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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. [ABSTRACT FROM AUTHOR]

The study investigates the quality of diabetes control and its economic implications in Bulgaria for the years 2012–2016. It is a retrospective study of the national diabetes register. Patients were categorized according to type of diabetes, gender, newly diagnosed cases per year, body-mass index (BMI) and achieved disease control. The relative risks for reducing the diabetes-related complications achieved through a 1% reduction of HbA1c were taken from literature data, and macrocosting was used to calculate the saved cost for diabetes complications. The new cases of type 1 diabetes decreased (10% lower in 2016 than in 2012) but the number of new cases with type 2 diabetes increased (12%). In 2012, the average percentage of glycosylated hemoglobin in the second recording at the end of the year was 7.59% (SD 1.85), whereas the second recording of values for 2016 revealed an average value of 7.3% (SD 1.32). The mean yearly reduction in 2012 was 0.05% (SD 1.1) with a slow increase to 0.07% (SD 0.46) in 2016. The absolute risk reduction for all diabetes-related complications was 20.6. The total prevented costs for all complications in the entire population were 20 million BGN. The results for the period 2012–2016 showed improved control of diabetes. The proportion of patients who achieved control increased over the period, reaching over 40% of the afflicted population. The achieved adequate control led to a reduced risk of developing diabetes-related complications, thereby saving costs of 20 million BGN associated with them, and decreasing the burden on the healthcare system. [ABSTRACT FROM AUTHOR]

The aim of this study was to retrospectively analyse the cost-effectiveness of different types of controlled ovarian hyperstimulation (COH) protocols and regimes used in in vitro fertilization procedures at a national level. Information was gathered from the National Centre for Assisted Reproduction (Bulgaria). Out of 2849 patients, 2757 were included in the study. The patients were treated with three main protocols: gonadotrophin-releasing hormone (GnRH)-antagonist protocol, GnRH-agonist protocol and COH protocols without GnRH-analogues. In all main COH protocols, different types of gonadotrophins were combined in seven therapeutic schemes. A decision tree model was built for the cost-effectiveness analysis. Each decision node representing the three main COH protocols included seven possible chance nodes representing the COH therapeutic regimens. The results were evaluated based on the number of live-born children. The mean cost differed statistically significant between the three main types of protocols (p = 0.0001) and between all seven COH regimens. In terms of live birth, the GnRH agonist protocols were more effective, followed by GnRH-antagonist protocols and those without GnRH-analogues. The decision tree model confirmed that considering the probability of the therapeutic regimens being prescribed, the GnRH-agonist protocol is the cost-effective one with the smallest cost per live-born child (5033, 51 BGN). The other two protocols could also be considered cost-effective because the incremental cost effectiveness ratio is very low and is below the gross domestic product per capita for 2015. The Governmental Authorities, considering also the cost-effectiveness criteria, should carefully revise the trend towards a wider use of GnRH-antagonist protocols. [ABSTRACT FROM AUTHOR]

Simple Summary: Myelofibrosis is a rare blood cancer, the onset of which usually occurs at an advanced age. Real-life studies on the influence of ruxolitinib on therapeutic results and patient survival are scarce for the disease both worldwide and in Bulgaria, provoking our interest towards this topic. The aim of this study was to analyze the therapeutic results and survival of patients with myelofibrosis treated with ruxolitinib in comparison to standard therapy. The aim of this study was to analyze the therapeutic results and survival of patients with myelofibrosis treated with ruxolitinib in comparison with a group on standard therapy. It is a cross-sectional, retrospective, non-interventional, real-life study that was performed between January 2000 and February 2023. Patients treated between 2000 and 2016, before the introduction of ruxolitinib, constituted the control group (n = 45), while those treated after May 2016, after ruxolitinib inclusion, constituted the active group (n = 66). Demographic characteristics, clinical indicators, the severity of the disease, and survival were explored using Kaplan–Meier survival analyses. Spearman's correlation, linear regression, and other statistical analyses were performed. According to the Kaplan–Meier analysis, there was a 75.33% reduction in the fatality risk in the sample. On a general-population level, the fatality risk in the group treated with ruxolitinib varied between 7.9% and 77.18% compared to that of the risk in the control group. There was a decrease in blood parameters (leukocytes, hemoglobin, and platelets) and spleen size. During the first six months, the spleen size of the patients on ruxolitinib decreased by 6%, and during the second six months, it decreased by another 9%. This study shows that patients in a real-life clinical setting treated with ruxolitinib exhibited improved clinical signs of the disease, had a lower symptom severity, and survived longer than patients on standard therapy before ruxolitinib's entrance into the national market. The improvements correlate with those reported in randomized clinical trials. [ABSTRACT FROM AUTHOR]

