How Managed Entry Agreements Influence the Patients' Affordability to Biological Medicines-Bulgarian Example.

Managed entry agreements are applied in almost all European countries in order to improve patients' access to therapy. The current study aims to evaluate the changes in the affordability of biological medicines for patients in Bulgaria during 2019-2022. The study is a top-down macroeconomic analysis of the key economic indicators and reimbursed costs of biologic therapies. Affordability was determined as the number of working hours needed to pay for monthly therapy. The average NHIF budget for pharmaceuticals increased significantly along with inflation in the healthcare sector. Bulgarian patients had to devote a large part of their income to buying medicines if a co-payment existed. The percentage of the monthly income of pensioners needed for therapy co-payment varied between 10% and 280%. The hours of work required to purchase a package of biologicals varied between 7 and 137 working hours. The global economic crisis has affected Bulgaria and led to worsening economic parameters. There are still no well-established practices to control public spending, as the measures taken to reduce the final cost of medicines mainly affect the pharmaceutical companies. This type of cost-containment policy provides an opportunity for innovative treatment with biologicals for patients with inflammatory diseases. Most of the therapies cost more than the patients' monthly income.

Medication Adherence among Patients with Diabetes Mellitus and Its Related Factors-A Real-World Pilot Study in Bulgaria.

Background and Objectives: The objective is to evaluate medication adherence level (MA) and the relevant determinants of MA among patients with type 2 diabetes mellitus (T2DM) monitored in ambulatory settings by general practitioners. Materials and Methods: A cross-sectional study was conducted among patients with T2DM monitored in a GP practice in Sofia, Bulgaria (September-December 2022). All patients were interviewed according to a predesigned questionnaire after granting informed consent. MA level was evaluated through the Morisky-Green four-item questionnaire, and health-related quality of life was evaluated by EQ-5D-5L and VAS (visual analogue scale). Data were aggregated and statistically evaluated. Results: The total number of observed patients was 93. Around 48.4% of patients were female, and 90.3% of patients were between 50 and 80 years of age. Multimorbidity was identified among 70% (n = 65) of the respondents. High and medium levels of MA were revealed in 64.51% and 33.3% of respondents, respectively. Patients treated with insulin secretagogues were most adherent to the therapy (n = 83.3%) in comparison with the other treatment groups. The onset of the disease, professional status, age, gender, number of therapies, and quality of life did not affect the level of MA (p > 0.05). VAS scores among nonsmokers (VAS = 63.16 ± 20.45 vs. 72.77 ± 14.3) and non-consumers of alcohol (VAS = 63.91 ± 19.34 vs. VAS = 72.54 ± 15.98) were statistically significant lower (p < 0.05). A significant related factor for MA was years lived with diabetes (OR = 3.039, 95% CI 1.1436-8.0759, p = 0.0258). The longer the disease duration, the more the odds for a high MA level increased. Conclusions: The number of nonadherent diabetic patients in Bulgaria is low, which might be evidence of patients' concern about their own health and understanding about the importance of prescribed therapy. Further comprehensive study with additional patients is required to confirm the results and investigate the predicting factors for a high level of MA.

Budget cap and pay-back model to control spending on medicines: A case study of Bulgaria.

Central and Eastern European countries (CEEC) have among the highest rates of increase in healthcare expenditure. External reference pricing, generics and biologics price capping, regressive scale for price setting, health technology assessment (HTA), and positive drug lists for reimbursed medicines are among the variety of implemented cost-containment measures aimed at reducing and controlling the rising cost for pharmaceuticals. The aim of our study was to analyze the influence of a recently introduced measure in Bulgaria-budget capping in terms of overall budget expenditure. A secondary goal was to analyze current and extrapolate future trends in the healthcare and pharmaceutical budget based on data from 2016 to 2021. The study is a retrospective, observational and prognostic, macroeconomic analysis of the National Health Insurance Fund's (NHIF) budget before (2016-2018) and after (2019-2021) the introduction of the new budget cap model. Subgroups analysis for each of the three new budget groups of medicines (group A: medicines for outpatient treatment, prescribed after approval by a committee of 3 specialists; group B: all other medicines out of group A; and group C: oncology and life-saving medicines out of group A) was also performed, and the data were extrapolated for the next 3 years. The Kruskal-Wallis test was applied to establish statistically significant differences between the groups. During 2016-2021, healthcare services and pharmaceutical spending increased permanently, observing a growth of 82 and 80%, respectively. The overall healthcare budget increased from European €1.8 billion to 3.3 billion. The subgroup analysis showed a similar trend for all three groups, with similar growth between them. The highest spending was observed in group C, which outpaced the others mainly due to the particular antineoplastic (chemotherapy) medicines included in it. The rising overall healthcare cost in Bulgaria (from European €1.8 billion to 3.3 billion) reveals that implementation of a mechanism for budget predictability and sustainability is needed. The introduced budget cap is a relatively effective measure, but the high level of overspending and pay-back amount (from European €34 billion to 59 billion during 2019-2021) reveals that the market environmental risk factors are not well foreseen and practically implemented.

