Insight into reimbursement decision-making criteria in Bulgaria: implications for orphan drugs.

OBJECTIVE: This article's objective is to critically assess the Bulgarian legislation on health technology assessment (HTA). It analyses how innovative therapies and orphan drugs in particular would respond to the regulators' decision-making criteria for reimbursement. MATERIALS AND METHODS: The study features critical analysis of current decision-making criteria for drug reimbursement in Bulgaria, as well as hypothetical scenario planning for orphan medicinal products. RESULTS: The approval for inclusion into the Positive Drug List (PDL) (which is a must for reimbursement) has been reorganised into an assessment scoring system with decision-making criteria (presence of therapeutic alternative, clinical effectiveness, safety, pharmacoeconomics and societal value) divided into weighted indicators. An explicit threshold has been set--a medicinal product must score 60 points at least to be included in PDL. Under the currently defined reimbursement decision-making criteria a hypothetical middle-of-the-road scenario planning shows that an orphan drug would score 20 points for therapeutic alternative, 28 for clinical effectiveness and 12 for safety. It would take no points for pharmacoeconomics and societal value. This leaves the orphan drugs with a total score of 60 points, making the final outcome of real-life assessment and decision-making heavily dependent on small fluctuations. CONCLUSIONS: The current reimbursement decision-making framework in Bulgaria seems to be generalised and not sufficiently transparent. It is unable to precisely assess innovative health technologies. The availability of a therapeutic alternative emerges as a key reimbursement decision-making criterion for orphan drugs, as these innovative products nominally provide the first medicinal therapy alternative to rare diseases.

Economic aspects of medical errors.

The critical problem of medical errors and the associated costs has recently been increasingly in the focus of attention of a number of world renowned experts. In the present article we review in detail and analyse the economic aspects of this problem. A methodology to assess the cost of medical errors and an algorithm for their prevention are presented. The cost of a medical error and the expenses required to avoid and prevent it are compared using graphical analysis of the prevention cost curve and the medical error compensation damages cost curve.

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.

Acute Management of Deep Facial Burns.

INTRODUCTION: Management of deep facial burns is a serious challenge for many reasons: a considerable anatomic and functional diversity is concentrated in a small space, a uniform treatment does not exist, late sequelae are frequent and may be severe, and the literature on the subject is ambiguous. AIM: To analyse management of deep facial burns. PATIENTS AND METHODS: A retrospective medical chart review was conducted for 569 patients with deep facial burns hospitalized between January 2005 and January 2015. Demographic data, type, depth and size of burns, chronology and type of surgical treatment, length of hospital stay, and type and incidence of late sequelae were analysed and compared. RESULTS: Over 10 years, 596 patients with deep facial burns, 216 (36.24%) females and 380 (63.76%) males, aged from 5 months to 95 years (mean 39.5±26 years) were treated. The most common burn agents were hot liquids and flames. The mean total body surface area (TBSA) burned was 17±13.3%. Concomitant eye injury was detected in 63 (10.6%) patients. Priority was given to the early, meticulous, staged surgical approach aimed at sparing the survived tissues and rapid wound closure. Follow-up ranged from 3 months to 5 years. Late functional sequelae were documented for 50 (8.38%) patients and ocular sequelae - for 33 (5.54%) of them. There was no incidence of secondary corneal perforation or definitive loss of vision. CONCLUSIONS: Adequate and up-to-date acute management of deep facial burns based on early, judicious, surgical approach could limit initial damage and reduce late sequelae.

Bisphosphonate-associated Osteonecrosis of the Jaws: a Survey of the Level of Knowledge of Dentists about the Risks of Bisphosphonate Therapy.

INTRODUCTION: Bisphosphonate-associated osteonecrosis of the jaws (BAONJ) is a side effect of treatment with bisphosphonate (BP). Reports of this complication have increased recently. AIM: To evaluate the level of knowledge of dentists from Plovdiv, Bulgaria, about possible complications of bisphosphonate therapy of patients in dental practice. MATERIALS AND METHODS: Three hundred and twenty-three dental practitioners from Plovdiv, Bulgaria, took part in an anonymous survey containing 25 questions, designed to evaluate the knowledge of dentists about the complications of BP therapy. RESULTS: Oral and maxillofacial surgeons have the best knowledge about the indications and side effects of BP therapy, while dentists with a specialty in Pediatric Dentistry and General Dentistry have insufficient knowledge. Of the respondents, 17.03% are absolutely uninformed about BP and their side effects, and 1/2 declare that they have never had a patient with complications from BP therapy in their practice, probably due to a lack of awareness of the problem. Approximately half of the dentists we surveyed agree to carry out prophylactic examinations of patients receiving BP and know what the prophylactic examination includes. Only 15.48% of the respondents have correctly responded that in order to be treated as clinically healthy, patients should have stopped taking BP for more than 10 years. CONCLUSION: With the exception of specialists in Oral and Maxillofacial Surgery, dental practitioners in Plovdiv and the region are poorly informed about the complications associated with BP therapy. Therefore, efforts must be made to make these dentists better informed about BAONJ, especially about the methods and means of preventing this condition.

Maternal Serum Concentrations of Corin, Endoglin, PP13, and sFlt-1 and their Changes with Advancement of Pregnancy and Correlation with Doppler of Uterine Arteries.

BACKGROUND: Pre-eclampsia (PE) affects 2% to 5% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. Since PE has complex pathogenesis and treatment is still not found, effective methods for prediction and prevention of PE are still actively searched. AIM: The aim of this study was to find the mean maternal serum concentration of four proteins in Bulgarian pregnant women and to investigate the correlation with uterine artery pulsatility index in the first and second trimester of pregnancy. MATERIALS AND METHODS: In this prospective case-control study, maternal serum concentrations of corin, sEndoglin, PP13, and sFlt-1 were measured, pulsatility index of uterine artery (PI-UA) was assessed in 40 women with Doppler, twice during pregnancy - at the 11th - 13th weeks of gestation and the 20th gestational week. They were randomized in two groups: an experimental group: with increased PIUA at gestational week 13 and a control group: with normal PI-UA. All pregnancies were followed up until the day of delivery and outcomes were recorded. RESULTS: There was no significant difference in the APGAR score and birth weight of the newborns between groups. We found no significant difference in the mean concentration of sEnd, sFlt-1 and PP13 between 11-13 weeks of gestation and 20 week of gestation in the control and experimental groups. Statistically significant difference was found only in the mean concentrations of corin between weeks 11-13 and week 20 in both control (t=3.27; p=0.004) and experimental group (t=3.22; p=0.005). Corin levels and the mean PI of uterine arteries tended to decrease with progression of pregnancy in both groups. CONCLUSIONS: Further prospective studies of larger populations are required to develop a panel of multiple predictors for PE.