Trend of suicide by self-immolation in a 13-year timeline: was the COVID-19 pandemic a potentially important stressor?

Introduction: Self-immolation is an uncommon way of attempting and committing a suicide, with a fatality rate of 80%. The risk factors in self-immolation victims vary depending on demographic characteristics, socio-economic and cultural factors as well as religious beliefs. Whether the COVID-19 pandemic was a potentially important stressor for self-immolation is still unknown, with insufficient studies examining this issue. Therefore, in this study, we aimed to examine the trend of self-immolation in a 13-year timeline, and the potential association of COVID-19 pandemic with the increase in the incidence and severity of self-immolation injuries in Serbia in 2021. Materials and methods: The study included hospitalized patients due to intentional burns caused by self-immolation in the period from January 1, 2008 to December 31, 2021. Joinpoint regression analysis was used for the analysis of continuous linear trends of self-immolation cases with change points. Results: While a rising trend was observed in the 2008-2013 time segment, followed by a decline in the upcoming 2013-2016 time segment, a significant increase reached its maximum during COVID-19 pandemic (2021), with annual percent change of 37.1% (p = 0.001). A significant increase in the median number of cases per year was observed during 2021 compared to the previous periods (7.5 vs. 2). Frequency of patients with a psychiatric diagnosis vs. those without a psychiatric diagnosis was significantly higher during than before the COVID-19 period (66.7 vs. 36.1%, p = 0.046). Conclusion: In our study, a significant increase in the frequency of suicide attempts by self-immolation during COVID-19 pandemic was noticed. There was also an increased frequency of pre-existing psychiatric illness among patients during the pandemic period. With limited high-quality data available, the study adds to a rising body of evidence for assessment of outcomes of the pandemic on mental health and recognition of stressors for self-immolation.

Lack of pollinators selects for increased selfing, restricted gene flow and resource allocation in the rare Mediterranean sage Salvia brachyodon.

Range contraction and habitat fragmentation can cause biodiversity loss by creating conditions that directly or indirectly affect the survival of plant populations. Fragmented habitats can alter pollinator guilds and impact their behavior, which may result in pollen/pollinator limitation and selection for increased selfing as a mechanism for reproductive assurance. We used Salvia brachyodon, a narrowly distributed and endangered sage from eastern Adriatic, to test the consequences of range contraction and habitat fragmentation. Molecular data indicate a severe and relatively recent species range reduction. While one population is reproductively almost completely isolated, moderate gene flow has been detected between the remaining two populations. The high pollen-to-ovule ratio and the results of controlled hand pollination indicate that S. brachyodon has a mixed mating system. Quantitative and qualitative differences in the community and behaviour of flower visitors resulted in limited pollination services in one population where no effective pollinator other than pollen and nectar robbers were observed. In this population, self-pollination predominated over cross-pollination. Various environmental factors, in which plant-pollinator interactions play a pivotal role, have likely created selection pressures that have led to genetic and phenotypic differentiation and different resource allocation strategies among populations.

The Role of Ketamine as a Component of Multimodal Analgesia in Burns: A Retrospective Observational Study.

Background: Burn wound dressing and debridement are excruciatingly painful procedures that call for appropriate analgesia-typically multimodal. Better post-procedural pain management, less opioid use, and consequently fewer side effects, which could prolong recovery and increase morbidity, are all benefits of this type of analgesia. Intravenously administered ketamine can be effective as monotherapy or in combination with opioids, especially with procedural sedation such as in burn wound dressing. Methods: This observational study investigated the effect of ketamine administered in subanesthetic doses combined with opioids during burn wound dressing. The study was conducted from October 2018 to October 2021. A total of 165 patients met the inclusion criteria. A total of 82 patients were in the ketamine group, while 83 patients were dressed without ketamine. The main outcome was the effect of ketamine on intraprocedural opioid consumption. The secondary outcome included the effect of ketamine on postprocedural pain control. Results: Patients dressed with ketamine were significantly older (p = 0.001), while the mean doses of intraoperatively administered propofol and fentanyl were significantly lower than in patients dressed without ketamine (150 vs. 220 mg, p < 0.001; and 0.075 vs. 0.150 mg, p < 0.001; respectively). Conclusions: Ketamine was an independent predictor of lower intraoperative fentanyl consumption, according to the multivariate regression analysis (p = 0.015). Contrarily, both groups of patients required postoperative tramadol treatment, while intraoperative ketamine administration had no beneficial effects on postoperative pain management.

