Clinical and epidemiological risk factors associated with hospitalization and mortality rate of COVID-19 patients in Banja Luka County: A retrospective observational cohort study on 40,000 patients.

Context: Since beginning of the coronavirus disease (COVID-19) it became clear that severe forms of this infection have primarily affected patients with chronic conditions. Aims: The aim of the study was to explore clinical and epidemiological characteristics associated with COVID 19 outcomes. Settings and Design: The retrospective observational study included 40,692 citizens of Banja Luka County, Bosnia and Herzegovina, who were confirmed as reverse transcriptase polymerase chain reaction (RT-PCR) positive on COVID-19 at a primary healthcare centre from March 2020 to September 2022. Methods and Materials: Epidemiological data were obtained from Web-Medic medical records of patients. The COVID-19 data were obtained from COVID-19 data sheets comprised of patients' RT-PCR testing forms, surveillance forms for severe acute respiratory syndrome coronavirus-2 status, and a map of their positive and isolated contacts. Statistical Analysis Used: Differences regarding the distributions of patients between groups were analysed using the Pearson chi-square test and Mantel-Haenszel chi-square test for trends, while differences in mean values were compared using an independent sample t-test. Results: The average age of hospitalised patients was significantly higher compared to the age of non-hospitalised patients (P < 0.001). The average age of patients with lethal outcomes was nearly twice as high in comparison to patients with non-lethal outcomes (P < 0.001). Male patients had a higher hospitalization and mortality rate (P < 0.001). The highest hospitalization rate was in patients with chronic renal failure (CRF), diabetes and cardiovascular diseases (CVDs), while the death rate was the highest among patients with CRF and hearth comorbidities. Patients with fatigue and appetite loss had a higher percentage of lethal outcomes. Vaccinated patients had a significantly lower rate of lethal outcome. Conclusions: Clinical symptoms, signs and outcomes, are posing as predictive parameters for further management of COVID-19. Vaccination has an important role in the clinical outcomes of COVID-19.

Burnout syndrome among preschool teachers in Serbia.

Pedagogical work, especially with preschool children, is one of the most stressful professions, and the incidence of stress-related illnesses among preschool teachers is higher than in the general population. The aim of this cross-sectional study, conducted between October 2018 and April 2019, was to examine the prevalence of the burnout syndrome in a representative sample of 482 preschool teachers in Serbia and the factors associated with it. For this purpose, the participants completed a questionnaire composed of six sections: the socio-demographic and socio-economic characteristics, health and lifestyle characteristics, workplace and employment characteristics; Copenhagen Burnout Inventory (CBI); Beck Depression Inventory (BDI), and the Zung Self-Rating Anxiety Scale (SAS). The frequency of the total burnout was 27.1 %. The frequency of burnout on the CBI was 25.4 % for personal burnout, 27.0 % for work-related burnout, and 23.4 % for client-related burnout. Multivariate logistic regression analysis with total burnout as an outcome variable showed that being single (OR: 0.18; 95 % CI: 0.05-0.58), having poor (OR: 6.05; 95 % CI: 1.05-34.91), or average (OR: 3.60; 95 % CI: 1.57-8.25) self-rated health, not having didactic/play tools (OR: 2.71; 95 % CI: 1.21-6.04), having a higher score on the BDI (OR: 1.19; 95 % CI: 1.09-1.29) or SAS (OR: 1.10; 95 % CI: 1.03-1.18) was significantly associated with the total burnout among our participants. Our study shows the worryingly high prevalence of the burnout syndrome among preschool teachers in Serbia and points to its association with mental health issues, depression, and anxiety.

Wearable Movement Exploration Device with Machine Learning Algorithm for Screening and Tracking Diabetic Neuropathy-A Cross-Sectional, Diagnostic, Comparative Study.

