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At least 19 recordsLinked to original sources
PubMed2006

Geographic variation in alcohol, drug, and mental health services utilization: what are the sources of the variation?

BACKGROUND: Studies have documented geographic variation in health services utilization over a range of medical, surgical, and psychiatric conditions. These geographic differences are of concern to policy makers, as they may represent either excessive levels of unnecessary care or inappropriately low utilization of necessary services. However, the sources of geographic variation are not well understood, and variation may not represent a quality problem, to the extent that geographic variation is due to sampling variability or variation in case-mix across sites. AIMS OF THE STUDY: Our aim was to determine the extent to which geographic variation in assessment and treatment rates for alcohol, drug, and mental disorders (ADM) was due to variation in case-mix across sites and to quantify the amount of geographic variation after case-mix adjustment. METHODS: We analyzed data from Healthcare for Communities, a nationally representative telephone survey of ADM disorders and treatment. We utilized fixed effects and random intercept models to analyze whether individuals received a brief primary care ADM assessment, any primary care ADM treatment, any specialty ADM treatment, or any ADM treatment. Using the coefficient of variation and intra-class correlation (ICC) as summaries, we simulated reference distributions for the amount of variability in ADM assessment and treatment rates expected due to variation in case mix across 60 geographic areas. We compared this with the actual variation among our 60 sites, and the variation that remained after adjusting for ADM disorders, physical health, and socioeconomic characteristics. RESULTS: The amount of the variation in assessment and treatment rates explained by geographic area in unadjusted fixed effects and random intercepts models was statistically significant with R2 statistics ranging from 1% to 2% in fixed effects models and ICC's ranging from 0.009 to 0.043. Considerably more variation was explained in analyses that included individual level characteristics such as ADM disorders, physical health, and socioeconomic status, with R2 statistics from 10% to 19%. In random intercept models the ICC's were decreased 20 to 100% in models that adjusted for ADM disorders, physical health, and socioeconomic status. DISCUSSION: We found significant variation in ADM assessment and treatment rates across geographic sites. However, the magnitude of geographic variation was relatively modest, with 0.9 to 4.3% of the total variation in ADM assessment and treatment occurring at the geographic level. Further, it appears that a moderate amount of this geographic variation may be due to differences in case mix across sites. IMPLICATIONS FOR HEALTH POLICY: Although geographic variation in assessment and treatment rates can signal variable quality, there may be only modest potential for improving quality by reducing geographic variation. Further, the success of efforts to decrease geographic variation by focusing on provider behavior may be limited by the extent to which systematic variation is explained by individual characteristics. IMPLICATIONS FOR FURTHER RESEARCH: Future work on geographic differences in mental health care as well as in health services more generally should pay particular attention to adjusting for individual differences in morbidity, which strongly predict treatment utilization.

Adolescent↗
PubMed1999

The contribution of assay variation and biological variation to the total variability of plasma HIV-1 RNA measurements. The Women Infant Transmission Study Clinics. Virology Quality Assurance Program.

OBJECTIVES: To assess the specific contributions of assay variation and biological variation to the total variation of plasma HIV-1 RNA measured by the Roche Monitor assay and the extent to which batch assays reduced both assay variability and total variability compared with real-time determinations. DESIGN: A retrospective analysis of data obtained from three trials conducted by the Adult and Pediatric AIDS Clinical Trials Groups (ATCG), the Women and Infants Transmission Study (WITS) and the NIAID-sponsored Virology Quality Assurance Program. METHODS: Within-subject variation was assessed from stored, serially collected plasma samples from 663 subjects enrolled in the ACTG and WITS studies. Interassay and intra-assay variation were estimated from two of the clinical trials and 22 laboratories that participated in a quality assurance program and were used to estimate the effect of real-time testing on total variation. RESULTS: The total variation (standard deviation) from a random effects model was 0.26 log10 RNA copies/ml. The estimated interassay variation was 0.08 log10 and intra-assay variation was 0.12 log10 RNA copies/ml. Biological variation accounted for 56-80% of total variation. The effect of real-time testing compared with batch testing was minimal. CONCLUSION: Our estimates of total within-subject HIV-1 RNA variation support the current recommendation to obtain at least two specimens, preferably obtained less than 2 weeks apart, for viral RNA measurement before starting therapy. The major contribution of biological variation to the total variation supports the use of real-time HIV-1 RNA assays, provided that consistent specimen collection procedures are followed and acceptable assay proficiency is maintained.

