Affect and cognition measures in preference-based decisions: Validity testing of the Ottawa Decisional Conflict Scale and a decision-specific anxiety measure with men eligible for prostate cancer screening

Background. At present, prostate cancer screening (PCS) guidelines require a discussion of risks, benefits, alternatives, and personal values, making decision aids an important tool to help convey information and to help clarify values. Objective: The overall goal of this study is to provide evidence of the reliability and validity of a PCS anxiety measure and the Decisional Conflict Scale (DCS). Methods. Using data from a randomized, controlled PCS decision aid trial that measured PCS anxiety at baseline and DCS at baseline (T0) and at two-weeks (T2), four psychometric properties were assessed: (1) internal consistency reliability, indicated by factor analysis intraclass correlations and Cronbach's α; (2) construct validity, indicated by patterns of Pearson correlations among subscales; (3) discriminant validity, indicated by the measure's ability to discriminate between undecided men and those with a definite screening intention; and (4) factor validity and invariance using confirmatory factor analyses (CFA). Results. The PCS anxiety measure had adequate internal consistency reliability and good construct and discriminant validity. CFAs indicated that the 3-factor model did not have adequate fit. CFAs for a general PCS anxiety measure and a PSA anxiety measure indicated adequate fit. The general PCS anxiety measure was invariant across clinics. The DCS had adequate internal consistency reliability except for the support subscale and had adequate discriminate validity. Good construct validity was found at the private clinic, but was only found for the feeling informed subscale at the public clinic. The traditional DCS did not have adequate fit at T0 or at T2. The alternative DCS had adequate fit at T0 but was not identified at T2. Factor loadings indicated that two subscales, feeling informed and feeling clear about values, were not distinct factors. Conclusions. Our general PCS anxiety measure can be used in PCS decision aid studies. The alternative DCS may be appropriate for men eligible for PCS. Implications: More emphasis needs to be placed on the development of PCS anxiety items relating to testing procedures. We recommend that the two DCS versions be validated in other samples of men eligible for PCS and in other health care decisions that involve uncertainty. ^

Factors that affect non-adherence to first line antiretroviral medications among HIV infected children and adolescents in Botswana

The aims of the study were to determine the prevalence of and factors that affect non-adherence to first line antiretroviral (ARV) medications among HIV infected children and adolescents in Botswana. The study used secondary data from Botswana-Baylor Children's Clinical Center of Excellence for the period of June 2008 to February 10th, 2010. The study design was cross-sectional and case-comparison between non-adherent and adherent participants was used to examine the effects of socio-demographic and medication factors on non-adherence to ARV medications. A case was defined as non-adherent child with adherence level < 95% based on pill count and measurement of liquid formulations. The comparison group consisted of children with adherence levels ≥95%.^ A total of 842 participants met the eligibility criteria for determination of the prevalence of non-adherence and 338 participants (169 cases and 169 individuals) were used in the analysis to estimate the effects of factors on non-adherence. ^ Univariate and multivariable logistic regression were used to estimate the association between non-adherence (outcome) and socio-demographic and medication factors (exposures). The prevalence of non-adherence for participants on first line ARV medications was 20.0% (169/842).^ Increase in age (OR (95% CI): 1.10 (1.04–1.17) p = 0.001) was associated with nonadherence, while increase in number of caregivers (OR (95% CI): 0.72 (0.56–0.93) p = 0.01) and increase in number of monthly visits (OR (95% CI): 0.92 (0.86–0.99) p = 0.02), were associated with good adherence in both the unadjusted and the adjusted models. For the categorical variables, having more than two caregivers (OR (95% CI): 0.66 (0.28–0.84), p = 0.002) was associated with good adherence even in the adjusted model. ^ Conclusion. The prevalence of non-adherence to antiretroviral medicines among the study population was estimated to be 20.0%. In previous studies, adherence levels of ≥ 95% have been associated with better clinical outcomes and suppression of virus to prevent development of resistance. Older age, fewer numbers of caregivers and fewer monthly visits were associated with non-adherence. Strategies to improve and sustain adherence especially among older children are needed. The role of caregivers and social support should be investigated further.^

