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Results for “Effect Modifier, Epidemiologic”

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PubMed1989

Effects of cluster sampling on epidemiologic analysis in population-based case-control studies.

We consider population-based case-control designs in which controls are selected by one of three cluster sampling plans from the entire population at risk. The effects of cluster sampling on classical epidemiologic procedures are investigated, and appropriately modified procedures are developed. In particular, modified procedures for testing the homogeneity of odds ratios across strata, and for estimating and testing a common odds ratio are presented. Simulations that use the data from the 1970 Health Interview Survey as a population suggest that classical procedures may be fairly robust in the presence of cluster sampling. A more extreme example based on a mixed multinomial model clearly demonstrates that the classical Mantel-Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) and Woolf-Haldane tests of no exposure effect may have sizes exceeding nominal levels and confidence intervals with less than nominal coverage under an alternative hypothesis. Classical estimates of odds ratios may also be biased with non-self-weighting cluster samples. The modified procedures we propose remedy these defects.

Biometry↗

PubMed1988

The Dienes effect as an epidemiological tool in a paraplegic unit.

The authors study the Dienes effect in 136 P.mirabilis and 2 P.vulgaris strains, isolated from different infection or colonization sites, in 27 spinal cord injured patients, admitted to a Paraplegic Unit, during a 9 month period. It is shown that 7 cross-infection and 18 cross-contamination episodes occurred, affecting 13 of 27 patients, which indicates the great spreading capacity of these microorganisms; 97% of the results obtained were observed once again after 6 months' storage of strains. In addition, in 7 of these strains their resistance to several antibiotics was cured by treating them with acriflavine salts, demonstrating that the Dienes effect persists even when resistance to antibiotics is modified; the authors conclude that the Dienes effect is an accurate stable epidemiological tool to identify cross-infections and its origins, and to facilitate the interruption of the chain of infection.

Cross Infection↗

PubMed1991

Epidemiology and preventive interventions: parental death in childhood as a case example.

Illustrates how standard epidemiologic principles form the knowledge base to justify a preventive intervention for an at-risk population. These principles were applied to a sample of 92 from the population of children aged 8 to 15 at alleged risk for mental health disorders because a parent died. Prior work on this alleged risk population is sparse and flawed. Validly determining the population effect of an alleged risk factor requires assessing the influence of sampling bias. The bias found, underrepresentation of deaths of a mother, did not influence the relations among death of a parent and children's depression and conduct disorder, and the modifiable mediators of risk to be changed by the preventive intervention. The epidemiologic measure of effect indicated that death of a parent is a risk factor for major depression but not for conduct disorder among youth. Families recruited for the preventive intervention by epidemiologic methods (ES families) did not differ significantly from the earlier families on whom the knowledge base was formed. Families referred to the intervention by self or others significantly differed from the ES families in two ways that constituted serious biases. The implications of these biases for prevention were discussed.

Adolescent↗

PubMed2003

Health status as a potential effect modifier of the relation between noise annoyance and incidence of ischaemic heart disease.

AIMS: Traffic noise is a psychosocial stressor. Epidemiological studies suggest chronic noise stress to be a risk factor for cardiovascular disorders. METHODS: In a prospective cohort study, the association between annoyance and disturbances due to road traffic noise and the incidence of ischaemic heart disease (IHD) was studied in 3950 middle aged men. RESULTS: Depending on the questionnaire item, non-significant odds ratios for IHD incidence ranging from 0.9 to 1.4 were found for the highly noise annoyed/disturbed subjects when compared with the less annoyed/disturbed subjects, over the six year follow up period. However, this relation was strongly modified by the prevalence of pre-existing chronic diseases. In subjects free of any chronic disease at the beginning of the follow up, significant odds ratios between 1.7 and 3.0 were seen. In the subgroup with chronic diseases no such noise effects were seen. This surprising result of no effect in the group of people with a potential risk, due to pre-existing health problems, may be because of the dilution of the true effect due to recall bias. CONCLUSIONS: Annoyance and disturbance due to road traffic noise is associated with a higher incidence of IHD. Prevalence of disease can be an important effect modifier of the relation between noise annoyance and health outcomes.

Aged↗

PubMed2003

Atopic manifestations, breast-feeding protection and the adverse effect of DDE.

