Trends in oesophageal cancer mortality in Montenegro, 1990-2018.

BACKGROUND: Oesophageal cancer (OC) is a significant public health issue, despite the decreasing trends in OC mortality rates observed globally in the past decades. The objective of our study is to analyze the pattern of OC mortality in Montenegro between 1990 and 2018 and contribute to the development of a national long-term strategy for the prevention and control of this malignancy. METHODS: The data on OC death cases in Montenegro between 1990 and 2018 were collected. The mortality rates were standardized according to the World Standard Population. The Joinpoint, Linear and Poisson regressions were applied to analyze the OC mortality trend. RESULTS: Joinpoint regression analysis showed an increase in death rates for men and the overall level which were not statistically significant. However, the number of cases increases significantly with an average annual percentage change (AAPC) increase of 2.6% for the overall level [AAPC (95% CI)=2.6 (1.0-4.2); P = 0.002] at the expense of the increase in men, which on average was 2.6% annually [AAPC (95%CI) = 2.6 (1.2-4.1); P = 0.001]. The age groups 55-64 and 65-74 have the highest percentage of deaths cases from OC with 30.6% and 31.4%, respectively. CONCLUSION: Montenegro has witnessed a recent increase in the number of deaths from OC, although the mortality rates remain stable. National strategies to further reduce mortality rates for OC are necessary. Individuals aged 55-64 and 65-74 need specific attention during the ongoing monitoring of this cancer.

Trends in gastric cancer mortality in Montenegro, 1990 - 2018: joinpoint regression.

Background Gastric cancer (GC) remains a significant global public health problem, despite the decreasing trends in GC mortality rates in the last five decades. Our study aimed to examine the pattern of GC mortality in Montenegro between 1990 and 2018 and to contribute to the future designing a national long-term strategy for the control and prevention of GC. Methods Gastric cancer mortality data in Montenegro from 1990 to 2018 were collected. Mortality rates were age-standardized to the World Standard Population for estimating both the overall and gender-specific trends. The joinpoint regression model was used to assess GC mortality and identified significant changes in the linear time trend. Linear and Poisson regressions were also applied for additional trend analyses. Results Joinpoint regression reveals a statistically significant decrease in the age-standardized rate for the overall level, on average by 1.4% per year (AAPC (95% IP)= -1.4 (-2.4)-(-0.4); P= 0.007), which was due to a decrease in the age-standardized rate in men with an average annual change of -1.8% (AAPC (95% IP)= -1.8 (-2.9)-(-0.6); P=0.003), while in women the rates were stable (p=0.565). The results for age groups indicate that a decline was registered at the overall level, and among men, as a consequence of the trend of decreasing age-specific rates for the age group 55-64 on average annually by 2% among men (AAPC (95% IP)= -2 ((-3.8)-(-0.1)); P=0.035), and for the overall level (AAPC (95% IP)= -2 ((-3.7)-(-0.3)); P=0.026). Conclusions Our findings indicate a noteworthy decline in age-standardized overall GC mortality rates among men in Montenegro, while rates for women have remained constant. National strategies to further reduce mortality rates for GC are necessary.

Risk Factors for Potential Drug-Drug Interactions in Outpatients with Dyslipidemia.

Background: Patients with dyslipidemia are usually multimorbid and require polypharmacy. Therefore, it is important to identify potential drug-drug interactions (pDDIs) in time to prevent their consequences. We aimed to identify and analyze risk factors contributing to their occurrence to guide health professionals. Methods: A prospective cross-sectional study of 216 outpatients with dyslipidemia was conducted from May 2021 to April 2022 in Podgorica, the capital of Montenegro. pDDIs were identified using Medscape, Epocrates, and Drugs online interaction checkers. Multivariate regression analysis was performed to evaluate the potential predictors of interactions. Results: pDDIs were detected in 212 (98.1%) participants, whereas pDDIs with high clinical significance were detected in 25.46%, 40.74%, and 58.8% of subjects by Drugs, Epocrates, and Medscape, respectively. Polypharmacy emerged as a risk factor for the occurrence of pDDIs in all three checkers in each category of clinical significance. The use of non-steroidal anti-inflammatory drugs and antiplatelet drugs contributes to the incidence of severe pDDIs B=1.014, 95%CI 0.681-1.346, P=0.000 and B=0.492, 95%CI 0.286-0.698, P=0.000, by Epocrates and Medscape respectively. The number of prescribers per patient was a protective factor against moderate pDDI B= -0.858, 95%CI -1.572-(-0.144), P=0.019 and B= -0.956, 95%CI -1.671-(-0.241), P=0.009, by Medscape and Epocrates, respectively, but a risk factor for the occurrence of minor pDDIs B=0.373, 95%CI 0.033-0.712 P=0.032 and B=0.143, 95%CI 0.042-0.244, P=0.006, by the same checkers. Conclusion: Knowledge of the risk factors contributing to the occurrence of pDDIs is important for the development and implementation of strategies for their prevention, and given the high prevalence of dyslipidemia, understanding these factors seems crucial nowadays.

