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The epidemiology of rheumatic diseases.

This review concentrates on certain areas of current interest in the major rheumatic diseases. In rheumatoid arthritis, there is some epidemiologic evidence that the disease is diminishing in incidence and severity. The possible protective effect on rheumatoid arthritis of the oral contraceptive pill has also attracted attention. There is some evidence that it may act by modifying the disease process. Parity may also be a protective factor in rheumatoid arthritis. Recent twin studies have suggested that the monozygotic concordance rate may be lower than previously believed, suggesting that genetic factors may only account for 20% of the disease. In osteoarthritis, new clinical criteria for the hand, knee, and hip have appeared that require further testing. The finding of a specific mutation of one amino acid of a procollagen II gene in family members with premature osteoarthritis has aroused considerable interest. There has been recent debate on the risk of developing ankylosing spondylitis in the population with HLA B27, although most believe this to be less than 7%. Scleroderma is a rare disease that may be increasing in incidence. One study has suggested the clustering of cases around airports. In the majority of countries, osteoporotic fractures appear to have increased at all ages over the last 30 years, although methods of screening using questionnaires or single bone density measurements are unlikely to be useful as widespread public health measures. The question of estrogen use is increasingly being dominated by the large cardiovascular benefit.

Humans↗

Local factors in osteoarthritis.

Osteoarthritis is widely believed to be the result of local factors acting within the context of systemic susceptibility. Local factors, which are specific to joint site and in some instances specific to joint compartment, are receiving increasing attention in natural history studies of osteoarthritis. This review focuses on epidemiologic investigations dealing with these local factors. Local factors may be further characterized as extrinsic or intrinsic to the joint organ. In the past, the epidemiologic literature has emphasized the extrinsic category, factors and events that have an origin external to the joint and its immediate environment--for example, physical activity and injury. In recent years, intrinsic factors such as alignment, strength, laxity, and proprioception have begun to receive more attention. Ultimately, epidemiologic studies aid the development of strategies to prevent disease development or modify its course. Such strategies may be especially powerful for local factors, given the vicious cycles set in motion by these factors and the effect of these factors on neighboring joint-organ structures.

Bone Malalignment↗

[Effect of hormone replacement therapy during the climacteric on cerebrovascular diseases].

In epidemiological and animal studies it could be shown that a hormone replacement therapy decreased the risk of stroke. Sonographical blood flow measurement shows a positive effects to the cerebrovascular system caused by estrogen which was not modified by gestagens. In morphometric investigations by sonographical measurements of intima-media-thickness, it could be demonstrated that a positive influence by hormone replacement therapy can be achieved for a longer time. The intima-media-thickness, as a sign of a complex atherosclerosis, is decreased. The number of atherosclerotic plaques is significantly lower in patients receiving hormone replacement therapy (HRT) in comparison to a control group. A regression of the plaques by estrogen replacement therapy could be shown in one study. Although the group of patients suffering from stroke is heterogeneous, the benefit of HRT for prevention of cerebrovascular diseases could clearly be demonstrated. HRT is not contraindicated in patients suffering from cerebrovascular diseases. In most of cases, HRT is recommended in these patients. The therapeutic effect of HRT for cerebrovascular disease should be proved in further prospective studies.

Cerebrovascular Disorders↗

Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.

OBJECTIVE: The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of the A and B isoforms and has been associated with an increased risk of endometrial and breast cancer. In this study, we sought to determine whether this polymorphism affects ovarian cancer risk. METHODS: The +331G/A polymorphism was genotyped in a population-based, case-control study from North Carolina that included 942 Caucasian subjects (438 cases, 504 controls) and in a confirmatory group from Australia (535 cases, 298 controls). Logistic regression analysis was used to calculate age-adjusted odds ratios (OR). RESULTS: There was a suggestion of a protective effect of the +331A allele (AA or GA) against ovarian cancer in the North Carolina study [OR, 0.72; 95% confidence interval (95% CI), 0.47-1.10]. Examination of genotype frequencies by histologic type revealed that this was due to a decreased risk of endometrioid and clear cell cancers (OR, 0.30; 95% CI, 0.09-0.97). Similarly, in the Australian study, there was a nonsignificant decrease in the risk of ovarian cancer among those with the +331A allele (OR, 0.83; 95% CI, 0.51-1.35) that was strongest in the endometrioid/clear cell group (OR, 0.60; 95% CI, 0.24-1.44). In the combined U.S.-Australian data that included 174 endometrioid/clear cell cases (166 invasive, 8 borderline), the +331A allele was significantly associated with protection against this subset of ovarian cancers (OR, 0.46; 95% CI, 0.23-0.92). Preliminary evidence of a protective effect of the +331A allele against endometriosis was also noted in control subjects (OR, 0.19; 95% CI, 0.03-1.38). CONCLUSIONS: These findings suggest that the +331G/A progesterone receptor promoter polymorphism may modify the molecular epidemiologic pathway that encompasses both the development of endometriosis and its subsequent transformation into endometrioid/clear cell ovarian cancer.

