Direct embryotoxicity of chromium (III) exposure during preimplantation development.

Chromium in its trivalent form (chromium (III)) is an essential component of a balanced diet, and its deficiency disturbs glucose and lipid metabolism in humans and animals. The prevailing view is that chromium (III) is notably less toxic than chromium (VI), which is genotoxic and carcinogenic. Thus, the biotransformation of environmental chromium (VI) to chromium (III) is a promising and environmentally friendly detoxification method. However, increasing evidence suggests that chromium (III) induces considerable cytotoxicity. However, the toxicity of chromium (III) to early embryos remains largely unknown. In the present study, we used in vitro fertilization (IVF) to produce mouse embryos and identified the direct embryotoxicity of chromium (III). On exposure to high concentrations of CrCl3, blastocyst formation almost completely failed and a large proportion of embryos were arrested at the 2- to 4-cell stage. At low concentrations of CrCl3, IVF embryos showed a significant decrease in blastocyst formation, reduced total cell numbers, aberrant lineage differentiation, increased oxidative stress, and apoptosis. We also found that chromium (III) exposure during the preimplantation stage, even at low concentrations, led to impaired post-implantation development. Thus, our study substantiates the direct embryotoxicity of chromium (III) during preimplantation development and prolonged impairment of development potential. The results further highlight the potential adverse effects of chromium (III) on public reproductive health with respect to increased environmental enrichment of and dietary supplementation with chromium (III) complexes.

Evidence needs, training demands, and opportunities for knowledge translation in social security and insurance medicine: A European survey.

OBJECTIVE: To perform a European survey of the evidence needs and training demands of insurance medicine professionals related to professional tasks and evidence-based practice. DESIGN: International survey. SUBJECTS: Professionals working in insurance medicine. METHODS: Experts designed an online questionnaire including 26 questions related to 4 themes: evidence needs; training demands; evidence-seeking behaviour; and attitudes towards evidence-based medicine. Descriptive statistics were presented by country/conference and the total sample. RESULTS: A total of 782 participants responded. Three-quarter of participants experienced evidence needs at least once a week, related to mental disorders (79%), musculoskeletal disorders (67%) and occupational health (65%). Guidelines (76%) and systematic reviews (60%) were the preferred types of evidence and were requested for assessment of work capacity (64%) and prognosis of return-to-work (51%). Evidence-based medicine was thought to facilitate decision-making in insurance medicine (95%). Fifty-two percent of participants felt comfortable finding, reading, interpreting, and applying evidence. Countries expressed similar needs for reviews on typical topics. CONCLUSION: This study reveals evidence gaps in key areas of insurance medicine, supporting the need for further research, guidelines and training in evidence-based insurance medicine. Importantly, insurance medicine professionals should recognize that evidence-based practice is crucial in producing high-quality assessments.

A conditional model predicting the 10-year annual extra mortality risk compared to the general population: a large population-based study in Dutch breast cancer patients.

OBJECTIVE: Many cancer survivors are facing difficulties in getting a life insurance; raised premiums and declinatures are common. We generated a prediction model estimating the conditional extra mortality risk of breast cancer patients in the Netherlands. This model can be used by life insurers to accurately estimate the additional risk of an individual patient, conditional on the years survived. METHODOLOGY: All women diagnosed with stage I-III breast cancer in 2005-2006, treated with surgery, were selected from the Netherlands Cancer Registry. For all stages separately, multivariable logistic regression was used to estimate annual mortality risks, conditional on the years survived, until 10 years after diagnosis, resulting in 30 models. The conditional extra mortality risk was calculated by subtracting mortality rates of the general Dutch population from the patient mortality rates, matched by age, gender and year. The final model was internally and externally validated, and tested by life insurers. RESULTS: We included 23,234 patients: 10,101 stage I, 9,868 stage II and 3,265 stage III. The final models included age, tumor stage, nodal stage, lateralization, location within the breast, grade, multifocality, hormonal receptor status, HER2 status, type of surgery, axillary lymph node dissection, radiotherapy, (neo)adjuvant systemic therapy and targeted therapy. All models showed good calibration and discrimination. Testing of the model by life insurers showed that insurability using the newly-developed model increased with 13%, ranging from 0%-24% among subgroups. CONCLUSION: The final model provides accurate conditional extra mortality risks of breast cancer patients, which can be used by life insurers to make more reliable calculations. The model is expected to increase breast cancer patients' insurability and transparency among life insurers.

Suitability of HIV-Infected Subjects for Insurance.

Objectives .- To ascertain the suitability of HIV-positive individuals for insurance coverage based on international data and practices. Background .- During the first decade of HIV epidemic, diagnosis of HIV-infection carried a poor prognosis. Since the introduction of Highly Active Anti-Retroviral Therapy (HAART or ART), HIV infection is more like other chronic diseases with infected individuals often living 20 or more years after the diagnosis of HIV infection Methods .- Review of peer-reviewed publications was undertaken to assess the risk of death in the HIV-infected population as a whole as well as subsets with favorable outcomes and those with additional comorbidities, such as co-infection with hepatitis viruses and drug use. Results .- Review of literature revealed that in well-educated, non-drug using individuals, negative for hepatitis B and C infection, who had CD 4 counts above 500/cmm, viral loads below 500 particles/mL, and were compliant with treatment, the mortality rate was similar to that of general population. Conclusions .- The risk of death, in at least a subset of HIV-positive subjects, is low enough that insurance providers should consider stratifying HIV-infected individuals according to mortality risk and offering insurance rates comparable to people with other diseases with similar mortality risks.

