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Confounding
Kinds of Confounding Terms modified by Confounding Selected AbstractsABORTION AND SUBSTANCE USE: CAUSE OR CONFOUNDING?ADDICTION, Issue 1 2009PREBEN AAVITSLAND No abstract is available for this article. [source] ABORTION, SUBSTANCE USE AND CONFOUNDING: A REPLY TO AAVITSLAND (2009)ADDICTION, Issue 1 2009WILLY PEDERSEN No abstract is available for this article. [source] A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factorsGENETIC EPIDEMIOLOGY, Issue 8 2009Huaqing Zhao Abstract Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=,0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors. Genet. Epidemiol. 33:679,690, 2009. © 2009 Wiley-Liss, Inc. [source] The standard of neutrality: still flapping in the breeze?JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 7 2010S. R. PROULX Abstract Neutrality plays an important role as a null model in evolutionary biology. Recent theoretical advances suggest that neutrality is not a unitary concept, and we identify three distinct forms of neutrality. Eu-neutrality means that types do not differ in any measurable way and is thus the idealized form of neutrality. However, individuals or species that do differ in important ways can behave neutrally under some circumstances, both broadening and complicating the applicability of the concept of neutrality. Our second two types of neutrality address two quite different forms of context-dependent neutrality. Circum-neutrality means that two character states have the same direct effect on fitness but do not evolve neutrally because of differences in their circumstances. Iso-neutrality means that two types are equivalent in some population or ecological contexts but not in others, producing an isocline. Confounding of these different definitions has created significant confusion about which models are truly neutral, why some models behave neutrally even when there are large differences in reproductive outputs, and what these different views of neutrality mean to practicing biologists. These complications call into question the acceptance of neutral models as null models and suggest that a better approach is to compare the predictions of models that differ in sources of stochasticity and degree of selection. [source] Impact of Collaborative Management and Early Admission in Labor on Method of DeliveryJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 2 2003Debra J. Jackson senior researcher Objective: This study compared the effects of early admission in labor and perinatal care provider on delivery method. Higher spontaneous vaginal delivery rates for certified nurse midwives as compared with physicians have been reported in observational studies and randomized clinical trials. Certified nurse midwives, with their more expectant approach to labor management, would be expected to admit women later in labor than obstetricians. Methods: Prospective cohort study of 2,196 low-risk pregnancies, with singleton, vertex infants admitted in spontaneous labor. Independent and joint effects of perinatal care provider and cervical dilation at admission on delivery method were evaluated. Confounding was addressed using restriction and multiple regression. Results: Fewer (23.4%) women in collaborative care were admitted in early labor (< 4 cm cervical dilation) than women managed by obstetricians (95% CI =,27.6 to ,19.2). Obstetrician care had 9% to 30% fewer spontaneous vaginal deliveries. Women admitted early in labor also had 6% to 34% fewer spontaneous vaginal deliveries. Evaluation of joint effects suggested that interaction between obstetrician provider and earlier admission increased the risk of operative delivery. Conclusion: Later admission in labor (at 4 cm or greater cervical dilation) and management of perinatal care by certified nurse midwives in collaboration with obstetricians increased the rate of spontaneous vaginal delivery in low-risk women. [source] Significance of hypocarbia in the development of periventricular leukomalacia in preterm infantsPEDIATRICS INTERNATIONAL, Issue 3 2004Christina Giannakopoulou AbstractBackground:,Despite rapid advances in the management of preterm infants, periventricular leukomalacia (PVL) remains a considerable problem in neonatal intensive care. The aim of this study was to determine whether hypocarbia is associated with the development of PVL in mechanically ventilated, preterm infants and to emphasize the importance of avoiding this disturbance. Methods:,The authors evaluated 52 mechanically ventilated infants with a gestational age of <34 weeks, who exhibited hypocarbia in the first three postnatal days (lowest carbon dioxide tension being <25 mmHg). These infants were then compared with 52 infants in a control group not exhibiting hypocarbia, matched for birthweight and gestational age. A diagnosis of PVL was made on the basis of the results of cranial ultrasonography. Confounding factors potentially associated with the development of PVL were controlled in logistic regression analyses. Results:,Of the 52 mechanically ventilated preterm infants with hypocarbia, 10 (19.2%) developed cystic PVL, and six (11.5%) developed periventricular echodensity. Of the 52 infants in the control group only two (3.8%) developed cystic PVL, and one (1.9%) infant developed periventricular echodensity. The authors observed no significant differences in other prenatal and perinatal risk factors between the two groups. Conclusion:,Hypocarbia in mechanically ventilated preterm infants during the first days of life is suggested as being an independent predictor of PVL, predisposing these infants to subsequent neurodevelopmental delay. [source] Methodological issues in the epidemiological study of the teratogenicity of drugsCONGENITAL ANOMALIES, Issue 2 2005Bengt A.J. Källén ABSTRACT The review presented here discusses and exemplifies problems in epidemiological studies of drug teratogenesis according to methodology: case,control studies, cohort studies, or total population studies. Sources of errors and the possibility of confounding are underlined. The review stresses the caution with which conclusions have to be drawn when exposure data are retrospective