To quantify the role of practice characteristics in patient-specific receipt of dental diagnostic radiographic services.
Data Source/Study Setting
Florida Dental Care Study (FDCS).
The FDCS was a 48-month prospective observational cohort study of community-dwelling adults. Participants' dentists were asked to complete a questionnaire about their practice characteristics.
Data Collection/Extraction Methods
In-person interviews and clinical examinations were conducted at baseline, 24, and 48 months, with 6-monthly telephone interviews in between. A single multivariate (four radiographic service outcomes) multivariable (multiple explanatory covariates) logistic regression was used to model service receipts.
These practice characteristics were significantly associated with patient-specific receipt of radiographic services: number of different practices attended during follow-up; dentist's rating of how busy the practice was; typical waiting time for a new patient examination; practice size; percentage of patients that the dentist reported as interested in details about the condition of their mouths; percentage of African American patients in the practice; percentage of patients in the practice who do not have dental insurance; and dentist's agreement with a statement regarding whether patients should be dismissed from the practice. Effects had differential magnitudes and directions of effect, depending upon radiograph type.
Practice characteristics were significantly associated with patient-specific receipt of services. These effects were independent of patient-specific disease level and patient-specific sociodemographic characteristics, suggesting that practitioners do influence receipt of these diagnostic services. These findings are consistent with the conclusion that practitioners act in response to a mix of patients' interests, economic self-interests, and their own treatment preferences.
Practice characteristics; practice pattern; health care utilization; dental; race
Exposure to carcinogenic metals, such as trivalent arsenic [As(III)] and hexavalent chromium [Cr(VI)], through drinking water is a major global public health problem and is associated with various cancers. However, the mechanism of their carcinogenicity remains unclear. In this study, we used azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse colitis-associated colorectal cancer model to investigate their tumorigenesis. Our results demonstrate that exposure to As(III) or Cr(VI), alone or in combination, together with AOM/DSS pretreatment has a promotion effect, increasing the colorectal tumor incidence, multiplicity, size, and grade, as well as cell inflammatory response. Two-dimensional differential gel electrophoresis coupled with mass spectrometry revealed that As(III) or Cr(VI) treatment alone significantly changed the density of proteins. The expression of β-catenin and phospho-GSK was increased by treatment of carcinogenic metals alone. Concomitantly, the expression of NADPH oxidase1 (NOX1) and the level of 8-OHdG were also increased by treatment of carcinogenic metals alone. Antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, were decreased. Similarly, in an in vitro system, exposure of CRL-1807 to carcinogenic metals increased reactive oxygen species (ROS) generation, the expression of β-catenin, phospho-GSK, and NOX1. Inhibition of ROS generation by addition of SOD or catalase inhibited β-catenin expression and activity. Our study provides a new animal model to study the carcinogenicity of As(III) and Cr(VI) and suggest that As(III) and Cr(VI) promote colorectal cancer tumorigenesis, at least partly, through ROS-mediated Wnt/β-catenin signaling pathway.
As(III); Cr(VI); tumorigenesis; colorectal cancer; ROS; Wnt/β-catenin pathway
To quantify racial and socioeconomic status (SES) disparities in oral health, as measured by tooth loss, and to determine the role of dental care use and other factors in explaining disparities.
Data Sources/Study Setting
The Florida Dental Care Study, comprising African Americans (AAs) and non-Hispanic whites 45 years old or older who had at least one tooth.
We used a prospective cohort design. Relevant population characteristics were grouped by predisposing, enabling, and need variables. The key outcome was tooth loss, a leading measure of a population's oral health, looked at before and after entering the dental care system. Tooth-specific data were used to increase inferential power by relating the loss of individual teeth to the disease level on those teeth.
Data Collection Methods
In-person interviews and clinical examinations were done at baseline, 24, and 48 months, with telephone interviews every 6 months.
African Americans and persons of lower SES reported more new dental symptoms, but were less likely to obtain dental care. When they did receive care, they were more likely to experience tooth loss and less likely to report that dentists had discussed alternative treatments with them. At the first stage of analysis, differences in disease severity and new symptoms explained tooth loss disparities. Racial and SES differences in attitudes toward tooth loss and dental care were not contributory. Because almost all tooth loss occurs by means of dental extraction, the total effects of race and SES on tooth loss were artificially minimized unless disparities in dental care use were taken into account.
