International Journal of Risk & Safety in Medicine - Volume 27, issue s1

Article Type: Other

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S1-S2, 2015

Authors: Burger, Edward J.

Article Type: Introduction

DOI: 10.3233/JRS-150667

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S3-S4, 2015

Article Type: Other

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S5-S5, 2015

Authors: Buzyan, L.O.

Article Type: Abstract

Abstract: BACKGROUND: Iron deficiency anemia is traditionally considered to be a pathological condition during pregnancy. According to the standards, prescription of iron supplements to pregnant women is required at hemoglobin levels of 110 g/l and lower. Numerous studies at different periods showed the relationship of anemia and premature birth [5 ], preeclampsia [1 ], low birth-weight [2 ]. Meanwhile, physiological hemodilution carries in pregnancy an important adaptive function. It is well known, that in the second half of pregnancy physiological hypercoagulability develops (increased activity of the plasma clotting factors, platelet aggregation, decreased activity and blood concentrations of physiological anticoagulants) aimed at …implementing adequate hemostasis in labor. Under these conditions, moderate hemodilution is an effective mechanism for preventing the development of severe disseminated intravascular coagulation (DIC) in labor, during surgery, in various forms of obstetric pathology. OBJECTIVE: To study the effect of anemia of varying severity on the pregnancy course and outcomes. METHODS: We conducted a “case-control” study based on cohort. The study included 421 pregnant women who received outpatient care under the monitoring of pregnancy in the antenatal clinic of the South Ural State Medical University and the antenatal clinic of Chelyabinsk Clinical Hospital №6. The inclusion period was from January to March 2014. Inclusion criteria were: confirmed pregnancy, informed consent to participate in the study. Exclusion criteria were multiple pregnancy, induced pregnancy, late first appearance in the antenatal clinic (after 25 weeks’ gestation), change of residence and medical supervision during pregnancy, the presence of severe mental disorders, severe somatic diseases in decompensation stage, HIV infection, cancer, active tuberculosis. Study design complies with the legislation of the Russian Federation, international ethical standards and was approved by the Ethics Committee of the South Ural State Medical University. Prospective observation was conducted. All pregnancy complications were registered, in particular, preeclampsia, placental insufficiency (violation of utero-placental blood flow), the presence and severity of anemia during pregnancy, as well as outcomes: the duration and mode of delivery, fetal weight at birth. The criteria for the diagnosis of anemia during pregnancy were: decrease of hemoglobin levels below 110 g/l. All pregnant women with confirmed anemia were treated with iron supplements. After the completion of follow-up the odds ratios analysis of presenting anemia was performed in subgroups: 1) a patient gave birth to a live child, and patient with the loss of the fetus at various stages of gestation; 2) patients who have given birth in time, and patients with premature birth; 3) patients with placental insufficiency (violation of utero-placental blood flow) during pregnancy and patients without placental insufficiency; 4) patients with preeclampsia and patients without pre-eclampsia; 5) patients who have delivered live births weighing less than 2,500 grams and birth weight over 2500. In each case, odds ratios (ORs) and confidence intervals (95% CI) were calculated. Statistical calculations were performed using the software package SPSS 22.0. RESULTS: Among all patients (n = 421) anemia of varying severity has been diagnosed in 190 (45.13%), including mild anemia in 161 (38.24%), moderate or severe anemia - in 29 patients (6.88%). In 16 (3.8%) cases, the pregnancy resulted in miscarriage or fetal death. Premature birth of live fetus before 34 weeks of gestation was recorded in 13 cases (3.2%; n = 405). Preeclampsia was diagnosed in 15 women (3.56%). Live births with weights less than 2,500 g were registered in 23 cases (5.67%; n = 405). An analysis of odds ratios was performed to compare the groups of women with anemia of any severity and without anemia, with mild anemia compared with women without anemia, and moderate/severe anemia compared to women with mild anemia or without anemia. According to our results, there was a statistically significant reduction in the chance of having anemia of any severity in patients whose pregnancy was completed by fetal loss. For mild anemia odds ratio in these subgroups was even lower. Thus, the odds of having mild anemia in the group of women who completed a pregnancy to a live birth, was 90.3%, which may indicate a protective role of mild anemia against the loss of the fetus. In all other cases, statistically significant results were not received. Thus, we didn’t receive significant positive association between anemia and development of preeclampsia, placental insufficiency during pregnancy, low birth weight and premature birth. There are other publications that show a protective role of anemia in pregnancy. Case control study [3 ] showed a protective role of anemia against the development of pre-eclampsia (n = 636, p = 0,01). In [4 ] anemia was a protective factor against stillbirth. There is evidence [6 ] of the higher risk of stillbirth in women with high hemoglobin level (146 g/l and above), while the link of the risk of stillbirth with anemia has not been confirmed (n = 1404). CONCLUSIONS: Our data suggest a protective role of mild anemia during pregnancy in relation to pregnancy loss. Show more

