Maternal Serum Copper and Some Metabolic Indexes in Late Second Trimester of Gestational Diabetes Mellitus Pregnancy.

BACKGROUND: Copper (Cu) is a physiologically important trace element during pregnancy. The study aim is to assess the altered level of serum Cu and its association with some metabolic indexes in Gestational Diabetes Mellitus (GDM). METHODS: A total of 108 pregnant women (aged 18 - 40, second trimester) are included in the study and divided into two groups (GDM n = 54; pregnant with normal glucose tolerance (NGT), n = 54) after performing a 2-hour 75-g oral glucose tolerance test (OGTT). Maternal blood samples are collected at 26 - 28 gestational week. All biochemical parameters are measured in serum from fasting venous blood. Serum Cu levels are analyzed by flame atomic absorption spectrophotometry (Perkin Elmer AAnalyst 300, USA). Body Mass Index (BMI), insulin sensitivity/resistance, triglyceride-glucose (TyG), TyG-BMI (triglyceride glucose-body mass) indexes are calculated by formulas. RESULTS: The following data were observed: significantly higher levels of serum Cu (p = 0.009), pre-pregnancy BMI (pre-pBMI), BMI at the GDM diagnosis (pBMI), TyG, pregnancy TyG-BMI (pTyG-BMI) p < 0.001, and triglycerides (Tgl) (p = 0.02) in GDM compared to NGT pregnancy. The study presents a positive correlation between serum Cu and pre-pBMI (p < 0.02), pBMI and pTyG-BMI (p < 0.001). Besides, pre-pBMI (mean ≥ 25 kg/m2), pBMI (mean ≥ 30 kg/m2), and pTyG-BMI are associated with 14.5% (OR 1.145, 95% CI: 1.064 - 1.232; p < 0.001), 15.3% (OR 1.153, 95% CI: 1.070 - 1.243; p < 0.001), and 5.9% (OR 1.059, 95% CI: 1.022 - 1.086; p < 0.001) increased risk for GDM development. No association is found between Cu and Tgl levels, fasting plasma glucose e(FPG) and TyG. ROC analysis suggests the serum Cu as a possible risk factor for GDM development. The analysis shows that at a cutoff point of ≥ 31.9 µmol/L, serum Cu presents a sensitivity and specificity of 64.8% and 66.7% in the prediction of GDM development (AUC = 0.659, p < 0.012). After adjustment for maternal age, gestational age, and family predisposition, the odds ratios (ORs) (95% CIs) still show association of Cu levels with increased GDM risk (OR 1.099, 95% CI 1.018 - 1.184, p = 0.013). CONCLUSIONS: pTyG-BMI index exhibits a better interaction than TyG index, Tgl, and glucose separately with serum Cu levels where BMI has a mediator's role.

First multi-center retrospective study assessed the compliance with and persistence of biological therapies in Bulgarian population with rheumatoid arthritis.

Rheumatoid arthritis is an inflammatory joint disease that causes progressive joint damage, leading to severe disability. Early diagnosis, optimal therapy, and strict adherence to the prescribed medication are key factors that allow for the cessation of the disease progression and the preserving of the patient's quality of life. The objective of this study was to estimate the compliance to and persistence of biologic disease-modifying anti-rheumatic drugs (bDMARDs) among the Bulgarian population with RA. This retrospective observational cohort study included 179 patients, who were tracked over a 36-month period. During baseline and subsequent follow-up visits (at months 6, 12, 24, and 36), we monitored the disease activity, side effects, medication tolerability and effectiveness, compliance, and persistence to the prescribed biologic agent. The compliance with bDMARDs among Bulgarian patients with RA was 85.5% in the first year, 76.0% in the second year, and 63.7% in the third year. The Infliximab cohort showed the lowest compliance rate (50%), with the other subgroups bDMARDs having similar results (64-70%) during the period of observation. The median therapy duration across all patient cohorts is 61.9 months (IQR 55.7-67.6). Our study did not establish any significant impact of gender, age and disease duration, concomitant treatment with methotrexate, type of biologic agent and previous exposure to biological agents on the treatment adherence. The compliance with and persistence of the prescribed bDMARD among the Bulgarian population with RA is unsatisfactory. Therapy interruption and nonadherence to recommended therapy are associated with disease progression and patient disability. The consequences include not only financial burdens but also psychosocial and physical impacts.