Despite the numerous studies on the possible protective effect of breast feeding against the onset of atopic manifestations during childhood, this issue remains controversial. As part of an environmental epidemiological study, we investigated whether different blood concentrations of dichlorodiphenyl-dichloroethylene (DDE) modified the protective effect of breast feeding against atopic manifestations in 338 children. DDE concentration, duration of breast feeding and manifestation of atopic disorders were measured in 1994-95 at age 7-8 years. Information gathered on asthma, atopic eczema and hay fever was based on questionnaire data. We measured the total serum concentration of immunoglobulin E (IgE) and specific IgE levels against inhalant allergens. In 1997, we also determined bronchial hyper-reactivity with a hypertonic saline challenge test. To estimate odds ratios from our cross-sectional analysis, we applied logistic regressions, controlling for confounders. Breast feeding had a protective effect on the two asthma variables (e.g.> 12 weeks breast feeding for doctor-diagnosed asthma, OR = 0.32 [95% CI 0.11, 0.87]; for 'ever' asthma, OR = 0.13 [95% CI 0.02, 0.68]), but not on bronchial hyper-reactivity, hay fever, atopic eczema or the two IgE variables. The protective effect became stronger in children with DDE blood levels below the median of 0.29 micro g/L (e.g. doctor-diagnosed asthma,> 12 weeks breast feeding, OR = 0.24 [95% CI 0.06, 0.95]). Also, for specific IgE against inhalant allergens, the association gained statistical significance. For children with a DDE concentration of 0.29 micro g/L and higher, breast feeding did not show a significant protective effect. Our results suggest that contaminants such as DDE may modify the protective effect and may have contributed to inconsistent findings on the protective effect of breast feeding in previous studies. We recommend determining levels of breast milk contaminants in children when assessing the impact of breast feeding on atopic manifestations.

Asthma↗

PubMed2005

Risk of functional ovarian cyst: effects of smoking and marijuana use according to body mass index.

Smoking is one of the few risk factors that have been identified for functional ovarian cysts, and results of one epidemiologic study suggest that body mass index (BMI; weight (kg)/height (m)(2)) may modify the effect of this exposure. The current study assessed the association of cigarette smoking and marijuana use with functional ovarian cyst risk by using data from a population-based 1990-1995 case-control study of 586 incident functional ovarian cyst cases and 757 age-matched controls in a large health maintenance organization in Washington State. In multivariate analyses controlling for age, education, and reference year, the authors found an increase in risk associated with current cigarette smoking among women whose BMI was <20 (odds ratio (OR) = 2.48, 95% confidence interval (CI): 1.32, 4.64) or 20-25 (OR = 1.60, 95% CI: 1.04, 2.46) but not >25 (OR = 0.85, 95% CI: 0.53, 1.37). Corresponding risks associated with current marijuana use were BMI <20, OR = 2.05 (95% CI: 0.89, 4.75); BMI 20-25, OR = 1.78 (95% CI: 1.00, 3.17); and BMI >25, OR = 0.72 (95% CI: 0.36, 1.42). Study results indicate that increased BMI may attenuate the adverse effect of smoking on the risk of functional ovarian cyst.

Adult↗

PubMed2004

Angiotensin converting enzyme inhibitors for cancer treatment?

Angiotensin converting enzyme inhibitors (ACEi) prescribed for cardiovascular and renal disease since 1980 are widely atoxic and several experimental studies and one epidemiological study have demonstrated an effect of ACEi on cancer. ACEi has the effect of modifying gene expression; inhibiting proliferation and invasion of cancer cells; reducing endothelial cell migration and angiogenesis in vitro, whereas tumour growth and metastasis were inhibited in vivo. Several mechanisms of action are possible but inhibition of matrix metalloprotease activity, reduced expression of vascular endothelial growth factor and interference with the renin-angiotensin system were demonstrated by the experimental studies. In this paper we review the laboratory investigations and epidemiological studies on the anti-cancer actions of ACEi and present a summary of the evidence regarding the potential use of ACEi in cancer treatment.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Habitual physical activity and estradiol levels in women of reproductive age.

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.

Adipose Tissue↗

PubMed2025

Gene-environment interaction analysis in atopic eczema: evidence from large population datasets and modelling in vitro.

BACKGROUND: Environmental factors play a role in the pathogenesis of complex traits including atopic eczema (AE) and a greater understanding of gene-environment interactions (G*E) is needed to define pathomechanisms for disease prevention. We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors. We tested for replication using a further 10 studies and in vitro modelling to independently assess findings. RESULTS: The discovery analysis showed suggestive evidence for interaction (p<0.05) between 7 environmental factors (antibiotic use, cat ownership, dog ownership, breastfeeding, elder sibling, smoking and washing practices) and at least one established variant for AE, 14 interactions in total (maxN=25,339). In replication analysis (maxN=252,040) dog exposure*rs10214237 (on chromosome 5p13.2 near IL7R) was nominally significant (ORinteraction=0.91 [0.83-0.99] P=0.025), with a risk effect of the T allele observed only in those not exposed to dogs. A similar interaction with rs10214237 was observed for siblings in the discovery analysis (ORinteraction=0.84[0.75-0.94] P=0.003), but replication analysis was under-powered ORinteraction=1.09[0.82-1.46]). Rs10214237 homozygous risk genotype is associated with lower IL-7R expression in human keratinocytes, and dog exposure modelled in vitro showed a differential response according to rs10214237 genotype. CONCLUSIONS: Interaction analysis and functional assessment provide evidence that early-life dog exposure may modify the genetic effect of rs10214237 on AE via IL7R, supporting observational epidemiology showing a protective effect for dog ownership. The lack of evidence for other G*E studied here implies that only weak effects are likely to occur.