Keywords: Anemia, pregnancy, pregnancy loss, mild anemia, protective factor

DOI: 10.3233/JRS-150668

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S7-S8, 2015

Authors: Safina, A.I. | Daminova, M.A. | Abdullina, G.A.

Article Type: Abstract

Abstract: BACKGROUND: The incidence of acute kidney injury (AKI) in neonates in the intensive care units and neonatal intensive care (NICU) according Plotz et al. ranges from 8% to 22% [3 ]. According to Andreoli, neonatal death due to AKI in NICU amounts up to 10–61% [1 ]. It should be in the reasons of AKI emphasize. The role of certain drugs, which are widely used in modern neonatology: nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (aminoglycosides, glycopeptides, carbapenems, 3rd generation cephalosporins), furosemide, enalapril, in contributing to AKI should be emphasized [2 ]. OBJECTIVE: To identify risk factors for acute kidney …injury in neonates in intensive care units and intensive care. METHODS: We performed a prospective observational case-control study of full-term newborns who were treated in the intensive care unit and neonatal intensive care of the “Children’s city hospital №1” Kazan and NICU №3 “Children’s Republican Clinical Hospital” in 2011–2014 years. The study included 86 term infants in critical condition, who were hospitalized to the NICU on the first days of life, - the main group. The main criterion of AKI in neonates according to neonatal AKIN classification (2011) is a serum creatinine concentration ≥1.5 mg/dL. We subdivided the main group into two subgroups: subgroup I, AKI+ consisted of 12 term infants in critical condition with the serum creatinine level ≥ 1,5 mg/dL at the age of not younger than 48 hours after birth, which was 14% of all full-term newborns who were at the NICU; subgroup II, AKI- consisted of 74 term infants in critical condition with the serum creatinine level <1.5 mg/dL at the age of not younger than 48 hours after birth. The control group was formed by random sampling, it consisted of 26 somatically healthy term infants. We used conventional methods for evaluating renal function, and enzyme immunoassay (ELISA) for the urine biomarker of AKI, IL-18. Statistical analysis was performed using SPSS, Statistics 20, and the IBM and Microsoft Office Excel 2007. The study results were subjected to statistical analysis using parametric and non-parametric methods of analysis. We present the findings as arithmetic means (M) with, standard deviation (σ) and standard error of the mean (m) according to standard formulas. RESULTS: All children were admitted to primary and emergency care with subsequent transfer to the NICU at 1-2 days of life and further treatment in the department of pathology of newborns (DPN). The duration of hospitalization of infants at the NICU for the main group averaged 5,9 ± 0,44 days; at the DPN (subsequent stage of nursing) - 11,42 ± 0,51 days; for the subgroup I, AKI+ newborns these were 7,83 ± 1,23 days and 13,75 ± 3,34 days, respectively; for the subgroup II, AKI– newborns these were 5,58 ± 0,47 (3-30) and 11,04 ± 0,3 (0–47) days, respectively. Neonates received daily average of 16,5 ± 0,3 various medicines while at NICU and 9,1 ± 0,7 while at DPN. Overall, over the entire period of hospitalization neonates of the main group received on average 25,6 ± 1,8 medicines. Of these, 2,9 ± 0,4 drugs were antibiotics, possessing nephrotoxic properties (aminoglycosides, cephalosporins, carbapenems, fluoroquinolones). Children of the main group in 100% (n = 86) of cases were treated with 3rd generation cephalosporins (ceftriaxone, cephaperazone/sulbactam (sulperazon)), in 55% od cases (n = 47) – with aminoglycosides (amikacin, gentamicin), in 1% (n = 1) – with vancomycin, in 7% (n = 6) – with carbapenems. Diuretics were prescribed to 57% (n = 49) of infants. Often, patients were treated with a combination of nephrotoxic medications. Aminoglycoside were prescribed statistically more often to neonates of the subgroup I, than of the subgroup II (p <0.01). Diuretic drugs were used more frequently and for longer periods of time in neonates of the subgroup I (AKI+), than in newborns of the subgroup II (AKI–), namely, in 83% (n = 10) for 4,6 ± 1.34 days versus 53% of cases (n = 39) for 2.84 ± 0.49 days, respectively (p <0.05). IL-18 urine level in neonates of subgroup I (AKI+) was 2 times higher than that in neonates of the subgroup II (AKI–), and 13 times higher than in neonates of the control group. The fact that the IL-18 urine level increased with progression of kidney damage, caused by nephrotoxic therapy, suggests that a significant role in the development and progression of AKI in neonates at NICU belongs to drug therapy. CONCLUSIONS: Full-term newborns in intensive care units are at high risk of AKI when they are treated with aminoglycosides in combination with diuretics for longer than 4.5 days. Show more