Adult↗
PubMed1999

Variations in 'avoidable' mortality: a reflection of variations in incidence?

BACKGROUND: Variations in 'avoidable' mortality may reflect variations in the quality of care, but they may also be due to variations in incidence or severity of diseases. We studied the association between regional variations in 'avoidable' mortality and variations in disease incidence. For a selection of conditions we also analysed whether the proportion of in-hospital deaths can explain the regional variations in incidence-adjusted mortality. METHODS: Relative risks for mortality, incidence, incidence-adjusted mortality and in-hospital mortality (1984-1994) were calculated by log-linear regression. Linear regression was used to examine the relationship between mortality and incidence on the one hand, and between incidence-adjusted mortality and in-hospital mortality on the other. RESULTS: Significant regional mortality variations were found for cervical cancer, cancer of the testis, hypertensive and cerebrovascular disease, influenza/pneumonia, cholecystitis/lithiasis, perinatal causes and congenital cardiovascular anomalies. Regional mortality differences in general were only partly accounted for by incidence variations. The only exception was cervical cancer, which no longer showed significant variations after adjustment for incidence. The contribution of inhospital mortality variations to total cause-specific mortality variations varied between conditions: the highest percentage of explained variance was found for mortality from CVA (60.1%) and appendicitis (29.2%). CONCLUSIONS: Incidence data are a worthy addition to studies on 'avoidable' mortality. It is to be expected that the incidence-adjusted mortality rates are more sensitive for quality-of-care variations than the 'crude' mortality variations. Nevertheless, further research at the individual level is needed to identify possible deficiencies in health care delivery.

Adolescent↗
PubMed1998

Genetic variation in paraoxonase-1 and paraoxonase-2 is associated with variation in plasma lipoproteins in Alberta Hutterites.

In a sample taken from the genetically isolated Alberta Hutterites, we previously found that PON1 variation was associated with variation in plasma lipoprotein traits, including LDL and HDL cholesterol. With the recent cloning of the PON1-related gene PON2, we undertook studies of the association between genetic variation in PON2 and variation in plasma quantitative traits variation in a sample of 745 Alberta Hutterites. We found novel genetic associations between PON2 variation and variation in fasting plasma concentrations of total cholesterol and apolipoprotein AI. We confirmed our previously observed significant associations in this study sample between PON1 genetic variation and variation in plasma apo B-related traits, such as LDL, non-HDL and HDL cholesterol and apo B itself. Furthermore, there was almost complete linkage disequilibrium between PON2 alleles G148 and C311. We found no association between PON2 variation and plasma glucose or insulin. Taken together, our results suggest that common genetic variation on chromosome 7q21.3-22.1 in both PON1 and PON2 that affects the amino acid sequence of the respective gene products is associated with significant variation in intermediate traits in plasma lipoprotein metabolism.

Alberta↗
PubMed2003

Overcoming technical variation and biological variation in quantitative proteomics.

Quantitative proteomics investigates physiology at the molecular level by measuring relative differences in protein expression between samples under different experimental conditions. A major obstacle to reliably determining quantitative changes in protein expression is to overcome error imposed by technical variation and biological variation. In drug discovery and development the issue of biological variation often rises in concordance with the developmental stage of research, spanning from in vitro assays to clinical trials. In this paper we present case studies to raise awareness to the issues of technical variation and biological variation and the impact this places on applying quantitative proteomics. We defined the degree of technical variation from the process of two-dimensional electrophoresis as 20-30% coefficient of variation. On the other hand, biological variation observed experiment-to-experiment showed a broader degree of variation depending upon the sample type. This was demonstrated with case studies where variation was monitored across experiments with bacteria, established cell lines, primary cultures, and with drug treated human subjects. We discuss technical variation and biological variation as key factors to consider during experimental design, and offer insight into preparing experiments that overcome this challenge to provide statistically significant outcomes for conducting quantitative proteomic research.

Animals↗
PubMed1998

Association and linkage of LDLR gene variation with variation in plasma low density lipoprotein cholesterol.

