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

Loss of treatment benefit due to low compliance with bisphosphonate therapy

Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit. Introduction: Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit. Methods: New female users of alendronate or risedronate between 1999-2004, aged ≥45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of ≥2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression. Results: The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR ≥80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR ≥90%. Conclusions: These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit

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

Time to onset of antifracture efficacy and year-by-year persistence of effect of zoledronic acid in women with osteoporosis

Oral bisphosphonates reduce fracture risk in osteoporotic patients but are often associated with poor compliance, which may impair their antifracture effects. This post hoc analysis assessed the time to onset and persistence of the antifracture effect of zoledronic acid, a once-yearly bisphosphonate infusion, in women with osteoporosis. Data from 9355 women who were randomized in two placebo-controlled pivotal trials were included. Endpoints included reduction in the rate of any clinical fracture at 6, 12, 18, 24, and 36 months in the zoledronic acid group compared with placebo, and the year-by-year incidence of all clinical fractures over 3 years. Cox proportional hazards regression was used to determine the timing of onset of antifracture efficacy. A generalized estimating equation model was used to assess fracture reduction for the 3 consecutive years of treatment, thereby evaluating persistence of effect. Safety results from women in the two studies were collated. Zoledronic acid reduced the risk of all clinical fractures at 12 months (hazard ratio [HR] = 0.75, 95% confidence interval [CI] 0.61–0.92, p = 0.0050) with significant reductions maintained at all subsequent time points. Year-by-year analysis showed that zoledronic acid reduced the risk for all clinical fractures compared with the placebo group in each of the 3 years (year 1: odds ratio [OR] = 0.74, 95% CI 0.60–0.91, p = 0.0044; year 2: OR = 0.53, 95% CI 0.42–0.66, p < 0.0001; year 3: OR = 0.61, 95% CI 0.48–0.77, p < 0.0001). This antifracture effect was persistent over 3 years, with the reductions in years 2 and 3 slightly larger than in year 1 (p = 0.097). This analysis shows that zoledronic acid offered significant protection from clinical fractures as early as 12 months. When administered annually, its beneficial effects persisted for at least 3 years

Managing bone mineral density with oral bisphosphonate therapy in women with breast cancer receiving adjuvant aromatase inhibition

The use of adjuvant aromatase inhibitors is associated with an increased risk of osteoporosis and fractures. The oral bisphosphonate, risedronate - dosed as the US Food and Drug Administration approved for the treatment or prevention of postmenopausal osteoporosis - appears to mitigate bone loss associated with 2 years of adjuvant anastrozole in women with early-stage breast cancer