BACKGROUND: Diabetic neuropathy is one of the most common complications of diabetes mellitus. The aim of this study is to evaluate the Moveo device, a novel device that uses a machine learning (ML) algorithm to detect and track diabetic neuropathy. The Moveo device comprises 4 sensors positioned on the back of the hands and feet accompanied by a mobile application that gathers data and ML algorithms that are hosted on a cloud platform. The sensors measure movement signals, which are then transferred to the cloud through the mobile application. The cloud triggers a pipeline for feature extraction and subsequently feeds the ML model with these extracted features. METHODS: The pilot study included 23 participants. Eleven patients with diabetes and suspected diabetic neuropathy were included in the experimental group. In the control group, 8 patients had suspected radiculopathy, and 4 participants were healthy. All participants underwent an electrodiagnostic examination (EDx) and a Moveo examination, which consists of sensors placed on the feet and back of the participant's hands and use of the mobile application. The participant performs six tests that are part of a standard neurological examination, and a ML algorithm calculates the probability of diabetic neuropathy. A user experience questionnaire was used to compare participant experiences with regard to both methods. RESULTS: The total accuracy of the algorithm is 82.1%, with 78% sensitivity and 87% specificity. A high linear correlation up to 0.722 was observed between Moveo and EDx features, which underpins the model's adequacy. The user experience questionnaire revealed that the majority of patients preferred the less painful method. CONCLUSIONS: Moveo represents an accurate, easy-to-use device suitable for home environments, showing promising results and potential for future usage.

Comprehensive Investigation of Angiogenesis, PASS Score and Immunohistochemical Factors in Risk Assessment of Malignancy for Paraganglioma and Pheochromocytoma.

A challenging task in routine practice is finding the distinction between benign and malignant paragangliomas and pheochromocytomas. The aim of this study is to conduct a comparative analysis of angiogenesis by assessing intratumoral microvascular density (MVD) with immunohistochemical (IHC) markers (CD31, CD34, CD105, ERG), and S100 immunoreactivity, Ki67 proliferative index, succinate dehydrogenase B (SDHB) expressiveness, tumor size with one the most utilized score Pheochromocytoma of Adrenal Gland Scales Score (PASS), using tissue microarray (TMA) with 115 tumor samples, 61 benign (PASS < 4) and 54 potentially malignant (PASS ≥ 4). We found no notable difference between intratumoral MVD and potentially malignant behavior. The group of potentially malignant tumors is significantly larger in size, has lower intratumoral MVD, and a decreased number of S100 labeled sustentacular cells. Both groups have low proliferative activity (mean Ki67 is 1.02 and 1.22, respectively). Most tumors maintain SDHB expression, only 6 cases (5.2%) showed a loss of expression (4 of them in PASS < 4 group and 2 in PASS ≥ 4). PASS score is easily available for assessment and complemented with markers of biological behavior to complete the risk stratification algorithm. Size is directly related to PASS score and malignancy. Intratumoral MVD is extensively developed but it is not crucial in evaluating the malignant potential.

Effect of special types of bread with select herbal components on postprandial glucose levels in diabetic patients.

BACKGROUND: Nutrition recommendations in patients with type 2 diabetes mellitus (T2DM) are to consume rye or integral bread instead of white bread. A positive effect on glucoregulation has been achieved by enriching food with various biologically active substances of herbal origin, so we formulated an herbal mixture that can be used as a supplement for a special type of bread (STB) to achieve better effects on postprandial glucose and insulin levels in patients with T2DM. AIM: To compare organoleptic characteristics and effects of two types of bread on postprandial glucose and insulin levels in T2DM patients. METHODS: This trial included 97 patients with T2DM. A parallel group of 16 healthy subjects was also investigated. All participants were given 50 g of rye bread and the same amount of a STB with an herbal mixture on 2 consecutive days. Postprandial blood glucose and insulin levels were compared at the 30th, 60th, 90th and 120th min. A questionnaire was used for subjective estimation of the organoleptic and satiety features of the two types of bread. RESULTS: Compared to patients who consumed rye bread, significantly lower postprandial blood glucose and insulin concentrations were found in T2DM patients who consumed STB. No relevant differences were found among the healthy subjects. Subjectively estimated organoleptic and satiety characteristics are better for STB than for rye bread. CONCLUSION: STB have better effects than rye bread on postprandial glucoregulation in T2DM patients. Subjectively estimated organoleptic and satiety characteristics are better for STB than for rye bread. Therefore, STB can be recommended for nutrition in T2DM patients.