Policy analysis of Texas Senate Bill 532 and the regulation of nurse practitioners in the convenience care model

Background. Retail clinics, also called convenience care clinics, have become a rapidly growing trend since their initial development in 2000. These clinics are coupled within a larger retail operation and are generally located in "big-box" discount stores such as Wal-mart or Target, grocery stores such as Publix or H-E-B, or in retail pharmacies such as CVS or Walgreen's (Deloitte Center for Health Solutions, 2008). Care is typically provided by nurse practitioners. Research indicates that this new health care delivery system reduces cost, raises quality, and provides a means of access to the uninsured population (e.g., Deloitte Center for Health Solutions, 2008; Convenient Care Association, 2008a, 2008b, 2008c; Hansen-Turton, Miller, Nash, Ryan, Counts, 2007; Salinsky, 2009; Scott, 2006; Ahmed & Fincham, 2010). Some healthcare analysts even suggest that retail clinics offer a feasible solution to the shortage of primary care physicians facing the nation (AHRQ Health Care Innovations Exchange, 2010). ^ The development and performance of retail clinics is heavily dependent upon individual state policies regulating NPs. Texas currently has one of the most highly regulated practice environments for NPs (Stout & Elton, 2007; Hammonds, 2008). In September 2009, Texas passed Senate Bill 532 addressing the scope of practice of nurse practitioners in the convenience care model. In comparison to other states, this law still heavily regulates nurse practitioners. However, little research has been conducted to evaluate the impact of state laws regulating nurse practitioners on the development and performance of retail clinics. ^ Objectives. (1). To describe the potential impact that SB 532 has on retail clinic performance. (2). To discuss the effectiveness, efficiency, and equity of the convenience care model. (3). To describe possible alternatives to Texas' nurse practitioner scope of practice guidelines as delineated in Texas Senate Bill 532. (4). To describe the type of nurse practitioner state regulation (i.e. independent, light, moderate, or heavy) that best promotes the convenience care model. ^ Methods. State regulations governing nurse practitioners can be characterized as independent, light, moderate, and heavy. Four state NP regulatory types and retail clinic performance were compared and contrasted to that of Texas regulations using Dunn and Aday's theoretical models for conducting policy analysis and evaluating healthcare systems. Criteria for measurement included effectiveness, efficiency, and equity. Comparison states were Arizona (Independent), Minnesota (Light), Massachusetts (Moderate), and Florida (Heavy). ^ Results. A comparative states analysis of Texas SB 532 and alternative NP scope of practice guidelines among the four states: Arizona, Florida, Massachusetts, and Minnesota, indicated that SB 532 has minimal potential to affect the shortage of primary care providers in the state. Although SB 532 may increase the number of NPs a physician may supervise, NPs are still heavily restricted in their scope of practice and limited in their ability to act as primary care providers. Arizona's example of independent NP practice provided the best alternative to affect the shortage of PCPs in Texas as evidenced by a lower uninsured rate and less ED visits per 1,000 population. A survey of comparison states suggests that retail clinics thrive in states that more heavily restrict NP scope of practice as opposed to those that are more permissive, with the exception of Arizona. An analysis of effectiveness, efficiency, and equity of the convenience care model indicates that retail clinics perform well in the areas of effectiveness and efficiency; but, fall short in the area of equity. ^ Conclusion. Texas Senate 532 represents an incremental step towards addressing the problem of a shortage of PCPs in the state. A comparative policy analysis of the other four states with varying degrees of NP scope of practice indicate that a more aggressive policy allowing for independent NP practice will be needed to achieve positive changes in health outcomes. Retail clinics pose a temporary solution to the shortage of PCPs and will need to expand their locations to poorer regions and incorporate some chronic care to obtain measurable health outcomes. ^

Single nucleotide polymorphisms (SNPs) associated with TGF-beta pathway and their significance in systemic sclerosis - A multilevel analysis

