Tapentadol Immediate Release (IR) versus Morphine Hydrochloride for Postoperative Analgesia of Patients Undergoing Total Abdominal Hysterectomy-A Prospective Cohort Study.

Background and Objectives: This study aimed to examine the efficacy of tapentadol immediate release (IR) and morphine hydrochloride in the treatment of acute postoperative pain after total abdominal hysterectomy, as well as to examine the frequency of opioid-related side effects in observed patients. Materials and Methods: The prospective observational study was conducted over five months, and it included a total number of 100 patients. The two cohorts had different types of postoperative analgesia, and the effects were observed for 24 h postoperatively, by following the pain scores on NRS (Numerical Pain Scale), contentment with analgesia, and opioid-related side effects. Results: Statistical significance was found when assessing pain 24 h after surgery while coughing, where patients in the tapentadol IR group had significantly higher mean pain scores (p < 0.01). The subjective feeling of satisfaction with postoperative analgesia was statistically significant in the tapentadol IR group (p = 0.005). Vertigo appeared significantly more in patients from the morphine group (p = 0.03). Conclusions: Tapentadol IR (immediate release) and morphine hydrochloride are both effective analgesics used in the first 24 h after total transabdominal hysterectomy. Overall satisfaction of patients with analgesia was good. The frequency of side effects was higher in the morphine group, with statistical significance regarding the vertigo.

Modulatory effect of neoadjuvant chemotherapy on the prognosis of patients with breast cancer.

PURPOSE: To evaluate the changes in biological markers ER, PR, HER2 and Ki67 in residual tumor after surgery for locally advanced breast cancer (LABC), and also to evaluate the outcome of breast cancer patients treated with neoadjuvant chemotherapy (NAC). METHODS: 144 breast cancer patients treated with NAC at the Oncology Institute of Vojvodina, Serbia from 2011 to 2015 were included in this study. Changes in biologic markers ER,PR, HER2/neu and Ki-67 were evaluated at diagnostic core biopsy and at the final surgery tissue specimens. RESULTS: Of 144 patients pathological complete response was achieved in 17 (12%) and these were excluded from the study. Evaluated were 127 patients with residual tumor after the final surgery. A change in hormone receptor status (ER,PR) occurred in 9.4% of the patients (ER in 5%, PR in 14.5%) and HER2 status in 4.7% of the patients. ER and PR status change from negative to positive was associated with better overall survival (OS), but without statistical significance (p=0.16). Patients with conversion of HER2 status from negative to positive lived longer (65 vs 42 months). Furthermore, it was determined that HER2 change from negative to positive was associated with better OS (p=0.03). Ki-67 changed in 17 (11.8%) patients. The decrease of Ki-67 expression after NAC was associated with better outcome. Median follow up was 37.5 months (range 16.2-76.8). CONCLUSION: Changes in hormone receptor status, HER2 status and Ki-67 occurred after NAC in patients with LABC. A change from negative to positive hormone receptor status and HER2 status offers new treatment options, like endocrine therapy, and/or trastuzumab therapy for breast cancer patients. The decrease of Ki-67 expression after NAC was associated with better outcome.

MIA, S100 and LDH as important predictors of overall survival of patients with stage IIb and IIc melanoma.

PURPOSE: Melanoma represents the most severe form of skin cancer. Detection of specific tumor markers is an important step in disease diagnosis and treatment, contributing to personalized therapy. The purpose of this study was to evaluate the potential of MIA, S-100 and LDH as biomarkers for the estimation of overall survival and disease-free survival rate in patients with stage IIa, IIb vs stage IIc melanoma. METHODS: Selected biomarkers MIA, S-100 and LDH were prospectively evaluated in 80 patients with melanoma. Patients were divided in two groups according to tumor thickness. The first group (group A) consisted of patients with primary tumor thickness between 2.0 - 4.0 mm (N=40), i.e. IIa and IIb stage of disease (16 males; 40%, and 24 females; 60%). The second group (group B) consisted of 40 patients with primary tumor thickness over 4.0 mm, i.e. IIc stage, which is considered as high risk group (26 males; 65%, and 14 females 35%). Statistical analyses were performed to estimate overall survival and disease-free survival in both patient groups. RESULTS: In group A a significant difference in overall survival was found among MIA1, MIA2 and MIA3 scores, while the other 2 markers didn't show significant differences. In group B statistically significant differences in overall survival were found regarding all three biomarkers. Statistically significant differences in disease-free survival were found for MIA1 score compared to MIA2 and MIA3 scores. Also, very significant difference was detected in patients with S-100 below 0.106 and above 0.106. The same was confirmed for normal and increased LDH level in group B for disease-free survival. CONCLUSION: MIA score, S100 protein and LDH in the IIC group B patients might be useful in the prediction of overall survival and disease free survival.