Keywords: Risk factor, acute kidney injury, neonates, intensive care

DOI: 10.3233/JRS-150669

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S9-S10, 2015

Authors: Yakimova, Y.

Article Type: Abstract

Abstract: BACKGROUND: Patients decide to take antibiotics themselves in 21% of cases of acute respiratory viral infections, influenza and acute respiratory infections [1 ]. The main factor of drug purchase at a pharmacy is pharmacist’s recommendation. In 14% of cases of purchase of antibiotics, patients describe the symptoms and do not name a specific drug. This provides opportunity for drug selection at a pharmacy [2 ]. In these circumstances the role of pharmacists in ensuring the rational use of antimicrobial agents increases significantly. OBJECTIVE: To evaluate the knowledge of pharmacists about antibiotics for systemic use. METHODS: Pharmacoepidemiological …study was based on surveying pharmaceutical workers using a questionnaire. The questionnaire included 2 groups of questions: general questions aimed at identifying the socio-demographic characteristics of respondents (gender, age) and professional status (level of qualification, work experience), as well as specific questions aimed at identifying perceptions and knowledge of respondents about the studied group of drugs (range of used drugs, the factors determining and limiting the choice of drug, properties of individual drugs, etc.). The study involved 182 pharmaceutical workers at the age of 20 to 52 years. When processing the received data, we used Microsoft Excel and BioStat, and methods of nonparametric statistics (χ2 -test). The survey was conducted anonymously, informed consent of the participants was not required. According to the recommendations of Ethical Committee of Saratov State Medical University n.a. V.I. Razumovsky (protocol No. 8 from 01.04.2014) the study is consistent with the basics of medical ethics. RESULTS: Interviewed pharmaceutical workers were mostly women (97%) with secondary pharmaceutical education (84%). The average age of the respondents was 27.0 ± 0.5 years. The work experience of the respondents ranged from 0.5 to 34 years (average experience 5.64 ± 0.41 years). Almost all pharmacists (97%) reported that they dispense antimicrobial drugs every day and consult patients about the choice and characteristics of antibiotic (99.5%). However, only 20% of the respondents indicated that they refuse to recommend antibiotics to the pharmacy visitors and send them to the doctor. Most often pharmaceutical employees recommended azithromycin (45%), amoxicillin in combination with clavulanic acid (41%), amoxicillin (26%). According to respondents, the choice of recommended antibiotic mostly depends (score on a scale of 1–5) on pharmacological characteristics of the drug: the effectiveness (of 4.66 ± 0.04) and safety (4.16 ± 0.07). Thus, pharmaceutical specialist should be knowledgeable about characteristics of antimicrobial agents to conduct proper consultation. According to the results of self-assessment of respondents’ knowledge about antibiotics it is at an average level. 36.3% of respondents state that they are familiar with the range and features of most of the drugs. 41.8% of professionals are familiar with the range of the most popular drugs and their main features. Only 16.5% of respondents assess their knowledge about antibiotics at the highest level, indicating that they are fully familiar with the range and features of the drugs. Aiming at identifying knowledge about the side effects of antibiotics pharmacists were asked to compare the most commonly prescribed drugs and their respective side effects, to position the drugs and groups of drugs in the range according to the degree of toxicity and to indicate which antibiotics can be used during pregnancy. Knowledge of pharmaceutical workers is mainly limited to the perceptions of non-specific side reactions that can occur when taking any antibiotic (dyspepsia, allergic reactions, headache, candidiasis). 54.9% of respondents rightly pointed out nonspecific reactions for all 7 mentioned drug, for individual drugs the proportion of correct answers varied from 65,4% (linezolid) to 81,3% (amoxicillin+clavulanic acid). The analysis revealed no relationship between respondents’ answers and their qualifications (χ2 = 0,053; p = 0,818), work experience (χ2 = 6,956; p = 0,096) and self-assessed knowledge about antimicrobial drugs (χ2 = 1,272; p = 1,000). There were no respondents who correctly reported specific adverse reactions (hearing disorder for azithromycin, hemopoiesis oppression for linezolid, etc.) for each antibiotic. The proportion of correct answers ranged from 6,0% for the combination amoxicillin+clavulanic acid to 43,4% for cefixime and doxycycline. The relationship between knowledge of respondents and frequency of recommendations of the same group of drugs could not be determined. Pharmacists assume that the safest antibiotics are macrolides (average rank place of 2,99 ± 0,15 of 8), cephalosporins (3,12 ± 0,15) and penicillins (3,38 ± 0,22), the most toxic are tetracyclines (5,61 ± 0,17). It should be noted that average rank places are quite similar, which means serious differences of opinion between the specialists. When assessing the toxicity of individual drugs a combination of amoxicillin+clavulanic acid (average rank place of 2,92 ± 0,29 of 15) and ampicillin (of 4,88 ± 0,36) were considered as the safest, the most toxic were tetracycline (10,13 ± 0,30) and gentamicin (10,14 ± 0,33). These perceptions are generally consistent with the views on the safety of antibiotics in outpatient practice [3 ]. Half of the respondents (51,1%) correctly identified the antibiotics that can be used during pregnancy (FDA category B). 45,1% of respondents said that no antibiotics can be used during pregnancy. Only 2,7% of respondents named drugs contraindicated during pregnancy (category C and D) – gentamicin, doxycycline, ciprofloxacin. CONCLUSIONS: The study identified gaps in the knowledge of pharmacists about the safety of antimicrobial agents. Views of professionals about antibiotics are mostly consistent with current data about the properties of drugs. However, detailed analysis shows that such views are not supported by clear knowledge of the properties of each drug and are mostly intuitive. In terms of the prevalence of self-medication with antibiotics and OTC dispensing of antimicrobial drugs it is necessary to improve the professional knowledge of pharmaceutical workers on antibiotics for systemic use. Show more