Systemic sclerosis (SSc) or Scleroderma is a complex disease and its etiopathogenesis remains unelucidated. Fibrosis in multiple organs is a key feature of SSc and studies have shown that transforming growth factor-β (TGF-β) pathway has a crucial role in fibrotic responses. For a complex disease such as SSc, expression quantitative trait loci (eQTL) analysis is a powerful tool for identifying genetic variations that affect expression of genes involved in this disease. In this study, a multilevel model is described to perform a multivariate eQTL for identifying genetic variation (SNPs) specifically associated with the expression of three members of TGF-β pathway, CTGF, SPARC and COL3A1. The uniqueness of this model is that all three genes were included in one model, rather than one gene being examined at a time. A protein might contribute to multiple pathways and this approach allows the identification of important genetic variations linked to multiple genes belonging to the same pathway. In this study, 29 SNPs were identified and 16 of them located in known genes. Exploring the roles of these genes in TGF-β regulation will help elucidate the etiology of SSc, which will in turn help to better manage this complex disease. ^

Analysis of participation in the federally mandated coal workers' health surveillance program

The Federal Coal Mine Health and Safety Act of 1969 required that periodic chest radiographs be offered to underground coal miners to protect the miners from the development of Coal Workers' Pneumoconiosis (CWP) and progression of the disease to progressive massive fibrosis (PMF). These examinations are administered by the National Institute for Occupational Safety and Health (NIOSH) through the Coal Workers' Health Surveillance Program (CWHSP). The mine operator is required to provide each miner with the opportunity to have the chest radiograph at no cost to the miner.^ Three rounds of examinations have been conducted since 1969 and the fourth is underway. The decrease in participation over rounds is of great concern if the incidence and progression of CWP are to be understood and controlled.^ This study developed rates of participation for each of 558 West Virginia underground coal mines who submitted or had NIOSH assigned plans for making chest radiographs available during the third round, July 1978 through December 1980. These rates were analyzed in relation to desired levels of participation and to reinforcing, predisposing and enabling factors presumed to affect rates of participation in disease prevention and surveillance programs.^ Two reinforcing factors, size of mine and inclusion of the mine in the National Coal Study (NCS) epidemiology research program, and the enabling factor, use of an on-site radiograph facility, demonstrated highly significant relationships to participation rates.^ The major findings of the study were: (1) Participation in the CWHSP is even lower than previously estimated; (2) CWHSP program evaluation is not systematic and program data base is not complete and comprehensive; and (3) NIOSH program policy is not clear and administration of the CWHSP is fragmented and lacks adequate fiscal and personnel resources. ^

Estimates of life expectancy gains from reducing/eliminating major causes of death in the USA: An update analysis for population in 2001--2008

Evaluation of the impact of a disease on life expectancy is an important part of public health. Potential gains in life expectancy (PGLE) that can properly take into account the competing risks are an effective indicator for measuring the impact of the multiple causes of death. This study aimed to measure the PGLEs from reducing/eliminating the major causes of death in the USA from 2001 to 2008. To calculate the PGLEs due to the elimination of specific causes of death, the age-specific mortality rates for heart disease, malignant neoplasms, Alzheimer disease, kidney diseases and HIV/AIDS and life table constructing data were obtained from the National Center for Health Statistics, and the multiple decremental life tables were constructed. The PGLEs by elimination of heart disease, malignant neoplasms or HIV/AIDS continued decreasing from 2001 to 2008, but the PGLE by elimination of Alzheimer's disease or kidney diseases revealed increased trends. The PGLEs (by years) for all race, male, female, white, white male, white female, black, black male and black female at birth by complete elimination of heart disease 2001–2008 were 0.336–0.299, 0.327–0.301, 0.344–0.295, 0.360–0.315, 0.349–0.317, 0.371–0.316,0.278–0.251, 0.272–0.255, and 0.282–0.246 respectively. Similarly, the PGLEs (by years) for all race, male, female, white, white male, white female, black, black male and black female at birth by complete elimination of malignant neoplasms, Alzheimer's disease, kidney disease or HIV/AIDS 2001–2008 were also uncovered, respectively. Most diseases affect specific population, such as, HIV/AIDS tends to have a greater impact on people of working age, heart disease and malignant neoplasms have a greater impact on people over 65 years of age, but Alzheimer's disease and kidney diseases have a greater impact on people over 75 years of age. To measure the impact of these diseases on life expectancy in people of working age, partial multiple decremental life tables were constructed and the PGLEs were computed by partial or complete elimination of various causes of death during the working years. Thus, the results of the study outlined a picture of how each single disease could affect the life expectancy in age-, race-, or sex-specific population in USA. Therefore, the findings would not only assist to evaluate current public health improvements, but also provide useful information for future research and disease control programs.^

