Landscape analysis of available European data sources amenable for machine learning and recommendations on usability for rare diseases screening.

BACKGROUND: Patient registries and databases are essential tools for advancing clinical research in the area of rare diseases, as well as for enhancing patient care and healthcare planning. The primary aim of this study is a landscape analysis of available European data sources amenable to machine learning (ML) and their usability for Rare Diseases screening, in terms of findable, accessible, interoperable, reusable(FAIR), legal, and business considerations. Second, recommendations will be proposed to provide a better understanding of the health data ecosystem. METHODS: In the period of March 2022 to December 2022, a cross-sectional study using a semi-structured questionnaire was conducted among potential respondents, identified as main contact person of a health-related databases. The design of the self-completed questionnaire survey instrument was based on information drawn from relevant scientific publications, quantitative and qualitative research, and scoping review on challenges in mapping European rare disease (RD) databases. To determine database characteristics associated with the adherence to the FAIR principles, legal and business aspects of database management Bayesian models were fitted. RESULTS: In total, 330 unique replies were processed and analyzed, reflecting the same number of distinct databases (no duplicates included). In terms of geographical scope, we observed 24.2% (n = 80) national, 10.0% (n = 33) regional, 8.8% (n = 29) European, and 5.5% (n = 18) international registries coordinated in Europe. Over 80.0% (n = 269) of the databases were still active, with approximately 60.0% (n = 191) established after the year 2000 and 71.0% last collected new data in 2022. Regarding their geographical scope, European registries were associated with the highest overall FAIR adherence, while registries with regional and "other" geographical scope were ranked at the bottom of the list with the lowest proportion. Responders' willingness to share data as a contribution to the goals of the Screen4Care project was evaluated at the end of the survey. This question was completed by 108 respondents; however, only 18 of them (16.7%) expressed a direct willingness to contribute to the project by sharing their databases. Among them, an equal split between pro-bono and paid services was observed. CONCLUSIONS: The most important results of our study demonstrate not enough sufficient FAIR principles adherence and low willingness of the EU health databases to share patient information, combined with some legislation incapacities, resulting in barriers to the secondary use of data.

Expression of HIF-1α, Ki67, SMA and E-cadherin in endometriosis, endometrial and ovarian carcinoma.

INTRODUCTION: Endometriosis is a benign gynecological condition that shares many characteristics with cancer cells, including immune evasion, survival, adhesion, invasion, and angiogenesis. The simultaneous investigation of tissue hypoxia, EMT, and proliferative index in endometriosis, endometrial, and ovarian carcinomas may provide new insight into the evolution and progression of gynecological neoplasms.

Clinical and virological profile of locally acquired acute hepatitis E in South Bulgaria.

INTRODUCTION: Acute hepatitis E virus (HEV) infection is recognized as a zoonosis in several European countries. We describe the characteristics and outcomes of locally acquired acute HEV hepatitis. METHODOLOGY: A prospective study was conducted among adult patients with acute HEV hepatitis at the University Hospital in Plovdiv, South Bulgaria between January 2020 and May 2022. An acute HEV infection case was a patient with acute hepatitis and laboratory-confirmed anti-HEV IgM antibodies and/or HEV RNA in serum. Demographic data, clinical manifestations, laboratory test results, and outcomes were recorded. RESULTS: A total of 46 patients were selected. Median age of 65 years (interquartile range [IQR] 50.8-74.3). 28 (60.87%) were male. 22 (47.83%) had comorbidities such as diabetes (15), liver cirrhosis (3), hepatitis B virus infection (2), and malignancies (2). Of the 46, 18 (39.13%) patients were viremic and, HEV genotype 3 was detected. The median (IQR) serum alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet, and international normalized ratio levels were 992 (495.8-1714.3) U/L, 715 (262.5-1259.3) U/L, 204 (132.3-235.5) µmol/L, 204 (132.3-235.5) ×109 L, and 1.0 (0.89-1.19), respectively. Six patients with underlying liver diseases had severe hepatitis. A young patient with osteoarthritis progressed to acute liver failure and died. The persistent HEV infection was ruled out in 2 malignant patients who tested HEV RNA negative three months after discharge. CONCLUSIONS: Acute HEV hepatitis is a diagnosis to consider after excluding other causes of acute viral hepatitis. A diagnostic workup should include timely testing for HEV to identify the most vulnerable to severe consequences.