Rare benign lung tumours presenting with high clinical suspicion for malignancy: a case series and review of the literature.

INTRODUCTION: Incidentally discovered lung nodules can be worrisome for both the patient and their physicians. Although 95% of solitary lung nodules are benign, it is important to distinguish which nodules have high clinical suspicion for malignancy. Existing clinical guidelines do not apply to patients with signs and symptoms related to the lesion and with an increased baseline risk of lung cancer or metastasis. This paper highlights the vital role of pathohistological analysis and immunohistochemistry in the definitive diagnosis of such incidentally discovered lung nodules. MATERIAL AND METHODS: The three cases presented were selected based on their similar clinical presentations. A review of the literature was performed using the online database PubMed, for articles published in the period between January of 1973 to February of 2023 using the following medical subject headlines: "primary alveolar adenoma," "alveolar adenoma," "primary pulmonary meningioma," "pulmonary meningioma," and "pulmonary benign metastasizing leiomyoma." Results (Case Series). The case series consists of three incidentally discovered lung nodule(s). Although they presented with high clinical suspicion for malignancy, detailed workup confirmed the diagnosis of three rare benign lung tumours: primary alveolar adenoma, primary pulmonary meningioma, and benign metastasizing leiomyoma. CONCLUSIONS: Clinical suspicion for malignancy in the presented cases arose from previous and current medical history of malignancy, family history of malignancy, and/or specific radiographic findings. This paper highlights the need for a multidisciplinary approach in the management of incidentally discovered pulmonary nodules. Excisional biopsy and pathohistological analysis remain the gold standard in confirming the presence of a pathologic process and determining the nature of the disease. Common features of the diagnostic algorithm utilized among the three cases include multi-slice computerized tomography, excisional biopsy via atypical wedge resection (if the nodule is peripherally located), and lastly, pathomorphological analysis using haematoxylin and eosin staining and immunohistochemistry.

Relationship between insulin-like growth factor-1, insulin resistance and metabolic profile with pre-obesity and obesity in children.

OBJECTIVES: Childhood obesity is a serious medical condition with alarmingly high rates worldwide. There is controversy regarding the relationship between insulin-like growth factor-1 (IGF-1) and pediatric obesity. We investigated the relationship between IGF-1, insulin resistance and metabolic profile with childhood pre-obesity/obesity. METHODS: The study involved 201 children aged 7-15 years, divided in three groups according to their nutritional status (International Obesity Task Force criteria): normal-weight (n=84), pre-obese (n=82), obese (n=35). Laboratory IGF-1, insulin, fasting blood glucose (FBG), lipid profile, alanine-aminotransferase (ALT), uric acid (UA), anthropometric and body composition parameters were analyzed. Body mass index and IGF-1 standard deviation score (SDS), waist-to-height ratio (WtHR) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score were calculated. RESULTS: Pre-obese/obese children had significantly higher IGF-1 SDS, FBG, insulin, HOMA-IR, UA, ALT, triglycerides, and lower high-density lipoprotein cholesterol (HDL-c); obese group had higher WtHR and low-density lipoprotein cholesterol (LDL-c) compared to controls (p<0.05). In obese group, IGF-1 SDS was positively correlated with fat free/muscle mass, total body water (p<0.05) and negatively correlated with LDL-c (p<0.05). In pre-obese/obese HOMA-IR and insulin were positively correlated with age, total body fat (TBF) (p<0.05) and negatively correlated with HDL-c (pre-obese) (p<0.05). Multivariate ordinal logistic regression analyses showed that IGF-1 SDS (OR=1.94; 95%CI: 1.21-3.11), TBF (OR=1.37; 95%CI: 1.21-1.54) were predictors of nutritional status (p<0.001). FBG (OR=42.39; 95%CI: 2.31-77.2) and UA (OR=1.03; 95%CI: 1.01-1.05) were predictors of IR (p<0.001). CONCLUSIONS: IGF-1 SDS and TBF were predictors of nutritional status. Further studies are required to clarify the role of IGF-1 in pathophysiology of obesity and its comorbidities.

Association between inflammation, oxidative stress, vitamin D, copper and zinc with pre-obesity and obesity in school children from the city of Podgorica, Montenegro.

