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Background: Given the high prevalence of unrecognized iron deficiency anemia (IDA) in Croatia and its negative impact on children's somatic and neurological outcomes, a comprehensive preventive and treatment approach is a necessity.  Methods: This was an observational, cross-sectional study of pediatric patients referred to the Children's Hospital Zagreb, Croatia, from 2017 to 2021, for IDA. Epidemiological and clinical data were extracted. Laboratory workup and therapeutic actions in the primary and tertiary care settings were recorded. The need for transfusion, parenteral iron therapy, and hospital admission was noted., Results: A total of 299 patients (52.2% female, median five years) were seen by the hematologist in the five-year study period. Almost half (45.1%) were referred by the primary care pediatrician. Only half of the patients (56.6%) received oral iron therapy prior to referral. The preferred preparation was Dextriferron (67.7%) during the mean period of 5.8 months, but more than one-third of the patients (36.5%) were non-compliant. Every 10th child seen by the hematologist for IDA was admitted to the hospital; 6.4% required transfusion therapy, and in only one patient, parenteral iron was administered.  Conclusions: The results of this survey established that IDA still represents an excessive burden in a tertiary care setting of a high-income country. Therefore, consistent implementation of national guidelines and additional education of primary healthcare providers is crucial to ameliorate this significant public health concern., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Matijasic Stjepovic et al.)

Iron deficiency anemia (IDA) continues to be a global public health concern, mostly in the developing countries. However, precise epidemiological data on childhood IDA in Croatia are lacking. In order to establish its frequency, underlying etiologies, the rationale for tertiary care visits, diagnostic practices, and current treatment regimens of IDA, medical records of children referred to pediatric hematologists for iron deficiency in a five-year period at tertiary institutions (Zagreb, Rijeka, Split, Osijek) throughout Croatia were retrospectively analyzed. Eight hundred and sixty-four children, predominately of preschool age, were referred mainly by the primary care pediatricians, who, in general, performed basic diagnostics but failed to initiate oral iron therapy in half of the patients. Approximately one-third of patients were symptomatic, with inadequate nutrition prevailing as underlying etiology. Dextriferron was the preferred iron formulation among hematologists, with a median dose of 5 mg/kg, with acceptable compliance rates (63.5-93.2%). Hospital admission rates varied among the centers (9.4-35%), and so did transfusion policies (6.4-22.9%). The greatest difference was observed in the frequency of parenteral iron administration (0.3-21.5%). In conclusion, the burden of childhood IDA, even in a high-income country, remains substantial, necessitating consistent implementation of national guidelines and additional education of primary health care providers.

Invasive fungal infections (IFI) are life-threatening complications of intensive chemotherapy treatment, with the incidence in pediatric patients ranging from 2% to 21%. In this article, we describe our 5-year experience of IFI in pediatric oncology patients and its clinical manifestations with radiological findings, treatment and outcome. A retrospective and descriptive survey of IFI in children with hematologic neoplasms was conducted at the Department of Oncology and Hematology, Zagreb Children's Hospital. Medical charts of children 0-17 years of age, of both sexes, treated for leukemias and lymphomas from January 2016 to December 2020 were reviewed. In a 5-year period, 60 patients were treated for hematologic malignancy, acute lymphoblastic leukemia (ALL) being the most prevalent diagnosis. IFI was verified in 9 (15%) children, predominantly in patients with ALL (75%). The specific causative agent was detected in one child, whereas other infections were classified as probable pulmonary aspergillosis. All the patients received standard prophylaxis with fluconazole and treatment with liposomal amphotericin B and voriconazole. The majority of our patients achieved recovery. IFI prevention, diagnosis and treatment remain a challenge. Uniform prophylaxis and therapy protocols, as well as environmental control are of vital importance for the development of better strategies in the prevention, early detection and treatment of IFI in pediatric hematology patients., (Sestre Milosrdnice University Hospital.)

Introduction:  The use of complementary and alternative medicine (CAM) has become a customary practice among pediatric cancer patients worldwide. The frequency of its use by pediatric cancer patients in Croatia has not been previously determined.  Methodology: In order to establish the frequency and detect factors affecting the use of CAM, a single-center, observational, cross-sectional study was conducted at the Children's Hospital Zagreb during a two-year period. The patients' parents and caregivers were offered an anonymous, multi-item questionnaire that collected socio-economic and clinical data, as well as details on CAM and dietary supplement practice.  Results: Almost half of the participants reported CAM and more than two-thirds reported dietary supplement consumption, predominantly in the intensive phase of the treatment. Factors regarding children or parents had no effect on CAM and supplement utilization. Herbal medicine, vitamins, and minerals were among the most commonly used items. Every 10th child experienced at least one adverse event during CAM and supplement use., Conclusion:  Awareness of the CAM and dietary supplement application in pediatric oncology patients needs to be raised due to the potential interactions with conventional treatment modalities. For this reason, it is extremely important to inform parents and caregivers of pediatric oncology patients about the use of CAM and dietary supplements to predict and mitigate the occurrence and intensity of the side effects. In the majority of our cases, the patient's guardians informed the healthcare professionals about the CAM and supplement implementation in their children, therefore, they were offered additional information about the possible negative impact of CAM and supplement use on standard medical care in a timely manner., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Kranjcec et al.)

