Developing the follow-up schedules for women with breast cancer

Background: The follow-up care for women with breast cancer requires an understanding of disease recurrence patterns and the follow-up visit schedule should be determined according to the times when the recurrence are most likely to occur, so that preventive measure can be taken to avoid or minimize the recurrence. Objective: To model breast cancer recurrence through stochastic process with an aim to generate a hazard function for determining a follow-up schedule. Methods: We modeled the process of disease progression as the time transformed Weiner process and the first-hitting-time was used as an approximation of the true failure time. The women's "recurrence-free survival time" or a "not having the recurrence event" is modeled by the time it takes Weiner process to cross a threshold value which represents a woman experiences breast cancer recurrence event. We explored threshold regression model which takes account of covariates that contributed to the prognosis of breast cancer following development of the first-hitting time model. Using real data from SEER-Medicare, we proposed models of follow-up visits schedule on the basis of constant probability of disease recurrence between consecutive visits. Results: We demonstrated that the threshold regression based on first-hitting-time modeling approach can provide useful predictive information about breast cancer recurrence. Our results suggest the surveillance and follow-up schedule can be determined for women based on their prognostic factors such as tumor stage and others. Women with early stage of disease may be seen less frequently for follow-up visits than those women with locally advanced stages. Our results from SEER-Medicare data support the idea of risk-controlled follow-up strategies for groups of women. Conclusion: The methodology we proposed in this study allows one to determine individual follow-up scheduling based on a parametric hazard function that incorporates known prognostic factors.^

Assessing the patterns of colorectal cancer treatment, adherence to treatment guidelines and survival in Texas

Colorectal cancer (CRC) is the third leading cancer in both incidence and mortality in Texas. This study investigated the adherence of CRC treatment to standard treatment guidelines and the association between standard treatment and CRC survival in Texas. The author used Texas Cancer Registry (TCR) and Medicare linked data to study the CRC treatment patterns and factors associated with standard treatment in patients who were more than 65 years old and were diagnosed in 2001 through 2007. We also determined whether adherence to standard treatment affect patients' survival. Multiple logistic regression and Cox regression analysis were used to analyze our data. Both regression models are adjusted for demographic characteristics and tumor characteristics. We found that for the 3977 regional colon cancer patients 80 years old or younger, 60.2% of them received chemotherapy, in adherence to the recommended treatment guidelines. People with younger age, female gender, higher education and lower comorbidity score are more likely adherent to this surgery guideline. Patients' adherence to chemotherapy in this cohort have better survival compared to those who are not (HR: 0.76, 95% CI: 0.68-0.84). For the 12709 colon cancer patients treated with surgery, 49.3% have more than 12 lymph nodes removed, in adherence to the treatment guidelines. People with younger age, female gender, higher education, regional stage, lager tumor size and lower comorbidity score are more likely to adherent to this surgery guideline. Patients with more than 12 lymph nodes removed in this cohort have better survival (HR: 0.86, 95% CI: 0.82-0.91). For the 1211 regional rectal cancer patients 80 years old or younger, 63.2% of them were adherent to radiation treatment. People with smaller tumor size and lower comorbidity score are more likely to adherent to this radiation guideline. There is no significant survival difference between radiation adherent patients and non-adherent patients (HR: 1.03, 95% CI: 0.82-1.29). For the 1122 regional rectal cancer patients 80 years old or younger who were treated with surgery, 76.0% of them received postoperative chemotherapy, in adherence to the treatment guidelines. People with younger age and smaller comorbidity score are related with higher adherence rate. Patients adherent with adjuvant chemotherapy in this cohort have better survival than those were not adherent (HR: 0.60, 95% CI: 0.45-0.79).^

Friends of the library groups in health sciences libraries.

The Houston Academy of Medicine--Texas Medical Center (HAM--TMC) Library collected data on friends of the library groups from 103 health sciences libraries, using a mail questionnaire. Sixteen of the responding libraries had independent friends groups; seven had friends groups that were subordinate to a university group. The sixteen independent groups gave as their major purposes (1) to raise money for their associated library and (2) to develop support for their library. These groups contributed an average of $4,870 a year to their libraries, the money being used primarily to purchase rare books and working-collection books and to sponsor social events. The subordinate groups contributed relatively little money to the health sciences libraries responding to the survey.

