 7 (0-211 mos) months in Group 1, and 14.5 (1-420 mos) months in Group 2 (p=0.592). Mean FIM scores were 71.9±28.0 in Group 1, and 68.1±21.0 in Group 2 (p=0.575).

Median Brunnstrom stages of recovery for upper (Group1, 3.5 and Group 2, 3; p=0.866), and lower extremities (Group 1: 3.5, and Group 2: 3; p=0.143), and hand (Group 1:2, and Group 2: 2.5; p=0.827) were recorded. Spasticity was detected in 45 (75%) Group 1, and 12 (60%) Group 2 patients (p=0.311). Pre-existing comorbidities were revealed in 51 (85%) Group 1, and 18 (95%) Group 2 patients. Distribution of comorbitites did not differ between groups (p=0.554). (hypertension: Group 1: 69.7%, Group 2: 52%; diabetes mellitus: Group 1: 32.2%, and Group 2: 27.4%; heart disease: Group 1, 23.8%, and Group 2, 19.8%). Comparative data related to patients’ symptoms, and patient groups are given in Table 1.

Memetoglu et al., Impact of stroke etiology on clinical symptoms and uunctional status

Table 1.

103

Intergroup comparisons

Age (years) Mean±SD Gender Female/Male (n) Location of the lesion FIM score Median Brunnstrom Stage

Spasticity (present/absence) Comorbid disease history and distribution

Group 1 (ischemic) n=60

Group 2 (hemorrhagic) n=20

p

62.2±13.2 24/36 33 (55%) right 71.9±28.0

55.8±17.1 10/10 15 (75%) right 68.1±21.0

0.592 0.726 0.372 0.575

Upper extremity: 3.5 Hand: 2 Lower extremity: 3.5 45 (75%)

Upper extremity: 3 Hand: 2.5 Lower extremity: 3 12 (60%)

0.866 0.827 0.143 0.311

51 (85%) 69.7% Diabetes Mellitus: 32.2% Heart disease: 23.8%

18 (95%) Hypertension: 52% Diabetes Mellitus 27.4% Heart disease: 19.8%

0.554

DISCUSSION Stroke is quiet an important public health problem which ranks third after heart diseases, and cancer among causes of mortality, and it is on top of the causes of morbidity.

Therefore, many studies have been performed which investigated the etiology, demographic characteristics of patients, location, and extent of the lesion, and comorbid diseases [8-12]. Besides, in most of these studies the impact of these factors on the outcomes of rehabilitation therapy has been analyzed [8, 11]. However we haven’t encountered any study in the medical literature which analysed functional state of the patient, and severity of clinical findings, and the impact of the hemorrhagic or ischemic stroke.

We have looked into whether clinical findings, and functional state differ in patients with stroke of different etiologies, and we couldn’t detect any difference between hemorrhagic, and ischemic stroke patients regarding demographic characteristics, clinical findings, and functional state of the patients.

Demographic characteristics of the patients can effect functional level of the patients. For example, incidence of stroke increases stepwise with aging

[6]. Though some studies have reported that age factor adversely effects functional state after an attack, some other studies suggested that it is not a major effective factor per se [13-16]. In a study performed by Hankey et al. 152 stroke patients were evaluated, and age factor was also reported among determinants of hospital stay, mortality, and disability 5 years after the onset of the stroke incident [10]. In the present study, mean age of our patients was 62.2±13.2 years in Group 1, and 55.8±17.1 in Group 2. Our estimates for Group 1 were close to those reported in Aegean Stroke Database, while they were lower than our values for Group 2 [17].

In a study conducted by Bonita et al. between 19701985 with patients aged 40-69 years of age, higher post-stroke mortality rates were reported in male patients, while post-stroke recovery rates were relatively enhanced in female patients [18]. In a study

by Hachisuka et al. although a significant difference was not detected in female, and male stroke patients as for motor function, among stroke patients FIM scores of the male patients were observedly lower than those of the female patients [19]. In our study, distribution of male, and female patients was not significantly different, despite general dominancy of the male gender.

104

Hypertension, diabetes mellitus, hyperlipidemia, hyperuricemia, atrial fibrillation, heart failure, smoking, family history of stroke are among risk factors for stroke [20-23]. In our study, the most frequently (65%) seen risk factor was hypertension. It was followed by diabetes mellitus (28%), and heart disease (27.2%). However between two diseases, distribution of comorbidities did not differ. In most of the studies performed, in support of our study, hypertension has been reported as the most important risk factor [5].

In one of the studies which investigated the impact of comorbid diseases on functional state, Giaquinto et al. detected a negative correlation between FIM scores, and severity of comorbid diseases [24]. Studies by Liu et al, and Karatepe et al. from our country also support this negative correlation [25-27].

Controversial outcomes have been retrieved from studies which investigated location, and severity of the lesion, and its functional level. According to the studies performed by Macciocchi et al. lesions located in the dominant hemisphere, and cortical level demonstrate more improved functional recovery [8]. In a study by Pantano et al. the authors could not detect a correlation between volume, and location of the lesion, severity of loss of motor functions, and whether ischemia involved the dominant hemisphere or not [12]. Since our study had a retrospective design, we couldn’t access data on location, and severity of the lesions which is one of the deficiencies of our study.

One of the studies which investigated the impact of Brunnstrom stages, and spasticity levels on functional level 88 stroke patients were evaluated after completion of the rehabilitation program, and a positive correlation was seen between spasticity levels of the patients evaluated by Brunnstrum stages, Ashworth scale and measurements of the final functional state [28]. In the present study any difference was not detected between patients who experienced hemorrhagic, and ischemic stroke as for Brunnstrom motor recovery stages, and spasticity. Even though we hadn’t any idea about location, and severity of the lesion, nearly similar clinical findings suggested that etiology of the stroke might not be very much effective on clinical symptoms.

Our inability to detect any difference between functional status of the patients suggests that the

North Clin Istanbul – NCI

etiology is not very effective on the outcomes of the rehabilitation. In studies where the effect of lesion type on functional improvement in stroke rehabilitation was investigated, it has been observed that in patients who suffered from hemorrhagic stroke had generally worser functional levels at the onset, while these patients demonstrated better motor recovery after termination of the rehabilitation therapy relative to those with ischemic etiology [29]. Some of our patients were also included in the rehabilitation program. However we didn’t either record pre-, and post-treatment FIM, Brunnstrom stage, and clinical information of the patients or compared levels of recovery in both groups which might be accepted as a limitation of our study.

In this study, since demographic data, comorbid diseases, time elapsed after the incident are not different between groups, we think that comparison of these two groups as for clinical, and functional perspectives is not inconvenient. However, with regression analysis, analyzing the effects on FIM scores, and clinical findings will enable achievement of more objective results. The outcomes of this study have demonstrated the necessity of performing more comprehensive retrospective analysis with higher number of patients.

In conclusion, although it is not possible to arrive at a definite conclusion, we have thought that the etiology of stroke has not any impact on clinical manifestations, and functional level. Therefore, we conceive that for stroke patients earlier, and more intensive physical therapy programs are not required on the basis of etiology. Therefore we think that there is no need to make a distinction, between different types of stroke patients for the purpose of implementation of earlier and intense rehabilitation programs.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Special report from the National Institute of Neurological Dis-

Memetoglu et al., Impact of stroke etiology on clinical symptoms and uunctional status

orders and Stroke. Classification of cerebrovascular diseases III. Stroke 1990;21:637-76.

2. American Heart Association. Heart and Stroke Facts. Dallas, 1991.

3. Broderick JP, Phillips SJ, O’Fallon WM, Frye RL, Whisnant JP. Relationship of cardiac disease to stroke occurrence, recurrence, and mortality. Stroke 1992;23:1250-6.

4. Kurtzke JF. Neuroepidemiology. Ann Neurol 1984;16:265-77.

5. Brandstater ME. İnme rehabilitasyonu In: Delisa AJ (Arasıl T çeviri editörü) Fiziksel Tıp ve Rehabilitasyon İlkeler ve Uygulamalar. Ankara: Güneş Tıp Kitapevler 2007. p. 1655-76.

6. Doğan A, Nakipoğlu GF, Aslan DM, Kaya ZA, Ozgirgin N. The rehabilitation results of hemiplegic patients. Turk J Med Sci 2004;34:385-9.

7. Gündüz B. İnme ve prognozu etkileyen faktörler. Türk Fiz Tıp Rehab Derg 2006;52:30-3.

8. Macciocchi SN, Diamond PT, Alves WM, Mertz T. Ischemic stroke: relation of age, lesion location, and initial neurologic deficit to functional outcome. Arch Phys Med Rehabil 1998;79:1255-7.

9. Feigin VL, Wiebers DO, Nikitin YP, O’Fallon WM, Whisnant JP. Risk factors for ischemic stroke in a Russian community: a population-based case-control study. Stroke 1998;29:34-9.

10. Hankey GJ, Jamrozik K, Broadhurst RJ, Forbes S, Anderson CS. Long-term disability after first-ever stroke and related prognostic factors in the Perth Community Stroke Study, 1989-1990.