Translation and Validation of the Sinus and Nasal Quality of Life Surgery Survey in Serbian.

Objective: The aim of this study was to translate the Sinus and Nasal Quality of Life Surgery Survey into the Serbian language to evaluate the test-retest reliability and validity. Study Design: The study included 49 consecutive patients between 12 and 18 years old with rhinologic symptoms. Patients were given a paper survey to complete along with a link to complete the online survey within the same day. Setting: The study was conducted at the University Children's Hospital Clinic for Pulmonology and Allergology between January 2023 and March 2023. Methods: Responses between the paper and online survey were compared and regression analysis was performed to evaluate the relationship. Internal reliability and test-retest reliability were assessed using Cronbach's α coefficient and intraclass correlation coefficient. All data were collected and analyzed using SPSS 29.0. Results: Pearson correlation coefficient between the paper and online survey was very high and statistically significant (r = 0.999; P < .001). Each item had a high correlation (0.993-1.000), where the lowest correlation coefficient was obtained from question 2 (0.993). Average scores in each item differed slightly for only item 2 (mean difference = -0.041), but not to the level of statistical significance. Bland-Altman plot indicated no proportional bias between the 2 versions. Linear regression analysis suggested a high level of agreement between the 2 versions (slope = 1.00, R 2 = 0.999). Conclusion: The survey is a useful questionnaire to evaluate the quality of life in patients with rhinologic symptoms. The high correlation between the paper and online survey shows the reliability of the questionnaire regardless of administration modality.

The Influence of High-Dose Parenteral Vitamin C on the Incidence and Severity of Postoperative Pulmonary Complications in Cardiac Surgery with Extracorporeal Circulation: A Randomized Controlled Trial.

Cardiac surgery (CS) with extracorporeal circulation (ECC), induces intense oxidative stress (OS) and systemic inflammatory response (SIR), which may seriously affect postoperative lung function. We aimed to test if high parenteral (200 mg/kg/24 h) daily doses of Vitamin C (VitC), given within 48 h after the beginning of the operation, may reduce the incidence and severity of postoperative pulmonary complications (PPCs) in CS patients. This single-center, prospective, randomized, single-blinded, interventional trial included 150 patients, assigned to control Group A (n = 75) and interventional Group B (n = 75). Group B intraoperatively received one-fourth (i.e., 50 mg/kg) of the planned daily Vit C dose, divided into three equal parts and diluted in 10 mL of normal saline, while Group A received an equal volume of normal saline at the same time frames (i.e., the induction of anesthesia, aortic cross-clamp release, and sternal closure). After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 50 mg/kg, 30 min i.v. infusion of VitC in 50 mL of normal saline, every 6 h, for the next 48 h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 h, for the next 48 h. Modified Kroenke's score was used to determine the incidence and severity of PPCs. The overall incidence of PPCs was 36.7% and was significantly lower in Group B (13.3% vs. 60.0%, p < 0.001). The PPCs severity score was also significantly lower in Group B (1 vs. 3, p < 0.001). In addition, patients from Group B had significantly less damaged lungs, better postoperative renal function, shorter ICU stays, fewer ICU re-admissions, and lower hospital mortality. No VitC-related adverse effects were recorded. High parenteral daily VitC doses given within 48 h after the beginning of CS are safe and effective in reducing the incidence and severity of PPCs. A multicenter RCT is needed to confirm these results.

Beneficial Effects of Ursodeoxycholic Acid on Metabolic Parameters and Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind, Placebo-Controlled Clinical Study.