Atopic eczema↗

PubMed2006

Epidemiology and reporting of randomized trials employing re-randomization of patient groups: a systematic survey.

Trials employing re-randomization of some or all participants provide opportunities for determining optimal dosing and dosing schedules, potential disease modifying effects, direct comparisons between drugs, and salvage therapy for patients failing their assigned treatments. To date, no data exists about their prevalence, epidemiology, or quality. We undertook a systematic review of all trials re-randomizing patients. Using explicit search criteria, we searched 11 electronic databases independently, in duplicate. We additionally searched pharmaceutical company websites for unpublished studies. We extracted data on the epidemiology of trials, year published, characteristics of the purpose of the re-randomization, what groups of patients were re-randomized, and methodological issues, including allocation, concealment, sequence generation, blinding, intention to treat, and appropriate sample size calculations. We found 65 trials. All trials were reported in English. Of these, 21 employed re-randomization to determine optimal dosing, 8 for optimal dose-scheduling, 3 for salvage therapy, 0 for estimating disease modifying effects, 24 as direct comparison trials, 9 as standard efficacy trials--that did not require re-randomization, and 3 as withdrawal of treatment trials. The median sample size of the period prior to re-randomization is 180 [interquartile range (IQR) 83-480] and after re-randomization is 104 [IQR 36 to 246]. Studies lost a median of 8% of eligible patients from period 1 to period 2 [IQR 0 to 17]. Studies were published between 1975 and 2005, with the vast majority (71%) published since 1995. The findings of our review indicate that trials employing re-randomization are relatively rare, have poor reporting of important methodological features, and, in some circumstances, fail to take advantage of the benefits that re-randomization can permit.

Dose-Response Relationship, Drug↗

PubMed1988

Morbidity as a focus of preventive health care in the elderly.

The broad spectrum of preventive health concerns in the elderly ranges from incident disease to prevalent disease to the effect (sequelae) of disease. A major component of the burden of illness for the elderly derives from prevalent chronic disease. For a substantial impact on this burden, unique preventive health care strategies specific to the elderly need to be clearly formulated and tested. These strategies must include as a goal the prevention of disability and the maintenance of functioning. Current recommendations for periodic health examinations and for preventive health care for the elderly include only minimal components for a geriatric preventive health care approach. The specific content and impact of a full geriatric strategy is yet to be defined. A comprehensive geriatric periodic health examination will ultimately be based on epidemiologic definitions of the issues regarding risk factors, modifiers, and incident and prevalent disease as described above, melded with improved understanding of 1) the dynamics or models of illness in the elderly, 2) meaningful and important outcomes, 3) the points before which intervention will be most effective, and 4) further definition of the problems that contribute most to the burden of illness across the elderly population. The goals of prevention focused on prevalent disease will include attenuating the progression of morbidity, the development of disability, and the incidence of superimposed acute illness and injuries, and maximizing functional autonomy and quality of life in older persons. To accomplish these goals, epidemiology has major contributions to make in understanding the illness burden of an aging population, including 1) defining risk factors and effect modifiers for, and natural history of, disease and associated disability in older persons, 2) defining outcomes meaningful to older persons which express the burden of illness, and 3) identifying critical points before which intervention is efficacious in preventing disability.

Aged↗

PubMed2006

Lycopene intake and prostate cancer risk: effect modification by plasma antioxidants and the XRCC1 genotype.