Stroke 2002;33:1034-40.

11. Lin JH, Hsiao SF, Chang CM, Huang MH, Liu CK, Lin YT. Factors influencing functional independence outcome in stroke patients after rehabilitation. Kaohsiung J Med Sci 2000;16:351-9.

12. Pantano P, Formisano R, Ricci M, Di Piero V, Sabatini U, Di Pofi B, et al. Motor recovery after stroke. Morphological and functional brain alterations. Brain 1996;119:1849-57.

13. Suputtitada A, Aksaranugraha S, Granger CV, Sankaew M. Results of stroke rehabilitation in Thailand. Disabil Rehabil 2003;25:1140-5.

14. Ingall T. Stroke--incidence, mortality, morbidity and risk. J Insur Med 2004;36:143-52.

15. Chiou-Tan FY, Keng MJ Jr, Graves DE, Chan KT, Rintala DH. Racial/ethnic differences in FIM scores and length of stay for underinsured patients undergoing stroke inpatient rehabilita-

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tion. Am J Phys Med Rehabil 2006;85:415-23.

16. Lin JH, Hsieh CL, Lo SK, Hsiao SF, Huang MH. Prediction of functional outcomes in stroke inpatients receiving rehabilitation.

J Formos Med Assoc 2003;102:695-700.

17. Kumral E, Ozkaya B, Vardarlı E, Sağduyu A, Şirin H, Pehlivan M. Ege İnme Veri Tabanı. Ege bolgesinde hastane tabanlı calışma 2000 inme hastasının analizi. Turk Norol Derg 1997;1-2:3-12.

18. Bonita R, Stewart A, Beaglehole R. International trends in stroke mortality: 1970-1985. Stroke 1990;21:989-92.

19. Hachisuka K, Tsutsui Y, Furusawa K, Ogata H. Gender differences in disability and lifestyle among community-dwelling elderly stroke patients in Kitakyushu, Japan. Arch Phys Med Rehabil 1998;79:998-1002.

20. Dalyan M, Çakçı A. İnme rehabilitasyonu In: Oğuz H, Dursun E, Dursun N, editörler. Tıbbi Rehabilitasyon. İstanbul: Nobel tıp kitapevleri 2004; p. 589-618.

21. Hankey GJ. Potential new risk factors for ischemic stroke: what is their potential? Stroke 2006;37:2181-8.

22. Sanossian N, Ovbiagele B. Multimodality stroke prevention.

Neurologist 2006;12:14-31.

23. Dimitroula HV, Hatzitolios AI, Karvounis HI. The role of uric acid in stroke: the issue remains unresolved. Neurologist 2008;14:238-42.

24. Giaquinto S. Comorbidity in post-stroke rehabilitation. Eur J Neurol 2003;10:235-8.

25. Liu M, Domen K, Chino N. Comorbidity measures for stroke outcome research: a preliminary study. Arch Phys Med Rehabil 1997;78:166-72.

26. Liu M, Tsuji T, Tsujiuchi K, Chino N. Comorbidities in stroke patients as assessed with a newly developed comorbidity scale.

Am J Phys Med Rehabil 1999;78:416-24.

27. Karatepe AG, Gunaydin R, Kaya T, Turkmen G. Comorbidity in patients after stroke: impact on functional outcome. J Rehabil Med 2008;40:831-5.

28. Oneş K, Yalçinkaya EY, Toklu BC, Cağlar N. Effects of age, gender, and cognitive, functional and motor status on functional outcomes of stroke rehabilitation. NeuroRehabilitation 2009;25:241-9.

29. Kelly PJ, Furie KL, Shafqat S, Rallis N, Chang Y, Stein J. Functionalrecovery following rehabilitation after hemorrhagic and ischemic. Stroke 2003;34:2861-5.

Case Report

OTORHINOLARYNGOLOGY

North Clin Istanbul 2014;1(2):106-108 doi: 10.14744/nci.2014.36035

Relapsing polychondritis and otologic findings Serhan Derin1, Abdulkadir Oran2, Fatma Demirkuru3, Selcuk Ucar4 Department of Otorhinolaryngology, Mugla Sitki Kocman University Faculty of Medicine, Mugla, Turkey;

1

Department of Otorhinolaryngology, Manisa State Hospital, Manisa, Turkey;

2

Department of Otorhinolaryngology, Seka State Hospital, Kocaeli, Turkey;

3

Department of Otorhinolaryngology, Corlu Tekirdag State Hospital, Tekirdag, Turkey

4

ABSTRACT Relapsing polychondritis is a cartilage tissue disease characterized by inflammatory and destructive episodes.

Elastic cartilage of the ear and nose, hyaline cartilage of the joints, hyaline cartilage of vertebra and trachea are the main involvement areas. Also organs having proteoglycan structure such as eyes, heart, blood vessels, and the inner ear can be affected. In this article otologic findings of a 54-year-old male patient with a diagnosis of relapsing polychondritis were presented and discussed in the light of the literature.

Key words: Polychondritis; relapsing; sensorineural hearing loss.

R

elapsing polychondritis is a disease coursing with recurrent inflammation of the organs with cartilaginous structures, and organ deformations developed secondary to these inflammatory attacks [1]. It was firstly described by Jaksch-Wartenhorst in 1923. Frequently middle-aged adults are affected. In the USA its median annual incidence is 3.5 per million [2]. Its pathogenesis is not determined completely. Chondritis most frequently involves external ear. In this article, symptoms of the relapsing polychondritis observed in ENT practice have been discussed together with a case presentation.

CASE REPORT A 54-year-old male patient consulted to our outpatient clinic with complaints of priorly swelling, erythema of the external ear, then eye redness, and arthralgia since 7 months. With time hearing loss was added to these complaints. It was learnt that the patient was treated with the diagnosis of corneal ulcer, and episcleritis. On her physical examination edematous, and inflamed ear lobes, and external auditory canal were observed. However ear lobule was not involved (Figure 1). Bilateral tympanic membranes were intact. Conjunctivas were hyper-

Received: July 24, 2014 Accepted: October 01, 2014 Online: December 08, 2014?? ??, ????

Correspondence: Dr. Serhan DERIN. Mugla Sitki Kocman Universitesi, Tip Fakultesi, Orhaniye Mah., Haluk Ozsoy Cad., 48000 Mugla, Turkey.

Tel: +90 252 - 211 48 00 e-mail: serhanderin@yahoo.com.tr Š Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Derin et al., Relapsing polychondritis and otologic findings

Figure 1. Deformed

right pinna observed during an

acute attack.

Figure 3. Right

pinna returned to its normal baseline appearance following medical therapy.

Pure tone thresholds 125

250

107

500

1000

2000

4000

8000

0 10 20 30 40 50 60 70 80 90 100 110 120

Figure 2. High, and mid-frequency sensorineural hearing loss.

emic, and edematous. Nasal septum, and cavity appeared to be normal. Biochemical tests revealed increased sedimentation rate (58 mm/h), and CRP level. (2.67) Total Ig E was 434 ku/L. Autoantibody panel, bleeding profile, and other biochemical test results were unremarkable. On audiological examinations bilateral type A tympanogram pattern, sensorineural hearing loss of 51 dB in the left, and of 43 dB in the right ear was observed (Figure 2).

Biopsy material was resected from the right helical cartilage. Cutaneous, and subcutaneous tissue were quiet edematous, and helical cartilage was very fragile. Postoperative healing process was completed

without any delay. Histopathology report indicated acute exacerbation of chronic perichondritis. Initially administered high- dose prednisolon therapy were tapered to maintenance doses with time. The patient attended routine control visits, and his ear lobe gained its normal appearance at 6. month of the medical therapy (Figure 3). However his hearing loss did not recover.

DISCUSSION Relapsing polychondritis is a multisystemic disease which courses with relapses, and causes progressive destruction of the cartilage tissue [3]. Although specific laboratory test for relapsing polychondritis is not available, most frequently increased sedimentation rate, and CRP levels are observed. In 50% of the cases, thrombocytosis, leukocytosis, and normochromic normocytic anemia are encountered.

Increased urinary levels of acid mucopolysaccharides, and in the blood samples antibodies developed against type 2 collagen can be detected. In our case, we typically detected increased sedimentation rate, and CRP levels. Its diagnostic algorithm was described in 1976 by McAdam et al. Diagnostic criteria include bilateral auricular chondritis, seronegative polyarthritis, nasal chondritis, ocular inflammation, respiratory system chondritis, and audiovestibular destruction. Accordingly, positivity of at least three

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108

criteria or treatment response to steroids and/or dapsone, presence of chondritis in two or more than two different regions are sufficient to establish the diagnosis of relapsing polychondritis [1]. Relapsing polychondritis most frequently (89%) presents with auricular involvement. Bilateral involvement is seen in 95% of the cases [1, 4]. Ear lobe is frequently painful, hyperemic, and lobulated. Since ear lobule does not contain cartilaginous structure, it remains intact.