or other possible bias exists. It also stresses the problem with the multiple testing situation that is usually present in the studies. It is therefore difficult to draw any firm conclusion from single studies and still more difficult to draw conclusions on causality. As randomized studies are in most cases out of the question, one has to rely on the type of studies which can be made, but the interpretation of the results should be cautious. The ideal study, next to a randomized one, is a large prospective study with detailed exposure information and detailed and unbiased outcome data. Even so, such a study can mainly be used for identifying possible associations which have to be verified or rejected in new studies. Nearly every finding of a risk increase, if not extremely strong, should only be regarded as a tentative signal to be tested in independent studies. [source] Insulin treatment and cardiovascular disease; friend or foe?DIABETIC MEDICINE, Issue 2 2005A point of view Abstract Background Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. Summary of comment Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. Conclusion Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area. [source] Early weaning and alcohol disorders in offspring: biological effect, mediating factors or residual confounding?ADDICTION, Issue 8 2009Rosa Alati ABSTRACT Aims This study explores associations between early weaning and alcohol use disorders in youth and mechanisms by which these associations may operate. Design We used data from the Mater University Study of Pregnancy and its outcomes, an Australian birth cohort study based in Brisbane. Setting and participants: This study is based on a subsample of 2370 participants for whom complete data were available at age 21 years. Length and method of breastfeeding were assessed at 6 months. Measurements Alcohol use disorders were assessed at age 21 using the life-time version of the Composite International Diagnostic Interview,computerized version (CIDI-Auto). We adjusted for maternal age, marital status, education, alcohol, tobacco use, anxiety, depression and maternal attitudes towards the baby. Attention Deficit and Hyperactivity Disorders (ADHD) and Intellect Quotient (IQ) were measured with the Child Behaviour Checklist (5 years) and the Ravens SM (14 years), respectively. Findings Those who had been weaned within 2 weeks of being born and breastfed at regular intervals were at increased risk of meeting criteria for alcohol use disorders at age 21 [odds ratio (OR) 1.71, 95% confidence interval (CI):1.07, 2.72]. Conclusion This study confirms a small but robust association between early weaning and increased risk of alcohol use disorders. [source] Early pubertal maturation in the prediction of early adult substance use: a prospective studyADDICTION, Issue 1 2009Mohammad R. Hayatbakhsh ABSTRACT Aims To examine whether self-reporting a later stage of pubertal development in early adolescence predicts young adults' use of illicit drugs. Design Population-based prospective birth cohort study. Setting Follow-up of a cohort of mothers and their children, recruited between 1981 and 1983. Participants Cohort of 2710 young adults who completed a self-report questionnaire about their use of cannabis and amphetamines at the 21-year follow-up. Measurements Young adults' use of cannabis and amphetamines were measured at the 21-year follow-up. Stage of pubertal development was assessed at the 14-year follow-up. Potential confounding and mediating variables were assessed between birth and when the child was 14 years. Findings Of 2710 young adults, 49.9% (47.3 females and 52.7% males) reported that they had used cannabis and 21.0% (18.9% females and 23.3% males) reported that they had used amphetamines and cannabis by 21 years. In multivariate analyses, adolescents with a later stage of puberty were more likely to use cannabis or amphetamines in young adulthood. This association was not confounded by mother's education or child's gender and age. Part of the relationship was explained by the higher frequency of child externalizing behaviour at 14 years. Conclusions The findings warrant further attention to puberty as a sensitive period in an individual's development. With regard to prevention, there is a need to understand more about the pathways between pubertal development, child behaviour problems and substance use. [source] Analytical ecological epidemiology: exposure,response relations in spatially stratified time seriesENVIRONMETRICS, Issue 6 2009Hagen Scherb Abstract An important task of environmental research is the investigation of a possible causal relationship between exposure and the frequency of a biologic trait. Major industrial accidents provide examples where the exposure status of large populations may change considerably within relatively short time intervals of days or weeks (e.g. Seveso herbicide plant explosion, Chernobyl Nuclear Power Plant catastrophe). Therefore, purely temporal change-points may be tested in time series of appropriate public health indicators (e.g. mortality, morbidity, sex ratio at birth). If, in addition, the spatial contamination is strong and variable enough and can be identified with sufficient precision at the level of regional units (e.g. districts), then a spatial-temporal approach makes sense. This essentially means that a global time trend model is adjusted for region-specific trend functions, allowing for local or global temporal jumps or broken sticks (change-points) at certain points in time. The local jump heights may be tested for associations with local exposure (exposure,response relation), and all other characteristics in the data that vary with locality and in time are automatically accounted for, thus minimizing confounding. Spatial-temporal approaches may help to strengthen the evidence of possible causal relationships. As an example, the human sex ratio at birth in several European countries before and after the Chernobyl Nuclear Power Plant accident was investigated. A long-term chronic impact of radioactive fallout on the secondary sex ratio has been found. Copyright © 2008 John Wiley & Sons, Ltd. [source] Seasonal confounding and residual