The role of common variation in the low density lipoprotein (LDL) receptor gene (LDLR) as a determinant of variation in plasma LDL cholesterol in normolipidemic populations is not well established. To address this question, we used both association and linkage analysis to evaluate the relationship between plasma LDL cholesterol and genetic variation in LDLR and in three other candidate genes for lipoprotein metabolism, namely, APOE, PONI, and LPL. We studied a sample of 719 normolipidemic Alberta Hutterites, who comprised 1217 sib pairs. Variation in each of the four candidate genes was significantly associated with variation in plasma LDL cholesterol, but the average effects of the alleles were small. In contrast, sib pair analysis showed that only the LDLR gene variation was linked with variation in plasma LDL cholesterol (P = 0.026). Thus, the common LDLR gene variation was both associated with and linked to variation in plasma LDL cholesterol, suggesting that there is a functional impact of structural variation in LDLR on plasma LDL cholesterol in this study sample. However, the absence of linkage of variation in LDL cholesterol with the other three candidate genes, in particular APOE, is consistent with a lower sensitivity of linkage analysis compared with association analysis for detecting modest effects on quantitative traits. Attributes such as the genetic structure of the study sample, the amount of variance attributable to the locus, and the information content of the marker appear to affect the ability to detect genotype-phenotype relationships using linkage analysis.

Adult↗
PubMed2002

Contributions of 18 additional DNA sequence variations in the gene encoding apolipoprotein E to explaining variation in quantitative measures of lipid metabolism.

Apolipoprotein E (ApoE) is a major constituent of many lipoprotein particles. Previous genetic studies have focused on six genotypes defined by three alleles, denoted epsilon2, epsilon3, and epsilon4, encoded by two variable exonic sites that segregate in most populations. We have reported studies of the distribution of alleles of 20 biallelic variable sites in the gene encoding the ApoE molecule within and among samples, ascertained without regard to health, from each of three populations: African Americans from Jackson, Miss.; Europeans from North Karelia, Finland; and non-Hispanic European Americans from Rochester, Minn. Here we ask (1) how much variation in blood levels of ApoE (lnApoE), of total cholesterol (TC), of high-density lipoprotein cholesterol (HDL-C), and of triglyceride (lnTG) is statistically explained by variation among APOE genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles; (2) how much additional variation in these traits is explained by genotypes defined by combining the two variable sites that define these three alleles with one or more additional variable sites; and (3) what are the locations and relative allele frequencies of the sites that define multisite genotypes that significantly improve the statistical explanation of variation beyond that provided by the genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles, separately for each of the six gender-population strata. This study establishes that the use of only genotypes defined by the epsilon2, epsilon3, and epsilon4 alleles gives an incomplete picture of the contribution that the variation in the APOE gene makes to the statistical explanation of interindividual variation in blood measurements of lipid metabolism. The addition of variable sites to the genotype definition significantly improved the ability to explain variation in lnApoE and in TC and resulted in the explanation of variation in HDL-C and in lnTG. The combination of additional sites that explained the greatest amount of trait variation was different for different traits and varied among the six gender-population strata. The role that noncoding variable sites play in the explanation of pleiotropic effects on different measures of lipid metabolism reveals that both regulatory and structural functional variation in the APOE gene influences measures of lipid metabolism. This study demonstrates that resequencing of the complete gene in a sample of >/=20 individuals and an evaluation of all combinations of the identified variable sites, separately for each population and interacting environmental context, may be necessary to fully characterize the impact that a gene has on variation in related traits of a metabolic system.

Alleles↗
PubMed2002

Mass variation tests for coating tablets and hard capsules: rational application of mass variation tests.

