Role of Patient and Practice Characteristics in Variance of Treatment Quality in Type 2 Diabetes between General Practices

BackgroundAccounting for justifiable variance is important for fair comparisons of treatment quality. The variance between general practices in treatment quality of type 2 diabetes (T2DM) patients may be attributed to the underlying patient population and practice characteristics. The objective of this study is to describe the between practice differences in treatment, and identify patient and practice level characteristics that may explain these differences.MethodsThe data of 24,607 T2DM patients from 183 general practices in the Netherlands were used. Treatment variance was assessed in a cross-sectional manner for: glucose-lowering drugs/metformin, lipid-lowering drugs/statins, blood pressure-lowering drugs/ACE-inhibitor or ARB. Patient characteristics tested were age, gender, diabetes duration, comorbidity, comedication. Practice characteristics were number of T2DM patients, practice type, diabetes assistant available. Multilevel logistic regression was used to examine the between practice variance in treatment and the effect of characteristics on this variance.ResultsTreatment rates varied considerably between practices (IQR 9.5–13.9). The variance at practice level was 7.5% for glucose-lowering drugs, 3.6% for metformin, 3.1% for lipid-lowering drugs, 10.3% for statins, 8.6% for blood pressure-lowering drugs, and 3.9% for ACE-inhibitor/ARB. Patient and practice characteristics explained 19.0%, 7.5%, 20%, 6%, 9.9%, and 13.4% of the variance respectively. Age, multiple chronic drugs, and ≥3 glucose-lowering drugs were the most relevant patient characteristics. Number of T2DM patients per practice was the most relevant practice characteristic.DiscussionConsiderable differences exist between practices in treatment rates. Patients’ age was identified as characteristic that may account for justifiable differences in especially lipid-lowering treatment. Other patient or practice characteristics either do not explain or do not justify the differences.     

Variance components of short-term biomarkers of manganese exposure in an inception cohort of welding trainees

Various biomarkers of exposure have been explored as a way to quantitatively estimate an internal dose of manganese (Mn) exposure, but given the tight regulation of Mn in the body, inter-individual variability in baseline Mn levels, and variability in timing between exposure and uptake into various biological tissues, identification of a valuable and useful biomarker for Mn exposure has been elusive. Thus, a mixed model estimating variance components using restricted maximum likelihood was used to assess the within- and between-subject variance components in whole blood, plasma, and urine (MnB, MnP, and MnU, respectively) in a group of nine newly-exposed apprentice welders, on whom baseline and subsequent longitudinal samples were taken over a three month period. In MnB, the majority of variance was found to be between subjects (94%), while in MnP and MnU the majority of variance was found to be within subjects (79% and 99%, respectively), even when controlling for timing of sample. While blood seemed to exhibit a homeostatic control of Mn, plasma and urine, with the majority of the variance within subjects, did not. Results presented here demonstrate the importance of repeat measure or longitudinal study designs when assessing biomarkers of Mn, and the spurious associations that could result from cross-sectional analyses.     

Inhibition by cocaine of the baroreflex in the rat.

Sprague-Dawley rats were fitted under pentobarbital anesthesia with a catheter in the caudal artery and their carotid arteries were exposed. The pressure signal from the caudal artery was treated on line by a microcomputer for continuous display of blood pressure and heart rate measurements. The animals were administered intraperitoneally either 50 mg/kg of cocaine or an equal volume of saline. Five minutes later, stimulation of the baroreflex was performed by bilateral clamping of the two carotids for a period of 2 min. The same maneuver was repeated at 12, 24, and 31 min. Analysis of variance for repeated measures indicated that before carotid artery clamping, there was no significant difference between blood pressure measurements of the saline- and cocaine-treated groups. A two-factor analysis of variance of the repeated measures of the maximal variation in systolic pressure after each clamping showed a significant difference between control and cocaine-administered groups (P < 0.001), with the former displaying a much greater increment in blood pressure after carotid clamping. Cocaine exerts an inhibitory effect on the baroreflex that may be mediated through the increased angiotension II caused by the alkaloid.     