Articular, and ocular findings previously thought to be meaningless in most of the cases have been clearly understood to be the components of relapsing perichondritis when auricular perichondritis became manifest. Our case was previously followed up with the diagnosis of episcleritis, however this symptom had not suggested the diagnosis of relapsing polychondritis. These symptoms regress spontaneously within days, rarely weeks, and relapses at varying intervals. At every episode cartilaginous destruction occurs, and deforms the pinna. Conductive, and sensorineural hearing loss are seen in cases with relapsing polychondritis [4-6]. Also in our case, in addition to histopathologic diagnosis, bilateral auricular chondritis, ocular findings, seronegative arthritis, sensorineural type hearing loss, and response to steroid therapy were detected. In 40% of the cases, audiovestibular findings are observed [2]. Most frequently, bilateral or unilateral sensorineural type hearing loss is seen. Mechanism of the destructive changes in the internal ear are not clearly known, but involvement of the internal ear with the inflammatory process has been implicated. Antilabyrinthine autoantibodies have been observed in some cases with relapsing polychondritis [7]. Though conductive type hearing loss is associated with serous otitis, and chronic otitis frequently secondary to involvement of the eustachian tube, it can be also related to the involvement of the external ear canal [8]. In the treatment, main medication is a corticosteroid.

Treatment starts with initial daily loading dose of 15 mg/kg/day which is tapered stepwise, and pre-

scribed based on the activity, and severity of the disease or it can be administered as a maintenance dose.

In our case following a bolus dose of a steroid, maintenance dose was given for a period of 6 months. At the end of the treatment auricular edema, and hyperemia regressed. However audiologic gain could not be obtained. Dapsone, colchicine, and immunosuppressives can be also used for its treatment. In conclusion, this clinical condition which progresses with multisystem involvement, due to its characterization by audiologic findings, and especially involvement of the pinna can confront otorhinolaryngology specialists who usually make initial diagnosis.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. McAdam LP, O’Hanlan MA, Bluestone R, Pearson CM. Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Medicine (Baltimore) 1976;55:193-215.

2. Puéchal X, Terrier B, Mouthon L, Costedoat-Chalumeau N, Guillevin L, Le Jeunne C. Relapsing polychondritis. Joint Bone Spine 2014 Mar;81:118-24.

3. Trentham DE, Le CH. Relapsing polychondritis. Ann Intern Med 1998;129:114-22.

4. Damiani JM, Levine HL. Relapsing polychondritis-report of ten cases. Laryngoscope 1979;89(6 Pt 1):929-46.

5. Michet CJ Jr, McKenna CH, Luthra HS, O’Fallon WM. Relapsing polychondritis. Survival and predictive role of early disease manifestations. Ann Intern Med 1986;104:74-8.

6. Bachor E, Blevins NH, Karmody C, Kühnel T. Otologic manifestations of relapsing polychondritis. Review of literature and report of nine cases. Auris Nasus Larynx 2006;33:135-41.

7. Issing WJ, Selover D, Schulz P. Anti-labyrinthine antibodies in a patient with relapsing polychondritis. Eur Arch Otorhinolaryngol 1999;256:163-6.

8. Estes SA. Relapsing polychondritis. A case report and literature review. Cutis 1983;32:471-6.

Case Report

OTORHINOLARYNGOLOGY

North Clin Istanbul 2014;1(2):109-113 doi: 10.14744/nci.2014.35744

Sudden sensorineural hearing loss in a multiple sclerosis case Muhammet Tekin1, Gul Ozbilen Acar1, Osman Halit Cam2, Fatih Mehmet Hanege3 Department of Otorhinolaryngology, Istanbul Medeniyet University Goztepe Training and Research Hospital, Istanbul, Turkey;

1

Department of Otorhinolaryngology, Delta Hospital, Istanbul, Turkey;

2

Department of Otorhinolaryngology, Op. Dr. Ergun Ozdemir GĂśrele Devlet Hastanesi, Giresun, Turkey

3

ABSTRACT Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. MS involves different regions of the central nervous system in different periods, and causes demyelination. MS is a neuromotor disorder which progresses with remissions and relapses. Symptoms of MS may regress completely or heal after the relapses leaving sequelae. Sudden sensorinerural hearing loss (SSHL) is hearing loss of 30 dB or more over at least three contiguous audiometric frequencies that develops over a period of a few hours to 3 days. In 4-10 % of the MS patients, sensorineural hearing loss occurs between relapses or remissions. In this case, audiotory brainstem response (ABR) test is the most appropriate test for the diagnosis of sensorineural hearing loss in MS patients. In this article, we will discuss a patient diagnosed as MS who presented with sudden sensorineural hearing loss during the remission of the disease.

Key words: Multiple sclerosis, sudden sensorineural hearing loss.

M

ultiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. MS is a neuromotor disorder which progresses with remissions and relapsing periods. More than 2 million patients in the world are estimated to be diagnosed with multiple sclerosis [1]. Multiple sclerosis is classified in four different groups by Multiple Sclerosis Association of America in 1996 as follows: 1- Relapsing remitting, 2- Secondary progressive, 3- Primary progressive, 4- Progressive relapsing [2]. Symptoms of MS plaques may regress

completely or heal by leaving a sequellae.

Symptomatology of MS may be very variable.

Hypoesthesia, paresthesia, muscle weakness, myoclonus, muscle spasms, ataxia, dysarthria, dysphagia, acute and chronic pain, and visual symptoms are common for the disease [3]. These symptoms usually show variations depending on the localization of demyelinated plaques in the central nervous system. In the presence of demyelinated plaques affecting pons or pontocerebellar area, sudden hearing loss may be encountered. In this article, we discuss

Received: June 22, 2014 Accepted: September 26, 2014 Online: December 08, 2014 Correspondence: Fatih Mehmet HANEGE. Trabzon Giresun Yolu, Bozcaali Mahallesi, Mehmet Burnu, Gorele, 28800 Giresun, Turkey.

Tel: +90 454 - 513 11 38 e-mail: hanege@hotmail.com Š Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

North Clin Istanbul – NCI

110

an MS case which was diagnosed based on symptoms of sudden hearing loss when the patient was in the remission phase of the disease.

CASE REPORT A 30-year-old female patient admitted to our hospital with sudden hearing loss and tinnitus in the right ear. These complaints had been continuing for three days. The patient was diagnosed as MS 3.5 years ago. Her medical history also included lumbar discopathy. She’d been using beta interferon at a dose of 0.3 mg on alternate days for the treatment of MS for the last 3.5 years. Physical examination of the patient demonstrated intact bilateral tympanic membranes, Weber test was lateralized to the left ear, Rinne test was positive (+/+) in the left, and false negative (+/-) in the right ear. Pure tone audiogram was performed on the patient with the initial diagnosis of sudden hearing loss (Figure 1). The final diagnosis was total hearing loss in the right ear (air conduction/bone conduction: 113/67 dB). The hearing acuity of the left ear was determined to be in normal hearing range (air conduction/bone conduction: 18/12 dB).

After the patient was admitted to our clinic, routine laboratory tests were run. In the laboratory tests; there were no abnormal findings except WBC; 12.7x103/mm3, triglycerides; 34 mg/dL, CK-MB; 25 U/l, UIBC; 366 ug/dL. Contrast-enhanced cranial magnetic resonance imaging (MRI) and neurology consultation were ordered for the patient.

As a result of the consultation, there was no active plaque on the cranial MRI at this time. Accordingly, a new MS attack was not anticipated. To investigate vascular, connective tissue pathologies or infectious etiologies, the results of new laboratory tests were as follows: rheumatoid factor <20, anti-nuclear antibody; negative (–), anti-phospholipid Ig G; negative (–), anti-phospholipid IgM; negative (–). Levels of protein C, protein S, Von Willebrant Factor antigen were in their normal ranges. In Elisa tests, levels of anti-toxoplasma Ig M, anti-CMV Ig M, EBV VCA Ig M, anti-HSV-1 Ig M, anti-HSV-2 Ig M, VDRL-RPR, anti-ds DNA were within their normal ranges. In the light of these findings, classical parenteral treatment protocol of sudden sensorineural hearing loss was prescribed as prednisolone kg/1 mg/day with tapering dose, ranitidine 50 mg/

Figure 1. The

audiogram reveals sudden senseurineural hearing loss on the right ear.

day, pentoxifylline 900 mg/day, low-molecularweight heparin 0.6 ml/day, acyclovir 2 g/day. Also hyperbaric oxygen therapy was administrated to the patient for 10 days at doses of 2.5 ATA/day.

Pure tone audiogram was performed totally 3 times during hospitalization period. In spite of all our medical treatments, there was no sign of hearing improvement either audiologically or clinically.

The patient was discharged with oral treatment and followed up in our outpatient clinic. At the end of our treatment, audiologic examinations were performed. In November, one month after the onset of the disease, there was not any hearing improvement as detected on her pure tone audiogram (Figure 2).