The mass variation test is a simplified alternative test version of the content uniformity test. In the case of coating tablets and capsules, the mass variation test is principally applied to test the inner cores or fillings containing the active ingredient. However, some exceptions exist in pharmacopoeias. The effects of tablet coating and capsule shell on the results of the mass variation test were studied. The mass variation of outer crusts (coatings, capsule shells) and inner cores (core tablets, fillings) was measured separately in several products. The effects of coating on weight variability were very large for sugar-coated tablets. Relative standard deviation (RSD) of the formulation weight (RSD(W)) of sugar-coated tablets (2.73%) was larger than that of plain tablets (0.77%). The cause of the large RSD(W) is the large variation the weight of sugar-coating accounting for 44% of formulation weight. In the case of film-coated tablets, the effect of coating weight on the mass variation test was very small because the rate of coating in comparison to the whole weight was small. In the case of hard capsules, the usage of whole formulation weight resulted in underestimation of variations of filling weight. The differences between dosage forms in the applicability of the mass variation test are caused by differing weight proportions and variability of the outer coatings or shells. To avoid the underestimation of mass variation for hard capsules, a corrected acceptance value is useful. For all the dosage units, the mass variation test can principally be applied to determine which mass is expected to be proportional to the content of the active ingredient. However, some modification of acceptance values enables application of the mass variation tests to inapplicable cases, such as when the RSD of drug concentration (RSD(C)) is larger than 2%.

Algorithms↗
PubMed2001

Mitochondrial DNA variation and GIS analysis confirm a secondary origin of geographical variation in the bushcricket Ephippiger ephippiger (Orthoptera: Tettigonioidea), and resurrect two subspecies.

Geographic variation within species can originate through selection and drift in situ (primary variation) or from vicariant episodes (secondary variation). Most patterns of subspecific variation within European flora and fauna are thought to have secondary origins, reflecting isolation in refugia during Quaternary ice ages. The bushcricket Ephippiger ephippiger has an unusual pattern of geographical variability in morphology, behaviour and allozymes in southern France, which has been interpreted as reflecting recent primary origins rather than historical isolation. Re-analysis of this variation using Geographical Information Systems (GIS) suggests a possible zone of hybridization within a complex pattern of geographical variation. Here we produce a genetic distance matrix from restriction fragment length polymorphism (RFLP) bandsharing of an approximately 4.5 kb fragment of mitochondrial DNA (mtDNA), and compare this with predictions resulting from the GIS analysis. The mtDNA variation supports a postglacial origin of geographical variation. Partial Mantel test comparisons of genetic distances with matrices of geographical distance, relevant environmental characteristics and possible refugia show refugia to be the best predictors of genetic distance. There is no evidence to support isolation by distance. However, environmental contrasts do explain significant variation in genetic distance after allowing for the effect of refugial origin. Also, a neighbour-joining tree has a major division separating eastern and western forms. We conclude that the major source of variation within the species is historical isolation in glacial refugia, but that dispersal, hybridization and selection associated with environmental features has influenced patterns of mtDNA introgression. At least two valid subspecies can be defined.

Animals↗
PubMed1994

Relationships between intra-speaker variation in aerodynamic measures of voice production and variation in SPL across repeated recordings.

Intra-speaker variation in aerodynamic and acoustic measures of voice production across repeated recordings was studied in relation to cross-recording variation in SPL for three normal female and three normal male speakers. Group data for 15 females and 15 males served as the statistical reference. The speech material consisted of syllable strings in soft, normal, and loud voice. Measures were made of (a) parameters characterizing the inverse filtered oral airflow waveform, (b) the inferred average transglottal air pressure and glottal airflow, and (c) SPL. The results showed that intra-speaker parameter variation across recordings was generally less than 2 standard deviations relative to group mean values. In terms of relation to variation in SPL, the measures could be divided into two main groups: (a) For air pressure, AC flow, and maximum flow declination rate, both intra-speaker variation across recordings and inter-speaker (group) variation was related systematically to variation of SPL. For these measures, it is suggested that variation across recordings was due in part to SPL differences, which can be adjusted for statistically, thus facilitating comparisons between absolute values. (b) For other measures, neither intra-speaker variation across recordings nor inter-speaker group variation was systematically related to SPL. However, some of these latter measures changed with SPL in an orderly fashion across soft, normal, and loud voice for individual speakers. The results are discussed in terms of the clinical use of these measures in studies of voice disorders.

Adult↗
PubMed1997

Genetic variation in factor VII associated with variation in plasma lipoprotein(a) concentration.

