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Öğe Acute evaluation of pituitary function in patients with Crimean-Congo haemorrhagic fever(WILEY-BLACKWELL, 2012) Kilicli, Fatih; Dokmetas, Hatice S.; Dokmetas, IlyasContext Crimean-Congo haemorrhagic fever (CCHF) can cause a fatal haemorrhagic syndrome. Pituitary ischaemia/infarction and necrosis are known causes of hypopituitarism, often remaining unrecognized because of subtle clinical manifestations.Öğe Adrenal Ganglioneuroma: Case Report(Galenos Yayincilik, 2011) Kilicli, Fatih; Acibucu, Feffah; Dokmetas, Hatice Sebila; Elagoz, Sahande; Gokce, Gokhan; Oztoprak, IbrahimGanglioneuroma (ON) is a rare benign tumor arising mainly from neural crest cells and consisting of Schwann and ganglion cells. GN rarely occurs from the adrenal medulla and is observed most commonly in children and young adults. It is not associated with hormonal activity and is clinically asymptomatic. We present a 35-year-old woman whose abdominal ultrasonography for abdominal pain revealed in the right adrenal gland, a biochemically normal mass that was minimally hypointense on Tl-weighted and hyperintense on T2-weighted magnetic resonance images (MRI) and which was pathologically diagnosed as GN after adrenalectomy.Öğe Allgrove syndrome(SINGAPORE MEDICAL ASSOC, 2012) Kilicli, Fatih; Acibucu, Fettah; Senel, Soner; Dokmetas, Hatice SebilaAllgrove syndrome is a rare autosomal recessive disorder. It is also known as the 3A syndrome and characterised by the triad of achalasia, alacrima and adrenal insufficiency. The AAAS gene is encoded on chromosome 12q13. We report the case of a 23-year-old woman who presented at the hospital with adrenal crisis that was triggered by infection of the urinary system and gastrointestinal bleeding. She had a known diagnosis of achalasia for eight years, and ophthalmologic examination revealed alacrima. Based on our findings, the patient was diagnosed with Allgrove syndrome.Öğe Assessment of bone mineral density in patients with Sheehan's syndrome(TAYLOR & FRANCIS LTD, 2014) Acibucu, Fettah; Kilicli, Fatih; Dokmetas, H. SebilaIntroduction: The number of studies concerning bone mineral density (BMD) in patients with Sheehan's syndrome (SS) are scarce. We aimed to investigate the relationship between BMD and deficient hormones in patients with newly diagnosed SS. Material and methods: Thirty-four patients with SS and age-gender-weight matched 22 controls were included in the study. Results: We found osteoporosis in 61.8%, osteopenia in 32.3%, and normal dual energy X-ray absorptiometry (DEXA) findings in 5.9% patients. In the control group, 68.2% of individuals were osteopenic and 31.8% of them were normal. The number of osteoporotic patients was found to be higher and BMD values were lower in the patient group compared with the control group. There was no relation of DEXA measurements with the period between the last delivery and the initial diagnosis and the estradiol levels. While there was no relation between insulin-like growth factor 1 (IGF-1) and T and Z scores of femur head, the relation between the IGF-1 and L1-L4 T scores was statistically significant. There was a significant relation between the IGF-1 and L1-L4 Z scores. Conclusions: SS patients should also be assessed in terms of osteoporosis at the time of diagnosis and then proper treatment should be initiated afterwards.Öğe Association of Insulin Resistance and Hyperandrogenemia with Serum Levels of FGF-23, IGF-1, and Bone Mineral Density in Polycystic Ovary Syndrome(ENDOCRINE SOC, 2014) Ciftel, Enver; Kilicli, Fatih; Dokmetas, Sebila…Öğe Atrial fibrillation is associated with increased mean platelet volume in patients with type 2 diabetes mellitus(TAYLOR & FRANCIS INC, 2013) Turgut, Okan; Zorlu, Ali; Kilicli, Fatih; Cinar, Ziynet; Yucel, Hasan; Tandogan, Izzet; Dokmetas, Hatice SebilaPlatelet abnormalities in diabetes mellitus (DM) and atrial fibrillation (AF) may underline the etiology of a prothrombotic state in these conditions. Increased mean platelet volume (MPV) is a marker of abnormal platelet function and activation. We aimed to investigate the possible association of chronic AF with MPV in patients who have type 2 DM. Patients who had type 2 DM with either chronic (>= 6 months) AF or normal sinus rhythm (NSR) were included in the study. A total