Adenocarcinoma, Clear Cell↗

Dietary prevention of hypertension in animal models and its applicability to human.

Experimental studies in animals and epidemiological studies have suggested that the interaction between genetic and environmental factors is important in hypertension associated with excess salt intake and other dietary factors such as K, protein and fatty acid intake greatly modify the effect of salt on blood pressure in individuals with low or high salt sensitivity. Thus, the detection of salt sensitivity and the modification of salt intake as well as other dietary factors are expected to contribute to the primary prevention of cardiovascular diseases associated with hypertension.

Animals↗

The changing epidemiology of SIDS following the national risk reduction campaigns.

Prone sleeping position is causally associated with SIDS. The change in the proportion of infants sleeping prone has resulted in a dramatic reduction in SIDS and total postneonatal mortality. The effect of prone sleeping position is modified by season, latitude, illness, thermal insulation and sheepskins. This suggests that the mechanism by which prone sleeping position causes SIDS is in some way related to temperature.

Case-Control Studies↗

Hazard identification in occupational injury: reflections on standard epidemiologic methods.

To prevent workplace injuries, epidemiologic research must continue to progress beyond methods originally used for acute or chronic diseases. For injury research, exposure assessment requires increased sophistication because exposures comprise multiple, transient factors and complex work activities. Frequently reported risk factors such as age, gender, seniority, or prior injury are often confounders or effect-modifiers of unknown exposures. Injury rate calculations across nominal categories, e.g., department or job classification, identify where hazards are concentrated but provide little insight into their nature; injury counts often perform almost as well. Calculation of rates in relation to time actually spent in plausible etiologic exposure conditions usually is not feasible. Generalization of the Haddon approach for individual injury events to systematically analyze injury case series can identify both the mechanism of injury and the relative occurrences of high-risk conditions. In some contexts, case-crossover designs may elucidate injury causation. National databases and information systems of employers, insurers, and equipment suppliers could contribute case series for injury hazard identification. By enhancing exposure assessment through a focus on case series, epidemiologic research can expand its contribution to preventing workplace injuries.

Accidents, Occupational↗

Appraisal of the epidemiology of fetal alcohol syndrome among Canadian native peoples.

Three recent studies suggest that Fetal Alcohol Syndrome (FAS) is more prevalent among Canadian Native children than non-Native children. The evidence does not appear to be conclusive. However, the Canadian research that is reviewed is important in defining areas which require further investigation. Efforts at research and intervention should be directed towards defining and modifying personal and social risk factors. Our review of current research on FAS and Native peoples suggests that it is important to consider pragmatic questions which can best contribute to the goal of preventing possible alcohol effects on the fetus.

British Columbia↗

The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study.

BACKGROUND: Few data are available about how social networks reduce the risk of cognitive impairment in old age. We aimed to measure this effect using data from a large, longitudinal, epidemiological clinicopathological study. METHODS: 89 elderly people without known dementia participating in the Rush Memory and Aging Project underwent annual clinical evaluation. Brain autopsy was done at the time of death. Social network data were obtained by structured interview. Cognitive function tests were Z scored and averaged to yield a global and specific measure of cognitive function. Alzheimer's disease pathology was quantified as a global measure based on modified Bielschowsky silver stain. Amyloid load and the density of paired helical filament tau tangles were also quantified with antibody-specific immunostains. We used linear regression to examine the relation of disease pathology scores and social networks to level of cognitive function. FINDINGS: Cognitive function was inversely related to all measures of disease pathology, indicating lower function at more severe levels of pathology. Social network size modified the association between pathology and cognitive function (parameter estimate 0.097, SE 0.039, p=0.016, R(2)=0.295). Even at more severe levels of global disease pathology, cognitive function remained higher for participants with larger network sizes. A similar modifying association was observed with tangles (parameter estimate 0.011, SE 0.003, p=0.001, R(2)=0.454). These modifying effects were most pronounced for semantic memory and working memory. Amyloid load did not modify the relation between pathology and network size. The results were unchanged after controlling for cognitive, physical, and social activities, depressive symptoms, or number of chronic diseases. INTERPRETATION: These findings suggest that social networks modify the relation of some measures of Alzheimer's disease pathology to level of cognitive function.

Aged↗

Health economics and cervical cancer prevention: a global perspective.

