Data quality and methodology in studies on maternal medication use in relation to congenital anomalies

In Nederland wordt ongeveer 1 op de 30 kinderen geboren met een aangeboren afwijking, zoals een open ruggetje (spina bifida), gespleten lip en/of gehemelte (schisis), of een gaatje in het hart (septum defect). Eén van de risicofactoren voor het ontstaan van een aangeboren afwijking is medicijngebruik door de moeder tijdens de zwangerschap. Veel vrouwen gebruiken medicijnen gedurende hun zwangerschap, terwijl van verschillende geneesmiddelen niet helemaal duidelijk is of deze mogelijk schadelijk kunnen zijn voor het ongeboren kind. Om onderzoek te doen naar mogelijke relaties tussen medicijngebruik van de moeder tijdens de zwangerschap en aangeboren afwijkingen, zijn speciale databases nodig met zo volledig mogelijke informatie over aangeboren afwijkingen, zoals de EUROCAT database. EUROCAT is een Europees netwerk van registraties van kinderen met aangeboren afwijkingen. Daarnaast is goede informatie over medicijngebruik tijdens de zwangerschap nodig. Uit dit promotieonderzoek is gebleken dat het koppelen van databases met gegevens over voorgeschreven medicijnen aan de EUROCAT-data van grote toegevoegde waarde is, omdat de EUROCAT-data voor wat betreft bepaalde medicatie, zoals antidepressiva, anti-astmamedicatie, antibiotica en bepaalde ovulatie-stimulerende middelen niet compleet zijn. Omdat het onduidelijk is of de medicijnen die tijdens de zwangerschap zijn voorgeschreven ook daadwerkelijk zijn gebruikt, hebben we ook hier onderzoek naar verricht. Voor de meeste geneesmiddelgroepen bleek dit wel het geval, waardoor we kunnen stellen dat voorschrijfgegevens gebruikt kunnen worden als een betrouwbare bron voor het onderzoek naar medicijngebruik tijdens de zwangerschap. Voor het goed kunnen monitoren van medicijngebruik tijdens de zwangerschap in relatie tot aangeboren afwijkingen bij het kind, zijn grote databases nodig die alleen gerealiseerd kunnen worden door internationale samenwerking, zoals in het EUROmediCAT project.In the Netherlands one in 30 children is born with a congenital anomaly, like spina bifida, cleft or a heart defect. One of the risk factors for congenital anomalies is maternal medication taken during pregnancy; this is very common, despite uncertainties about the safety of many medicines. Special databases to record full information on congenital anomalies are needed to be able to investigate possible associations with maternal medication use during pregnancy. EUROCAT maintains one such database. EUROCAT is an European network of congenital anomalies registries. In addition, good information on maternal medication use during pregnancy is needed.This thesis shows that linking prescription databases to EUROCAT data supplements the data recorded on mother’s medication use, which is not always complete for specific medications like certain antidepressants, anti-asthmatics, antibacterials, and some ovulation stimulants. However, from prescription databases it is still unclear whether the prescribed medication was actually taken. We therefore studied the actual use of medicines during pregnancy. It seems that most medication is indeed taken, which means that data from prescription records can be used as a reliable source of data for research into medication use during pregnancy. Very large databases are needed for monitoring possible associations between maternal medication use in pregnancy and congenital anomalies and these can only be realised by international collaborations, as formed for the EUROmediCAT project, for example

Data quality and methodology in studies on maternal medication use in relation to congenital anomalies

In Nederland wordt ongeveer 1 op de 30 kinderen geboren met een aangeboren afwijking, zoals een open ruggetje (spina bifida), gespleten lip en/of gehemelte (schisis), of een gaatje in het hart (septum defect). Eén van de risicofactoren voor het ontstaan van een aangeboren afwijking is medicijngebruik door de moeder tijdens de zwangerschap. Veel vrouwen gebruiken medicijnen gedurende hun zwangerschap, terwijl van verschillende geneesmiddelen niet helemaal duidelijk is of deze mogelijk schadelijk kunnen zijn voor het ongeboren kind. Om onderzoek te doen naar mogelijke relaties tussen medicijngebruik van de moeder tijdens de zwangerschap en aangeboren afwijkingen, zijn speciale databases nodig met zo volledig mogelijke informatie over aangeboren afwijkingen, zoals de EUROCAT database. EUROCAT is een Europees netwerk van registraties van kinderen met aangeboren afwijkingen. Daarnaast is goede informatie over medicijngebruik tijdens de zwangerschap nodig. Uit dit promotieonderzoek is gebleken dat het koppelen van databases met gegevens over voorgeschreven medicijnen aan de EUROCAT-data van grote toegevoegde waarde is, omdat de EUROCAT-data voor wat betreft bepaalde medicatie, zoals antidepressiva, anti-astmamedicatie, antibiotica en bepaalde ovulatie-stimulerende middelen niet compleet zijn. Omdat het onduidelijk is of de medicijnen die tijdens de zwangerschap zijn voorgeschreven ook daadwerkelijk zijn gebruikt, hebben we ook hier onderzoek naar verricht. Voor de meeste geneesmiddelgroepen bleek dit wel het geval, waardoor we kunnen stellen dat voorschrijfgegevens gebruikt kunnen worden als een betrouwbare bron voor het onderzoek naar medicijngebruik tijdens de zwangerschap. Voor het goed kunnen monitoren van medicijngebruik tijdens de zwangerschap in relatie tot aangeboren afwijkingen bij het kind, zijn grote databases nodig die alleen gerealiseerd kunnen worden door internationale samenwerking, zoals in het EUROmediCAT project

