Budgetary Impact of Medicinal Therapies for Rare Diseases in Bulgaria.

BACKGROUND: Rare diseases have been continually outlined as one of the causes for the National Health Insurance Fund's (NHIF) deficit spending in Bulgaria. AIM: To estimate the budgetary impact of rare disease medicinal therapies from NHIF perspective for 2014 and 2016. MATERIALS AND METHODS: Budgetary impact of rare diseases is calculated as a percentage of NHIF total pharmaceutical spending. Total expenditure per ICD-10 code, mean annual number of patients reimbursed and mean annual cost per patient are analysed. RESULTS: Budgetary impact of rare diseases reached a plateau of about 9% of NHIF total pharmaceutical spending for 2014-2016. Mean number of patients reimbursed and mean annual cost per patient increased by median rates of 4.27% and 2.54%, respectively. Glycogen storage disease, neuropathic heredofamilial amyloidosis and C1 esterase inhibitor deficiency stood out, as they had the second, fourth and fifth most expensive medicinal treatment cost. While accounting for only 92 patients in 2016, these three conditions contributed for 22.89% of NHIF total expenditure on rare disease medicinal therapies. For comparison, coagulation defects, with the biggest total cost per indication, had a similar budgetary impact - 24.88%, but for 277 patients reimbursed. CONCLUSIONS: Our study does not support the concerns about uncontrolled growth of expenditures for rare disease medicinal therapies. Nevertheless, there is a need for enhanced post-marketing surveillance and performance-based payment of these treatments. Development, collection and analysis of local real-world data have been increasingly applied as a tool to advance these health policy goals.

Economic Burden And Health-Related Quality Of Life Of Patients With Cystic Fibrosis In Bulgaria.

OBJECTIVE: The aim of this study was to determine the economic burden from a societal perspective and health-related quality of life (HRQOL) of patients with cystic fibrosis (CF) in Bulgaria. MATERIALS AND METHODS: We conducted a cross-sectional study of 33 patients with CF and 17 caregivers from Bulgaria. Data on socio-demographic characteristics, health resource utilisation, informal care, labor productivity losses and HRQOL were collected from questionnaires completed by patients or their caregivers. HRQOL was evaluated with the EuroQol 5-domain (EQ-5D-3L) questionnaire. RESULTS: Median annual costs of CF in Bulgaria were € 24 152 per patient in 2012 as a reference year. Median annual costs for children were found to be significantly higher than those for adults - € 31 945 vs. € 15 714 (p = 0.012). This outcome came from statistically significant differences in costs for main informal carer (p < 0.001) and costs for other informal carers (p = 0.022). As a single cost item, drugs had the biggest monetary impact. Median annual drug costs were € 13 059. Bulgarian CF patients showed low HRQOL results - 50 median VAS score and 0.592 median health utilities. A quarter of patients even rated their health state as worse than death. CONCLUSION: CF patients from Eastern Europe remain a vulnerable population with risk factors for worse health outcomes. Our study provided a state-of-the art analysis that facilitates the elaboration, adoption and application of targeted public health policies to tackle CF-related problems at national and European level.

Micromeritic procedures in assessing antinuclear antibody patterns in immunofluorescent assay.

AIM: The aim of this study was to introduce a micromeritic procedure (a statistical approach for small objects) in indirect immunofluorescence assay (IFA) to find objective quantitative parameters of antinuclear antibody (ANA) patterns which could support a diagnosis of auto-immune diseases. MATERIALS AND METHODS: Sera of patients with systemic autoimmune diseases, McCoy-Plovdiv serum-free cell line, goat anti-human immunoglobulin-G FITC-conjugate, fluorescent microscope, computer-assisted digital image processing, analysis using a micromeritic procedure, ANOVA. RESULTS: Three ANA fluorescent patterns (homogeneous, rim and speckled) were analyzed by the micromeritic procedure. Parameters for the image brightness of the pixels (pixel grey value) were obtained and discussed as objective characteristics of fluorescent patterns: maximum ANA-linkage volume and surface density were established for the objects with speckled localization pattern. CONCLUSION: The micromeritic method for getting objective quantitative values of ANA fluorescent patterns in indirect immunofluorescent assay might be a valuable tool aiding in immunological diagnosing if integrated in a laboratory software package.

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.

Diagnostic value of combinations of symptoms of migraine and tension-type headache included in the diagnostic criteria for children and adolescents in the International Classification of Headache Disorders 2nd Edition.