Evaluation of the quality of life after implantation of light or standard polypropylene hernia meshes.

Abstract.

Analysis of Healthcare Expenditures in Bulgaria.

The growth of public expenditure worldwide has set the priority on assessment of trends and establishment of factors which generate the most significant public costs. The goal of the current study is to review the tendencies in public healthcare expenditures in Bulgaria and to analyze the influence of the demographic, economic, and healthcare system capacity indicators on expenditures dynamics. A retrospective, top-down, financial analysis of the healthcare system expenditures was performed. Datasets of the National Statistical Institute (NSI), National Health Insurance Fund (NHIF), and National Center of Public Health and Analysis (NCPHA) were retrospectively reviewed from2014-2019 to collect the information in absolute units of healthcare expenditures, healthcare system performance, demographics, and economic indicators. The research showed that increasing GDP led to higher healthcare costs, and it was the main factor affecting the cost growth in Bulgaria. The number of hospitalized patients and citizens in retirement age remained constant, confirming that their impact on healthcare costs was negligible. In conclusion, the population aging, average life expectancy, patient morbidity, and hospitalization rate altogether impacted healthcare costs mainly due to the multimorbidity of older people and the rising need for outpatient hospital services and medications.

The effects of age and sex on the elastic mechanical properties of human abdominal fascia.

BACKGROUND: The abdominal hernias become more prevalent with age, that can adversely affect life quality. The mechanical properties of abdominal wall layers are supposed to play a significant role in developing of an abdominal hernia.The objective of this study was to determine the mechanical properties of the human abdominal layer - fascia and the effects of age and sex on it for choosing the proper brand of hernia mesh. METHODS: 78 samples harvested from 19 fresh cadavers were subjected to uniaxial tension tests and divided into four groups according to age. Group A corresponds to age up to 60 years, Group B to age 61-70 years, Group C to age 71-80 years and Group D to 81-90 years. Median stress-stretch ratio curves with respect to age, sex and direction of loading were obtained. Median values of the maximum tensile stress, stretch at maximum stress and elastic modulus calculated at 5% strain were determined. FINDINGS: The abdominal fascia showed large variations between specimens depending on age and sex. The stiffness of the fascia increased with age. There is statistically significant differences between the median curves of male samples (P = 0.008) and female samples (P = 0.019) according to age in the L direction. Statistically significant differences between the values of maximum stress (P = 0.01) and elastic modulus (P = 0.003) from Group C in the L direction and maximum stress (P = 0.03) from Group D in the T direction was established. INTERPRETATION: The female samples are stiffer than male samples especially after 80 years.

Availability and reimbursement of biological products for severe asthma in Bulgaria.

OBJECTIVES: This study aims to analyze the reimbursement and cost of biological therapy for severe asthma in Bulgaria during 2014-2019 from the perspective of the National Health Insurance Fund. METHODS: It is a retrospective, Marco-costing, top-down study of the expenditures for biological products for severe asthma. The changes in the cost paid by the National Health Insurance Fund per year, per product, and per patient during 2015-2020 were systematized and calculated. The utilization of biologicals was analyzed by calculating the defined daily dose/1000inh/day. Three databases were searched-the European Medicines Agency for the date of marketing authorization of biological products, National Council of Prices and Reimbursement for the date of their respective inclusion in the positive drug list, and National Health Insurance Fund about the number of patients with asthma, reimbursed sum for all asthma patients, and number of packages sold of biological products. RESULTS: At the end of 2019, five international non-proprietary names of biologicals with indication for severe asthma had received European marketing authorization, and three of them were included in the Bulgarian positive drug list-omalizumab, mepolizumab, and benralizumab with a 75% reimbursement. Upon their introduction into the positive drug list, the reimbursed expenditures for asthma therapy started to increase from 27 million in 2014 to 33 million BGN in 2019 (€13.5-€16.5 million). The cost of therapy with biologicals rose from 16% to 24% of all anti-asthmatic medicines budget. The National Health Insurance Fund database reported that between 47,000 and 52,000 of patients with asthma, 466 are on biological therapy. The yearly cost of one asthma patient ranges between 512 and 615 BGN (€258-€307), and the yearly per-patient cost of severe asthma is 16,666 BGN (appr. €8333). Total utilization in defined daily dose/1000inh/day increases from 0.0199 to 0.0383 from 2015 to 2019. CONCLUSION: The access to biological therapy through the reimbursement system has improved during the last 3 years. The cost of therapy is posing a high burden on the National Health Insurance Fund and on the patients and is expected to increase due to the small number of patients on biological therapy currently in comparison to all reimbursed asthmatics.