Background: Oxidative stress and inflammation are closely related pathophysiological processes, both occurring in type 2 diabetes mellitus (T2DM). In addition to the standard treatment of T2DM, a potential strategy has been focused on the use of bile acids (BAs) as an additional treatment. Ursodeoxycholic acid (UDCA), as the first BA used in humans, improves glucose and lipid metabolism and attenuates oxidative stress. The aim of this study was to evaluate the potential metabolic, anti-inflammatory, and antioxidative effects of UDCA in patients with T2DM. Methods: This prospective, double-blind, placebo-controlled clinical study included 60 patients with T2DM, randomly allocated to receive UDCA or placebo. Subjects were treated with 500 mg tablets of UDCA or placebo administered three times per day (total dose of 1500 mg/day) for eight weeks. Two study visits, at the beginning (F0) and at the end (F1) of the study, included the interview, anthropometric and clinical measurements, and biochemical analyses. Results: UDCA treatment showed a significant reduction in body mass index (p = 0.024) and in diastolic blood pressure (p = 0.033), compared to placebo. In addition, there was a statistically significant difference in waist circumference in the UDCA group before and after treatment (p < 0.05). Although no statistical significance was observed at the two-month follow-up assessment, an average decrease in glucose levels in the UDCA group was observed. After two months of the intervention period, a significant decrease in the activity of liver enzymes was noticed. Furthermore, a significant reduction in prooxidative parameters (TBARS, NO2-, H2O2) and significant elevation in antioxidative parameters such as SOD and GSH were found (p < 0.001). Conclusions: The eight-week UDCA administration showed beneficial effects on metabolic and oxidative stress parameters in patients with T2DM. Thus, UDCA could attenuate the progression and complications of diabetes and should be considered as an adjuvant to other diabetes treatment modalities. This trial is registered with NCT05416580.

Impact of haemoglobin A1c on wound infection in patients with diabetes with implanted synthetic graft.

OBJECTIVE: The aim of this study was to assess the relationship between haemoglobin A1c (HbA1c) values and operative wound infection. METHOD: During the period from 2013-2016, consecutive patients with type 2 diabetes were prospectively evaluated. Data were retrospectively analysed. All included patients were admitted for an elective surgical procedure, requiring the use of prosthetic graft in a groin wound. The patients were divided into two groups according to their preoperative HbA1c values. The main outcome was groin wound infection. The association between preoperative long-term glycoregulation and wound infection was evaluated, as well as the impact of postoperative glycaemic values, regardless of the level of HbA1c. RESULTS: Of the 93 participating patients, wound infection occurred in 20 (21.5%). Wound infection occurred in 28.2% of patients with uncontrolled diabetes (HbA1c >7%) and 16.7% of patients with controlled diabetes (HbA1c <7%); however, the difference did not reach statistical significance (p=0.181). In regression modelling, operative time (p=0.042) was a significant predictor of wound infection, while patients' age (p=0.056) was on the borderline of statistical significance. Females had a higher probability for wound infection (odds ratio (OR): 1.739; 95% confidence interval (CI):0.483-6.265), but there was no statistical significance (p=0.397). Patients with elevated levels of HbA1c had a higher chance of wound infection compared with patients with controlled diabetes (OR: 2.243; 95% CI: 0.749-6.716), nevertheless, this was not statistically significant (p=0.149). CONCLUSION: We found no statistically significant correlation between elevated values of preoperative HbA1c and postoperative groin wound infection.

Acquired von Willebrand syndrome and post-operative drainage: a comparison of patients with aortic stenosis versus coronary artery disease.

OBJECTIVE: Degenerative aortic stenosis and coronary artery disease are considered to be the most prevalent cardiovascular diseases in industrialized countries. This study aims to determine the change over time in von Willebrand factor antigen, von Willebrand factor activity, and factor VIII and where there is a correlation with total post-operative drainage. METHODS: The single-center retrospective study included 203 consecutive patients (64.5% male), undergoing coronary artery bypass surgery between March 1, 2019 and June 30, 2020 at the University Clinical Center of Serbia in the Clinic for Cardiac Surgery in Belgrade, Serbia. All patients 18 years or older who presented with isolated, hemodynamically significant aortic stenosis were included. The control group consisted of patients who presented with only coronary artery disease. RESULTS: Between patients with only coronary artery disease and patients with coronary artery diseases and aortic stenosis, there was a statistically significant difference between pre-op and 1-month post-op fibrinogen, factor VIII, von Willebrand factor antigen, and von Willebrand factor (p < 0.001), post-op drainage, with overall lower drainage in coronary artery disease patients, and consistent increase in von Willebrand factor antigen, von Willebrand factor activity, and Factor VIII post-operatively in patients with coronary artery diseases and aortic stenosis. CONCLUSION: This study has shown that there is a correlation between von Willebrand factor antigen, von Willebrand factor activity and total drainage to the level of statistical significance in aortic stenosis patients and in the overall study population.

