Oncologic outcomes in diabetic patients with colon cancer

Type II diabetes mellitus is a growing problem worldwide and although its association with increased cardiovascular morbidity and mortality is well known, its role in the development of cancer is now being further elucidated. Recently, there has been increasing evidence that not only are diabetics more susceptible towards development of particular types of cancer, but also have worse oncologic outcomes. This retrospective chart review investigates whether diabetics with colon cancer have a poorer prognosis than their nondiabetic counterparts. Patients with high risk Stage II and Stage III colon cancer who were diagnosed and/or treated at The University of Texas M.D. Anderson Cancer Center from 1/1/2000 till 12/1/2004 were included in our study. We carried out a survival analysis using Kaplan-Meier method and multivariable analysis to assess differences in outcomes of the two population groups. We found that the decreased overall survival in diabetics did not reach statistical significance but this could be due to a lower event rate in our study. Larger studies are required to investigate this further. ^

Employment outcomes in liver transplant recipients: A policy analysis

Liver transplantation is a widely accepted treatment for end stage liver disease. Research has shown that people with end-stage liver disease experience improved survival and health-related quality of life after transplantation. However, the unemployment rate among liver transplant recipients remains high. The reasons for this were the subject of a study that was used as the primary dataset for this policy analysis. According to the primary data and background supporting data, many transplant recipients remain unemployed for fear of losing needed healthcare and disability benefits. When employment is considered as a health outcome, it is important in an era of evidence based medicine to ensure that healthcare interventions such as liver transplantation produce improved health outcomes. Therefore, the high unemployment rate among liver transplant recipients is a poor health outcome that should be addressed. In this policy analysis, it is proposed that policy might affect this outcome. The problem of unemployment after liver transplantation is structured and policies affecting the problem are evaluated according to the validated criteria - Effectiveness, Equity, Efficiency, and Feasibility. A policy solution is proposed, evaluated, and ultimately recommended to effectively address the problem, to make healthcare coverage more equitable for liver transplant recipients, and to provide a more cost-effective healthcare coverage model during this time of healthcare crisis.^

A systematic review of selected birth outcomes in diabetic women who received preconception care and/or used multivitamins prior to pregnancy

Objective. To conduct a systematic review of published literature on preconception care in pre-existing diabetic women looking at the effect of glycemic control and multivitamin usage on the frequency of spontaneous abortion and birth defects.^ Methods. Articles were retrieved from Medline (1950–Dec 2007), Cochrane Library (1800–Dec 2007), Academic Search Complete (Ebsco) (Jan 1800–Dec 2007) and Maternal and Child Health Library (1965–Dec 2007). Studies included women with pre-existing, non-gestational diabetes and a comparison group. Participants must have either received preconception care and/or consumed a multivitamin as part of the study.^ Results. Overall, seven studies met the study criteria and applicability to the study objectives. Four of these reported the frequency of spontaneous abortion. Only one found a statistically significant increased risk of spontaneous abortion among pregnant women who did not receive preconception care compared with those who did receive care, odds ratio 4.32; 95% CI 1.34 to 13.9. Of the seven studies, six reported the frequency of birth defects. Five of these six studies found a significantly increased rate of birth defects among pregnant women who did not receive preconception care compared with those who did receive care, with odds ratios ranging from 1.53 to 10.16. All seven studies based their preconception care intervention on glycemic control. One study also used multivitamins as part of the preconception care.^ Conclusion. Glycemic control was shown to be useful in reducing the prevalence of birth defects, but not as useful in reducing the prevalence of spontaneous abortion. Insulin regimen options vary widely for the diabetic woman. No author excluded or controlled for women who may have been taking a multivitamin on their own. Due to the small amount of literature available, it is still not known which preconception care option, glucose control and/or multivitamin usage, provides better protection from birth defects and spontaneous abortion for the diabetic woman. An area for future investigation would be glycemic control and the use of folic acid started before pregnancy and the effects on birth defects and spontaneous abortion.^

A study of the relationship of support systems and adolescent pregnancy outcomes in an adolescent family life project