The relationship between obesity, autoimmune disease, and C-reactive protein: A secondary data analysis of the National Health and Nutrition Examination Survey (NHANES) 2009--2010

Autoimmune diseases are a group of inflammatory conditions in which the body's immune system attacks its own cells. There are over 80 diseases classified as autoimmune disorders, affecting up to 23.5 million Americans. Obesity affects 32.3% of the US adult population, and could also be considered an inflammatory condition, as indicated by the presence of chronic low-grade inflammation. C-reactive protein (CRP) is a marker of inflammation, and is associated with both adiposity and autoimmune inflammation. This study sought to determine the cross-sectional association between obesity and autoimmune diseases in a large, nationally representative population derived from NHANES 2009–10 data, and the role CRP might play in this relationship. Overall, the results determined that individuals with autoimmune disease were 2.11 times more likely to report being overweight than individuals without autoimmune disease and that CRP had a mediating affect on the obesity-autoimmune relationship. ^

Gene-gene interaction and gene-pathway analysis of genome-wide association for schizophrenia

Schizophrenia (SZ) is a complex disorder with high heritability and variable phenotypes that has limited success in finding causal genes associated with the disease development. Pathway-based analysis is an effective approach in investigating the molecular mechanism of susceptible genes associated with complex diseases. The etiology of complex diseases could be a network of genetic factors and within the genes, interaction may occur. In this work we argue that some genes might be of small effect that by itself are neither sufficient nor necessary to cause the disease however, their effect may induce slight changes to the gene expression or affect the protein function, therefore, analyzing the gene-gene interaction mechanism within the disease pathway would play crucial role in dissecting the genetic architecture of complex diseases, making the pathway-based analysis a complementary approach to GWAS technique. ^ In this study, we implemented three novel linkage disequilibrium based statistics, the linear combination, the quadratic, and the decorrelation test statistics, to investigate the interaction between linked and unlinked genes in two independent case-control GWAS datasets for SZ including participants of European (EA) and African (AA) ancestries. The EA population included 1,173 cases and 1,378 controls with 729,454 genotyped SNPs, while the AA population included 219 cases and 288 controls with 845,814 genotyped SNPs. We identified 17,186 interacting gene-sets at significant level in EA dataset, and 12,691 gene-sets in AA dataset using the gene-gene interaction method. We also identified 18,846 genes in EA dataset and 19,431 genes in AA dataset that were in the disease pathways. However, few genes were reported of significant association to SZ. ^ Our research determined the pathways characteristics for schizophrenia through the gene-gene interaction and gene-pathway based approaches. Our findings suggest insightful inferences of our methods in studying the molecular mechanisms of common complex diseases.^

Patenting genes and gene sequences: Analysis of public health implications and the law