Comparison of a traditional and a multilevel Cox Proportional Hazards model

Hierarchically clustered populations are often encountered in public health research, but the traditional methods used in analyzing this type of data are not always adequate. In the case of survival time data, more appropriate methods have only begun to surface in the last couple of decades. Such methods include multilevel statistical techniques which, although more complicated to implement than traditional methods, are more appropriate. ^ One population that is known to exhibit a hierarchical structure is that of patients who utilize the health care system of the Department of Veterans Affairs where patients are grouped not only by hospital, but also by geographic network (VISN). This project analyzes survival time data sets housed at the Houston Veterans Affairs Medical Center Research Department using two different Cox Proportional Hazards regression models, a traditional model and a multilevel model. VISNs that exhibit significantly higher or lower survival rates than the rest are identified separately for each model. ^ In this particular case, although there are differences in the results of the two models, it is not enough to warrant using the more complex multilevel technique. This is shown by the small estimates of variance associated with levels two and three in the multilevel Cox analysis. Much of the differences that are exhibited in identification of VISNs with high or low survival rates is attributable to computer hardware difficulties rather than to any significant improvements in the model. ^

Effects of health disparities on Helicobacter pylori infection among children on the US-Mexico border

The objective of this study is to determine whether health disparities influence the odds of developing H. pylori infections among the children enrolled in the Pasitos Cohort Study on the US-Mexico border. The study variables were the number of prenatal care visits, ways of transportation, car in household, location of health services and insurance coverage. The study recruited eligible pregnant women to complete baseline questionnaires. Every six months after the birth of the child, infection status is measure by the 13-C urea breath test. Results indicate that having medical insurance consistently decreases the odds of being infected. Children with mothers who went to a private physician had decreased odds of infection compared to those utilizing public clinics, and having a car in the household increased the odds of infection. Limitations include bias due to loss to follow-up and the transient nature of the infection.^

Maternal nutrition and oral health factors in early childhood caries

Background. Early Childhood Caries (ECC) is the most common chronic infectious disease of childhood worldwide. Seven of ten American children have one or more decayed or filled primary teeth by age five. ECC prevalence is especially high in lower socio-economic ethnic populations. Commonly recognized as a diet-induced disease, focal etiological factors include cariogenic bacteria, fermentable carbohydrates, and a susceptible newly erupted tooth. Sequencing of breast and/or bottle feeding and introduction of beikost come at a time when children's defense mechanisms and, perhaps maternal direction of children's dietary patterns, are not yet fully developed or mature. To date, most research has examined biological factors, while maternal factors, especially psychosocial ones, have received scant attention. Objective. To examine the association of psychosocial factors in terms of maternal nutrition and oral health knowledge, attitudes, and beliefs, as well as social support and self-efficacy (KABS2) in a population of socio-economically disadvantaged infants and young children. A secondary aim was to describe ECC prevalence in this population. Methods. This study examined cross-sectionally the relationship between selected maternal psychosocial variables and ECC in a convenience sample of Mexican-American women and very young children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in San Antonio, Texas. Mothers were surveyed by use of a criteria- and content-valid, reliable questionnaire, and dental examinations were conducted on 191 children, aged 5 to 47 months old. Results. Thirty-nine percent of the children had ECC. As assessed on a 30-question scale, women in whose children were diagnosed with ECC were found to demonstrate lower Knowledge ( p=0.03), Attitudes (p=0.02), Beliefs (p=0.04), and Social Support (p<0.01) scores, compared to women whose children were found to be caries-free. No differences in Self-Efficacy scores were found between the groups. Conclusions. These data indicate that current etiological model depicting relevant factors associated with ECC in Mexican-American infants and children of low socio-economic status should be broadened to include consideration of maternal psychosocial factors such as nutrition and oral health knowledge, attitudes, beliefs, and social support, and that these factors should be considered when planning educational approaches to reduce the occurrence of ECC. ^

Modifier genes and susceptibility to colorectal cancer in individuals with Lynch syndrome