Oncogene-induced senescence in meningiomas-an immunohistochemical study.

PURPOSE: Meningiomas are tumours originating from meningothelial cells, the majority belonging to grade 1 according to the World Health Organization classification of the tumours of the Central Nervous System. Factors contributing to the progression to the higher grades (grades 2 and 3) have not been elucidated yet. Senescence has been proposed as a potential mechanism constraining the malignant transformation of tumours. Senescence-associated beta-galactosidase (SA-ß-GAL) and inhibitors of cyclin-dependent kinases p16 and p21 have been suggested as senescence markers. METHODS: We analysed 318 meningiomas of total 343 (178 grade 1, 133 grade 2 and 7 grade 3). Tissue microarrays were constructed and stained immunohistochemically, using antibodies for SA-ß-GAL, p16 and p21. RESULTS: The positive correlation of the tumour grade with the expression of p16 (p = 0.016) and SA-ß-GAL (p = 0.002) was observed. The expression of p16 and SA-ß-GAL was significantly higher in meningiomas grade 2 compared to meningiomas grade 1 (p = 0.006 and p = 0.004, respectively). SA-ß-GAL positivity positively correlated with p16 and p21 in the whole cohort. In grade 2 meningiomas, a positive correlation was only between SA-ß-GAL and p16. Correlations of senescence markers in meningiomas grade 2 were not present. CONCLUSION: Our findings suggest the senescence activation in meningiomas grade 2 as a potential mechanism for the restraining of tumour growth and give hope for applying of promising senolytic therapy.

Management of acute appendicitis during COVID-19 pandemic. Single center data from a tertiary care hospital in Germany.

Objectives: The unexpected global overload of the health system during COVID-19 pandemic has caused changes in management of acute appendicitis worldwide. Whereas conservative treatment was widely recommended, the appendicectomy remained standard therapy in Germany. We aimed to investigate the impact of COVID-19 pandemic on treatment routine for acute appendicitis at University Hospital of Magdeburg. Methods: Adult patients with clinical and/or radiological diagnosis of acute appendicitis were included in the single center retrospective study. Data was collected to patient demographics, treatment modality and outcomes including morbidity and length of stay. The patient data related to COVID-19 period from March 22, 2020 to December 31, 2021 (649 days) were compared to the Non-COVID-19 period from June 12, 2018 to March 21, 2020 (649 days). Subgroup analysis related to conservative or surgical treatment has been performed. Results: A total of 385 patients was included in the study, 203 (52.73 %) during Non-COVID-19 period and 182 (47.27 %) during COVID-19 period. Mean age of entire collective was 43.28 years, containing 43.9 % female patients (p=0.095). Conservative treatment was accomplished in 49 patients (12.7 % of entire collective), increasing from 9.9 % to 15.9 % during COVID-19 period (p=0.074). Laparoscopic appendicectomy was performed in 99.3 % (n=152) of operated patients during COVID-19 period (p=0.013), followed by less postoperative complications compared to reference period (23.5 % vs. 13.1 %, p=0.015). The initiation of antibiotic therapy after the diagnosis increased from 37.9 % to 53.3 % (p=0.002) during COVID-19 period regardless the following treatment modality. Antibiotic treatment showed shorter duration during pandemic period (5.57 days vs. 3.16 days, p<0.001) and it was given longer in the conservative treatment group (5.63 days vs. 4.26 days, p=0.02). The overall length of stay was shorter during COVID-19 period (4.67 days vs. 4.12 days, p=0.052) and in the conservative treatment group (3.08 days vs. 4.47 days, p<0.001). However, the overall morbidity was lower during the COVID-19 period than before (17.2 % vs. 7.7 %, p=0.005) and for conservative therapy compared to appendicectomy (2 % vs. 14.3 %, p=0.016). There was no mortality documented. Conclusions: According to our findings the COVID-19 pandemic had a relevant impact on treatment of acute appendicitis, but it was possible to maintain the traditional diagnostic and treatment pathway. Although laparoscopic appendicectomy remains a recommended procedure, the conservative treatment of uncomplicated appendicitis with excellent short-term outcome can be a safe alternative to surgery during potential new wave of COVID-19 pandemic and in the daily routine.