Hepatitis C is a public health problem worldwide. Currently recommended therapy for the treatment of hepatitis C, pegylated interferon-alpha and ribavirin, when applied in combination, are often associated with the risk of developing mood disorders, depression and anxiety. Previously, the existence of psychiatric comorbidity was the reason for therapy discontinuation, but current guidelines allow such treatment despite the presence of psychiatric illness. Close cooperation with psychiatrists is highly recommended for the treatment of patients with psychiatric comorbid disease in order to motivate the patient for treatment, stabilize his mental condition, educate him about the possible side effects, and regularly monitor the patient, so the treatment can be carried out safely and successfully. Therefore, a multidisciplinary approach is essential for successful treatment of hepatitis C virus infections.

Oral lichen planus (OLP) is a T-cell mediated disease directed to a still unknown antigen, which may affect oral mucosa. The aim of this study was to determine whether differences in anxiety, depression and stress could be seen in patients with OLP in acute stage and in remission, as well as in comparison with healthy control subjects. The study included 50 OLP patients aged 22-79 (mean age 61.04) years and 50 control subjects who had healthy oral mucosa aged 38-80 (mean age 58.70) years. Patients with OLP filled out the State-Trait Anxiety Inventory for Adults and Beck Depression Inventory II test in acute stage and in remission. Control subjects also filled out the same tests. On detailed medical history, study subjects were asked about the possible stressors, which might have happened in the previous year. Statistical analysis was performed by use of descriptive statistics and t-test. There were no differences in the level of anxiety, depression and stress between the two stages of OLP disease (acute vs. remission period). Patients with OLP were significantly more anxious, depressed and stressed in both OLP stages as compared with healthy controls. It might be that psychological disturbances precede OLP development rather than worsening the disease process itself.

Low back pain (LBP) is a very common condition with high costs of patient care. Medical doctors of various specialties from Croatia have brought an up-to-date review and guidelines for diagnosis and conservative treatment of low back pain, which should result in the application of evidence-based care and eventually better outcomes. As LBP is a multifactorial disease, it is often not possible to identify which factors may be responsible for the onset of LBP and to what extent they aggravate the patient's symptoms. In the diagnostic algorithm, patient's history and clinical examination have the key role. Furthermore, most important is to classify patients into those with nonspecific back pain, LBP associated with radiculopathy (radicular syndrome) and LBP potentially associated with suspected or confirmed severe pathology. Not solely a physical problem, LBP should be considered through psychosocial factors too. In that case, early identification of patients who will develop chronic back pain will be helpful because it determines the choice of treatment. In order to make proper assessment of a patient with LBP (i.e. pain, function), we should use validated questionnaires. Useful approach to a patient with LBP is to apply the principles of content management. Generally, acute and chronic LBP cases are treated differently. Besides providing education, in patients with acute back pain, advice seems to be crucial (especially to remain active), along with the use of drugs (primarily in terms of pain control), while in some patients spinal manipulation (performed by educated professional) or/and short-term use of lumbosacral orthotic devices can also be considered. The main goal of treating patients with chronic LBP is renewal of function, even in case of persistent pain. For chronic LBP, along with education and medical treatment, therapeutic exercise, physical therapy and massage are recommended, while in patients with a high level of disability intensive multidisciplinary biopsychosocial approach has proved to be effective.

Recurrent aphthous ulceration (RAU) are a disease of an unknown etiology and mediated through T-cell lymphocytes. Evidence suggests that RAU is connected with chronic bowel disease, haematinic deficiencies, AIDS, food hypersensitivity and severe stress. The aim of this study was to determine whether differences in anxiety and depression could be seen in patients with RAU during acute phase and remision period and in comparison to the healthy controls. There were 30 patients with RAU (age range 36.27 +/- 15.308) and 30 controls aged 29.83 +/- 9.082. Every participant with RAU fullfilled STAI and Beck Depression Inventory II test during acute phase and during remission period as well as controls. Statistical analysis was performed by use of descriptive statistics and t-test. There are no differences in the level of depression and stress between the two phases of the RAU (acute versus remission period) as well as in comparison to the controls. Patients with acute RAU are more anxious than patients with RAU during remission period. We might conclude that psychological disturbances do not preceed the development of RAU and that the patients with acute RAU are more anxious when compared to the condition when they do not have RAU due to the discomfort they experience.

