Predisposition and Working Conditions for the Occurrence of Lumbar Syndrome in Medical Workers of the Clinical Center of Montenegro during the COVID-19 Pandemic.

Background: Lumbar pain is a condition of discomfort in the lower back caused by numerous factors, lasting for short or longer periods of time. Healthcare professionals, regardless of the type of care they are engaged in, are at risk of lumbar pain. This is the first study that deals with the problem of lumbar syndrome in health workers in Montenegro. Methods: This cross-sectional study included full-time health workers employed in the Clinical Center of Montenegro who were involved in the treatment of COVID-19 patients during 2020 and 2021. The survey consisted of general questions for collecting socio-demographic and COVID-19 engagement data; the Modified Nordic questionnaire was used for the analysis of musculoskeletal symptoms, and the EQ-5D-questionnaire was used to measure the quality of life associated with health. Results: The one-year prevalence of lumbar pain was 68.1%. Factors associated with lumbar pain were as follows: a higher degree of physical inactivity (each subject with a higher degree of physical inactivity had a 24% higher chance of occurrence of lumbar pain); a higher degree of load and over-engagement during the COVID-19 pandemic (each subject with a higher degree of workload had a nearly 50% higher chance of occurrence of lumbar pain); duration of engagement during the COVID-19 pandemic (subjects engaged up to a month were 4 times more likely to develop lumbar pain, and subjects engaged for 1-3 months were 3.5 times more likely to develop lumbar pain compared to those who were not engaged in COVID-19 treatment). This study also confirms that lumbar syndrome affects the quality of life of health workers. Conclusions: Lumbar syndrome is highly prevalent among healthcare professionals in the Clinical Center of Montenegro, especially in the population of nurses, where evidence-based preventive measures are needed.

Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study.

OBJECTIVES: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA). METHODS: Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days. RESULTS: HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p<0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR. CONCLUSION: The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel- HTPR in patients with carotid artery stenosis undergoing CEA.

Influence of Cyp2c19*2 Gene Variant on Therapeutic Response During Clopidogrel Treatment in Patients with Carotid Artery Stenosis.

BACKGROUND: Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. METHODS: One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). RESULTS: Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01). CONCLUSIONS: The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy.

Rationalized DNA sequencing-based protocol for genotyping patients receiving coumarin therapy.

During the last decade genetic factors affecting coumarin therapy have been extensively investigated. The most important genes appear to be CYP2C9 and VKORC1, and different studies have shown that DNA testing can dramatically improve the safety and effectiveness of the therapy. However, the implementation of pharmacogenetic testing in everyday practice is still not a reality. Facilities and ability to get results before the start of therapy are very important. The implementation of specific methodology and equipment for particular type of diagnostics can represent a serious, even impossible, financial hurdle to overcome (especially in developing countries). For this reason, the use of every tool that contributes to rationalization of the existing methods can be a considerable asset. Therefore, we set the goal to rationalize our current DNA sequencing based protocol for analysis of the VKORC1 c.-1639G> A, CYP2C9*2 and CYP2C9*3 variant alleles, in order to obtain shorter and easier procedure. Simplification of the protocol was achieved by setting up multiplex PCR and omitting DNA extraction. This rationalization of the existing DNA sequencing based procedure allows getting results in 12 hours. The new protocol was tested on 118 samples. Obtained results have shown full accordance to those obtained with previous, non-modified protocol. Therefore, given the circumstances, we consider that protocol for pharmocogenetic testing should be made more accessible - both to doctors and patients. It is one of the prerequisites in order to make genotyping prior to the therapy common practice.