At issue is whether or not isolated DNA is patent eligible under the U.S. Patent Law and the implications of that determination on public health. The U.S. Patent and Trademark Office has issued patents on DNA since the 1980s, and scientists and researchers have proceeded under that milieu since that time. Today, genetic research and testing related to the human breast cancer genes BRCA1 and BRCA2 is conducted within the framework of seven patents that were issued to Myriad Genetics and the University of Utah Research Foundation between 1997 and 2000. In 2009, suit was filed on behalf of multiple researchers, professional associations and others to invalidate fifteen of the claims underlying those patents. The Court of Appeals for the Federal Circuit, which hears patent cases, has invalidated claims for analyzing and comparing isolated DNA but has upheld claims to isolated DNA. The specific issue of whether isolated DNA is patent eligible is now before the Supreme Court, which is expected to decide the case by year's end. In this work, a systematic review was performed to determine the effects of DNA patents on various stakeholders and, ultimately, on public health; and to provide a legal analysis of the patent eligibility of isolated DNA and the likely outcome of the Supreme Court's decision. ^ A literature review was conducted to: first, identify principle stakeholders with an interest in patent eligibility of the isolated DNA sequences BRCA1 and BRCA2; and second, determine the effect of the case on those stakeholders. Published reports that addressed gene patents, the Myriad litigation, and implications of gene patents on stakeholders were included. Next, an in-depth legal analysis of the patent eligibility of isolated DNA and methods for analyzing it was performed pursuant to accepted methods of legal research and analysis based on legal briefs, federal law and jurisprudence, scholarly works and standard practice legal analysis. ^ Biotechnology, biomedical and clinical research, access to health care, and personalized medicine were identified as the principle stakeholders and interests herein. Many experts believe that the patent eligibility of isolated DNA will not greatly affect the biotechnology industry insofar as genetic testing is concerned; unlike for therapeutics, genetic testing does not require tremendous resources or lead time. The actual impact on biomedical researchers is uncertain, with greater impact expected for researchers whose work is intended for commercial purposes (versus basic science). The impact on access to health care has been surprisingly difficult to assess; while invalidating gene patents might be expected to decrease the cost of genetic testing and improve access to more laboratories and physicians' offices that provide the test, a 2010 study on the actual impact was inconclusive. As for personalized medicine, many experts believe that the availability of personalized medicine is ultimately a public policy issue for Congress, not the courts. ^ Based on the legal analysis performed in this work, this writer believes the Supreme Court is likely to invalidate patents on isolated DNA whose sequences are found in nature, because these gene sequences are a basic tool of scientific and technologic work and patents on isolated DNA would unduly inhibit their future use. Patents on complementary DNA (cDNA) are expected to stand, however, based on the human intervention required to craft cDNA and the product's distinction from the DNA found in nature. ^ In the end, the solution as to how to address gene patents may lie not in jurisprudence but in a fundamental change in business practices to provide expanded licenses to better address the interests of the several stakeholders. ^

Molecular and genetic analysis of Myxococcus xanthus early *development

To identify more mutations that can affect the early development of Myxococcus xanthus, the synthetic transposon TnT41 was designed and constructed. By virtue of its special features, it can greatly facilitate the processes of mutation screening/selection, mapping, cloning and DNA sequencing. In addition, it allows for the systematic discovery of genes in regulatory hierarchies using their target promoters. In this study, the minimal regulatory region of the early developmentally regulated gene 4521 was used as a reporter in the TnT41 mutagenesis. Both positive (P) mutations and negative (N) mutations were isolated based on their effects on 4521 expression.^ Four of these mutations, i.e. N1, N2, P52 and P54 were analyzed in detail. Mutations N1 and N2 are insertion mutations in a gene designated sasB. The sasB gene is also identified in this study by genetic and molecular analysis of five UV-generated 4521 suppressor mutations. The sasB gene encodes a protein without meaningful homology in the databases. The sasB gene negatively regulates 4521 expression possibly through the SasS-SasR two component system. A wild-type sasB gene is required for normal M. xanthus fruiting body formation and sporulation.^ Cloning and sequencing analysis of the P52 mutation led to the identification of an operon that encodes the M. xanthus high-affinity branched-chain amino acid transporter system. This liv operon consists of five genes designated livK, livH, livM, livC, and livF, respectively. The Liv proteins are highly similar to their counterparts from other bacteria in both amino acid sequences, functional motifs and predicted secondary structures. This system is required for development since liv null mutations cause abnormality in fruiting body formation and a 100-fold decrease in sporulation efficiency.^ Mutation P54 is a TnT41 insertion in the sscM gene of the ssc chemotaxis system, which has been independently identified by Dr. Shi's lab. The sscM gene encodes a MCP (methyl-accepting chemotaxis protein) homologue. The SscM protein is predicted to contain two transmembrane domains, a signaling domain and at least one putative methylation site. Null mutations of this gene abolish the aggregation of starving cells at a very early stage, though the sporulation levels of the mutant can reach 10% that of wild-type cells. ^