Mapping the Bulgarian Diabetes Register to OMOP CDM: Application Results.

BACKGROUND: The Bulgaria Diabetes Register (BDR) contains more than 380 millions of pseudonymized outpatient records with proprietary data structures and format. OBJECTIVES: This paper presents the application results and experience acquired during the process of mapping such observational health data to OMOP CDM with the objective of publishing it in the European Health Data and Evidence Network (EHDEN) Portal. METHODS: The data mapping follows the activities of the well-structured Extract-Transform-Load process. Unlike other publications, we focus on the need for preprocessing the data structures of raw data, cleaning data and procedures for assuring quality of data. RESULTS: This paper provides quantitative and statistical measures for the records in the CDM database as published in the EHDEN Portal. CONCLUSION: The mapping of data from the BDR to OMOP CDM provides the EHDEN community with opportunities for including these data in large-scale project for evidence generation by applying standard analytical tools.

Application of OMOP Common Data Model for Data Integration: The Bulgarian Diabetes Register.

This paper considers mapping of the Bulgarian Diabetes Register(BDR) onto OMOP Common Data Model (CDM). Research results are referenced and plans for analysis of drug shortages from federated data sources are outlined.

Occupational health assessment summary designed for semantic interoperability.

BACKGROUND: Geopolitical and economic crises force a growing number of people to leave their countries and search better employment opportunities abroad. Meanwhile, the highly competitive labor market provides opportunities for employees to change workplaces and job positions. Health assessment data collected during the occupational history is an essential resource for developing efficient occupational disease prevention strategies as well as for ensuring the physical and psychological well-being of newly appointed workers. The diversity in data representation is source for interoperability problems that are insufficiently explored in the existing literature. OBJECTIVES: This research aims to design a worker's occupational health assessment summary (OHAS) dataset that satisfies the requirements of an international standard for semantic interoperability in the use case for exchanging extracts of such data. The focus is on the need for a common OHAS standard at EU level allowing seamless exchange of OHAS at both cross-border and at the worker's country of origin level. RESULTS: This paper proposes a novelty systematic approach ensuring semantic interoperability in the exchange of OHAS. Two use cases are explored in terms of UML sequence diagram. The OHAS dataset reflects common data requirements established in the national legislation of EU countries. Finally, an EN 13606 archetype of OHAS is designed by satisfying the requirements for semantic interoperability in the exchange of clinical data. Semantic interoperability of OHAS is demonstrated with realistic use case data. CONCLUSIONS: The designed static, non-volatile and reusable information model of OHAS developed in this paper allows to create EN 13606 archetype instances that are valid with respect to the Reference model and the datatypes of this standard. Thus, basic activities in the OHAS use case can be implemented in software, for example, by means of a native XML database as well as integrated into existing information systems.

Diabetes Prevalence and Duration Data Extracted from Outpatient Records Representative for the Bulgarian Population.

This paper presents new data about diabetes prevalence and illness duration from a population of patients with diabetes Type 1(43,818) and Type 2 (457,247). Unlike the usual approach that employs adjusted estimates in similar prevalence reports, this study extracts data from a large number of original clinical documents such as all the outpatient records (6,887,876) issued in Bulgaria to all the 501,065 patients with diabetics during 2018 (9.77% of all the 5,128,172 patients recorded in 2018, 4.43% male and 5.35% female). Diabetes prevalence data are described in terms of distributions of Type 1 and Type 2 diabetes over age and gender. It is mapped to an Observational Medical Outcomes Partnership Common Data Model that is publicly available. The distribution of Type 2 diabetics agrees with peak values of BMI established in related research. A major novelty in this research are the data about the diabetes illness duration. It is an essential metric for evaluating the quality of processes evolving over time. Accurate estimates are obtained for the duration measured in years of Type 1 (95% CI 10.92, 11.08) and Type 2 (95% CI 7.97, 8.02) diabetics from the Bulgarian population. The patients with diabetes Type 1 have longer diabetes duration relatively to those with Type 2. It is recommended to include this metric in official diabetes prevalence reports.

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.

Diabetes and Obesity in Bulgaria. Study of a Large Number of Outpatient Records from 2018.

This paper considers the association between diabetes and obesity by examining body mass index (BMI) values and ICD-10 codes for obesity illnesses. The BMI values are extracted from 6,887,876 anonymized outpatient records describing all the visits of diabetics to general practitioners and specialists in ambulatory care from the latest Bulgarian nationally representative data. The number of adults in this sample having BMI ≥ 25 is 253,841 i.e. 84.121% of the adult diabetics with BMI records are overweight or obese. The objective of the study is to reveal how the BMI recorded values in outpatient records relate diabetics with overweight or obesity illness. In the existing literature sources there is scant empirical data of this subject where the conclusions are founded on a nationally representative sample. A secondary objective is to obtain the distribution of BMI values of adults with respect to their age and gender. The initial computer experiments prove that there is no immediate and unconditional relation between BMI and the obesity illnesses. These results underpin the role of BMI as a risk factor that should be observed regularly as an important part of proactive public health policies.