Time Dependent Relative Risks in Life Insurance Medical Underwriting.

Introduction .- Life insurance medicine focuses on mortality hazards in specified periods. People are free to insure their lives for shorter or longer terms. Because the chosen terms range from 1 year to a life time, life insurers have to take into account the fact that the predictive value of risk indicators can and will change over time. The time a risk indicator keeps its predictive value, will be dependent on its biological effects, volatility, and treatability. For a given applicant this implies that the relative hazard (RH) calculated for his/her medical condition should be dependent on the term of the insurance. The main objective of this study is to determine if some commonly used risk indicators - previously used to study age dependency of relative risks - have a predictive value that increases with the observation period. (1) Methods .- This population-based cohort study uses NHANES-data files from the Third National Health and Nutrition Examination Survey (NHANES III) and the NHANES Linked Mortality Files 2010. Only participants aged 20 to 69 that were examined in mobile examination centers, without a history of some prevalent high risk diseases were included. The observed mortality was compared to the expected mortality in a Generalized Linear Model (GLM) with Poisson error structure with two reference populations, which both can serve as preferred reference for life insurers: The United States Life Tables 2008 (USLT) and the 2008 Valuation Basic Tables (VBT) based on the insured population of 35 US Life insurers. The time dependency of the RHs of the systolic blood pressure (SBP), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), serum albumin and albuminuria, was assessed, with correction for ethnicity, household income, history of diabetes mellitus, BMI and serum cholesterol. To be able to compare the results with the results of the Age Dependency Study (ADS), the same data, risk indicators, statistical analysis method, and the Generalized Linear Model (GLM) were used. Results .- Contrary to the results in the univariate analyses, the multivariate analyses show no difference between the USLT and VBT models. In both models the RHs of SBP and albuminuria increase over time, while the RH of LDH decreases over time. Only the slopes are different, reflecting the rate of mortality increase between USLT and VBT. The RHs of ASAT and serum albumin are independent of time in both models. Discussion .- Time dependency of RHs can be assumed to exist with many risk indicators. Time dependency may take two forms: decreasing the RH and increasing the RH of a variable as time passes. Medical underwriting guidelines should therefore differentiate between short term and long term life insurances. Medical directors should realize that the presence of time dependency diminishes the value of short term clinical studies for life insurance medical underwriting. Life insurance mortality studies should always contain a discussion of the time dependency of the predictive value of the variables under study.

Age dependent decline of relative risks in life insurance medical underwriting.

UNLABELLED: INTRODUCTORY: Life insurance medicine focuses on mortality hazards. People are free to insure themselves for small or large amounts and for short or long-terms. This freedom makes it necessary for life insurers to assess and select the mortality risks in a medical underwriting process. Medical underwriting guidelines are based on company statistics, population surveys following (clinical) epidemiological principles and clinical studies. Mortality of potential life insurance applicants is compared to life tables of insured populations, or to adjusted life tables of the general population. Because many risk determinants have higher normal values at higher ages, it is reasonably to assume that the relative hazards (RHs) or mortality ratios calculated for these risk determinants should be age dependent. This is also common use in underwriting guidelines, and can have much influence on the accessibility of life insurances for (chronically) diseased people. A proof of principle is therefor warranted. METHODS: This population-based cohort study uses NHANES- datafiles from the Third National Health and Nutrition Examination Survey (NHANES III) and the NHANES Linked Mortality Files 2010. Only participants aged 20 to 69 that were examined in mobile examination centers, without a history of some prevalent high risk diseases were included. The observed mortality was compared to the expected mortality in a Generalized Linear Model (GLM) with Poisson error structure with two reference populations, which theoretically both can serve as preferred reference for life insurers: The United States Life Tables 2008 and the 2008 Valuation Basic Tables based on the insured population of 35 US life insurers. The age dependency was assessed of the values and the RH s of the systolic blood Pressure (SBP), aspartate aminotranseferase (ASAT), lactate dehydrogenase (LDH), serum albumin and albuminuria, with correction for ethnicity, household income, history of diabetes mellitus, BMI and serum cholesterol. RESULTS: All 5 continuous risk determinants had age dependent values in the comparison between ages 20-54 and 55-69 (Mann-Whitney U P < 0.001). Graphical inspections using age at time of interview revealed only for the SBP an increase with age. In the GLM again only SBP had a significant interaction term with age at time of interview. It made no difference which life tables were used for the calculation of the expected mortality. DISCUSSION: Age dependency of RHs of risk determinants can be assumed if the risk determinants themselves are age dependent on statistical and graphical inspection. In other cases age dependency might not be significant, or cannot be modelled with some form of linear function as customary in many underwriting guidelines. The RHs or mortality ratios in current medical underwriting guidelines for life insurances should be checked for age dependency by analysing the underlying data statistically and graphically and by using GLM and appropriate life tables.

Fracastoro and the prognosis of applicants with HIV.

OBJECTIVES: Discuss the relevance of the study "Trends in mortality of insurance applicants with HIV infection" by highlighting the key elements for underwriting HIV-positive life insurance applicants. METHODS: Discussion on the basis of a comparison of HIV with syphilis, as presented by Giralmo Fracastoro; and by comparing HIV prevalence in applicants and the background population. RESULTS: As with syphilis, adherence to therapy is a key element; different from syphilis is the importance of co-morbidity. The prevalence in life insurance applicants remains stab, while the prevalence in the population increases. CONCLUSIONS: The self selection of applicants with co-morbidity is the major reason for the continuing high relative mortality of HIV-positive applicants.