A cost-minimisation analysis of performing point-of-care ultrasonography on patients with vaginal bleeding in early pregnancy in general practice:a decision analytical model

BACKGROUND: Spotting and light vaginal bleeding are common and usually harmless symptoms in early pregnancy. Still, vaginal bleeding may be the first sign of an abortion and often causes distress to pregnant women and leads to an expectation of an ultrasonography examination of the uterus. As point-of-care ultrasonography (POCUS) is increasingly being integrated into general practice, these patients may be clinically evaluated and managed by general practitioners (GPs). This can potentially reduce referrals of patients from the primary to the secondary healthcare sector resulting in societal cost-savings. The primary purpose of this study was to investigate whether the accessibility of POCUS in general practice for patients with vaginal bleeding in early pregnancy is cost-saving compared to usual practice where GPs do not have access to POCUS. A secondary purpose of this study was to estimate a remuneration for GPs performing POCUS on these patients in general practice. METHODS: A cost-minimisation analysis was based on a decision tree model reflecting the two alternatives: general practice with and without GPs having access to POCUS. The robustness of the model results was investigated using probabilistic sensitivity analysis and the following deterministic sensitivity analyses: one-way analyses for the model input parameters and a scenario analysis with a change from a societal to a healthcare sector perspective. An expected remuneration reflecting the add-on cost of Danish GPs performing POCUS was estimated based on the related costs: cost of an ultrasonography scanner, GP’s time consumption, ultrasonography training, and utensils per scanning. RESULTS: The difference in average cost between the two alternatives from a societal perspective was estimated to be €110, in favour of general practice with GPs using POCUS. The deterministic sensitivity analyses demonstrated robustness of the results to plausible changes in the input parameters. The expected remuneration for performing POCUS in this specific setting was estimated to be €32 per examination. CONCLUSION: Having GPs perform POCUS on patients with vaginal bleeding in early pregnancy is cost-saving compared to usual practice. The results should be taken with caution as this study was based on early modelling with uncertainties associated with the input parameters in the model. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-07463-y

Critical review of analytical methods for the determination of flame retardants in human matrices

Human biomonitoring is a powerful approach in assessing exposure to environmental pollutants. Flame retardants (FRs) are of particular concern due to their wide distribution in the environment and adverse health effects. This article reviews studies published in 2009-2020 on the chemical analysis of FRs in a variety of human samples and discusses the characteristics of the analytical methods applied to different FR biomarkers of exposure, including polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), novel halogenated flame retardants (NHFRs), bromophenols, incl. tetrabromobisphenol A (TBBPA), and organophosphorous flame retardants (PFRs). Among the extraction techniques, liquid-liquid extraction (LLE) and solid phase extraction (SPE) were used most frequently due to the good efficiencies in the isolation of the majority of the FR biomarkers, but with challenges for highly lipophilic FRs. Gas chromatography-mass spectrometry (GC-MS) is mainly applied in the instrumental analysis of PBDEs and most NHFRs, with recent inclusions of GC-MS/MS and high resolution MS techniques. Liquid chromatography-MS/MS is mainly applied to HBCD, bromophenols, incl. TBBPA, and PFRs (including metabolites), however, GC-based analysis following derivatization has also been used for phenolic compounds and PFR metabolites. Developments are noticed towards more universal analytical methods, which enable widening method scopes in the human biomonitoring of FRs. Challenges exist with regard to sensitivity required for the low concentrations of FRs in the general population and limited sample material for some human matrices. A strong focus on quality assurance/quality control (QA/QC) measures is required in the analysis of FR biomarkers in human samples, related to their variety of physical-chemical properties, low levels in most human samples and the risk of contamination.This study was part of the HBM4EU project receiving funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 733032. The authors acknowledge Berith E. Knudsen for her help with the literature search.S

Pulmonary phthalate exposure and asthma - is PPAR a plausible mechanistic link?

Due to their extensive use as plasticisers in numerous consumer products, phthalates have become ubiquitous environmental contaminants. An increasing number of epidemiological studies suggest that exposure to phthalates may be associated with worsening or development of airway diseases. Peroxisome Proliferation Activated Receptors (PPAR)s, identified as important targets for phthalates in early studies in rodent liver, have been suggested as a possible mechanistic link. In this review we discuss the likelihood of an involvement of PPARs in asthma development and exacerbation due to pulmonary phthalate exposure. First, we go through the literature on indoor air levels of phthalates and pulmonary phthalate kinetics. These data are then used to estimate the pulmonary phthalate levels due to inhalation exposure. Secondly, the literature on phthalate-induced activation or modulation of PPARs is summarized. Based on these data, we discuss whether pulmonary phthalate exposure is likely to cause PPAR activation, and if this is a plausible mechanism for adverse effects of phthalates in the lung. It is concluded that the pulmonary concentrations of some phthalates may be sufficient to cause a direct activation of PPARs. Since PPARs mainly mediate anti-inflammatory effects in the lungs, a direct activation is not a likely molecular mechanism for adverse effects of phthalates. However, possible modulatory effects of phthalates on PPARs deserve further investigation, including partial antagonist effects and/or cross talk with other signalling pathways. Moreover other mechanisms, including interactions between phthalates and other receptors, could also contribute to possible adverse pulmonary effects of phthalates

Risk assessment of dioxins, furans, and dioxin-like PCBs in food in Norway - Scientific Opinion of the Panel on Contaminants of the Norwegian Scientific Committee for Food and Environment

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European interlaboratory comparison investigations (ICI) and external quality assurance schemes (EQUAS) for the analysis of bisphenol A, S and F in human urine: Results from the HBM4EU project

The Human Biomonitoring for Europe initiative (HBM4EU) aims to study the exposure of citizens to chemicals and potentially associated health effects. One objective of this project has been to build a network of laboratories able to answer to the requirements of European human biomonitoring studies. Within the HBM4EU quality assurance and quality control scheme (QA/QC), a number of interlaboratory comparison investigations (ICIs) and external quality assurance schemes (EQUASs) were organized to ensure data consistency, comparability and reliability. Bisphenols are among the prioritized substance groups in HBM4EU, including bisphenol A (BPA), bisphenol S (BPS) and bisphenol F (BPF) in human urine. In four rounds of ICI/EQUAS, two target concentration levels were considered, related to around P25 and P95 of the typical exposure distribution observed in the European general population. Special attention was paid to the conjugated phase II metabolites known to be most dominant in samples of environmentally exposed individuals, through the analysis of both native samples and samples fortified with glucuronide forms. For the low level, the average percentage of satisfactory results across the four rounds was 83% for BPA, 71% for BPS and 62% for BPF. For the high level, the percentages of satisfactory results increased to 93% for BPA, 89% for BPS and 86% for BPF. 24 out of 32 participating laboratories (75%) were approved for the analyses of BPA in the HBM4EU project according to the defined criterion of Z-scores for both low and high concentration levels in at least two ICI/EQUAS rounds. For BPS and BPF, the number of qualified laboratories was 18 out of 27 (67%) and 13 out of 28 (46%), respectively. These results demonstrate a strong analytical capability for BPA and BPS in Europe, while improvements may be needed for BPF.We gratefully acknowledge funding by the European Union's Horizon 2020 research and innovation programme under the grant agreement No. 733032 HBM4EU. The authors would like to thank the HBM4EU Secretariat at the German Environment Agency for administrative support. The authors acknowledge all the participating and expert laboratories (Table A1, SM) that made the HBM4EU QA/QC programme possible as well as the Management and Advisory Boards of HBM4EU.S