We aimed to explore symptom severity and adherence to therapy for patients with myelofibrosis treated with ruxolitinib in Bulgaria. It is a prospective, non-interventional study performed at the specialized hospital for active treatment of hematological diseases in Sofia during 2022–2023. Date of diagnosis, demographic characteristics, clinical indicators, ruxolitinib dose, and other data points were collected. Clinical indicators were assessed at baseline, in the middle, and at the end of observation. Severity of symptoms was measured with MPN-SAF TSS and adherence to therapy with the Morisky 4 questionnaire six times during the observation. The mean age of diagnosis was 58.5 years, with the average duration of disease of 3 years. Patients' laboratory results were within physiological ranges, with spleen size experiencing a constant decrease. The average value for the severity of the symptoms per MPN-SAF TSS results decreased significantly, indicating better disease control. The average adherence to therapy did not change and remained high at around 9 points, except for one patient. In conclusion the treatment of myelofibrosis patients with ruxolitinib decreased symptom severity and spleen size. Patients were adherent to the therapy over the observed period, but as treatment duration increases, the risk of adherence decreases. [ABSTRACT FROM AUTHOR]

The purpose was to assess the level of medication adherence (MA) and related factors among individuals with acromegaly. The secondary goal was to assess the quality of life of patients and whether and how it correlates with the level of adherence. A prospective one-year study was conducted among patients with acromegaly diagnosed, treated, and monitored in the reference center for rare endocrine diseases in Bulgaria in 2021. Clinical data, patients reported outcomes, and health economics data were collected to define the predictors of non-adherence to medicines. Medication adherence level was assessed through a free Morisky–Green 4-item questionnaire. A total of 179 patients with acromegaly were observed. Approximately 62% were female, 50% were between 41 and 60 years, and the mean age at diagnosis was 40.4 years. The response rate to the questionnaires was 53% (n = 95; mean age 53.5 years, 73% female and 26% male). Patients with high levels of MA reported higher median values for the 36-Item Short Form Health Survey (SF-36) in comparison with those with low levels: 65.5 vs. 48.5 (p = 0.017). Similar results for EQ-5D-3L (3-level EuroQol 5D version) values and the level of MA were found: 0.656 vs. 0.796 (p = 0.0123). A low level of adherence was revealed in 34.7% of the patients, with no difference among different age groups. A significant positive determinant for adherence was years lived with acromegaly (OR = 5.625, 95% CI 1.7401–18.1832, p = 0.0039), as shorter duration was related to higher odds for high level of adherence. The current study demonstrates the importance of MA assessment for patients with acromegaly in Bulgaria. The medication adherence to the prescribed therapy among the observed group of patients with acromegaly varied as the percentage of adherent patients was around 65%. Still, there are low-adherent patients, and the responsible factors should be further investigated. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the economic burden of Chronic Obstructive Pulmonary Disease (COPD)-related hospitalizations on a macro and micro level. Macro analysis was performed on the rate of DDD utilisation of COPD medicines, time of their inclusion in the reimbursement lists and the number of hospitalizations. On a micro level, a study of 426 patients with COPD was conducted to investigate the exacerbation and hospitalization rate relative to pharmacotherapy. A regression model, descriptive analysis, and Kruskal–Wallis non-parametric analysis were conducted. New drugs enter the market relatively quickly but are slow to be introduced into prescribing practices. The medicines' utilization in Bulgaria has increased from 20 to 21 million DDD for all therapeutic groups, especially for long-acting beta-agonists/long-acting muscarinic antagonists (LABA/LAMA) fixed-dose combinations. A marked increase in hospitalization rates was observed despite lower numbers of registered and monitored COPD patients nationally. However, the hospitalization rates due to exacerbations remained around 18–19%. Variation was observed in the number of hospitalizations for the studied period: increasing during the period 2013–2014 and decreasing over the following two years. This trend was also observed for the number of health insured COPD patients. The hospitalization costs increased from 5.2 to 5.7 million BGN. A statistically significant decrease in the number of hospitalizations for LAMA/LABA patients vs. LABA/inhaled corticosteroids (ICS) patients was observed. Overall, frequent hospitalizations increased the total cost of COPD therapy. Patients on new medicines with improved inhaler devices seem to suffer fewer hospitalizations. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the therapeutic results of rheumatoid arthritis (RA) therapy with different biologic disease-modifying antirheumatic drugs (bDMARDs) and the first Janus-activated kinase (JAK) inhibitor in real-life clinical settings. This is a prospective, observational, longitudinal study at the largest rheumatology clinic in Bulgaria conducted during the period 2012–2020. One hundred seventy-four patients were followed up for a period of one year. Patients naïve to biological therapy were consecutively assigned on the available at the time bDMARDs (infliximab, etanercept, adalimumab, rituximab, golimumab, cetrolizumab, tocilizumab) or tofacitinib. We evaluated the disease activity score (DAS28-CRP), Health assessment questionnaires (HAQ) and short form 36 (SF-36) were applied at the initiation of biological therapy, after 6, and 12 months of follow-up. We analyze the changes in the two major subgroups of SF36—physical (MCS) and mental health (PCS). The age and gender distribution were similar between the groups on bDMARDs and tsDMARD. All observed indicators for disease control and QoL improve after the initiation of the biological or JAK inhibitor therapy. We also analyze the effect of therapies on DAS28—CRP, HAQ, SF-36 (PCS, MCS). Dispersion analysis for the effect of therapy measured through DAS28 between 1st and 3rd measurement shows a statically significant difference in between the average effect of therapies (p = 0.005). According to the average change in DAS28 between the first and third measurement the most effective is the golimumab (Median difference = 2.745), followed by rituximab (median = 2.305) and etanercept (median = 2.070). According to the average change in HAQ between first and third the most effective is tofacitinib (median 0.563), followed rituximab and infliximab (median 0.500 for both). Less effective in term of HAQ changes between the first and third measurement appears to be etanercept (median difference 0.250). All differences are statistically significant (p < 0.05). Regarding the changes in the QoL measured with SF-36 MCS and PCS there is no statistically significant differences in the average effect of different therapeutic agents. Tofacitinib is non-inferior in comparison to bDMARDs and improve both—disease activity and QoL in patients with RA. [ABSTRACT FROM AUTHOR]