Background Childhood obesity is a serious health condition with increasing rates worldwide. The aim of this study was to investigate the association between inflammation, oxidative stress, vitamin D, copper and zinc in pre-obese and obese children compared to controls. Methods The study involved 202 children aged 7-15 years (63.9% boys), randomly chosen from 10 elementary schools in Podgorica, Montenegro. Participants were divided into three groups according to their nutritional status (International Obesity Task Force [IOTF] criteria): normal-weight (42.1%), pre-obese (40.6%) and obese (17.3%). Serum biochemical analyses were performed (C-reactive protein [CRP], retinol-binding protein [RBP], total antioxidant status [TAS], total vitamin D [VD], copper and zinc). Results Serum TAS and CRP concentrations were higher in pre-obese and obese children compared to controls (p < 0.001). Serum VD concentrations were lower in pre-obese and obese children compared to their normal-weight peers (p = 0.027 and p = 0.054, respectively). Copper, zinc and RBP concentrations did not differ significantly among the groups (p > 0.05). In pre-obese and obese children, a positive correlation was found between CRP and copper (r = 0.305, p = 0.011 and r = 0.440, p = 0.013, respectively), and TAS and RBP (r = 0.528, p < 0.001 and r = 0.434, p = 0.015, respectively). Standard regression analyses showed that CRP and TAS increase (p < 0.001) whereas VD decreases (p = 0.011) with the body mass index (BMI). Conclusions We show that pre-obesity and obesity in childhood are positively associated with oxidative stress and inflammation, and inversely associated with VD status. Copper and zinc concentrations were not associated with excess fat in children.

Lung cancer mortality in Montenegro, 1990 to 2015.

AIM: To analyze the trend of lung cancer mortality in Montenegro from 1990 to 2015. METHODS: Data on lung cancer mortality were collected from death certificates obtained from the Statistical Office of Montenegro for the period 1990-2009 and the Institute for Public Health for the period 2010-2015. Population data were obtained from the Statistical Office of Montenegro. Rates were age-standardized to the World Standard Population, and mortality trends were analyzed with the joinpoint regression. RESULTS: In 2015, lung cancer accounted for 5.44% of all deaths and 22.92% of all cancer deaths. It was the leading cause of all cancer deaths and the third-leading cause of all deaths. A joinpoint was observed in 2004 in women and in the entire population, and in 2005 in men. The overall mortality rates increased from 1990 to 2004 by an average of 3.91% per year and decreased from 2004 to 2015 by an average of 1.95%; which in the entire observed period resulted in an average increase of 1.3% per year. A particularly strong growth rate was observed in women, even 7.14% in the period from 1990 to 2004. CONCLUSION: The observed increase in lung cancer mortality warrants improved tobacco control.

Increased Serum Level of IGF-1 Correlates With Better Cognitive Status in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Prevalence of cognitive function decline in end stage renal disease (ESRD) patients undergoing hemodialysis is higher than in the general population. We analyzed risk factors for cognitive function decline in those patients. This study included 93 ESRD patients undergoing hemodialysis two or three times a week in three centers for hemodialysis in Montenegro. The cognitive status of patients was assessed using the mini mental score examination (MMSE) test. All 93 patients have been divided into three groups according to the results of MMSE. Patients in the first group had severe cognitive impairment and MMSE score below 17 (26.88%), patients in the second group with MMSE score 18-23 had moderate cognitive impairment (40.86%) and third group of patients have MMSE >24 and no cognitive impairment (32.26%). There were no significant differences between groups for gender, smoking habits and level of parathyroid hormone. Level of schooling was significantly different between groups of patients (P < 0.001). Laboratory markers observed in this study with significant differences between groups were: IGF 1, IGFBP 3, erythrocytes and hemoglobin (P < 0.001, P = 0.004, P < 0.001, P = 0.002, respectively). IGF 1 proved to be of great importance for evaluating cognitive status in our study. This marker was statistically different between groups (P < 0.001) and Tukey post hoc analysis showed significant differences between all three groups (first and second group P = 0.045, second and third group P = 0.015, first and third group P < 0.001). Our data suggest that IGF 1 can be considered as novel biomarker for assessment of cognitive functioning in CKD patients, which can be of huge clinical importance.

Determination of Microelements in Human Milk and Infant Formula Without Digestion by ICP-OES.

The concentrations of zinc (Zn), iron (Fe) and copper (Cu) in both human milk and infant formula were determined using a new sample preparation method, by inductively coupled plasma - optical emission spectometry (ICP-OES) and flame atomic absorption spectrometry (FAAS). Human milk samples were diluted in ultrapure water. The infant formula of powder samples (suitable for an infant 1-6 months of age) and standard reference material (SRM-1849) were analyzed in parallel. The results have shown that FAAS method was more sensitive for Fe determination in human milk while ICP-OES was more sensitive for both Zn and Cu detection. The limit of quantification for both Zn and Cu was 5 µg L-1 and 10 µg L-1 for Fe and the recovery for Zn, Fe and Cu was ranged from 90% to 94%, 97% to 103% and 90% to 102%, respectively. Mean concentrations of Zn, Fe, and Cu in human milk samples were 5.35, 0.47 and 0.83 mg L-1, respectively while these values in infant formula were ranged from 3.52-4.75 mg L-1, 3.37-4.56 mg L-1 and 0.28-0.41 mg L-1, respectively. Despite the sample complexity, the proposed method using dilution of milk samples with water was simple, rapid, effective and accurate. ICP-OES was a better method for Zn determination while FAAS was a better method for Fe determination. In the case of Cu both methods were comparable.