Race and SES are strong determinants of tooth loss. African Americans and lower SES persons had fewer teeth at baseline and still lost more teeth after baseline. Tooth-specific case-mix adjustment appears, statistically, to explain social disparity variation in tooth loss. However, when social disparities in dental care use are taken into account, social disparities in tooth loss that are not directly due to clinical circumstance become evident. This is because AAs and lower SES persons are more likely to receive a dental extraction once they enter the dental care system, given the same disease extent and severity. This phenomenon underscores the importance of understanding how disparities in health care use, dental insurance coverage, and service receipt contribute to disparities in health. Absent such understanding, the total effects of race and SES on health can be underestimated.
Tooth loss; health disparities; race; socioeconomic status
To test five hypotheses that non-Hispanic African Americans (AAs) and non-Hispanic whites (NHWs) differ in responsiveness to new dental symptoms by seeking dental care, and differ in certain predictors of dental care utilization.
Data Sources/Study Setting
Florida Dental Care Study, comprising AAs and NHWs 45 years old or older, who had at least one tooth, and who lived in north Florida.
We used a prospective cohort design. The key outcome of interest was whether dental care was received in a given six-month period, after adjusting for the presence of certain time-varying and fixed characteristics.
Data Collection/Extraction Methods
In-person interviews were conducted at baseline and 24 months after baseline, with six-monthly telephone interviews in between.
African Americans were less likely to seek dental care during follow-up, with or without adjusting for key predisposing, enabling, and oral health need characteristics. African Americans were more likely to be problem-oriented dental attenders, to be unable to pay an unexpected $500 dental bill, and to report postbaseline dental problems. However, the effect of certain postbaseline dental signs and symptoms on postbaseline dental care use differed between AAs and NHWs. Although financial circumstance was predictive for both groups, it was more salient for NHWs in separate NHW and AA regressions. Frustration with past dental care, propensity to use a homemade remedy, and dental insurance were significant predictors among AAs, but not among NHWs. The NHWs were much more likely to have sought care for preventive reasons.
Racial differences in responsiveness to new dental symptoms by seeking dental care were evident, as were differences in other predictors of dental care utilization. These differences may contribute to racial disparities in oral health.
Dental care; health disparities; race; socioeconomic status; longitudinal
Lung cancer rates in Appalachian Kentucky are almost twice national rates; colorectal cancer rates are also elevated. Although smoking prevalence is high, it does not explain all excess risk. The area is characterized by poverty, low educational attainment, and unemployment. Coal production is a major industry. Pyrite contaminants of coal contain established human carcinogens, arsenic (As), chromium (Cr), and nickel (Ni). We compared biological exposure to As, Cr, and Ni for adults living in Appalachian Kentucky with residents of Jefferson, a non-Appalachian, urban county. We further compared lung and colon cancer rates, demographics, and smoking prevalence across the study areas. Toenail clipping analysis measured As, Cr, and Ni for residents of 23 rural Appalachian Kentucky counties and for Jefferson County. Reverse Kaplan-Meier statistical methodology addressed left-censored data. Appalachian residents were exposed to higher concentrations of As, Cr, and Ni than Jefferson County residents. Lung cancer incidence and mortality rates in Appalachia are higher than Jefferson County and elsewhere in the state, as are colorectal mortality rates. Environmental factors may contribute to the increased concentration of trace elements measured in residents of the Appalachian region. Routes of human exposure need to be determined.
arsenic; chromium; nickel; Appalachia; toenail; cancer; mining; environmental
Faith Moves Mountains assessed the effectiveness of a faith-placed lay health advisor (LHA) intervention to increase Papanicolaou (Pap) test use among middle-aged and older women in a region disproportionately affected by cervical cancer and low screening rates (regionally, only 68% screened in prior 3 years).
This community-based RCT was conducted in four Appalachian Kentucky counties (December 2005 – June 2008). Women aged 40–64 and overdue for screening were recruited from churches and individually randomized to treatment (n=176) or wait-list control (n=169). The intervention provided LHA home visits and newsletters addressing barriers to screening. Self-reported Pap test receipt was the primary outcome.
Intention-to-treat analyses revealed that treatment group participants (17.6% screened) had over twice the odds of wait-list controls (11.2% screened) of reporting Pap test receipt post-intervention, OR=2.56, 95%CI: 1.03–6.38, p=0.04. Independent of group, recently screened participants (last Pap >1 but <5 years ago) had significantly higher odds of obtaining screening during the study than rarely or never screened participants (last Pap ≥5 years ago), OR=2.50, 95%CI: 1.48–4.25, p=0.001.