This study analysed the changes in the reimbursed cost, prices and utilization of biological medicines for a 5-year time horizon, encompassing three major arthropathic diagnoses, rheumatoid arthritis (RA), psoriatic arthropathies (PsA) and ankylosing spondylitis (AS), from the point of view of the third-party payer in Bulgaria. National; population based; macroeconomic; top-down budget analysis was performed based on official data about the number of inhabitants, reimbursed diagnoses and medicines, reimbursed cost, treated patients, and prices of medicines. The utilization of medicines was calculated in DDD per 1000/inh/day. There was an increase of 41% in the number of patients treated with biological medicines. The reimbursement cost of biologicals increased by 21%; however, the per-patient reimbursement costs per diagnosis fell by 40% due to price decreases. Out of 21 reimbursed diagnoses, we saw a significant difference in prevalence (612 SD in 2016 to 1216 SD in 2020; p < 0.05). RA accounted for 2736 patients in 2016, increasing by 131% to 4662 patients in 2020; AS with 1933 patients in 2016 reached 3196 patients by 2020, and PsA with 1128 patients ranked third with a 75% increase. The cost of therapy of RA was the highest, accounting for appr. 15 mill Euro in 2016. The utilization decreased only for 2 INNs (infliximab and rituximab). All INNs experienced a nearly two-fold increase in their utilization: from 0.5244 to 0.9252 DDD/1000inh/day. The cost analysis shows an important place of biologicals for arthropathic diseases therapy; introduction of biosimilars leads to prices and cost decreases. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. It is also associated with significant concomitant diseases which affect the disease progression course, and contribute to the exacerbation of health status and overall mortality rate. The aim of this study was to identify the most frequent Cardio-vascular disease (CVD) comorbidities among patients with COPD in Bulgaria and their effect on the hospitalization rate, hospital stay duration and health status. A retrospective national observational study was conducted among a statistically representative cohort of 426 patients in Bulgaria. Demographic data, smoking, clinical data for COPD severity and co-morbidity were collected. Health status was assessed through the specific COPD assessment test (CAT). CVD co-morbidity was evaluated by type, considering the GOLD guidelines and number. More than 80% of the patients reported two and more CVD co-morbidities and all of them reported more than two exacerbations and more than two hospitalizations over the last year. The most frequently reported CVD co-morbidity was hypertension, which was present in 88% of the men and in 89% of the women. The data showed a positive correlation between the cardiovascular risk and the progression of the disease. Hypertension, ischemic heart disease and heart failure prevailed in the observed population. With the advancement of COPD, the number of CVDs diseases per patient and CAT score, average hospitalization rate and hospital stay increased. [ABSTRACT FROM AUTHOR]

