Perception of drug teratogenicity among general practitioners and specialists in obstetrics/gynecology:a regional and national questionnaire-based survey

Cover letter to participants and online questionnaire. (DOC 27 kb

Reducing αENaC expression in the kidney connecting tubule induces pseudohypoaldosteronism type 1 symptoms during K+ loading.

Genetic inactivation of the epithelial Na(+) channel α-subunit (αENaC) in the renal collecting duct (CD) does not interfere with Na(+) and K(+) homeostasis in mice. However, inactivation in the CD and a part of the connecting tubule (CNT) induces autosomal recessive pseudohypoaldosteronism type 1 (PHA-1) symptoms in subjects already on a standard diet. In the present study, we further examined the importance of αENaC in the CNT. Knockout mice with αENaC deleted primarily in a part of the CNT (CNT-KO) were generated using Scnn1a(lox/lox) mice and Atp6v1b1::Cre mice. With a standard diet, plasma Na(+) concentration ([Na(+)]) and [K(+)], and urine Na(+) and K(+) output were unaffected. Seven days of Na(+) restriction (0.01% Na(+)) led to a higher urine Na(+) output only on days 3-5, and after 7 days plasma [Na(+)] and [K(+)] were unaffected. In contrast, the CNT-KO mice were highly susceptible to a 2-day 5% K(+) diet and showed lower food intake and relative body weight, lower plasma [Na(+)], higher fractional excretion (FE) of Na(+), higher plasma [K(+)], and lower FE of K(+). The higher FE of Na(+) coincided with lower abundance and phosphorylation of the Na(+)-Cl(-) cotransporter. In conclusion, reducing ENaC expression in the CNT induces clear PHA-1 symptoms during high dietary K(+) loading

Enamel maturation: a brief background with implications for some enamel dysplasias

The maturation stage of enamel development begins once the final tissue thickness has been laid down. Maturation includes an initial transitional pre-stage during which morphology and function of the enamel organ cells change. When this is complete, maturation proper begins. Fully functional maturation stage cells are concerned with final proteolytic degradation and removal of secretory matrix components which are replaced by tissue fluid. Crystals, initiated during the secretory stage, then grow replacing the tissue fluid. Crystals grow in both width and thickness until crystals abut each other occupying most of the tissue volume i.e. full maturation. If this is not complete at eruption, a further post eruptive maturation can occur via mineral ions from the saliva. During maturation calcium and phosphate enter the tissue to facilitate crystal growth. Whether transport is entirely active or not is unclear. Ion transport is also not unidirectional and phosphate, for example, can diffuse out again especially during transition and early maturation. Fluoride and magnesium, selectively taken up at this stage can also diffuse both in an out of the tissue. Crystal growth can be compromised by excessive fluoride and by ingress of other exogenous molecules such as albumin and tetracycline. This may be exacerbated by the relatively long duration of this stage, 10 days or so in a rat incisor and up to several years in human teeth rendering this stage particularly vulnerable to ingress of foreign materials, incompletely mature enamel being the result

Acetaminophen in Pregnancy:A Population-Level Drug-Utilization Study of Prescription-Based Acetaminophen Use Among Pregnant Women in Denmark From 2001 to 2023

Acetaminophen is the most used analgetic drug for pain management during pregnancy. A recent academic controversy concerns the safety of acetaminophen during pregnancy related to a potentially increased risk of adverse neurodevelopmental effects. We investigated the population-level trends in prescription-based use of acetaminophen among pregnant women in Denmark between 2001 and 2023. Prescription-based sals of acetaminophen among pregnant women and comparison groups were retrieved from ‘eSundhed’, a publicly available dataset curated by the Danish Health Authorities. The number of prescription-based drug users per 1000 pregnant women increased slightly from 2001 to 2012 (3.9 to 6.5 per 1000) and 2015 to 2023 (52 to 76 per 1000), interrupted by a drastic increase in 2013/2014. Acetaminophen use among pregnant women (2023: 76 per 1000) was lower than in women in an age-matched comparison group (137 per 1000) and in women 12–3 months prior to pregnancy (124 per 1000). Time trends did not notably differ between age groups or comparison groups. Prescription-based acetaminophen sales among pregnant women increased by 50% from 2015 to 2023. A general shift in the prescription pattern towards a substantial increase in prescription-based exposure was observed following legislation changes in 2013, restricting sales of large packages to prescription.</p

Serotonin syndrome—A focused review

Background: Serotonin syndrome is a potentially life-threatening syndrome with manifestations spanning from mild adverse effects to life-threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation. Objectives: This review aims to provide a clinically focused overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis and treatment, as well as classifying serotonergic drugs and their mechanism of action. The pharmacological context is emphasized, as it is crucial for the detection and management of serotonin syndrome. Methods: Focused review based on a literature search using the PubMed database. Findings and conclusion: Serotonin syndrome can occur through therapeutic use or overdose of a single serotonergic drug or as a drug interaction between two or more serotonergic drugs. Central clinical features consist of neuromuscular excitation, autonomic dysfunction and altered mental status, occurring in a patient undergoing new or altered serotonergic therapy. Early clinical recognition and treatment are crucial to prevent significant morbidity.</p

Congenital malformations in Denmark:Considerations for the use of danish health care registries

Background: Danish health registers are used widely to examine associations between specific risk factors and congenital malformations. Various overall prevalence rates of malformations have been reported in Denmark indicating differences in the underlying data sources or malformation definitions. We described trends in registration of malformations in Denmark 1997–2017 and identified potential caveats for the use of Danish health registries in epidemiological studies. We composed a Danish adaptation of EUROCATs definition of malformations. Methods: Using nationwide Danish health registries, we identified all recorded pregnancies and followed livebirths for up to 5 years. We described the different data sources, ways to identify malformations, the overall rate of malformations over time, and identified the 10 most common major malformations. Results: A total of 1,340,774 foetuses and infants from 1,313,281 pregnancies among 747,144 women from 1997 to 2017 were analysed. Using primary and secondary diagnoses from all available sources and restricting hip malformations to diagnoses after 6 weeks postpartum, we found that 65,411 (49/1000) foetuses or infants had at least one major malformation defined by our Danish translation of EUROCATs definition of malformations. The prevalence of major malformations increased over time from 39/1000 in 1997 to 53/1000 in 2017. The most common specific malformations were malformations of cardiac septa (Q21) and great arteries (Q25) with a peak of 10 and 6/1000 births in 2010 and 2009, respectively. Conclusion: Malformations should be identified using primary and secondary diagnoses from the Birth register, the Patient register, and the Cause of Death register. To increase transparency and external validity, classification of major malformations should be based on the Danish adaptation of EUROCATs classification of malformations.</p