This study analyzed the relationship of family support systems and adolescent pregnancy outcomes. The population for the study was 390 adolescents who had attended the Marion County Health Department Adolescent Family Life Project in Indianapolis, Indiana during a two-year period.^ The study is unique in that it afforded the opportunity to compare adolescent pregnancy-related characteristics, of white and non-white adolescents in the same study.^ The pregnancy outcomes studied were: Infant birthweight, school attendance, and pregnancy recidivism.^ Significant results were found in the analysis that supported other research in regard to factors that are associated with school attendance when family support, adolescent's age, and ethnicity were controlled. Infant birthweight and repeat pregnancy outcome relationships were not found to have any consistently significant relationship with independent variables anticipated to be associated. However, the comparisons of infant birthweight among the adolescents with, and without, family support, by ethnicity resulted in some interesting findings. Repeat pregnancy proved an enigma, in that there seemed to be almost no variables in this study that were associated with the adolescent having a repeat pregnancy.^ Familial support in this study seemed to be of less importance as a factor in adolescent pregnancy outcomes than was ethnicity. The non-white adolescents in this study had a better record for remaining in school, both those non-white adolescents who lived with parents, and those who did not live with parents. More low birthweight occurred in the non-white adolescent, both those adolescents who lived with parents, and those who did not live with parents. Repeat pregnancy occurred more in the non-white adolescent whether she lived with parents, or did not live with parents. ^

INTAKE VARIABLES AS PREDICTORS OF ASSESSMENT AND REFERRAL PROCEDURE OUTCOMES IN EMPLOYEE ASSISTANCE PROGRAMS

While reported prevalence rates of troubled employees vary considerably, even conservative estimates indicate a major public health problem. For example, alcohol and drug related problems alone cost U.S. industry more than 45 billion dollars annually.^ Of the alternatives available to deal with these problems, e.g., dismissal or disciplinary actions, the most viable and cost effective are employee assistance programs (EAP), designed to provide professional assistance to employees experiencing alcohol, drug, emotional or personal crisis.^ The principal component of an EAP is that of assessment and referral, and this study was developed to determine which EAP client intake variables are the most efficacious predictors of assessment and referral procedures.^ Although, specific client intake variables were statistically significant the discriminant classification analysis was demonstrably inadequate. Nevertheless, the identification of A/R procedure phases which were not efficacious, as well as EAP client populations for whom services were not effective, were extremely valuable discernments. Identifying the less efficacious components of the A/R process provided an opportunity to recommend alternatives to current program procedures and practices, which may ameliorate program effectiveness. ^

