Describe the trends of exposure to harmful drugs during pregnancy over recent years in France.
Nationwide cohort study.
The French National administrative health Data System (SNDS).
Pregnancies ...starting between 2013 and 2019 and outcomes corresponding to live births, medical terminations of pregnancy, and stillbirths.
Each pregnancy was divided into a preconceptional period of 90 days before conception and three trimesters from conception to birth. Harmful drugs were defined according to their risks to the fetus: teratogenicity or fetotoxicity. Exposure was defined using the critical period during pregnancy for each type of harmful drug: preconceptional period or first trimester for teratogenic drugs and second or third trimesters for fetotoxic drugs.
Prevalence of pregnancies exposed to at least one harmful drug.
Among 5,253,284 pregnancies, 204,402 (389 per 10,000) pregnancies were exposed to at least one harmful drug during the critical periods: 48,326 (92 per 10,000) pregnancies were exposed to teratogenic drugs during the preconceptional period or the first trimester, and 155,514 (299 per 10,000) pregnancies were exposed to fetotoxic drugs during the second or third trimesters. Teratogenic drugs were mainly retinoids for topical use (44 per 10,000 pregnancies), antiepileptics (13 per 10,000 pregnancies) and statins (13 per 10,000 pregnancies). Fetotoxic drugs were mainly non-steroidal anti-inflammatory drugs (NSAIDs), for systemic (128 per 10,000 pregnancies) and topical use (122 per 10,000 pregnancies). Exposure to teratogenic drugs decreased from the preconceptional period to the first trimester. Exposure to fetotoxic drugs decreased from the second to the third trimester. Between 2013 and 2019, we found a decrease in harmful drug exposure overall, mainly for topical and systemic NSAIDs and for topical retinoids.
In this nationwide study, about one in 25 pregnancies was exposed to at least one harmful drug, mainly NSAIDs and topical retinoids. Although the prevalence of harmful drug exposure decreased over the study period, NSAID exposure in the second and third trimester remains of concern.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to ...specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT.
Objective
Even though systemic vasculitides (SVs) affect primarily patients over 50 years of age, they can occur among women of childbearing age. Preterm birth (PTB) and hypertensive disorders are ...frequent complications of pregnancy in SVs. This study aims to evaluate the risk of hypertensive disorders and PTB among pregnant women with SVs, and to identify associated risk factors.
Method
Using the French health insurance data warehouse, we conducted a nationwide cohort study including all pregnancies between 2013 and 2018 in women with SVs. Theses pregnancies were matched to pregnancies among women without SVs. We estimated risk of hypertensive disorders and PTB risk during pregnancy among women with SVs and investigated associated risk factors using a nested case‐control design.
Results
Among 3,155,723 pregnancies, we identified 646 pregnancies in women with SVs, matched to 3,230 controls. SVs were significantly associated with hypertensive disorders (odds ratio OR 1.7, 95% confidence interval 95% CI 1.3–2.2) and PTB (OR 1.8, 95% CI 1.4–2.3). Chronic renal failure before pregnancy, history of or treated arterial hypertension, the occurrence of vasculitides flare during pregnancy, and the subgroup of SVs were independently associated with the occurrence of hypertensive disorders. Maternal age at delivery, chronic renal failure before conception, and the occurrence of vasculitides flare during pregnancy were independently associated with the occurrence of PTB.
Conclusion
About one of seven pregnancies in women with SVs is associated with hypertensive disorders or preterm birth. The occurrence of vasculitides flare was associated with these complications. Our findings support the importance of prepregnancy counseling to ensure disease stability.
Given the high prevalence of antibiotic prescription during pregnancy in France and previous studies suggesting an increased risk of infection in offspring with such exposures, our study aimed to ...investigate the association between prenatal exposure to systemic antibiotics and serious infections in full-term infants during their first year of life.
We conducted a retrospective population-based cohort study on singleton, full-term liveborn non-immunocompromised infants, using the French National Health Data System (SNDS) between 2012 and 2021. Systemic antibiotic dispensing in ambulatory care settings during pregnancy defined the exposure. Outcomes concerned serious infections (i.e., infections requiring hospitalization) in offspring identified between 3 and 12 months of life, hence excluding infections of maternal origin. Adjusted odds ratios (aORs) were estimated using logistic regression with multivariate models to control for potential confounders.
