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.

Drug Utilisation Patterns of Alternatives to Ranitidine-Containing Medicines in Patients Treated with Ranitidine: A Network Analysis of Data from Six European National Databases.

INTRODUCTION: Ranitidine, a histamine H2-receptor antagonist (H2RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives. OBJECTIVES: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications. METHODS: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H2RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H2RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders). RESULTS: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18-74 years. Ranitidine was the most commonly prescribed H2RA in the pre-referral period (September 2017-August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3-3.8/1000 PY was observed in the referral period (September 2019-March 2020), eventually dropping to 0.0-0.4/1000 PY in the post-referral period (April 2020-March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time. CONCLUSIONS: Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs.

Incidence of second primary malignancies in relapsed/refractory B-cell non-Hodgkin's lymphoma patients in England.

BACKGROUND: Treatments for relapsed/refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) may be associated with an increased risk of second primary malignancies (SPMs). Currently available SPM incidence benchmarks are unreliable due to small sample sizes. METHODS: The Cancer Analysis System (CAS), a population-level cancer database in England, was used to identify patients with incident B-cell NHL diagnosed during 2013-2018 with evidence of r/r disease. Incidence rates (IRs) of SPMs after r/r disease diagnosis were calculated per 1000 person-years (PYs) and stratified by age, sex, and SPM type. RESULTS: We identified 9444 patients with r/r B-cell NHL disease. Of those who were eligible for SPM analysis, nearly 6.0% (470/7807) developed at least one SPM after r/r disease diagnosis (IR: 44.7; 95% confidence interval [CI]: 40.9-48.9). Of note, 205 (2.6%) had a non-melanoma skin cancer (NMSC) SPM. IR of SPMs was the highest for patients with r/r chronic lymphocytic leukemia/small lymphocytic leukemia (80.0) and lowest for diffuse large B-cell lymphoma (DLBCL) (30.9). Patients with DLBCL had the shortest overall survival after r/r disease diagnosis. CONCLUSIONS: This real-world data study suggests that the IR of SPM among patients with r/r B-cell NHL is 44.7 per 1000 PY and that most SPMs diagnosed after r/r disease diagnosis are NMSCs, establishing a basis for the comparison of safety outcomes for new treatments being developed for r/r B-cell NHL.

Impact of European Union Label Changes for Fluoroquinolone-Containing Medicinal Products for Systemic and Inhalation Use: Post-Referral Prescribing Trends.

INTRODUCTION: Concerns of the persistence and severity of the adverse effects of fluoroquinolones, mainly involving the nervous system, muscles and joints, resulted in the 2018 referral procedure led by the European Medicines Agency (EMA). They advised to stop prescribing fluoroquinolones for infections of mild severity or of a presumed self-limiting course and for prevention of infections, plus to restrict prescriptions in cases of milder infections where other treatment options are available, and restrict in at-risk populations. We aimed to examine whether the impact of EMA regulatory interventions implemented throughout 2018-2019 had an impact on fluoroquinolone prescribing rates. METHODS: A retrospective population-based cohort study was conducted using electronic health care records from six European countries between 2016 and 2021. We analysed monthly incident fluoroquinolone use rates overall and for each fluoroquinolone active substance through flexible modelling via segmented regression to detect time points of trend changes, in monthly percentage change (MPC). RESULTS: The incidence of fluoroquinolone use ranged from 0.7 to 8.0/1000 persons per month over all calendar years. While changes in fluoroquinolone prescriptions were observed over time across countries, these were inconsistent and did not seem to be temporally related to EMA interventions (e.g., Belgium: February/May 2018, MPC - 33.3%, 95% confidence interval [CI] - 35.9 to - 30.7; Germany: February/May 2019, MPC - 12.6%, 95% CI - 13.7 to - 11.6]; UK: January/April 2016, MPC - 4.9%, 95% CI - 6.2 to - 3.6). CONCLUSION: The regulatory action associated with the 2018 referral did not seem to have relevant effects on fluoroquinolone prescribing in primary care.

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.