Adherence to biological therapies in patients with rheumatoid arthritis: a retrospective cohort study.

The advent of biologic disease-modifying antirheumatic drugs has dramatically changed the comprehensions of treatment and long-term prognosis in patients with rheumatoid arthritis. The potent therapeutic results can only be achieved if the patients adhere to prescribed medications. The objective of this study was to estimate the impact of age, gender, duration of the disease, concomitant Methotrexate therapy, prior exposure to biologic agents, disease activity, functional capacity, and health-related quality of life on adherence to biologic treatment among Bulgarian population with rheumatoid arthritis. This was a retrospective observational cohort study that included 179 patients. At the baseline visit and subsequent follow-up assessments at 6, 12, 24 and 36 months, patients were interviewed by a physician and underwent physical examinations. We monitored the changes in disease activity, functional capacity and health-related quality of life on each time point. Univariate and multivariate binary logistic regression was used to determine the prognostic value of possible predictors of treatment adherence. Our findings showed that only DAS28 score [odd ratio (OR) = 1.174; 95% CI 1.74-2.362] and HAQ score (OR 2.803; 95% CI 1.428-5.503) remained significant for the treatment adherence throughout the study period. The adherence to the biologic disease-modifying anti-rheumatic drugs among Bulgarian patients with rheumatoid arthritis is suboptimal. A multifaceted and comprehensive knowledge of the influencing factors can be useful for the development of different strategies that can improve treatment adherence.

Economic Burden of Cervical Cancer in Bulgaria.

Bulgaria is among the European Union (EU) countries with the highest burden of cervical cancers and life expectancy below the EU average. The majority of cervical cancer cases (more than 95%) are caused by the human papillomavirus (HPV). The aim of this retrospective, cost of illness study is to identify direct healthcare costs of cervical cancer in Bulgaria from the payer perspective and to calculate indirect costs and the associated years of life lost. Costs data were sourced from the National Health Insurance Fund from January 2018 to December 2020. Years of life lost were calculated based on the country and gender-specific life expectancy. Indirect costs due to productivity loss were calculated using the human capital approach. The total treatment costs for 3540 patients with cervical cancer are EUR 5,743,657 (2018), EUR 6,377,508 (2019), and EUR 6,751,182 (2020). The costs associated with drug acquisition and administration accounted for the majority (63%) of total healthcare costs followed by hospital management costs (14%). An estimated total of 20,446 years of life were lost due to cervical cancer for the period 2018-2020. The costs of productivity losses are estimated at EUR 7,578,014. Our study showed that the economic burden of cervical cancer in Bulgaria is substantial. Focus on cervical cancer prevention via vaccination against the human papillomavirus, timely screening, early diagnosis, and higher vaccine coverage rates could reduce its economic burden in Bulgaria.

Benefits of using a microencapsulated vitamin D delivery system in women with polycystic ovary syndrome.

OBJECTIVE: To compare and assess the efficacy of two vitamin D delivery systems (oil-based and microencapsulated) on 25-hydroxy-vitamin D (25(OH)D) levels, body mass index (BMI) and insulin resistance (IR) in women with established polycystic ovary syndrome (PCOS) and vitamin D deficiency. MATERIALS AND METHODS: A monocentric, retrospective study was conducted, using the data of 70 female patients, who visited the endocrinology department of the "Dr. Shterev" Hospital, Sofia, Bulgaria between May 2020 and September 2020. The patients were divided into two groups according to the type of vitamin D3 supplementation: either a microencapsulated liposomal form (n=35), or a conventional oil-based form (n=35). The following clinical measures were analysed and compared: BMI, serum levels of 25(OH)D, fasting plasma glucose levels, fasting immunoreactive insulin (IRI), homeostatic model assessment (HOMA) index, levels of antimullerian hormone (AMH) II generation, and testosterone. In all selected patients, these measurements were performed at baseline and 3 months after initiation of vitamin D supplementation. RESULTS: Significantly increased serum levels of 25(OH)D were observed in patients supplemented with the microencapsulated form of vitamin D3 in the third month from the beginning of therapy, compared with the control group (p=0.003). In the microencapsulated vitamin D group, there was a decrease in IRI serum levels (p=0.023), HOMA-IR (p=0.021), serum AMH (p=0.010) and testosterone levels (p=0.006). The fasting plasma glucose levels did not change significantly. CONCLUSION: The results of our study show that the patients supplemented with a microencapsulated form of vitamin D3 achieved faster compensation of 25(OH)D levels, which in turn, under equal conditions, led to significant improvement in the metabolic profile, in particular insulin sensitivity.

