Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data: A Multinational Network Cohort Study

INTRODUCTION: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. METHODS: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. RESULTS: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. CONCLUSION: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date

Phenotype Algorithms for the Identification and Characterization of Vaccine-Induced Thrombotic Thrombocytopenia in Real World Data:A Multinational Network Cohort Study

INTRODUCTION: Vaccine-induced thrombotic thrombocytopenia (VITT) has been identified as a rare but serious adverse event associated with coronavirus disease 2019 (COVID-19) vaccines. OBJECTIVES: In this study, we explored the pre-pandemic co-occurrence of thrombosis with thrombocytopenia (TWT) using 17 observational health data sources across the world. We applied multiple TWT definitions, estimated the background rate of TWT, characterized TWT patients, and explored the makeup of thrombosis types among TWT patients. METHODS: We conducted an international network retrospective cohort study using electronic health records and insurance claims data, estimating background rates of TWT amongst persons observed from 2017 to 2019. Following the principles of existing VITT clinical definitions, TWT was defined as patients with a diagnosis of embolic or thrombotic arterial or venous events and a diagnosis or measurement of thrombocytopenia within 7 days. Six TWT phenotypes were considered, which varied in the approach taken in defining thrombosis and thrombocytopenia in real world data. RESULTS: Overall TWT incidence rates ranged from 1.62 to 150.65 per 100,000 person-years. Substantial heterogeneity exists across data sources and by age, sex, and alternative TWT phenotypes. TWT patients were likely to be men of older age with various comorbidities. Among the thrombosis types, arterial thrombotic events were the most common. CONCLUSION: Our findings suggest that identifying VITT in observational data presents a substantial challenge, as implementing VITT case definitions based on the co-occurrence of TWT results in large and heterogeneous incidence rate and in a cohort of patints with baseline characteristics that are inconsistent with the VITT cases reported to date. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40264-022-01187-y

Relationship between fluoride intake in Serbian children living in two areas with different natural levels of fluorides and occurrence of dental fluorosis

The amount of fluoride present naturally in drinking water is highly variable, being dependent upon the individual geological environment from which the water is obtained. Chronic exposure to exceeding fluoride doses induces set of toxic effects, i.e. fluorosis. The aim of this study was to examine fluoride content in water and in the most frequently used vegetables, potato and bean, grown in two different Serbian regions. Le. control region (Valjevo) and high naturally occurring fluoride region (Vranjska Banja), and moreover, to correlate estimated daily intake with dental fluorosis occurrence as an adverse effect of fluoride exposure of schoolchildren in Serbia. Study confirmed significant difference in fluoride content in water, potato and bean, consumed by 12-year-old children in two investigated municipalities. Results of the study indicated positive and statistically significant correlation between daily intake of fluoride and dental fluorosis level in the fluorotic municipality of Vranjska Banja (r = 0.61: p = 0.000017). Obtained relationship could be evaluated by means of binary logistic regression analysis, whereas probability for fluorosis occurrence could be predicted using the following equation: fluorosis occurence (%) (34.852 x C-water - 12.644 x C-potato - 9.362 x C-bean - 7.673) x 100 (Chi-square (3) = 33.033; p lt 0.001)

Methicillin-resistant Staphylococcus aureus nasal cariage among hospitalized patients and healthcare workers in the Clinical center of Serbia

The aim of the present study was to provide the first comprehensive analysis of methicillin-resistant Staphylococcus aureus (MRSA) carriage among patients and healthcare workers (HCWs) in the largest healthcare facility in Serbia. Specimens from anterior nares obtained from 195 hospitalized patients and 105 HCWs were inoculated after broth enrichment onto chromogenic MRSA-ID medium. In total, 21 of 300 specimens yielded MRSA. Among hospitalized patients, 7.7% were colonized with MRSA, and 5.7% HCWs were colonized with MRSA. Five out of 21 (23.8%) tested MRSA strains were classified as community-associated MRSA (CA-MRSA), and four of them were isolated from HCWs. The remaining 16 MRSA strains had characteristics of healthcare-associated MRSA (HA-MRSA), and two of them were isolated from HCWs. The HA-MRSA strains isolated from HCWs were indistinguishable from HA-MRSA of the same cluster isolated from patients. This finding reveals the circulation of HA-MRSA strains between patients and HCWs in the Clinical Center of Serbia. [Projekat Ministarstva nauke Republike Srbije, br. ON 175039

Hesperetin—Between the Ability to Diminish Mono- and Polymicrobial Biofilms and Toxicity