Using QR Code for Uniform Representation of Content in Cross-Border Exchange of ePrescriptions in the EU.

This paper proposes an approach and demonstrates its application for cross-border exchange of ePrescriptions in the European Union. A business process model of the main use case for exchange of prescription content in the eHealth Digital Service Infrastructure is created and analyzed. The novelty in this approach is the proposed encoding of the basic dataset in a Quick Response (QR) code in terms of an XML scheme that is independent of clinical models or proprietary database structures. It allows to inverse the dataflow control in the chain of message exchanges between Dispenser and National Contact Points. The proposed inversion of control positions the citizen with the QR code of the prescription in the center of that chain of message exchanges between the main actors of the business process. The independent format of content representation in the QR code allows the actors in the message exchange to auto-populate data in their registers when the medicine is dispensed. Initial results are reported and reveal the advantages of embedding prescription details in QR code employing a common independent XML scheme.

System of Criteria for Treatment Evaluation of Acromegaly in Bulgaria.

Acromegaly is a rare endocrine disorder caused by excessive and longstanding secretion of growth hormone (GH) by the pituitary somatotroph and resulting from this overproduction of insulin-like growth factor-1 hormone (IGF-1) by the liver. There are few registers and rather limited clinical data about acromegaly treatment. The analysis of acromegaly data is rarely subject to a system of criteria for evaluating acromegaly treatment. The novelty of this paper is that it presents a real- life practice case study about the implementation results of such a system in Bulgaria. The case study analysis illustrates a clinical information approach to manage thousands of records in the Bulgarian Acromegaly Database. The here reported results provide evidence about the difficulties in maintaining both GH and IGF-1 levels inside their reference values in acromegaly treatment. Ongoing research extends the evaluation results by enabling semantic interoperability between acromegaly databases based on openEHR specification.

Cross-Border Exchange of Clinical Data Using Archetype Concepts Compatible with the International Patient Summary.

This paper proposes an approach and demonstrates its application for cross-border exchange of clinical documents oriented towards the use of archetype concepts and international patient summary standards adopted in the European Union. A novelty in this approach is the management of native XML instances of an archetype concept in the CEN 13606 standard by means of a native XML database and XML technologies. The computer experiments demonstrate that it is suitable for representing relatively small clinical datasets such as those describing rare diseases like the Acromegaly illness, where the semantic context in the relatively small number of symptoms is practicable to tag in terms of SNOMED-CT terminology codes. Additionally, we demonstrate that the semantically enriched information model can facilitate secondary use of clinical data by visualizing the execution of queries based on standard terminologies. Finally, the compatibility of the information model with the IPS standard enables sharing of clinical data among different information models.

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.

Incretins and SGLT-2i Therapy of Type 2 Diabetes - Real Life Study of Their Therapeutic and Economic Effects.

AIM: Incretins [dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide 1 RA (GLP-1 RA)] and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) groups are now routinely used for type 2 diabetes therapy and comprise a large number of medicinal products. The long term therapeutic and economic effect of the incretins' and SGLT-2i in real life setting is not well documented. The goal of the current study is to analyze the cost and results of incretins and SGLT-2i based therapy for type 2 diabetes in Bulgaria. METHODS: The study uses information about the changes in glycated hemoglobin (HbA1c) level from the National diabetes register for 6122 patients and cost paid by the National Health Insurance Fund (NHIF) for diabetes complications, and medicine prices. RESULTS: The results show that after the therapy patients achieved excellent diabetes control. There were no HbA1c values less than 6% before treatment. After the therapy, 3356 people showed values less than 7% HbA1c. It is considered very good diabetic control. The number of people with HbA1c above 8% is decreasing significantly. The number of people with values above 9% is decreasing by almost four times. HbA1c level decreases with the highest percentage for the patients treated with GLP-1 RA, followed by those treated with DPP-4i and SGLT-2i. For a year NHIF reimbursed 5.25 million BGN for incretins and SGLT-2i therapy. NHIF can save between 306 and 510 thousand BGN from incidents that have not occurred as a result of 5 years of therapy. CONCLUSION: Incretins [dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA)] and sodium-glucose linked transporter-2 inhibitors (SGLT-2i) therapy steadily decreases the HbA1c level, and risk of developing diabetic incidents is reduced to between 333 and 465 cases among 6122 treated patients. Avoided cost for therapy of diabetes incidents account for between 305 and 510 thousand BGN.

Cushing's Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century.

Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing's disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing's disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.

Mining comorbidity patterns using retrospective analysis of big collection of outpatient records.

