Terrace Review, May, 28, 1986

Thrombosis and Hemostasi

Characteristics and quality of oral anticoagulation treatment in pediatric patients in the Netherlands based on the CAPS cohort

Essentials: The knowledge of quality and safety of acenocoumarol and phenprocoumon use in children is limited. We used data from a multicenter retrospective follow-up study in children in the Netherlands. The quality of anticoagulation control in the first month of use was low, but improved thereafter. No thromboembolic events occurred, however bleeding events occurred in 1-3 out of 10 patients. Summary: Background: The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives: To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods: The Children Anticoagulation and Pharmacogenetics Study (C

Primary care diagnostic and treatment pathways in Dutch women with urinary incontinence

OBJECTIVE: To investigate how GPs manage women with urinary incontinence (UI) in the Netherlands and to assess whether this is in line with the relevant Dutch GP guideline. Because UI has been an underreported and undertreated problem for decades despite appropriate guidelines being created for general practitioners (GPs). DESIGN: Retrospective cohort study. SETTING: Routine primary care data for 2017 in the Netherlands. SUBJECTS: We included the primary care records of women aged 18-75 years with at least one contact registered for UI, and then extracted information about baseline characteristics, diagnosis, treatment, and referral to pelvic physiotherapy or secondary care. RESULTS: In total, 374 records were included for women aged 50.3 ± 15.1 years. GPs diagnosed 31.0%, 15.2%, and 15.0% women with stress, urgency, or mixed UI, respectively; no diagnosis of type was recorded in 40.4% of women. Urinalysis was the most frequently used diagnostic test (42.5%). Education was the most common treatment, offered by 17.9% of GPs; however, no treatment or referral was reported in 15.8% of cases. As many as 28.7% and 21.7% of women were referred to pelvic physiotherapy and secondary care, respectively. CONCLUSION: Female UI is most probably not managed in line with the relevant Dutch GP guideline. It is also notable that Dutch GPs often fail to report the type of UI, to use available diagnostic approaches, and to provide appropriate education. Moreover, GPs referred to specialists too often, especially for the management of urgency UI.Key pointsUrinary incontinence (UI) has been an underreported and undertreated problem for decades. Despite various guidelines, UI often lies outside the GPs comfort zone.•According to this study: general practitioners do not treat urinary incontinence according to guidelines.•The type of incontinence is frequently not reported and diagnostic approaches are not fully used.•We believe that increased awareness will help improve treatment and avoidable suffering

Incidence of bleeding and thrombotic events in non-institutionalized paediatric patients using warfarin in the united kingdom

Background: Dosing of vitamin K antagonists (VKA) is complex with large inter- and intra-individual variability in patients' required VKA dose. Over- and underdosing can result in bleeding and thrombotic events. The incidence of these events in paediatric patients on warfarin therapy in a European population is unknown. Objectives: To estimate the incidence of bleeding and thrombotic events in warfarin using paediatric patients in the UK and to characterise patients who do or do not experience a bleeding or thrombotic event. Methods: Data were obtained from the UK CPRD in the period between January 1998 and November 2016. Using a cohort design, we identified all patients with ≥1 prescription for warfarin and who were ≤18 years. The date of the first prescription marked the start of the follow-up. Follow-up was classified into periods of warfarin use and non-use. Patients were followed until 19 years of age, death or departure from the practice. The incidence of non-fatal bleeding and thrombotic events was assessed using both information from CPRD and the linked Hospital Episode Statistics (HES). Fatal events were identified usings the linked mortality data from the Office for National Statistics (ONS). For calculating the incidence of thrombotic events only patients without a history of thrombosis were included. Results: In total, 685 patients were identified (median age 15 years, 45.4% female) of whom 372 could be linked to the HES and ONS databases. The incidence of bleeding and thrombotic events during warfarin use was 4.08 and 1.27/100 patient years, respectively. The incidence of bleeding events during non-use was 2.65/100 patient years (relative risk 1.58, 95% confidence interval [0.89-2.80]). Only 2 fatal events occurred, one bleeding and one thrombotic event. Patients with a bleeding event tended to have a higher percentage of INR measurements with a value above 4 (9.4 vs 3.9%) and a lower fraction below 2 (18.4 vs 39.1%) compared to patients without a bleeding event during the whole follow-up. Patients with a thrombotic event showed the opposite trend, a higher percentage of INRs below 2 (45.8 vs 29.5%) and a lower percentage of INRs above 4 (2.7 vs 5.3%). All differences were not statistically significant which maybe due to the small sample size. Conclusions: The incidence of bleeding events was higher than of thrombotic events. The trends in percentages of INRs under and above therapeutic range suggest that keeping the INR within range could decrease the occurence of these events