of 162 patients (aged 38-89 years) were divided into 2 groups according to the presence of either AF or NSR. Group 1 consisted of 81 diabetic patients with AF, and group 2 consisted of 81 diabetic patients with NSR. The two groups were not significantly different in terms of age, and gender, as well as in hypertension, smoking, history of coronary artery disease, previous cerebrovascular accidents, microalbuminuria, retinopathy, duration of DM, body mass index, hemoglobin A(1c), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride (p > 0.05 for all variables). Although no significant difference was present between groups concerning platelet count; for patients with AF, MPV was higher compared with patients with NSR (9.0 +/- 0.2 fl vs. 8.4 +/- 0.2 fl; p = 0.001). Furthermore, no significant difference was noted between groups regarding routine medications received by patients. In multivariate logistic regression analysis, MPV was the only variable independently related to AF (OR = 2.659; 95% CI, 1.286-5.498; p = 0.008). Consequently, it is concluded that AF is associated with increased MPV in patients with type 2 DM, suggesting the presence of tentatively related processes leading to reciprocal interaction.Öğe Characteristic features of 20 patients with Sheehan's syndrome(TAYLOR & FRANCIS LTD, 2006) Doekmetas, Hatice Sebila; Kilicli, Fatih; Korkmaz, Serdal; Yonem, OzlemSheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. The aim of the present study was to determine the clinical characteristics of Sheehan's syndrome in 20 patients (mean age 60.15 +/- 3.41 years) with typical obstetric history. The mean duration between time of diagnosis and date of the last delivery was 26.82 +/- 2.52 years (range 2-40 years). All patients had a history of massive hemorrhage at delivery and physical signs of Sheehan's syndrome. Fourteen patients (70.0%) lacked postpartum milk production and did not menstruate following delivery. Baseline and stimulated anterior pituitary hormone levels were measured in all patients. According to the hormonal values, 18 (90.0%) patients had secondary hypothyroidism, 11 (55.0%) had adrenal failure and all of them had hypogonadism, prolactin and growth hormone deficiency. Hyponatremia was present in seven patients (35.0%). Total or partially empty sella was revealed in all patients by magnetic resonance imaging. Diabetes insipidus was not found in any patient. We found that lack of lactation in the postpartum period and early menopause seemed the most important clues for diagnosis of Sheehan's syndrome, and inadequate prolactin and gonadotropin responses to stimulation tests were the most sensitive diagnostic signs in patients with severe postpartum hemorrhage.Öğe Effects of acute thyroxine depletion on hearing in differentiated thyroid carcinoma patients(Wolters Kluwer Medknow Publications, 2014) Hasbek, Zekiye; Karakus, Canan Filiz; Altuntas, Emine Elif; Kilicli, FatihIntroduction: Radioiodine ablation refers to the destruction of functioning remnants of normal thyroid tissue or metastatic foci remaining after thyroidectomy. Effective thyroid ablation requires adequate stimulation of thyroid-stimulating hormone. Our aim in this study was to evaluate the hearing changes of patients before ablation therapy in the iatrogenic hypothyroid period, which has been constituted with the purpose of treatment success and following the ablation therapy in the euthyroid period 1 month after the thyroid hormone (TH) replacement therapy was initiated. Materials and Methods: Patients who were diagnosed with thyroid cancer, treated with total/near-total thyroidectomy and referred for I-131 therapy or low-dose I-131 whole body scan were included in our study. Hearing tests as high-frequency audiometry, autoacoustic emission and tympanometry were made during hypothyroid and euthyroid periods on all the patients included in the study. Results: In the present study were enrolled 75 patients with a mean age of 46.6 +/- 12 years (range: 19-69 years). In hypothyroid period, while there was not any hearing-loss in 124 of 150 (82.7%) ears of 75 patients; mild hearing-loss in 18 (12%) ears, moderate hearing-loss in 7 (4.7%) ears and severe hearing-loss in 1 (0.07%) ear were detected. In euthyroid period, while there was not any hearing-loss in 132 of 150 (88%) ears; there were mild hearing-loss in 11 (7.3%), moderate hearing-loss in 6 (4%), and severe hearing-loss in 1 (0.07%) ear. However, there could not be found any significant difference between hearing levels of patients before and after treatment (P = 0.317). Conclusion: Although THs play an important role in the physiology of hearing, the hypothyroidism made in 4 weeks period causes serious damages on hearing functions of patients. However, with regard to temporary hearing losses that hearing levels could improved with treatment, we believe that hearing should also be questioned in the follow-up of patients with differentiated thyroid cancer.