Oral glucose tolerance test reduces arterial baroreflex sensitivity in older adults

Although postprandial decreases in blood pressure are a common cause of syncope in the older adult population, the postprandial effects of the oral glucose tolerance test on blood pressure and the arterial baroreflex remain poorly characterized in older adults. Therefore, arterial blood pressure and the arterial baroreflex were studied in 19 healthy older adults (mean age 71.7 +/- 1.1 years) who were given a standardized oral glucose load (75 g) or an isovolumetric sham drink during 2 separate sessions. All measures were taken for 120 min after treatment. Baroreflex function was assessed by using the spontaneous baroreflex method (baroreflex sensitivity, BRS). Subjects demonstrated a decrease in BRS after oral glucose that was not seen in the placebo session (two-way analysis of variance, p = 0.04). There was no significant change in systolic, mean, or diastolic blood pressure; together with a drop in BRS, this resulted in a significant tachycardia post glucose (two-way analysis of variance, p < 0.001). We conclude that healthy older adults can successfully maintain blood pressure during an oral glucose tolerance test despite a decrease in arterial BRS. Decreased BRS resulted in a tachycardic response to glucose.     

Blood pressure in rats: a comparison of a multifactorial experimental design to measurements in an outbred stock

Systolic blood pressure was measured in males of 8 inbred strains and 1 outbred stock of rats 5 times over a period of 20 min on 5 consecutive days. The strain means ranged between 107.9 mmHg and 149.3 mmHg. The estimated variance between strains (V = 248.7 mmHg) was about 5 times higher than the variance within strains (V = 54.3 mmHg). The intraindividual variance within strains was relatively constant (V = 24.0-37.6 mmHg), while the interindividual variance varied to a great extent (V = 4.5-44.5 mmHg) from strain to strain. The outbred stock showed values of blood pressure and components of variance similar to those of a single inbred strain. Thus, by investigation of a battery of 8 inbred strains in a multifactorial experimental design a greater phenotypic variability due to genetic strain differences is achieved than by measurements in a single outbred stock.     

Relationship of visceral adiposity to cardiovascular disease risk factors in black and white teens

Objective: We tested the hypothesis that visceral adiposity, compared with general adiposity, would explain more of the variance in cardiovascular disease (CVD) risk factors. Research Method and Procedures: Subjects were 464 adolescents (238 black and 205 girls). Adiposity measures included visceral adipose tissue (VAT; magnetic resonance imaging), percent body fat (%BF; DXA), BMI, and waist girth (anthropometry). CVD risk factors were fasting insulin, fibrinogen, total to high‐density lipoprotein‐cholesterol ratio, triglycerides (TGs), systolic blood pressure, and left ventricular mass indexed to height^2.7. Results: After adjustment for age, race, and sex, all adiposity indices explained significant proportions of the variance in all of the CVD risk factors; %BF tended to explain more variance than VAT. Regression models that included both %BF and VAT found that both indices explained independent proportions of the variance only for total to high‐density lipoprotein‐cholesterol ratio. For TGs, the model that included both %BF and VAT found that only VAT was significant. For systolic blood pressure and left ventricular mass indexed to height^2.7, anthropometric measures explained more of the variance than VAT and %BF. Discussion: The hypothesis that visceral adiposity would explain more variance in CVD risk than general adiposity was not supported in this relatively large sample of black and white adolescents. Only for TGs did it seem that VAT was more influential than %BF. Perhaps the deleterious effect of visceral adiposity becomes greater later in life as it increases in proportion to general adiposity.     

Relative roles of heredity and physical activity in adolescence and adulthood on blood pressure.

Part of the association between physical activity and low blood pressure (BP) may be a consequence of genetic selection. We investigated the association of genetic factors and physical activity in adolescence and adulthood with BP. BP was measured with a Finapres device in 71 monozygotic and 104 dizygotic male twin pairs using no antihypertensive medication. Subjects' mean age was 50.4 yr (range 40-72 yr). Subjects were interviewed about their lifetime exercise and other health habits. Exercise was classified as aerobic, power, or other, and these were further divided into adolescence (12-20 yr of age), the previous year, and lifetime. Genetic modeling was conducted to estimate genetic and environmental components of variance of systolic and diastolic BP. Aerobic exercise in adolescence and high-intensity aerobic exercise throughout the lifetime were associated with low diastolic BP in adulthood. Of the variance in diastolic BP, genetic factors accounted for 35% and aerobic exercise in adolescence for 5%. For systolic BP, genetic factors accounted for 39% of the variance. In turn, genetic factors accounted for 44% of the variance in aerobic exercise in adolescence. The genetic factors in part accounting for the variance in diastolic BP and those in part accounting for variance in aerobic exercise in adolescence were correlated. The association between aerobic exercise in adolescence and low diastolic BP in adulthood is a new finding, as is the observation that the factors partly share the same genes.     