Diabetes management, dietary supplements use and the effect of coronavirus pandemic on diabetes patients in Serbia: a cross-sectional study.

OBJECTIVES: Diabetes mellitus (DM) is a significant public health challenge in Serbia, mirroring the situation in other European middle-income countries. The aims of this study were to examine the disease-related characteristics and management of diabetes, as well as the prevalence of use of dietary supplements (DS) among diabetes patients in Serbia, and to analyze the effects of the coronavirus pandemic on DM patients in Serbia. METHODS: The study was carried out as an online, observational, cross-sectional study involving 422 adult diabetes type 1 (DM1) and type 2 (DM2) patients residing in Serbia. RESULTS: DM1 patients were more likely than DM2 patients to self-control glucose levels (p < 0.001). Almost one-third of DM2 patients (31.4%) did not know their HbA1c value. Polypharmacy has been reported by 9.7% of DM1 patients and 23.5% of DM2 patients. During the coronavirus pandemic increased anxiety levels for one-third of respondents was noticed. The prevalence of DS use among DM patients was very high (95.3%), with vitamin C, zinc, vitamin D and magnesium being the most commonly used. Women were more likely to use vitamin D (p = 0.001) and magnesium DS (p = 0.005) than men. Most patients (76.9%) faced limited access to healthcare services during the coronavirus pandemic with, sometimes, detrimental consequences. A significant portion of respondents (41.2%) consulted a pharmacist more often in 2021 than in previous years. CONCLUSIONS: Special caution is needed regarding the potential interactions of DS with chronic therapy. To enhance diabetes care, Serbia needs more accessible mental health support, improved diabetes education, expanded CGM availability, and carefully planned emergency healthcare measures for chronic patients.

Motives and attitudes of parents toward HPV vaccination: Results from the initial period of HPV vaccine rollout in Serbia.

Human papillomavirus (HPV) infection is one of the most common viral infections in sexually active population worldwide, and is the main cause of cervical cancer, which is the fourth most common cancer among women. Serbia ranks third in incidence and mortality rate of cervical cancer in Europe. We conducted a cross-sectional study considering parents' motivation for the HPV vaccination of their children. Statistical analysis included descriptive statistics and a logistic regression model. We found that the strongest motive was "Recommendation from paediatrician" (20.2%), followed by the attitude that HPV vaccine protects against cancers in different localization (15.4%), the motive "It is better to vaccinate a child than expose them to potential risk of HPV infection" (13.3%) and "Feeling anxiety due to a possible infection and cancer in the child" (13.1%). For those parents that vaccinated their child for some other strongest motive, reasons like "Vaccine is free of charge", "Recommendation from friends and family" and motive "My child received all obligatory vaccines, so I want to receive this one as well", were significantly more frequently selected. In the group where paediatricians' recommendation was not a motive for accepting the HPV vaccine, the largest percentage of parents (89.6%) selected motive "HPV vaccine protects against cancers in different localization" and the motive "It is better to vaccinate a child than expose them to potential risk of HPV infection" (78.1%). Paediatrician's recommendation is very important for parents' decision to vaccinate, however, other motives also influenced and had significance in making the parents' decision to vaccinate their children against HPV. Encouraging trust in public health authorities in Serbia, highlighting the advantages of the HPV vaccine and further encouraging healthcare workers to give stronger recommendations can increase the HPV vaccine uptake. Finally, we provided the basis to create more targeted messages that will empower parents to vaccinate their children.

Self-Medication Perceptions and Practice of Medical and Pharmacy Students in Serbia.