Lycopene has been associated with reduced prostate cancer risk, although the results of epidemiological studies have varied. We hypothesize that an effect of lycopene may be modified by XRCC1 genotype and other antioxidants. We used a food-frequency questionnaire to assess lycopene intake in a case-control study of prostate cancer in North Carolina. Plasma alpha-tocopherol and beta-carotene levels were measured using high-performance liquid chromatography. XRCC1 genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism. The final dataset included 77 cases and 174 controls with complete questionnaires, genotyping, and plasma analyses. Among men with the Arg/Arg genotype at codon 399, odds ratios (ORs) for prostate cancer risk associated with medium (732-1,529 microg/day) and high (>1,529 microg/day) lycopene intake were 0.59 (95% confidence interval = 0.23-1.50) and 0.21 (0.06-0.71), respectively (P(trend) < 0.01). Similar analyses for persons with Arg/Gln or Gln/Gln genotypes produced null results. Above-median (1,048 microg/day) lycopene intake combined with above-median levels of alpha-tocopherol and beta-carotene was associated with an OR of 0.11 (0.02-0.65) among men with the Arg/Arg genotype but not those with at least one Gln allele (P(interaction) = 0.01). Although limited by small sample size, these findings indicate that the association between lycopene and prostate cancer is complex and may be modified by other antioxidants and by XRCC1 genotype.

Aged↗

PubMed1999

Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns.

The results of previous epidemiologic research on the possible association between maternal smoking during pregnancy and risk of oral clefts in offspring have been inconsistent. This may be due in part to methodological limitations, including imprecise measurement of tobacco use, failure to consider etiologic heterogeneity among types of oral clefts, and confounding. This analysis, based on a large case-control study, further evaluated the effect of first trimester maternal smoking on oral facial cleft risk by examining the dose-response relationship according to specific cleft type and according to whether or not additional malformations were present. A number of factors, including dietary and supplemental folate intake and family history of clefts, were evaluated as potential confounders and effect modifiers. Data on 3,774 mothers interviewed between 1976 and 1992 by the Slone Epidemiology Unit Birth Defects Study were used. Study subjects were actively ascertained from sites in areas around Boston, Massachusetts and Philadelphia, Pennsylvania; the state of Iowa; and southeastern Ontario, Canada. Cases were infants with isolated defects--cleft lip alone (n = 334), cleft lip and palate (n = 494), or cleft palate alone (n = 244)--and infants with clefts plus (+) additional malformations: cleft lip+ (n = 58), cleft lip and palate+ (n = 140), or cleft palate+ (n = 209). Controls were infants with defects other than clefts, excluding defects possibly associated with maternal cigarette use. There were no associations with maternal smoking for any oral cleft group, except for a positive dose response among infants with cleft lip and palate+ (for light smokers, odds ratio (OR) = 1.09 (95% confidence interval (CI): 0.6, 1.9); for moderate smokers, OR = 1.84 (95% CI: 1.2, 2.9); and for heavy smokers, OR = 1.85 (95% CI: 1.0, 3.5), relative to nonsmokers). This finding may be related to the additional malformations rather than to the cleft itself.

Abnormalities, Multiple↗

PubMed2004

Insulin-like growth factor (IGF)-I and IGF-binding protein 3 and the risk of premenopausal breast cancer: a meta-analysis of literature.

Biologic evidence suggests substantial effect of insulin-like growth factor (IGF)-I in mammary cell carcinogenesis. However, controversy remains regarding the association between circulating IGF-I levels and the risk of premenopausal breast cancer in epidemiologic studies. In addition, the association of IGF-binding protein (IGFBP)-3, which binds with and modifies the effect of IGF-I, is unclear. To clarify these associations, we performed a meta-analysis of all the published studies. A systematic review of literature was conducted. Eligible study designs were nested case-control and population-based case-control studies that give estimates for menopausal women. The studies published between January 1990 and March 2003 were obtained from Medline. We obtained 7 studies, consisting of 688 premenopausal incident breast cancer cases and 1,366 controls, for our final evaluation. Summary statistics were odds ratios (ORs) comparing the highest and the lowest levels of IGF-I and IGFBP-3 adjusted for confounders other than IGF-I or IGFBP-3. There was neither evidence of heterogeneity between studies nor evidence of publication bias. The confounders considered and the contrast used for the ORs were the major source of variation. The subjects with higher circulating levels of IGF-I had marginally significant increased risk of breast cancer with an OR of 1.74 (95% CI = 0.97-3.13; p = 0.06). No significant difference was observed for IGFBP-3 group (OR = 1.60; 95% CI = 0.84-3.02; p = 0.15). In conclusion, we found a marginally significant association between circulating IGF-I levels and the risk of premenopausal breast cancer.

Adult↗

PubMed1996

Assessment of mood state in patients undergoing electroconvulsive therapy: the utility of visual analog mood scales developed for cognitively impaired patients.