MMEF25-75 may predict significant BDR and future risk of exacerbations in asthmatic children with normal baseline FEV1.

(1) Background: Several recent studies on the clinical value of spirometry indexes demonstrated high sensitivity of FEF25-75 as a marker of bronchial obstruction in asthmatics with normal baseline spirometry. Our study aims to evaluate the clinical value of maximal mid-expiratory flow in children with asthma. (2) Methods: For two years, 257 children were included - 211 with asthma and 46 healthy controls. Pre- and post-bronchodilator spirometry, atopic status determination and asthma control assessment were performed. (3) Results: The small airway obstruction (SAO) group (FEV1≥80%, ММEF25/75<65%) demonstrated significantly lower values for FEV1, FEV1/FVC, PEFR, МMMF25/75 and a significant higher bronchodilator response (BDR, ΔFEV1% init. ≥12%) compared to normal baseline spirometry group (FEV1>80%, MMEF25/75≥65%) (Р<0.0001). In addition, we found a statistically significant difference in FEF25-75/FVC median between asthmatics and healthy controls (Р<0.0001) regardless of the FEV1 value. Children with SAO have a 2.338-fold higher risk of poor asthma outcome (OR 95% CI [1.077-5.294]) and a 6.171-fold (OR 95% CI [2.523-15.096]) greater probability of demonstrating positive BDR, compared to children with normal baseline spirometry. MMEF25/75 was found to be a good predictor for positive BDR with AUC 0.843 (CI 0.781-0.845) and a best cut-off value of 58.1% (77.8% sensitivity and 78.8% specificity). (4) Conclusion: Our results confirmed that a small but substantial group of asthmatic children with normal baseline FEV1 and low MMEF25-75 are at higher risk for poor asthma outcomes.

The Role of Placental Growth Factor in the Prediction of Carbohydrate and Thyroid Disorders during Pregnancy.

Background and objectives: To assess whether placental growth factor (PlGF) levels may have a predictive value for the onset of gestational diabetes mellitus (GDM) and thyroid dysfunction during pregnancy. Materials and Methods: This single-center retrospective analysis was conducted at the Specialized Hospital for Active Treatment in Obstetrics and Gynecology "Dr. Shterev", Sofia, Bulgaria, from December 2017 to December 2019. Using pregnant women's electronic records, we analyzed and compared the data of 412 women diagnosed with GDM and 250 women without evidence for carbohydrate disorders. Thyroid function was tested in all patients at the time of performing GDM screening. The following measurements were compared and assessed: body mass index (BMI), fasting blood glucose levels, thyroid-stimulating hormone levels (TSH), free thyroxine, and triiodothyronine (FT4 and FT3) levels, and serum placental growth factor (PlGF). The sensitivity and specificity of PlGF as a predictive marker for GDM and thyroid dysfunction were analyzed using receiver operating characteristic (ROC) curves. Results: There were no significant differences between GDM and control groups in terms of age and BMI (p > 0.05). In patients with established GDM, the PlGF corrected multiple of the median (MoM) was significantly higher compared to the control group (0.9 vs. 0.7, p < 0.001). The ROC-AUC for the prediction of GDM and thyroid dysfunction during pregnancy was 0.68 (95% CI 0.64-0.72) and 0.61 (95% CI 0.57-0.65), respectively. Conclusions: Our results underscore the potential role of PlGF as a biomarker in the prediction and diagnosis of GDM and thyroid dysfunction during pregnancy.

Process evaluation of a bio-behavioural HIV research combined with prevention among GBMSM in 13 European countries.

