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1.  Medication effectiveness may not be the major reason for accepting cardiovascular preventive medication: A population-based survey 
Shared decision-making and patients’ choice of interventions are areas of increasing importance, not least seen in the light of the fact that chronic conditions are increasing, interventions considered important for public health, and still non-acceptance of especially risk-reducing treatments of cardiovascular diseases (CVD) is prevalent. A better understanding of patients’ medication-taking behavior is needed and may be reached by studying the reasons why people accept or decline medication recommendations. The aim of this paper was to identify factors that may influence people’s decisions and reasoning for accepting or declining a cardiovascular preventive medication offer.
From a random sample of 4,000 people aged 40–59 years in a Danish population, 1,169 participants were asked to imagine being at increased risk of cardiovascular disease and being offered a preventive medication. After receiving ‘complete’ information about effectiveness of the medication they were asked whether they would accept medication. Finally, they were asked about reasons for the decision.
A total of 725 (67%) of 1,082 participants accepted the medication offer. Even quite large effects of medication (up to 8 percentage points absolute risk reduction) had a smaller impact on acceptance to medication than personal experience with cardiovascular disease. Furthermore, increasing age of the participant and living with a partner were significantly associated with acceptance. Some 45% of the respondents accepting justified their choice as being for health reasons, and they were more likely to be women, live alone, have higher income and higher education levels. Among those who did not accept the medication offer, 56% indicated that they would rather prefer to change lifestyle.
Medication effectiveness seems to have a moderate influence on people’s decisions to accept preventive medication, while factors such as personal experience with cardiovascular disease may have an equally strong or stronger influence, indicating that practitioners could do well to carefully identify the reasons for their patients’ treatment decisions.
PMCID: PMC3465182  PMID: 22873796
Decision-making; Risk assessment; Risk communication; Preventive health services; Primary prevention; Cardiovascular disease; Health behavior
2.  Xeno‐oestrogenic activity in serum as marker of occupational pesticide exposure 
An increasing number of currently used pesticides are reported to possess oestrogen‐like properties or to disturb the endocrine system in other ways.
To investigate if xeno‐oestrogenic activity in serum can be used as a biomarker of the combined exposure to pesticides with oestrogen‐like properties in an occupational setting.
Serum samples were obtained from two separate cohorts representing non‐pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non‐pregnant women and 173 pregnant women were analysed for xeno‐oestrogenic activity. A fraction containing major xeno‐oestrogens but without pharmaceutical and endogenously produced oestrogens was isolated from each serum sample by solid‐phase extraction and tested for oestrogenic response in a MCF‐7 cell proliferation assay. The pesticide exposure for each woman was categorised as low, medium or high based on information collected by detailed interviews of the women and the employers.
In both cohorts, an exposure‐associated increase in the xeno‐oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno‐oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week.
The study illustrates the usefulness of this biomarker for qualitative assessment of the combined exposure to mixtures of oestrogen‐like pesticides. Although the individual pesticides responsible for the xeno‐oestrogenic response were not identified, the study demonstrates that, even within highly‐controlled greenhouse operations, occupational exposure to oestrogen‐like pesticides can result in detectable impacts on hormonal activity in the blood.
PMCID: PMC2078395  PMID: 17478572
3.  Assessment of xenoestrogenic exposure by a biomarker approach: application of the E-Screen bioassay to determine estrogenic response of serum extracts 
Environmental Health  2003;2:12.
Epidemiological documentation of endocrine disruption is complicated by imprecise exposure assessment, especially when exposures are mixed. Even if the estrogenic activity of all compounds were known, the combined effect of possible additive and/or inhibiting interaction of xenoestrogens in a biological sample may be difficult to predict from chemical analysis of single compounds alone. Thus, analysis of mixtures allows evaluation of combined effects of chemicals each present at low concentrations.
We have developed an optimized in vitro E-Screen test to assess the combined functional estrogenic response of human serum. The xenoestrogens in serum were separated from endogenous steroids and pharmaceuticals by solid-phase extraction followed by fractionation by high-performance liquid chromatography. After dissolution of the isolated fraction in ethanol-DMSO, the reconstituted extract was added with estrogen-depleted fetal calf serum to MCF-7 cells, the growth of which is stimulated by estrogen. After a 6-day incubation on a microwell plate, cell proliferation was assessed and compared with the effect of a 17-beta-estradiol standard.