The short-term effect of glucosamine-sulfate, nonanimal chondroitin-sulfate, and S-adenosylmethionine combination on ultrasonography findings, inflammation, pain, and functionality in patients with knee osteoarthritis: A pilot, double-blind, randomized, placebo-controlled clinical trial.

Objectives: This study aimed to investigate the efficacy of glucosamine-sulfate (GS), nonanimal chondroitin-sulfate (naCS), and S-adenosylmethionine (SAMe) combination on ultrasound findings, inflammation, pain, and functionality in knee osteoarthritis. Patients and methods: In the prospective, randomized, double-blind, placebo-controlled pilot study conducted between August 2019 and November 2019, 120 participants (28 males, 92 females; mean age: 66.4±7.9 years; range, 42.4 to 74.5 years) were randomized at a 1:1:1 ratio to the placebo group, the first experimental group (a combination of GS, naCS, and SAMe was administered to the experimental groups. The first experimental group received 375 mg of GS, 300 mg of naCS, and 100 mg of SAMe, whereas the second experimental group received 750 mg of GS, 600 mg of naCS, and 200 mg of SAMe). Laboratory (erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor alpha, interleukin [IL]-1ß, IL-6, IL-17), clinical (Visual Analog Scale [VAS], short form health survey [SF-36], the Western Ontario and McMaster Universities Arthritis Index [WOMAC], and the Tegner Lysholm Knee Scoring Scale [TLKS]), and musculoskeletal ultrasound (MSUS) assessments were performed at baseline and after three and six months. Results: A minor increase was observed in the second experimental group after six months using ultrasonography to evaluate articular cartilage thickness (p<0.05). The investigational product's superiority in reducing osteoarthritis ultrasonographic findings was not proven. A moderately negative association was found between cartilage thickness and VAS scores at baseline (ρ=-0.36, p<0.01), while the presence of massive osteophytes on MSUS showed a low to moderate association with all clinical outcomes. There was no difference in the delta changes between groups for the VAS, TLKS, WOMAC, and SF-36. The only serum inflammatory marker outside the reference range was IL-1ß, but no significant changes were observed after six months. Conclusion: According to the results of our investigation, treatment for knee osteoarthritis should be evaluated using more objective outcomes. The most important conclusion of our study is that IP may result in a slight increase in articular cartilage thickness, which was associated with a decrease in pain intensity at baseline. Clarification of the potential influence of this combination on radiographic progression and laboratory markers of inflammation requires further exploration.

Transcultural adaptation and validation of the Serbian version of Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-Patient Satisfaction (FACIT-TS-PS) questionnaire.

OBJECTIVE: Transcultural adaptation and validation of FACIT-TS-PS questionnaire to Serbian language. METHODS: Standard forward and backward translation from English to Serbian language was performed. Pilot testing of FACIT-TS-PS was conducted on 12 patients with a confirmed diagnosis of malignant tumor. The study included 154 patients with malignant disease. The Questionnaire of Patient Satisfaction was used as a validated tool to evaluate concurrent validity of FACIT-TS-PS questionnaire. Reproducibility was tested on 30 subjects who answered the questionnaire for the second time two weeks later. RESULTS: Three FACIT-TS-PS subscales (Physician Communication, Treatment Staff Communication and Nurse Communication) demonstrated satisfactory construct validity using Cronbach's alpha, the remaining two subscales (Technical Competence and Confidence & Trust) showed high ceiling effect. Treatment Staff Communication subscale showed large floor effect. Concurrent validity was demonstrated by correlation with the two dimensions of the Questionnaire of Patient Satisfaction. Satisfactory reproducibility was demonstrated on 30 patients who filled the questionnaire for the second time two weeks after initial interview. CONCLUSION: The Serbian version of FACIT-TS-PS with the omission of Treatment Staff Communication subscale could be used as a valid instrument to assess patient and treatment satisfaction in chronically ill patients in the Serbian population. Omission of Treatment Staff Communication subscale is necessary because it contains questions not relevant for patients in Serbian healthcare system.