Keywords: Antibiotics, safety, knowledge, pharmacists, pharmacoepidemiology

DOI: 10.3233/JRS-150670

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S11-S12, 2015

Authors: Khudaibergenova, M.S.

Article Type: Abstract

Abstract: BACKGROUND: The problem of antimicrobial resistance has become topical and alarming all over the world, including Kazakhstan. Nosocomial strains of microorganisms are widespread, being resistant to the majority of available antimicrobials. This results in longer periods of hospital stay, increases in financial expenditures, and sometimes, in lethal outcomes. The social importance of antimicrobial resistance is preconditioned by the spread of resilient strains of microorganism beyond the hospital environment, which leads to lower effectiveness of antibiotic therapy against infectious diseases and growth in their incidence [1, 2 ]. Our in-patient health facility is a multifunctional one. It provides therapeutic, surgical and …oncology and hematology care including organ transplantation. Measures to reduce antibiotic resistance are very important. OBJECTIVE: To develop a standardized approach to the use of antimicrobial drugs aimed at reducing of antimicrobial resistance, postoperative complications and mortality rates along with financial expenditures. The expected result of this approach should be the enhancement of quality of care. METHODS: In September 2014 we developed and introduced a local protocol of the antimicrobials use, namely antibiotics for surgical prophylaxis and treatment, based on the evidence of international clinical guidelines evidence-based medicine approach, taking into account the microbial landscape and antibiotic resistance patterns to major pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae [3 ]. We planned to assess the effectiveness of this policy by the following criteria: the percentage of post-surgical sequela, the number of bed days, the percentage of resistant cases and antibiotic expenditures. In order to improve the quality of bacteriological studies, together with microbiologists we trained the medical staff on the methods of obtaining of biological material for microbiological testing. RESULTS: We analyzed the indicators of antibiotic resistance from October 2014 to March 2015 (hereafter period I) on the basis of the data from the microbiological laboratory with data of April–August 2015 (hereafter period II). The analysis on the basis of other criteria has yet to be carried out. The bio-material was obtained from different loci, including blood. The results of the oncology and hematology were analyzed separately. We received the following results of sensitivity of the listed microorganisms to various antimicrobials in the period I and the period II respectively expressed as percentages: Staphylococcus aureus: Oxacillin – 95% and 100%, Azythromycin – 62% and 100%, Vancomycin – 100% and 100%, Levofloxacin/Moxifloxacin – 100% and 100%. Pseudomonas aeruginosa: Ceftazidime – 34% and 67%, Piperacillin/Tazobactam – 91% and 84%, Cefepime – 59% and 81%, Amikacin – 95% and 100%, Meropenem – 100% and 100%, Ciprofloxacin – 97% and 100%. Escherichia coli: Gentamicin – 93% and 96%, Piperacillin/Tazobactam – 86% and 92%, Ceftriaxone – 82% and 100%, Amikacin – 99% and 100%,Ciprofloxacin – 69% and 80%, Amoxycillin/Clavulanate – 44% and 46% respectively. Klebsiella pneumoniae: Gentamicin – 50% and 100%, Piperacillin/Tazobactam – 95% and 100%, Cefepime – 100% and 100%, Ceftriaxone – 96% and 100%, Amikacin – 99% and 100%, Ciprofloxacin – 100% and 100%, Amoxycillin/Clavulanate – 22% and 23%. Acinetobacter baumannii: Gentamicin – 83% and 83%, Piperacillin/Tazobactam – 33% and 58%, Cefepime – 0% and 33%, Ceftriaxone – 0% and 33%, Amikacin – 50% and 83%, Ciprofloxacin – 83% and 67%, Meropenem/Imipenem-Cilastin – 83% and 83%. CONCLUSIONS: During the analyzed periods we observed some improvement in the sensitivity of the main pathogens to antibiotics. At the same time, the resistance of Acinetobacter baumannii to carbapenems and fluoroquinolones increased. Limitations of the study There are many other than antibiotic use factors, which influence these results. Further analysis is planned to be carried out. Nevertheless, this analysis makes us believe that we are, probably, on the right path for improving the use of antibacterial drugs. Show more

Keywords: Antimicrobial, antibiotic, use, hospital, resistance

DOI: 10.3233/JRS-150671

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S13-S14, 2015

Authors: Rozhkov, A. | Sychev, D.A. | Kazakov, R.E.

Article Type: Abstract

Abstract: BACKGROUND: Oral anticoagulant drugs (AD) are commonly used to treat patients with thromboembolic diseases. The ADs have narrow therapeutic index and wide pharmacokinetic and pharmacodynamic interindividual variability. Some genetic variations could influence interindividual variability in response to AD. Acenocoumarol (AC) is a coumarin, vitamin K derivate with antagonistic activity, used as anticoagulant therapy mainly in Central Europe and Latin America. P – glycoprotein (PGP), a transporter encoded by the ABCB1 gene, plays a major role in the drug disposition [1 ]. PGP is expressed in normal tissues, where it performs a defensive role against potentially toxic substances in intestinal cells …and endothelial cells of the brain capillary endothelium. ABCB1 – is highly polymorphic, C3435T polymorphism in exon 26 has been associated with the expression of PGP [2 ]. There is some evidence that PGP could influence coumarin sensitivity. OBJECTIVE: To assess effects of the ABCB1 pilymorphisms on safety profile and dosing regimen of acenocoumarol in the patients with valvular atrial fibrillation. METHODS: 50 patients (34 male and 16 female), 40–70 years of age were included. All patients received acenocoumarol at doses of 1–6 mg daily with a target international normalized ratio (INR) of 2.0 to 3.0. Genotyping for polymorphism marker C3435T of ABCB1 gen was performed using PCR and RFLP (restriction fragment length polymorphisms) techniques. Statistics were performed by Fishers exact tests. All enrolled patients provided written informed consent. RESULTS: Genotype CC was found in 10 patients (20%), genotype CT in 25 patients (50%) and genotype TT in 15 patients (30%). In the CC group (n = 10) bleeding was found in 1 patient (2%). There were 19 patients (38%) with bleedings in combined group of CT and TT genotype (p = 0.0366). We compared the average doses of acenocoumarol in groups identified according to their genotypes: CC (3.45 mg/day), CT (2.64 mg/day), TT (3.07 mg/day) and found no significant differences. CONCLUSIONS: ABCB1 CT and TT genotypes were found to be significantly associated with higher risk of bleeding. There was no influence of ABCB1 polymorphisms on dosing regimens of acenocoumarol. Show more