correlation in analyses of health effects of air pollutionENVIRONMETRICS, Issue 4 2007Isabella R. Ghement Abstract To investigate the health effects of air pollution via a partially linear model, one must choose an appropriate amount of smoothing for accurate estimation of the linear pollution effects. This choice is complicated by the dependencies between the various covariates and by the potential residual correlation. Most existing approaches to making this choice are inadequate, as they neither target accurate estimation of the linear pollutant effects nor handle residual correlation. In this paper, we illustrate two new adaptive and objective methods for determining an appropriate amount of smoothing. We construct valid confidence intervals for the linear pollutant effects, intervals that account for residual correlation. We use our inferential methods to investigate the same-day effects of PM10 on daily mortality in two data sets for the period 1994 to 1996: one collected in Mexico City, an urban area with high levels of air pollution, and the other collected in Vancouver, British Columbia, an urban area with low levels of air pollution. For Mexico City, our methodology does not detect a PM10 effect. In contrast, for Vancouver, a PM10 effect corresponding to an expected 2.4% increase (95% confidence interval ranging from 0.0% to 4.7%) in daily mortality for every 10,µg/m3 increase in PM10 is identified. Copyright © 2006 John Wiley & Sons, Ltd. [source] Autosomal Dominant Inheritance of Centrotemporal Sharp Waves in Rolandic Epilepsy FamiliesEPILEPSIA, Issue 12 2007Bhavna Bali Summary Purpose: Centrotemporal sharp (CTS) waves, the electroencephalogram (EEG) hallmark of rolandic epilepsy, are found in approximately 4% of the childhood population. The inheritance of CTS is presumed autosomal dominant but this is controversial. Previous studies have varied considerably in methodology, especially in the control of bias and confounding. We aimed to test the hypothesis of autosomal dominant inheritance of CTS in a well-designed family segregation analysis study. Methods: Probands with rolandic epilepsy were collected through unambiguous single ascertainment. Siblings in the age range 4,16 years underwent sleep-deprived EEG; observations from those who remained awake were omitted. CTS were rated as present or absent by two independent observers blinded to the study hypothesis and subject identities. We computed the segregation ratio of CTS, corrected for ascertainment. We tested the segregation ratio estimate for consistency with dominant and recessive modes of inheritance, and compared the observed sex ratio of those affected with CTS for consistency with sex linkage. Results: Thirty siblings from 23 families underwent EEG examination. Twenty-three showed evidence of sleep in their EEG recordings. Eleven of 23 recordings demonstrated CTS, yielding a corrected segregation ratio of 0.48 (95% CI: 0.27,0.69). The male to female ratio of CTS affectedness was approximately equal. Conclusions: The segregation ratio of CTS in rolandic epilepsy families is consistent with a highly penetrant autosomal dominant inheritance, with equal sex ratio. Autosomal recessive and X-linked inheritance are rejected. The CTS locus might act in combination with one or more loci to produce the phenotype of rolandic epilepsy. [source] Tests of causal linkages between cannabis use and psychotic symptomsADDICTION, Issue 3 2005David M. Fergusson ABSTRACT Aim To examine possible causal linkages between cannabis use and psychosis using data gathered over the course of a 25-year longitudinal study. Design A 25-year longitudinal study of the health, development and adjustment of a birth cohort of 1265 New Zealand children (635 males, 630 females). Setting The Christchurch Health and Development Study, a general community sample. Participants A total of 1055 participants from the Christchurch Health and Development Study (CHDS) cohort for whom data on cannabis use and psychotic symptoms were available on at least one occasion from 18, 21 and 25 years. Measurements As part of this study, data were gathered on frequency of cannabis use and psychotic symptoms at ages 18, 21 and 25 years. Findings Regression models adjusting for observed and non-observed confounding suggested that daily users of cannabis had rates of psychotic symptoms that were between 1.6 and 1.8 times higher (P < 0.001) than non-users of cannabis. Structural equation modelling suggested that these associations reflected the effects of cannabis use on symptom levels rather than the effects of symptom levels on cannabis use. Conclusions The results of the present study add to a growing body of evidence suggesting that regular cannabis use may increase risks of psychosis. The present study suggests that: (a) the association between cannabis use and psychotic symptoms is unlikely to be due to confounding factors; and (b) the direction of causality is from cannabis use to psychotic symptoms. [source] Effects of sand sedimentation on the macroinvertebrate fauna of lowland streams: are the effects consistent?FRESHWATER BIOLOGY, Issue 1 2006BARBARA J. DOWNES Summary 1. In lowland streams sand sedimentation can produce sand slugs: very slow moving, discrete volumes of sand that are created episodically. Hypothetically, such sedimentation causes losses of habitat and fauna but little is known about the effects of sand slugs. In south-eastern Australia sand slugs are widespread, especially in streams with granitic catchments. 2. This study in north-central Victoria was centred on three streams that rise in the Strathbogie Ranges and flow out onto lowland plains, where they contain sand slugs. Below the sand slugs, the streams are slow-flowing ,chains of ponds' with a clay streambed. To correct for potential upstream-downstream confounding of comparisons, two unsanded, nearby streams were included as potential controls. Habitat measurements and faunal samples were taken in Spring 1998, from three sites in the sand slug and three sites in the clay-bed, downstream sections of each impacted stream, as well as from three sites in commensurate upstream and downstream sections of the control streams. 