The aim of this study was to explore the role of inflammatory markers in the occurrence of depression. The concentrations of inflammatory markers were analyzed in the groups of healthy subjects and subjects with major depressive disorder (MDD) initially and after one-month antidepressant therapy in the latter. The intention was to demonstrate the role of inflammatory markers in the development of MDD by differences in their concentrations and to explain the mechanism of depression development. This would help us expand our understanding of the occurrence of depression and enable introduction of some new methods in the treatment and diagnosis of depression. Study results showed a statistically significant difference in the concentrations of inflammatory markers (C-reactive protein (CRP), interleukin-6 and tumor necrosis factor alpha) between the group of MDD subjects and control group of healthy subjects. These concentrations were higher in MDD subjects. A statistically significant difference was also found in CRP concentration before and after antidepressant therapy administered to MDD patients, i.e. it was lower after antidepressant therapy. Study results pointed to the efficacy of antidepressant therapy for depression by reducing the concentration of this inflammatory marker.

Objective: Cushing's disease which is a consequence of ACTH-secreting pituitary adenoma leads to hypercortisolism. Cushing's disease is associated with several psychiatric disturbances. The aim of the present study was to identify which psychiatric disorders were present in patients with Cushing's disease over a 2-year period and to monitor their general psychiatric condition. Additionally, the study aimed to examine the relationship between the duration of Cushing's disease, and the severity of psychiatric conditions based on psychiatric rating scales., Method: The study included 39 patients with Cushing's disease that underwent neurosurgery for ACTH-secreting pituitary adenomas. The transsphenoidal approach (the standard microsurgery technique) was performed in all patients. ACTH-secreting pituitary adenomas were confirmed based on immunohistochemistry in all patients. Psychiatric conditions in the patients were identified using the Clinical Global Impression Scale (CGI) and ICD 10 diagnostic criteria at 3 time points: prior to surgery, and 6 and 48 months post surgery., Results: The Cushing's disease patients exhibited statistically significant improvement in their psychiatric condition, according to the CGI, 6 and 48 months post surgery. There wasn't any significant correlation between the duration of Cushing's disease and psychiatric status, as measured by the CGI prior to surgery, 6 months post surgery, or 48 months post surgery., Conclusion: Patients with Cushing's disease had a significant level psychiatric disturbance that remitted after surgery. There wasn't a significant correlation between the duration of Cushing's disease and psychiatric status.

Delusions of parasitosis (DP) is a primary psychiatric disorder, a type of monosymptomatic hypochondriac psychosis in which patients believe that 'bugs' or 'parasites' have infested their skin or that they have even spread into their visceral organs. Patients with DP usually approach different medical specialists, mostly dermatologists and primary care physicians because of symptoms presenting as crawling under their skin. Therefore, the exact prevalence of DP is unknown. It is believed that it is a rare disorder but different studies indicate that the prevalence is greater than presented. The etiology of this disorder is still unclear. Patients with DP come to a physician with a stereotypic history. Usually the patient has previously addressed many other different specialists and symptoms are usually present for several months to years. The main cutaneous symptom is crawling, biting and pruritus due to 'burrowing of parasites, insects or bugs' under the skin. Patients with DP are rare but can be very challenging for making the correct diagnosis and for the treatment as well. It is essential to distinguish primary from secondary disorder since the approach to these patients is different. Dermatologists who have good knowledge in diagnosis, both dermatologic and psychodermatologic, and who dare prescribe antipsychotics after consulting liaison-psychiatrist, can have good results in treating patients with DP. When treating patients with DP, multidisciplinary approach by collaboration between a dermatologist and a psychiatrist is necessary to provide complete and meaningful treatment for these patients.

Psoriasis is a chronic, hereditary disease generally characterized by eruption of erythematous, silvery-scaled plaques, predominantly on the elbows, knees, scalp and trunk, affecting between 1-2% of the population worldwide. Psoriasis is a multifactorial disease of unknown etiology. It has been shown that in some patients alcohol abuse has been associated with psoriasis. Chronic alcohol abuse results in the impairment of health-related, social and occupational functioning. Therefore the association of psoriasis and alcoholism represents one of the major psychodermatological issues where a multidisciplinary approach (including dermatologist, psychiatrist, psychologist and others) is crucial for optimal outcome.