Comparative European data using Second Generation Surveillance System (SGSS) are scarce among gay, bisexual and other men who have sex with men. This study evaluated the implementation of Sialon II, a bio-behavioural HIV research combined with targeted HIV prevention in 13 European cities conducted in collaboration with community partners. A mixed-methods process evaluation assessed the project's coverage, outputs, quality, challenges and opportunities for improvement. Data collected through structured questionnaire from 71 data collectors from community-based organisations and semi-structured interviews with 17 managers of participating gay venues were analysed. Overall implementation was successful, achieving 4901 valid behavioural questionnaires and obtaining 4716 biological samples. Challenges in conducting bio-behavioural research in gay venues related to strict research protocols and unfavourable characteristics of venues. Formative research, collaboration with community gay venues, and offering HIV prevention emerged as facilitators. Community researchers' training was crucial for fidelity to research protocols, increased trust amongst communities and enabled data collectors to effectively address practical problems in the field. Scientifically sound SGSS with community participation is feasible and allows for including 'hard-to-reach' populations. Prevention benefits include awareness raising, capacity building and sexual health promotion in gay venues. The findings are beneficial for epidemiological research among other HIV key populations.

Estimating the percentage of European MSM eligible for PrEP: insights from a bio-behavioural survey in thirteen cities.

OBJECTIVES: This paper aims to estimate the percentage of European men who have sex with men (MSM) who may benefit from pre-exposure prophylaxis (PrEP), applying the three most widely used HIV risk indices for MSM (MSM Risk Index, Menza score, San Diego Early Test (SDET) score) and drawing on a large-scale multisite bio-behavioural survey (Sialon II). METHODS: The Sialon II study was a bio-behavioural survey among MSM implemented in 13 European cities using either time-location sampling or respondent-driven sampling. Biological and behavioural data from 4901 MSM were collected. Only behavioural data of HIV-negative individuals were considered. Three widely used risk indices to assess HIV acquisition risk among MSM were used to estimate individual HIV risk scores and PrEP eligibility criteria. RESULTS: 4219 HIV-negative MSM were considered. Regardless the HIV risk score used and the city, percentages of MSM eligible for PrEP were found to range between 5.19% and 73.84%. Overall, the MSM Risk Index and the Menza score yielded broadly similar percentages, whereas the SDET Index provided estimates constantly lower across all cities. Although all the three scores correlated positively (r>0.6), their concordance was highly variable (0.01

Being in the Closet. Correlates of Outness Among MSM in 13 European Cities.

Data for MSM continue to show a high risk of acquiring HIV-STIs. Within this population, outness seems to have an impact on both risk-taking and on health seeking behaviors. The objective of this study was to assess the relationship between socio-demographic, behavioral characteristics, testing behaviors, and outness level among MSM using data from a multi-center bio-behavioral cross-sectional study carried out in 13 EU cities. A multilevel analysis was conducted to identify factors associated with being open ("out") versus not being open ("in"). A total of 4,901 MSM were enrolled in the study and were classified as "out" in 71% of the cases. MSM "out" were more likely to report HIV testing and being reached by HIV prevention programs compared to MSM who were "in." The results confirm the key role of outness in relation to different healthy and risky behavior, ranging from testing to party-drug use.

Study of clinical experience with different approaches to controlled ovarian hyperstimulation: a focus on safety and efficacy.

OBJECTIVES: Current retrospective cohort study analyses clinical database records of 4792 assisted reproduction procedures to assess the significance of target effectiveness endpoints from a safety perspective. METHODS: Stimulation protocols with urinary, recombinant or combination of both types gonadotrophin preparations are compared according to the following primary endpoints: incidence of ovarian hyperstimulation syndrome (OHSS), cycle cancellation, follicle count, induced estradiol values, clinical pregnancy achieved and cycles reached embryo transfer/freezing. We have investigated the incidence of cases evaluated as 'risky for OHSS' by secondary efficacy endpoints (exogenous gonadotrophin exposure, luteinising hormone and progesterone values, oocyte yield, eggs with normal maturation). The following statistical methods were applied: descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson chi-square test, Fisher's exact test, binary logistic regression. RESULTS: Only 16 cases (0.42%) of moderate and delayed OHSS were established. Three hundred and seven (8.6%) stimulation cycles have been cancelled, principally among urinary protocols. Although the clinical pregnancy rate does not differ significantly in compared groups, punctured follicle count, oocyte yield and progesterone level were higher for recombinant preparations, followed by combined and urinary protocols. Follicle count, mean estradiol and luteinising hormone levels are within the 'safe window' for all investigated groups, associated with minimised risk of stimulation cancellation. The mean follicle-stimulating hormone (FSH) dose was highest in urinary protocols at the same duration of stimulation compared with recombinant products. The younger age, bigger follicle count, oocytes yield, mature oocytes count, percentage of fertilised oocytes, more embryos transferred and the later day of embryo transfer are critical for both assisted reproduction techniques (ART) success rate and the safety profile of sterility treatment. CONCLUSIONS: Safety surveillance of ART exceeds the incidence of OHSS. Suboptimal effectiveness of stimulation protocols may also jeopardise the well-being of ART patients. Gonadotrophin exposure, induced values of sex hormones, and quantity and quality of extracted oocytes should be considered to minimise any unintended suffering of treated couples.

