Partial volume correction incorporating Rb-82 positron range for quantitative myocardial perfusion PET based on systolic-diastolic activity ratios and phantom measurements.

BACKGROUND: Quantitative myocardial PET perfusion imaging requires partial volume corrections. METHODS: Patients underwent ECG-gated, rest-dipyridamole, myocardial perfusion PET using Rb-82 decay corrected in Bq/cc for diastolic, systolic, and combined whole cycle ungated images. Diastolic partial volume correction relative to systole was determined from the systolic/diastolic activity ratio, systolic partial volume correction from phantom dimensions comparable to systolic LV wall thicknesses and whole heart cycle partial volume correction for ungated images from fractional systolic-diastolic duration for systolic and diastolic partial volume corrections. RESULTS: For 264 PET perfusion images from 159 patients (105 rest-stress image pairs, 54 individual rest or stress images), average resting diastolic partial volume correction relative to systole was 1.14 ± 0.04, independent of heart rate and within ±1.8% of stress images (1.16 ± 0.04). Diastolic partial volume corrections combined with those for phantom dimensions comparable to systolic LV wall thickness gave an average whole heart cycle partial volume correction for ungated images of 1.23 for Rb-82 compared to 1.14 if positron range were negligible as for F-18. CONCLUSION: Quantitative myocardial PET perfusion imaging requires partial volume correction, herein demonstrated clinically from systolic/diastolic absolute activity ratios combined with phantom data accounting for Rb-82 positron range.

Estimation of male-to-female ratios of mutation rate in primates and rodents

Haldane (1935) developed a method for estimating the male-to-female ratio of mutation rate ($\alpha$) by using sex-linked recessive genetic disease, but in six different studies using hemophilia A data the estimates of $\alpha$ varied from 1.2 to 29.3. Direct genomic sequencing is a better approach, but it is laborious and not readily applicable to non-human organisms. To study the sex ratios of mutation rate in various mammals, I used an indirect method proposed by Miyata et al. (1987). This method takes advantage of the fact that different chromosomes segregate differently between males and females, and uses the ratios of mutation rate in sequences on different chromosomes to estimate the male-to-female ratio of mutation rate. I sequenced the last intron of ZFX and ZFY genes in 6 species of primates and 2 species of rodents; I also sequenced the partial genomic sequence of the Ube1x and Ube1y genes of mice and rats. The purposes of my study in addition to estimation of $\alpha$'s in different mammalian species, are to test the hypothesis that most mutations are replication dependent and to examine the generation-time effect on $\alpha$. The $\alpha$ value estimated from the ZFX and ZFY introns of the six primate specise is ${\sim}$6. This estimate is the same as an earlier estimate using only 4 species of primates, but the 95% confidence interval has been reduced from (2, 84) to (2, 33). The estimate of $\alpha$ in the rodents obtained from Zfx and Zfy introns is ${\sim}$1.9, and that deriving from Ube1x and Ube1y introns is ${\sim}$2. Both estimates have a 95% confidence interval from 1 to 3. These two estimates are very close to each other, but are only one-third of that of the primates, suggesting a generation-time effect on $\alpha$. An $\alpha$ of 6 in primates and 2 in rodents are close to the estimates of the male-to-female ratio of the number of germ-cell divisions per generation in humans and mice, which are 6 and 2, respectively, assuming the generation time in humans is 20 years and that in mice is 5 months. These findings suggest that errors during germ-cell DNA replication are the primary source of mutation and that $\alpha$ decreases with decreasing length of generation time. ^

Development and validation of the Neuro Symptom Inventory in the primary brain tumor patient population