Metastatic Breast Cancer Presenting as Acute Appendicitis: A Rare Case Study and Review of Current Knowledge.

This manuscript discusses a rare case of acute appendicitis caused by metastasis from invasive breast carcinoma of no special type in a 70-year-old female previously diagnosed with breast cancer. It delves into the diagnostic challenges and management complexities of such unusual clinical presentations. The paper includes an analysis of 19 documented cases, enriching the understanding of metastatic patterns and treatment strategies in breast cancer. It underlines the importance of considering a history of malignancy when diagnosing acute abdominal conditions and emphasizes a comprehensive approach in interpreting diagnostic imaging in patients with past oncological issues to effectively manage metastatic breast cancer exhibiting atypical manifestations.

The clinical and histopathological characteristics of thyroid gland diseases in adolescents requiring surgical treatment: a ten-year follow-up study.

The present research aimed to determine the clinical and pathohistological characteristics of thyroid gland diseases in adolescents who were previously surgically treated at the Endocrine Surgery Center of the University Medical Center of Serbia from 01/01/2001 to 01/01/2011. The study covered 170 patients of both sexes from the population of adolescents (aged 16 to 20 years) with various malignant and benign thyroid gland diseases. The data for this study were extracted from the medical histories of patients and the electronic database of the Center for Endocrine Surgery. Detailed data analysis included diagnosis, symptomatology, surgical intervention type, and disease stage. The following thyroid status parameters were analyzed from preoperative data: thyroxine (T4), thyroxine free fraction (FT4), triiodothyronine (T3), triiodothyronine free fraction (FT3), and thyroid stimulating hormone (TSH). In addition, the pathohistological features of diagnosed thyroid diseases were also determined, with a special focus on the presence of well-differentiated cancers. Papillary carcinomas were the most common of well-differentiated cancers in adolescents over the ten-year follow-up period. Based on the assessed data, total thyroidectomy was the most commonly used type of surgical intervention in these patients. The conducted research provides essential information related to both the biological characteristics and diagnostics of these cancers and their surgical treatment in such a sensitive population. Moreover, research showed that the clinical presentation of thyroid cancer in adolescents is almost identical to that in adults.

Primary Melanoma Histopathologic Predictors of Sentinel Lymph Node Positivity: A Proposed Scoring System for Risk Assessment and Patient Selection in a Clinical Setting.

Background and Objectives: The careful selection of adequate SLNB candidates not only aims at reducing the surgical risk while identifying SLN metastasis, but also plays a crucial role in identifying the patients eligible for adjuvant therapy. Objectives: The purpose of our study was to investigate the clinical and histologic aspects of primary melanomas that correlate with the likelihood of a positive SLNB result. Materials and Methods: A total of 101 primary melanoma patients who underwent sentinel lymph node biopsies were included in the study. General patient demographics were obtained as well as localization and melanoma-specific characteristics of primary melanoma from histologic reports in addition to data derived from SLNB melanoma histopathology reports. Results: The patients with positive SLN results had a statistically significant increased Breslow thickness (3.8 mm vs. 1.97 mm, p = 0.002), higher mitotic index rate (5/mm2 vs. 2/mm2, p = 0.009), as well as the presence of ulceration (68.4% vs. 31.6%, p = 0.007). Univariate regression analysis showed the Breslow thickness (p = 0.008), the mitotic index rate (p = 0.054), the presence of ulceration (p = 0.009), as well as the pT3-4 stage (p = 0.009) to be significant predictors of SLN positivity. The optimal cut-off values for Breslow thickness and the number of mitoses scores were determined based on ROC curve analysis. Using the Breslow thickness, mitotic index rate, presence of ulceration, and pT3-4 stage significant coefficients from the univariate regression model, a chance prediction score was developed. Conclusions: The newly developed and proposed scoring system can aid in patient selection for SLN biopsy by facilitating a more efficient risk assessment in the detection of lymph node metastases in melanoma patients.

Galectin-3's Complex Interactions in Pancreatic Ductal Adenocarcinoma: From Cellular Signaling to Therapeutic Potential.