Three months later spontaneous recovery was observed on her pure tone audiogram Air /bone conduction 13/7 dB, 30/27 dB were reported for the left, and the right ear, respectively (Figure 3). Ad-

Tekin et al., Sudden sensorineural hearing loss in a multiple sclerosis case

111

Figure 2. The audiogram after the treatment shows no

Figure 3. The audiogram shows spontaneous recovery

improvement.

of the right ear.

Table 1.

The elongation in third and fifth wave latencies and III â&#x20AC;&#x201C; V interpeak latencies as well

BAER Protocol/Run Aud.Stim I III V I-V I-III III-V Rep.Rate Type

dB ms ms ms ms ms pps L - Threshold 1 2 3 4 R - Threshold 1 2 3 4

70nHL 70nHL 80nHL 80nHL

1.72 3.92 5.48 3.76 2.20 1.56 1.76 3.82 5.54 3.78 2.06 1.72 1.62 3.90 5.54 3.92 2.28 1.64 1.46 3.84 5.40 3.94 2.38 1.56

13 13 13 13

Click Click Click Click

80nHL 80nHL 70nHL 70nHL

1.96 4.04 6.00 4.04 2.08 1.96 1.96 4.04 6.00 4.04 2.08 1.96 2.10 4.10 5.94 3.84 2.00 1.84 1.92 4.08 5.96 4.04 2.16 1.88

13 13 13 13

Click Click Click Click

North Clin Istanbul – NCI

112

ditionally, auditory brain response (ABR) test was performed. Prolongation of the absolute latency of 3. and 5. waves, and interpeak latency of 3.-5. waves were found in ABR of the right ear (Table 1). Depending on these findings, the patient’s sudden hearing loss of the right ear might be related to MS disease.

DISCUSSION Sudden hearing loss (SHL) is a hearing loss of 30 dB or more, over at least three contiguous audiometric frequencies, that develops over a period of a few hours to 3 days [4, 5, 6, 7, 8, 9]. The etiology of the disease is not certain, but autoimmune vascular malformations, thrombotic, and central nervous system diseases are among the main reasons [4, 5].

MS is a demyelinating disease of the central nervous system that involves the white substance. The disease often has periods of remissions and relapses. Its etiopathogenesis is not totally understood.

In genetically inclined patients, viral infection may trigger the autoimmunity that causes the disease.

Demyelinated plaques typically effect the periventricular white substance of the central nervous system. Rarely cerebellum, brain stem and spinal cord can be effected by MS. As a result of autoimmunity, intravascular T cells attack the myelin sheath, and nerve fibers, then it starts as an inflammatory process. On the other hand, neural regeneration begins in order to stop the damage at a minimum level. In 4-10 % of MS patients, sensorineural hearing loss occurs during periods of relapse or remission [5, 6]. Detection of brain lesions of MS in MRI, can provide evidence concerning the dissemination of MS lesions in space and time. Therefore a diagnosis of MS should be guided by the defined criteria of MRI for this abnormality [10].

Hearing loss in MS disease may be due to plaques which are placed on brain stem, any area of entrance of cochlear nerve into the brain stem, and auditory cortex [6, 7]. In this situation, auditory brainstem response (ABR) test is the most appropriate test for the diagnosis of sensorineural hearing loss in MS patients. Typical findings are the elongations in all waves’ absolute latencies except I. wave. Also, elongations in interpeak latencies of IIII, III-V waves or changes in the morphology and amplitudes of III and V wave’s may be observed [7,

8]. In the right ear ABR of our patient, we observed elongation in absolute latencies of waves III and V, as well as III-V waves’ interpeak latencies.

If sudden hearing loss is related with MS, it usually recovers without sequellae. In a retrospective study of Hellman and his colleagues, 253 MS patients with sensorineural hearing loss were scanned, and sudden hearing loss was diagnosed in 11 of them. Nine of these patients recovered without audiological deficits [8, 9]. In our patient, sudden hearing loss recovered with a mild sensorineural hearing loss, and no recurrence was observed in one year follow-up.

In conclusion, whenever sudden hearing loss is diagnosed in a patient, physicians should request cranial imaging to differentiate for cranial pathologies such as MS. Sudden hearing loss can be the first symptom of MS or may indicate relapse of the disease.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Peterson JW, Trapp BD. Neuropathobiology of multiple sclerosis. Neurol Clin 2005;23:107-29.

2. Tiong TS. Prognostic indicators of management of sudden sensorineural hearing loss in an Asian hospital. Singapore Med J 2007;48:45-9.

3. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 1996;46:907-11.

4. Compston A, Coles A. Multiple sclerosis. Lancet 2008;372:150217.

5. Conlin AE, Parnes LS. Treatment of sudden sensorineural hearing loss: I. A systematic review. Arch Otolaryngol Head Neck Surg 2007;133:573-81.

6. Peyvandi A, Naghibzadeh B, Ahmady Roozbahany N. Neurootologic manifestations of multiple sclerosis. Arch Iran Med 2010;13:188-92.

7. Oh YM, Oh DH, Jeong SH, Koo JW, Kim JS. Sequential bilateral hearing loss in multiple sclerosis. Ann Otol Rhinol Laryngol 2008;117:186-91.

8. Protti-Patterson E, Young ML. The use of subjective and objective audiologic test procedures in the diagnosis of multiple sclerosis. Otolaryngol Clin North Am 1985;18:241-55.

9. Hellmann MA, Steiner I, Mosberg-Galili R. Sudden sensori-

Tekin et al., Sudden sensorineural hearing loss in a multiple sclerosis case

neural hearing loss in multiple sclerosis: clinical course and possible pathogenesis. Acta Neurol Scand 2011;124:245-9.

10. McDonald WI, Compston A, Edan G, Goodkin D, Hartung

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HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001;50:121-7.

Case Report

DERMATOLOGY

North Clin Istanbul 2014;1(2):114-116 doi: 10.14744/nci.2014.32042

Annular sarcoidosis mimicking granuloma annulare: a case report Zafer Turkoglu1, Burce Can1, Ebru Zemheri2, Ilkin Zindanci1, Filiz Topaloglu Demir1, Mukaddes Kavala1 Department of Dermatology, Istanbul Medeniyet University, Goztepe Research and Training Hospital, Istanbul, Turkey;

1

Department of Pathology, Istanbul Medeniyet University, Goztepe Research and Training Hospital, Istanbul, Turkey

2

ABSTRACT Cutaneous sarcoidosis is a great imitator and we have to remember this mimicker also in the differential diagnosis of erythematous annular lesions. We report the case of a 50-year- old man with a 7-year history of erythematous, annular or serpiginous, scaly plaques on his scalp, forehead, preauricular region and around his mouth who was misdiagnosed as granuloma annulare.

Key words: Annular lesions; annular sarcoidosis; sarcoidosis.

S

arcoidosis is a multisystemic granulomatous disease which frequently involves lungs with unknown origin, and characterized by hyperactivity of cellular immune system. Skin lesions develop in 25-35% of the patients with systemic sarcoidosis which are the first, and single manifestations of the disease [1, 2].

Lesions of cutaneous sarcoidosis which are called ‘‘Great Mimickers” are divided in 2 groups as specific lesions histopathologically manifesting typical sarcoid granulomas or nonspecific lesions demonstrating inflammatory signs [3, 4]. Papular and maculopapular lesions are the most frequently seen manifestations. In this article, a case of sarcoidosis with annular, archiform, and serpiginous lesions on face, and scalp is presented because of its rarely seen clinical presentation.

CASE REPORT A 50-year-old male patient presented to our outpatient clinics with complaints of annular skin rashes on his face, and scalp which did not regress with previously administered topical therapies. His lesions emerged 7 years ago for which he consulted to other medical centers. He was then diagnosed as tinea facialis, and granuloma annulare, and treated accordingly. His personal, and family history was unremarkable except for long-lasting complaints of respiratory distress, and coughing. On dermatological examination, multiple archiform, serpiginous, erythematous, annular and partly squamous plaque lesions localized on face, scalp, and inner aspect of the ears were detected (Figure 1). Direct fungal examination of the material retrieved from lesions

Received: May 01, 2014 Accepted: June 09, 2014 Online: December 08, 2014?? ??, ????

Correspondence: Dr. Filiz TOPALOGLU DEMIR. Istanbul Medeniyet Universitesi, Goztepe Egitim ve Arastirma Hastanesi, Dermatoloji Anabilim Dali, Istanbul, Turkey.

Tel: +90 216 - 566 66 00 e-mail: filizsvet@yahoo.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

Turkoglu et al., Annular sarcoidosis mimicking granuloma annulare

could not reveal fungal elements. Histopathological examination of the biopsy material disclosed granulomas containing giant cells localized superficially within the dermis. The lesions were devoid of lymphocytes (naked granuloma) and concomitant necrosis (Figure 2). On laboratory analysis, ESR, CRP, serum calcium levels, calcium concentration in 24-hour urine, and angiotensin converting enzyme levels were within normal limits, while purified protein derivative test (PPD) result was evaluated as anergic (0 mm). On chest roentgenograms, and thoracic computed tomograms, bilateral hilar lymphadenopathies were detected, and together with clinical, and histopathological findings, diagnosis of stage 1 sarcoidosis was made. Topical steroidal therapy was initiated for the patient with only pulmonary and cutaneous involvement, and he was included in our follow-up protocol.