3. The sand-slugged sections had significantly higher velocities, shallower depths and less coarse woody debris than the unsanded downstream sections. Macroinvertebrate taxon richness and abundance showed some significant differences between the sand and clay sections compared with commensurate up- and downstream locations in the control streams. Effects were not uniform, however. In Castle Creek there were no significant differences between the sand and clay sections, in Pranjip-Ninemile Creek taxon richness and abundances were higher in sand than in the clay sections, whereas in Creightons Creek the ,expected' results of lower taxon richness and abundance in the sand were found. 4. Of the 40 most common taxa, only eight provided a clear signal related to sand and, of these, one (Slavina sp.) occurred only in the sand slugs, whereas the other seven had significantly higher numbers in the clay sections. Of these taxa, three were ostracods, three were chironomids and one was a tubificid oligochaete, all taxa that live in detritus-rich environments. Overall faunal composition did not show a clear distinction though, between sandy and clay sites. The sand slug community of Creightons Creek was very different from the other communities in all of the streams. There were clear differences in community composition between the sand-affected and the control streams, even for downstream, clay sections, suggesting they cannot act as controls for the impacted sections of the sand-slugged streams. 5. Differences between streams within categories (particularly between sand-slugged streams) and between sites in the same section of stream accounted for most of the variability in species richness and the abundances of each of the 40 most common taxa. That finding was repeated when data were examined at the family level, for both numbers of families per sample and collated lists of families occurring across sites. These results strongly suggest that the effects of sedimentation by sand slugs do not overwhelm background variation in macroinvertebrate density and diversity. Overall the results suggest that many taxa may respond individually, and that there is much variation between sand-affected streams even over relatively small (approximately <10 km) spatial scales. [source] Sibship analysis of associations between SNP haplotypes and a continuous trait with application to mammographic densityGENETIC EPIDEMIOLOGY, Issue 4 2010J. Stone Abstract Haplotype-based association studies have been proposed as a powerful comprehensive approach to identify causal genetic variation underlying complex diseases. Data comparisons within families offer the additional advantage of dealing naturally with complex sources of noise, confounding and population stratification. Two problems encountered when investigating associations between haplotypes and a continuous trait using data from sibships are (i) the need to define within-sibship comparisons for sibships of size greater than two and (ii) the difficulty of resolving the joint distribution of haplotype pairs within sibships in the absence of parental genotypes. We therefore propose first a method of orthogonal transformation of both outcomes and exposures that allow the decomposition of between- and within-sibship regression effects when sibship size is greater than two. We conducted a simulation study, which confirmed analysis using all members of a sibship is statistically more powerful than methods based on cross-sectional analysis or using subsets of sib-pairs. Second, we propose a simple permutation approach to avoid errors of inference due to the within-sibship correlation of any errors in haplotype assignment. These methods were applied to investigate the association between mammographic density (MD), a continuously distributed and heritable risk factor for breast cancer, and single nucleotide polymorphisms (SNPs) and haplotypes from the VDR gene using data from a study of 430 twins and sisters. We found evidence of association between MD and a 4-SNP VDR haplotype. In conclusion, our proposed method retains the benefits of the between- and within-pair analysis for pairs of siblings and can be implemented in standard software. Genet. Epidemiol. 34: 309,318, 2010. © 2009 Wiley-Liss, Inc. [source] Centralizing the non-central chi-square: a new method to correct for population stratification in genetic case-control association studiesGENETIC EPIDEMIOLOGY, Issue 4 2006Prakash Gorroochurn Abstract We present a new method, the ,-centralization (DC) method, to correct for population stratification (PS) in case-control association studies. DC works well even when there is a lot of confounding due to PS. The latter causes overdispersion in the usual chi-square statistics which then have non-central chi-square distributions. Other methods approach the non-centrality indirectly, but we deal with it directly, by estimating the non-centrality parameter , itself. Specifically: (1) We define a quantity ,, a function of the relevant subpopulation parameters. We show that, for relatively large samples, , exactly predicts the elevation of the false positive rate due to PS, when there is no true association between marker genotype and disease. (This quantity , is quite different from Wright's FST and can be large even when FST is small.) (2) We show how to estimate ,, using a panel of unlinked "neutral" loci. (3) We then show that ,2 corresponds to , the non-centrality parameter of the chi-square distribution. Thus, we can centralize the chi-square using our estimate of ,; this is the DC method. (4) We demonstrate, via computer simulations, that DC works well with as few as 25,30 unlinked markers, where the markers are chosen to have allele frequencies reasonably close (within ±.1) to those at the test locus. (5) We compare DC with genomic control and show that where as the latter becomes overconservative when there is considerable confounding due to PS (i.e. when , is large), DC performs well for all values of ,. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Do nutrition labels improve dietary outcomes?,HEALTH ECONOMICS, Issue 6 2008Jayachandran N. Variyam Abstract The disclosure of nutritional characteristics of most packaged foods became mandatory in the United States with the implementation of the Nutrition Labeling and Education Act (NLEA) in 1994. Under the NLEA regulations, a ,Nutrition Facts' panel displays information on nutrients such as calories, total and saturated fats, cholesterol, and sodium in a standardized format. By providing nutrition information in a credible, distinctive, and easy-to-read format, the new label was expected to help consumers choose healthier, more nutritious diets. This paper examines whether the disclosure of nutrition information through the mandatory labels impacted consumer diets. Assessing the dietary effects of labeling is problematic due to the confounding of the label effect with unobserved label user characteristics. This self-selection problem is addressed by exploiting the fact that the NLEA exempts away-from-home foods from mandatory labeling. Difference-in-differences models that account for zero away-from-home intakes suggest that the labels increase fiber and iron intakes of label users compared with label nonusers. In comparison, a model that does not account for self-selection implies significant label effects for all but two of the 13 nutrients that are listed on the label. Published in 2007 by John Wiley & Sons, Ltd. [source] Is the Association Between Helicobacter pylori and Gastric Cancer Confined to CagA-Positive Strains?HELICOBACTER, Issue 3 2004Maria Held ABSTRACT Background., Infection with Helicobacter pylori is associated with an increased risk of gastric cancer. Several studies have indicated that the association differs with strain type. We aimed to find out if infection with strains lacking the virulence factor CagA is linked to gastric cancer risk. Materials and methods., In a hospital-based case,control study, we collected sera from 100 case patients with a newly diagnosed gastric adenocarcinoma and 96 control patients with diseases unrelated to H. pylori status. Antibodies to H. pylori were analyzed by enzyme-linked immunosorbent assay (ELISA), and antibodies to CagA were detected by immunoblot. Logistic regression was used to obtain odds ratios (ORs) as estimates of relative risk, adjusted for potential confounding. Results., Among the case patients, 81% were ELISA positive and 86% had antibodies to CagA. The corresponding numbers among the controls were 58% and 55%, respectively. ELISA positivity was associated with an increased risk of gastric adenocarcinoma compared to ELISA negativity (OR for gastric cancer regardless of site 3.9, 95% CI 1.9,8.2). The OR was 7.4 (95% CI 3.3,16.6) for CagA-positive relative to CagA-negative subjects. Among ELISA-positive subjects the presence of CagA antibodies increased the risk 3.6 times (95% CI 1.2,11.1). ELISA-positive CagA-negative infections were associated with a fourfold increased risk (OR = 4.2, 95% CI 1.0,17.0) compared to no infection (ELISA-negative and CagA-negative). Conclusions., Although patients with antibodies to CagA have the greatest risk of developing gastric cancer, those with CagA-negative infections run a significantly greater risk than uninfected persons. [source] Critical review of epidemiological studies of the association between smoking and non-Hodgkin's lymphomaHEMATOLOGICAL ONCOLOGY, Issue 2 2001Hedley G. Peach Abstract Smoking has been suggested to increase the risk of non-Hodgkin's lymphoma (NHL) but the results of epidemiological studies have been inconsistent. The aim of this work was to assess whether the findings of individual studies might have arisen by chance, bias or confounding and whether any associations found between smoking and NHL represent cause-and-effect. Reports of the association between smoking and NHL were identified from Medline. Confidence intervals on relative risks and odds ratios, use of multiple comparisons, and information on source, direction, actual existence and size of potential biases and confounding and features of any associations were abstracted. Four out of five cohort studies found no association between current smoking and NHL but three may have been biased against doing so. One found an association with follicular lymphoma but without a convincing exposure,risk gradient. The fifth found a strong association and an exposure,response gradient with ever smoking but excluded living cases from the end-point. Only one study found an association with past smoking which lacked features of causality. Eight out of 14 case,control studies found no association between current and/or past smoking and NHL but five may have been biased against doing so. Of six positive studies, three involved multiple comparisons, the association of one became non-significant after eliminating bias, four did not explore features of causality and one found an association only in heavy smokers, particularly under 45 years old. There are no grounds to reject the null hypothesis but associations should continue to be sought particularly in subgroups of smokers and with NHL subtypes. Copyright © 2001 John Wiley & Sons, Ltd. [source] Coffee drinking and hepatocellular carcinoma risk: A meta-analysis,HEPATOLOGY, Issue 2 2007Francesca Bravi Several studies suggest an inverse relation between coffee drinking and risk of hepatocellular carcinoma (HCC). We conducted a meta-analysis of published studies on HCC that included quantitative information on coffee consumption. Ten studies were retrieved (2,260 HCC cases), including 6 case,control studies from southern Europe and Japan (1551 cases) and 4 cohort studies from Japan (709 cases). The summary relative risk (RR) for coffee drinkers versus non-drinkers was 0.54 (95% confidence interval [CI] 0.38-0.76) for case,control studies and 0.64 (95% CI 0.56-0.74) for cohort studies. The overall RR was 0.59 (95% CI 0.49-0.72), with significant heterogeneity between studies. The overall summary RR for low or moderate coffee drinkers was 0.70 (95% CI 0.57-0.85), and that for high drinkers was 0.45 (95% CI 0.38-0.53). The summary RR for an increase of 1 cup of coffee per day was 0.77 (95% CI 0.72-0.83) from case,control studies, 0.75 (95% CI 0.65-0.85) from cohort studies, and 0.77 (95% CI 0.72-0.82) overall. The consistency of an inverse relation between coffee drinking and