Climate Anxiety:A Research Agenda Inspired by Emotion Research

Climate anxiety refers to persistent, difficult-to-control apprehensiveness and worry about climate change. Research to better understand the prevalence, indicators, causes, and consequences of climate anxiety is needed, to which emotion researchers can make substantial contributions. First, emotion theory can inform an integrative and functional theory of climate anxiety, mapping interactions between its cognitive, emotional, behavioural, and physiological indicators. Second, appraisal theories can help to understand the reasons why people experience climate anxiety. Third, emotion researchers can contribute to theorizing when climate anxiety motivates climate action, accounting for non-linearity, interactions with other emotions and cognitions, and temporal dynamics. Fourth, emotion researchers can contribute to developing strategies to cope with climate anxiety, for example, by building on emotion regulation theory.</p

The influence of volume and intensive care unit organization on hospital mortality in patients admitted with severe sepsis: a retrospective multicentre cohort study

Contains fulltext : 52407.pdf ( ) (Open Access)INTRODUCTION: The aim of the study was to assess the influence of annual volume and factors related to intensive care unit (ICU) organization on in-hospital mortality among patients admitted to the ICU with severe sepsis. METHODS: A retrospective cohort study was conducted using the database of the Dutch National Intensive Care Evaluation (NICE) registry. Analyses were based on consecutive patients admitted between 1 January 2003 and 30 June 2005 who fulfilled criteria for severe sepsis within the first 24 hours of admission. A 13-item questionnaire was sent to all 32 ICUs across The Netherlands that participated in the NICE registry within this period in order to obtain information on ICU organization and staffing. The association between in-hospital mortality and factors related to ICU organization was investigated using logistic regression analysis, combined with generalized estimation equations to account for potential correlations of outcomes within ICUs. Correction for patient-related factors took place by including Simplified Acute Physiology Score II, age, sex and number of dysfunctioning organ systems in the analyses. RESULTS: Analyses based on 4,605 patients from 28 ICUs (questionnaire response rate 90.6%) revealed that a higher annual volume of severe sepsis patients is associated with a lower in-hospital mortality (P = 0.029). The presence of a medium care unit (MCU) as a step-down facility with intermediate care is associated with a higher in-hospital mortality (P = 0.013). For other items regarding ICU organization, no independent significant relationships with in-hospital mortality were found. CONCLUSION: A larger annual volume of patients with severe sepsis admitted to Dutch ICUs is associated with lower in-hospital mortality in this patient group. The presence of a MCU as a step-down facility is associated with greater in-hospital mortality. No other significant associations between in-hospital mortality and factors related to ICU organization were found

Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients

Introduction The aim of this study was to investigate whether in-hospital mortality was associated with the administered fraction of oxygen in inspired air (FiO(2)) and achieved arterial partial pressure of oxygen (PaO(2)). Methods This was a retrospective, observational study on data from the first 24 h after admission from 36,307 consecutive patients admitted to 50 Dutch intensive care units (ICUs) and treated with mechanical ventilation. Oxygenation data from all admission days were analysed in a subset of 3,322 patients in 5 ICUs. Results Mean PaO(2) and FiO(2) in the first 24 h after ICU admission were 13.2 kPa (standard deviation (SD) 6.5) and 50% (SD 20%) respectively. Mean PaO(2) and FiO(2) from all admission days were 12.4 kPa (SD 5.5) and 53% (SD 18). Focusing on oxygenation in the first 24 h of admission, in-hospital mortality was shown to be linearly related to FiO(2) value and had a U-shaped relationship with PaO(2) (both lower and higher PaO(2) values were associated with a higher mortality), independent of each other and of Simplified Acute Physiology Score (SAPS) II, age, admission type, reduced Glasgow Coma Scale (GCS) score, and individual ICU. Focusing on the entire ICU stay, in-hospital mortality was independently associated with mean FiO(2) during ICU stay and with the lower two quintiles of mean PaO(2) value during ICU stay. Conclusions Actually achieved PaO(2) values in ICU patients in The Netherlands are higher than generally recommended in the literature. High FiO(2), and both low PaO(2) and high PaO(2) in the first 24 h after admission are independently associated with in-hospital mortality in ICU patients. Future research should study whether this association is causal or merely a reflection of differences in severity of illness insufficiently corrected for in the multivariate analysis

Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients

Introduction The aim of this study was to investigate whether in-hospital mortality was associated with the administered fraction of oxygen in inspired air (FiO(2)) and achieved arterial partial pressure of oxygen (PaO(2)). Methods This was a retrospective, observational study on data from the first 24 h after admission from 36,307 consecutive patients admitted to 50 Dutch intensive care units (ICUs) and treated with mechanical ventilation. Oxygenation data from all admission days were analysed in a subset of 3,322 patients in 5 ICUs. Results Mean PaO(2) and FiO(2) in the first 24 h after ICU admission were 13.2 kPa (standard deviation (SD) 6.5) and 50% (SD 20%) respectively. Mean PaO(2) and FiO(2) from all admission days were 12.4 kPa (SD 5.5) and 53% (SD 18). Focusing on oxygenation in the first 24 h of admission, in-hospital mortality was shown to be linearly related to FiO(2) value and had a U-shaped relationship with PaO(2) (both lower and higher PaO(2) values were associated with a higher mortality), independent of each other and of Simplified Acute Physiology Score (SAPS) II, age, admission type, reduced Glasgow Coma Scale (GCS) score, and individual ICU. Focusing on the entire ICU stay, in-hospital mortality was independently associated with mean FiO(2) during ICU stay and with the lower two quintiles of mean PaO(2) value during ICU stay. Conclusions Actually achieved PaO(2) values in ICU patients in The Netherlands are higher than generally recommended in the literature. High FiO(2), and both low PaO(2) and high PaO(2) in the first 24 h after admission are independently associated with in-hospital mortality in ICU patients. Future research should study whether this association is causal or merely a reflection of differences in severity of illness insufficiently corrected for in the multivariate analysis

Improving Information on Maternal Medication Use by Linking Prescription Data to Congenital Anomaly Registers: A EUROmediCAT Study

Research on associations between medication use during pregnancy and congenital anomalies is significative for assessing the safe use of a medicine in pregnancy. Congenital anomaly (CA) registries do not have optimal information on medicine exposure, in contrast to prescription databases. Linkage of prescription databases to the CA registries is a potentially effective method of obtaining accurate information on medicine use in pregnancies and the risk of congenital anomalies. We linked data from primary care and prescription databases to five European Surveillance of Congenital Anomalies (EUROCAT) CA registries. The linkage was evaluated by looking at linkage rate, characteristics of linked and non-linked cases, first trimester exposure rates for six groups of medicines according to the prescription data and information on medication use registered in the CA databases, and agreement of exposure. Of the 52,619 cases registered in the CA databases, 26,552 could be linked. The linkage rate varied between registries over time and by type of birth. The first trimester exposure rates and the agreements between the databases varied for the different medicine groups. Information on anti-epileptic drugs and insulins and analogue medicine use recorded by CA registries was of good quality. For selective serotonin reuptake inhibitors, anti-asthmatics, antibacterials for systemic use, and gonadotropins and other ovulation stimulants, the recorded information was less complete. Linkage of primary care or prescription databases to CA registries improved the quality of information on maternal use of medicines in pregnancy, especially for medicine groups that are less fully registered in CA registries

Multivalent Anchoring and Oriented Display of Single-Domain Antibodies on Cellulose

Antibody engineering has allowed for the rapid generation of binding agents against virtually any antigen of interest, predominantly for therapeutic applications. Considerably less attention has been given to the development of diagnostic reagents and biosensors using engineered antibodies. Recently, we produced a novel pentavalent bispecific antibody (i.e., decabody) by pentamerizing two single-domain antibodies (sdAbs) through the verotoxin B subunit (VTB) and found both fusion partners to be functional. Using a similar approach, we have engineered a bispecific pentameric fusion protein consisting of five sdAbs and five cellulose-binding modules (CBMs) linked via VTB. To find an optimal design format, we constructed six bispecific pentamers consisting of three different CBMs, fused to the Staphylococcus aureus-specific human sdAb HVHP428, in both orientations. One bispecific pentamer, containing an N-terminal CBM9 and C-terminal HVHP428, was soluble, non-aggregating, and did not degrade upon storage at 4 °C for over six months. This molecule was dually functional as it bound to cellulose-based filters as well as S. aureus cells. When impregnated in cellulose filters, the bispecific pentamer recognized S. aureus cells in a flow-through detection assay. The ability of pentamerized CBMs to bind cellulose may form the basis of an immobilization platform for multivalent display of high-avidity binding reagents on cellulosic filters for sensing of pathogens, biomarkers and environmental pollutants