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Figure 1. Archiform,

serpiginous, and annular plaque lesions with patchy scales.

DISCUSSION Sarcoidosis is a multisystemic inflammatory disease characterized by noncaseified epitheloid granulomas whose etiology is not known completely. It has been conceived that in genetically predisposed individuals, multiple extrinsic antigens (microbial antigens, and environmental agents) induce hyperactivation of inflammatory pathways leading to sarcoidal granulomas [5, 6]. Most frequently lungs, lymph nodes, and skin are affected. Though skin lesions can emerge at any stage of the disease, usually naked granuloma is present from the onset of the disease.

In sarcoidosis, cutaneous manifestations are classified histopathologically as “specific”, and “nonspecific” based on the presence or absence of typical granuloma. Specific lesions consist of macula, papula, nodule, plaque, subcutaneous nodule, infiltrated scar, and lupus pernio. Nonspecific lesions are erythema nodosum, ichthyosis, erythema multiforme, erythroderma, pruritus, calcifications, and Sweet syndrome [6, 7]. Nonspecific lesions frequently emerge during acute phase of the sarcoidosis, and they are associated with good prognosis. Most frequently erythema nodosum is seen. Specific lesions have a more chronic course, and worse prognosis [2, 4].

Papular, and maculopapular lesions are the most frequently seen specific lesions. Generally, they demonstrate symmetrical distribution on eyelids,

Figure 2. Caseified

granulomas containing epitheloid cells, and Langhans-type giant cells (H&E x 40).

periorbital region, neck, and nasolabial sulci. In patients with sarcoidosis, rarely cutaneous involvement, erythroderma, keloid formation, angiolupoid, ichthyosiform, verrucose or annular eruptions have been reported [8]. As is seen in our case, in the differential diagnosis of annular, and serpiginous lesions localized on cutaneous regions exposed to sun light, priorly annular elastolytic giant cell granuloma, then granuloma annulare, fungal infections, lepra, subacute cutaneous lupus erythematosus, and eyrthema annular centrifugum should be thought [4, 9, 10].

For the diagnosis of sarcoidosis, consistent clini-

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cal, and radiological findings together with presence of noncaseified granulomas in one or more than one tissues including skin, paratracheal lymph nodes, and salivary glands are required. All patients with skin eruptions should be evaluated as for systemic involvement of mainly lungs, eye, liver, and heart [10]. Classical histopathological findings in sarcoidosis comprise epitheloid histiocytes, and noncaseified granulomas rarely containing Langhans type giant cells. Typically, scarce number of lymphocytes, and inflammatory cells are seen on the periphery of a granuloma (naked granuloma) During diagnostic procedures, one should not forget that these histopathological findings are not specific to sarcoidosis, and histopathologically in differential diagnosis, tuberculosis, atypical mycobacterial infections, fungal infections, reactions to foreign substances, and rheumatoid nodules should be taken into consideration [7, 11].

Histopathologically presence of granuloma, and characteristic features of granuloma facilitate the process of differential diagnosis, and as a clinical appearance, presence, and location of scales on the lesion have an utmost importance. In fungal infections, subacute cutaneous lupus erythematosus, lepra, erythema annulare centrifugum, squamae are observed, but they are not anticipated findings in granuloma annulare. In sarcoidosis, generally epidermal alterations are observed [12].

In conclusion, in sarcoidosis, annular and serpiginous lesions on the face are rarely seen. Since these lesions are evaluated as superficial fungal infection, annular elastolytic giant cell granuoloma, and granuloma annulare, diagnosis may be delayed for years. As seen in our case, sarcoidosis should be

considered in the differential diagnosis of annular, archiform or serpiginous lesions localized on face, and the patients should be questioned as for potentially concomitant systemic findings.

REFERENCES 1. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med 1997;336:1224-34.

2. Mañá J, Marcoval J, Graells J, Salazar A, Peyrí J, Pujol R. Cutaneous involvement in sarcoidosis. Relationship to systemic disease.

Arch Dermatol 1997;133:882-8.

3. Tchernev G. Cutaneous sarcoidosis: the “great imitator”: etiopathogenesis, morphology, differential diagnosis, and clinical management. Am J Clin Dermatol 2006;7:375-82.

4. Fernandez-Faith E, McDonnell J. Cutaneous sarcoidosis: differential diagnosis. Clin Dermatol 2007;25:276-87.

5. Newman LS, Rose CS, Bresnitz EA, Rossman MD, Barnard J, Frederick M, et al. A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med 2004;170:1324-30.

6. Lazarus A. Sarcoidosis: epidemiology, etiology, pathogenesis, and genetics. Dis Mon 2009;55:649-60.

7. Marchell RM, Judson MA. Chronic cutaneous lesions of sarcoidosis. Clin Dermatol 2007;25:295-302.

8. Samtsov AV. Cutaneous sarcoidosis. Int J Dermatol 1992;31:38591.

9. Harrison PV. The annular erythemas. Int J Dermatol 1979;18:282-90.

10. Costabel U, Ohshimo S, Guzman J. Diagnosis of sarcoidosis.

Curr Opin Pulm Med 2008;14:455-61.

11. Tchernev G, Patterson JW, Nenoff P, Horn LC. Sarcoidosis of the skin--a dermatological puzzle: important differential diagnostic aspects and guidelines for clinical and histopathological recognition. J Eur Acad Dermatol Venereol 2010;24:125-37.

12. Hsu S, Le EH, Khoshevis MR. Differential diagnosis of annular lesions. Am Fam Physician 2001;64:289-96.

Case Report

PM&R

North Clin Istanbul 2014;1(2):117-120 doi: 10.14744/nci.2014.98698

Use of ESWT in avascular necrosis of bilateral femoral heads: case report Levent Ozgonenel1, Hilal Yesil2, Murat Yesil3 Department of Physical Medicine and Rehabilitation, Medical Park Bahcelievler, Istanbul, Turkey;

1

Department of Physical Medicine and Rehabilitation, Usak State Hospital, Usak, Turkey;

2

Department of Orthopedics and Traumatology, Banaz Public Hospital, Usak, Turkey

3

ABSTRACT A 57-year-old female patient was admitted to the department of physical medicine and rehabilitation with lumbar and left hip pain lasting for 1.5 months. Physical examination and magnetic resonance imaging revealed stage 1 avascular necrosis of bilateral femoral heads. Extracorporeal Shock Wave Therapy (ESWT) was utilized for early stage disease and a significant reduction in pain and functional recovery was noted.

Key words: Avascular necrosis; conservative; extracorporeal shockwave; femoral head.

A

vascular necrosis (AVN) of the femoral head is a progressive disease with sequalae which can cause complete destruction of the femoral head, and requires surgery a few years after its onset [1].

The etiopathogenesis of the avascular necrosis of the femoral head involves histological death of the osteocytes because of insufficient supply of blood flow [2]. Based on our current information about AVN of the femoral head, increased intraosseous pressure developed following an ischemic attack in addition to enhanced edema in functionally constrained region of the bone marrow compartment creates a vicious cycle just like a compartment syndrome which compresses venules, and arterioles [3].

Essentially, diagnosis of AVN of the femoral head is made based on radiograms obtained at antero-

posterior, lateral, and frog leg positions. However, in the early stage AVN of the femoral head these radiograms have lower diagnostic sensitivity. Magnetic resonance imaging (MRI) has a 99% diagnostic sensitivity, and 98% specificity even in the early stage of AVN of the femoral head [4]. International classification system proposed by Association Research Circulation Osseous (ARCO) in 1993 also includes previous classifications [5, 6].

Though current treatments in the management of AVN of the femoral head are still debatable, in cases of failed conservative treatment, as surgical methods, osteotomy, vascularized or non-vascularized bone grafting, and femoral head preservation surgery as core decompression are used, while in advanced stages (especially ARCO III, and IV) total

Received: May 30, 2014 Accepted: August 14, 2014 Online: December 08, 2014? ??, ????

Correspondence: Dr. Hilal YESIL. Afyon Kocatepe Universitesi Tip Fakultesi Fiziksel Tip ve Rehabilitasyon Bolumu, Dumlupinar, Afyonkarahisar, Turkey.

Tel: +90 272 - 246 33 04 e-mail: dradanur@yahoo.com Š Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

North Clin Istanbul – NCI

118

Table 1.