Blood constituents during the estrous cycle and early pregnancy in dairy cows

The objective of this study was to determine if maternal platelet count, white blood cell count or other blood constituents undergo sustained alterations in concentration following fertilization. Blood samples from 17 Holstein females were collected over an 18-d period starting at estrus. Blood was analyzed for levels of platelets, white blood cells, red blood cells, hemoglobin and hematocrit. Results were analyzed for differences between nonpregnant and pregnant groups. Analysis of variance revealed a day-by-group interaction in the platelet count (P<0.01). White blood cell count showed both a day-by-group interaction and a difference between days (P<0.01). Red blood cell count, hematocrit and hemoglobin levels resulted in no significant difference between the two groups (P>0.05). While statistically significant differences were observed in platelet and white blood cell count, neither of these were sustained over a period longer than 2 d.     

Chronobiologic blood pressure assessment: maturation of the daily rhythm in newborn foals

Circadian rhythmicity of physiological processes in animals has been described for some variables. In order to investigate the daily rhythmicity of blood pressure, seven foals (Equus caballus) were used for 40 days after birth. Measurements of blood pressure were done by means of an oscillometric apparatus (Argus TM-7, Schiller, Barr Switzerland) with the foals in a standing position and the cuff placed around the tail. Blood pressure was recorded twice a day, 1 hour before dawn and 1 hour before dusk for the first 10 days of life, every 2 days from the 11th to the 32nd day, on the 36th and on the 40th day. Two-way repeated measures analysis of variance (ANOVA) were used to determine statistically significant differences between the mean values recorded at dawn and dusk during the study. Analysis of variance showed a significant effect of time (p<0.0001), during the first 40 days of life. This study confirms a strong correlation between age and blood pressure in horse and the absence of blood pressure maturation in foals 40 days old. The results on the maturation of the daily rhythm of blood pressure in foals is a contribution to the study of the development of circadian rhythms in mammals. These results are also useful for the chronophysiological assessment of blood pressure in the horse.     

Reliability and short-term intra-individual variability of telomere length measurement using monochrome multiplexing quantitative PCR

Background

Studies examining the association between telomere length and cancer risk have often relied on measurement of telomere length from a single blood draw using a real-time PCR technique. We examined the reliability of telomere length measurement using sequential samples collected over a 9-month period.

Methods and Findings

Relative telomere length in peripheral blood was estimated using a single tube monochrome multiplex quantitative PCR assay in blood DNA samples from 27 non-pregnant adult women (aged 35 to 74 years) collected in 7 visits over a 9-month period. A linear mixed model was used to estimate the components of variance for telomere length measurements attributed to variation among women and variation between time points within women. Mean telomere length measurement at any single visit was not significantly different from the average of 7 visits. Plates had a significant systematic influence on telomere length measurements, although measurements between different plates were highly correlated. After controlling for plate effects, 64% of the remaining variance was estimated to be accounted for by variance due to subject. Variance explained by time of visit within a subject was minor, contributing 5% of the remaining variance.

Conclusion

Our data demonstrate good short-term reliability of telomere length measurement using blood from a single draw. However, the existence of technical variability, particularly plate effects, reinforces the need for technical replicates and balancing of case and control samples across plates.     

Relationship between African admixture and blood pressure variation in the Caribbean

The genetic contribution to blood pressure variance is examined by studying a selected group of genes. Of 368 individuals, 48.1% received one-half or more of their genes from an African ancestor and of this group 18.1 and 17.0% exhibit systolic and diastolic hypertension, respectively. A chi-square test was used to examine the dependence of blood pressure on percentage African ancestry. The chi-square values were not significant for systolic or diastolic pressures. It is likely that other factors are strongly related to African admixture and these factors are the true modifiers of blood pressure.     