HCC across study design and geographic areas weighs against a major role of bias or confounding. Coffee drinking has also been related to reduced risk of other liver diseases, thus suggesting a continuum of the favorable effect of coffee on liver function. However, subjects with liver conditions may selectively reduce their coffee consumption. Conclusion: The present analysis provides evidence that the inverse relation between coffee and HCC is real, though inference on causality remains open to discussion. (HEPATOLOGY 2007.) [source] Caffeine, cognitive failures and health in a non-working community sampleHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 1 2009Andrew P Smith Abstract Rationale Most studies of the effects of caffeine on performance have been conducted in the laboratory and further information is required on the real-life effects of caffeine consumption on cognition. In addition, possible effects of caffeine consumption on a range of health outcomes should also be assessed in these studies to enable cost-benefit analyses to be conducted. Objectives Secondary analyses of a large epidemiological database (N,=,3223 non-working participants, 57% female, with a mean age of 49.6 years, range 17,92 years) were conducted to examine associations between caffeine consumption (mean caffeine consumption was 140,mg/day, range 0,1800,mg) and cognitive failures (errors of memory, attention and action) in a non-working sample. Associations between caffeine consumption and physical and mental health problems were also examined. Methods The study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. Associations between caffeine consumption and frequency of cognitive failures and health outcomes were examined in a sample of non-workers. Results After controlling for possible confounding factors significant associations between caffeine consumption and fewer cognitive failures were observed. Initial analyses suggested that many health variables were associated with regular level of caffeine consumption. However, most of the significant effects of caffeine disappeared when demographic and lifestyle factors were controlled for. Consumption of caffeine was, however, associated with a reduced risk of depression. These effects were also observed in separate analyses examining the source of the caffeine (coffee and tea). Conclusions Overall, the results show that caffeine consumption may benefit cognitive functioning in a non-working population. This confirms earlier findings from working samples. This beneficial effect of caffeine was not associated with negative health consequences. Indeed, consumption of caffeine was found to be associated with a reduced risk of depression. Copyright © 2008 John Wiley & Sons, Ltd. [source] Epidemiologic evaluation of pharmaceuticals with limited evidence of carcinogenicityINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Gary D. Friedman Abstract Thorough review by the International Agency for Research on Cancer (IARC) has resulted in classifying many substances, including pharmaceuticals, as probably or possibly carcinogenic to humans, based on experiments on animals or limited data on humans. We evaluated 9 such pharmaceuticals for evidence of carcinogenicity in patients receiving them in a large medical care program with automated pharmacy records and a cancer registry. Nested case,control analyses were performed in a cohort of 6.5 million subscribers with up to 12 years of follow-up, focusing on cancer sites suggested by previous evidence and other sites with odds ratio of at least 1.50, p < 0.01 and some evidence of dose,response. Unmeasured confounding was estimated in sensitivity analyses. We found some supportive evidence for carcinogenicity of griseofulvin, metronidazole and phenytoin and for the known carcinogen, cyclophosphamide, which was added for validation of our data and analyses. Findings for chloramphenicol, iron-dextran complex, phenoxybenzamine and phenobarbital were essentially non-contributory. Confounding by cigarette smoking and prior thyroid disease could account, respectively, for associations of oxazepam with lung cancer and propylthiouracil with thyroid cancer. Although not definitive, these findings should be considered in the evaluations of these pharmaceuticals. © 2009 UICC [source] CYP1A1 variants and smoking-related lung cancer in San Francisco bay area Latinos and African AmericansINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Margaret R. Wrensch Abstract We examined CYP1A1 T6235C (M1) and A4889G (M2) polymorphisms in San Francisco Bay Area African Americans and Latinos who were newly diagnosed with primary lung cancer from September 1998 to November 2002 and in age-gender-ethnicity frequency-matched controls. Owing mainly to rapid mortality of cases, overall percentages of cases genotyped were 26% and 32% for Latinos and African Americans, respectively. CYP1A1 variants were genotyped for Latinos (104 cases, 278 controls) and African Americans (226 cases, 551 controls). M1 and M2 frequencies in controls were 0.23 and 0.02 for African Americans and 0.38 and 0.29 for Latinos. In Latinos, the overall inverse odds ratio (OR) of 0.51 (95% CI = 0.32,0.81) for M1 variant genotype resulted from an inverse interaction with smoking. Nonsmokers with M1 genotype had a slight elevated OR (1.5; 0.59,3.7), but those with less than 30 or 30 or more pack-year history had 0.20 (0.06,0.70) and 0.21 (0.06,0.81) times (about 1/5) the odds expected if smoking and genotype were independent lung cancer risk factors. African Americans had interactions of similar magnitude that were not statistically significant. Results for M2 were very similar. Inverse interactions of CYP1A1 variants and smoking-associated lung cancer risk in Latinos might be causal, due to undetected bias or confounding, or represent a unique linkage disequilibrium between a new lung cancer locus and CYP1A1 in this highly admixed population. [source] Using spaced retrieval and Montessori-based activities in improving eating ability for residents with dementia,INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 10 2010Li-Chan Lin Abstract Objectives To construct a training protocol for spaced retrieval (SR) and to investigate the effectiveness of SR and Montessori-based activities in decreasing eating difficulty in older residents with dementia. Methods A single evaluator, blind, and randomized control trial was used. Eighty-five residents with dementia were chosen from three special care units for residents with dementia in long-term care facilities in Taiwan. To avoid any confounding of subjects, the three institutions were randomized into three groups: spaced retrieval, Montessori-based activities, and a control group. The invention consisted of three 30,40,min sessions per week, for 8 weeks. Results After receiving the intervention, the Edinburgh Feeding Evaluation in Dementia (EdFED) scores and assisted feeding scores for the SR and Montessori-based activity groups were significantly lower than that of the control group. However, the frequencies of physical assistance and verbal assistance for the Montessori-based activity group after intervention were significantly higher than that of the control group, which suggests that residents who received Montessori-based activity need more physical and verbal assistance during mealtimes. In terms of the effects of nutritional status after intervention, Mini-Nutritional Assessment (MNA) in the SR group was significantly higher than that of the control group. Conclusion This study confirms the efficacy of SR and Montessori-based activities for eating difficulty and eating ability. A longitudinal study to follow the long-term effects of SR and Montessori-based activities on eating ability and nutritional status is recommended. Copyright © 2010 John Wiley & Sons, Ltd. [source] Estimating causal effects from observational data with a model for multiple biasINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 2 2007Michael Höfler Abstract Conventional analyses of observational data may be biased due to confounding, sampling and measurement, and may yield interval estimates that are much too narrow because they do not take into account uncertainty about unknown bias parameters, such as misclassification probabilities. We used a simple, multiple bias adjustment method to estimate the causal effect of social anxiety disorder (SAD) on subsequent depression. A Monte Carlo sensitivity analysis was applied to data from the Early Developmental Stages of Psychiatry (EDSP) study, and bias due to confounding, sampling and measurement was modelled. With conventional logistic regression analysis, the risk for depression was elevated in the presence of SAD only in the older cohort (age 17,24 years at baseline assessment); odds ratio (OR) = 3.06, 95% confidence interval (CI) 1.64,5.70, adjusted for sex and age. The bias-adjusted estimate was 2.01 with interval limits of 0.61 and 9.71. Thus, given the data and the bias model used, there was considerably more uncertainty about the real effect, but the probability that SAD increases the risk for subsequent depression (OR > 1) was 88.6% anyway. Multiple bias modelling, if properly used, reveals the necessity for a better understanding of bias, suggesting a need to conduct larger and more adequate validation studies on instruments that are used to diagnose mental disorders. Copyright © 2007 John Wiley & Sons, Ltd. [source] Amiodarone or Procainamide for the Termination of Sustained Stable Ventricular Tachycardia: An Historical Multicenter ComparisonACADEMIC EMERGENCY MEDICINE, Issue 3 2010Keith A. Marill MD Abstract Objectives:, The objective was to compare the effectiveness of intravenous (IV) procainamide and amiodarone for the termination of spontaneous stable sustained ventricular tachycardia (VT). Methods:, A historical cohort study of consecutive adult patients with stable sustained VT treated with IV amiodarone or procainamide was performed at four urban hospitals. Patients were identified for enrollment by admissions for VT and treatment with the study agents in the emergency department (ED) from 1993 to 2008. The primary measured outcome was VT termination within 20 minutes of onset of study medicine infusion. A secondary effectiveness outcome was the ultimate need for electrical therapy to terminate the VT episode. Major adverse effects were tabulated, and blood pressure responses to medication infusions were compared. Results:, There were 97 infusions of amiodarone or procainamide in 90 patients with VT, but the primary outcome was unknown after 14 infusions due to administration of another antidysrhythmic during the 20-minute observation period. The rates of VT termination were 25% (13/53) and 30% (9/30) for amiodarone and procainamide, respectively. The adjusted odds of termination with procainamide compared to amiodarone was 1.2 (95% confidence interval [CI] = 0.4 to 3.9). Ultimately, 35/66 amiodarone patients (53%, 95% CI = 40 to 65%) and 13/31 procainamide patients (42%, 95% CI = 25 to 61%) required electrical therapy for VT termination. Hypotension led to cessation of medicine infusion or immediate direct current cardioversion (DCCV) in 4/66 (6%, 95% CI = 2 to 15%) and 6/31 (19%, 95% CI = 7 to 37%) patients who received amiodarone and procainamide, respectively. Conclusions:, Procainamide was not more effective than amiodarone for the termination of sustained VT, but the ability to detect a significant difference was limited by the study design and potential confounding. As used in practice, both agents were relatively ineffective and associated with clinically important proportions of patients with decreased blood pressure. ACADEMIC EMERGENCY MEDICINE 2010; 17:297,306 © 2010 by the Society for Academic Emergency Medicine [source] A Population-Based Osteoporosis Screening Program: Who Does Not Participate, and What Are the Consequences?