I&R-oormerktransponders en randapparatuur

De I&R-oormerken met transponder functioneren technisch goed, maar voor het verbeteren van de bruikbaarheid in de praktijk zijn aanpassingen nodig

The influence of morbid obesity on the pharmacokinetics and pharmacodynamics of drugs in adolescents and adults : focus on propofol and nadroparin.

For most commonly used drugs in morbidly obese patients evidence based dosing guidelines are not available. Therefore, current dosing is based on experience of the prescriber rather than on clinical evidence. Pharmacokinetic and pharmacodynamics data in non-obese patients are extrapolated without proper exploration of influence of overweight on the dose-exposure-effect relationship. The research described in this thesis focused on two commonly used drugs, propofol and the low-molecular-weight heparin (LMWH) nadroparin with the aim to develop weight appropriate dosing algorithms for these drugs in morbidly obese patients based on population pharmacokinetic and pharmacodynamics analysis. A non-linear relationship was found between propofol clearance and total body weight in both morbidly obese and non-obese adults, adolescents and children. Furthermore, the influence of age on propofol clearance was described using a bilinear function. A model based dosing algorithm using an adjusted dosing weight for propofol maintenance infusion was successfully evaluated in a prospective study in morbidly obese adults and can therefore be implemented in daily practice. For nadroparin in both morbidly obese and non-obese patients, total body clearance increased linearly with total body weight whereas the central of volume distribution increased linearly with lean body weight, suggesting that lean body weight is clinically useful for nadroparin dosing. The developed pharmacodynamic model for nadroparin in non-obese and morbidly obese patients can be used as a starting point to further identify the appropriate anti-Xa targets in morbidly obese patients.UBL - phd migration 201

The subtypes of developmental coordination disorder

Aim: To identify subtypes in a large group of children clinically diagnosed with developmental coordination disorder (DCD) based on their pattern of motor, cognitive, and visual-motor abilities. Method: Standardized scores for verbal IQ, total IQ, Movement Assessment Battery for Children, Second Edition (MABC-2) balance, MABC-2 manual dexterity, MABC-2 ball skills, and Beery-Buktenica Developmental Tests of Visual-Motor Integration (Beery-VMI), Motor Coordination (Beery-MC), and Visual Perception (Beery-VP) were used. The NbClust complete procedure was used to best partition the data on 98 children (84 males, 14 females, mean [SD] age: 8 years [2 years 1 month]) into clusters. Deviation contrasts, multivariate analysis of variance, and post hoc comparisons were used to characterize the clusters. Results: Four clusters were revealed: two clusters with a broad motor skill problem, one with relatively preserved visual-motor integration and Beery-MC skills, and a second with abnormal ball skills, balance, and Beery-MC skills. A third cluster with more specific gross-motor problems, and a fourth with relatively preserved ball skills but low Beery-MC and performance IQ, were identified. Balance scores were 'at risk' or 'abnormal' in all four clusters. Interpretation: DCD is a heterogeneous condition. However, subtypes can be discriminated on the basis of more severe difficulties in fine-motor performance, gross-motor performance, or both. There was evidence for generalized motor impairments in around half of all children. Importantly, at least borderline level reduced balance was evident in each subtype. What this paper adds: Four subtypes were identified in a large clinical group of children with developmental coordination disorder (DCD). Subtypes were based on motor, cognitive, and visual-motor abilities. There was evidence of generalized motor impairments in around 50% of children with DCD. A generalized balance problem is present across all subtypes of DCD

Development of a clinical prediction model for an international normalised ratio ≥ 4·5 in hospitalised patients using vitamin K antagonists

Vitamin K antagonists (VKAs) used for the prevention and treatment of thromboembolic disease, increase the risk of bleeding complications. We developed and validated a model to predict the risk of an international normalised ratio (INR) ≥ 4·5 during a hospital stay. Adult patients admitted to a tertiary hospital and treated with VKAs between 2006 and 2010 were analysed. Bleeding risk was operationalised as an INR value ≥4·5. Multivariable logistic regression analysis was used to assess the association between potential predictors and an INR ≥ 4·5 and validated in an independent cohort of patients from the same hospital between 2011 and 2014. We identified 8996 admissions of patients treated with VKAs, of which 1507 (17%) involved an INR ≥ 4·5. The final model included the following predictors: gender, age, concomitant medication and several biochemical parameters. Temporal validation showed a c statistic of 0·71. We developed and validated a clinical prediction model for an INR ≥ 4·5 in VKA-treated patients admitted to our hospital. The model includes factors that are collected during routine care and are extractable from electronic patient records, enabling easy use of this model to predict an increased bleeding risk in clinical practice

Antithrombotic stewardship: A multidisciplinary team approach towards improving antithrombotic therapy outcomes during and after hospitalisation