Ventilator-Associated Pneumonia in the Neonatal Intensive Care Unit-Incidence and Strategies for Prevention.

The second most prevalent healthcare-associated infection in neonatal intensive care units (NICUs) is ventilator-associated pneumonia (VAP). This review aims to update the knowledge regarding the incidence of neonatal VAP and to summarize possible strategies for prevention. The VAP incidence ranges from 1.4 to 7 episodes per 1000 ventilator days in developed countries and from 16.1 to 89 episodes per 1000 ventilator days in developing countries. This nosocomial infection is linked to higher rates of illness, death, and longer hospital stays, which imposes a substantial financial burden on both the healthcare system and families. Due to the complex nature of the pathophysiology of VAP, various approaches for its prevention in the neonatal intensive care unit have been suggested. There are two main categories of preventative measures: those that attempt to reduce infections in general (such as decontamination and hand hygiene) and those that target VAP in particular (such as VAP care bundles, head of bed elevation, and early extubation). Some of the interventions, including practicing good hand hygiene and feeding regimens, are easy to implement and have a significant impact. One of the measures that seems very promising and encompasses a lot of the preventive measures for VAP are the bundles. Some preventive measures still need to be studied.

Are the European reference networks for rare diseases ready to embrace machine learning? A mixed-methods study.

BACKGROUND: The delay in diagnosis for rare disease (RD) patients is often longer than for patients with common diseases. Machine learning (ML) technologies have the potential to speed up and increase the precision of diagnosis in this population group. We aim to explore the expectations and experiences of the members of the European Reference Networks (ERNs) for RDs with those technologies and their potential for application. METHODS: We used a mixed-methods approach with an online survey followed by a focus group discussion. Our study targeted primarily medical professionals but also other individuals affiliated with any of the 24 ERNs. RESULTS: The online survey yielded 423 responses from ERN members. Participants reported a limited degree of knowledge of and experience with ML technologies. They considered improved diagnostic accuracy the most important potential benefit, closely followed by the synthesis of clinical information, and indicated the lack of training in these new technologies, which hinders adoption and implementation in routine care. Most respondents supported the option that ML should be an optional but recommended part of the diagnostic process for RDs. Most ERN members saw the use of ML limited to specialised units only in the next 5 years, where those technologies should be funded by public sources. Focus group discussions concluded that the potential of ML technologies is substantial and confirmed that the technologies will have an important impact on healthcare and RDs in particular. As ML technologies are not the core competency of health care professionals, participants deemed a close collaboration with developers necessary to ensure that results are valid and reliable. However, based on our results, we call for more research to understand other stakeholders' opinions and expectations, including the views of patient organisations. CONCLUSIONS: We found enthusiasm to implement and apply ML technologies, especially diagnostic tools in the field of RDs, despite the perceived lack of experience. Early dialogue and collaboration between health care professionals, developers, industry, policymakers, and patient associations seem to be crucial to building trust, improving performance, and ultimately increasing the willingness to accept diagnostics based on ML technologies.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems.

High vaccine confidence and strong approval of the mandatory immunization schedule among Bulgarian general practitioners in 2022.