COMPARISON OF RADIATION DOSE AND IMAGE QUALITY IN CTA OF THE PERIPHERAL ARTERIES.

The aim of this study is to investigate the possibility of replacing the standard CTA protocol for peripheral arteries with a low dose CTA protocol without affecting the diagnostic image quality. Therefore a single centre retrospective study was conducted involving 200 exams of patients undergoing lower limb angiography. All exams were performed on a 64-row detector CT and the vascular density, muscle density, noise and radiation dose of each image were assessed. The subjective image quality was evaluated additionally by an experienced radiologist. Significant differences were observed in radiation dose and image quality between the standard CTA protocol and the lower dose CTA protocol. No differences were found between objective and subjective image quality. Using 80kVp instead of 120kVp as the tube voltage for lower limb CTA reduces the radiation dose without affecting the diagnostic image quality.

Behavioural and demographic correlates of undiagnosed HIV infection in a MSM sample recruited in 13 European cities.

BACKGROUND: Reducing the number of people with undiagnosed HIV infection is a major goal of HIV control and prevention efforts in Europe and elsewhere. We analysed data from a large multi-city European bio-behavioural survey conducted among Men who have Sex with Men (MSM) for previously undiagnosed HIV infections, and aimed to characterise undiagnosed MSM who test less frequently than recommended. METHODS: Data on sexual behaviours and social characteristics of MSM with undiagnosed HIV infection from Sialon II, a bio-behavioural cross-sectional survey conducted in 13 European cities in 2013/2014, were compared with HIV-negative MSM. Based on reported HIV-testing patterns, we distinguished two subgroups: MSM with a negative HIV test result within 12 months prior to the study, i.e. undiagnosed incident infection, and HIV positive MSM with unknown onset of infection. Bivariate and multivariate associations of explanatory variables were analysed. Distinct multivariate multi-level random-intercept models were estimated for the entire group and both subgroups. RESULTS: Among 497 participants with HIV-reactive specimens, 234 (47.1%) were classified as previously diagnosed, 106 (21.3%) as incident, and 58 (11.7%) as unknown onset based on self-reported status and testing history. MSM with incident HIV infection were twice as likely (odds ratio (OR) = 2.22, 95% confidence interval (95%CI): 1.17-4.21) to have used recreational substances during their last anal sex encounter and four times more likely (OR = 3.94, 95%CI: 2.14-7.27) not to discuss their HIV status with the last anal sex partner(s). MSM with unknown onset of HIV infection were 3.6 times more likely (OR = 3.61, 95%CI: 1.74-7.50) to report testing for a sexually transmitted infection (STI) during the last 12 months. CONCLUSIONS: Approximately one third of the study participants who are living with HIV were unaware of their infection. Almost two-third (65%) of those with undiagnosed HIV appeared to have acquired the infection recently, emphasizing a need for more frequent testing. Men with the identified behavioural characteristics could be considered as primary target group for HIV Pre-Exposure Prophylaxis (PrEP) to avoid HIV infection. The increased odds of those with unknown onset of HIV infection to have had an STI test in the past year strongly suggests a lost opportunity to offer HIV testing.

HIV serostatus knowledge and serostatus disclosure with the most recent anal intercourse partner in a European MSM sample recruited in 13 cities: results from the Sialon-II study.