_Introduction:_ Antithrombotic therapy carries high risks for patient safety. Antithrombotics belong to the top 5 medications involved in potentially preventable hospital admissions related to medication. To provide a standard for antithrombotic therapy and stress the importance of providing optimal care to patients on antithrombotic therapy, the Landelijke Standaard Ketenzorg Antistolling (LSKA; Dutch guideline on integrated antithrombotic care) was drafted. However, the mere publication of this guideline does not guarantee its implementation. This may require a multidisciplinary team effort. Therefore, we designed a study aiming to determine the influence of hospital-based antithrombotic stewardship on the effect and safety of antithrombotic therapy outcomes during and after hospitalisation. _Methods and analysis:_ In this study, the effect of the implementation of a multidisciplinary antithrombotic team is compared with usual care using a pre-post study design. The study is performed at the Erasmus University Medical Center Rotterdam and the Reinier de Graaf Hospital Delft. Patients who are or will be treated with antithrombotics are included in the study. We aim to include 1900 patients, 950 in each hospital. Primary outcome is the proportion of patients with a composite end point consisting of ≥1 bleeding or ≥1 thrombotic event from the beginning of antithrombotic therapy (or hospitalisation) until 3 months after hospitalisation. Bleeding is defined according to the International Society of Thrombosis and Haemostasis (ISTH) classification. A thrombotic event is defined as any objectively confirmed arterial or venous thrombosis, including acute myocardial infarction or stroke for arterial thrombosis and deep venous thrombosis or pulmonary embolism or venous thrombosis. An economic evaluation is performed to determine whether the implementation of the multidisciplinary antithrombotic team will be cost-effective. _Ethics and dissemination:_ This protocol was approved by the Medical Ethical Committee of the Erasmus University Medical Center. The findings of the study will be disseminated through peer-reviewed journals and presented at relevant conferences

The effect of hospital-based antithrombotic stewardship on adherence to anticoagulant guidelines

Background: Anticoagulant therapy is associated with a high risk of complications. Adherence to anticoagulant therapy protocols may lower this risk but adherence is often suboptimal. The introduction of a multidisciplinary antithrombotic team may improve adherence to anticoagulant guidelines among physicians. Objective: To determine the efect of hospital-based multidisciplinary antithrombotic stewardship on adherence to anticoagulant guidelines among prescribing physicians. Setting This prospective non-randomised before-and-after study was conducted in patients hospitalized between October 2015 and December 2017 and treated with anticoagulant therapy. Method: A multidisciplinary antithrombotic team focusing on education, medication reviews, drafting of local anticoagulant therapy protocols, patient counseling and medication reconciliation at admission and discharge was implemented in two Dutch hospitals. Main outcome measure Primary outcome was the proportion of the admitted patients in which the prescribing physician did adhere to the anticoagulant guidelines. Results: The study comprised 1886 patients, of which 941 patients were included in the usual care period and 945 patients in the intervention period. Multivariable logistic regression analysis indicated that adherence was observed signifcantly more often during the intervention period (adjusted odds ratio [ORadj] 1.58, 95% confdence interval [95% CI] 1.21–2.05). Detailed analysis identifed that the signifcantly higher overall adherence in the intervention period was attributed to dosing of LMWHs (odds ratio [OR] 1.58, 95% CI 1.16–2.14). Conclusion: This study shows that introduction of a multidisciplinary antithrombotic stewardship leads to a signifcantly higher overall adherence to anticoagulant guidelines among prescribing physicians, mainly based on the improvement of dosing of low-molecular-weight-heparins

Effect of antithrombotic stewardship on the efficacy and safety of antithrombotic therapy during and after hospitalization

Background Although the benefits of antithrombotic drugs are indisputable to reduce thrombotic events, they carry a high risk of compromising patient safety. No previous studies investigated the implementation and (cost-) effectiveness of a hospital-based multidisciplinary antithrombotic team on bleeding and thrombotic outcomes. The primary aim of this study was to compare the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. Methods and findings A prospective, multicenter before-after intervention study was conducted in two Dutch hospitals. Adult patients hospitalized between October 2015 and December 2017 treated with anticoagulant therapy were included. The primary aim was to estimate the proportion of patients with a composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization. The intervention was the implementation of a multidisciplinary antithrombotic team focusing on education, medication reviews by pharmacists, implementing of local anticoagulant therapy guidelines based on national guidelines, patient counselling and medication reconciliation at admission and discharge. The primary endpoint was analysed using segmented linear regression. We obtained data for 1,886 patients: 941 patients were included in the usual care period and 945 patients in the intervention period. The S-team study showed that implementation of a multidisciplinary antithrombotic team over time significantly reduced the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs (-1.83% (-2.58% to -1.08%) per 2 month period). Conclusions This study shows that implementation of a multidisciplinary antithrombotic team over time significantly reduces the composite end point consisting of one or more bleeding episodes or one or more thrombotic event from hospitalization until three months after hospitalization in patients using anticoagulant drugs