Indications, and Containdications according to the Guidelines of International Society of Musculoskeletal Shock Wave Treatment (ISMST)

Indications Contraindications Pseudoarthrosis/nonunion Soft tissue / acute infections of the bone Tendinosis of the shoulder joint Malignancy Chronic radial epicondylitis Coagulopathies Plantar fasciitis (± heel spur) Pregnancy

Previously implanted pacemaker

Epiphysiolysis at the site of application

Lung tissue at the site of application

Presence of cerebral, spinal cord tissue or major vessels at the site of application

hip prosthesis is preferred [7]. Conservative treatments include prostacycline analogues, enoxaparine, and alendronate therapies. The most frequently used treatment agents include pulsed electromagnetic field (PEMF), and extracorporeal shock wave therapies (ESWT) Essentially ESWT is thought to activate cellular processes critical for neurovascularization, and tissue regeneration [7-10]. Ma et al. concluded that therapeutic effects of ESWT might be associated with vascular endothelial growth factor (VEGF). VEGF has a mitogenic effect on vascular endothelial cells, and stimulates neovascularization. Still another study performed by Ma et al. in the year 2008, detected that expression of BMP2 (bone morphogenic protein) increased on femoral heads of the patients treated with ESWT. BMP-2 mobilizes osteoprogenitor (precursor) cells inducing osteoblastic differentiation process leading to stimulation of new bone formation [9]. Other current studies have also emphasized favourable effects of ESWT in the management of AVN of the femoral head [10, 11, 12]. In summary, ESWT exerts its effectiveness in the management of avascular necrosis of femoral head through neovascularization, and regeneration of the bone.

CASE REPORT A 57-year-old female patient was admitted to the department of physical medicine and rehabilitation with lumbar and left hip pain present for 1. 5

months. Patient indicated that she hadn’t any pain at night, and her pains aggravated with movement.

Physical examination revealed restricted internal rotation, tense left tensor fascia lata band (+) Fabere Fader, and Laseque test negativity. Magnetic resonance imaging demonstrated subchondral edematous ring on both femoral heads, and interpreted as stage I AVN of the femoral head. For preprocedural indication, containdications, and application methods, ESWT protocol published by International Society for Musculoskeletal Shock Wave Therapy was taken into consideration (Table 1). Under regional anesthesia, the patient was transferred on operation table in supine position. For maximum visualization of the femoral head the affected hip was brought into “ frog leg “ position. Priorly the place of the femoral artery was determined by ultrasonography, and marked with a pencil. Then k-wire was placed on the course of the femoral artery so as to facilitate its visualization under scopy. The site of the necrotic changes on the femoral head where therapy will be applied was determined with the aid of fluoroscopy, and marked on the headpiece with 4 dots. Then k-wire was removed, then using a Zimmer® brand ESWT device, from a site far away from the artery, 3 times 2000 impacts at 0.11 to 0,28 mJ/ mm2 were applied. Before, and after the procedure, hip muscles demonstrated full muscular strength.

Before the procedure the patient complained of pain when she ascended two stairs, while after the procedure she climbed 4 stairs, and walked for 30

Ozgonenel et al., Use of ESWT in avascular necrosis of bilateral femoral heads

minutes without pain. Evaluation with Visual Analogue Scale (VAS) demonstrated marked alleviation in her hip pain, and 15 days after she didnâ&#x20AC;&#x2122;t use her walking stick any more.

DISCUSSION The functional state of the hips affected by AVN of the femoral head tends to worsen because of progressive collapse of the femoral head. Most frequently AVN causes articular destruction which consequently leads to requirement for hip arthroplasty. In a study performed by Ohzono et al., the authors reported that the lesions were localized on the weightbearing areas of the femoral head, and incidence of collapsed femoral head within 5 years ranged between 94, and 100 percent [13]. Even though AVN treatment was debatable, generally, surgery is used in cases with failed conservative treatment. Nonsurgical treatment alternatives in the management of early stage AVN include controlled weight-loading, ESWT, and PEMF. Though complete mechanism of activity of the ESWT is not already known, in various studies performed, it has been associated with increases in the levels of BMP-2, and VEGF. Increases in both of these markers stimulate neovascularization together with new bone formation [9, 14]. In a recent study performed by Hausdorf et al., the authors reported that ESWT penetrates into targeted femoral head in proportion with the distance between the ESW device, and the femoral head. The authors also indicated that despite 10 mm safe bone margin, ESWT achieves a 50% decrease in the therapeutic effect, and they also asserted that adequate clinical evidence was available suggesting the presence of a biological response characterized by increased bone formation by means of neovascularization process [15]. Besides, ESWT plays an important role in the alleviation of hip pain, recovery of functions, and increase in the quality of life of the patient especially in the management of early stage femoral head AVN (ARCO stage I, and II) [7, 10, 11, 12]. In a study by Wang et al., the authors reported that ESWT was more effective than core-decompression, and non-vascularized fibula grafting [12]. In a study conducted in 2008 in the treatment of AVN of the femoral head synergistic therapeutic effects of ESWT, and alendronate were reported [10]. Finally, Wang et al. evaluated effec-

119

tiveness of ESWT in the management of AVN of the femoral head in a long-term (8-9 years) followup study, and reported that in the early stage AVN, ESWT was more significantly effective than surgical alternatives including core decompression, and non-vascularized fibula grefting [16].

In conclusion, substantial amount of information in the current medical literature advocates effectiveness of ESWT especially in the early stage of AVN of the femoral head. Also we have obtained improved treatment outcomes in the early stage (Stage 1) AVN of the femoral head, and pain, and functional restriction of the patient resolved markedly.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

REFERENCES 1. Lee MS, Hsieh PH, Shih CH, Wang CJ. Non-traumatic osteonecrosis of the femoral head - from clinical to bench. Chang Gung Med J 2010;33:351-60.

2. Chandler FA. Coronary disease of the hip. J Int Coll Surg 1948;11:34-6.

3. Vulpiani MC, Vetrano M, Trischitta D, Scarcello L, Chizzi F, Argento G, et al. Extracorporeal shock wave therapy in early osteonecrosis of the femoral head: prospective clinical study with long-term follow-up. Arch Orthop Trauma Surg 2012;132:499508.

4. Theodorou DJ, Malizos KN, Beris AE, Theodorou SJ, Soucacos PN. Multimodal imaging quantitation of the lesion size in osteonecrosis of the femoral head. Clin Orthop Relat Res 2001;386:54-63.

5. Gardeniers JWM. The ARCO perspective for reaching one uniform staging system of osteonecrosis. In: Scoutens A, Arlet J, Gardeniers JWM, Hughes SPF, editors. Bone circulation and vascularization in normal and pathologic conditions. New York: Plenum; 1993. p. 375-80.

6. Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg Br 1995;77:34-41.

7. Wang CJ, Wang FS, Ko JY, Huang HY, Chen CJ, Sun YC, et al. Extracorporeal shockwave therapy shows regeneration in hip necrosis. Rheumatology (Oxford) 2008;47:542-6.

8. Hopper RA, VerHalen JP, Tepper O, Mehrara BJ, Detch R, Chang EI, et al. Osteoblasts stimulated with pulsed electromagnetic fields increase HUVEC proliferation via a VEGF-A independent mechanism. Bioelectromagnetics 2009;30:189-97.

9. Ma HZ, Zeng BF, Li XL, Chai YM. Temporal and spatial ex-

120 pression of BMP-2 in sub-chondral bone of necrotic femoral heads in rabbits by use of extracorporeal shock waves. Acta Orthop 2008;79:98-105.

10. Wang CJ, Wang FS, Yang KD, Huang CC, Lee MS, Chan YS, et al. Treatment of osteonecrosis of the hip: comparison of extracorporeal shockwave with shockwave and alendronate. Arch Orthop Trauma Surg 2008;128:901-8.

11. Russo S, Corrado EM, Corrado B, Benigno T. The role of extracorporeal shock waves. In: Santori FS, Santori N, Piccinato A, editors. Avascular necrosis of the femoral head: current trends.

Milan: Springer; 2004. p. 45-54.

12. Wang CJ, Wang FS, Huang CC, Yang KD, Weng LH, Huang HY. Treatment for osteonecrosis of the femoral head: comparison of extracorporeal shock waves with core decompression and bone-grafting. J Bone Joint Surg Am 2005;87:2380-7.

North Clin Istanbul â&#x20AC;&#x201C; NCI 13. Ohzono K, Saito M, Sugano N, Takaoka K, Ono K. The fate of nontraumatic avascular necrosis of the femoral head. A radiologic classification to formulate prognosis. Clin Orthop Relat Res 1992;277:73-8.

14. Ma HZ, Zeng BF, Li XL. Upregulation of VEGF in subchondral bone of necrotic femoral heads in rabbits with use of extracorporeal shock waves. Calcif Tissue Int 2007;81:124-31.

15. Hausdorf J, Lutz A, Mayer-Wagner S, Birkenmaier C, Jansson V, Maier M. Shock wave therapy for femoral head necrosis-Pressure measurements inside the femoral head. J Biomech 2010;43:2065-9.