New Epidemiological, Clinical and Economic Data for Patients With Acromegaly in Bulgaria.

Background: Acromegaly and its comorbidities affect the patients' quality of life, each healthcare system and the society. This study aimed to evaluate clinical characteristics and treatment patterns and the economic burden of acromegaly. Materials and methods: All patients with acromegaly treated with expensive medicines and regularly followed up at the main expert clinical center for acromegaly in the country were included in this nationwide, retrospective, observational, population-based study. Patient characteristics, treatment patterns, healthcare resource use, and costs were assessed for 1-year period (01.01.2018-31.12.2018). Results were processed through statistical analysis using MedCalc software version 16.4.1. Results: A total of 191 acromegaly patients were observed. Approximately 67% were female, 45.5% were between 41 and 60 years and the mean age at diagnosis was 40.73 years. Surgical treatment was preferred as a first-line therapy among almost 89% of all diagnosed patients. The level of comorbidities was very high as more than 95% suffered from at least one concomitant disease. The most frequent comorbidities were other endocrine and metabolic diseases (96.7%), followed by cardiovascular diseases (70.7%). The most common first-line pharmacotherapy was long-acting somatostatin analogs (SSA) (38%) followed by dual combination SSA + pegvisomant (21%). The total economic burden of acromegaly was estimated to be 2,674,499.90 € in 2018 as the direct costs (medication costs, hospitalization costs covered by the patients and the National Health Insurance Fund) outnumbered indirect costs (loss of productivity due to hospitalization): 2,630,568.58 € vs. 43,931.32 €. The average annual per-patient direct and indirect costs were 14,002.62 €. Conclusions: The current study demonstrates a significant clinical and socio-economic burden of acromegaly in the country. Proper diagnosing and regular follow up of acromegaly patients in a specialized pituitary center ensure appropriate innovative pharmacotherapy with achievement of disease control.

Age-related changes in mechanical properties of human abdominal fascia.

The purpose of this study is to assess and model age-related changes in the mechanical properties of human fascia. The samples were divided into three age groups: group A-up to 60 years (mean age 52.5 ± 6 years), group B-61-80 years (mean age 70.4 ± 5.2 years), and group C-81-90 years (mean age 83.2 ± 2 years). A uniaxial tensile test was applied to fascia specimens cut perpendicular and parallel to fibers. The secant modulus at 5% strain, the maximum stress, and the stretch at maximum stress were calculated from the stress-stretch ratio curves. The results indicated an increase in the secant modulus with the increased age. The trend is clearer in the longitudinal direction. Considering the strain energy function which accounts the isotropic and non-isotropic response of the fascia where isotropic and anisotropic parts are split, we evaluated which material model is the most suitable to present isotropic mechanical behavior of the tissue. The experimental stress-stretch ratio curves were approximated using Mooney-Rivlin, Yeoh, and neo-Hookean strain energy functions and a good match between theoretical and experimental results was obtained. On the basis of objective function values and normalized mean square root error, we recommend using the Yeoh model to describe the isotropic mechanical behavior of human abdominal fascia. Graphical abstract .

Life expectancy and survival analysis of patients with diabetes compared to the non diabetic population in Bulgaria.