Öğe Etiologies of patients admitted to emergency department with hypoglycemia(ACADEMIC JOURNALS, 2010) Eren, Sevki Hakan; Caliskan, Haci Mehmet; Kilicli, Fatih; Korkmaz, Ilhan; Acibucu, Fettah; Dokmetas, Hatice SebilaHypoglycemia is the most common endocrinologic problem seen in emergency departments. To explore its causes in patients who admitted to the emergency department with symptoms resembling hypoglycemia, 225 hypoglycemia cases were evaluated from January 2000 to May 2008. Of 225 hypoglycemia cases, 158 (70.2%) were receiving treatment for diabetes mellitus, which was the most common group (94 patients were using insulin, 55 were receiving oral anti-diabetics (OAD) and 9 patients both OAD and insulin). The other causes for hypoglycemia were as follows: reactive hypoglycemia cases (11.6%), insulinoma (2.7%), malignancies (2.2%), Sheehan syndrome (0.9%), chronic liver disease (0.9%), gestational diabetes mellitus (0.4%), OAD use by mistake (3.6%), and use of OAD for suicidal purposes (13%). In eight of the cases, the reason could not be identified. The study revealed that diabetes mellitus constitute the most common reason for hypoglycemia among the patients seen in emergency departments. Efforts should be made to prevent hypoglycemia by giving the patients better education.Öğe Evaluation of Response to Vitamin D Treatment in Patients with Osmeomalacia(ENDOCRINE SOC, 2014) Dincer, Selin; Dokmetas, Sebila; Kilicli, Fatih…Öğe Importance of Postoperative Stimulated Thyroglobulin Level at the Time of I-131 Ablation Therapy for Differentiated Thyroid Cancer(ASIAN PACIFIC ORGANIZATION CANCER PREVENTION, 2014) Hasbek, Zekiye; Turgut, Bulent; Kilicli, Fatih; Altuntas, Emine Elif; Yucel, BirsenBackground: Serum thyroglobulin detection plays an essential role during the follow-up of thyroid cancer patients treated with total/near total thyroidectomy and radioiodine ablation. The aim of this retrospective study was to evaluate the relationship between stimulated serum thyroglobulin (Tg) level at the time of high dose I-131 ablation and risk of recurrence, using a three-level classification in patients with differentiated thyroid cancer (DTC) according to the ATA guidelines. Also we investigated the relationship between postoperative stimulated Tg at the time of ablation and DxWBS results at 8-10 months thereafter. Materials and Methods: Patients with radioiodine accumulation were regarded as scan positive (scan+). If there was no relevant pathological radioiodine accumulation or minimal local accumulation in the thyroid bed region, this were regarded as scan negative (scan-) at the time of DxWBS. We classified patients in 3 groups as low, intermediate and high risk group for assessment of risk of recurrence according to the revised ATA guidelines. Also, we divided patients into 3 groups based on the stimulated serum Tg levels at the time of I-131 ablation therapy. Groups 1-3 consisted of patients who had Tg levels of <= 2 ng/ml, 2-10 ng/ml, and >= 10 ng/ml, respectively. Results: A total of 221 consecutive patients were included. In the high risk group according to the ATA guideline, while 45.5% of demonstrated Scan(+) Tg(+), 27.3% of patients demonstrated Scan(-) Tg(-); in the intermediate group, the figures were 2.3% and 90.0% while in the low risk group, they were 0.6% and 96.4%. In 9 of 11 patients with metastases (81.8%), stimulated serum Tg level at the time of radioiodine ablation therapy was over 10, however in 1 patient (9.1%) it was <2ng/mL and in one patient it was 2-10ng/mL (p=0.005). Aggressive subtypes of DTC were found in 8 of 221 patients and serum Tg levels were <= 2ng/ml in 4 of these 8. Conclusions: We conclude that TSH-stimulated serum thyroglobulin level at the time of ablation may not determine risk of recurrence. Therefore, DxWBS should be performed at 8-12 months after ablation therapy.