16. Wang CJ, Huang CC, Wang JW, Wong T, Yang YJ. Long-term results of extracorporeal shockwave therapy and core decompression in osteonecrosis of the femoral head with eight- to nine-year follow-up. Biomed J 2012;35:481-5.

revıew

PSYCHIATRY

North Clin Istanbul 2014;1(2):121-126 doi: 10.14744/nci.2014.44153

Synthetic cannabinoids Rabia Bilici Erenkoy Mental Health and Neurology Training and Research Hospital, Istanbul, Turkey

ABSTRACT Use of cannabinoids is increasing at an alarming rate. Their easy availability, cheapness, perceptive legality and difficulty in detecting its presence with standard urine toxicologic tests, and similar factors probably contribute to the increased use, and popularity of synthetic cannabinoids. Although laws, and regulations concerning auditing of these substances have been implemented in many countries, production of new types of synthetic cannabinoids rapidly takes place. Primary psychoactive ingredient of cannabis is ∆ 9-tetrahydrocannabinoid which is partial agonist of cannabinoid receptors, while synthetic cannabinoids are potent, and complete agonists of these receptors.

Therefore it is not surprising that synthetic cannabinoids exert more powerful effects than cannabinoids. Clinical effects of synthetic cannabinoids can cause referrals to emergency services, and hospitalizations. Despite lack of any specific therapy benzodiazepines, antipsychotics, and fluid replacement may be required. Clinical follow-up studies are needed for better comprehension of its clinical effects, and treatment outcomes.

Key words: Cannabis; CB1; synthetic cannabinoid.

I

nvestigators, and clinicians have not adequate information about synthetic cannabinoids (SCs) which are becoming increasingly prevalent. In this article, we aimed to deal with available information about SCs in the light of the literature findings.

Cannabinoids basically divide into 3 groups as natural, endogenous, and synthetic cannabinoids.

THC (∆9-tetrahydrocannabinoid) contained in the cannabis is the mostly known natural cannabinoid. From ancient times, their therapeutic effects have been utilized. However, its addictive potential was discerned at the beginning of the 20. century which led to restriction of their use [1]. Synthetic cannabinoids constitute a group of compounds

which were produced in the laboratory during 1990s, with the intention to investigate endogenous cannabinoids, and create new treatment alternatives for medical use [1, 2]. These heterogenous compounds are dissolved in a solvent, and sprayed on the plants. Solvent vaporizes, the plant is dried, pressed, and packaged [3]. Thus SCs are packaged as loose leaves or previously wrapped product, and rarely sold in powder form [4]. They are smoked like a hookah using a water pipe or wrapped in a cigarette paper before smoking. Various aromas are presumably added into some SC products so as to make its purchase more reasonable [2].

Substances containing synthetic cannabinoids

Received: November 22, 2014 Accepted: November 25, 2014 Online: December 08, 2014 Correspondence: Dr. Rabia BILICI. Erenkoy Ruh ve Sinir Hastaliklari Egitim ve Arastirma Hastanesi, Amatem Klinigi, Sinan Ercan Cad., No: 29, Erenköy, Kadikoy 34736, Istanbul, Turkey.

Tel: +90 216 - 302 59 59 e-mail: rabiabilici@hotmail.com © Copyright 2014 by Istanbul Northern Anatolian Association of Public Hospitals - Available online at www.kuzeyklinikleri.com

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are generally called “Spice” in Europe, “K2” in USA, “Bonzai” or “Jamaika” in Turkey [1]. The name “spice” might be a reference to the spacecraft ‘Spice’ used for intergalactic journey mentioned in Frank Herbert’s novel Dune [2].

In Europe, at the start of 2000s, SCs were synthetized in the laboratories, and marketed as legal cannabis alternatives in bright gelatin packages, and under various trade names. They soon became popular as “legal intoxicating agents” or “herbal intoxicating agents”. They are sold as fine parfumes, incense, plant refreshing agents, and bath salt in some special “smart shops” or “head shops.”, gas stations, and on-line with labels indicating that they are not for human use, but can be used for investigatonal purposes [5]. On the package labels only herbal ingredients of the product are listed without any mention of its synthetic cannabinoid content [1, 2].

John W. Huffman ( JWH) listed the most detailed series of SC with cannabis-like effects on animals, and these indicated substances have become the main active agent of newly produced synthetic cannabinoids [6, 7]. Other SCs developed within the last 20 years belonged to AM (Alexandros Makriyannis) series, and they are indazolecarboxamide derivatives [7]. Up to now hundreds of synthetic cannabinoids have been categorized in various structural groups. These groups include adamantoil indoles, aminoalkyl indoles, benzoyl indoles, cyclohexylphenoles, dibenzopyrans, naphthyl methyl indoles, naphthyl methyl indenes, naphthoyl pyrroles, phenylacetylwne indoles, and indazole caboxamide products [7].

Many SCs are still categorized as pharmacologic agents, and subjected to USA Controlled Substances Act. As synthetic cannabinoids are included in the group of illicit substances, structurally different cannabimimetic compounds are produced which are not covered by laws, and regulations [7].

The first Spice products widely contained JWH018, and JWH-073, while with time new products have been added to the list. In the EMCDDA 2012 report 30 of 73 new psychoactive agents were indicated to be SC [8].

As reports indicate, most of the SC users also abuse other illicit substances, most frequently cannabis [9, 10]. Other most commonly used substances include alcoholic drinks, cigarette, hallusinogens,

North Clin Istanbul – NCI

prescribed opiates, benzodiazepines, amphetamines, and cocaine [2].

Prevalence The prevalence of synthetic cannabinoids is not known completely. However despite all efforts against their use, as admitted worldwide, SCs have been used increasingly with their psychiatric, medical, and social outcomes [2].

In a recent review by Castaneto et al. nine SC epidemiological studies have been analyzed. The first of the two internationally organized self-reported studies was conducted on-line, and 13 countries, and 42 US states participated in the study. Most of the participants were single (67%), male (83%), and at least high school graduates (96%). They began to use illicit substances at an average age of 27 years.

Almost all of them were using alcoholic beverages (92%), and marihuana (84%). Most frequently SCs are smoked like a cigarette (water pipe/bong, cigarette, pipe, vs). However they are used via oral or rectal route or their vapours are inhaled. Curiosity is the first reason for starting to use these substances.The rates of abuse, addiction, and emergence of withdrawal symptoms related to SC use have been reported as 37, 15, and 15%, respectively [7].

In the second globally conducted anonymous survey study, data of 14.966 participants were collected. The study participants consisted mostly (2/3) of male individuals with a mean age of 26 years, and 2513 (17%) of them reported that they had been using SC [10]. Most (n=980; 98%) of the study participants who used SCs within the previous year had prevalently utilized cannabis, and other drugs. Despite rapid onset of activity of SCs relative to cannabis, later on 92.8% (n=887) of the study participants preferred to use cannabis because of unwanted effects of SCs. However 7.2% of the participants indicated that they had opted to use SC rather than cannabis. As rationale of their preference for SCs they set forward arguments as their easy availability, lower cost, effects, and inability to detect SCs with laboratory analyses [7].

As observed in many field studies, SCs are mostly used by adolescents, and adults, and more frequently attract the attention of cannabis, and multiple illicit substance users. Men prefer to use SCs 2-fold more frequently than women. US high school students

Bilici, Synthetic cannabinoids

perceive SCs as safer than other drugs. Military personnel, and athletes have also used SC to refrain from being caught doping [2, 7, 9, 11].

Cannabis users have begun to use SCs while they were undergoing regular laboratory tests for the detection of illicit substance during supervised release period [2].

Pharmacology It has been detected that synthetic cannabinoids exert their effects by binding to CBI, and CB2 receptors just like THC which is the primary psychoactive substance of cannabis [12]. CB1 receptors are found in central, and peripheral nervous system, bone, heart, liver, lungs, vascular endothelium, and reproductive system [13]. However they are primarily located in the brain, and they are responsible for psychoactive effects of cannabinoids. CB2 receptors are primarily found in the immune system, and also in the central nervous system. CB2 receptors are detected in smaller numbers relative to CB1 receptors, and mediate immunoregulatory effects of cannabinoids [7].

Contrary to THC, SCs are potent, and complete agonists of cerebral CB1 receptors [10] Synthetic cannabinoids activate CB1 receptors. G-protein mediated receptors primarily located at presynaptic terminals. Activation of CB1 receptors decrease cyclic adenosin monophosphate (cAMP) activity, and disclose cannabimimetic responses [14]. SC agonists interact with voltage-gated ion channels, decrease membrane potential, and consequently inhibit potassium, sodium, and N-, and P/Q type calcium channels [7].

THC which is the primary psychoactive substance of cannabis is a partial agonist of cannabinoid receptors, while SCs are potent, and complete agonists of these receptors. More intensive effects produced with SCs when compared with cannabis should not be surprising [15].

Contrary to synthetic cannabinoids, cannabis contains approximately 70 flavonoids, and other cannabinoids which can alter the effects of THC. For example, cannabidiol (CBD) which is a type of cannabinoid with established anxiolytic, and antipsychotic effects can balance some anxiogenic, and psychomimetic effects of THC [2, 16].

123

Packages of synthetic cannabinoids contain synthetic cannabinoids from different chemical categories, and their composition is continually modified.

Composition, and amount of the same product produced at different time periods, even products in the same package differ considerably. In addition to synthetic cannabinoids, as indicated in various studies, these packages also contain additives, preservatives, fatty acids, esthers, benzodiazepines, and active metabolite of tramadol [7, 17, 18].