BACKGROUND: Attitudes towards conventional and complementary medicine among future healthcare professionals can impact their future pharmacotherapy practice. This study aimed to determine the prevalence and predisposing factors related to self-medication among medical and pharmacy students. METHODS: This cross-sectional questionnaire-based study was performed at the Faculty of Medicine, University of Novi Sad, Serbia, on first- and final-year students of medicine and pharmacy. The multivariate Poisson regression model with robust variance was used to identify the main predictors of self-medication. RESULTS: The overall self-medication prevalence in the past year was 81.3%. Independent risk factors for self-medication identified in the regression analysis were the final study year, housing condition, i.e., living in a leased apartment or in a student dormitory in comparison to living with parents, and cigarette consumption. The conventional drugs were the most frequently used, mostly for the symptoms of cold and pain. Final-year students had more confidence in conventional medicines than in herbal drugs and were more aware of the risks of their concomitant use. CONCLUSION: Self-medication is highly prevalent among students of medical sciences, especially among final-year students. Increased medical knowledge led to the higher awareness of the drug interaction risks.

Hallmarks of tumor-associated microglia response to experimental U87 human glioblastoma xenograft.

Glioblastoma (GBM) is one of the deadliest primary brain neoplasm, heavily infiltrated with tumor-associated microglia/macrophages (TAM), which has received a great deal of interest. Bearing in mind that the number of peripheral macrophages by the 14th day is negligible, in our study TAM were referred to as microglia. Here we evaluated histopathological characterization of TAM and kinetics of their infiltration in U87 orthotopic GBM, a commonly used model in preclinical research. To mimic different stages of GBM growth, we evaluated three-time points. Our data showed that the highest areal density of TAM was 7 days after GBM inoculation, with ability to proliferate early after initiation of GBM growth. The areal density of TAM within the tumor correlated with GBM growth and proliferation. Moreover, microglia underwent substantial morphological changes upon exposure to GBM cells. A transition from ramified morphology in peritumoral area to ameboid shape with larger soma and shortened, thick branches in the tumor core was observed. Higher areal fraction of blood vessels also correlated with the areal density of TAM. Given these pro-invasive features of microglia, this GBM model represents a good basis for further testing microglia as a target and new strategy to fight with.

Increase and Change in the Pattern of Antibiotic Use in Serbia (2010-2019).

The aim of this study was to determine and describe trends in antibiotics utilization in Serbia over a ten-year period. Data were retrieved from publicly available annual reports (2010-2019). The results were expressed as Defined Daily Dose (DDD) per 1000 inhabitants per day (DID). All calculations were performed using the DDD values for the 2020 Anatomical Therapeutic Chemical/Defined Daily Dose (ATC/DDD) version for each year of the study, to account for the DDD changes during the study period. Antibiotics were classified using the WHO Access, Watch, Reserve (AWaRe) classification. Total utilization of antibacterials for systemic use increased from 17.25 DID in 2010 to 28.65 DID in 2019. A statistically significant increasing trend in the use of the Watch category antibiotics was observed. A tendency towards use of broad-spectrum antibiotics, apparent by a statistically significant increase in the rate of utilization of broad-spectrum macrolides, quinolones and third-generation cephalosporins vs. narrow-spectrum ones, as well as a significant increasing trend in the use of quinolones was identified. Total antibiotic utilization was found to be well above the European average. Several specific problem areas were identified, which requires further efforts to improve antibiotic prescribing. The present study provides the information needed to facilitate antibiotic stewardship in Serbia further and proposes specific interventions to optimize antibiotic use in Serbia.

COVID-19 vaccines and cancer patients: acceptance, attitudes and safety.

