Extent Of Variation In Rates Research Articles

Abstract 29: Appropriateness of Percutaneous Coronary Intervention in Patients with Stable Coronary Artery Disease: Department of Veterans Affairs, 2013-2015

Background: Percutaneous coronary intervention (PCI) for patients with stable coronary artery disease is commonly performed in Veterans Affairs (VA) hospitals. However, the appropriateness of these procedures in contemporary practice is unknown. Methods: We performed a multi-center, retrospective study of patients within the VA Clinical Assessment, Reporting, and Tracking (CART) Program with stable coronary artery disease undergoing elective PCI between November 1, 2013, and October 31, 2015. Trained personnel abstracted data on patient symptoms and stress testing results. Using criteria issued by multiple cardiovascular professional societies in 2012, the level of risk indicated by stress testing was adjudicated and PCI appropriateness was assessed. The extent of hospital-level variation in rates of inappropriate PCI was characterized. Results: Of 2622 PCIs at 66 hospitals, 800 (30.5%) were classified as appropriate, 1583 (60.4%) were classified as uncertain, and 239 (9.1%) were classified as inappropriate. Inappropriate PCIs were performed in patients with low-risk ischemia on stress testing (n=223/382, 58.4%), with < 1 classes of antianginal medication (n=235/1936, 12.1%), or without symptoms (n=14/23, 60.9%). Hospital-level variation in the proportion of inappropriate PCIs was observed ( Figure 1: median hospital rate for inappropriate PCI, 9.3%; interquartile range 6.2%-11.8%). Conclusions: In contemporary VA practice, most PCIs were classified as appropriate or uncertain. However, 9.1% were classified as inappropriate with variation across hospitals. These findings may inform ongoing efforts to identify elements of hospital performance and enhance PCI-related quality of care. Figure 1: Hospital-Level Variation in Rates of Inappropriate PCI

Exploring the variation in paediatric tonsillectomy rates between English regions: a 5‐year NHS and independent sector data analysis

Tonsillectomy rates vary between locations and socio-economic groups and have been noted to do so since the 1930s. We aimed, first, to illustrate the current extent of variation in rates in the NHS across England and, second, to explore whether any observed geographical variation could be accounted for by combining independent sector data with standard NHS datasets. Analysis of NHS Hospital Episode Statistics data for tonsillectomy in people aged under 15 years, from April 1 2000 to March 31 2005; addition of data from a major independent sector provider of surgery; ranking of local authority areas according to tonsillectomy rates including and excluding independent sector data. The national annual average tonsillectomy rate for the NHS was 304 per 100 000 population aged <15 (95% CI 320-324). The highest rate was 754 (95% CI 690-822) and the lowest 102 (95% CI 83-125). This seven-fold difference cannot simply be explained by a small number of high or low 'outliers'. When rates in the NHS were ranked and compared with the ranking of rates in the independent sector data, a Kendall tau rank correlation coefficient of 0.003 showed that there was no inverse correlation between the two rankings. That is, low NHS rates were not associated with high independent sector rates or vice versa. There is currently a seven-fold variation in tonsillectomy rates across local authority areas in England. The variation in tonsillectomy rates found in NHS data on surgical workload does not appear to be explained by the exclusion of data from the independent sector.

Correlation between the substitution rate and rate variation among sites in protein evolution.

It is well known that the rate of amino acid substitution varies among different proteins and among different sites of a protein. It is, however, unclear whether the extent of rate variation among sites of a protein and the mean substitution rate of the protein are correlated. We used two approaches to analyze orthologous protein sequences of 51 nuclear genes of vertebrates and 13 mitochondrial genes of mammals. In the first approach, no assumptions of the distribution of the rate variation among sites were made, and in the second approach, the gamma distribution was assumed. Through both approaches, we found a negative correlation between the extent of among-site rate variation and the average substitution rate of a protein. That is, slowly evolving proteins tend to have a high level of rate variation among sites, and vice versa. We found this observation consistent with a simple model of the neutral theory where most sites are either invariable or neutral. We conclude that the correlation is a general feature of protein evolution and discuss its implications in statistical tests of positive Darwinian selection and molecular time estimation of deep divergences.

Maximum-Likelihood Models for Combined Analyses of Multiple Sequence Data

Abstract. Models of nucleotide substitution were constructed for combined analyses of heterogeneous sequence data (such as those of multiple genes) from the same set of species. The models account for different aspects of the heterogeneity in the evolutionary process of different genes, such as differences in nucleotide frequencies, in substitution rate bias (for example, the transition/transversion rate bias), and in the extent of rate variation across sites. Model parameters were estimated by maximum likelihood and the likelihood ratio test was used to test hypotheses concerning sequence evolution, such as rate constancy among lineages (the assumption of a molecular clock) and proportionality of branch lengths for different genes. The example data from a segment of the mitochondrial genome of six hominoid species (human, common and pygmy chimpanzees, gorilla, orangutan, and siamang) were analyzed. Nucleotides at the three codon positions in the protein-coding regions and from the tRNA-coding regions were considered heterogeneous data sets. Statistical tests showed that the amount of evolution in the sequence data reflected in the estimated branch lengths can be explained by the codon-position effect and lineage effect of substitution rates. The assumption of a molecular clock could not be rejected when the data were analyzed separately or when the rate variation among sites was ignored. However, significant differences in substitution rate among lineages were found when the data sets were combined and when the rate variation among sites was accounted for in the models. Under the assumption that the orangutan and African apes diverged 13 million years ago, the combined analysis of the sequence data estimated the times for the human-chimpanzee separation and for the separation of the gorilla as 4.3 and 6.8 million years ago, respectively.

Molecular phylogeny and man's place in Hominoidea.

Branching order among man, chimpanzee and gorilla was inferred with orangutan as an outgroup from the data of the 28S rRNA gene and of the ribosomal internal transcribed spacer recently sequenced by GONZALEZ et al. (1990). The analysis was performed by the maximum likelihood method without assuming constancy of the evolutionary rate. It was strongly suggested that chimpanzee is the closest relative of man, consistently with GONZALEZ et al.'s analysis. After establishing the branching order, the extent of rate variation among lineages was evaluated, and the branching dates were estimated for the ribosomal internal transcribed spacer by taking into account a possible rate variation. The overall evidence from the DNA sequence data accumulated up to date suggests that man separated from chimpanzee some 4-5 million years ago.