AIMS: To evaluate the expected life expectancy in patients with diabetes in Bulgaria and to compare it to the expected life expectancy of the non-diabetic population in the country. METHODS: It is a retrospective observational population study on individuals diagnosed with diabetes, compared to the non-diabetic population in Bulgaria for the period 2012-2015. Data from the national diabetes register and national statistical institute were used to construct life-tables with probability of survival with t-test and Chi Square test. Confounder analysis was done by age, sex, and type of diabetes. All-cause mortality and deaths in diabetic patients were analyzed. Kaplan-Meier survival curves were constructed for each age group and a log-rank analysis was conducted. RESULTS: Average life expectancy in the non-diabetic population, patients with Type 1 DM and with Type 2 DM is 74.8; 70.96 and 75.19 years, respectively. For 2012-2015 the mortality in the non-diabetic population remained constant and lower (average-1.48%) compared to type-1 DM (5.25%) and Type-2 (4.27%). Relative risk of death in diabetics was higher overall (12%), after the age of 70 before which the relative risk was higher for the non-diabetic population. This was observed as a trend in all analyzed years. CONCLUSION: Patients with type 2 DM have a longer life-expectancy than patients with type-1 DM and overall Diabetics life expectancy equals that of the non-diabetic population, which could suggest improved disease control and its associated complications in Bulgaria. Male diabetics show slightly longer life expectancy than their counterparts in the non-diabetic population, by a marginal gain of 0.6 years for the entire observed period. Life expectancy in diabetic women increased by 1.3 years, which was not observed in the non-diabetic population. Prevalence of diabetes was higher for women. Improved diabetes control may explain this gain in life; however other studies are needed to confirm this.

Chronic obstructive pulmonary disease exacerbations and progression in relation to ambient air pollutants exposure.

BACKGROUND: The information for the impact of air pollutants on the severity of chronic obstructive pulmonary disease (COPD) and hospital admissions in Bulgaria is scarce. The aim of the study is to assess the relationship between some ambient air pollution and exacerbations levels as well as hospital admissions of patients with COPD in Bulgaria. METHODS: A multi-center, prospective, one-year observational study was conducted among 426 COPD patients. Data from pollution monitoring are collected from the Executive Environment Agency (EEA). RESULTS: The results showed that the pollution with sulfur dioxide (SO2) is less than limit concentrations recommended by the European Union and World Health Organization (WHO), while the pollution with PM exceeds limits values of WHO two times. The mean rate of exacerbations in selected towns are between 0.5-3, the number of exacerbations with hospitalization are between 0.2-1.8 and length of hospital stay is between 1-14 days. CONCLUSIONS: The study confirms that air pollution leads to increased number of exacerbations and hospital stay. The patients with mild level of COPD have 0.86 exacerbations and 2.61 days in hospital per year, while in case of very severe COPD these values increase 4 times. Outside pollutions lead to worsening of the disease severity and hospitalizations due to a higher rate of COPD exacerbations.

Pilot Study on the Cost of Some Oncohematology Diseases in Bulgaria.

The goal of the current study is to perform a pilot study of the cost of some oncohematology diseases in Bulgaria. This is a pilot broader burden of disease research. The official report of the National health insurance fund provided information about the total expenditures paid for medicines, ambulatory services, and hospitalizations in 2015 and 2016. To evaluate the costs from a patient perspective, an internet inquiry was organized with the support of the patient organization. The inquiry contained questions regarding the patients' demography, type of oncohematology disease, year of diagnosis, quality of life (EuroQol v5D), and additional out of pocket expenditures. Quality of Life data were statistically analyzed and Kruskal-Wallis analysis of variance was performed. From 2015 to 2016 the number of patients with oncohematological diseases decreased by approximately 3000 people. Less than 30% were hospitalized and the hospitalization cost decreased, but the cost for medicines increased by nearly 1.5 million Euros. Cost for medicines almost tripled the hospitalization cost. The reported mean quality of life was 0.749 (SD 0.203). There was positive correlation between QoL and current disease state (p = 0.008) and age (p = 0.025). 42% reported to have additional expenditures related to their oncohematology disease, 22% reported other expenditures (diet, change of everyday habits etc.) and 42% reported to have productivity loses due to loss of employment or change of work, 44% of the respondents reported additional payment for medicines for concomitant diseases. Thus, the total cost (public funds and patients) accounted for 37,708,764 Euro. Despite the high public expenditures, the indirect costs due to productivity loses are higher. Costs for medicines are higher than costs of inpatient treatment, but this tendency is observed in all European countries. The increases in the costs of medicines are compensated by reduced costs of hospitalization. Despite their higher costs, newer medicines are an effective and reasonable investment from a societal perspective. Currently the higher levels of copayment increase the burden on the patients.