Assessing the co-variability of DNA methylation across peripheral cells and tissues: Implications for the interpretation of findings in epigenetic epidemiology

Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated DNAm variation is specific to an individual cellular population. We collected three peripheral tissues (whole blood, buccal epithelial and nasal epithelial cells) from thirty individuals. Whole blood samples were subsequently processed using fluorescence-activated cell sorting (FACS) to purify five constituent cell-types (monocytes, granulocytes, CD4⁺ T cells, CD8⁺ T cells, and B cells). DNAm was profiled in all eight sample-types from each individual using the Illumina EPIC array. We identified significant differences in both the level and variability of DNAm between different sample types, and DNAm data-derived estimates of age and smoking were found to differ dramatically across sample types from the same individual. We found that for the majority of loci variation in DNAm in individual blood cell types was only weakly predictive of variance in DNAm measured in whole blood, although the proportion of variance explained was greater than that explained by either buccal or nasal epithelial samples. Covariation across sample types was much higher for DNAm sites influenced by genetic factors. Overall, we observe that DNAm variation in whole blood is additively influenced by a combination of the major blood cell types. For a subset of sites, however, variable DNAm detected in whole blood can be attributed to variation in a single blood cell type providing potential mechanistic insight about EWAS findings. Our results suggest that associations between whole blood DNAm and traits or exposures reflect differences in multiple cell types and our data will facilitate the interpretation of findings in epigenetic epidemiology.     

Hormonal factors in the control of heart rate in normoxaemic and hypoxaemic fetal, neonatal and adult sheep

The relationship of plasma levels of adrenaline, noradrenaline, arginine vasopressin (AVP) and plasma renin activity (PRA) to heart rate were studied in normoxaemic and hypoxaemic fetal, neonatal and adult sheep. The mean heart rate response of fetuses at the end of a 30 minute period of 10% oxygen delivery to the maternal ewe was tachycardia. However bradycardia, usually of a transient nature, was observed in 9 of the 12 fetuses (P less than 0.05). Multiple regression analysis was used to determine the contribution of blood gas, blood pressure and plasma hormone levels to the variance in heart rate in the perinatal sheep. 22% of the variance in fetal heart rate was provided by PRA and age from conception (P less than 0.001). Tachycardia was the invariable heart rate response of the neonates and adults to hypoxaemia. 61% of the variance in neonatal heart rate was contributed by PaO2, PaCO2, AVP, PRA and systolic blood pressure (SBP, P less than 0.001). PaO2 and plasma levels of adrenaline were significantly related to adult heart rate (P less than 0.001). Those fetuses which developed bradycardia had lower PaO2 but higher AVP and PRA during hypoxaemia than those which did not develop bradycardia. The major determinant of the area of the fetal bradycardia response was found, by multiple regression analysis, to be plasma adrenaline concentration (P less than 0.05). Thus different hormonal factors may play a role in the regulation of heart rate in normoxaemic and hypoxaemic fetal, neonatal and adult sheep.     

Indoleamines in blood plasma of schizophrenics a critical study with sensitive and selective methods

Plasma samples from 9 schizophrenics, selected according to diagnostic criteria which are discussed, were analysed for the presence of indoleamines. Care was taken to exclude an underlying organic, manic-depressive, or cycloid psychosis. Control samples were taken from 4 non-psychotics under treatment on the same ward. Several different methods of extraction, chromatography, and detection were used, and the detection limit for different amines was determined. No indoleamine, except 5-hydroxytryptamine, could be detected in any of the plasma samples, despite good recoveries of added standard substances. This is at variance with the findings of other authors, who have used whole blood samples. The conclusion is that the indoleamines supposed to be present in the blood of normals and psychotics are presumably confined to the blood cells.     

Turbulence in the canine ascending aorta and the blood pressure.

Turbulent velocity fluctuations were measured and analyzed in the canine ascending aorta using a hot-film anemometer. Blood flow rate and temperature were stabilized using a special bypass technique. Blood pressure was elevated by Methoxamine infusion. Turbulence components were extracted from measured data using an ensemble averaging technique. Turbulence intensity correlated best with blood flow rate although the variance was relatively large, especially when the blood flow velocity was high. When pooled data were grouped into subclasses using peak aortic flow velocity as the criteria, turbulence intensity correlated well with aortic systolic blood pressure in each of the subclasses. Spectral bandwidth correlated with aortic pressure in the same manner. In summary, turbulence in the aorta developed when blood pressure was high. Both an increase of turbulence intensity and an widening of turbulence spectra may be ascribed to a stiffening of the aortic wall due to an elevation of blood pressure.     