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2004Diana S. M. Buist PhD Objectives: To describe differences in osteoporosis risk factors and rates of fracture and antiresorptive therapy use in women who did and did not participate in an osteoporosis screening program. Setting: Group Health Cooperative, a health maintenance organization in western Washington state. Participants: A total of 9,268 women (aged 60,80) who were not using any antiresorptive therapy were invited to participate in an osteoporosis screening program. This study compares the 35% who participated with the 65% who did not. Design: This observational cohort study of women invited to participate in a randomized, controlled trial of an osteoporosis screening program provided all participants with personalized feedback on their risk of osteoporosis. Some participants also received bone density testing. Automated administrative data were used to examine differences between participants and nonparticipants in fracture outcomes and medication initiation before and after invitation. Results: Baseline fracture rates did not differ between participants and nonparticipants. After age adjustment, nonparticipants had a higher hip fracture rate (14.1 vs 8.3 per 1,000) and a lower rate of initiating any antiresorptive therapy (10.3 vs 17.9 per 100) than participants after an average of 28 to 29 months of follow-up. Conclusion: Participants had reduced hip fracture rates and increased initiation of antiresorptive therapy compared with nonparticipants. It was not possible to determine whether participating in the screening program, unmeasured confounding, or selection bias accounted for differences in hip fracture or therapy initiation rates. These results suggest that women who do not participate in osteoporosis screening should be pursued to idenepsy individuals who could benefit from primary and secondary osteoporosis prevention. [source] Effect of Statin (HMG-Co-A-Reductase Inhibitor) Use on 1-Year Mortality and Hospitalization Rates in Older Patients with Cardiovascular Disease Living in Nursing HomesJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2002Charles B. Eaton MD OBJECTIVES: To quantify the effect of statins on 1-year mortality, hospitalizations, and decline in physical function among patients with cardiovascular disease (CVD) aged 65 and older living in nursing homes. DESIGN: Retrospective cohort study. SETTING: All Medicare/Medicaid certified nursing homes (N = 1,492) in Maine, New York, Mississippi, and South Dakota. PARTICIPANTS: We identified 51,559 older patients with CVD from a population database that merged sociodemographic data and functional, clinical, and drug treatments from more than 300,000 newly admitted nursing home residents from 1992 to 1997. Statin users (n = 1,313) were matched with nonusers (n = 1,313) in the same facilities. MEASUREMENTS: All-cause mortality, hospitalization, combined endpoint of mortality or hospitalization, and decline in physical function were determined at 1 year, and survival analysis was performed. RESULTS: Prevalence of statin use in this frail older cohort with CVD was 2.6%. Statin use varied by age, gender, comorbid condition, medication use, and cognitive and physical function. One-year mortality was 229/1,000 person-years in the statin group and 404/1,000 person-years in the nonusers, with an adjusted hazard rate ratio (HRR) of 0.69, 95% confidence interval (CI) = 0.58,0.81. The estimated number needed to treat was seven (95% CI = 5,13). This association with improved all-cause mortality was evident for women and men and for age groups 75 to 84, and 85 and older. CONCLUSION: Statin therapy is associated with improved clinical outcomes, including reduction in 1-year all-cause mortality, and the combined endpoint of death or hospitalization in a frail older population with CVD. Some caution should be taken in interpreting these results because potential bias from residual confounding could affect these results. [source] Estimation of genetic parameters for canine hip dysplasia in the Swiss Newfoundland populationJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 3 2003E. Dietschi Summary Variance components and genetic parameters for hip dysplasia (HD) in a population of 1372 Newfoundlands were estimated using restricted maximum likelihood method applied to animal models comprising fixed effects of gender, screening expert and HD grading system. All models investigated included a random direct genetic effect, but differed for combinations of random maternal genetic effect, permanent maternal environmental effect and kennel effect. Although kennels had no effect on HD, the permanent maternal environmental effects, however were significant. The results for the maternal genetic effect were ambiguous. These results suggest a confounding of these three random effects. The model that included the fixed effects, the direct genetic effect and the permanent maternal environmental effect was the most parsimonious combined with an optimal fit. The heritability estimated with this model was 0.28 and the proportion of the permanent maternal environmental effect of the phenotypic variance was 0.10. The effects of gender and screening expert were significant but not the one of HD grading system. Zusammenfassung Schätzung genetischer Populationsparameter für die Hüftgelenksdysplasie bei den Neufundländern in der Schweiz In einer Hundepopulation von 1372 Neufundländern wurden für die Hüftgelenksdysplasie mit Hilfe der "restricted maximum likelihood method" Varianzkomponenten und genetische Parameter geschätzt, wobei ein Tiermodell zu Grunde gelegt wurde. Alle verwendeten Modelle enthielten einen zufälligen direkten genetischen Effekt und in unterschiedlichen Kombinationen einen zufälligen maternalen Effekt, einen zufälligen permanent maternalen Umwelteffekt und einen zufälligen Zwinger-Effekt. Als fixe Effekte wurden das Geschlecht, der Auswertungs-Experte und das HD-Einteilungssystem berücksichtigt. Der Zwinger hat keinen Einfluss auf die Hüftgelenksdysplasie, aber der permanent maternale Umwelteffekt ist signifikant. Der maternal genetische Effekt verhält sich je nach Modell unterschiedlich. Diese Resultate legen eine Vermengung dieser drei Effekte nahe. Die beste Anpassung an die Daten zeigt dasjenige Modell, das die fixen Effekte, den direkten genetischen Effekt und den permanent maternalen Umwelteffekt enthält. Die mit diesem Modell geschätzte Heritabilität beträgt 0,28 und der Anteil des permanent maternalen Umwelteffektes an der phänotypischen Varianz 0,10. Das Geschlecht und die Auswertungs-Experten sind signifikant, das HD-Einteilungssystem nicht. [source] | |||||||||||||||||||||||||||||||||||||||||||