The pediatric acenocoumarol dosing algorithm:The Children Anticoagulation and Pharmacogenetics Study

Essentials: A pediatric pharmacogenetic dosing algorithm for acenocoumarol has not yet been developed. We conducted a multicenter retrospective follow-up study in children in the Netherlands. Body surface area and indication explained 45.0% of the variability in dose requirement. Adding the genotypes of VKORC1, CYP2C9 and CYP2C18 to the algorithm increased this to 61.8%. Summary: Background: The large variability in dose requirement of vitamin K antagonists is well known. For warfarin, pediatric dosing algorithms have been developed to predict the correct dose for a patient; however, this is not the case for acenocoumarol. Objectives: To develop dosing algorithms for pediatric patients receiving acenocoumarol with and without genetic information. Methods: The Children Anticoagulation and Pharmacogenetics Study was designed as a multicenter retrospective follow-up study in Dutch anticoagulation clinics and children's hospitals. Pediatric patients who used acenocoumarol between 1995 and 2014 were selected for inclusion. Clinical information and saliva samples for genotyping of the genes encoding cytochrome P450 (CYP) 2C9, vitamin K epoxide reductase complex subunit 1 (VKORC1), CYP4F2, CYP2C18 and CYP3A4 were collected. Linear regression was used to analyze their association with the log mean stable dose. A stable period was defined as three or more consecutive International Normalized Ratio measurements within the therapeutic range over a period of ≥ 3 weeks. Results: In total, 175 patients were included in the study, of whom 86 had a stable period and no missing clinical information (clinical cohort; median age 8.9 years, and 49% female). For 80 of these 86 patien

EEG-based visual deviance detection in freely behaving mice

The mouse is widely used as an experimental model to study visual processing. To probe how the visual system detects changes in the environment, functional paradigms in freely behaving mice are strongly needed. We developed and validated the first EEG-based method to investigate visual deviance detection in freely behaving mice. Mice with EEG implants were exposed to a visual deviant detection paradigm that involved changes in light intensity as standard and deviant stimuli. By subtracting the standard from the deviant evoked waveform, deviant detection was evident as bi-phasic negativity (starting around 70 ms) in the difference waveform. Additionally, deviance-associated evoked (beta/gamma) and induced (gamma) oscillatory responses were found. We showed that the results were stimulus-independent by applying a "flip-flop " design and the results showed good repeatability in an independent measurement. Together, we put forward a validated, easy-to-use paradigm to measure visual deviance processing in freely behaving mice.Functional Genomics of Muscle, Nerve and Brain Disorder

The Ataxic Cacna1a-Mutant Mouse Rolling Nagoya: An Overview of Neuromorphological and Electrophysiological Findings

Homozygous rolling Nagoya natural mutant mice display a severe ataxic gait and frequently roll over to their side or back. The causative mutation resides in the Cacna1a gene, encoding the pore-forming α1 subunit of Cav2.1 type voltage-gated Ca2+ channels. These channels are crucially involved in neuronal Ca2+ signaling and in neurotransmitter release at many central synapses and, in the periphery, at the neuromuscular junction. We here review the behavioral, histological, biochemical, and neurophysiological studies on this mouse mutant and discuss its usefulness as a model of human neurological diseases associated with Cav2.1 dysfunction