Overanticoagulation on coumarin anticoagulants

Most of the extensive research on oral anticoagulant therapy has focussed on its pharmacological- and biochemical action, prothrombin time calibration, optimal therapeutic intensity and hemorrhagic complications. However, whlle the risks of overanticoagulation are clear, its treatment and determinants have received little attention. Therefore, the aim of this thesis was to study aspects of overanticoagulation on coumarin anticoagulants among outpatients of an anticoagulation clinic. Overanticoagulation was defined as an INR:>6.0, since at this INR-value the risk of hemorrhage sharply increases (28, 41). Chapter 2 relates to the treatment of overanticoagulation and describes the course of the INR in response to oral vitamin K1 in overanticoagulated patients. Chapter 3 concerns the incidence of and risk factors for overanticoagulation and includes five studies. Chapter 3.1 focusses on characteristics of antic

Existing data sources for clinical epidemiology: The pharmo database network

The PHARMO Database Network provides a unique opportunity to gain insight in the complete patient journey and healthcare in the Netherlands. The PHARMO Database Network is a population-based network of electronic healthcare databases and combines anonymous data from different primary and secondary healthcare settings in the Netherlands. Healthcare settings include general practitioners, out-patient and in-patient pharmacies, hospitals and clinical laboratories. Furthermore, databases are linked with external registries suc

Respiratory morbidity, healthcare resource use, and cost burden associated with extremely preterm birth in The Netherlands

Background: Extremely preterm (EP) infants have high rates of respiratory morbidity and correspondingly high healthcare resource utilization. Objectives: Data from the PHARMO Perinatal Research Network were analyzed to quantify the burden of EP birth in the Netherlands. Methods: A retrospective analysis included infants &lt;28 weeks gestational age with a birth record in the Perinatal Registry (1999–2015) and data in the PHARMO Database Network. Outcomes of interest included select comorbidities, hospital readmissions, and costs of hospitalization and medication up to 1- and 2-years corrected age. Outcomes were stratified by birth period (1999–2005, 2000–2009, 2010–2015) and by diagnosis of bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD). Results: The cohort included 168 EP infants (37 born 1999–2005, 51 born 2006–2009, 80 born 2010–2015). Median (Q1–Q3) birth weights decreased by birth period from 970 (840–1,035) g in 1999–2005 to 853 (695–983) g in 2010–2015. Overall, BPD and CLD were reported during the birth hospitalization in 40% and 29% of infants, respectively; rates of BPD increased and rates of CLD decreased by birth period. Eighty-four percent of EP infants had an additional comorbidity. Mean (standard deviation) costs of birth hospitalization were €110,600 (€73,000) for 1999–2005, €119,350 (€60,650) for 2006–2009, and €138,800 (€130,100) for 2010–2015. Birth hospitalization and total costs for up to 1- and 2-years corrected age were higher for infants with BPD and/or CLD than for those without either complication. Conclusion: Healthcare resource utilization and costs for EP infants, especially for those with respiratory morbidities, increased between 1999 and 2015. Future cost-effectiveness analyses are essential to determine the economic impact of this change and underscore the need for new therapeutic interventions to decrease clinical sequelae in this vulnerable population.</p

Occurrence of Comorbidities before and after Soft Tissue Sarcoma Diagnosis

Background. Data is limited on the burden of common comorbidities, such as cardiovascular disease (CVD), respiratory disease and diabetes, or comorbidities related to cancer and its treatment, such as anemia and depression, in patients with soft tissue sarcoma (STS). Patients and Methods. From the Dutch Pathology Registry linked to the PHARMO database (including data on drug use and hospitalizations), 533 patients with STS were selected during 2000–2007 and matched 1 : 10 to cancer-free controls. The occurrences of comorbidities were assessed in the 12 months before and after STS diagnosis. Results. STS patients were 2–4 times more likely to have comorbidities at diagnosis compared with cancer-free controls. The incidence of CVD, anemia, and depression after STS diagnosis differed significantly from cancer-free controls and decreased during followup from 40–124 per 1,000 person-years (py) during the first six months to 11–38 per 1,000 py more than 12 months after diagnosis. The incidence of respiratory disease and diabetes among STS patients remained stable during followup (5–21 per 1,000 py) and did not differ significantly from cancer-free controls. Conclusions. STS patients were more likely to have comorbidities before cancer diagnosis and to develop CVD, anemia, and depression after diagnosis compared to cancer-free controls