Galectin-3 (Gal-3) plays a multifaceted role in the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). This review offers a comprehensive examination of its expression in PDAC, its interaction with various immune cells, signaling pathways, effects on apoptosis, and therapeutic resistance. Additionally, the prognostic significance of serum levels of Gal-3 is discussed, providing insights into its potential utilization as a biomarker. Critical analysis is also extended to the inhibitors of Gal-3 and their potential therapeutic applications in PDAC, offering new avenues for targeted treatments. The intricate nature of Gal-3's role in PDAC reveals a complex landscape that demands a nuanced understanding for potential therapeutic interventions and monitoring.

Population size as a major determinant of mating system and population genetic differentiation in a narrow endemic chasmophyte.

BACKGROUND: Mating system is one of the major determinants of intra- and interspecific genetic structure, but may vary within and between plant populations. Our study model included all known populations of Moehringia tommasinii (Caryophyllaceae), a narrow endemic plant inhabiting rock crevices in the northwestern Adriatic, and some populations of co-occurring and widespread M. muscosa, an ecologically divergent relative with an overlapping flowering period. We performed reciprocal crosses within and between taxa and used molecular markers to assess the extent of gene flow within and between populations and taxa. Using coefficient of inbreeding, population size, seed weight, pollen-to-ovule ratio, and flower display size, we also looked for evidence of a selfing syndrome. RESULTS: A surprisingly high variation in mating systems was observed among populations of M. tommasinii. These populations exhibited genetic structuring, with their size positively correlated with both seed weight and pollen production. Although a selfing syndrome could not be confirmed as the majority of selfing resulted from allogamous treatments, the occurrence of selfing was notable. In the presence of M. muscosa, at a site where both species coexist closely, a distinct pattern of fruit production was observed in M. tommasinii following various pollination treatments. Molecular and morphometric data provided evidence of hybridization followed by local extinction at this site. CONCLUSIONS: Population size proved to be the most important factor affecting the mating system in genetically structured populations of M. tommasinii. Lighter seeds and lower pollen production observed in populations with pronounced selfing do not provide enough evidence for the selfing syndrome. Detected gene flow between M. tommasinii and the sympatric M. muscosa suggested weak reproductive barriers between the taxa, which could pose a conservation problems for the former species. Hybridization leading to local extinction may also resulted in floral polymorphism and disruption of mating patterns of M. tommasinii.

Towards the Investigation of the Adaptive Divergence in a Species of Exceptional Ecological Plasticity: Chromosome-Scale Genome Assembly of Chouardia litardierei (Hyacinthaceae).

One of the central goals of evolutionary biology is to understand the genomic basis of adaptive divergence. Different aspects of evolutionary processes should be studied through genome-wide approaches, therefore maximizing the investigated genomic space. However, in-depth genome-scale analyses often are restricted to a model or economically important species and their closely related wild congeners with available reference genomes. Here, we present the high-quality chromosome-level genome assembly of Chouardia litardierei, a plant species with exceptional ecological plasticity. By combining PacBio and Hi-C sequencing technologies, we generated a 3.7 Gbp genome with a scaffold N50 size of 210 Mbp. Over 80% of the genome comprised repetitive elements, among which the LTR retrotransposons prevailed. Approximately 86% of the 27,257 predicted genes were functionally annotated using public databases. For the comparative analysis of different ecotypes' genomes, the whole-genome sequencing of two individuals, each from a distinct ecotype, was performed. The detected above-average SNP density within coding regions suggests increased adaptive divergence-related mutation rates, therefore confirming the assumed divergence processes within the group. The constructed genome presents an invaluable resource for future research activities oriented toward the investigation of the genetics underlying the adaptive divergence that is likely unfolding among the studied species' ecotypes.

Impact of the COVID-19 Pandemic on Melanoma Diagnosis: Increased Breslow Thickness in Primary Melanomas-A Single Center Experience.

