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PubMed1995

Dietary fat and obesity: evidence from epidemiology.

The epidemiological evidence that a high-fat diet promotes the development of obesity is considered suggestive but not definitive. The purpose of this paper is to provide a review of various epidemiological methods that have been used to address this issue as well as an updated summary of the existing evidence. Ecological studies describing dietary fat intake and obesity at the population level provide mixed results and are likely to be biased by both confounding and unknown data quality factors that differ systematically across the populations studied. Cross-sectional studies are generally in agreement that the concentration of fat in the diet is positively associated with relative weight. Prospective studies of diet in relation to subsequent weight change give inconsistent results. This may be due to behavioural factors such as dieting in response to weight gain; in addition, this type of study rarely takes into account the possible interaction between genetic predisposition and dietary fat in promoting weight gain. Finally, intervention studies in free-living subjects are considered, providing evidence of a consistent but short-lived period of active weight loss on low-fat diets. The experimental evidence on this relationship is more conclusive than the epidemiological evidence, although biological mechanisms remain controversial. Some areas for future epidemiological research involve: longitudinal studies of dietary fat intake as a predictor of growth in children; observational studies relating total dietary fat and specific types of fat to overall as well as regional adiposity; and randomized intervention studies of the effect of low-fat diets with particular emphasis on and familial predisposition to obesity and other possible modifying factors.

Adult↗
PubMed2002

Increase in lifetime adverse drug reactions, service utilization, and disease severity among patients who will start COX-2 specific inhibitors: quantitative assessment of channeling bias and confounding by indication in 6689 patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: Nonrandom assignment of therapy in observational studies and clinical practice can be accompanied by channeling bias and confounding by indication. This in turn can lead to unreliable conclusions about treatment effectiveness. Although widely acknowledged as important, no studies in rheumatology have measured the extent of these biases. We identified variables contributing to confounding and investigated the strength of the confounding effect. Analytical methods (propensity scores) are available to mitigate the effect of nonrandom assignment if the full extent of confounding can be understood. METHODS: A population of 6637 patients with rheumatoid arthritis (RA) and osteoarthritis (OA) from the practices of 433 US rheumatologists completed 2 sets of detailed questionnaires concerning (1) the last 6 months in 1998 and (2) the first 6 months of 1999, generally prior to and after the release of celecoxib and rofecoxib. Patients who received the COX-2 specific inhibitors in period 2 were identified (n = 1517), and their characteristics were compared to the 5120 who did not start a new COX-2 specific inhibitor during Period 1. RESULTS: Patients starting a new COX-2 specific inhibitor had a greater lifetime history of adverse reactions of all kinds, but particularly gastrointestinal adverse drug reactions. They also had more severe scores for pain, functional disability, fatigue, helplessness, and global severity, and they used more inpatient and outpatients services than patients who would not switch to COX-2 specific inhibitors. CONCLUSION: Confounding by indication and channeling bias result in an overall increase in severity of about 25% for the above measures. Observational studies should account for these biases by a broadly defined propensity score that includes the variables identified in this report. These observations are germane to observational studies of disease modifying antirheumatic drugs and biologics, as well, and suggest the need for careful control of confounders when assessing treatment effects in rheumatic disease observational studies.

Aged↗
PubMed2004

Framingham and European risk algorithms: implications for African Americans.

Based on data from the African American population, it appears that the Framingham estimates for the risk of coronary heart disease are reasonably predictive of cardiovascular outcomes in this group. However, a variety of factors exist in this population that may lead to a greater degree of misclassification than might be expected. Therefore, caution should be exercised when implementing risk algorithms, especially when effects in observational studies are incongruent with the experience of controlled clinical trials. Estimation of risk for cardiovascular events is a dynamic field, and current approaches will likely be modified as newer information is obtained.

Algorithms↗
PubMed2003

Modelling the cost-effectiveness of etanercept in adults with rheumatoid arthritis in the UK.