Recent scientific advances are providing an opportunity to revisit strategies for cervical cancer prevention. How to invest health resources wisely, such that clinical benefits are maximized-and opportunity costs are minimized-is a critical question in the setting of new technology. In addition to an intervention's effectiveness, public health decision-making requires consideration of its feasibility, sustainability and affordability. No clinical trial or single cohort study will be able to simultaneously consider all of these components. A mathematical simulation model can be a useful tool with which to evaluate alternative cervical cancer control strategies by extending the knowledge from empirical studies to real-world situations. Models combine information about the natural history of disease with other relevant demographic, epidemiological, and economic characteristics. We describe a comprehensive Cervical Cancer Policy Model with a flexible structure that may be modified as new data on the biology of disease become available. This model provides an analytic framework to synthesize data on costs and benefits, to help design clinical guidelines, and to inform development of sound health policy. Examples of cost-effectiveness analyses conducted in the US and South Africa illustrate inevitable tradeoffs when choosing among a variety of interventions to decrease cervical cancer mortality, and demonstrate how these methods can facilitate a bridge between research and health policy.

Cost-Benefit Analysis↗

Estimating human cancer risk from the results of animal experiments: relationship between mechanism and dose-rate and dose.

Experimental animals are often used as surrogate models in estimating human cancer risk from environmental agents when adequate epidemiological data are not available. Studies in experimental animals have usually evaluated the effects of exposure to single substances; however, humans receive combinations of exposures, to both initiators and promoters of carcinogenesis. Exposure to several agents may modify the carcinogenic process of one of them. For many agents, the relationship between dose and carcinogenic response depends on both dose-rate and cumulative dose. For a given total dose, dose-rate may affect carcinogenic potency both qualitatively (target organ) and quantitatively. The effects of dose-rate are a function of total dose, species, and most importantly, the mechanism by which the agent exerts its carcinogenic effect. Prediction of the effects of different dose-rates of potentially carcinogenic agents can be based on knowledge of its mechanism of action.

Animals↗

A scaled sample space cube used to illustrate attributable fractions.

A three-dimensional graphic method is proposed for displaying the association structure between multiple explanatory variables and their relation to a categorical response. The method combines the techniques of mosaic displays and scaled Venn diagrams, and is especially useful for illustrating attributable fractions in epidemiology. The primary purpose is to show the reduction of disease risk in a population if the joint exposure distribution or the conditional risk function is modified, and the method can be extended to illustrate the potential effects of successive removal of exposures on the overall risk of disease. The scaled sample space cube may be used for communicating the difficult concept of attributable fraction to statisticians, the medical community and the general public in an easily understandable way. Demonstrations of the method use theoretical models as well as data from the Hordaland study on the effect of smoking and occupational exposure on obstructive lung disease. Also, the general principle of adding a third dimension to a mosaic display, instead of using shading or colouring, to show an attribute of a cell in a multiway contingency table, can be helpful for other purposes, as in residual analysis of a loglinear model fitting.

Algorithms↗

Theileriosis control modelling (experiences from Southern Province, Zambia).

Effects of different tick-borne disease control strategies on cattle productivity are simulated based on a 30-year herd projection, calculated by a modified Markov Chain model. Input data can be grouped in technical, economic and epidemiological parameters. The output is a set of economic parameters such as benefit/cost ratio (BCR), net present value (NPV) of the profit, internal rate of return (IRR), total economic cost (TEC) as well as graphs showing animal production over time. Shadow prices are obtained for input and output in kind. Throughout the calculations a distinction is made between transactions in cash and transactions in kind. A case study was run for Southern Province, Zambia, to illustrate the model. Either vector control or treatment, or a combination of these, controls theileriosis at farm level after natural infection. Preventive immunization against the parasite is also possible. Although the calculations are based on a mixture of data obtained from literature, field experience, expert opinion and assumptions, the importance of theileriosis control is clearly indicated. Immunization gives better economic results than chemotherapy. Vector control can only be used as a last resort.

Animals↗

Traditional fermentation increases goitrogenic activity in pearl millet.

Epidemiological evidence suggests that millet might play a role in the etiology of endemic goiter. Recently, we showed that a traditional fermentation procedure of two pearl millet (Pennisetum americanum L. Lecke) cultivars grown in Sudan modified their effects on the weight of the thyroid gland and thyroid hormone profile in rats. In the present study, we report that this fermentation procedure reduced the ash contents of millet by about 40% and removed considerable amounts of Mg (>50%), Zn (27-39%) and K (45%). Other minerals (Ca, Fe, Cu) were not affected. Feeding of one fermented cultivar resulted in significant reduction in bone Mg and Zn contents, whereas feeding of the other fermented cultivar resulted in reduction of bone Mg only. Dietary Mg intake and bone Mg contents correlated negatively with serum T3. Groups fed the millet diets had higher serum Se level compared to those fed wheat or casein diets and feeding of fermented millet resulted in a further increase in serum Se level. Thus our data indicate that in rats the enhanced effects of millet on the thyroid induced by fermentation is likely related to removal of minerals from millet and/or chemical transformation of the goitrogens contained in millet.