Demonstration of T lymphocytes in human blood and cerebrospinal fluid with Helix pomatia A hemagglutinin

Peroxidase-labelled Helix pomatia A hemagglutinin (HPH) was used as a T-cell marker for neuraminidase-treated human lymphocytes from blood or cerebrospinal fluid (CSF). Lymphocytes from the blood of 22 patients with noninflammatory diseases of the central nervous system and from the CSF of 16 patients with noninfectious diseases and 29 patients suffering from meningitis or meningoencephalitis were studied. Most HPH-binding cells were found in normal CSF. The variance in the number of reactive lymphocytes was higher in the CSF from patients with inflammatory diseases than in the other types of samples.     

Apportionment of racial diversity: A review

It has become increasingly popular to theorize and assert significant genetic differences between arbitrary regional, ethnic, and racial groupings of humans. Beginning with Livingstone, Brace, and Newman is the early 1960s, biological anthropologists have shown that variation in human traits is non‐concordant along racial lines, as they are products of overlapping, dynamic selective pressures. In 1972, Lewontin analyzed blood groups, serum protein, and red blood cell enzyme variants and found that only about 6% of total genetic variance was accounted for by race, while the majority of variance is accounted for by differences between individuals. Using similar assays, Latter obtained similar results in 1980. In 1982, Nei and Roychoudhury analyzed 62 protein variants and 23 blood groups, finding that roughly 10% of genetic variance was accounted for by race. Analyzing protein, blood group, and HLA variants, Ryman and coworkers obtained similar figures in 1983. More recently, Dean and coworkers (1994) and Barbujani and coworkers (1997) have used PCR techniques to analyze RFLP and microsattelite loci, again yielding estimates of around 10% for the amount of genetic variance accounted for by race. Furthermore, recent research on regional and racial variance in mtDNA (Excoffier and coworkers, 1992), a traditional marker for human racial groupings, shows a higher proportion of variance within than across racial categories. These studies used a variety of assays and analytical techniques, some of which are designed to maximize the amount of variance accounted for by race. In light of this, the low proportion of genetic variance across racial groupings strongly suggests a re‐examination of the race concept. It no longer makes sense to adhere to arbitrary racial categories, or to expect that the next genetic study will provide the key to racial classification. Evol. Anthropol. 10:34–40, 2001. © 2001 Wiley‐Liss, Inc.     

Reliability of using urinary and blood trichloroacetic acid as a biomarker of exposure to chlorinated drinking water disinfection byproducts

This study was designed to analyse the reliability of using urinary and blood trichloroacetic acid (TCAA) as a biomarker of exposure. A total of 46 healthy women consumed supplied TCAA-containing tap water for 15 days and provided urine and blood samples for TCAA measurements. The findings revealed that the reliability of measurements was excellent by using measures of TCAA ingestion, blood concentration and urinary excretion (intraclass correlation coefficients (ICC)?>?0.75, p??0.95, p?相似文献   

Genetic and environmental causes of variation in basal levels of blood cells.

The genetic and environmental determinants of variation in blood cell size and number were investigated in 392 pairs of 12-year-old twins. The following blood cell indices were measured: haemoglobin, red blood cell count, haematocrit, mean corpuscular volume, platelet number, total white cell count, level of neutrophils, monocytes, eosinophils, total lymphocytes, CD3+ lymphocytes, CD4+ lymphocytes, CD8+ lymphocytes, CD19+ lymphocytes, CD56+ lymphocytes and CD4+/CD8+ ratio. Genetic factors contributed significantly to all blood cell measures accounting for between 61 and 96% of variance. Heritability estimates did not differ significantly between males and females, although the sample size of the present study was not large enough to exclude the possibility of sex-limited gene expression. Common environmental factors were important in determining red blood cell count and haematocrit, but were not important in determining basal levels of any white blood cell type.