OBJECTIVES: This model examines the cost-effectiveness of etanercept monotherapy under British Society for Rheumatology guidelines, i.e. adults previously failing two disease-modifying anti-rheumatic drugs (DMARDs). It compares a DMARD sequence with etanercept third line against the same sequence excluding etanercept. METHOD: The 6-monthly trend in Health Assessment Questionnaire (HAQ) disability score is simulated for 10 000 patients' lifetimes using clinical trial data and published literature. Switching to the next treatment is triggered by lack of response, loss of efficacy or adverse events. Patient mortality depends on rheumatoid arthritis life-tables and on epidemiological evidence relating reduced risk to HAQ improvement. Regression of HAQ/EuroQol (EQ-5D) utility provides quality-adjusted life years (QALY) gained. Primary analysis includes drug costs, monitoring and hospitalizations. RESULTS: The central estimate cost per QALY is pound 16 330. Sensitivity analyses ( pound 7800 to pound 42 000) showed long-term HAQ progression (etanercept, DMARDs, non-responders) as most sensitive variables. The inclusion of potential avoided nursing home admissions and indirect costs/lost employment further improves the cost-effectiveness. CONCLUSIONS: For adults in the UK, the results suggest that etanercept is cost-effective when compared with non-biologic agents. The National Institute for Clinical Excellence has accepted that etanercept is cost-effective and recommended its availability for use in patients who have failed at least two DMARDs. This model was an important component of that decision. The model is further suitable for use for a wide range of other cost-effectiveness questions in rheumatoid arthritis.

Antirheumatic Agents↗
PubMed1999

Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia?

The central nervous system is increasingly being recognised as a target organ for vitamin D via its wide-ranging steroid hormonal effects and via the induction of various proteins such as nerve growth factor. This paper proposes that low maternal vitamin D may impact adversely on the developing foetal brain, leaving the affected offspring at increased risk of adult-onset schizophrenia. The hypothesis can parsimoniously explain diverse epidemiological features of schizophrenia, such as the excess of winter births, increased rates of schizophrenia in dark-skinned migrants to cold climates, the increased rate of schizophrenia births in urban versus rural setting, and the association between prenatal famine and schizophrenia. Studies that will allow rejection of the hypothesis are proposed.

Adult↗
PubMed1998

An overview of the marine food poisoning in Mexico.

In the course of the last decade, huge events related to harmful algal blooms (HAB) have severely affected the environment in Mexico, even causing several human casualties. The tally of the toxins known up to date in Mexican waters includes: neurotoxin shellfish poisoning (NSP), paralytic shellfish poisoning (PSP), amnesic shellfish poisoning (ASP), tetrodotoxin (TTX) or puffer fish poisoning, ciguatera fish poisoning (CFP) and diarrhetic shellfish poisoning (DSP). Actual epidemiological figures profoundly modified the trends manifested on previous decades. Notwithstanding that the red tides are a long time known phenomena in Mexican coasts, no regular observation of the marine environment has been set up. Although there are monitoring activities for PSP toxins on the shellfish culturing facilities that are exploited for export to the U.S.A., these are only effectively applied on specific spots of the Mexican coasts, implying that the biggest part of the country coastal zones are not formerly surveyed. The misleads caused by the medical conception that food poisoning events are mainly due to microbial contamination, is among the factors why the marine food poisoning events are a neglected disease. In spite of the fact that no official statistics consider HAB related events as a subject of research or further monitoring by the health authorities, sporadic scientific documents related to poisoning events were produced in Mexico. An interesting picture is presented for most of the marine toxins mentioned. Trend and prognosis estimates made with such scarce information, provide a minimum measurement of the reality and urge the need for a permanent monitoring program on the Mexican coasts, a place with one of the greatest marine toxin diversity worldwide.

Animals↗
PubMed2001

Genetic contributions to rare childhood lung diseases.

Epidemiological studies have suggested that many rare diseases with respiratory involvement have a genetic component. Molecular advances have increased the understanding of the pathophysiology of these diseases which has led to better diagnostic and prognostic methods. There may be many genes responsible for diseases such as primary ciliary dyskinesia and systemic lupus erythematosus in addition to the effect of modifier genes. The genotype:phenotype correlation in these diseases remains to be elucidated. In some diseases, such as familial dysautonomia and sickle cell, the gene has been identified which allows for accurate pre-natal testing. Further, in diseases where the genetic abnormality is known, such as chronic granulomatous disease, gene therapy remains a realistic prospect and phase I studies are about to commence or currently underway. This article reviews those rare diseases in which there is or is likely to be a significant genetic contribution.

Anemia, Sickle Cell↗
PubMed2006

Diallylsulfide and allylmethylsulfide are uniquely effective among organosulfur compounds in inhibiting CYP2E1 protein in animal models.

Garlic is a popular culinary herb that is also used throughout the world as a traditional medicine for the prevention and treatment of disease. Epidemiologic studies have suggested that long-term consumption of garlic reduces risk for certain cancers, most notably stomach and colon cancer. This article summarizes the key findings behind one important mechanism explaining the anticarcinogenic effects of garlic-derived agents in animal models: the inhibition of cytochrome p4502E1 (CYP2E1), with some commentary on other aspects of carcinogen metabolism modified by these unique phytochemicals.