The aim of the study was to determine the level of anxiety and depression in patients with and without burning mouth syndrome, and to assess the possible association between the intensity of burning mouth and incidence of depression and anxiety. The study was conducted in a sample of 120 randomly chosen adult patients from two dentist offices in Nova Gradiska (Croatia). Patient data were collected by use of a questionnaire that consisted of four parts: history questionnaire, Beck's anxiety inventory (BAI), Zung's self-evaluation scale for rating depression, and visual analogue scale (VAS) for estimating the intensity of burning mouth syndrome. The presence of the symptoms of burning mouth syndrome was recorded in 35% of 120 subjects. A statistically more significant mean level of depression and anxiety was detected in the group of subjects with the symptoms of burning mouth syndrome. The association between the burning mouth syndrome, anxiety and depression was tested by Pearson correlation. The levels of burning mouth syndrome, anxiety and depression in subjects showed positive correlation. Study results indicated the level of anxiety and the level of depression to be higher in the group of subjects with the burning mouth syndrome. The intensity of the symptoms of anxiety and depression also was in positive correlation with the intensity of the burning mouth syndrome. This clearly points to the role of psychogenic factors, anxiety and depression in the etiology of the burning mouth syndrome, which should be taken in consideration when treating patients with the burning mouth syndrome.

Lithium, besides mood stabilization, might be involved in neuroprotection. Previously we have found that the treatment with lithium increased the levels of p21(WAF/Cip1 and survivin in human glioblastoma A1235 cells. The aim of the present study was to examine the cytotoxic effect of glutamate on these cells, and to determine whether lithium can protect A1235 cells against toxic effects of glutamate. Cytotoxicity of glutamate was examined by spectrophotometric MTT assay, while the expression of apoptosis related genes was examined by Western blot method. Glutamate was excessively cytotoxic for A1235 cells only in concentrations higher than 100 mM. It did not induce apoptosis, but rather suppressed survivin expression and increased the level of p21(WAf/Cip1). Pretreatment with lithium (2 mM) partially reverted change in survivin expression induced by glutamate, suggesting that lithium may have beneficial effect on glutamate induced cell damage in glioblastoma cells.

The aim of this study was to assess eventual differences in serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, LDL-C/HDL-C ratio between veterans with combat-related post-traumatic stress disorder (PTSD) only or comorbid with major depressive disorder (MDD), veterans with combat experiences with MDD, and healthy control group. PTSD and/ or MDD were diagnose according to structured clinical interview based on DSM-IV criteria. Additional criteria to diagnose PTSD were Clinician Administered PTSD Scale (CAPS), and to diagnose MDD Montgomery-Asberg Depression Rating Scale (MADRAS). Serum lipid concentrations were determined by using the enzyme-assay method. Veterans with combat-related PTSD as well as veterans with combat-related PTSD comorbid with MDD showed significantly higher concentrations of cholesterol (F=9.858, p<0.01), triglycerides (F=10.112, p<0.01), LDL-C (F=11.145, p<0.01), and LDL-C/HDL-C ratio (F=8.346, p<0.01) vs. veterans with MDD or healthy control group. Contrary healthy control group and veterans with MDD showed significantly higher concentrations of HDL-C (F=8.421, p<0.01), vs. veterans with PTSD or PTSD comorbid with MDD. In conclusion, there are no differences in serum lipid concentrations between veterans with combat-related PTSD and PTSD comorbid with MDD, but they have higher lipid concentrations than veterans with MDD or healthy control subjects.

The aim of our study was to assess concentrations of serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides in soldiers with combat-related posttraumatic stress disorder (PTSD), in comparison with combat-experienced soldiers without PTSD. The second aim of our study was to explore the relationship between PTSD symptoms such as re-experiencing, avoidance, increased arousal, and serum lipid levels. In 53 soldiers with combat-related PTSD and 49 with combat experiences without PTSD, serum cholesterol, LDL-C, HDL-C, and triglycerides were assayed by an enzyme-assay method. Soldiers with combat-related PTSD were found to have significantly higher concentrations of cholesterol (P = 0.001), LDL-C (P = 0.002), and triglycerides (P = 0.001) than soldiers without current PTSD. HDL-C was statistically lower (P < 0.001) in soldiers with combat-related PTSD than in those without PTSD. A positive correlation was found between increased arousal and cholesterol (r = 0.464; P = 0.039), or LDL-C (r = 0.479; P = 0.021) concentrations.

Authors believe that drinking alcoholic beverages can be associated with customs and habits specific to small communities, societies and even entire nations. The primary family, as the foundation of customs and habits of the first generation, has a role in stimulating drinking and alcoholism. The authors have examined some sociocultural factors, mostly taking into consideration relations in the primary family, by means of a questionnaire filled out by alcoholics (N = 200) and non-alcoholics (N = 100). The alcoholics usually have their first drink earlier, start drinking regularly earlier, and in the primary family there is a high tolerance towards the use of alcoholic beverages. The authors believe that the prevention should be directed primary towards the primary family with a view to changing their customs and habits as well as attitudes towards the use of alcoholic beverages.