In a context of recently decreasing childhood immunization coverage and low uptake of COVID-19 vaccines in Bulgaria, this study measures vaccine hesitancy among general practitioners (GPs) in the country, as they are central to forming patients' attitudes. In 2022, a face-to-face survey was conducted through a simple random sample from an exhaustive national database of Bulgarian GPs. This study measured attitudes on vaccine importance, safety, and effectiveness, and attitudes toward the Bulgarian immunization schedule. Information was collected on demographic and GP practice characteristics and possible predictors of vaccine confidence in order to test for associations with attitudes toward immunization. GP attitudes toward vaccines and the immunization schedule in Bulgaria were generally positive. Among 358 respondents, 351 (98%,95%CI96-99%) strongly agreed/agreed that vaccines are important, 352 (98%,95%CI96-99%) that vaccines are effective, and 341 (95%,95%CI93-97%) that vaccines are safe. 347 respondents (97%,95%CI95-98%) affirmed that "it's good that vaccines from the children's immunization schedule are mandatory", and 331 (92%,95%CI89-95%) agreed with the statement "Bulgaria's childhood immunization has my approval". Trust in information from official institutions was among the strongest predictors of vaccine confidence. Respondents' vaccine confidence levels are within the ranges reported by GPs in other European countries and above those reported within the general Bulgarian population. GPs' vaccine confidence is highly associated with trust in official institutions. It is important to maintain trust in official institutions and to support GPs in communicating vaccine knowledge with patients so that vaccine hesitancy in the general population is countered.

Hepatitis E Virus (HEV) Infection among Hemodialysis Patients from Southern Bulgaria.

Viral hepatitis B and C are widely recognized problems in hemodialysis (HD) patients. There have been increasing reports of the importance of the hepatitis E virus (HEV) in recent years, but the worldwide data on the seroprevalence of HEV among them are conflicting. The aim of the present study was to assess the seroprevalence of HEV in HD patients and to analyze the predictors of seropositivity. This study was conducted in 2020 in the central part of southern Bulgaria. A total of 225 patients were enrolled. An enzyme-linked immunosorbent assay for the determination of anti-HEV IgM/IgG was used. All patients were tested for the presence of HEV RNA. Anti-HEV IgM alone and anti-HEV IgG alone were found in 6 (2.7%) and 14 (6.2%) patients, respectively, and in 4 (1.8%) patients, they were found simultaneously. All patients were HEV RNA-negative. The overall HEV seroprevalence was 10.7% (24/225). The binominal logistic regression analysis of available predictors confirmed the role of vascular access and a duration of dialysis treatment over 5 years as predictors significantly associated with increased risk for HEV, and the consumption of bottled water with lower levels of HEV IgG seroprevalence among hemodialysis patients. The accumulated data are the basis for comparative analysis in subsequent trials in the same dialysis centers and for enhancing the range of screening markers used in this particular patient group.

Challenges in mapping European rare disease databases, relevant for ML-based screening technologies in terms of organizational, FAIR and legal principles: scoping review.

Background: Given the increased availability of data sources such as hospital information systems, electronic health records, and health-related registries, a novel approach is required to develop artificial intelligence-based decision support that can assist clinicians in their diagnostic decision-making and shorten rare disease patients' diagnostic odyssey. The aim is to identify key challenges in the process of mapping European rare disease databases, relevant to ML-based screening technologies in terms of organizational, FAIR and legal principles. Methods: A scoping review was conducted based on the PRISMA-ScR checklist. The primary article search was conducted in three electronic databases (MEDLINE/Pubmed, Scopus, and Web of Science) and a secondary search was performed in Google scholar and on the organizations' websites. Each step of this review was carried out independently by two researchers. A charting form for relevant study analysis was developed and used to categorize data and identify data items in three domains - organizational, FAIR and legal. Results: At the end of the screening process, 73 studies were eligible for review based on inclusion and exclusion criteria with more than 60% (n = 46) of the research published in the last 5 years and originated only from EU/EEA countries. Over the ten-year period (2013-2022), there is a clear cycling trend in the publications, with a peak of challenges reporting every four years. Within this trend, the following dynamic was identified: except for 2016, organizational challenges dominated the articles published up to 2018; legal challenges were the most frequently discussed topic from 2018 to 2022. The following distribution of the data items by domains was observed - (1) organizational (n = 36): data accessibility and sharing (20.2%); long-term sustainability (18.2%); governance, planning and design (17.2%); lack of harmonization and standardization (17.2%); quality of data collection (16.2%); and privacy risks and small sample size (11.1%); (2) FAIR (n = 15): findable (17.9%); accessible sustainability (25.0%); interoperable (39.3%); and reusable (17.9%); and (3) legal (n = 33): data protection by all means (34.4%); data management and ownership (22.9%); research under GDPR and member state law (20.8%); trust and transparency (13.5%); and digitalization of health (8.3%). We observed a specific pattern repeated in all domains during the process of data charting and data item identification - in addition to the outlined challenges, good practices, guidelines, and recommendations were also discussed. The proportion of publications addressing only good practices, guidelines, and recommendations for overcoming challenges when mapping RD databases in at least one domain was calculated to be 47.9% (n = 35). Conclusion: Despite the opportunities provided by innovation - automation, electronic health records, hospital-based information systems, biobanks, rare disease registries and European Reference Networks - the results of the current scoping review demonstrate a diversity of the challenges that must still be addressed, with immediate actions on ensuring better governance of rare disease registries, implementing FAIR principles, and enhancing the EU legal framework.