AIM: To suggest diagnostic combinations of symptoms for migraine and tension type headache (TTH), and for differentiation of overlapping headache (classified as either migraine or TTH) through evaluation of the diagnostic value of combinations of characteristics included in the International Headache Society diagnostic criteria for migraine and TTH in children and adolescents. PATIENTS AND METHODS: The study comprised an epidemiological school-based study (412 of 1029 pupils with chronic/recurrent headache) and a clinical study conducted in the Pediatric Neurology Ward and outpatient clinic at Plovdiv Medical University Hospital (203 patients with chronic/recurrent headache). An inclusion criterion was at least two episodes of headache during the last year. Exclusion criteria were: headache occurring only during acute infections; withdrawal of informed consent. Headache was classified according to the International Classification of Headache Disorders 2nd edition (ICHD-II) The diagnostic value of all combinations of items in criteria C and D for migraine and TTH was measured by sensitivity, specificity, and odds ratio. RESULTS: The combination "unilateral location, severe intensity, aggravation by physical activity" had 100% specificity for migraine. The combination "bilateral location, pressing-tightening quality, mild intensity, no aggravation by physical activity" had 100% specificity for TTH. The combinations: "migrainous location, severe intensity, aggravation by physical activity", "severe intensity, nausea", "pulsating quality, nausea", "pulsating quality, migrainous location, aggravation by physical activity" seemed to pose the greatest risk for developing migraine. These combinations--"no nausea, no photophobia", "bilateral location, mild intensity and either no aggravation by physical activity or pressing-tightening quality, or no nausea or no photophobia" increased the most the TTH risk. Using these combinations as additional criteria for overlapping headache we classified 50% of overlapping headache as TTH and 8.3% as migraine. CONCLUSIONS: Some combinations of symptoms clarify the diagnosis of migraine and TTH. More than 50% of overlapping headache could be differentiated as TTH or MWA by the proposed combinations.

Prevalence of cytomegalovirus infection in hospitalized infants.

UNLABELLED: Data on cytomegalovirus infection (CMV) prevalence and course in hospitalized infants are rather scarce, obsolete and considerably inconsistent. AIM: to determine the prevalence, rate of clinical manifestations, risk factors and predictive capacity of clinical manifestations of CMV infection in hospitalized infants during their first year of life. PATIENTS AND METHODS: All 163 infants hospitalized in the Pediatric Ward for Nonrespiratory Pathology in a tertiary hospital were serologically screened for cytomegalovirus infection for 10 months. In infants up to 6 months old that were CMV IgG (+) and CMV IgM (-) we followed up the CMV IgG concentration or compared it with that of their mothers. RESULTS: The CMV prevalence for the entire study sample was 33.1 +/- 3.7% (54 seropositive out of 163 examined infants); in newborns it was 19.4 +/- 6.7% (7 of 36), in infants aged 1-3 months--23.8 +/- 5.4% (15 of 63), in 4-6-month olds--28.1 +/- 8.1% (9 of 32), and in 7-12-month old--71.9 +/- 8.1% (23 of 32). The rates of clinically apparent infections in the respective groups was 33.3 +/- 6.5%, 57.01 +/- 20.2%, 53.3 +/- 13.3%, 33.3 +/- 16.6%, and 13.0 +/- 7.17%. The overall rate of clinically apparent CMV infection in all 163 children was between 11.0 +/- 2.5% and 17.2 +/- 2.9%. The probability of CMV infection increased with age and duration of breastfeeding. Hepatitis, cerebral vasculopathy and pneumonia (alone or combined) turned out to be predictors of CMV infection, but none of these symptoms had a frequency greater than 22%. CONCLUSIONS: We found a high rate of cytomegalovirus infections in hospitalized infants less than one year of age. This infection is the reason why at least 10% of the newborns and 12% of the children aged 1 to 3 months were hospitalised. The course was clinically apparent in over half of the infected children of up to 3 months of age.

Psychomotor development after ganciclovir selectively treated congenital and perinatal cytomegalovirus infection.

AIM: To study the development of children with selectively treated cytomegalovirus infection. PATIENTS AND METHODS: We studied prospectively a risk group of 12 children with cytomegalovirus infection. These children were diagnosed by serological screening in the first three months after birth and are defined as congenital and perinatal infections. Thirteen infants with no serological evidence of previous or present cytomegalovirus infection at 4-12 months of age were used as controls. Ganciclovir in a dose of 10-15 mg/kg/day for at least 2 weeks followed by 5-7.5 mg/kg/day administered intravenously for at least 2 weeks more was given to 4 children from the risk group with PCR confirmed cytomegalovirus infection: to one with suspected congenital infection that presented with encephalitis, to two children with abnormal auditory evoked potentials (AEPs) and other non-neurological symptoms of a suspected congenital infection, and to one child with proven congenital infection with systemic manifestations. There was no infant with cytomegalic inclusion disease in the study. All other children in the risk group that had clinically manifested infection received isoprinosine in a dose of 50 mg/kg for one month. RESULTS: Psychomotor development delay at age three was found in two children from the risk group and in one child in the control group. There was no difference between the two groups regarding the frequency of paroxysmal events, sensory deficiency or frequent illnesses. CONCLUSIONS: The prognosis in cases of cytomegalovirus infection diagnosed at three years of age and treated selectively can be similar to that in infection free 3-year-old children (if there are no cases of CMV inclusion disease).

Case-Control Study to Evaluate the Oral Hygiene Habits in 31 Children with Hemophilia in Bulgaria Using the Oral Health Impact Profile-14 (OHIP-14) Questionnaire.