Cross-sectional and prospective studies have shown that individuals with high plasma lipoprotein(a) [Lp(a)] concentrations are at increased risk for coronary heart disease. Size polymorphism of the apolipoprotein(a) [apo(a)] glycoprotein accounts for approximately 35% of the variation in plasma Lp(a) concentrations. However, there is no convincing evidence for associations between plasma Lp(a) and common genetic variation outside APO(a), the gene that encodes apo(a). We tested for association of common genetic variation of candidate genes in lipid metabolism and also of F7 with variation of plasma Lp(a) concentrations in Alberta Hutterites. Variation at codon 353 of F7 has been associated with variation in the plasma factor VII activity (FVIIc), with the 353Q allele associated with lower FVIIc and the 353R allele associated with higher FVIIc. We found significant associations between variation in plasma concentrations of Lp(a) and both apo(a) isoform size and F7 codon 353 genotype (both P < .0001). The effects on plasma Lp(a) concentration of the alleles at codon 353 were additive. The average effects of the F7 353Q and 353R alleles were, respectively, to decrease by 1.71 micrograms/mL and to increase by 0.301 microgram/mL plasma Lp(a) concentration from the sample mean. This suggests that common genomic variation in F7 is associated with variation in plasma Lp(a) concentration.

Alleles↗
PubMed1994

Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels.

Genetic factors have been shown to play an important role in determining interindividual variation in plasma HDL-C levels, but the specific genetic determinants of HDL cholesterol (HDL-C) levels have not been elucidated. In this study, the effects of variation in the genomic regions encoding hepatic lipase, apolipoprotein AI/CIII/AIV, and the cholesteryl ester transfer protein on plasma HDL-C levels were examined in 73 normotriglyceridemic, Caucasian nuclear families. Genetic factors accounted for 56.5 +/- 13% of the interindividual variation in plasma HDL-C levels. For each candidate gene, adjusted plasma HDL-C levels of sibling pairs who shared zero, one, or two parental alleles identical-by-descent were compared using sibling-pair linkage analysis. Allelic variation in the genes encoding hepatic lipase and apolipoprotein AI/CIII/AIV accounted for 25 and 22%, respectively, of the total interindividual variation in plasma HDL-C levels. In contrast, none of the variation in plasma HDL-C levels could be accounted for by allelic variation in the cholesteryl ester transfer protein. These findings indicate that a major fraction of the genetically determined variation in plasma HDL-C levels is conferred by allelic variation at the hepatic lipase and the apolipoprotein AI/CIII/AIV gene loci.

Apolipoprotein A-I↗
PubMed2004

Genetic variation in femur extrinsic strength in 29 different inbred strains of mice is dependent on variations in femur cross-sectional geometry and bone density.

The femurs from groups of mice from 29 different inbred strains were characterized to study the genetic variations in bone parameters. For these analyses, we used peripheral quantitative computed tomography to assess bone size and density in addition to three-point bend testing to assess bone mechanical properties. Highly significant differences between inbred strains were found for all size, density, and mechanical parameters measured (P < 0.0001). Correcting femoral cross-sectional geometry values or bone mechanical properties values for body weight or femur length reduced but did not eliminate the variations in bone geometry or bone mechanical properties. Mice of similar body size had as much as a 40% difference in the midshaft total area of the femur. Regression analysis suggested that 50.9% of the variation in maximum load among strains was related to variations in section modulus, i.e., cross-sectional geometry, 21.5% was related to variations in material bone density, and 27.7% to variations in quality. These components were further analyzed to show that 3.9-27.8% of the variation in maximum load was related to adaptation to mechanical stress. These findings indicate that there is a significant genetic variation in the femur cross-sectional area, density, and mechanical properties between inbred mouse strains. These studies identify inbred mouse strains suitable for future studies identifying genes regulating bone geometry and mechanical properties.

Animals↗
PubMed1982

Naturally occurring enzyme activity variation in Drosophila melanogaster. I. Sources of variation for 23 enzymes.

The genetic component of variation of enzyme activity levels in Drosophila melanogaster was investigated by using 48 second- and 48 third-chromosome isogenic substitution lines derived from natural populations. The results confirm those of our earlier experiments with the same lines and extend them to a number of additional enzymes. All 23 enzymes show a significant genetic component to the variation in one or both sets of lines and only a small part of this variation is accounted for by variation among the lines in the amount of tissue per fly. The magnitude of line effects is, in most cases, considerably larger than the magnitude of environmental and measurement error effects, and the line effects are approximately continuous in distribution. Variation in the geographic origin and karyotype of the chromosomes generally does not contribute to the line component of variation, but allozymes provide an important source of variation for a few of the enzymes. Many of the enzymes show evidence for variation of activity modifiers that are not linked to the structural locus of the enzyme.