Early melanoma diagnosis plays a key role in ensuring best prognosis with good survival rates. The ongoing global COVID-19 pandemic has greatly impacted global and national healthcare systems, thus making it a real challenge. The aim of this study was to evaluate the impact of the pandemic on diagnostic delay in melanoma patients in Serbia. In this retrospective study, we included patients treated at the university hospital in Serbia's capitol over a period of five years and three months. We compared the prepandemic (01/JAN/17-14/MAR/20) and pandemic periods (15/MAR/20-31/MAR/22) by evaluating patient demographic data, melanoma subtype, Breslow thickness, Clark level, ulceration status, mitotic index rate and pT staging. We observed a significant reduction in the number of diagnosed patients (86.3 vs. 13.7%; p = 0.036), with melanomas having an increased median Breslow thickness (1.80 vs. 3.00; p = 0.010), a higher percentage of Clark IV-V level lesions (44.0% vs. 63.0%; p = 0.009), an increase in median mitotic index rate (2 vs. 5; p < 0.001) and a trend of increase in lesions thicker than 2 mm (37.8% vs. 53.7%; p = 0.026). We believe that this study can be a useful scenario guide for future similar events, highlighting the importance of preventive measures and timely diagnosis for the best patient outcomes.

Phytochemicals and Their Correlation with Molecular Data in Micromeria and Clinopodium (Lamiaceae) Taxa.

A study of the phytochemical and molecular characteristics of ten Micromeria and six Clinopodium taxa (family Lamiaceae) distributed in the Balkan Peninsula was carried out. The phytochemicals detected in essential oils by gas chromatography, mass spectrometry, and molecular data amplified fragment length polymorphism were used to study the taxonomic relationships among the taxa and the correlations between phytochemical and molecular data. STRUCTURE analysis revealed three genetic groups, while Bayesian Analysis of Population Structure grouped the studied taxa into 11 clusters nested in the groups obtained by STRUCTURE. Principal components analysis performed with the 21 most represented compounds in the essential oils yielded results that were partly consistent with those obtained by STRUCTURE and neighbour-joining analyses. However, their geographic distributions did not support the genetic grouping of the studied taxa and populations. The Mantel test showed a significant correlation between the phytochemical and genetic data (r = 0.421, p < 0.001). Genetic distance explained 17.8% of the phytochemical distance between populations. The current taxonomic position of several of the studied taxa is yet to be satisfactorily resolved, and further studies are needed. Such future research should include nuclear and plastid DNA sequences from a larger sample of populations and individuals.

Phylogeographic structure of common sage (Salvia officinalis L.) reveals microrefugia throughout the Balkans and colonizations of the Apennines.

Studying the population-genetic and phylogeographic structures of a representative species of a particular geographical region can not only provide us with information regarding its evolutionary history, but also improve our understanding of the evolutionary processes underlying the patterns of species diversity in that area. By analysing eight highly polymorphic microsatellite loci and two chloroplast DNA regions, we have investigated the influence of Pleistocene climate fluctuations on the evolutionary history of Salvia officinalis L. (common sage). The populations with the highest genetic diversity were located in the central parts of the Balkan distribution range. A large group of closely related haplotypes was distributed throughout the Balkans and the central Apennines, while the private lineage occupied the southern Apennines. In addition, two highly differentiated lineages were scattered only over the Balkans. The results suggest that a single refugium of the studied species from the last glacial period was located in the central part of the range in the Balkans. Numerous microrefugia, probably spanning several glaciation cycles, were scattered across the Balkans, while colonisation of the Apennines from the Balkans occurred at least on two occasions.

Development of Microsatellite Markers for Tanacetum cinerariifolium (Trevis.) Sch. Bip., a Plant with a Large and Highly Repetitive Genome.

Dalmatian pyrethrum (Tanacetum cinerariifolium (Trevis.) Sch. Bip.) is an outcrossing plant species (2n = 18) endemic to the eastern Adriatic coast and source of the natural insecticide pyrethrin. Due to the high repeatability and large genome (1C-value = 9.58 pg) our previous attempts to develop microsatellite markers using the traditional method were unsuccessful. Now we have used Illumina paired-end whole genome sequencing and developed a specific procedure to obtain useful microsatellite markers. A total of 796,130,142 high-quality reads (approx. 12.5× coverage) were assembled into 6,909,675 contigs using two approaches (de novo assembly and joining of overlapped pair-end reads). A total of 31,380 contigs contained one or more microsatellite sequences, of which di-(59.7%) and trinucleotide (25.9%) repeats were the most abundant. Contigs containing microsatellites were filtered according to various criteria to achieve better yield of functional markers. After two rounds of testing, 17 microsatellite markers were developed and characterized in one natural population. Twelve loci were selected for preliminary genetic diversity analysis of three natural populations. Neighbor-joining tree, based on the proportion of shared alleles distances, grouped individuals into clusters according to population affiliation. The availability of codominant SSR markers will allow analysis of genetic diversity and structure of natural Dalmatian pyrethrum populations as well as identification of breeding lines and cultivars.