Genetic Predictors of Clinical Outcomes in Non-Small Cell Lung Cancer Patients

Lung cancer is the leading cause of cancer-related mortality in the US. Emerging evidence has shown that host genetic factors can interact with environmental exposures to influence patient susceptibility to the diseases as well as clinical outcomes, such as survival and recurrence. We aimed to identify genetic prognostic markers for non-small cell lung cancer (NSCLC), a major (85%) subtype of lung cancer, and also in other subgroups. With the fast evolution of genotyping technology, genetic association studies have went through candidate gene approach, to pathway-based approach, to the genome wide association study (GWAS). Even in the era of GWAS, pathway-based approach has its own advantages on studying cancer clinical outcomes: it is cost-effective, requiring a smaller sample size than GWAS easier to identify a validation population and explore gene-gene interactions. In the current study, we adopted pathway-based approach focusing on two critical pathways - miRNA and inflammation pathways. MicroRNAs (miRNA) post-transcriptionally regulate around 30% of human genes. Polymorphisms within miRNA processing pathways and binding sites may influence patients’ prognosis through altered gene regulation. Inflammation plays an important role in cancer initiation and progression, and also has shown to impact patients’ clinical outcomes. We first evaluated 240 single nucleotide polymorphisms (SNPs) in miRNA biogenesis genes and predicted binding sites in NSCLC patients to determine associations with clinical outcomes in early-stage (stage I and II) and late-stage (stage III and IV) lung cancer patients, respectively. First, in 535 early-stage patients, after correcting multiple comparisons, FZD4:rs713065 (hazard ratio [HR]:0.46, 95% confidence interval [CI]:0.32-0.65) showed a significant inverse association with survival in early stage surgery-only patients. SP1:rs17695156 (HR:2.22, 95% CI:1.44-3.41) and DROSHA:rs6886834 (HR:6.38, 95% CI:2.49-16.31) conferred increased risk of progression in the all patients and surgery-only populations, respectively. FAS:rs2234978 was significantly associated with improved survival in all patients (HR:0.59, 95% CI:0.44-0.77) and in the surgery plus chemotherapy populations (HR:0.19, 95% CI:0.07-0.46).. Functional genomics analysis demonstrated that this variant creates a miR-651 binding site resulting in altered miRNA regulation of FAS, providing biological plausibility for the observed association. We then analyzed these associations in 598 late-stage patients. After multiple comparison corrections, no SNPs remained significant in the late stage group, while the top SNP NAT1:rs15561 (HR=1.98, 96%CI=1.32-2.94) conferred a significantly increased risk of death in the chemotherapy subgroup. To test the hypothesis that genetic variants in the inflammation-related pathways may be associated with survival in NSCLC patients, we first conducted a three-stage study. In the discovery phase, we investigated a comprehensive panel of 11,930 inflammation-related SNPs in three independent lung cancer populations. A missense SNP (rs2071554) in HLA-DOB was significantly associated with poor survival in the discovery population (HR: 1.46, 95% CI: 1.02-2.09), internal validation population (HR: 1.51, 95% CI: 1.02-2.25), and external validation (HR: 1.52, 95% CI: 1.01-2.29) population. Rs2900420 in KLRK1 was significantly associated with a reduced risk for death in the discovery (HR: 0.76, 95% CI: 0.60-0.96) and internal validation (HR: 0.77, 95% CI: 0.61-0.99) populations, and the association reached borderline significance in the external validation population (HR: 0.80, 95% CI: 0.63-1.02). We also evaluated these inflammation-related SNPs in NSCLC patients in never smokers. Lung cancer in never smokers has been increasingly recognized as distinct disease from that in ever-smokers. A two-stage study was performed using a discovery population from MD Anderson (411 patients) and a validation population from Mayo Clinic (311 patients). Three SNPs (IL17RA:rs879576, BMP8A:rs698141, and STK:rs290229) that were significantly associated with survival were validated (pCD74:rs1056400 and CD38:rs10805347) were borderline significant (p=0.08) in the Mayo Clinic population. In the combined analysis, IL17RA:rs879576 resulted in a 40% reduction in the risk for death (p=4.1 × 10-5 [p=0.61, heterogeneity test]). We also validated a survival tree created in MD Anderson population in the Mayo Clinic population. In conclusion, our results provided strong evidence that genetic variations in specific pathways that examined (miRNA and inflammation pathways) influenced clinical outcomes in NSCLC patients, and with further functional studies, the novel loci have potential to be translated into clinical use.

Are anatomic brain locations important in determining the clinical outcomes in acute ischemic stroke? --- An exploratory analysis of the NINDS Stroke Trial data

Background and purpose. Brain lesions in acute ischemic stroke measured by imaging tools provide important clinical information for diagnosis and final infarct volume has been considered as a potential surrogate marker for clinical outcomes. Strong correlations have been found between lesion volume and clinical outcomes in the NINDS t-PA Stroke Trial but little has been published about lesion location and clinical outcomes. Studies of the National Institute of Neurological Disorders and Stroke (NINDS) t-PA Stroke Trial data found the direction of the t-PA treatment effect on a decrease in CT lesion volume was consistent with the observed clinical effects at 3 months, but measure of t-PA treatment benefits using CT lesion volumes showed a diminished statistical significance, as compared to using clinical scales. ^ Methods. We used the global test to evaluate the hypothesis that lesion locations were strongly associated with clinical outcomes within each treatment group at 3 months after stroke. The anatomic locations of CT scans were used for analysis. We also assessed the effect of t-PA on lesion location using a global statistical test. ^ Results. In the t-PA group, patients with frontal lesions had larger infarct volumes and worse NIHSS score at 3 months after stroke. The clinical status of patients with frontal lesions in t-PA group was less likely to be affected by lesion volume, as compared to those who had no frontal lesions in at 3 months. For patients within the placebo group, both brain stem and internal capsule locations were significantly associated with a lower odd of having favorable outcomes at 3 months. Using a global test we could not detect a significant effect of t-PA treatment on lesion location although differences between two treatment groups in the proportion of lesion findings in each location were found. ^ Conclusions. Frontal, brain stem, and internal capsule locations were significantly related to clinical status at 3 months after stroke onset. We detect no significant t-PA effect on all 9 locations although proportion of lesion findings in differed among locations between the two treatment groups.^