The aim of this study was to calculate the economic and social burden of chronic obstructive pulmonary disease (COPD) in Bulgaria generated from the loss of productivity due to absence from work (absenteeism), due to premature retirement, due to reduced productivity (presenteeism), and the disability adjusted life years (DALY). An observational study among 426 Bulgarian COPD patients was conducted for the period 2014–2015. Human capital approach was used to calculate the productivity losses and the DALY methodology of the World Health Organization was applied. The patients with moderate (50%) and severe (48%) disease were absent from work more frequently than those with mild COPD (2%) and generated productivity losses of 521.45€ per patient per year. The average indirect costs per patient for the remaining working ages due to premature retirement account for 25,000€ (6250 per patient on average), while those due to presenteeism, for about 3750.64€ per year. Accordingly, the DALYs in the group of patients with mild severity were lowest due to the low disutility index and number of patients in this sample group. On average, a patient with mild COPD spends 0.62 years of his life in disability due to the disease, while those with moderate and severe disease spend 6.00 and 9.00 years, respectively. This amounted to the following indirect costs experienced by patients: 3596.52€; 34,204.01€; 51,332.20€, respectively. We demonstrated a significant indirect financial and societal burden of COPD in Bulgaria, which is in correlation with the severity of the disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the cost-effectiveness of short protocols including different types of gonadotropins for controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). A retrospective, observational study of the real-life practice in a specialized IVF gynaecology clinic in 2009–2013 was carried out. All women on short COH protocols were recruited into three groups: COH including recombinant follicle stimulating hormone (rFSH) and urinary-FSH (urFSH) (n = 173); including urFSH alone (n = 289); and including rFSH alone (n = 212). The cost-effectiveness of the COH protocols was explored in two different case scenarios for possible outcomes. The first case scenario took into consideration a successful live birth, and the second one, the women to achieve pregnancy with live birth. Decision modelling was done using the TreeAge 2014 Software. According to the results in the first case scenario, the rFSH plus urFSH COH approach showed the highest weighted probability (p = 0.38) of live birth, but the urFSH alternative was cost-effective. The results in the second case scenario demonstrated that the urFSH protocol was again the cost-effective alternative. These results suggest that the strategy with urFSH should be preferred in both cases, but rFSH could also be considered as a cost-effective alternative for successful live birth and achieving pregnancy and delivery, since the incremental cost-effectiveness ratio in comparison with the urFSH protocol is below the gross domestic product per capita. The combined approach of rFSH and urFSH was shown not to be cost-effective in both explored scenarios. [ABSTRACT FROM AUTHOR]

This study aims to analyze and compare the disease activity control and quality of life of patients with rheumatoid arthritis (RA) who were treated with biological products in real-life settings. We tried to determine whether there is a symmetry in the performance of the biological molecules between each other and with the first Janus kinase (JAK) inhibitor. This is an observational, longitudinal, real-life study performed in the biggest rheumatology clinic during the period 2012–2020 comparing quality of life, cost of therapy, and disease control via different clinical measures. In all three disease activities measurement instruments, we observed an improvement for all biologic and target synthetic medicines. The disease activity score (DAS28) score decreased from 5.06 to 3.01, on average, for all INNs, suggesting that the majority of patients move away from moderate to low disease activity. The clinical disease activity index (CDAI) score decreased from 25.9 to 9.4, also indicating that patients with moderate disease activity reached a low level of activity. Similar results are reflected in the score, which fell from 27.7 to 10.3, again confirming the improvement to a low level of disease activity for patients treated with all INNs. Logically, with the successful control of disease activity, the quality of life (QoL) of the observed patients improved from 0.77 to 0.83 after a one-year follow up, as measured with the EuroQuol 5D-3L (EQ5D). Based on these results, we can consider that the observed biological INNs perform symmetrically in terms of the control of disease activity and improvement in the QoL of the observed patients. Biological therapy improves the disease control and quality of life of suitable patients with RA in real-life settings. All available biological therapies could be used interchangeably. [ABSTRACT FROM AUTHOR]