PURPOSE: Recommendations and guidelines consider cancer patients a high-priority population for COVID-19 immunization. Vaccination process in Serbia began in January 2021 with four available vaccines. We have conducted a cross-sectional study investigating cancer patients' acceptability of anti SARS-COV2 vaccines. METHODS: The study included 767 patients with solid and hematologic malignancies treated at the Oncology Institute of Vojvodina, Serbia. During July and August 2021 patients filled in an individual paper questionnaire on anti SARS-COV2 vaccination acceptance, preferences, side effects and information origin. Data on treatment phase, diagnosis and treatment was collected from electronic health records. RESULTS: During the first six months of vaccination campaign in Serbia 41% (320/767) of the investigated oncology patients received COVID-19 vaccines. The median age of vaccinated patients was 65 years (28-84). Most of them (75%) were in active treatment of cancer. Half of the unvaccinated patients (52%) wish to get vaccinated after the end of their cancer treatment. Around 10% of the patients definitely refused vaccination. The majority of information on COVID-19 vaccines cancer patients got from their oncologist, television and newspapers. Side effects were reported by 10.93% of the patients after the first dose and 13,31% after the second dose. No serious side effects were reported. CONCLUSION: We have confirmed that patients are reluctant of receiving vaccine due to fear of side effects, especially during the active cancer treatment. However, real-world evidence and clinical trials data have gathered enough evidence to reassure any doubts of the patients and their oncologists on safety and efficacy of anti SARS-COV2 vaccines.

Trend analyses of breast cancer incidence and mortality in Vojvodina.

PURPOSE: Breast cancer is the most common type of malignant tumor in women and one of the most significant public health problems in the world. The purpose of this work was to determine breast cancer epidemiology in the Autonomous Province of Vojvodina in a 20-year period (1993 to 2012) by determining breast cancer incidence and mortality in female population and analyzing the trend in the specified period. METHODS: The research involved the population of women in Vojvodina in the period from 1993 to 2012. Data were obtained from the Register for malignant neoplasms of Vojvodina. Incidence and mortality trends were analyzed by a joinpoint regression analysis. RESULTS: A total of 20,242 cases of breast cancer were registered in the observed period. Standardized incidence ratio in 2012 was 71.2/100,000. The trend of incidence increased with an average annual percentage of growth of 2.10. A total 10,062 deaths due to breast cancer were documented. Standardized incidence ratio in 2012 was 28.6/100,000. An increase of mortality rate by 1.70% per year was recorded in the period from 1992 to 2006 and a decline in the mortality rate by 1.56% was noticed afterwards. The highest percentage of deaths due to breast cancer was recorded in a group aged 60-69 years (26.7%).

Consumer willingness to pay for a pharmaceutical disposal program in Serbia: A double hurdle modeling approach.

Proper collection and disposal of pharmaceutical waste from households can reduce the negative influence of medicines on the environment. The aim of this paper is to examine the current methods of disposal of unused medicines from households, as well as the willingness of Serbian residents to participate and bear the costs of an organized collection program. Moreover, this research aims to define factors contributing to an individual's willingness to participate and pay for a medicine collection program. The survey included randomly selected patients older than 18 years visiting private pharmacies in the four largest Serbian cities. The questionnaire included information regarding the presence of unwanted medicines within the household, general medicine disposal practices, the likelihood to participate in a medicine take-back program, willingness to pay for a medicine disposal program (per prescription and per visit), importance to the environment, and demographic variables from participants. Approximately 80% of surveyed respondents are very or somewhat likely to participate, however less than half of the respondents are willing to pay for the collection of their unused medicines. The factors that influenced willingness to participate are environmental awareness and income, while the factors affecting willingness to pay, are previously received advice about proper disposal, education level, number of unwanted medicines in the household and gender. The majority of Serbian people dispose unused medicines improperly, mostly into household garbage. Well-organized and easily accessible collection programs are essential in order to enable the general public to return unused medicines for proper disposal.

Increasing frequency of soft tissue sarcomas in Vojvodina - comparison with the literature.

BACKGROUND: Soft tissue sarcomas (STS) represent 1% of all malignant lesions. In this study the authors analyzed the incidence of STS in Vojvodina (the north region of Serbia) in the period from 1985 to 2009. A number of studies conducted worldwide indicate that STS incidence rates are tending to increase. MATERIALS AND METHODS: On the basis of data from the Cancer Registry of Vojvodina, age standardized STS incidence rates were established as well as their linear trend, with data on histological structure, age, gender and STS distribution at specific locations. RESULTS: The total number of registered patients was 1,308. Average age standardized rate was 1.90/100,000 per year. The investigated period showed a slight increase in the incidence rate (average annual percent increase=0.77%). The most frequent histological type was sarcoma not otherwise specified-NOS (27%), followed by leiomyosarcoma (21%), liposarcoma (14%), rhabdomyosarcoma (11%) and malignant fibrous histiocytoma (9%). The male/female ratio was 0.73:1. Every fifth patient was younger than 39. CONCLUSIONS: Comparison among eight international STS epidemiology studies show that the incidence rate range is between 1.4/100,000-5.0/100,000, though our finding is closer to the lower limit. Furthermore, the incidence rate increase was lower than that characteristic for the half of the analyzed studies. A partial explanation for that should be looked for among changes in diagnostic criteria and STS classifications.