Reliable, valid, and brief measures of mood state are essential to the evaluation of electroconvulsive therapy (ECT) efficacy. However, existing measures of mood state may be inappropriate for patients with transient cognitive impairment. Stern and colleagues have recently developed a set of Visual Analog Mood Scales (VAMS) for use in neurologically impaired patients. These brief scales (including measures of sad, confused, afraid, happy, tired, angry, and energetic states) are easily administered and have documented reliability and validity in neurologically impaired patients and in healthy adult and geriatric samples. In the present study, we assessed the validity and sensitivity of the VAMS to detect ECT-related mood change. Twenty-five inpatients who were diagnosed with major depressive episode and referred for ECT were administered the VAMS and the Hamilton Depression Rating Scale (HDRS) both pre- and post-ECT. Results indicate that the VAMS are as sensitive to the therapeutic effects of ECT as is the more lengthy and verbally demanding HDRS. In addition, the VAMS were highly correlated with the clinician's Clinical Global Improvement rating and the patient's self-report using a modified Center for Epidemiological Studies-Depression scale. The VAMS are brief, reliable scales that are sensitive to the treatment effects of ECT and that are appropriate for patients with transient cognitive impairment.

Adult↗

PubMed1988

Guinea worm disease in Northern Uganda: a major public health problem controllable through an effective water programme.

A modified cluster survey was conducted in northwestern Uganda in 1984 to provide descriptive epidemiological data on dracunculiasis in a water programme target area. A total of 2014 people participated from 58 randomly selected clusters. Interviewers elicited information on age and sex of household members, number, date of emergence and location of Guinea worms, and type of and distance from water source in an endemic area. The survey yielded an incidence rate of 193 cases/1000 people per year, and a prevalence rate of 43 active cases/1000. Respondents who reported using ponds, reservoirs, valley tanks or rivers as their primary water source had the highest attack rates; those using boreholes, the lowest. Adolescents and adults differed little in risk, but the disease was less common among young children. Guinea worm disease displayed a bimodal seasonal pattern. We concluded that the survey method used for determining dracunculiasis incidence was appropriate in this setting. The incidence of this disease may be significantly reduced in Uganda through the country's commitment to the International Drinking Water Supply and Sanitation Decade.

Adolescent↗

PubMed2006

Development of real-time reverse transcriptase PCR assays to detect and serotype dengue viruses.

Serotyping dengue virus (DENV) from suspect human specimens is crucial for developing sound epidemiological control measurements early in the transmission season and for effective patient management. We modified DENV consensus D1 (mD1) and serotype-specific TS2 (mTS2) and redesigned serotype-specific TS1 (rTS1) and TS4 (rTS4) as described previously in the conventional capsid and premembrane gene (C-prM) protocol (R. S. Lanciotti, C. H. Calisher, D. J. Gubler, G.-J. Chang, A. V. Vorndam, J. Clin. Microbiol. 30:545-551, 1992). In addition, we designed two new sets of amplimers and probes, located at nonstructural protein 5 (NS5) and the 3' noncoding region (3'NC) of DENV. The NS5 protocol utilizes two flaviviral consensus outer amplimers (mFU1 and CFD2) and four dengue virus serotype-specific TaqMan fluorogenic probes. The 3'NC protocol uses two DENV consensus amplimers, DC10418 and CDC10564. The conventional gel-based, heminested detection method was adapted for the C-prM protocol for detecting and serotyping dengue viruses. In addition, we developed the real-time SYBR green I and postamplification melting temperature curve analysis for the mD1/TS and 3'NC protocols using identical amplification conditions. The NS5 amplimer/probe set was formulated as a one-tube, multiplex, real-time reverse transcriptase PCR for serotype identification. Three sets of amplimers and probes were verified for their specificity in tests with yellow fever, Japanese encephalitis, St. Louis encephalitis, and West Nile viruses; optimized against 109 DENV strains; and validated for detection of the virus in sera from two different panels of acute-phase human dengue serum specimens and one panel of virus isolates from dengue patients' serum specimens. Clinical evaluation by two separate laboratories indicated that the C-prM was more sensitive (100%) than the NS5 (91%) or the 3'NC (91%) protocol.

3' Untranslated Regions↗

PubMed1994

Violence and women's health. The role of epidemiology.

Survival, a basic indicator of health, indicates that violence is a threat to the health of women. Furthermore, the quality of women's lives is compromised by the threat of violence, which creates a sense of chronic endangerment. "Stranger danger" is a misplaced emphasis; community-based investigations in the past decade have underscored that women are at highest risk of homicide, physical assault, and sexual assault at the hands of a man they know, often their husband or male intimate. Potential contributions of the science of epidemiology are identified and the relative absence of epidemiologists working in the field is noted. Violence against women may be an important, although often ignored, confounding variable or effect modifier in studies of women's health.

Adolescent↗