RECENT INCIDENCE OF TYPE 1 DIABETES MELLITUS IN MONTENEGRO: A SHIFT TOWARD YOUNGER AGE AT DISEASE ONSET.

In the last several decades, a great number of studies have pointed to a dramatic increase of type 1 diabetes mellitus (T1DM) incidence in the whole world, especially in younger age groups. Therefore, the aim of the study was to assess changes in the age distribution at onset of T1DM in Montenegro children aged < 15 years during a 15-year period (1997-2011) and analyze the seasonal pattern. Primary case ascertainment was from diabetes register, secondary and tertiary independent data sources were hospital case records and register of children receiving free test stripes in pharmacy. Standardized incidence rates were calculated using the Poisson regression. Case ascertainment was 100% complete using the capture-recapture method. The mean age-standardized incidence was 18.6/100,000 (95% CI: 13.0-24.1) from 2007 to 2011 compared with 13.4/100,000 95% CI, 11.5-15.5) from 1997 to 2006. The incidence of T1DM increased predominantly in younger age groups. Relative increase of incidence per 5-year period was largest in boys aged 0-4 and 5-9 years: 64.7% (95% CI: 20.6-10.7; p = 0.004) and 52.8% (95% CI: 16.9-88.8; p = 0.004), respectively. Seasonality in monthly case counts of T1DM was apparent. The greatest number of cases were diagnosed during autumn and winter months. In conclusion, the onset of T1DM was found to occur at an ever younger age in Montenegro children. Our results indicated a seasonal pattern of the disease onset.

Assessment of Ecological Risk of Heavy Metal Contamination in Coastal Municipalities of Montenegro.

Assessment of heavy metal concentrations in the soil samples of urban parks and playgrounds is very important for the evaluation of potential risks for residents, especially children. Until recently, there has been very little data about urban parks pollution in Montenegro. To evaluate the sources of potential contamination and concentration of heavy metals, soil samples from coastal urban parks and kindergartens of Montenegro were collected. Based on the heavy metal concentrations, multivariate analysis combined with geochemical approaches showed that soil samples in coastal areas of Montenegro had mean Pb and Cd concentrations that were over two times higher than the background values, respectively. Based on principal component analysis (PCA), soil pollution with Pb, Cd, Cu, and Zn is contributed by anthropogenic sources. Results for Cr in the surface soils were primarily derived from natural sources. Calculation of different ecological contamination factors showed that Cd is the primary contribution to ecological risk index (RI) origins from anthropogenic, industry, and urbanization sources. This data provides evidence about soil pollution in coastal municipalities of Montenegro. Special attention should be paid to this problem in order to continue further research and to consider possible ways of remediation of the sites where contamination has been observed.

Rising incidence of childhood type 1 diabetes in Montenegro.

Introduction: The incidence rate of childhood type1 diabetes continues to rise across Europe by an average of approximately 3­4% per annum. Objective: The aim of this study was to examine incidence and trends of type 1 diabetes in children aged 0­14 years in Montenegro from 1997 to 2011. Methods: This was a prospective study. Primary case ascertainment was from a diabetes register, and a secondary independent data source was from hospital notifications. Case ascertainment was 100% complete using the capture-recapture method. Standardized incidence rates were calculated and trends estimated using the Poisson regression. Results: A total of 298 children (157 boys and 141 girls) were diagnosed with type 1 diabetes before 15 years of age during 1997­2011. The mean age-standardized incidence was 15.0/100,000 persons (95% CI: 12.3­17.6) during this period, increasing from 11.7/100,000 in 1997 to 18.8/100,000 in 2011. The agespecific rates per 100,000 persons per year were 10.7, 17.2, and 18.2 at ages 0­4 years, 5­9 years, and 10­14 years, respectively. A significant linear trend in incidence (p = 0.002) has been observed over time, with an average annual increase of 4.2%. The increase in incidence was present in both genders, with the largest relative increase in the 0­4 years age group for boys (11.0%; p = 0.006). Conclusion: The incidence of type 1 diabetes in Montenegro children continues to increase. We need further monitoring and additional research in order to explain the cause.