Lynch syndrome, is caused by inherited germ-line mutations in the DNA mismatch repair genes resulting in cancers at an early age, predominantly colorectal (CRC) and endometrial cancers. Though the median age at onset for CRC is about 45 years, disease penetrance varies suggesting that cancer susceptibility may be modified by environmental or other low-penetrance genes. Genetic variation due to polymorphisms in genes encoding metabolic enzymes can influence carcinogenesis by alterations in the expression and activity level of the enzymes. Variation in MTHFR, an important folate metabolizing enzyme can affect DNA methylation and DNA synthesis and variation in xenobiotic-metabolizing enzymes can affect the metabolism and clearance of carcinogens, thus modifying cancer risk. ^ This study examined a retrospective cohort of 257 individuals with Lynch syndrome, for polymorphisms in genes encoding xenobiotic-metabolizing enzymes-- CYP1A1 (I462V and MspI), EPHX1 (H139R and Y113H), GSTP1 (I105V and A114V), GSTM1 and GSTT1 (deletions) and folate metabolizing enzyme--MTHFR (C677T and A1298C). In addition, a series of 786 cases of sporadic CRC were genotyped for CYP1A1 I462V and EPHX1 Y113H to assess gene-gene interaction and gene-environment interaction with smoking in a case-only analysis. ^ Prominent findings of this study were that the presence of an MTHFR C677T variant allele was associated with a 4 year later age at onset for CRC on average and a reduced age-associated risk for developing CRC (Hazard ratio: 0.55; 95% confidence interval: 0.36–0.85) compared to the absence of any variant allele in individuals with Lynch syndrome. Similarly, Lynch syndrome individuals heterozygous for CYP1A1 I462V A>G polymorphism developed CRC an average of 4 years earlier and were at a 78% increased age-associated risk (Hazard ratio for AG relative to AA: 1.78; 95% confidence interval: 1.16-2.74) than those with the homozygous wild-type genotype. Therefore these two polymorphisms may be additional susceptibility factors for CRC in Lynch syndrome. In the case-only analysis, evidence of gene-gene interaction was seen between CYP1A1 I462V and EPHX1 Y113H and between EPHX1 Y113H and smoking suggesting that genetic and environmental factors may interact to increase sporadic CRC risk. Implications of these findings are the ability to identify subsets of high-risk individuals for targeted prevention and intervention. ^

Investigator/IRB-led community communication in genetic research: A descriptive feasibility pilot study

This pilot study, conducted in the Houston, TX, area, established a structured dialogue among a university Institutional Review Board, its researchers, and its local community members (i.e. pool of potential research participants) for the purpose of further educating all three parties about genetic research and community concerns related to such research. An IRB-designed educational presentation aimed at assisting potential subjects in making an informed decision to participate in genetic research was provided to four community groups (n=54); this presentation also included a current example of genetic research being conducted in the community as explained by the researcher, and a question-and-answer session designed to assist the IRB and the researcher in understanding the community's concerns about genetic research. Comparisons of pre- and post- presentation community questionnaires indicate that the joint presentation was effective in increasing community knowledge about genetic research, most notably related to the risks and benefits of this research to the individual, as well as the understanding that protections are in place for research participants. While researchers are optimistic about the idea of a collaborative effort with the IRB and the community, the feasibility of such a program and the benefit to the participating researchers remain unclear; additional research is necessary to establish the most effective method of communication for all groups involved, as well as to obtain statistically significant results with regard to race/ethnicity, gender, and education levels of community participants. ^

The epidemiology of Hepatitis B and Hepatitis C virus infection among college students who are not US/Canadian born in Houston

Introduction. A vast majority of studies conducted in both developed and developing nations have focused on the epidemiology of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) in high-risk populations; low-risk populations have been neglected. Recently Hwang et al conducted a unique large cross-sectional study in American university students that focused on cosmetic procedures and drug use for acquiring these infections among a low-risk young adult population In Houston. ^ Methods. This study is a secondary data analysis of the cross-sectional study conducted by Hwang et al. Data for this anonymous study were collected from 7,960 college students, among whom were the 2,561 non US/Canadian born students included in this study. All students completed a self-administered questionnaire and provided a blood sample. The epidemiology of HBV/HCV and risk factors for acquiring HBV/HCV infection was studied by comparing those with HBV/HCV infection versus those without. Both univariate and multivariate logistic regression was used to analyze the data. ^ Results. Overall prevalence of HBV and HCV infections were 22% and 0.8% respectively. By multivariable analysis, the factors that were independently associated with increased prevalence of HBV infection were increasing age per year (OR=1.06, 95% C.I=1.04-1.08), Black or Asian race (OR=6.21, 95% C.I=3.14-12.27), history of household contact with hepatitis (OR=1.87, 95% C.I=1.15-3.05), and having sexual partner with hepatitis (OR=5.20, 95% C.I=1.5-18.00). For HCV these factors included increasing age per year (OR= 1.08, 95% C.I=1.03-1.14), history of blood transfusion prior to 1991 (OR=25.45, 95% C.I=7.58-85.40), and Injection drug use. (OR=78.15, 95% C.I=12.19-500.85). Cosmetic procedures like tattooing were not significant risk factors for either HBV or HCV infection. ^ Conclusions. In a low-risk adult foreign born population, cosmetic procedures are not significant risk factors for HBV or HCV infection. The prevention strategies of these infections in this population should focus on safe sexual practices/abstinence and HBV vaccination should be provided to adolescents and sexually active adults. ^

Clinical relevance of polymorphic DNA copy number variation (CNV) in African American women with stage I-II breast cancer