Symptoms has been shown to predict quality of life, treatment course and survival in solid tumor patients. Currently, no instrument exists that measures both cancer-related symptoms and the neurologic symptoms that are unique to persons with primary brain tumors (PBT). The aim of this study was to develop and validate an instrument to measure symptoms in patients who have PBT. A conceptual analysis of symptoms and symptom theories led to defining the symptoms experience as the perception of the frequency, intensity, distress, and meaning that occurs as symptoms are produced, perceived, and expressed. The M.D. Anderson Symptom Inventory (MDASI) measures both symptoms and how they interfere with daily functioning in patients with cancer, which is similar to the situational meaning defined in the analysis. A list of symptoms pertinent to the PBT population was added to the core MDASI and reviewed by a group of experts for validity. As a result, 18 items were added to the core MDASI (the MDASI-BT) for the next phase of instrument development, establishing validity and reliability through a descriptive, cross-sectional approach with PBT patients. Data were collected with a patient completed demographic data sheet, an investigator completed clinician checklist, and the MDASI-BT. Analysis evaluated the reliability and validity of the MDASI-BT in PBT patients. Data were obtained from 201 patients. The number of items was reduced to 22 by evaluation of symptom severity as well as cluster analysis. Regression analysis showed more than half (56%) of the variability in symptom severity was explained by the brain tumor module items. Factor analysis confirmed that the 22 item MDASI-BT measured six underlying constructs: (a) affective; (b) cognitive; (c) focal neurologic deficits; (d) constitutional symptoms; (e) treatment-related symptoms; and (f) gastrointestinal symptoms. The MDASI-BT was sensitive to disease severity and if the patient was hospitalized. The MDASI-BT is the first instrument to measure symptoms in PBT patients that has demonstrated reliability and validity. It is the first step in a program of research to evaluate the occurrence of symptoms and plan and evaluate interventions for PBT patients. ^

The Spanish translation, cultural adaptation and validation of the Powe Fatalism Inventory

Background/significance. The scarcity of reliable and valid Spanish language instruments for health related research has hindered research with the Hispanic population. Research suggests that fatalistic attitudes are related to poor cancer screening behaviors and may be one reason for low participation of Mexican-Americans in cancer screening. This problem is of major concern because Mexican-Americans constitute the largest Hispanic subgroup in the U.S.^ Purpose. The purposes of this study were: (1) To translate the Powe Fatalism Inventory, (PFI) into Spanish, and culturally adapt the instrument to the Mexican-American culture as found along the U.S.-Mexico border and (2) To test the equivalence between the Spanish translated, culturally adapted version of the PFI and the English version of the PFI to include clarity, content validity, reading level and reliability.^ Design. Descriptive, cross-sectional.^ Methods. The Spanish language translation used a translation model which incorporates a cultural adaptation process. The SPFI was administered to 175 bilingual participants residing in a midsize, U.S-Mexico border city. Data analysis included estimation of Cronbach's alpha, factor analysis, paired samples t-test comparison and multiple regression analysis using SPSS software, as well as measurement of content validity and reading level of the SPFI. ^ Findings. A reliability estimate using Cronbach's alpha coefficient was 0.81 for the SPFI compared to 0.80 for the PFI in this study. Factor Analysis extracted four factors which explained 59% of the variance. Paired t-test comparison revealed no statistically significant differences between the SPFI and PFI total or individual item scores. Content Validity Index was determined to be 1.0. Reading Level was assessed to be less than a 6th grade reading level. The correlation coefficient between the SPFI and PFI was 0.95.^ Conclusions. This study provided strong psychometric evidence that the Spanish translated, culturally adapted SPFI is an equivalent tool to the English version of the PFI in measuring cancer fatalism. This indicates that the two forms of the instrument can be used interchangeably in a single study to accommodate reading and speaking abilities of respondents. ^

Toxics Release Inventory facilities and childhood cancer: Geographic information systems based approach

Purpose. To examine the association between living in proximity to Toxics Release Inventory (TRI) facilities and the incidence of childhood cancer in the State of Texas. ^ Design. This is a secondary data analysis utilizing the publicly available Toxics release inventory (TRI), maintained by the U.S. Environmental protection agency that lists the facilities that release any of the 650 TRI chemicals. Total childhood cancer cases and childhood cancer rate (age 0-14 years) by county, for the years 1995-2003 were used from the Texas cancer registry, available at the Texas department of State Health Services website. Setting: This study was limited to the children population of the State of Texas. ^ Method. Analysis was done using Stata version 9 and SPSS version 15.0. Satscan was used for geographical spatial clustering of childhood cancer cases based on county centroids using the Poisson clustering algorithm which adjusts for population density. Pictorial maps were created using MapInfo professional version 8.0. ^ Results. One hundred and twenty five counties had no TRI facilities in their region, while 129 facilities had at least one TRI facility. An increasing trend for number of facilities and total disposal was observed except for the highest category based on cancer rate quartiles. Linear regression analysis using log transformation for number of facilities and total disposal in predicting cancer rates was computed, however both these variables were not found to be significant predictors. Seven significant geographical spatial clusters of counties for high childhood cancer rates (p<0.05) were indicated. Binomial logistic regression by categorizing the cancer rate in to two groups (<=150 and >150) indicated an odds ratio of 1.58 (CI 1.127, 2.222) for the natural log of number of facilities. ^ Conclusion. We have used a unique methodology by combining GIS and spatial clustering techniques with existing statistical approaches in examining the association between living in proximity to TRI facilities and the incidence of childhood cancer in the State of Texas. Although a concrete association was not indicated, further studies are required examining specific TRI chemicals. Use of this information can enable the researchers and public to identify potential concerns, gain a better understanding of potential risks, and work with industry and government to reduce toxic chemical use, disposal or other releases and the risks associated with them. TRI data, in conjunction with other information, can be used as a starting point in evaluating exposures and risks. ^