Allyl Compounds↗
PubMed1997

The effect of antioxidant vitamin supplementation on traditional cardiovascular risk factors.

BACKGROUND: Evidence from observational epidemiologic studies has indicated that antioxidants consumed through the diet or as dietary supplements lower the risk of developing atherosclerotic cardiovascular disease. Evidence suggesting that the major mechanism for the protective effect of antioxidants is mediated through decreased oxidation of lipids, particularly low-density lipoprotein (LDL) cholesterol is accumulating. Other evidence, however, suggests that antioxidants may influence traditional modifiable cardiovascular risk factors such as the blood pressure and serum lipids favorably. The purpose of this study was to determine the effect of antioxidant vitamin supplementation on modifiable risk factors for atherosclerotic cardiovascular disease. DESIGN: A randomized, placebo-controlled, clinical trial of antioxidant vitamin supplementation, conducted at a single community-based clinical research center. METHODS: We assigned 297 retired teachers who were members of the Maryland Retired Teachers Association randomly to 2-4 months of dietary supplementation with placebo or combined antioxidant vitamin capsules providing 400 IU/day vitamin E, 500 mg/day vitamin C, and 6 mg/day beta-carotene. The outcome measures were the blood pressure, fasting serum total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, and fasting glucose. RESULTS: After 2-4 months of supplementation the combined antioxidant supplement had had no significant effect on the systolic and diastolic blood pressures, fasting serum lipids (total cholesterol, high-density lipoprotein cholesterol, and LDL cholesterol) and fasting glucose, with unadjusted and adjusted analyses. CONCLUSION: Data from this trial suggest that the protective effect from antioxidant vitamin supplementation, if there is one, likely results from mechanisms other than modification of traditionally modifiable cardiovascular risk factors.

Antioxidants↗
PubMedDate not supplied

[Use of heart rate variability as a marker of cardiovascular effects associated with air pollution].

Epidemiological studies have shown the association between atmospheric pollutants and increase in mortality due to cardiovascular causes, especially in patients with previous cardio-respiratory diseases. However, the pathophysiological mechanisms by which these events take place have not been elucidated. One of the proposed mechanisms by which suspended respirable particles and other pollutants produce their effect is that they modify autonomic heart control. The analysis of changes in heart rate variability (HRV) is an indicator of pollutant effect on this mechanism. The article reviews the physiologic basis of this non-invasive method, its advantages and disadvantages, and the results obtained to date through HRV analysis associated with air pollution. After reviewing the available literature, we suggest alternatives for study design, selection of risk population, exposure assessment methods, and statistical analysis methods that may be used to improve the analysis of the ambulatory ECG record to assess the cardiac risk related to exposure to air pollution.

Air Pollution↗
PubMed2003

Efficacy and cost-effectiveness of the first generation of HIV prevention interventions for people with severe and persistent mental illness.