Hesperetin is the aglycone of citrus flavonoid hesperidin. Due to the limited information regarding hesperetin antimicrobial potential and emerging need for novel antimicrobials, we have studied its antimicrobial activity (microdilution assay), antibiofilm activity with different assays in two models (mono- and polymicrobial biofilm), and toxicity (MTT and brine shrimp lethality assays). Hesperetin inhibited growth of all Candida isolates (minimal inhibitory concentration, MIC, 0.165 mg/mL), while it’s inhibitory potential towards Staphylococcus aureus was lower (MIC 4 mg/mL). Hesperetin (0.165 mg/mL) reduced ability of Candida to form biofilms and moderately reduced exopolysaccharide levels in biofilm matrix. Effect on the eradication of 24 h old C. albicans biofilms was promising at 1.320 mg/mL. Inhibition of staphylococcal biofilm formation required higher concentrations of hesperetin (C. albicans-S. aureus biofilm was significantly inhibited with the lowest examined hesperetin concentration (1 mg/mL) in crystal violet and CFU assays. Hesperetin toxicity was examined towards MRC-5 fibroblasts (IC50 0.340 mg/mL) and in brine shrimp lethality assay (LC50 > 1 mg/mL). Hesperetin is efficient in combating growth and biofilm formation of Candida species. However, its antibacterial application should be further examined due to the cytotoxic effects provoked in the antibacterial concentrations

Landslide susceptibility zonation in the Kolubara River Basin (western Serbia) - analysis of input data

According to estimates, 25% of the territory of the Republic of Serbia is affected by landslide processes. In the spring, when snowmelt is accompanied by the maximum amount of precipitation, a great number of landslides have been activated within the territory of Serbia. The year 2006 had a particularly large number of registered landslides accompanied by huge material damages. Because a landslide data base for the territory of Serbia does not exist, it is very difficult to carry out the regular assignment of land use and to make a spatial development strategy. This imposed a need for methodological development of landslide hazard zonation (LHZ) for the territory of Serbia. The Kolubara River Basin was selected as an area with a significant number of landslides occurence. The spatial distribution of landslides is a result of the interaction of many parameters. Landslide susceptibility zones in the Kolubara River basin were identified by heuristic analysis of landslide causal factors - local topography, morphological and geological setting, and the existing and past landslides identified the study area. Based on the results obtained in this study, it was found that 243.75 km(2) or 6.69% of the total area was prone to landsliding. The results can be implemented as a base for development of LHZ model for the overall territory of Serbia, and will represent the first step for compilation of a landslide data base

Landslide susceptibility zonation in the Kolubara River Basin (western Serbia) - analysis of input data

According to estimates, 25% of the territory of the Republic of Serbia is affected by landslide processes. In the spring, when snowmelt is accompanied by the maximum amount of precipitation, a great number of landslides have been activated within the territory of Serbia. The year 2006 had a particularly large number of registered landslides accompanied by huge material damages. Because a landslide data base for the territory of Serbia does not exist, it is very difficult to carry out the regular assignment of land use and to make a spatial development strategy. This imposed a need for methodological development of landslide hazard zonation (LHZ) for the territory of Serbia. The Kolubara River Basin was selected as an area with a significant number of landslides occurence. The spatial distribution of landslides is a result of the interaction of many parameters. Landslide susceptibility zones in the Kolubara River basin were identified by heuristic analysis of landslide causal factors - local topography, morphological and geological setting, and the existing and past landslides identified the study area. Based on the results obtained in this study, it was found that 243.75 km(2) or 6.69% of the total area was prone to landsliding. The results can be implemented as a base for development of LHZ model for the overall territory of Serbia, and will represent the first step for compilation of a landslide data base

Fluoride in drinking water and dental fluorosis

In this study we determined the fluoride content in drinking water and hair of 12-year-old schoolchildren from different Serbian municipalities, i.e. Valley, Veliko Gradiste, Kacarevo and Vranjska Banja. The analyses were performed using composite fluoride ion-selective electrode. Average fluoride levels were 0.10, 0.15, 0.79 and 11 ppm in well water, 0.07, 0.10, 0.17 and 0.15 ppm in tap water, 19.3, 21.5, 25.4, and 32.5 ppm in hair samples, in Valjevo, Veliko Gradiste, Kacarevo and Vranjska Banja, respectively. Correlation analysis indicated statistically significant positive relationship between fluoride in wells water and fluoride in hair, for all municipalities: correlation coefficients were 0.54 (p lt 0.05), 0.89, 0.97 and 0.99 (p lt 0.001), in Vranjska Banja, Valjevo, Veliko Gradiste, and Kacarevo, respectively. Positive correlation was obtained also between fluoride in tap water and hair samples in all regions under the study, with statistical significance only in Valjevo municipality, p lt 0.05. Dental examination of schoolchildren confirmed dental fluorosis only in the region of Vranjska Banja. Moreover, in endemic fluorotic region of Vranjska Banja, positive and statistically significant correlations were confirmed between fluoride in well water and dental fluorosis level (r = 0.61; p lt 0.01) and additionally between fluoride in hair and dental fluorosis level (0.62; p lt 0.01). The primary findings from this study have shown that fluoride content in hair is highly correlated with fluoride content in drinking water and dental fluorosis level, indicating that hair may be regarded as biomaterial of high informative potential in evaluating prolonged exposure to fluorides and to individuate children at risk of fluorosis regardless of the phase of teeth eruption