Objectives. The chief goal of this study was to analyze copy number variation (CNV) in breast cancer tumors from 25 African American women with early stage breast cancer (BC) using molecular inversion probes (MIP) in order to: (1) compare the degree of CNV in tumors compared to normal lymph nodes, and (2) determine whether gains and/or losses of genes in specific chromosomes differ between pathologic subtypes of breast cancer defined by known prognostic markers, (3) determine whether gains/losses in CN are associated with known oncogenes or tumor suppressor genes, and (4) determine whether increased gains/losses in CN for specific chromosomes were associated with differences in breast cancer recurrence. ^ Methods. Twenty to 37 nanograms of DNA extracted from 25 formalin-fixed paraffin embedded (FFPE) tumor samples and matched normal lymph nodes were added to individual tubes. Oligonucleotide probes with recognition sequences at each terminus were hybridized with a genomic target sequence to form a circular structure. Probes are released from genomic DNA obtained from FFPE samples, and those which have been correctly "circularized" in the proper allele/nucleotide reaction combination are amplified using polymerase chain reaction (PCR) primers. Amplicons were fluorescently labeled and the tag sequences released from the genome homology regions by treatment with uracil-N-glycosylase to cleave the probe at the site where uracils are present, and detected using a complementary tag array developed by Affymetrix. ^ Results. Analysis of CN gains and losses from tumors and normal tissues showed marked differences in tumors with numerous chromosomes affected. Similar changes were not observed in normal lymph nodes. When tumors were stratified into four groups based on expression or lack of expression of the estrogen receptor and HER2/neu, distinct patterns of CNV for different chromosomes were observed. Gains or losses in CN for specific chromosomes correlated with amplifications/deletions of particular oncogenes or tumor suppressor genes (i.e. such as found on chromosome 17) known to be associated with aggressive tumor phenotype and poor prognosis. There was a trend for increases in CN observed for chromosome 17 to correlate inversely with time to recurrence of BC (p=0.14 for trend). CNV was also observed for chromosomes 5, 8, 10, 11, and 16, which are known sites for several breast cancer susceptibility alleles. ^ Conclusions. This study is the first to validate the MIP technique, to correlate differences in gene expression with known prognostic tumor markers, and to correlate significant increases/decreases in CN with known tumor markers associated with prognosis. The results of this study may have far reaching public health implications towards identifying new high-risk groups based on genomic differences in CNP, both with respect to prognosis and response to therapy, and to eventually identify new therapeutic targets for prevention and treatment of this disease. ^

Increased sensitivity of ETEC detection in stool cultures by increasing the number of E. coli colonies tested

The cause of infection of about a third of all travelers' diarrhea patients studied is not identified. Stools of these diarrhea patients tested for known enteric pathogens are shown to be negative, and identified as pathogen negative stools. We proposed that the third of these diarrhea patients might not only include at present unknown pathogens, but also known pathogens that go undetected. Conventionally, a probability sample of five E. coli colonies are used detect enterotoxigenic E. coli (ETEC) and other diarrhea-producing E. coli from stool cultures. We compared this conventional method of using five E. coli colonies, to the use of up to twenty E. coli colonies. Testing for up to fifteen E. coli colonies detected about twice as many ETEC when compared to the detection of ETEC, testing for five E. coli colonies. When the number of E. coli colonies tested was increased from 5 to 15, the detection of ETEC increased from 19.0% to 38.8%. The sensitivity of the assay with 5 E. coli colonies was statistically significantly different to the sensitivity of the assay with 10 E. coli colonies, suggesting that for the detection of ETEC at least 10 colonies of E. coli should be tested.^

Genotypic spectrum and genotype-phenotype correlation of trimethylaminuria

Trimethylaminuria (TMAU) or Fish odor syndrome is an autosomal recessive disease that is characterized by pungent body odor with subsequent psychosocial complications. There are limited studies of the sequence variants causing TMAU in the literature with most studies describing only one or two patients and lacking genotype-phenotype correlations. Also to date, there is no laboratory in the US or Europe that offers TMA genetic testing on a clinical basis. We have recently validated genetic testing in the University of Colorado DNA Diagnostic Laboratory. We have a database of a few dozen patients with a biochemical diagnosis of TMA at the University of Colorado at Denver Health Sciences Center (UCDHSC) which includes a few patients with the classical form of the disease. We have used the newly established clinical test in our institution to attempt to characterize the genotype (sequence variants including mutations and polymorphisms) of classical TMAU patients and to establish a genotype-phenotype (biochemical and clinical) association. The questionnaire results confirmed most of the previously reported epidemiological findings of TMAU and also indicated that TMAU patients use multiple intervention measures in attempt to control their symptoms with dietary control being most effective. Despite the complexity of intervention, most patients did not have any medical follow up and there was underutilization of specialist care. In a set of our patients, two deleterious mutations were identified in 4/12 patients including a novel T237P sequence variant, while the majority of our patients (8/12) did not reveal any mutations. Some of the latter were double heterozygous for the E158K and E308G polymorphisms which could explain a mild phenotype while others had only the E158K variant which raised the question of undetected mutations. These results indicate that further experiments are needed to further delineate the full mutational spectrum of the FMO3 gene. ^