Effect of Er:YAG Laser Exposure on the Amorphous Smear Layer in the Marginal Zone of the Osteotomy Site for Placement of Dental Screw Implants: A Histomorphological Study.

The placement of dental screw implants typically involves the use of rotary techniques and drills to create a bone bed. This study explores the potential benefits of combining this method with an Er:YAG laser. Split osteotomies were performed on 10 jaws of euthanized domestic pigs (Sus scrofa domestica), with 12 mandibular implant osteotomies in each jaw, divided into 4 groups. In order to make a comprehensive assessment of the effect of Er:YAG lasers, histomorphological techniques were used to measure the reduction in amorphous layer thickness after Er:YAG laser treatment, both with and without the placement of dental screw implants from different manufacturers. Following bone decalcification and staining, the thickness of the amorphous layer was measured in four groups: Group A-osteotomy performed without Er:YAG laser treatment-had amorphous layer thicknesses ranging from 21.813 to 222.13 µm; Group B-osteotomy performed with Er:YAG laser treatment-had amorphous layer thicknesses ranging from 6.08 to 64.64 µm; Group C-an implant placed in the bone without laser treatment-had amorphous layer thicknesses of 5.90 to 54.52 µm; and Group D-an implant placed after bone treatment with Er:YAG laser-had amorphous layer thicknesses of 1.29 to 7.98 µm. The examination and photomicrodocumentation was performed using a LEICA DM1000 LED microscope (Germany) and LAS V 4.8 software (Leica Application Suite V4, Leica Microsystems, Germany). When comparing group A to group B and group C to D, statistically significant differences were indicated (p-value = 0.000, p < 0.05). The study demonstrates the synergistic effects and the possibility of integrating lasers into the conventional implantation protocol. By applying our own method of biomodification, the smear layer formed during rotary osteotomy can be reduced using Er:YAG lasers. This reduction leads to a narrower peri-implant space and improved bone-to-implant contact, facilitating accelerated osseointegration.

Age and Gender Trends in the Prevalence of Markers for Hepatitis E Virus Exposure in the Heterogeneous Bulgarian Population.

The prevalence of hepatitis E virus (HEV) in the Bulgarian population remains underestimated. The aim of the present study was to evaluate age and gender trends in HEV prevalence in the heterogeneous Bulgarian population. Stored serum samples from blood donors and different patient sub-populations-kidney recipients (KR), patients with Guillain-Barre syndrome (GBS), Lyme disease (LD), patients with liver involvement and a clinical diagnosis other than viral hepatitis A and E (non-AE), hemodialysis (HD) and HIV-positive patients (HIV)-were retrospectively investigated for markers of past and recent/ongoing HEV infection. The estimated overall seroprevalence of past infection was 10.6%, ranging from 5.9% to 24.5% for the sub-populations evaluated, while the seroprevalence of recent/ongoing HEV infection was 7.5%, ranging from 2.1% to 20.4%. The analysis of the individual sub-populations showed a different prevalence with respect to sex. In regard to age, the cohort effect was preserved, as a multimodal pattern was observed only for the GBS sub-population. Molecular analysis revealed HEV 3f and 3e. The type of the population is one of the main factors on which the anti-HEV prevalence depends, highlighting the need for the development of guidelines related to the detection and diagnosis of HEV infection with regard to specific patient populations.

Application of bioceramic endodontic sealers in clinical practice.