Psychosocial school factors and mental health of first grade secondary school students-Results of the Health Behaviour in School-aged Children Survey in Serbia.

This cross-sectional study aimed to investigate the association between psychosocial school factors and life satisfaction, symptoms of depression and psychosomatic health complaints among first grade secondary school students in Serbia. We analysed data from the 2018 Health Behaviour in School-aged Children (HBSC) study in the Republic of Serbia. Analyzed psychosocial school factors included satisfaction with school, schoolwork pressure, teacher support, classmate support and being bullied at school. Life satisfaction was assessed by the 11-step Cantril's ladder (cutoff >5). Symptoms of depression were measured by the Center for Epidemiologic Studies Depression Scale (CESD-10) and psychosomatic health complaints by using the HBSC symptom checklist. Univariable and multivariable binary logistic regression was used to determine independent predictors of students' life satisfaction, symptoms of depression and psychosomatic health complaints in the school environment, while also considering their socio-demographic characteristics and perceived family and friend support. The study included 1605 students (average age 15.26 ±0.44 years), of whom 50.3% were females. Results from the binary logistic regression analyses showed that life satisfaction was positively related to school satisfaction and classmate support, and negatively to being bullied at school. Symptoms of depression were positively associated with schoolwork pressure and being bullied at school, and negatively with teacher and classmate support. All analyzed factors of the school environment were significantly related to psychosomatic health complaints, whereby schoolwork pressure and being bullied at school were positively associated, while teacher and classmate support and satisfaction with school were negatively associated. Given the established association of psychosocial school factors with mental health, there is a need for targeted measures both at school and community level with the aim of improving social support in the school environment, reducing schoolwork burden and preventing bullying at school, potentially resulting in the overall improvement of mental health of the first grade secondary school students.

Clinical Characteristics and Treatment Experiences of Pediatric Acute Mastoiditis and Its Complications at the University Tertiary Care Center in the 10-Year Prevaccinal Period.

Introduction: We aim to provide an overview of the clinical characteristics and treatment of pediatric acute mastoiditis (AM) and its complications in the prevaccinal pneumococcal period. Materials and methods: Retrospective case series. An analysis of pediatric patients with AM treated at a university tertiary care center from 2008 to 2018 was performed. Results: The research included 121 children, and 27.3% of them had some form of complication. The mean age at presentation of AM was 3.7 years (range = 0-18 years). The most common extracranial complication of AM was a subperiosteal abscess (n = 25, 75.8%) and the most common intracranial complication was meningoencephalitis (n = 2, 6%). The most common pathogen isolated in the complicated AM was Streptococcus pneumoniae (n = 17, 51.5%). A total of 60% of patients reported antibiotic use before hospital admission, mostly third-generation cephalosporins (37.5%). There was a statistically significant difference between age group and occurrence of complications (P = .001). Females had complications more frequently than males (P = .035). There were no statistically significant differences in levels of inflammatory parameters (C-reactive protein and leukocyte count) between patients with or without complications (P = .373 and P = .124; respectively). All patients with complications of AM were surgically treated. Mortality was 0% and all children completely recovered. Conclusion: Extracranial and intracranial complications of AM required surgical treatment and extended antibiotic therapy. Inflammation parameters did not have a predictive role in identifying children with complications of AM. Further investigations will determine whether the introduction of the mandatory pneumococcal vaccine in our country has led to a reduction in the incidence of AM and its complications.

The KINETIC phase 2 randomized controlled trial of oral pamapimod-pioglitazone in non-critically ill COVID-19 inpatients.

