| 1. |
|
|
| 2. |
- Lyngso, J., et al.
(författare)
-
Menstrual cycle characteristics in fertile women from Greenland, Poland and Ukraine exposed to perfluorinated chemicals: a cross-sectional study
- 2014
-
Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 29:2, s. 359-367
-
Tidskriftsartikel (refereegranskat)abstract
- Does perfluorooctane sulfonate (PFOS) and perfluorooctanate (PFOA) exposure disrupt the menstrual cyclicity? The female reproductive system may be sensitive to PFOA exposure, with longer menstrual cycle length at higher exposure. PFOS and PFOA are persistent man-made chemicals. Experimental animal studies suggest they are reproductive toxicants but epidemiological findings are inconsistent. A cross-sectional study including 1623 pregnant women from the INUENDO cohort enrolled during antenatal care visits between June 2002 and May 2004 in Greenland, Poland and Ukraine. Information on menstrual cycle characteristics was obtained by questionnaires together with a blood sample from each pregnant woman. Serum concentrations of PFOS and PFOA were measured by liquid chromatography tandem mass spectrometry. Multiple imputations were performed to account for missing data. The association between PFOS/PFOA and menstrual cycle length (short cycle: 24 days, long cycle: 32 days) and irregularities (7 days in difference between cycles) was analyzed using logistic regression with tertiles of exposure. Estimates are given as adjusted odds ratios (ORs) with 95 confidence intervals (CIs). Higher exposure levels of PFOA were associated with longer menstrual cycles in pooled estimates of all three countries. Compared with women in the lowest exposure tertile, the adjusted OR of long cycles was 1.8 (95 CI: 1.0; 3.3) among women in the highest tertile of PFOA exposure. No significant associations were observed between PFOS exposure and menstrual cycle characteristics. However, we observed a tendency toward more irregular cycles with higher exposure to PFOS [OR 1.7 (95 CI: 0.8; 3.5)]. The overall response rate was 45.3 with considerable variation between countries (91.3 in Greenland, 69.1 in Poland and 26.3 in Ukraine). Possible limitations in our study include varying participation rates across countries; a selected study group overrepresenting the most fertile part of the population; retrospective information on menstrual cycle characteristics; the determination of cut-points for all three outcome variables; and lacking information on some determinants of menstrual cycle characteristics, such as stress, physical activity, chronic diseases and gynecological disorders, thus confounding cannot be excluded. The generalizability of the study results is restricted to fertile women who manage to conceive and women who do not use oral contraceptives when getting pregnant or within 2 months before getting pregnant. To our knowledge only one previous epidemiological study has addressed the possible association between perfluorinated chemical exposure and menstrual disturbances. Though pointing toward different disturbances in cyclicity, both studies suggest that exposure to PFOA may affect the female reproductive function. This study contributes to the limited knowledge on effects of exposure to PFOA and PFOS on female reproductive function and suggests that the female reproductive system may be affected by environmental exposure to PFOA. Supported by a scholarship from Aarhus University Research Foundation. The collection of questionnaire data and blood samples was part of the INUENDO project supported by The European Commission (Contract no. QLK4-CT-2001-00 202), . The Ukrainian part of the study was possible by a grant from INTAS (project 012 2205). Determination of PFOA and PFOS in serum was part of the CLEAR study () supported by the European Commissions 7th Framework Program (FP7-ENV-2008-1-226217). No conflict of interest declared.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Reilev, M, et al.
(författare)
-
Methodology of the brodalumab assessment of hazards: a multicentre observational safety (BRAHMS) study
- 2023
-
Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 13:2, s. e066057-
-
Tidskriftsartikel (refereegranskat)abstract
- Safe and effective pharmacological treatment is of paramount importance for treating severe psoriasis. Brodalumab, a monoclonal antibody against interleukin (IL) 17 receptor A, was granted marketing authorisation in the EU in 2017. The European Medicines Agency requested a postauthorisation safety study of brodalumab to address potential safety issues raised during drug development regarding major adverse cardiovascular events, suicidal conduct, cancer and serious infections.Methods and analysisBRodalumab Assessment of Hazards: A Multinational Safety is a multicentre observational safety study of brodalumab running from 2017 to 2029 using population-based healthcare databases from Denmark, Sweden, Norway, Netherlands, Germany and three different centres in Italy. A distributed database network approach is used, such that only aggregate data are exchanged between sites.Two types of designs are used: a case-time-control design to study acute effects of transient treatment and a variation of the new user active comparator design to study the effects of transient or chronic treatment. As comparators, inhibitors of TNF-α, inhibitors of IL-12 and IL-23, and other inhibitors of cytokine IL-17A are included.In the self-controlled case-time-control design, the risk of developing the outcome of interest during periods of brodalumab use is compared within individuals to the risk in periods without use.In the active comparator cohort design, new users of brodalumab are identified and matched to new users of active comparators. Potential baseline confounders are adjusted for by using propensity score modelling. For outcomes that potentially require large cumulative exposure, an adapted active comparator design has been developed.Ethics and disseminationThe study is approved by relevant authorities in Denmark, Norway, Sweden, the Netherlands, Germany and Italy in line with the relevant legislation at each site. Data confidentiality is secured by the distributed network approach. Results will be published in peer-reviewed journals.Trial registration numberEUPAS30280.
|
|