Some difficulties encountered in the detection of synthetic cannabinoids in urine, sputum, and serum samples of synthetic cannabinoid users. Some synthetic cannabinoids including JWH-018, and their metabolites in the serum can be measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), and gas chromatography mass spectrometry (GC/MS). However LC-MS/MS and GC/MS methods are time consuming, and it is difficult to use these methods in a field study [2].

Their clinical efects Randomized controlled studies have not been conducted with synthetic cannabinoids so far. Very scarce number of cannabinoids have been tested in human beings [19]. Most of the information on this subject comes from on-line interactive live forums, emergency service calls, Poison Control Centers, and case reports in the medical literature. Medical literature mostly retrieve information from case reports related to addicts consulted to emergency services [2].

Most of the acute phase effects of synthetic cannabinoids resemble those of the cannabis, while significant differences exist in the variety, and severity of these effects. It is not known whether these differences stem from the differences between SCs, and cannabis or originate from non-cannabinoid components contained in the composition of SC [2]. Interactions between more than one SC components contained in a single product may effect clinical manifestations.

Clinical symptoms may onset immediately within minutes or hours after use of SC, however, duration of symptoms are variable, and they may persist for hours. Some users may experience residual effects lasting for hours. Cases of agitated delirium lasting for hours have been reported [2, 19, 20, 21].

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Calls made at The American Association Poison Control Centers, and referrals to emergency services have increased rapidly from the year 2010 on [21, 22].

Number of referrals to emergency services increased tremendously (n=11406 in 2010, and 28.531 in 2014) [7]. In 2010, 464 SC users (males, 739%, and females 25%; age range 12-67 years) consulted to Texas Poison Control Centers [7, 23]. Adverse clinical effects were grouped as neurological (61.9%), cardiovascular (43.9%), gastrointestinal (21.1%), respiratory (8.0%), ocular (5.0%), cutaneous (2.6%), renal (0.9%), hematologic (0.4%), and other side (acidosis, hyperglycemia, diaphoresis etc.) (25.9%) effects. Any case of fatality was not reported in association with synthetic cannaboid use, while 59.9% of the patients demonstrated “moderate or major” toxicity symptoms. Treatment modalities consisted of i.v. fluids (38.8%), benzodiazepines (18.5%), oxygen therapy (8.0%), and antiemetics [23].

Intoxication: In 51 articles on synthetic cannabinoid intoxication more than 200 cases have been reported. The age distribution of these cases has ranged between 13, and 59 years (mean, 22; median 20 yrs) [7].

Symptoms of the acute phase (within the frst 24 hours): Symptoms of this phase include agitation or irritability, restlessness, anxiety, confusion, short-lived impairment of memory, and cognition, changes in perception, and psychosis. Physical findings include dilated pupils, conjunctival hyperemia, nausea and vomiting, impaired speech, shortness of breath, hypertension, tachycardia, chest pain, muscle twitchings, and sweating or pale skin. Physical examination, clinical, and laboratory tests, and electrocardiographic (ECG) examination results are within normal limits, however in some patients with leucocytosis (WBC counts 13.000-14.000/mm3) or hypokalemia (<3.5 mEq/L) some abnormalities could be seen. Hyperglycemia was observed. Some patients reported that the effect of SCs started within minutes after intake of the SC, and signs of intoxication became manifest 2-5 hours after its use. They also indicated that the symptoms of intoxication resolved within less than 24 hours [7]. After synthetic cannabinoid use panic attacks, suicidal thoughts, and attempts have been also reported [2].

Subacute phase: (24 hours after their intake): Serious medical complications developed during

North Clin Istanbul – NCI

this phase include myocardial infarction, ischemic stroke, seizures, and acute renal injury. In some patients who developed acute renal injury required hemodialysis, and corticosteroid therapy, while health state of others improved within 3 days after admission to hospital [7].

Withdrawal symptoms: In two case reports cited in the medical literature, diaphoresis (sweating), uneasy feelings, tremor, somatic pain, palpitations, insomnia, tachycardia, hypertension, hyperventilation, headache, diarrhea, nausea, vomiting, and depressive mood have been documented. Even some withdrawal symptoms which lasted for longer periods have resolved within a week [2, 5].

Psychotic Reactions: Among psychotic symptoms associated with synthetic cannabinoids, changes in perception, illusions, auditory, and visual hallucinations, paranoia, agitation, aggression, depersonalization, catatonia, and dissociation can be enumerated. The users have indicated fascinating visual effects, and defined them as “impressions”, “bursts of colour”, and “geometric patterns”. Hallucinations are typically different from those reported for endogenous psychoses. Psychotic symptoms typically do not last more than a few hours, in some case reports, patients with prolonged psychotic symptoms have been presented [2].

Some publications have advocated that synthetic cannabinoids trigger psychosis in apparently healthy individuals aged 20-30 years without any previously experienced psychiatric disease. Following use of synthetic cannabinoids new cases of psychosis associated with paranoias, thought disorders, and suicidal thoughts have been detected. These individuals required hospitalization in psychiatry clinics for antipsychotic therapy. Psychotic periods vary between 1 week and 5 months [7]. Exposure to cannabis, and cannabinoid agonists, and development of psychosis are related to activation of CBI receptors [2, 24].

THC which is the main active ingredient of cannabis has been suspected to be the principal agent responsible for the development of psychosis. However cannabidiol (CBD) which is among its other ingredients can weaken psychotic effects of THC. However synthetic cannabinoids do not contain cannabinoids like CBD [2].

In adolescents, exposure to cannabis is thought

Bilici, Synthetic cannabinoids

to contribute to the increased risk of psychosis during advanced stages of life [2, 24]. In addition, a linear dose-response relationship is apparent. Longer exposures increase the risk of psychosis. In consideration of higher potency of synthetic cannabinoids relative to THC, increasing rates of SC use which lead to newly diagnosed cases of psychosis is also an alarming issue. It is acknowledged that in individuals with psychotic disorders SCs can precipitate psychosis [2].

Neurological side efects: Among side effects reported for synthetic cannabinoids, tremor, ataxia, nystagmus, fasciculations, hypertonicity, hyperreflexion, and hyperextension can be enumerated. The most common cognitive effect of synthetic cannabinoids is impairment of attention, concentration, memory, and operational skills. These effects are generally seen during intoxication period, however they can extend beyond this period [2, 25]. Epileptic seizures can be observed due to synthetic cannabinoid use [26].

Cardiovascular side effects: Most prevalent side effects of SCs include tachycardia, and hypertension. Patients can present with palpitations, chest pain or arrhytmia. In rare cases, synthetic cannabinoids have been suspected to induce myocardial infarction or even death. However coronary artery spasms can be presumably associated with other ingredients of SC [2, 26, 27].

Gastrointestinal side efects: Synthetic cannabinoids can induce vomiting, and nausea, and increase appetite. However their users have indicated that SCs increased appetite less frequently than cannabis [2, 10].

Other side effects: Synthetic cannabinoids can at the same time cause pupillary changes as mouth dryness, conjunctival hyperemia, miosis, and midriasis, blurred vision, sensitivity to light, coughing, and pulmonary inflammation. Other symptoms as hyperthermia, rhabdomyolysis, tinnitus, and symptoms suggesting their anticholinergic effects have been also reported [2].

Mortality: Only four cases of mortality have been reported which were directly associated with synthetic cannabinoid use [7].

Their effects on laboratory parameters: Hyperglycemia, hypokalemia, increased creatinine, creatinine phosphokinase levels, acidosis, and leu-

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kocytosis have been reported related to synthetic cannabinoid use [2].

Treatment A specific antidote for synthetic cannabinoid does not exist. Limited data suggest that benzodiazepines or antipsychotics can be effective as supportive, and symptomatic treatment. Among benzodiazepines, more frequently lorazepam, and as antipsychotics more often haloperidol, olanzapine, and quetiapine have been used. Theoretically, CBI receptor antagonists can reverse CBI agonistic effects of SCs, however commercially marketed CBI receptor antagonists are not available [2]. Vital signs of the patients should be monitored, fluid replacement should be made to prevent dehydration, and rhabdomyolysis.

Diphenhydramine can be used to relieve muscular rigidity [2, 28, 29, 30].

DISCUSSION Despite many measures, and legal prohibitions, use of synthetic cannabinoids are increasing at an alarming speed. Although many regulations, and laws are implemented to audit the use of these illicit substances, novel synthetic cannabinoids are produced in no time at all [2, 7]. Problems related to these substances with increasing prevalence seem to continue to engage health care professionals during their daily practice. Therefore health care professionals should be knowledgeable about diagnosis, and treatment of clinical entities related to SC use, and they should be able to differentiate among various clinical manifestations of SCs. Besides forensic medicine specialists should not forget that during evaluation process standard toxicology tests may not detect SC. Since limited number of epidemiological data are available on synthetic cannabinoid use, their pharmacokinetics, and distribution patterns in tissues/organs, elimination, drug-drug interactions, and clinical effects, larger-scale investigation should be performed on these issues.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study has received no financial support.

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