Results and conclusions
To determine the applicability of this approach, we assessed the estrogenicity of serum samples from 30 pregnant and 60 non-pregnant Danish women thought to be exposed only to low levels of endocrine disruptors. We also studied 211 serum samples from pregnant Faroese women, whose marine diet included whale blubber that contain a high concentration of persistent halogenated pollutants. The estrogenicity of the serum from Danish controls exceeded the background in 22.7 % of the cases, while the same was true for 68.1 % of the Faroese samples. The increased estrogenicity response did not correlate with the lipid-based concentrations of individual suspected endocrine disruptors in the Faroese samples. When added along with the estradiol standard, an indication of an enhanced estrogenic response was found in most cases. Thus, the in vitro estrogenicity response offers a promising and feasible approach for an aggregated exposure assessment for xenoestrogens in serum.
PMCID: PMC270076  PMID: 14613489
4.  Mercury-induced autoimmunity in mice. 
Environmental Health Perspectives  2002;110(Suppl 5):877-881.
We have studied the effect of gender, genetics, and toxicokinetics on immune parameters in mercury-induced autoimmunity in mice. Data strongly suggest that the mechanism for mercury-induced autoimmunity involves modification of the autoantigen fibrillarin by mercury followed by a T-cell-dependent immune response driven by the modified fibrillarin. Mice with different H-2 haplotypes were treated with (203)HgCl(2) in a dose of 0.5-16 mg Hg/L drinking water for 10 weeks. Whole-body accumulation and renal accumulation of mercury were assessed. Serum antinuclear antibodies were used to evaluate the autoimmune response, and serum immunoglobulin E (IgE) to study effects on T-helper cells of type 2. Strains with a susceptible H-2 haplotype developed autoantibodies to the nucleolar protein fibrillarin (AFA) in a dose-dependent pattern within 2 weeks. The substantially lower whole-body and organ mercury level needed to induce AFA in the susceptible A.SW strain compared with the H-2 congenic B10.S strain demonstrates that genetic factors outside the H-2 region modify the autoimmune response. Mouse strains without the susceptible haplotype did not develop any autoimmune reaction irrespective of dose and organ deposition of mercury. In susceptible mouse strains, males and females had different thresholds for induction of autoimmune reactions. In susceptible strains, serum IgE increased dose dependently and reached a maximum after 1-2.5 weeks. A susceptible H-2 haplotype is therefore a prerequisite for the autoimmune response. Mercury exposure will modulate the response, qualitatively through the existence of dose-related thresholds for autoimmune response and quantitatively as increasing doses cause increasing autoimmune response. Further, gender and non-H-2 genes modulate both the induction and subsequent development of AFA. Induction of IgE seems not to be mechanistically linked to the AFA response.
PMCID: PMC1241265  PMID: 12426151
5.  Impact of effectiveness information format on patient choice of therapy and satisfaction with decisions about chronic disease medication: the "Influence of intervention Methodologies on Patient Choice of Therapy (IMPACT)" cluster-randomised trial in general practice 
Risk communication is an integral part of shared decision-making in health care. In the context of interventions for chronic diseases it represents a particular challenge for all health practitioners. By using two different quantitative formats to communicate risk level and effectiveness of a cholesterol-lowering drug, we posed the research question: how does the format of risk information influence patients’ decisions concerning therapy, patients’ satisfaction with the communication as well as confidence in the decision. We hypothesise that patients are less prone to accept therapy when the benefits of long-term intervention are presented in terms of prolongation of life (POL) in months compared to the absolute risk reduction (ARR). We hypothesise that patients presented with POL will be more satisfied with the communication and confident in their decision, suggesting understanding of the time-related term.
In 2009 a sample of 328 general practitioners (GPs) in the Region of Southern Denmark was invited to participate in a primary care-based clinical trial among patients making real-life clinical decisions together with their GP. Interested GPs were cluster-randomised to inform patients about cardiovascular disease (CVD) risk and the effectiveness of statin therapy using either POL or ARR. The GPs attended a training session before informing their patients. Before training and after the trial period they received a questionnaire about their attitudes to risk communication and the use of numerical information. Patients’ redemptions of statin prescriptions will be registered in a regional prescription database to evaluate a possible association between redemption rates and effectiveness format. The Combined Outcome Measure for Risk Communication And Treatment Decision Making Effectiveness (COMRADE) questionnaire will be used to measure patients’ confidence and satisfaction with the risk communication immediately after the conversation with their GPs.
This randomised clinical trial compares the impact of two effectiveness formats on real-life risk communication between patients and GPs, including affective patient outcomes and actual choices about acceptance of therapy. Though we found difficulties in recruiting GPs, according to the study protocol we have succeeded in engaging sufficient GPs for the trial, enabling us to perform the planned analyses.
Trial registration Protocol Registration System
PMCID: PMC3599428  PMID: 23442351
RCT; Shared decision making; Risk communication; Prognosis; Absolute risk reduction; Prolongation of life; Cardiovascular disease; Primary prevention; Health behaviour; General practice

Results 1-5 (5)