Investigation of mechanical compatibility of hernia meshes and human abdominal fascia.

OBJECTIVE: Understanding the biomechanical properties of hernia meshes is essential in facilitating their selection. The aim of this study was to evaluate the mechanical compatibility of hernia meshes and human abdominal fascia and assess their applicability in hernia repair. METHODS: Uniaxial tensile tests were performed. A total of eight hernia meshes were tested - three standard meshes (Surgimesh®, Surgipro™, TecnoMesh®) and five light-weight meshes (Optilene®, TiO2Mesh™, Parietex™, Vypro™ II, Ultrapro™). RESULTS: The secant modulus at 5% strain and the level of orthotropy (the ratio between tensile stress in the longitudinal and the transversal direction) at 5% strain were calculated from the stress-stretch ratio curves. The impact of pore size and thickness on the elastic properties of these meshes was determined. The relationships between density and elasticity as well as between elasticity and the strain developed at 16 N/cm load were presented. The resulting mechanical properties of meshes were compared to the elasticity, orthotropy and deformability of human abdominal fascia. CONCLUSIONS: Vypro™ II and Parietex™ brands display properties similar to those of fascia in both directions. The TiO2Mesh™ and Ultrapro™ display deformability close to the deformability at 16 N/cm of the fascia transversalis. Only the Vypro™ II brand's orthotropy is similar to that of fascia.

Clinical characteristics, treatment patterns, and socio-economic burden of COPD in Bulgaria.

BACKGROUND: While the impact of COPD in Western-Europe is known, data from Eastern-Europe is scarce. This study aimed to evaluate clinical characteristics, treatment patterns, and the socio-economic burden of COPD in Eastern-Europe, taking Bulgaria as a reference case. METHODS: A representative sample of Bulgarian patients with COPD was randomly chosen by pulmonologists, based on the following inclusion criteria: COPD diagnosis with at least 1 year of living with COPD, ≥40 years of age, and use of COPD medication. Patient characteristics, treatment, quality-of-life, healthcare resource use, and costs were systematically assessed. RESULTS: A total of 426 COPD patients were enrolled. Approximately 69% were male, 40% had occupational risk factors, 45% had severe and 11% had very severe COPD. Mean CAT scores were 13.80 (GOLD A), 21.80 (GOLD B), 17.35 (GOLD C), and 26.70 (GOLD D). Annual per-patient costs of healthcare utilization were €579. Yearly pharmacotherapy costs were €693. Indirect costs (reduced and lost work productivity) outnumbered direct costs three times. CONCLUSIONS: Bulgaria has relatively high percentages of (very) severe COPD patients, resulting in considerable socio-economic burden. High smoking rates, occupational risk factors, air pollution, and a differential health system may be related to this finding. Eastern-European COPD strategies should focus on prevention, risk-factor awareness, and early detection.

The effects of strain amplitude and localization on viscoelastic mechanical behaviour of human abdominal fascia.

PURPOSE: The purpose of the paper is to examine and compare the viscoelastic mechanical properties of human transversalis and umbilical fasciae according to chosen strain levels. METHODS: A sequence of relaxation tests of finite deformation ranging from 4 to 6% strain with increment 0.3% was performed at strain rate 1.26 mm/s. Initial and equilibrium stresses T0, Teq, initial modulus E and equilibrium modulus Eeq, reduction of the stress during relaxation process ΔT, as well as the ratio (1 - Eeq /E) were calculated. RESULTS: The range in which parameters change their values are (0.184-1.74 MPa) for initial stress, (0.098-0.95 MPa) for equilibrium stress, (43.5-4.6 MPa) for initial modulus E. For Eeq this interval is (23.75-2.45 MPa). There are no statistically significant differences between the values of these parameters according to localization. The differences in viscoelastic properties of both fasciae are demonstrated by reduction of the stress during relaxation process and ratio (1 - Eeq /E). The values of ΔT and (1 - Eeq /E) ratio for umbilical fascia are significantly greater than that of fascia transversalis. An increase of 2% in strain leads to change of the normalized relaxation ratio of fasciae between 28%-66%. There is a weak contribution of viscous elements in fascia transversalis samples during relaxation, while in umbilical fascia the contribution of viscous component increases with strain level to 0.66 at 5.3% strain. CONCLUSIONS: This study adds new data for the material properties of human abdominal fascia. The results demonstrate that in chosen range of strain there is an influence of localization on visco-elastic tissue properties.