Keywords: ABCB1 polymorphism, acenocoumarol, safety, valvular atrial fibrillation, bleeding

DOI: 10.3233/JRS-150672

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S15-S16, 2015

Authors: Chertovskikh, Y.V. | Malova, E.U. | Maksimova, N.R. | Popova, N.V. | Sychev, D.A.

Article Type: Abstract

Abstract: BACKGROUND: Vitamin K antagonists are effective in the prevention and treatment of thromboembolic disorders. Warfarin is one of the most widely prescribed vitamin K antagonists in the world [1, 2 ]. It has a narrow therapeutic range and a given dose may result in a large inter-individual variation of response. Insufficient dose may fail to prevent thromboembolism, while an overdose increases the risk of bleeding. Patient-specific factors (e.g., age, body size, race, concurrent diseases, and medications) explain some of the variability in warfarin dosage, but genetic factors influencing warfarin response explain a significantly higher proportion of this variability [3 ]. …Molecular analysis of the gene that encodes the target enzyme vitamin K epoxide reductase complex 1 (VKORC1 ) strongly suggests that its genetic variations greatly affect the individual response to oral anticoagulants [4–7 ]. OBJECTIVE: To evaluate effects of VKORC1 polymorphisms on warfarin dose excess anticoagulation (INR >4.0) in the population of Sakha (S) patients. METHODS: 53 patients (29-women, 24-men) with atrial fibrillation (68%), congestive heart failure (60%), hypertension (49%) and cardiac valve replacement (26%) were recruited. The age range was 26–80 years, with a mean age of 62.87 ± 12.57 years. International normalized ratio and plasma warfarin concentrations were determined. Genotyping was carried out by RT-PCR (real-time PCR). The three genetic polymorphisms of the gene VKORC1 G3673A (rs9923231) were studied: normal (GG) , heterozygous (GA) and homozygous (AA) . Fisher exact probability test and chi-square test (with Yates correction) were applied to compare data among the AA and GG + GA groups; also Mann-Whitney test was used. RESULTS: The median maintenance daily dose of warfarin among AA carriers was 3.0 mg/day [1.25–7.5 mg], while in GG and GA patients it was 3.13 mg/day [1.88–7.92 mg]. The mean daily warfarin dosage was higher in GG and GA genotype carriers 4.05 mg/day (SD ± 1.7) than in patients with AA genotype 3.13 (SD ± 1.5). Differences are of borderline significance (p = 0.054). Of the 41 patients who required warfarin doses of less than 5 mg, 28 (63%) were found to be AA carriers and 14 (37%) were GG, GA carriers. Differences were not quite significant (p = 0.072). Among 31 homozygous polymorphism carriers 2 (4%) patients developed overanticoagulation (INR >4.0), while among 22 normal and heterozygous polymorphisms carriers only 3 (6%) patients developed overanticoagulation (INR >4.0). Differences were not statistically significant (p = 0.36). CONCLUSIONS: No significant association between VKORC1 polymorphisms and the frequency of excess anticoagulation (INR >4.0) was found. This may be explained by the number of cases included. AA polymorphisms compared to other polymorphisms shows borderline difference in the warfarin dose. The results can be used for the development of a pharmacogenetic-guided warfarin dosing algorithm. Show more

Keywords: Polymorphisms of the VKORC1 gene on maintenance warfarin dose in the population of sakha (yakuts)

DOI: 10.3233/JRS-150673

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S17-S18, 2015

Authors: Kiku, P. | Voronin, S. | Golokhvast, K.