Differences in health status of HIV infected children cared for by parents as compared to those cared for by grandparents

Purpose. The purpose of the study was to use measures of an HIV positive child's health to examine whether or not there is a difference in their health status according to caretaker and household economic status. ^ Study design. This was a case comparison study between HIV infected children living with parents and those living with grandparents. ^ Study setting. The study was conducted at the Pediatric Infectious Disease Clinic (PIDC) in Mulago, Kampala, Uganda. ^ Participants. 369 HIV-infected children aged seven months to 15 years attending the PIDC between June 13th and August 15th 2007 as well as their caretakers. ^ Method. Patients were recruited during their clinic visits after they had seen the health care providers and waited to receive their medication. Methods used included a survey of all the 369 caregiver participants and abstraction of data from the 369 patient charts. ^ Results. There was no significant association between staging and caretaker status (OR: 0.73 95%CI 0.44–1.21 p=0.09). Children taken care of by grandparents were more likely to have low height for age z-scores and higher weight for height z-scores (OR: 0.32, 95%CI: 0.14–0.74, p = 0.005). There was no difference is social support seeking behavior between parents and grandparents. ^ Conclusion. There was no statistically significant association observed between caretaker status and presenting in advanced stages. This implies that the stage at which HIV-infected children present for care is not determined by the type of caretaker. Caretakers for HIV-infected children need a lot of support beyond medical care. ^

Racial disparities in CD4 counts at initial HIV-1 diagnosis: Analysis of the Adult Spectrum of HIV disease dataset and public health implications

Introduction. The HIV/AIDS disease burden disproportionately affects minority populations, specifically African Americans. While sexual risk behaviors play a role in the observed HIV burden, other factors including gender, age, socioeconomics, and barriers to healthcare access may also be contributory. The goal of this study was to determine how far down the HIV/AIDS disease process people of different ethnicities first present for healthcare. The study specifically analyzed the differences in CD4 cell counts at the initial HIV-1 diagnosis with respect to ethnicity. The study also analyzed racial differences in HIV/AIDS risk factors. ^ Methods. This is a retrospective study using data from the Adult Spectrum of HIV Disease (ASD), collected by the City of Houston Department of Health. The ASD database contains information on newly reported HIV cases in the Harris County District Hospitals between 1989 and 2000. Each patient had an initial and a follow-up report. The extracted variables of interest from the ASD data set were CD4 counts at the initial HIV diagnosis, race, gender, age at HIV diagnosis and behavioral risk factors. One-way ANOVA was used to examine differences in baseline CD4 counts at HIV diagnosis between racial/ethnic groups. Chi square was used to analyze racial differences in risk factors. ^ Results. The analyzed study sample was 4767. The study population was 47% Black, 37% White and 16% Hispanic [p<0.05]. The mean and median CD4 counts at diagnosis were 254 and 193 cells per ml, respectively. At the initial HIV diagnosis Blacks had the highest average CD4 counts (285), followed by Whites (233) and Hispanics (212) [p<0.001 ]. These statistical differences, however, were only observed with CD4 counts above 350 [p<0.001], even when adjusted for age at diagnosis and gender [p<0.05]. Looking at risk factors, Blacks were mostly affected by intravenous drug use (IVDU) and heterosexuality, whereas Whites and Hispanics were more affected by male homosexuality [ p<0.05]. ^ Conclusion. (1) There were statistical differences in CD4 counts with respect to ethnicity, but these differences only existed for CD4 counts above 350. These differences however do not appear to have clinical significance. Antithetically, Blacks had the highest CD4 counts followed by Whites and Hispanics. (2) 50% of this study group clinically had AIDS at their initial HIV diagnosis (median=193), irrespective of ethnicity. It was not clear from data analysis if these observations were due to failure of early HIV surveillance, HIV testing policies or healthcare access. More studies need to be done to address this question. (3) Homosexuality and bisexuality were the biggest risk factors for Whites and Hispanics, whereas for Blacks were mostly affected by heterosexuality and IVDU, implying a need for different public health intervention strategies for these racial groups. ^