BACKGROUND: Knowledge of HIV status can be important in reducing the risk of HIV exposure. In a European sample of men-who-have-sex-with-men (MSM), we aimed to identify factors associated with HIV serostatus disclosure to the most recent anal intercourse (AI) partner. We also aimed to describe the impact of HIV serostatus disclosure on HIV exposure risks. METHODS: During 2013 and 2014, 4901 participants were recruited for the bio-behavioural Sialon-II study in 13 European cities. Behavioural data were collected with a self-administered paper questionnaire. Biological specimens were tested for HIV antibodies. Factors associated with HIV serostatus disclosure with the most recent AI partner were examined using bivariate and multilevel multivariate logistic regression analysis. We also describe the role of serostatus disclosure for HIV exposure of the most recent AI partner. RESULTS: Thirty-five percent (n = 1450) of the study participants reported mutual serostatus disclosure with their most recent AI partner or disclosed having HIV to their partner. Most of these disclosures occurred between steady partners (74%, n = 1077). In addition to the type of partner and HIV diagnosis status, other factors positively associated with HIV serostatus disclosure in the multilevel multivariate logistic regression model were recent testing, no condom use, and outness regarding sexual orientation. Disclosure rates were lowest in three south-eastern European cities. Following condom use (51%, n = 2099), HIV serostatus disclosure (20%, n = 807) was the second most common prevention approach with the most recent AI partner, usually resulting in serosorting. A potential HIV exposure risk for the partner was reported by 26% (111/432) of HIV antibody positive study participants. In 18% (20/111) of exposure episodes, an incorrect HIV serostatus was unknowingly communicated. Partner exposures were equally distributed between steady and non-steady partners. CONCLUSIONS: The probability of HIV exposure through condomless AI is substantially lower after serostatus disclosure compared to non-disclosure. Incorrect knowledge of one's HIV status contributes to a large proportion of HIV exposures amongst European MSM. Maintaining or improving condom use for anal intercourse with non-steady partners, frequent testing to update HIV serostatus awareness, and increased serostatus disclosure particularly between steady partners are confirmed as key aspects for reducing HIV exposures amongst European MSM.

Socio-demographic Characteristics, Sexual and Test-Seeking Behaviours Amongst Men Who have Sex with Both Men and Women: Results from a Bio-behavioural Survey in 13 European Cities.

Within the MSM population, men who have sex with both men and women (MSMW) are identified as a high-risk group both worldwide and in Europe. In a multi-centred bio-behavioural cross-sectional study, we aimed to assess the relationship(s) between socio-demographic factors, stigma, sexual behavioural patterns, test seeking behaviour and sero-status amongst MSMW. A multi-level analysis was conducted to identify factors associated with being MSMW versus Men who have Sex with Men Only (MSMO). A total of 4901 MSM were enrolled across the 13 study sites. Participants were categorised as MSMW in the 12.64% of the cases. Factors such as educational status, perceived homonegativity, testing facilities knowledge and HIV testing lifetime seem to be relevant factors when characterising the MSMW group. The results highlight the vulnerability of MSMW and the wide spectrum of risky behavioural and psycho-social patterns, particularly in terms of HIV testing, 'outness', and perceived stigma.

Delayed intraventricular hemorrhage in moderate-to-severe traumatic brain injury: prevalence, associated risk factors, and prognosis.

BACKGROUND: The presence of traumatic intraventricular hemorrhage (tIVH) on an admission CT scan is related to a worse outcome and increased mortality in patients with moderate and severe TBI. Currently, there is no available data regarding the predictive value of the appearance of tIVH as a delayed finding on follow-up CT scan. The purpose of this study was to determine the prevalence, associated risk factors, and prognosis of delayed tIVH. METHODS: The study is based on 401 consecutive adult patients (age ≥ 18 years) with moderate-to-severe TBI admitted in our hospital for a 5-year period. At least one control CT was performed in 320 (79.8 %) patients. The prevalence of delayed tIVH was assessed and the potential risk factors and mortality were analyzed. RESULTS: Delayed tIVH appeared in 38 cases (11.9 % of the second CT scans and 9.5 % of all patients). The patients with delayed tIVH are significantly older (57.39 vs. 48.63 years, p = 0.009) and developed statistically significant more frequent enlargement of an existing lesion (47.4 vs. 20.2 %, p = 0.001) and appearance of a new lesion (100 vs. 33.7 %, p < 0.001). Delayed tIVH appeared significantly more frequent in surgically treated patients with ICH as a main surgical lesion (p = 0.010) and is associated with significantly higher mortality (p < 0.001). CONCLUSIONS: Delayed tIVH as a progression of injury in moderate-to-severe TBI has a relatively high occurrence and is associated with increased mortality. The only factor independently related to a new appearance of tIVH is the presence of ICH as a main surgical lesion on the control preoperative CT scans.

EGFR mutations in patients with non small-cell lung cancer in Bulgaria and treatment with gefitinib.