The intervention was associated with increased cervical cancer screening. The faith-placed LHA addressing barriers comprises a novel approach to reducing cervical cancer disparities among Appalachian women.
cervical cancer screening; randomized controlled trial; faith-placed; Appalachia
Mobile health units are increasingly utilized to address barriers to mammography screening. Despite the existence of mobile mammography outreach throughout the US, there is a paucity of data describing the populations served by mobile units and the ability of these programs to reach underserved populations, address disparities, and report on outcomes of screening performance. To evaluate the association of variables associated with outcomes for women undergoing breast cancer screening and clinical evaluation on a mobile unit. Retrospective analysis of women undergoing mammography screening during the period 2008–2010. Logistic regression was fitted using generalized estimating equations to account for potential repeat annual visits to the mobile unit. In total, 4,543 mammograms and/or clinical breast exams were conducted on 3,923 women with a mean age of 54.6, 29 % of whom had either never been screened or had not had a screening in 5 years. Age < 50 years, lack of insurance, Hispanic ethnicity, current smoking, or having a family relative (<50 years of age) with a diagnosis of cancer were associated with increased odds of a suspicious mammogram finding (BIRADS 4,5,6). Thirty-one breast cancers were detected. The mobile outreach initiative successfully engaged many women who had not had a recent mammogram. Lack of insurance and current smoking were modifiable variables associated with abnormal screens requiring follow up.
Breast cancer; Mobile mammography; Underserved populations; Outcomes; Disparities
The tumor suppressor protein Par-4 (prostate apoptosis response-4) is spontaneously secreted by normal and cancer cells. Extracellular Par-4 induces caspase-dependent apoptosis in cancer cell cultures by binding, via its effector SAC domain, to cell surface GRP78 receptor. However, the functional significance of extracellular Par-4/SAC has not been validated in animal models. We show that Par-4/SAC-transgenic mice express systemic Par-4/SAC protein and are resistant to the growth of non-autochthonous tumors. Consistently, secretory Par-4/SAC pro-apoptotic activity can be transferred from these cancer-resistant transgenic mice to cancer-susceptible mice by bone marrow transplantation. Moreover, intravenous injection of recombinant Par-4 or SAC protein inhibits metastasis of cancer cells. Collectively, our findings indicate that extracellular Par-4/SAC is systemically functional in inhibition of tumor growth and metastasis progression, and may merit investigation as a therapy.
Par-4; metastasis; systemic protein
Natural killer (NK) cells are essential for healthy aging. NK cell activation is controlled by MHC class I-specific CD94/NKG2 receptors and killer immunoglobulin-like receptors (KIR). To assess NK cytotoxic function in isolation from MHC receptor engagement, we measured the ability of purified NK cells to kill mouse P815 target cells in the presence of anti-CD16 mAb. CD16-mediated cytotoxicity did not change with age, indicating that NK activation and cytotoxic granule release remained functional. We then investigated MHC class I receptor expression on NK cells. There was an age related decrease in CD94 and NKG2A expression and a reciprocal age related increase in KIR expression. NKG2A expression also declined with age on CD56+ T cells. CD94/NKG2A receptor function was proportional to expression, indicating that NK cell inhibitory signaling pathways were intact. NKG2A and KIR expression were complementary, suggesting that CD94/NKG2A function could substitute for inhibitory KIR function during polyclonal NK cell development in both young and elderly adults. The distinct roles of CD94/NKG2A and KIR receptors suggest that shifting MHC class I receptor expression patterns reflect age related changes in NK cell and CD56+ T cell turnover and function in vivo.
Natural killer; Aging; Receptor; MHC class I; KIR; CD94; NKG2A; Cytotoxicity; NKT
Natural killer (NK) cells are essential for health, yet little is known about human NK turnover in vivo. In both young and elderly women, all NK subsets proliferated and died more rapidly than T cells. CD56bright NK cells proliferated rapidly, but died relatively slowly, suggesting that proliferating CD56bright cells differentiate into CD56dim NK cells in vivo. The relationship between CD56dim and CD56bright proliferating cells indicates that proliferating CD56dim cells both self renew and are derived from proliferating CD56bright NK cells. Our data suggests that some dying CD56dim cells become CD16+CD56− NK cells and that CD16−CD56low NK cells respond rapidly to cellular and cytokine stimulation. We propose a model in which all NK cell subsets are in dynamic flux. About half of CD56dim NK cells expressed CD57, which was weakly associated with low proliferation. Surprisingly, CD57 expression was associated with higher proliferation rates in both CD8+ and CD8− T cells. Therefore, CD57 is not a reliable marker of senescent, nonproliferative T cells in vivo. NKG2A expression declined with age on both NK cells and T cells. KIR expression increased with age on T cells, but not on NK cells. Although the percentage of CD56bright NK cells declined with age and the percentage of CD56dim NK cells increased with age, there were no significant age-related proliferation or apoptosis differences for these two populations or for total NK cells. In vivo human NK cell turnover is rapid in both young and elderly adults.