BACKGROUND: People with serious mental illness are at elevated risk for human immunodeficiency virus (HIV) infection. A small body of published research has evaluated the efficacy of HIV prevention interventions that aim to help persons with mental illness modify sexual behaviors that place them at risk for HIV infection. Additional research has evaluated the economic efficiency ('cost-effectiveness') of these interventions. AIMS OF THE STUDY: We provide a detailed and critical review of the efficacy and cost-effectiveness of randomized, controlled trials of HIV prevention interventions for this population. We present a brief overview of the epidemiology of HIV among men and women with serious mental illness and describe HIV risk factors for members of this population. The efficacy literature is critically reviewed, and the results of the available studies are compared using a common effect size metric. The cost-effectiveness of HIV prevention interventions for mentally ill adults is then reviewed. METHODS: The efficacy of interventions at reducing risk behaviors and increasing preventive behaviors was summarized using effect size estimation techniques. First, we reviewed interventions that have been evaluated in randomized clinical trials and published in the peer-reviewed scientific literature so as to summarize the interventions that have been subjected to the most rigorous evaluation. For each of the five studies that met the inclusion criteria, we briefly described the methodology and intervention content, summarized the evidence for intervention efficacy, and calculated appropriate effect size estimates. A narrative review of two cost-effectiveness studies published to date was included. RESULTS: The review of intervention efficacy indicated that the risk reduction interventions evaluated to date have had only limited success at helping people with severe mental illness reduce their HIV risk behavior. Most effect sizes indicating successful condom use increases were in the small or small to moderate range. Overall, studies with the largest sample sizes, and presumably the most generalizable results, produced smaller intervention effect sizes than studies with smaller samples. The cost-effectiveness literature revealed similarly mixed results: economic efficiency varied from not cost-effective to highly cost-effective. DISCUSSION: Limited information is presently available regarding the efficacy and cost-effectiveness of HIV prevention interventions for people with severe and persistent mental illness. Encouraging results were obtained in some, but not all studies. Methodological limitations will need to be addressed in the next generation of HIV risk reduction intervention studies for this population. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Persons with severe mental illness warrant attention from health care providers due to elevated risk for HIV infection. Interventions discussed herein, focusing on information and behavioral skills training, can be employed until strategies with stronger results are developed. IMPLICATIONS FOR HEALTH POLICIES: Effective and cost-effective HIV risk reduction interventions are available for adults with mental illness and should be more widely implemented. The cost-effectiveness of these interventions could be further enhanced by screening potential participants for high-risk sexual behaviors. IMPLICATIONS FOR FURTHER RESEARCH: To advance the field, the next generation of intervention research for people with severe mental illness will need to improve upon the designs and intervention strategies of the first generation, include larger samples, and devote increased attention to the life circumstances and particular mental health issues of intervention participants.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms.

The focus of this review is the molecular genetics, including consensus NAT1 and NAT2 nomenclature, and cancer epidemiology of the NAT1 and NAT2 acetylation polymorphisms. Two N-acetyltransferase isozymes, NAT1 and NAT2, are polymorphic and catalyze both N-acetylation (usually deactivation) and O-acetylation (usually activation) of aromatic and heterocyclic amine carcinogens. Epidemiological studies suggest that the NAT1 and NAT2 acetylation polymorphisms modify risk of developing urinary bladder, colorectal, breast, head and neck, lung, and possibly prostate cancers. Associations between slow NAT2 acetylator genotypes and urinary bladder cancer and between rapid NAT2 acetylator genotypes and colorectal cancer are the most consistently reported. The individual risks associated with NAT1 and/or NAT2 acetylator genotypes are small, but they increase when considered in conjunction with other susceptibility genes and/or aromatic and heterocyclic amine carcinogen exposures. Because of the relatively high frequency of some NAT1 and NAT2 genotypes in the population, the attributable cancer risk may be high. The effect of NAT1 and NAT2 genotype on cancer risk varies with organ site, probably reflecting tissue-specific expression of NAT1 and NAT2. Ethnic differences exist in NAT1 and NAT2 genotype frequencies that may be a factor in cancer incidence. Large-scale molecular epidemiological studies that investigate the role of NAT1 and NAT2 genotypes and/or phenotypes together with other genetic susceptibility gene polymorphisms and biomarkers of carcinogen exposure are necessary to expand our current understanding of the role of NAT1 and NAT2 acetylation polymorphisms in cancer risk.

Acetylation↗
PubMed2003

Thrombin, inflammation, and cardiovascular disease: an epidemiologic perspective.

The exploration of coagulation led to identifying inflammation as a major factor in arterial disease throughout life. "Integrative molecular physiology" reflects our emerging understanding of how coagulation and inflammation integrate with one another, in both normal physiology and in pathophysiology. Our own responses to environmental challenge provide much of the damage that cumulatively results in chronic cardiovascular disease. Only by intervening in exquisitely precise ways can we hope to effectively and safely modify the course of lifelong chronic diseases, such as atherosclerosis.

Arteriosclerosis↗
PubMed2005

Integrating epidemiology and genetic association: the challenge of gene-environment interaction.

Recent advances in human genomics have made it possible to better understand the genetic basis of disease. In addition, genetic association studies can also elucidate the mechanisms by which "non-genetic" exogenous and endogenous exposures influence the risk of disease. This is true both of studies that assess the marginal effect of a single gene and studies that look at the joint effect of genes and environmental exposures. For example, gene variants that are known to alter enzyme function or level can serve as surrogates for long-term biomarker levels that are impractical or impossible to measure on many subjects. Evidence that genetic variants modify the effect of an established risk factor may help specify the risk factor's biologically active components. We illustrate these ideas with several examples and discuss design and analysis challenges, particularly for studies of gene-environment interaction. We argue that to increase the power to detect interaction effects and limit the number of false positive results, large sample sizes will be needed, which are currently only available through planned collaborative efforts. Such collaborations also ensure a common approach to measuring variation at a genetic locus, avoiding a problem that has led to difficulties when comparing results from genetic association studies.