REGRESSION ANALYSIS FOR STANDARDIZED MORTALITY RATIOS WITH APPLICATION TO OCCUPATIONAL FOLLOW-UP STUDIES

Traditional comparison of standardized mortality ratios (SMRs) can be misleading if the age-specific mortality ratios are not homogeneous. For this reason, a regression model has been developed which incorporates the mortality ratio as a function of age. This model is then applied to mortality data from an occupational cohort study. The nature of the occupational data necessitates the investigation of mortality ratios which increase with age. These occupational data are used primarily to illustrate and develop the statistical methodology.^ The age-specific mortality ratio (MR) for the covariates of interest can be written as MR(,ij...m) = ((mu)(,ij...m)/(theta)(,ij...m)) = r(.)exp (Z('')(,ij...m)(beta)) where (mu)(,ij...m) and (theta)(,ij...m) denote the force of mortality in the study and chosen standard populations in the ij...m('th) stratum, respectively, r is the intercept, Z(,ij...m) is the vector of covariables associated with the i('th) age interval, and (beta) is a vector of regression coefficients associated with these covariables. A Newton-Raphson iterative procedure has been used for determining the maximum likelihood estimates of the regression coefficients.^ This model provides a statistical method for a logical and easily interpretable explanation of an occupational cohort mortality experience. Since it gives a reasonable fit to the mortality data, it can also be concluded that the model is fairly realistic. The traditional statistical method for the analysis of occupational cohort mortality data is to present a summary index such as the SMR under the assumption of constant (homogeneous) age-specific mortality ratios. Since the mortality ratios for occupational groups usually increase with age, the homogeneity assumption of the age-specific mortality ratios is often untenable. The traditional method of comparing SMRs under the homogeneity assumption is a special case of this model, without age as a covariate.^ This model also provides a statistical technique to evaluate the relative risk between two SMRs or a dose-response relationship among several SMRs. The model presented has application in the medical, demographic and epidemiologic areas. The methods developed in this thesis are suitable for future analyses of mortality or morbidity data when the age-specific mortality/morbidity experience is a function of age or when there is an interaction effect between confounding variables needs to be evaluated. ^

Efficiency from pharmacy inventory technology: A means to improving quality in non-profit hospitals

Hospitals, like all organizations, have both a mission and a finite supply of resources with which to accomplish that mission. Because the inventory of therapeutic drugs is among the more expensive resources needed by a hospital to achieve its mission, a conceptual model of structure plus process equals outcome posits that adequate emphasis should be placed on optimization of the organization's investment in this important structural resource to provide highest quality outcomes. Therefore emphasis should be placed on the optimization of pharmacy inventory because lowering the financial investment in drug inventory and associated costs increases productive efficiency, a key element of quality. ^ In this study, a post-intervention analysis of a hospital pharmacy inventory management technology implementation at The University of Texas M.D. Anderson Cancer Center was conducted to determine if an intervention which reduced a hospital's financial investment in pharmaceutical inventory provided an opportunity to incrementally optimize the organization's mix of structural resources thereby improving quality of care. The results suggest that hospital pharmacies currently lacking technology to support automated purchasing logistics and perpetual, real-time inventory management for drugs may achieve measurable benefits from the careful implementation of such technology, enabling the hospital to lower its investment in on-hand inventory and, potentially, to reduce overall purchasing expenditures. ^ The importance of these savings to the hospital and potentially to the patient should not be underestimated for their ability to generate funding for previously unfunded public health programs or in their ability to provide financial relief to patients in the form of lower drug costs given the current climate of escalating healthcare costs and tightening reimbursements.^