Background South Asian populations in the United Kingdom have a high risk of cardiovascular disease (CVD) mortality. Risk prediction models appear to be inaccurate in South Asians. Objective To ...explore the predictive capacity of the FINRISK, Framingham (1991) and SCORE risk prediction models in the Newcastle Heart Project population (n = 1301). Methods Mortality data for England and Wales were used to define the expected ranking of CVD risk by country of birth. CVD mortality in the Newcastle Heart Project sample was examined. Risk factor measures were obtained from the Newcastle Heart Project, where 90 percent of South Asians were born in the Indian Subcontinent. The predicted outcomes for FINRISK were acute myocardial infarction and CHD mortality, for Framingham CHD mortality, myocardial infarction, new angina and coronary insufficiency and for SCORE CHD and non‐CHD CVD mortality. Results The FINRISK model predicted in South Asian men combined, compared with Europeans, a risk ratio of 122 per cent (SMR 142) with substantial subgroup heterogeneity, e.g. 154 per cent in Bangladeshis (SMR 151), 129 per cent in Pakistanis (SMR 148), 99 per cent in Indians (SMR 142). The FINRISK risk ratios for South Asian women combined were 160 per cent (SMR 145), for Bangladeshis 184 per cent (SMR 91), Pakistanis 172 per cent (SMR 111) and for Indians 145 per cent (SMR 158). The Framingham model results were very similar to FINRISK, but the SCORE model showed comparatively low 10 year risk in all South Asian groups. Both the Framingham stroke model and the SCORE non‐CHD CVD model predicted comparatively low rates, while national data showed these to be high. Control of the five major risk factors was modelled by FINRISK to reduce risk by about 59 per cent in South Asian men and 67 per cent in South Asian women, with some subgroup heterogeneity, compared to 50 per cent in European men and 48 per cent in European women. The Framingham model results were similar. The absolute rates for each ethnic group varied by model. Conclusion The Framingham and FINRISK models gave similar results, mostly following expected patterns, but the SCORE model did not, probably reflecting its lack of inclusion of HDL and diabetes as risk factors. National mortality data and modelled predictions agreed reasonably well for South Asians combined, and Bangladeshi and Pakistani men, but not for Indian men and Pakistani and Bangladeshi women. The varying rates show the limits of modelling. The models suggest the potential gains from controlling major established risk factors could be substantial in South Asians and greater than in Europeans.
Occupational radiation doses in interventional radiology can potentially be high. Therefore, reliable methods to assess the effective dose are needed. In the present work, the relationship between ...the personal dose equivalent, H(p)(10), the reading of a personal dosimeter and the effective dose of the radiologist were studied using Monte Carlo simulations. In particular, the protection provided by a lead apron was investigated. Emphasis was placed on sensitivity of the results to changes in irradiation conditions. In our simulations a 0.35 mm thick lead apron and thyroid shield reduced the effective dose, on average, by a factor of 27 (the range of these data was 15-41). Without the thyroid shield the average reduction factor was 15 (range 6-22). The reduction sensitively depended on the projection and the X-ray tube voltage. The dosimeter reading, when the dosimeter was worn above the apron and a thyroid shield was used, overestimated the effective dose on average by a factor of 130 (range 44-258) when the dosimeter was located on the breast closest to the primary X-ray beam. Without the thyroid shield the average overestimation was 69 (range 32-127). If the dosimeter was worn under the apron its reading generally underestimated the effective dose (on average by 20% with the thyroid shield). Our study indicates that, even though large variations are present, the often used conversion coefficient from the dosimeter reading above the apron to the effective dose, around 1/30, generally overestimates the effective dose by a factor of two or more.