The combination of pamapimod and pioglitazone (KIN001) has a synergetic antiviral, anti-inflammatory, and antifibrotic activity, which may prevent evolution toward COVID-19-associated severe respiratory failure. In a randomized, placebo-controlled, double-blind, phase 2, multicenter trial, 128 non-critically ill hospitalized patients with confirmed COVID-19 were treated with KIN001 or a placebo for 28 days. The proportion of patients alive and free of oxygen or respiratory support at the end of the therapy was lower than anticipated but not different in the two groups (KIN001 n = 19, 29%, placebo n = 21, 33%). 85 participants had at least one adverse event, with no difference in the number and distribution of events between the two groups. The clinical trial was stopped for futility, mainly due to a lower-than-expected incidence of the primary endpoint. KIN001 was safe and well-tolerated but had no significant effect on clinical outcome.

Personal Listening Device Use and Attitude to Noise in Relation to Depression and Anxiety among Medical Students.

Background: High levels of environmental noise may lead to psychological symptoms. The present study has hypothesized that personal listening device (PLD) use and a negative attitude to noise are significantly related to anxiety and/or depression. Methods: This is a cross-sectional study conducted on 431 six-grade students (35% male) at the Faculty of Medicine, University of Belgrade. All students completed the questionnaires related to socio-demographic data, noise/music exposure habits, behaviors related to PLD use, tinnitus, headaches, consumption of alcohol, coffee, energy drinks and cigarettes, YANS (Youth Attitude to Noise Scale), CES-D (The Center for Epidemiologic Studies Depression), and GAD-7 (Generalised Anxiety Disorder Assessment - 7 item scale) questionnaires. Results: There were 396 (91.9%) of investigated students who used PLD, with more frequent use among girls compared to boys (95.0% and 86.8%, respectively; p = 0.002). We found no significant relationship between the frequency of PLD use and depression and anxiety. However, continuous daily PLD use longer than 1 hour was significantly and positively related to depression (p = 0.006). Students with depression had a lower total YANS score compared to those without depression, indicating a more negative attitude toward noise (p = 0.042). Students with no difficulties to concentrate in noise and with a positive attitude to daily noises had about 37% lower chance to suffer from depression and anxiety, respectively. Conclusions: PLD use is common among medical students and may be associated with their mental health. Longer than 1 hour of continuous daily use of PLD may be positively related to depression. We also found a significant relationship between difficulties concentrating in noisy environments and depression, and between negative attitudes to daily noises and anxiety.

Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission.

The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.

Cost-effectiveness of the Perioperative Pain Management Bundle a registry-based study.

Introduction: The Perioperative Pain Management Bundle was introduced in 10 Serbian PAIN OUT network hospitals to improve the quality of postoperative pain management. The Bundle consists of 4 elements: informing patients about postoperative pain treatment options; administering a full daily dose of 1-2 non-opioid analgesics; administering regional blocks and/or surgical wound infiltration; and assessing pain after surgery. In this study, we aimed to assess the cost-effectiveness of the Bundle during the initial 24 h after surgery. Materials and methods: The assessment of cost-effectiveness was carried out by comparing patients before and after Bundle implementation and by comparing patients who received all Bundle elements to those with no Bundle element. Costs of postoperative pain management included costs of the analgesic medications, costs of labor for administering these medications, and related disposable materials. A multidimensional Pain Composite Score (PCS), the effectiveness measurement, was obtained by averaging variables from the International Pain Outcomes questionnaire evaluating pain intensity, interference of pain with activities and emotions, and side effects of analgesic medications. The incremental cost-effectiveness ratio (ICER) was calculated as the incremental change in costs divided by the incremental change in PCS and plotted on the cost-effectiveness plane along with the economic preference analysis. Results: The ICER value calculated when comparing patients before and after Bundle implementation was 181.89 RSD (1.55 EUR) with plotted ICERs located in the northeast and southeast quadrants of the cost-effectiveness plane. However, when comparing patients with no Bundle elements and those with all four Bundle elements, the calculated ICER was -800.63 RSD (-6.82 EUR) with plotted ICERs located in the southeast quadrant of the cost-effectiveness plane. ICER values differ across surgical disciplines. Conclusion: The proposed perioperative pain management Bundle is cost-effective. The cost-effectiveness varies depending on the number of implemented Bundle elements and fluctuates across surgical disciplines.