Öğe Inspiratory Muscle Strength is Correlated with Carnitine Levels in Type 2 Diabetes(TAYLOR & FRANCIS INC, 2010) Kilicli, Fatih; Dokmetas, Sebila; Candan, Ferhan; Ozsahin, Sefa; Korkmaz, Serdal; Amasyali, Elvan; Fakioglu, Koray; Dal, Kuersat; Acibucu, Fettah; Cakir, IlkayIntroduction. Plasma carnitine insufficiency has been known to cause muscle weakness. Carnitine levels and pulmonary functions were lower in patients with diabetes. Patients and Methods. To determine whether pulmonary functions are correlated with carnitine levels in patients with type 2 diabetes. In this study, we evaluated pulmonary functions and carnitine concentrations in 49 patients with type 2 diabetes and 34 healthy controls. Results. Carnitine levels were lower in type 2 diabetes group than control group (52.56 +/- 12.38 and 78.96 +/- 10.66 hmol/mL, respectively, p < 0.0001). Pulmonary functions were not significantly different between groups. Carnitine levels were not correlated with age, duration of diabetes, fasting blood glucose levels, and glycemic control (HbA1c%) in patients with type 2 diabetes. However, carnitine levels in patient group were correlated with % forced vital capacity (FVC%) (r = 0.35, p = 0.016), % forced expiratory volume in 1 s (FEV1%) (r = 0.318, p= 0.029), FEV1/FVC (r= 0.302, p= 0.039), inspiratory muscle strength (PImax) (r = 0.407, p = 0.023), and PImax% (r = 0.423, p= 0.018). Conclusion. This study suggests that low carnitine levels may be associated with lower PImax and PImax% in type 2 diabetes.Öğe Is sensorineural hearing loss related with thyroid metabolism disorders(WOLTERS KLUWER MEDKNOW PUBLICATIONS, 2015) Karakus, Canan Filiz; Altuntas, Emine Elif; Kilicli, Fatih; Durmus, Kasim; Hasbek, ZekiyeObjectives: In this study, we measured hearing thresholds in patients diagnosed with hyperthyroidism or hypothyroidism with high-frequency audiometry and otoacoustic emission before and after treatment to determine whether hearing losses were cochlear or retrocochlear and whether they would improve with medical therapy. Materials and Methods: This study was conducted on patients diagnosed with hyperthyroidism and hypothyroidism at Cumhuriyet University, Faculty of Medicine, Department of Endocrinology and Metabolism and accepting to participate in the study. We measured the hearing thresholds of the study population during the pretreatment period and in posttreatment euthyroid period. Result: The audiometric findings of patients with hyperthyroidism were better than those of the control group especially at high frequencies. Sensorineural hearing loss was detected in the euthyroid period. We compared the audiometric findings of the patients with hypothyroidism and the controls. We found sensorineural hearing loss in patients with hypothyroidism, especially at low frequencies. Conclusions: The results of this study showed that both hyperthyroidism and hypothyroidism may have an effect on hearing pathway disorders. Medical therapy may lead to hearing loss in patients with hyperthyroidism, and the underlying factors should be investigated in detailed future studies. It was shown in our study that the hearing loss induced by hypothyroidism may improve with medical therapy. Therefore, in all patients with thyroid dysfunction, hearing levels should be monitored closely with audiometric tests.Öğe Low L-carnitine levels: Can it be a cause of nocturnal blood pressure changes in patients with toe 2 diabetes mellitus?(TURKISH SOC CARDIOLOGY, 2011) Korkmaz, Serdal; Yildiz, Gursel; Kilicli, Fatih; Yilmaz, Abdulkerim; Aydin, Huseyin; Icagasioglu, Serhat; Candan, FerhanObjective: The nocturnal blood pressure (NBP) reduction is less than normal in the patients with type 2 diabetes mellitus (type 2 DM). L-carnitine deficiency may cause changes of NBP by leading to hyperglycemia, insulin resistance and endothelial dysfunction in patients with type-2 DM. The purpose of the study was to investigate whether there is a difference in levels of L-carnitine in dipper and nondippers patients with type 2 DM. Methods: This is a cross-sectional observational cohort study. We compared the 50 (33 females, 17 males) patients with type 2 DM and the 