Evaluation of CHIP perinatal program outcomes in Harris County, Texas

This study compared initial year trends in prenatal care and birth outcomes of women enrolled in the Texas Children's Health Insurance Program (CHIP) Perinatal program to trends in Medicaid program women. The study utilized claims data from Community Health Choice (CHC), a health plan in Harris County, Texas that provides coverage to both populations. Quarterly data was analyzed and compared for the first two years of the CHIP Perinatal program (2007-2008) to determine if outcome trends for the CHIP program improved over the outcome trends seen with those enrolled in Medicaid. Study findings indicate an increase in the quarterly prenatal care utilization for the CHIP Perinatal population from 2007 to 2008 and the associated birth weights of babies delivered also had marginal improvements during the same timeframe. Enrollees in Medicaid continued to have overall better outcomes than those enrolled within the CHIP Perinatal program. However, the study showed that the rate of improvement in both prenatal care utilization and birth outcomes were greater for the CHIP Perinatal enrollees than those enrolled in Medicaid. ^ The majority of these improvements were significant when comparing each coverage program and from year to year. Lastly, the study showed that there was a correlation between prenatal care utilization and birth outcomes. However, further analysis of the data could not conclusively indicate that access to prenatal care services provided by the CHIP Perinatal program contributed to the increases observed in utilization and birth outcomes for the study's sample population.^

The effects of adequacy and content of prenatal care on birth outcomes in a high -risk Missouri population

The purpose of this observational study was investigation of the relationship between quantitative adequacy of prenatal care, specific prenatal care content and pregnancy outcome in a high risk Missouri population. A sample of 1484 women from three Missouri regions known to have high rates of low birth weight, infant mortality, and inadequate prenatal care rates participated in structured post-partum interviews. Approximately one-half of the sample had received adequate prenatal care and the other half inadequate prenatal care as determined by an index utilized by the Missouri Department of Health.^ Prenatal care content was assessed by reports of prenatal education in six different areas: Diet, smoking, alcohol, drug, preterm labor counseling, and advice on when to call the health provider if preterm labor was suspected by the woman. Low birth weight, in both term and preterm infants, were the two birth outcomes examined. A variety of maternal socio-demographic variables were also considered.^ The results of this study suggest that specific educational content, delivered during prenatal care, may have lessen the risk of giving birth to a preterm-low birth weight infant. Prenatal education for recognition of preterm labor, and advice on when to call the health provider if preterm labor was suspected were found to be associated with a decreased risk of preterm delivery. Specific educational content was not, however, associated with risk of term-low weight birth nor was quantitative adequacy of care associated with the risk of either term- or preterm-low birth weight.^ These findings reinforce a body of literature which stresses the importance of appropriate prenatal care in preventing preterm low birth weight. Additionally, the findings suggest interventions that may be specifically effective for prematurity prevention. ^

Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age. DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability.

Self -management behavior in patients with cystic fibrosis

Self-management is being promoted in cystic fibrosis (CF). However, it has not been well studied. Principal aims of this research were (1) to evaluate psychometric properties of a CF disease status measure, the NIH Clinical Score; (2) to develop and validate a measure of self-management behavior, the SMQ-CF scale, and (3) to examine the relation between self-management and disease status in CF patients over two years.^ In study 1, NIH Clinical Scores for 200 patients were used. The scale was examined for internal consistency, interrater reliability, and content validity using factor analysis. The Cronbach's alpha (.81) and interrater reliability (.90) for the total scale were high. General scale items were less reliable. Factor analysis indicated that most of the variance in disease status is accounted for by Factor 1 which consists of pulmonary disease items.^ The SMQ-CF measures the performance of CF self-management. Pilot testing was done with 98 CF primary caregivers. Internal consistency reliability, social desirability bias, and content validity using factor analysis were examined. Internal consistency was good (alpha =.95). Social desirability correlation was low (r =.095). Twelve factors identified were consistent with conceptual groupings of behaviors. Around two hundred caregivers from two CF centers were surveyed and multivariate analysis of variance was used to assess construct validity. Results confirmed expected relations between self-management, patient age, and disease status. Patient age accounted for 50% and disease status 18% of the variance in the SMQ-CF scale.^ It was hypothesized that self-management would positively affect future disease status. Data from 199 CF patients (control and education intervention groups) were examined. Models of hypothesized relations were tested using LISREL structural equation modeling. Results indicated that the relations between baseline self-management and Time 1 disease status were not significant. Significant relations were observed in self-management behaviors from time 1 to time 2 and patterns of significant relations differed between the two groups.^ This research has contributed to refinements in the ability to measure self-management behavior and disease status outcomes in cystic fibrosis. In addition, it provides the first steps in exploratory behavioral analysis with regard to self-management in this disease. ^