In similarity to many other western countries, the burden of allergic diseases in Finland is high. Studies worldwide have shown that an environment rich in microbes in early life reduces the ...subsequent risk of developing allergic diseases. Along with urbanization, such exposure has dramatically reduced, both in terms of diversity and quantity. Continuous stimulation of the immune system by environmental saprophytes via the skin, respiratory tract and gut appears to be necessary for activation of the regulatory network including regulatory T-cells and dendritic cells. Substantial evidence now shows that the balance between allergy and tolerance is dependent on regulatory T-cells. Tolerance induced by allergen-specific regulatory T-cells appears to be the normal immunological response to allergens in non atopic healthy individuals. Healthy subjects have an intact functional allergen-specific regulatory T-cell response, which in allergic subjects is impaired. Evidence on this exists with respect to atopic dermatitis, contact dermatitis, allergic rhinitis and asthma. Restoration of impaired allergen-specific regulatory T-cell response and tolerance induction has furthermore been demonstrated during allergen-specific subcutaneous and sublingual immunotherapy and is crucial for good therapeutic outcome. However, tolerance can also be strengthened unspecifically by simple means, e.g. by consuming farm milk and spending time in nature. Results so far obtained from animal models indicate that it is possible to restore tolerance by administering the allergen in certain circumstances both locally and systemically. It has become increasingly clear that continuous exposure to microbial antigens as well as allergens in foodstuffs and the environment is decisive, and excessive antigen avoidance can be harmful and weaken or even prevent the development of regulatory mechanisms. Success in the Finnish Asthma Programme was an encouraging example of how it is possible to reduce both the costs and morbidity of asthma. The time, in the wake of the Asthma Programme, is now opportune for a national allergy programme, particularly as in the past few years, fundamentally more essential data on tolerance and its mechanisms have been published. In this review, the scientific rationale for the Finnish Allergy Programme 2008-2018 is outlined. The focus is on tolerance and how to endorse tolerance at the population level.
Oxidation of
d-limonene, which is a common monoterpene, can lead to new aerosol particle formation in indoor environments. Thus, products containing
d-limonene, such as citrus fruits, air ...refresheners, household cleaning agents, and waxes, can act as indoor air aerosol particle sources. We released
d-limonene into the room air by peeling oranges and measured the concentration of aerosol particles of three different size ranges. In addition, we measured the concentration of
d-limonene, the oxidant, and the concentration of ozone, the oxidizing gas. Based on the measurements we calculated the growth rate of the small aerosol particles, which were 3–10
nm in diameter, to be about
6300
nm
h
-
1
, and the losses of the aerosol particles that were due to the coagulation and condensation processes. From these, we further approximated the concentration of the condensable vapour and its source rate and then calculated the formation rate of the small aerosol particles. For the final result, we calculated the nucleation rate and the maximum number of molecules in a critical cluster. The nucleation rate was in the order of
10
5
cm
-
3
s
-
1
and the number of molecules in a critical-sized cluster became 1.2. The results were in agreement with the activation theory.
Rapidly declining biodiversity may be a contributing factor to another global megatrend—the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations ...worldwide. According to the "biodiversity hypothesis," reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 x 150 km, we show that environmental biodiversity in the surroundings of the study subjects’ homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the Gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general.
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder associated with an elevated risk of colorectal cancer (CRC). IBD-associated CRC (IBD-CRC) may represent a distinct ...pathway of tumorigenesis compared to sporadic CRC (sCRC). Our aim was to comprehensively characterize IBD-associated tumorigenesis integrating multiple high-throughput approaches, and to compare the results with in-house data sets from sCRCs.
Whole-genome sequencing, single nucleotide polymorphism arrays, RNA sequencing, genome-wide methylation analysis, and immunohistochemistry were performed using fresh-frozen and formalin-fixed tissue samples of tumor and corresponding normal tissues from 31 patients with IBD-CRC.
Transcriptome-based tumor subtyping revealed the complete absence of canonical epithelial tumor subtype associated with WNT signaling in IBD-CRCs, dominated instead by mesenchymal stroma-rich subtype. Negative WNT regulators AXIN2 and RNF43 were strongly down-regulated in IBD-CRCs and chromosomal gains at HNF4A, a negative regulator of WNT-induced epithelial–mesenchymal transition (EMT), were less frequent compared to sCRCs. Enrichment of hypomethylation at HNF4α binding sites was detected solely in sCRC genomes. PIGR and OSMR involved in mucosal immunity were dysregulated via epigenetic modifications in IBD-CRCs. Genome-wide analysis showed significant enrichment of noncoding mutations to 5′untranslated region of TP53 in IBD-CRCs. As reported previously, somatic mutations in APC and KRAS were less frequent in IBD-CRCs compared to sCRCs.
Distinct mechanisms of WNT pathway dysregulation skew IBD-CRCs toward mesenchymal tumor subtype, which may affect prognosis and treatment options. Increased OSMR signaling may favor the establishment of mesenchymal tumors in patients with IBD.