35 healthy persons (18 females, 17 males) as a control group. In all cases, ambulatory blood pressure monitoring (ABPM) was performed and L-carnitine was measured. The independent samples t test, Chi-square test, Mann-Whitney U test and Pearson correlation analysis were used in the statistical evaluation of data. Results: We found that the percentage of nondipper pattern was 72% in patients with type 2 DM. L-carnitine levels were lower in patients with type 2 DM (52.77+/-12.34 mu mol/L) than those of control group (79.18+/-10.59 mu mol/L), and these differences were statistically significant (p<0.05). L-carnitine levels were lower in nondipper cases (50.02+/-16.30 mu mol/L) than those of dipper cases (53.83+/-10.50 mu mol/L), but these differences were not statistically significant (p=0.125). Conclusion: Nondipper pattern is common in patients with type 2 DM. Nondipper pattern is associated with damage of target organ. Therefore, determination of nondipper pattern by ABPM is very important. L-carnitine levels were found to be lower in nondipper patients than in dipper patients with type 2 DM. Although, these differences were statistically nonsignificant, more detailed studies should be performed to determine the frequencies and relationship between nondipper pattern and L-carnitine levels in patients with type-2 DM. (Anadolu Kardiyol Derg 2011 1: 57-63)Öğe Relationship between homocysteine and non-dipper pattern in patients with type 2 diabetes mellitus(SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA, 2012) Korkmaz, Serdal; Yilmaz, Abdulkerim; Yildiz, Gursel; Kilicli, Fatih; Icagasioglu, SerhatObjective: The rate of reduction of nocturnal blood pressure (NBP) is lesser than normal in patients with type 2 diabetes mellitus (type 2 DM). Hyperhomocysteinemia (HHC) disrupts vascular structure and function, no matter the underlying causes. The risk of development of vascular disease is greater in diabetic patients with hyperhomocysteinemia than in patients with normal homocystein levels. The aim of the study was to investigate whether there are differences of homocystein levels in dipper and non-dippers patients with type 2 DM. Subjects and methods: We compared 50 patients (33 females, 17 males) with type 2 DM and 35 healthy individuals (18 females, 17 males 1 in a control group. Ambulatory blood pressure monitoring (ABPM) was performed and homocysteine levels were measured in all patients. Results: We found that the percentage of non-dipper pattern was 72% in patients with type 2 DM and 57% in control group. In diabetic and control individuals, homocystein levels were higher in non-dipper (respectively 13.4 +/- 8.1 mu mol/L and 11.8 +/- 5 mu mol/L) than in dipper subjects (respectively, 11.8 +/- 5.8 mu mol/L and 10.1 +/- 4.2 mu mol/L), but there was no significant difference between the two groups (respectively, p = 0.545, p = 0.294). Conclusion: In both groups, homocystein levels were higher in non-dipper than in dipper participants, but there was no significant difference between the groups. High homocystein levels and the non-dipper pattern increases cardiovascular risk. Therefore, the relationship between nocturnal blood pressure changes and homocystein levels should be investigated in a larger study. Arq Bras Endocrinol Metab 2012;56(5):285-90Öğe Serum cortisol and dehydroepiandrosterone-sulfate levels in schizophrenic patients and their first-degree relatives(WILEY-BLACKWELL, 2011) Yildirim, Osman; Dogan, Orhan; Semiz, Murat; Kilicli, FatihAims: Alterations in cortisol and dehydroepiandrosterone sulfate (DHEA-S) levels are thought to play a role in the pathophysiology of neuropsychiatric disorders, including schizophrenia. The aim of this study was to investigate the role of serum cortisol and DHEA-S in the pathophysiology of schizophrenia. Methods: Sixty schizophrenic patients, 70 healthy first-degree relatives, and 60 healthy volunteers were included. Sociodemographic characteristics, data regarding disease duration and severity, as well as ongoing and previous drug use were recorded. Serum cortisol and DHEA-S levels were measured. Results: Serum cortisol and DHEA-S levels were significantly higher in the schizophrenia group compared with the first-degree relatives and controls (P < 0.05). Serum cortisol levels in the first-degree relatives were significantly