Environmental Exposure↗
PubMed1984

[Quantitative methods of assessing the severity of an epizootic situation].

n order to evaluate the epizootic status of a particular territory for a given moment or a period of time with regard to the infectious diseases one has adopted Tarshis ' formula. The present work deals with the comparative approbation of this formula, using a modified formula in which a parameter characterizing the intensity of the epizootic process was introduced. The epizootic situation and its severity was determined by the two formulas for each district of the country with regard to the following infectious diseases: gangrenous mastitis and listeriosis of sheep, swine erysipelas, and anthrax of all kinds of farm animals--all for the 1970-1981 period. A categorization of the districts is effected according to the values obtained. It was found that the modified formula is important for the objectivization of the severity of the epizootic status as it reflected also the territorial spread and intensity of the epizootic process.

Animals↗
PubMedDate not supplied

Technical and economic evaluation method for use in improving infectious animal disease surveillance networks.

With hope of improving the increasing number of epidemiological surveillance networks for animal diseases set up in recent years, a qualitative and quantitative technical and economic evaluation tool was developed and then applied to three epidemiological surveillance networks: RENESA (a French surveillance network for salmonella and mycoplasma contamination in poultry production units subject to official sanitary controls), the French Foot and Mouth Disease Epidemiovigilance Network and REPIMAT (the epidemiological surveillance network in Chad for major cattle diseases). We identified critical points in epidemiological surveillance networks using a modified version of the hazard analysis: critical control point (HACCP) method. An evaluation grid was then developed and validated by experts who were consulted in accordance with the Delphi method. A questionnaire to collect the information required for the evaluation and a scoring guide were then designed. Our evaluation procedure also included a calculation of the annual operating costs for two of the three networks studied. On the basis of the detailed results of the technical and economic evaluation, we formulated specific suggestions for improving the networks. The cost of implementing these proposals was calculated. We then simulated the effects of implementing each of the proposed improvements and a new global evaluation score was determined for each network. The 'cost per point' of each improvement was then calculated and discussed. This tool for the technical and economic evaluation of epidemiological surveillance networks for animal diseases is proposed so that it may be tested on a far wider scale and eventually be used in improving the functioning of such networks and for risk analysis in international trade.

Animals↗
PubMed2005

Contributing factors to preschool unintentional injury.

Injury is the leading cause of death and disability for preschoolers in the United States. Young children suffer disproportionate morbidity and mortality when injured. Pediatric nurses modify injury risk through injury prevention strategies and child and family education. Effective injury prevention programs cannot be designed, implemented, or evaluated without a fundamental understanding of the factors that contribute to the phenomenon of preschool unintentional injury. This article includes a discussion of the factors that contribute to preschool unintentional injury occurrence and is based on a combination of epidemiology theory and the health belief model. Evidence-based suggestions for modification of nursing practice are provided.

Accident Prevention↗
PubMed2005

[A connection between allergic rhinitis and allergic asthma? The "one-airway-one-disease"-hypothesis].

As outlined in part 1, numerous data from immunologic, genetic and epidemiologic studies point to a systemic link between allergic asthma and rhinitis which can be seen as manifestations of a common atopic syndrome. In part 2 clinical manifestations, diagnostics and most importantly therapeutic options effecting on both nasal and bronchial symptoms will be discussed. Allergen avoidance is the first step in therapeutic management of allergic diseases. Specific immunotherapy (SIT), leukotriene modifying compounds (in Germany exclusively Montelukast), and corticosteroids inhibit inflammation in the epithelium of the upper and the lower airways. Although SIT has a widely accepted indication in the treatment of allergic rhinitis, it is just provisionally recommended for the treatment of asthmatic patients. Most recently Montelukast, a potent leukotriene receptor inhibitor, has been approved for the treatment of asthma as well as for allergic rhinitis. Local administration of corticosteroids requires that they be given both nasally and bronchially. Just on the i. v. or oral route corticosteroids may inhibit the allergic inflammation in both compartments. Newly developed IgE-inhibitor Omalizumab, which has no approval in Germany yet, has been reported to have similar effects. Thus, various therapeutic options are available to treat asthma and rhinitis at the same time. Furthermore, multilateral clinical efficacy of antiinflammatory drugs support the "One-Airway-One-Disease" hypothesis.

Asthma↗