PURPOSE: To evaluate the EGFR mutations in non small cell lung cancer (NSCLC) patients in Bulgaria, as well as to summarize the outcomes of patients with EGFR mutations, treated with gefitinib as first- or subsequent-line therapy. METHODS: From January 2010 to March 2012 tumor samples from773 NSCLC patients were evaluated for EGFR mutations. RESULTS: Seventy-one mutations were found and 34 patients were treated with gefitinib. Complete remission (CR) was achieved in 2 patients (6.9%), partial remission (PR) in 11 (37.9%), stable disease (SD) in 13 (44.8%), and disease progression (PD) in 3 (10.3%). Higher objective response rate was seen in women and in never-smokers.The mean progression-free survival (PFS) was 11.1 months (95% CI 9.1-13.1), registered in 29 patients (median PFS 10 months ; 95% CI 8.9-11.1).Tolerability to gefitinib was acceptable, with prevalence of skin toxicity, and it did not lead to any significant decline of the patients' quality of life. CONCLUSION: This is the first study in Bulgaria to evaluate EGFR mutations in NSCLC patients,which were encountered in 9.4% of the studied population. The present study confirms the benefits of first- and subsequent-lines of gefitinib for the treatment of this patient group. Our data give grounds for the conclusion that gefitinib is an effective and well-tolerated therapeutic option for patients with locally advanced and metastatic NSCLC harboring EGFR mutations.

Comparison of health-related quality-of-life measurement instruments in diabetic patients.

The objective of the study was to compare three different questionnaires (Short Form (SF)-6D, EuroQuol (EQ)-5D and WHO-5) to establish which one is more sensitive and which one gives an adequate assessment of the quality of life in patients with diabetes. In an observational and transversal study with duration of 4 months, in 5 Bulgarian cities, 146 patients were randomly selected. The following quality-of-life measuring instruments were applied: 146 questionnaires SF-6D, 146 questionnaires EQ-5D and 103 questionnaires of WHO-5. Descriptive statistics, chi-Square and correlation coefficients were used for data analysis. The study assessed the quality of life of patients suffering from diabetes mellitus with a mean age of 57.39 years (standard deviation (SD) 17.087); 95% confidence interval (CI) 54.60-60.19; 76% of the patients had diabetes type 2. The patients received a mean SF-6D score of 0.6290, an EQ-5D score of 0.6272, a visual analogue scale score of 0.7158 and a WHO-5 score of 0.4635. Preferences measured by the SF-6D and by the EQ-5D showed significant correlations with one another, and the Pearson coefficient was r = 0.906 (p < 0.01). The most current version of SF-6D, based on the 2002 model, was found to be valid and reliable when compared to the EQ-5D and is a questionnaire alternative to assess preferences in economic analysis carried out in health care.

Physicians' knowledge and attitude towards adverse event reporting system and result to intervention--randomized nested trial among Bulgarian physicians.

AIM: To identify the factors that influence physicians' under-reporting in Bulgaria and their attitude towards adverse event reporting system and to estimate the role of self-education by providing educational materials. METHODS: A randomized nested trial among physicians-general practitioners and specialists in Bulgaria was conducted by a validated questionnaire in order to evaluate their knowledge and attitude towards adverse event reporting system. One month after the intervention the participants were re-visited and were asked to answer the same questions again in order to estimate the change in their knowledge and attitude towards pharmacovigilance system and to obtain their evaluation for the materials provided. RESULTS: The response rate was 91. Fifty seven (46.3%) physicians were not familiar with the pharmacovigilance system. The most common reason for non-reporting adverse drug reactions (ADRs) was uncertainty concerning the relationship between the suspected drug and ADRs, the ADRs were already known and the fact that the physician was not aware where they should report. Although 103 (83.7%) respondents in the entry survey and by 102 (82.9%) of those participating in the exit survey consider ADRs reporting as their obligation (p more than 0.05), only 50 (40.7%) and 31 (25.2%), respectively answered that they had ever reported ADRs; 109 (88.6%) of the surveyed physicians assessed the provided educational materials as useful for them. CONCLUSION: The physicians in Bulgaria have poor knowledge for the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude towards ADRs reporting system. National drug regulatory authority should play a more active role in improving physicians' adherence to the ADRs reporting systems and the developed educational pack can be used in nationwide campaign.