Animals↗

Should women with familial ovarian cancer undergo prophylactic oophorectomy?

OBJECTIVES: To estimate the lifetime probabilities of ovarian cancer in women from families with hereditary ovarian cancer syndromes and those with a family history of ovarian cancer, and to assess the needs for prevention and surveillance in such women. DATA SOURCES: We searched for studies of familial ovarian cancer published since 1966 and used ovarian cancer incidence data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. METHODS: Pooled estimates of relative risk of ovarian cancer among women with a family history of ovarian cancer were derived using statistical methods based on fixed effects. Modified life-table methods were used to estimate the lifetime probability of ovarian cancer. DATA SYNTHESIS: The lifetime probability of ovarian cancer increases from about 1.6% in a 35-year-old woman without a family history of ovarian cancer to about 5% if she has one relative and 7% if she has two relatives with ovarian cancer. The lifetime probability may decrease to about 3-4% if she takes oral contraceptives for 5-9 years. Women from families with hereditary ovarian cancer syndromes may have as high as a 50% lifetime risk of ovarian cancer. CONCLUSIONS: The risk of ovarian cancer in women from families with hereditary ovarian cancer syndromes is sufficiently high to warrant prophylactic oophorectomy. Among women with one relative with ovarian cancer, the lifetime probability of ovarian cancer is not high enough to recommend oophorectomy. However, some women may choose oophorectomy depending on their attitudes concerning risk-taking, surgery, and hormone replacement. Oral contraceptives should be considered as preventive therapy to decrease the risk of ovarian cancer in women with a family history of ovarian cancer.

Adult↗

[New approaches to prophylaxis of oncologic morbidity associated with environmental chemical hazards].

The author suggested a new algorithm of State Sanitary Epidemiologic Supervision activities on oncologic morbidity prophylaxis. The algorithm takes into account environmental content not only of chemical carcinogens, but also of so-called modifiers--nonspecific chemical pollutants that lower threshold of human sensitivity to carcinogenic effects and intensify carcinogenesis.

Algorithms↗

Suppression of chemically-induced liver tumors by castration or estradiol-3-benzoate treatment in F344 rats.

Epidemiological data reveal that the incidence of liver cancer is markedly higher in men than women. To clarify the mechanism responsible for the induction of higher incidence of liver tumors in male animals, we investigated the modifying effect of sex hormones in diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. F344 male rats (n=120) were divided into two experiments, experiment I (Exp I) and experiment II (Exp II). In each experiment, 60 rats were randomly allocated into four groups. The mini-osmotic pumps containing doses of 47.5 mg (Exp I) or 23.75 mg (Exp II) of DEN were inserted into the abdominal cavity of each animal to initiate liver carcinogenesis. Animals in group 2 were castrated one week prior to DEN treatment, and animals in groups 3 and 4 were treated with 1 or 10 microg of estradiol-3-benzoate (EB), respectively, one week prior to DEN treatment. Animals in group 1 were treated with DEN alone and sham-operated at the same time. All animals were sacrificed 26 weeks after DEN treatment. In Exp I, liver tumor incidence of group 3 decreased significantly compared with that of group 1 (p<0.05), and tumor multiplicities of groups 2, 3 and 4 were decreased significantly compared to that of group 1 (p<0.01). In Exp II, tumor incidence of group 3 was significantly different (p<0.05) when compared to that of group 1. Immunohistochemical expression of ERalpha was shown in normal appearing cells, but not in tumor cells. Western blot analysis confirmed that ERalpha expression was higher in normal liver tissue compared to tumor tissues. Taken together, we conclude that castration or EB treatment has an inhibitory effect in DEN-induced hepatocarcinogenesis in F344 rats. The reason for ERalpha loss in tumor cells should be further elucidated.

Animals↗

Methodologic issues in hospital epidemiology. IV. Risk ratios, confounding, effect modification, and the analysis of multiple variables.

Most information in hospital epidemiology comes from observational studies of hospitalized patients, not from planned experiments. Data from observational studies have frequently been used to investigate the effect of exposure to a single factor as a cause or determinant of a discrete outcome, such as infection or death. In such observational studies, the characteristics of study patients may vary widely even within a single hospital. In these investigations, extraneous variables such as differing severity of underlying illness, acting in concert with the exposure variable being studied, may distort the apparent effect of the exposure on the outcome through confounding or may modify the effect of the exposure on the outcome without distorting the relation between them. The data from six published studies are reanalyzed through the use of stratification by severity of underlying illness in order to demonstrate the impact of confounding and effect modification by a third, extraneous variable. Simple methods for dealing with confounding and effect modification in data from hospital epidemiology are presented.

Analysis of Variance↗