Risk factors for adverse drug reactions associated with clopidogrel therapy.

This study aimed to investigate the possible influence of genetic and non-genetic factors on the incidence of clopidogrel adverse drug reactions (ADRs) in cardiology patients, including the most important CYP2C19 alleles, namely *2 and *17, as well as compliance, dose, drug interactions, and clinical factors. A total of 102 clopidogrel-treated adult Caucasian patients hospitalized at the Cardiology Department of the Clinical Center of Montenegro were enrolled in the study. Data on clinical outcomes of interest were obtained by intensive monitoring ADRs during hospitalization and one year after hospital discharge. Genotyping for CYP2C19*2 and *17 was conducted using the real-time polymerase chain reaction method. ADRs were characterized using the Rawlins and Thompson classification and the World Health Organization criteria. Causality was assessed using the Naranjo probability scale. ADRs to clopidogrel were observed in 9 of 102 patients (8.8%). The observed frequencies of CYP2C19*2 and *17 were 13.2 and 25.5%, respectively. Our study, which is the first to report the frequency of CYP2C19 polymorphism in the Montenegrin population, as well as to link the pharmacovigilance of clopidogrel with CYP2C19 gene variability, shows that the incidence of ADRs of clopidogrel in cardiac patients is high and depends on CYP2C19 polymorphisms, comedication/drug interactions, and gastrointestinal comorbidity.

IL-10-1082G>A polymorphism, use of opioids and age affect the course of acute pancreatitis.

PURPOSE: We aimed to determine the association of two of the most important functional polymorphisms of IL-8 and IL-10 with the clinical course and outcome of acute pancreatitis. METHOD: Ninety-three patients with acute pancreatitis were genotyped for IL-8-251T>A and IL-10-1082G>A using PCR-RFLP. The severity of the disease was determined based on the Atlanta Classification system. RESULTS: In patients treated with opioids, the odds for severe form of acute pancreatitis, its complications, and death were increased. Advanced age was associated with higher odds of organ/multiple organ failure and other systemic complications. Multivariate logistic regression analyses confirmed the observed effect of age and use of opioids, and revealed higher odds for the development of severe form of acute pancreatitis [P = 0.017, odds ratio (OR): 4.324, 95% confidence interval (CI): 1.305-14.323], its complications in general (P = 0.011, OR: 4.936, 95% CI: 1.442-16.897), pancreatic necrosis (P = 0.032, OR: 3.922, 95% CI: 1.122-13.707) and systemic inflammatory response syndrome (P = 0.037, OR: 3.838, 95% CI: 1.085-13.583) in the absence of IL-10-1082G>A variant allele. The effect of IL-8 -251T>A on acute pancreatitis severity or mortality was not detected. CONCLUSION: Our study suggests the IL-10 -1082A allele as a protective factor in acute pancreatitis. Opioid analgesics treatment in acute pancreatitis is associated with severity, complications and mortality, while advanced age increases the risk of systemic complications.

The Influence of a Seedling Recruitment Strategy and a Clonal Architecture on a Spatial Genetic Structure of a Salvia brachyodon (Lamiaceae) Population.

By performing a high-resolution spatial-genetic analysis of a partially clonal Salvia brachyodon population, we elucidated its clonal architecture and seedling recruitment strategy. The sampling of the entire population was based on a 1 × 1 m grid and each sampled individual was genotyped. Population-genetic statistics were combined with geospatial analyses. On the population level, the presence of both sexual and clonal reproduction and repeated seedling recruitment as the prevailing strategy of new genets establishment were confirmed. On the patch level, a phalanx clonal architecture was detected. A significant negative correlation between patches' sizes and genotypic richness was observed as young plants were not identified within existing patches of large genets but almost exclusively in surrounding areas. The erosion of the genetic variability of older patches is likely caused by the inter-genet competition and resulting selection or by a random die-off of individual genets accompanied by the absence of new seedlings establishment. This study contributes to our understanding of how clonal architecture and seedling recruitment strategies can shape the spatial-genetic structure of a partially clonal population and lays the foundation for the future research of the influence of the population's clonal organization on its sexual reproduction.