higher than in the healthy controls (P < 0.05). There was no significant difference between the first-degree relatives and healthy-controls in terms of DHEA-S levels and between the three groups in terms of serum cortisol/DHEA-S ratios. Conclusions: Elevated serum cortisol levels in schizophrenic patients might be associated with the role of cortisol in the pathophysiology of schizophrenia. Also, the elevation of serum cortisol levels in first-degree relatives compared to controls suggests that similar pathophysiological processes might have a role in individuals without any disease symptoms, but with a genetic predisposition for schizophrenia. Elevated serum DHEA-S levels might be the result of a compensatory response to elevated cortisol levels. Serum cortisol and DHEA-S levels may be used as a biological marker for the diagnosis of schizophrenia; however, further studies with larger sample sizes are warranted to support this finding.Öğe Serum Levels of Angiopoietin-Related Growth Factor (AGF) Are Increased in Polycystic Ovary Syndrome(LIPPINCOTT WILLIAMS & WILKINS, 2012) Boztosun, Abdullah; Deveci, Koksal; Kilicli, Fatih; Soylemez, Melike Sinem; Muhtaroglu, Sabahaddin; Muderris, Iptisam IpekBackground: Polycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance. Recently, angiopoietins were identified in the systemic circulation and have been designated angiopoietinlike proteins (ANGPTL). More recently, it is shown that angiopoietin-related growth factor (AGF, also called ANGPTL6) directly regulate lipid, glucose, and energy metabolism independent of angiogenic effects in animal studies. The aim of this study was to determine whether there is an association between AGF and PCOS. Methods: The study included 35 patients with PCOS and 30 healthy control women. We analyzed serum levels of AGF and other biochemical and anthropometric markers in all the subjects. Results: This study showed that serum AGF levels were significantly higher in the subjects with PCOS (102.28 ng/mL) than those in the healthy control group (63.08 ng/mL; P < 0.001). Body mass index (24.33 vs 22.11 kg/m(2); P = 0.017), free testosterone (2.81 vs 2.17 pmol/L; P = 0.009), androstenedione (3.28 vs 2.92 nmol/L; P = 0.033), 17-hydroxyprogesterone (2.72 vs 2.09 ng/mL; P = 0.039), homeostasis model of assessment-insulin resistance (2.65 vs 1.9; P = 0.016), and fasting glucose (107.09 vs 96.18 mmol/L; P = 0.001) were found significantly higher in PCOS group than in control group. But there was no correlation between AGF and these parameters in PCOS group. In addition, no correlation between the AGF and other distinctive features of PCOS was found. Conclusions: Serum AGF levels were paradoxically increased in patients with PCOS in comparison with data of animal experiments. Further studies are needed to better elucidate the physiologic significance of circulating AGF in human disease.Öğe Sheehan's syndrome(INFORMA HEALTHCARE, 2013) Kilicli, Fatih; Dokmetas, Hatice Sebila; Acibucu, FettahSheehan's syndrome (SS) is characterized by various degrees of hypopituitarism, and develops as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. Increased pituitary volume, small sella size, disseminated intravascular coagulation and autoimmunity are the proposed factors in the pathogenesis of SS. Hormonal insufficiencies, ranging from single pituitary hormone insufficiency to total hypopituitarism, are observed in patients. The first most important issue in the diagnosis is being aware of the syndrome. Lack of lactation and failure of menstrual resumption after delivery that complicated with severe hemorrhage are the most important clues in diagnosing SS. The most frequent endocrine disorders are the deficiencies of growth hormone and prolactin. In patients with typical obstetric history, prolactin response to TRH seems to be the most sensitive screening test in diagnosing SS. Other than typical pituitary deficiency, symptoms such as anemia, pancytopenia, osteoporosis, impairment in cognitive functions and impairment in the quality of life are also present in these patients. Treatment of SS is based on the appropriate replacement of deficient hormones. Growth hormone replacement has been found to have positive effects; however, risk to benefit ratio, side effects and cost of the treatment should be taken into account.