OBJECTIVE: To assess the attitude of dental medicine practitioners towards the usage of bioceramic endodontic sealers in their clinical practice. METHODS: The survey-based study was conducted from March 2019 to February 2020 in Plovdiv, Bulgaria, after approval from the ethics review committee of the Medical University of Plovdiv, and comprised dentists of either gender who attended in person events organised by the Bulgarian Dental Association. Data was collected using a self-reporting 20-item questionnaire. Data was analysed using SPSS 26. RESULTS: Of the 200 forms distributed, 164(82%) were duly filled; 52(32%) from males and 112(68%) from females. The overall median age was 46.50 years (interquartile range: 21 years). Mean work experience was 23.68±11.43 years. Significant differences were found between the application of bioceramic sealers and the type of acquired specialty, the endodontic obturation technique and the final irrigation solution (p<0.05). CONCLUSIONS: Majority of the respondents did not feel the need to change the endodontic obturation technique in order to adopt the usage of bioceramic sealers.

Preconception-Health-Related Attitudes of Bulgarian Women of Reproductive Age.

Preconception care (PC) is relatively new area of practice. While the volume and quality of PC activities depend on local settings, the awareness of women is critical for the successful promotion of PC services. The aim of this study was to examine the preconception-health-related attitudes and experiences of Bulgarian women of reproductive age. A qualitative study conducted among 20 women aged 18 to 49 years was performed between May and July 2022. Two focus groups were used with mixed samples of nulligravida, pregnant, and postpartum women. The participants thought that the Internet and their obstetrician-gynecologist were the only places where they could learn about getting pregnant. Only two of them discussed their PC plans with their physicians. Women pointed out that general practitioners (GPs) need to be more proactive in promoting PC. All respondents outlined the need for a web-based educational platform that could serve as a primary source of health information for future families. The role and functions of GPs in the continuum of PC should be reconsidered. We recommend targeted educational measures for all stakeholders, including women and GPs. In this regard, an easily accessible, knowledge-based web platform could enhance Bulgarian women's awareness and perceptions of PC.

Chest CT diagnostic potential as a tool for early detection of suspected COVID-19 cases in pandemic peaks.

INTRODUCTION: The emergence of severe acute respiratory syndrome coronavirus disease (COVID-19) in China at the end of 2019 caused a massive global outbreak that has become a major public health issue. AIM: Our aim was to investigate the diagnostic potential of chest CT in screening patients suspected of having COVID-19 in high-prevalence settings. MATERIALS AND METHODS: This is a real-life, prospective, observational study involving 260 patients. All patients received chest CT scan at the emergency department (ED) of Kaspela University Hospital, Plovdiv, Bulgaria and RT-PCR testing for suspected COVID-19 from March 27 to December 31, 2020. COVID-19 likelihood was assessed by assigning each CT scan to a particular category of the COVID-19 Reporting and Data System (CO-RADS). IBM SPSS v. 26 was used to process the data. RESULTS: The male-to-female distribution ratio was 1.4:1 - 150 (57.7%) males vs. 110 (42.3%) females (p=0.014). The median age was 55 yrs (range 46-65 yrs). Discharged patients were 247 (95.0%), the rest died in the COVID-19 intensive care unit. Males were 4.13 times more likely to be diagnosed with CO-RADS≥3 score than females. Increasing age was associated with an increased likelihood of being classified with higher CO-RADS scores. The ROC curves analysis demonstrated that CO-RADS ≥3 was the optimal cutoff for discrimi-nating between a positive and negative PCR (Youden's index J=0.67), with an AUC of 0.825 (95% CI 0.72-0.93), sensitivity of 91.9% (95% CI 87.7%-95.1%), specificity of 75.0% (95% CI 53.3%-90.2%) and accuracy of 76.4% (95% CI 70.7%-81.4%). CONCLUSIONS: The results of this study reveal that a CT examination can provide a quick and accurate diagnosis of patients with sus-pected COVID-19 infection, whereas the PCR test is time-consuming, and the delay in receiving results can be substantial when the incidence curve begins to grow rapidly.