BACKGROUND For patients with hereditary coagulopathies such as hemophilia, the most common dental problem is spontaneous oral bleeding caused by daily oral hygiene habits like tooth brushing. Because of fear of bleeding, children with hemophilia often skip routine oral hygiene procedures, which can lead to dental caries and periodontal diseases. This case control study aimed to evaluate the oral hygiene awareness and hygiene practices of children with hemophilia from 6 to 18 years of age in Bulgaria. MATERIAL AND METHODS This study was conducted over 4 years and included 31 patients (children). A sociological approach was used, with direct individual questionnaires for self-assessment of dental habits. Statistical analyses were performed using SPSS. RESULTS There was no significant difference between groups in methods of oral hygiene. The duration of oral hygiene procedures was 1 min (n=5, 16.13±6.61%) or 2 min (n=13, 41.94±8.86%), which was considered insufficient for proper oral hygiene. Children who had received oral hygiene advice by a dentist brushed their teeth significantly longer (n=9, 69.23±12.80%) than those who had not. There was a considerable difference between the reasons for the last dental visit between the groups of children (χ²=5.18, P.

Between-birth intervals in newly married Bulgarian families.

UNLABELLED: An essential component of the family planning of a newly married couple is determining not only the number of children but also the spacing of births. AIM: To study the preferences of newly married couples of Bulgarian ancestry from Plovdiv for between-birth intervals and factors that have effect on them. METHODS: The present transversal study was designed to investigate family planning in young families of Bulgarian origin from the town of Plovdiv at the time of submission of documents for state registration of marriage. The primary sociological information was gathered by a direct individual inquiry of 384 families. The data were compared with data from a similar study performed in 1995. RESULTS: Only one third of the women are willing to have a child immediately after marriage. Men prefer this to happen 1.61 +/- 0.07 year after the marriage while women favour longer protogenetic interval--1.84 +/- 0.06. The opinion of the spouses inquired about the age of women at last birth shows that there is statistically significant increase in this variable from 34.89 +/- 0.29 years in 1995 to 36.33 +/- 0.32 years in 2000. No statistically significant difference was found between the protogenetic intervals of 2000 and 1995. CONCLUSIONS: The increased age at marriage, the postponement of childbirth and increase in the anticipated age of last birth supports the thesis that the Bulgarian family type has undergone changes towards the family type characteristic for the countries in Western Europe.

Opinion of newly wed Greek couples about the nature and functions of modern family. Similarities and differences with the opinion of Bulgarian couples.

BACKGROUND: Among the European countries, Greece has exhibited a significant decline in its total fertility rate. Unlike Bulgaria, Greece conducts little in-depth research to study comprehensively the attitudes of newlywed couples toward family planning and reproductive behaviour. AIM: The present study aimed at exploring the opinion of newly married Greek couples about the nature and functions of modern family and comparing them with those of Bulgarian couples. MATERIAL AND METHODS: We conducted two parallel cross-sectional studies gathering the primary data by individual questionnaire survey using established methods. RESULTS: More than half of the respondents planned to have a child within two years after marriage. Most of the respondents think that the main purpose of having children in a family is to give meaning to a person's life. In both Greece and Bulgaria giving birth to a child in a family is believed to be the consequence of merely life-experience related and emotional prerequisites that arise from the deeply rooted traditional attitudes in these countries towards the value and role of family. The prevailing opinion is that children should be raised by the parents in their parents' home until they become three years of age. Greek women are more inclined than Bulgarian women to stay at home and raise their children even until they complete school and are ready to care for them after graduation and marriage.

Specific peculiarities in the family model of the Turkish minority in Bulgaria.

INTRODUCTION: There is a significant decrease in the average number of children in Bulgarian families during the 80s and 90s. This phenomenon is noticed even in some regions with usually higher natality, like Kurdjali, Pazardjik, Blagoevgrad, etc. AIM: The aim of this study was to characterize the reproductive behaviour of Turkish minority in Bulgaria. METHODS: 260 women in reproductive age with Turkish ethnical origin from the town of Kurdjali (Bulgaria) were approached by a direct individual inquiry. Data were analysed by descriptive statistics and non-parametric tests. RESULTS AND DISCUSSION: The average number of children in the Turkish families in Bulgaria is 1.69 +/- 0.04 and in 78.2% of cases, the pregnancy has been wanted and approved by both spouses. This fact determines the reproduction of this ethnos to be a realized necessity. The comparison of indices, characterizing the reproductive behaviour of Turkish and Bulgarian population shows a statistically significant difference between the real and desired number of children in the family (P < 0.001). However, the analysis failed to find a statistically significant difference in the opinion of both compared groups about the ideal number of children in the family (P > 0.05). CONCLUSIONS: There are no changes in the traditional conceptions of Turkish people about the family and role of women. We observe significant differences in the reproductive plan and behaviour between the Bulgarian and Turkish population.