Change of initial oral antidiabetic therapy in type 2 diabetic patients

Objective To explore the 'real-life' therapy of type 2 diabetes mellitus with oral antidiabetic drugs (OADs). Methods From the PHARMO Record Linkage System comprising linked drug dispensing and clinical laboratory data from approximately 2.5 million individuals in the Netherlands, among others, new users of OADs were identified in the period 1999-2004. New users, aged 30 years and older, without insulin use before cohort entry date and with at least one year follow-up were included. We determined per initial therapy patient characteristics and first therapy change. Results Overall 35,514 patients were included. Metformin and sulfonylureas (SU) were the most frequent initial therapy. Patients on thiazolidinedione (TZD) monotherapy had lower percentages baseline HbA1c ≥ 7% compared to patients on metformin and SU. The proportion of patients still on initial therapy after one year ranged from 46% (TZDs) to around 60% (SU). Among patients starting on monotherapy, add-on (15-20%) and discontinuation (16-25%) of therapy occurred most frequently. In patients starting on combination therapy, a switch occurred in 30% of the patients. Conclusion In more than 40% of the patients a change in initial OAD-therapy is already observed in the first year of therapy. Maintaining patients on initial therapy remains a challenge

Dupuytren's contracture: a retrospective database analysis to determine hospitalizations in the Netherlands

Background: Dupuytren's contracture is a condition of the palmar fascia involving contractures of the fascia and skin in the hand. Current treatment for Dupuytren's contracture is mainly limited to surgery. In the Netherlands, little is known about the prevalence of Dupuytren's contracture. In this study we determined the prevalence of patients with a hospitalization for Dupuytren's contracture in the Netherlands and characterized their (re)hospitalizations. Methods. From the PHARMO database, which consists of multiple observational databases linked on a patient level, all patients hospitalized for Dupuytren's contracture between 2004 and 2007 were included in the source population (ICD-9-CM code 728.6). Numbers from this source population were used to provide estimates of hospitalizations for Dupuytren's contracture in the Netherlands. Patients with a medical history in the PHARMO database of at least 12 months before their hospitalization were included in the study cohort and followed until end of data collection, death, or end of study period, whichever occurred first. Type of admission, length of stay, recorded procedures, treating specialty, number of rehospitalizations for Dupuytren's contracture, and time to first rehospitalization were assessed. Results: Of 3, 126 patients included in the source population, 3, 040 were included in the study population. The overall prevalence of patients with a hospitalization for Dupuytren'

Glycemic control and long-acting insulin analog utilization in patients with type 2 diabetes

Introduction: The objective was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands. Methods: Insulin-naïve patients with T2D, starting treatment with IDet or IGlar between January 1, 2004 and June 30, 2008, were selected from the PHARMO data network. Glycemic control (hemoglobin A1c [HbA1c]), target rates (HbA1c <7%), daily insulin dose, and weight gain were analyzed comparing IDet and IGlar for patients with available HbA1c levels both at baseline and at 1-year follow-up. Analysis of all eligible patients (AEP) and a subgroup of patients without treatment changes (WOTC) in the follow-up period were adjusted for patient characteristics, propensity scores, and baseline HbA1c. Results: A total of 127 IDet users and 292 IGlar users were included in the WOTC analyses. The mean HbA1c dropped from 8.4%-8.6% at baseline to 7.4% after 1 year. Patients at HbA1c goal increased from 9% at baseline to 32% for IDet and 11% to 35% for IGlar, which was not significantly different (OR 0.75, 95% CI 0.46, 1.24). Weight gain (n=90) was less among IDet users (+0.4kg) than among IGlar users (+1.1kg), albeit not significant. The AEP analysis (252 IDet