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OBJECTIVE: To investigate trends in body mass index (BMI) and prevalence of obesity among adults in Finland from 1982 to 1997, and to identify population groups with increasing obesity. SUBJECTS: ...Random samples from the national population register including men and women aged 25-64 y (n = 24604, total). DESIGN: Four cross-sectional surveys carried out in three areas in Finland every fifth year since 1982. MEASUREMENTS: Weight and height were measured, and data on occupation and education level were collected by a self-administered questionnaire. RESULTS: The mean BMI increased in both genders. In men, the upward trend was greatest (the increase of 1.3 kg/m2 in 15 y) in the oldest age group (55-64 y), and was found also (the increase of 0.6 kg/m2) in the youngest age group (25-34 y), whereas in women, the upward trend was most prominent (the increase of 0.9 kg/m2) in the youngest age group. BMI increased in all educational groups in men, but in women the upward trend seemed to be greatest in the lowest educational group. The upward trends were most prominent among retired and unemployed men, while in women changes in BMI were similar in all occupational groups. CONCLUSION: The strongest upward trend in BMI was found in the oldest men, in the youngest age group in both genders and, in particular, among men who were outside the labor force. Education is still a strong determinant of obesity, especially in women, although the social gradient in BMI has not widened in the 1990s.
Experimental and epidemiological studies show a positive association between coronary disease and various infections in different organs, both viral and bacterial and both acute and chronic. Most ...attention has been paid to dental infections and infections in the respiratory tract. We have studied how chronic respiratory infection predicts coronary disease.
We defined chronic respiratory infection by the occurrence of symptoms of chronic bronchitis. We also analysed whether any association with coronary disease incidence and mortality is independent of the known major cardiovascular risk factors and whether it is similar among persons in different occupations. Our cohort study was a 13-year follow-up of 19 444 randomly selected eastern Finnish men and women born between 1913 and 1947 and examined in either 1972 or 1977.
During follow-up, there were 1419 first coronary events, either fatal or non-fatal, and 614 coronary deaths. Among men, the age-adjusted and study-year-adjusted risk ratio of long lasting-symptoms of chronic bronchitis (during as much as 3 months in a year) was 1·52 (95% CI 1·33-1·75) for coronary disease and 1·74 (CI 1·43-2·11) for coronary death. Among women the risk ratios were 1·38 (1·07-1·78) and 1·49 (0·98-2·27), respectively. Inclusion of smoking, serum cholesterol, and systolic blood pressure into the models decreased risk ratios to 1·36 (1·17-1·56) and 1·55 (1·26-1·90) in men and to 1·34 (1·04-1·74) and 1·41 (0·92-2·16) in women, respectively. The risk of coronary disease associated with the symptoms of chronic bronchitis was similar among blue-collar and white-collar workers but the association was not found among farmers.
Symptoms of chronic bronchitis predicted the risk of coronary disease independently from the known major cardiovascular risk factors. If the observed association is causal, prevention and improved management of chronic infections may have played a role in the decrease in coronary disease mortality observed in eastern Finland in the past two decades.
A substantial variation in the association of asthma, rhinitis and eczema with elevated serum allergen-specific immunoglobulin E (sIgE) levels between different populations has been reported. Here, ...we wanted to clarify whether these proportions are different in Finnish and Russian Karelia, and compared the ability of questionnaires, skin prick tests (SPT) and sIgE measurements to detect atopic conditions in these adjacent areas with different living conditions. Randomly selected schoolchildren, aged 6-16 years, and their mothers from Finland (n = 344 children, 344 mothers) and Russia (427 and 284 respectively) participated. SPTs and sIgE measurements to common inhalant and food allergens were performed. The occurrence of asthma, rhinitis, eczema and related symptoms was assessed with an International Study of Asthma and Allergies in Childhood-based questionnaire. Correlation between SPT and sIgE was estimated using the Spearman correlation coefficient. The rate of positive sIgE results was significantly higher in Finland among both mothers and children. Seventy-seven per cent of Finnish children and 43% of Russian children with asthma were sIgE positive. The respective figures for hay fever were 94% and 67%, and for eczema 68% and 41%. This discrepancy was similar but of lower magnitude among mothers. The overall occurrence of asthma, rhinitis and eczema was very low in Russian Karelia. The correlation between SPT and sIgE results was generally good. Asthma, rhinitis and eczema in Russian Karelia are not only rare but also, to a large extent, have no sIgE component. Therefore, the ability of questionnaires to detect sIgE-mediated atopic conditions in this area of Russia is poor.
To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, ...we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.
In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance.
Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40–64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt.
We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.
World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.
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