Animals↗
PubMed1996

Allelic variation in the gene encoding the cholesteryl ester transfer protein is associated with variation in the plasma concentrations of cholesteryl ester transfer protein.

The cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high density lipoproteins (HDL) to triglyceride-rich lipoproteins. Mutations that abolish CETP function are associated with very high levels of HDL cholesterol, but the effect of more common allelic variation at this locus is less clear. In this study, we have measured plasma CETP concentration and plasma HDL cholesterol concentrations in 694 individuals from 106 nuclear families. Robust sibling-pair methods indicated linkage between the CETP locus and inter-individual variation in plasma CETP concentrations. Allelic variation at the CETP locus accounted for 20% of the variation in plasma CETP concentration. No relation between allelic variation at the CETP locus and plasma HDL cholesterol levels was detected. These data indicate that polymorphism in the CETP gene confers variation in plasma CETP concentration. However, this degree of variation in CETP function is not systematically associated with variation in plasma HDL-C concentrations.

Alleles↗
PubMed1988

Diabetic autonomic neuropathy--Part II. Coefficient of variation of RR-variation and Valsalva maneuver tests.

To confirm the reliability and validity of cardiovascular autonomic nervous system tests, RR-variation and Valsalva maneuver, coefficient of variation for triplicate tests was calculated. The testing data were collected from patients participating in the Statil Neuropathy Trial. Triplicate testing was done within a three-week period at three different time points: baseline, 12 months, and 18 months. BMDP Statistical Software was used in the analysis. There is no significant difference between the coefficients of variation between clinics for either RR-variation or Valsalva maneuver tests. The coefficient of variation of pooled data was not significantly different from the coefficient of variation of individual clinics. Furthermore, there was no evidence that there was a significant worsening of coefficient of variation with time. Thus, RR-variation and Valsalva maneuver provide reliable and reproducible results that do not vary in consistency over time.

Autonomic Nervous System Diseases↗
PubMed2004

Potential relationships among myocardial stiffness, the measured level of myocardial backscatter ("image brightness"), and the magnitude of the systematic variation of backscatter (cyclic variation) over the heart cycle.

BACKGROUND: In a number of recently published studies comparing measurements from patients with those from control subjects, a decreased magnitude of the systematic variation of backscattered energy over the heart cycle (cyclic variation) is accompanied by an increased level of overall myocardial backscatter (calibrated myocardial image brightness) when measured at a specific phase of the heart cycle (eg, end systole or end diastole). The goal of this study was to investigate whether this observation is consistent with predictions based on a model of the mechanisms of cyclic variation incorporating changes in relative intracellular and extracellular acoustic impedance over the heart cycle. METHODS: A previously described 3-component Maxwell-type model of muscle mechanics representing cardiac cell mechanical behavior was utilized to predict the systematic variation in the relative acoustic impedance differences between intracellular and extracellular elastic properties over the heart cycle and hence the observed magnitude of cyclic variation and overall myocardial scattering level. Predictions were obtained for a series of specific values of relative intracellular and extracellular acoustic impedance. RESULTS: Results indicate that the predicted magnitude of cyclic variation can be directly related to the overall myocardial backscatter level. For example, specific changes in the acoustic impedance (stiffness properties) of the extracellular matrix without any change in the intracellular acoustic impedance result in predicted values of -43.5 dB, -38.5 dB, and -33.5 dB for end-diastolic myocardial backscatter levels with corresponding values of 5.0 dB, 2.5 dB, and 1.3 dB for the predicted magnitude of cyclic variation, respectively. CONCLUSION: This study suggests that observed decreases in the magnitude of cyclic variation with concomitant increases in the measured overall myocardial backscatter level are consistent with predictions from a model based on the relative acoustic impedance differences between intracellular and extracellular elastic properties over the heart cycle. These results suggest that ultrasonic backscatter measurements may provide a noninvasive approach for assessing some relationships among myocardial stiffness, degree of fibrosis, and contractile performance.

Computer Simulation↗