BACKGROUND: Studying comorbidities of disorders is important for detection and prevention. For discovering frequent patterns of diseases we can use retrospective analysis of population data, by filtering events with common properties and similar significance. Most frequent pattern mining methods do not consider contextual information about extracted patterns. Further data mining developments might enable more efficient applications in specific tasks like comorbidities identification. METHODS: We propose a cascade data mining approach for frequent pattern mining enriched with context information, including a new algorithm MIxCO for maximal frequent patterns mining. Text mining tools extract entities from free text and deliver additional context attributes beyond the structured information about the patients. RESULTS: The proposed approach was tested using pseudonymised reimbursement requests (outpatient records) submitted to the Bulgarian National Health Insurance Fund in 2010-2016 for more than 5 million citizens yearly. Experiments were run on 3 data collections. Some known comorbidities of Schizophrenia, Hyperprolactinemia and Diabetes Mellitus Type 2 are confirmed; novel hypotheses about stable comorbidities are generated. The evaluation shows that MIxCO is efficient for big dense datasets. CONCLUSION: Explicating maximal frequent itemsets enables to build hypotheses concerning the relationships between the exogeneous and endogeneous factors triggering the formation of these sets. MixCO will help to identify risk groups of patients with a predisposition to develop socially-significant disorders like diabetes. This will turn static archives like the Diabetes Register in Bulgaria to a powerful alerting and predictive framework.

Autoimmune hypothyroidism is three times more frequent in female prolactinoma patients compared to healthy women: data from a cross-sectional case-control study.

BACKGROUND: The potent immunomodulatory action of prolactin has been demonstrated in many experimental in vitro studies. In accordance with these data, our retrospective analyses revealed higher prevalence of autoimmune thyroid diseases in prolactinoma patients compared to general population. PURPOSE: A cross-sectional case-control study was carried out in a single tertiary referral centre. The main aim was to assess the frequency of newly diagnosed autoimmune thyroid diseases in female patients with prolactinomas. METHODS: The study population consisted of 260 females (154 patients and 106 sex-matched, ethnicity-matched, and age-matched healthy controls) enroled in a prospective manner. Physical exam, thyroid ultrasound, and laboratory testing (measurement of antibodies to thyroglobulin, thyroid peroxidase, TSH-receptor, serum TSH and FT4 levels) were performed in all study participants. RESULTS: Autoimmune thyroid diseases were diagnosed in 29.9% of the patients and 10.4% of the healthy subjects (p = 0.0002). Subclinical hypothyroidism was found in 9.7% of the patients versus 2.8% of the controls (p = 0.044). Autoimmune hyperthyroidism was observed in 1.3% of all patients. CONCLUSIONS: The prevalence of newly diagnosed autoimmune thyroid diseases, and especially the subclinical hypothyroidism, was significantly higher in our female prolactinoma patients in comparison to age-matched healthy women. Based on our results, we suggest routine screening for autoimmune thyroid diseases (thyroid function, immunology and ultrasound examination) in all female patients with prolactinoma at the time of diagnosis. We also recommend a close follow-up of thyroid function in these women in case of pregnancy and after delivery.

Contextualization in automatic extraction of drugs from hospital patient records.

Information Extraction (IE) from medical texts aims at the automatic recognition of entities and relations of interests. IE is based on shallow analysis and considers only sentences containing important words. Thus IE of drugs from discharge letters can identify as 'current' some past or future medication events. This article presents heuristic observations enabling to filter drugs that are taken by the patients during the hospitalization. These heuristics are based on the default PR structure and linguistic expressions signaling temporal and conditional markers. They are integrated in a system for drug extraction from hospital Patient Records (PRs) in Bulgarian language. Present evaluation results are summarized as well.

Hypoglycemia anticipation, awareness and treatment training (HAATT) reduces occurrence of severe hypoglycemia among adults with type 1 diabetes mellitus.

Severe hypoglycemia (SH) can be a significant problem for patients around the world with Type 1 Diabetes Mellitus (T1DM). To avoid SH, patients need to better manage, and reduce the occurrence of, preceding mild hypoglycemia. Hypoglycemia Anticipation, Awareness and Treatment Training (HAATT), developed in the United States specifically to address such issues, was evaluated at short- and long-term follow-up in a medically, economically and culturally different setting; Bulgaria. Sixty adults with T1DM and a history of recurrent SH (20 each from Sofia, Russe, and Varna, Bulgaria) were randomized to Self-Monitoring of Blood Glucose (SMBG) or SMBG+ HAATT. For 6 months before and 1 to 6 and 13 to 18 months after intervention, participants recorded occurrence of moderate, severe, and nocturnal hypoglycemia. For 1-month pre- and post-intervention, participants completed daily diaries concerning their diabetes management. Relative to SMBG, HAATT produced significant improvement in occurrence of low BG, moderate, severe, and nocturnal hypoglycemia, and detection and treatment of low BG (p values < .05 to < .001), with no compromise in metabolic control. At long-term follow-up, HAATT participants continued to have significantly fewer episodes of moderate and severe hypoglycemia. These findings suggest that a structured, specialized psycho-educational treatment program (HAATT) can be highly effective in managing hypoglycemia.