Of 2,836,630 infants included, 39.6% were prenatally exposed to systemic antibiotics. Infants prenatally exposed to antibiotics had a higher incidence of serious infections compared with unexposed infants {aOR 1.12 95% confidence interval (95% CI) 1.11-1.13}. Similar associations were observed according to the timing of exposure during pregnancy, antibiotic class, and site of infections. The strongest association was observed when infants were prenatally exposed to three or more antibiotic courses during pregnancy aOR 1.21 (95% CI 1.19-1.24). Limitations include residual confounders, such as genetic susceptibility to infections and the role of the underlying pathogen agent.
Prenatal exposure to systemic antibiotics is very common and is associated with a weak yet significant associations with subsequent serious infectious events during the first year of life. While our study revealed associations, it is important to note that causation cannot be established, given the acknowledged limitations, including potential confounding by indication.
•About 40% of women with systemic vasculitis were treated by immunosuppressive drugs during pregnancy.•The number of patients treated with non-recommended immunosuppressant during pregnancy gradually ...decreased before pregnancy.•Proportion of systemic vasculitis flare did not increase significantly during pregnancy.
Systemic vasculitis (SV) rarely affects women of childbearing age and only small series have been reported to date in pregnant patients. The discovery of an unplanned pregnancy can be an urgent cause for modifying treatments. This study aimed to describe immunosuppressive drugs use before, during and after pregnancy in women with SV.
We conducted a cohort study using the French nationwide claims database. We included all women with SV being pregnant between 2013 and 2018. Exposure of interest was defined as exposure to oral systemic or injectable immunosuppressive drug identified using out-hospital reimbursement data and in-hospital reimbursement for expensive drugs.
Of 3,246,454 pregnancies, 649 pregnancies were observed in 606 women with SV. Immunosuppressant and glucocorticoids use decreased before pregnancy and then increased after pregnancy (48.4%, 40.7%, 50.4%, respectively before, during, after). Prevalence of glucocorticoids use was broadly stable during pregnancy from 27.9% to 27.6% and 23.7% in the 1st, 2nd and 3rd trimesters, respectively, with a daily dose of about 5 mg. The number of patients treated with non-recommended immunosuppressant during pregnancy gradually decreased before pregnancy and then increased after delivery, whereas proportion of systemic vasculitis flare, estimated from the glucocorticoids daily dose, did not increase significantly during pregnancy.
Immunosuppressants and glucocorticoids use decreased before pregnancy and remained stable throughout, suggesting a vasculitis control during this period. Our findings support the importance of pre-conceptional consultations to review medications, and switch not-recommended and teratogenic medications to drugs considered being safe during pregnancy.
Flamelet models, which enable the storing of precomputed detailed chemistry into lookup tables, are widely used in combustion simulations. They allow the computation of accurate results at low ...computational cost, but standard implementations can lead to numerical problems due to a non-smooth representation, and their applicability is limited by memory requirements. Here, the methods used by a newly developed and optimised lookup table generator based on B-spline interpolation are presented. The creation of smooth representations of flamelet solutions requiring less than one fifth of the number of points in each direction compared to the non-smooth representations of standard lookup tables based on linear interpolation is shown to be possible. The new B-spline interpolation based tables are also applied within a large-eddy simulation of the Swirling Methane/Hydrogen Flame 1 and the results are compared to simulations using lookup tables based on linear interpolation or optimised artificial neural networks. Better performance of the B-spline interpolation based tables with respect to physical accuracy and numerical performance is demonstrated.
THE CURRENCY OF PROCUREMENT COST Collier, George; Johnson, Deanne F.; Mathis, Carl
Journal of the experimental analysis of behavior,
July 2002, Letnik:
78, Številka:
1
Journal Article
Recenzirano
Odprti dostop
As the number of instrumental responses required to procure access to food is increased, animals decrease the frequency of initiating meals and increase meal size, conserving total intake while ...limiting the increase in the overall cost of feeding. In two studies, one using wheel turns and one using bar presses as the instrumental response, we asked whether freely feeding laboratory rats measure cost according to the energy or the time they expend. In each study we varied both the price (i.e., number of wheel turns or bar presses) and the force required to make a response (i.e., torque on the wheel or weight of the bar). Price affected both procurement time (from the first to the last procurement response) and procurement work, whereas torque and bar weight affected work without altering time in most cases. Meal patterns were altered by all manipulations of price, but changes in torque and bar weight had little effect on meal patterns, except in the conditions in which they altered procurement time. These results suggest that time is a critical currency of procurement cost in rats.
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