Article Type: Abstract

Abstract: BACKGROUND: According to WHO hereditary diseases and congenital malformations contribute significantly to the health of population. Thus, the problems of epidemiology, clinical presentation, diagnosis and treatment of congenital abnormalities are of interest for many researchers [2 ]. In addition, the dynamic accounting for the incidence of congenital malformations and hereditary diseases allows the researchers to assess the ecological situation in the region [1 ]. The occurrence of congenital anomalies in the world varies; it depends heavily on how carefully the data is collected [4 ]. Multifactorial or polygenic diseases develop under the influence of environmental factors in the presence of …defective genes. They can constitute up to 90% of all chronic pathology [2–5 ]. OBJECTIVE: To determine the incidence of congenital anomalies under the influence of environmental factors. METHODS: The study used the methodology of system evaluation of congenital anomalies incidence in Primorsky region, depending on bio-climatic and environmental conditions. The authors used health statistics for the period from 2000 to 2014, F.12 class for congenital abnormalities in adolescents and children that were compared in geographical and temporal aspects with environmental factors of 33 settlements in Primorsky region. The environment is represented by nature and climate (6 factor modules) and sanitation (7 factor modules) blocks of factors. When formalizing the information database of the environment a specially developed 10-point assessment scale was used. Statistical processing of the information was carried out using Pearson’s chi-squared test and multiple regression method from SSPS application program package. RESULTS: The study found that over the 15-year period the level of congenital abnormalities in children increased by 27.5% and in adolescents – by 35.1%, and in 2014 it amounted to 1687.6 and 839.3 per 100 000 people, respectively. The predictive model shows a steady further growth of this pathology. The incidence has increased dramatically since 2000. This was due to the beginning of activities of medicogenetic service since 1998: the legal framework and information database were created, the flow of pregnant women was formed actively, and invasive prenatal diagnosis was introduced. Incidence of congenital anomalies has a reliable statistical association (chi-square) with bioclimatic zones and ecological situation. The high level of pathology is observed in both teenagers and children in the critical environmental situation areas, where there are enterprises of coal, mining and chemical industry, ship repair, construction, engineering sites, and areas with intensive chemical use and improvement of agriculture. For the most part these are cities and districts of the region where more than a half of the major manufacturing plants of the 1st and 2nd hazard classes are located. Exceeding the maximum allowable concentrations (MAC) of harmful substances in the air, soil, and water in these areas often reaches tenfold. It should be noted that in the territories with the critical environmental situation a relatively high level of malformations is observed in adolescents in the continental bioclimatic zone, and in children – on the coast, suggesting the influence of different climatic factors. Also a high level of the same congenital anomalies was revealed in children in bioclimatic zones of the coast and transition zones with the intense environmental situation. According to the results of the regression analysis, the varying degrees of influence of ecological and hygienic factors on the incidence of congenital anomalies were determined. In children, up to 77.3% of the spread of pathology depends on the complex of parameters of the environment; the proportion of the influence of sanitary and hygienic indicators is 63.1%, and natural and climatic indicators - 14.2%. Such factors as the characteristics of the soil condition, the level of air pollution, chemical pollution and adverse physical factors in urban and rural settlements, transport load, the presence of hazard-class companies, and observance of sanitary protection zones are of the most significance. The influence of a complex of ecological and hygienic factors on the incidence of pathology in adolescents was 60.0%. The contribution of sanitary and hygienic parameters was 44.5%, and natural and climatic ones - 15.5%. Chemical pollution and adverse physical factors in urban and rural areas, the level of air pollution, traffic loads, and condition of the soil influence the most. Assessing the results of the analysis one should note that the incidence of congenital abnormalities in both children and adolescents depends largely on the same modular sanitary factors, but with varying degrees of influence. At the same time the natural and climatic block of factors has almost the same degree of influence in these age groups. CONCLUSIONS: A significant increase of congenital anomalies in children and adolescents is registered in Primorsky Region, and the same is projected for the next 5 years. – The incidence of congenital anomalies in the region depends on bioclimatic zones and ecological situation. The highest level of pathology is observed in children in the coastal bioclimatic zone, and in adolescents, in the continental bioclimatic zone in areas with critical environmental situation. – Varied degree of influence on the level of congenital anomalies by a complex of sanitary and climatic factors is determined. The leading role (44.5–63.1%) belongs to sanitary and hygienic parameters of the life environment. – The results obtained make it possible to develop a set of organizational, diagnostic and treatment, and preventive measures for the correction of health of the population. Show more

Keywords: Congenital, malformations, anomalies, hereditary diseases, population, children, adolescents

DOI: 10.3233/JRS-150674

Citation: International Journal of Risk & Safety in Medicine, vol. 27, no. s1, pp. S19-S20, 2015