Diagnostic benefits of 18F-FDG PET/CT in cases of prosthetic infective endocarditis.

Infective endocarditis (IE) is a difficult-to-diagnose provocative disease that causes significant morbidity and mortality. The first-line imaging test for the diagnosis of IE is echocardiography. However, in cases of prosthetic IE or IE associated with intracardiac devices, its sensitivity is limited. A new diagnostic tool, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT), improves diagnosis in these difficult cases. The most recent European guidelines for IE (2015) include this imaging modality as a primary diagnostic criterion. We present a case of culture-negative prosthetic IE diagnosed with 18F-FDG PET/CT.

Laser biomodification of the bone bed surface for placement of spiral dental implants: a study based on scanning electron microscopy.

INTRODUCTION: Various rotary and mechanical instruments are used in conventional oral surgery for osteotomies. Despite the implementation of effective cooling systems, it is difficult to prevent thermal damage to the adjacent bone caused by heat generated during the procedure. A smear layer forms on the surface, which can impede the interaction of blood elements with the underlying tissue, resulting in a delayed healing process.

Stochastic modelling of scalar time series of varicella incidence for a period of 92 years (1928-2019).

INTRODUCTION: Varicella is an acute, highly contagious disease, characterised by generalised vesicular exanthema caused by the initial infection with varicella zoster virus (VZV) which usually affects children aged 2 to 8 years. AIM: To analyse the changes of varicella incidence in Bulgaria over the period of 1928-2019. MATERIALS AND METHODS: The time series analysis is based on the official data for varicella incidence (per 100,000) in Bulgaria for ninety-two years (1928-2019), obtained from three major sources. We utilized the method to construct a time series model of overall incidence (1928-2019) using time series modeller in SPSS v. 25. We followed all three steps of the standard ARIMA methodology to establish the model - identification, parameter estimation, and diagnostic checking. RESULTS: Stochastic scalar time series modelling of the varicella incidence from 1928 to 2019 was performed. The stochastic ARIMA (0,1,1) was identified to be the most appropriate model. The decomposition of varicella incidence time series into a stochastic trend and a stationary component was reasoned based on the model defined. In addition, we assessed the importance of the long-term and immediate effect of one shock. The long-term forecast was also under discussion. CONCLUSIONS: The ARIMA model (0,1,1) in our study is an adequate tool for presenting the varicella incidence trend and is suitable to forecast near future disease dynamics with acceptable error tolerance.

Ventilator-Associated Pneumonia in Neonates Admitted to a Tertiary Care NICU in Bulgaria.

Ventilator-associated pneumonia (VAP) is the second most common hospital-acquired infection (HAI) among neonatal patients in the intensive care units (ICUs) and is a serious challenge for neonatologists because it affects critically ill patients who need prolonged mechanical ventilation. In Bulgaria, there is no detailed data at regional and national levels on the characteristics of VAP in newborns, which imposes a necessity for specific studies of risk factors and etiology of VAP. The aim of the study was to analyze the frequency, characteristics and risk factors for the occurrence of VAP in newborns hospitalized in intensive care unit. This was a prospective study, conducted between January 2017 and June 2018 in the NICU of University Hospital "St. George" Plovdiv, Bulgaria. The sample consisted of 507 neonates, followed up prospectively, 107 of whom were placed on mechanical ventilation for ≥48 h. VAP was diagnosed in 33 out of 107 neonates (31%). The VAP incidence rate was 35.06/1.000 ventilator days. We confirmed differences between the median birth weight (1,310 vs. 1,690 g, p = 0.045) and average gestational age (31.08 g.w. vs. 33.08 g.w, p = 0.04) of the patients with and without VAP. The average stay of patients with VAP in the NICU was statistically significantly longer than the hospital stay of non-VAP patients (35.70 ± 21.84 days vs. 21.77 ± 17.27 days (t = 3.241, p = 0.002). In neonates with VAP, the duration of mechanical ventilation was statistically significantly longer compared with non-VAP patients (16.88 ± 11.99 vs. 5.42 ± 4.48; t = 5.249, p = 0.000). A statistically significant prevalence of Gram-negative bacteria among VAP patients was demonstrated (91%) compared to the Gram-positive (9%), p < 0.05. The leading causative agent of VAP was Klebsiella pneumoniae ESBLs + (27%), followed by Acinetobacter baumannii (14%), Pseudomonas aeruginosa (12%) and Escherichia coli (12%). In multivariate logistic regression, mechanical ventilation >7 days was established as an independent risk factor for VAP (OR 3.6; 95% CI: 1.7-6.5, p = 0.003). VAP remains a serious and outstanding issue in pediatric and neonatal intensive care units. The findings of the current study emphasize that the birth weight, gestational age, and duration of hospital stay have a significant association with ventilator-associated pneumonia.