Divergent selection and genetic structure of Sideritis scardica populations from southern Balkan Peninsula as revealed by AFLP fingerprinting.

Sideritis scardica Giseb. is a subalpine/alpine plant species endemic to the central part of the Balkan Peninsula. In this study, we combined Amplified Fragment Length Polymorphism (AFLP) and environmental data to examine the adaptive genetic variations in S. scardica natural populations sampled in contrasting environments. A total of 226 AFLP loci were genotyped in 166 individuals from nine populations. The results demonstrated low gene diversity, ranging from 0.095 to 0.133 and significant genetic differentiation ranging from 0.115 to 0.408. Seven genetic clusters were revealed by Bayesian clustering methods as well as by Discriminant Analysis of Principal Components and each population formed its respective cluster. The exception were populations P02 Mt. Shara and P07 Mt. Vermio, that were admixed between two clusters. Both landscape genetic methods Mcheza and BayeScan identified a total of seven (3.10%) markers exhibiting higher levels of genetic differentiation among populations. The spatial analysis method Samßada detected 50 individual markers (22.12%) associated with bioclimatic variables, among them seven were identified by both Mcheza and BayeScan as being under directional selection. Four bioclimatic variables associated with five out of seven outliers were related to precipitation, suggesting that this variable is the key factor affecting the adaptive variation of S. scardica.

Morphological, genetic and epigenetic aspects of homoploid hybridization between Salvia officinalis L. and Salvia fruticosa Mill.

The inheritance of phenotypic, genetic and epigenetic traits in hybridization events is difficult to predict, as numerous evolutionary, ecological, and genetic factors can play a crucial role in the process of hybridization. In the middle Adriatic island of Vis, we investigated hybridization between Salvia officinalis and S. fruticosa at morphological, genetic and epigenetic levels. SSR results revealed that hybrid individuals were characterized by diploid set of chromosomes suggesting homoploid hybridization. A well-defined group that mostly comprised of F1 generation individuals was detected. For the majority of analysed morphological characteristics, hybrids were placed in-between parental taxa, while at the same time, values of different genetic parameters were mostly higher in hybrids than in parental species. The results revealed a high contrast in the levels of phenotypic variability and epigenetic excitation between parental taxa. Environmental niche modelling confirmed that in the studied location S. officinalis experiences optimal climatological conditions, while S. fruticosa struggles with unsuitable conditions. Very low levels of gene flow between the parental species were detected. In addition, contrasting levels of epigenetic excitation in the studied groups clearly demonstrated the importance of an epigenetic response to an altered environment and confirmed the trans-generational nature of the epigenetic changes.

CFTR IVS8 Poly-T Variation Affects Severity of Acute Pancreatitis in Women.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) is important for normal pancreatic function. Its coding gene is polymorphic, and the variations have been associated with the increased risk for acute pancreatitis. However, their impact on the disease severity is still unknown. Therefore, the aim of our study was to determine the functional importance of common cystic fibrosis transmembrane conductance regulator variations IVS8-poly T, R117H, and M470V for the severity of acute pancreatitis. METHOD: The study involved 98 acute pancreatitis patients. The severity of the disease was determined based on the Atlanta Classification system. IVS8-poly T, R117H, and M470V genotyping was performed using PCR-RFLP method. RESULTS: IVS8-5T, IVS8-7T, IVS8-9T, and M470V alleles were found at the frequencies of 5.7, 75.5, 18.9, and 55.7%, respectively, while R117H was not observed. Among women, the severe form of the disease was more frequent in carriers of at least one IVS8 9T allele (RR for 9T/9T + 9T/non-9T vs. non-9T/non-9T: 2.115; 95% CI: 1.241-3.605). This association was not detected in men and was not affected by M470V. In addition, co-morbidities increased the severity of acute pancreatitis (p = 0.022). CONCLUSION: Our study reveals that IVS8 poly-T variation affects severity of acute pancreatitis in women and that existent co-morbidities worsen the clinical course of the disease.

Factors affecting the development of adverse drug reactions to ß-blockers in hospitalized cardiac patient population.

The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of ß-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any ß-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients' medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to ß-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs' occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to ß-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.