Knowledge and attitudes of health care workers from the Primary Health Centre in Indija, Serbia on professional exposures to blood-borne infections.

Exposure to blood-borne infections (HIV, hepatitis B, hepatitis C) poses a serious risk to health care workers (HCWs). The aim of this cross-sectional study was to determine the level of knowledge and attitudes on occupational exposure in primary health care. In 2009, a total of 100 health care workers from the Primary Health Care Centre in Indija, Autonomous Province of Vojvodina, Serbia were included in the study. The results suggested that the health care workers who participated in the survey possess basic knowledge about blood-borne virus transmission routes. Most incorrect answers were related to the transmission of blood-borne viruses by tears, saliva, urine and stool. This study also demonstrated that health workers tend to unrealistically estimate the risk of HIV infections. As for the level of education about the prevention and control of blood-borne infections, 49 % of the participants had never had any education on this topic, while 22 % had been educated during the last five years. Around 75 % consider education on blood-borne infection and protective measures at work unnecessary.

Information sources for Serbian women on cervical carcinoma risk factors.

BACKGROUND: The epidemiological situation regarding cervical carcinoma in Serbia is rather unfavorable and one of contributing factors is the insufficient interest of women concerning the risk factors responsible for occurrence of this disease. The aim of this study was to determine the sources of relevant information for women METHODS: An anonymous questionnaire was used for questioning of patients, students and women undergoing systematic examinations. There were 600 women in total in 2006, 2009 and 2010, and the data were statistically processed by the χ 2 test with Yates correction and the Fisher test. RESULTS: When observed for certain groups of tested women, and summed up for all three periods, there was a statistically significant difference for the answer "without any knowledge" (p=0.0001). When observed for certain years and summed up for all three tested groups, there was a statistically significant difference in answers regarding the source of information, the "doctor" (p=0.0011), "media" (p=0.0349) and "encyclopedia-internet" (p=0.0136). CONCLUSION: The media are a dominant source of information for women on risk factors for cervical cancer. The significance of the Internet increased during the three observed periods, while the students considered themselves least informed of all concerning risk factors.

[Linear trend in patients with ovarian cancer in period 2001-2008 at Oncology Institute of Vojvodina].

INTRODUCTION: Ovarian cancer is one of the leading health problems, as it is the underlying cause of disease and deaths of a large number of women around the world. Postmenopausal female population, in whom ovarian carcinoma is most often diagnosed in advanced stages of the disease, is primarily affected. MATERIAL AND METHODS: We used data from Hospital Registry for Malignant Neoplasms at Oncology Institute of Voijvodina for the period from 2001 to 2008, according to which 422 cases of ovarian carcinoma were reported. The obtained data were classified into three groups according to FIGO classification of ovarian malignant neoplasms. The statistical assessment of data employed the method of linear trend and tests of statistical significance (t-test). RESULTS: The results of our study showed that most cases of diagnosed disease were advanced forms of ovarian cancer, FIGO stages II and IV. The linear trend of the reported cases in stage 1 for the period 2001/2008 showed a descending trend. According to the processed data, in the same period of time, stage II showed an ascending trend, while stages III and IV described together showed a moderate ascending linear trend. CONCLUSION: A vast majority of cases of ovarian cancer are detected in advanced stages of the disease, which is at the same time the group with the worst prognosis. Special attention should be paid to the group of patients with positive family history, as well as the presence of BRCA 1 and BRCA 2 genetic mutations. Currently existing diagnostic procedures have not given good results individually in terms of high sensitivity for diagnosis of early stages.