Cost Analysis for Patients with Ventilator-Associated Pneumonia in the Neonatal Intensive Care Unit.

The concept of improving the quality and safety of healthcare is well known. However, a follow-up question is often asked about whether these improvements are cost-effective. The prevalence of nosocomial infections (NIs) in the neonatal intensive care unit (NICU) is approximately 30% in developing countries. Ventilator-associated pneumonia (VAP) is the second most common NI in the NICU. Reducing the incidence of NIs can offer patients better and safer treatment and at the same time can provide cost savings for hospitals and payers. The aim of the study is to assess the direct costs of VAP in the NICU. This is a prospective study, conducted between January 2017 and June 2018 in the NICU of University Hospital "St. George" Plovdiv, Bulgaria. During this period, 107 neonates were ventilated for more than 48 h and included in the study. The costs for the hospital stay are based on the records from the Accounting Database of the setting. The differences directly attributable to VAP are presented both as an absolute value and percentage, based on the difference between the values of the analyzed variables. There are no statistically significant differences between patients with and without VAP in terms of age, sex, APGAR score, time of admission after birth and survival. We confirmed differences between the median birth weight (U = 924, p = 0.045) and average gestational age (t = 2.14, p = 0.035) of the patients in the two study groups. The median length of stay (patient-days) for patients with VAP is 32 days, compared to 18 days for non-VAP patients (U = 1752, p < 0.001). The attributive hospital stay due to VAP is 14 days. The median hospital costs for patients with VAP are estimated at €3675.77, compared to the lower expenses of €2327.78 for non-VAP patients (U = 1791.5, p < 0.001). The median cost for antibiotic therapy for patients with VAP is €432.79, compared to €351.61 for patients without VAP (U = 1556, p = 0.024). Our analysis confirms the results of other studies that the increased length of hospital stays due to VAP results in an increase in hospital costs. VAP is particularly associated with prematurity, low birth weight and prolonged mechanical ventilation.

Reporting adverse events of COVID-19 vaccines: The case of Bulgaria.

As a member state of the European Union, where vaccines against COVID-19 are available and affordable, Bulgaria reports the lowest immunization coverage and the most pronounced vaccine distrust. The present study aimed to assess the self-reported adverse reactions following COVID-19 vaccination as a possible tool to increase the trust in vaccines. A cross-sectional survey-based study, covering 761 vaccinated respondents, was conducted in Plovdiv (469 with an mRNA vaccine and 292 with an adenoviral vector vaccine). Descriptive statistics parametric and non-parametric methods were applied. Statistical significance was set at p<0.05. The median age of the respondents was 42 years, females (72.5%). At least one adverse reaction was reported in 89.9% of those immunized with mRNA vaccine and 93.8% in the adenoviral vector vaccine group (p>0.05). They were mild to moderate and resolved within several days. The levels of local reactions were comparable: 91.7% in those who received mRNA and 89.7% in those who received an adenoviral vector vaccine (p = 0.366). The most common types of systemic reactions were fatigue, headache, and muscle pains. An association was found between the systemic reactions and the type of vaccine administered: 59.7% in mRNA recipients and 89.4% in adenoviral vector vaccinees (p<0.001). None of the registered systemic reactions required medical attention. There were 3 reports of generalized urticaria after an mRNA and 2 after an adenoviral vector vaccine. The reported reactions are relatively high but expected and no adverse events have been reported that are not listed in the official Summary of Product Characteristics.