This study explored using a novel diffuse correlation spectroscopy (DCS) flow-oximeter to noninvasively monitor blood flow and oxygenation changes in head and neck tumors during radiation delivery. A fiber-optic probe connected to the DCS flow-oximeter was placed on the surface of the radiologically/clinically involved cervical lymph node. The DCS flow-oximeter in the treatment room was remotely operated by a computer in the control room. From the early measurements, abnormal signals were observed when the optical device was placed in close proximity to the radiation beams. Through phantom tests, the artifacts were shown to be caused by scattered x rays and consequentially avoided by moving the optical device away from the x-ray beams. Eleven patients with head and neck tumors were continually measured once a week over a treatment period of seven weeks, although there were some missing data due to the patient related events. Large inter-patient variations in tumor hemodynamic responses were observed during radiation delivery. A significant increase in tumor blood flow was observed at the first week of treatment, which may be a physiologic response to hypoxia created by radiation oxygen consumption. Only small and insignificant changes were found in tumor blood oxygenation, suggesting that oxygen utilizations in tumors during the short period of fractional radiation deliveries were either minimal or balanced by other effects such as blood flow regulation. Further investigations in a large patient population are needed to correlate the individual hemodynamic responses with the clinical outcomes for determining the prognostic value of optical measurements.
(170.0170) Medical optics and biotechnology; (170.3660) Light propagation in tissues; (170.3880) Medical and biological imaging; (170.6480) Spectroscopy, speckle
Toxoplasma IgG and IgA, but not IgM, antibody titers were significantly higher in immunocompetent mice with cerebral proliferation of tachyzoites during the chronic stage of infection than those treated with sulfadiazine to inhibit the parasite growth. Their IgG and IgA antibody titers correlated significantly with the amounts of tachyzoite-specific SAG1 mRNA in their brains. In contrast, neither IgG, IgA, nor IgM antibody titers increased following two different doses of challenge infection in chronically infected mice. Increased antibody titers in IgG and IgA but not IgM may be a useful indicator suggesting an occurrence of cerebral tachyzoite growth in immunocompetent individuals chronically infected with T. gondii.
Toxoplasma gondii; IgG; IgA; IgM; Cerebral toxoplasmosis; Schizophrenia; Epilepsy
The NCI-60 is a collection of tumor cell lines derived from a variety of human adult cancer tissue types and is commonly used for genetic analysis and screening of potential chemotherapeutic agents. We wanted to understand the contributions of specific mechanisms of genomic instability to the etiology of cancers represented by the NCI-60.
We screened the NCI-60 for dysregulated homologous recombination by using the gene cluster instability (GCI) assay we pioneered, and for defects in base excision repair by sensitivity to 5-hydroxymethyl-2'-deoxyuridine (hmdUrd). We identified subsets of the NCI-60 lines that either displayed the characteristic molecular signature of GCI or were sensitive to hmdUrd. With the exception of the NCI-H23 lung cancer line, these phenotypes were not found to overlap. None of the lines examined in either subset exhibited significant changes in the frequency of sister chromatid exchanges (SCE), neither did any of the lines in either subset exhibit microsatellite instability (MSI) indicative of defects in DNA mismatch repair.
Gene cluster instability, sensitivity to hmdUrd and sister chromatid exchange are mechanistically distinct phenomena. Genomic instability in the NCI-60 appears to involve only one mechanism of instability for each individual cell line.
AR-67 is a novel third generation camptothecin selected for development based on the blood stability of its pharmacologically active lactone form and high potency in preclinical models. Here we report the initial phase I experience with intravenous AR-67 in adults with refractory solid tumors.
Experimental Design and Methods
AR-67 was infused over 1 hour daily × 5, every 21-days, using an accelerated titration trial design. Plasma was collected on the 1st and 4th day of cycle 1 to determine pharmacokinetic parameters.
Twenty six patients were treated at 9 dosage levels (1.2–12.4mg/m2/day). Dose limiting toxicities (DLTs) were observed in 5 patients and consisted of grade 4 febrile neutropenia, grade 3 fatigue, and grade 4 thrombocytopenia. Common toxicities included: leukopenia (23%), thrombocytopenia (15.4%), fatigue (15.4%), neutropenia (11.5%), and anemia (11.5%). No diarrhea was observed. The maximum tolerated dosage (MTD) was 7.5 mg/m2/day. The lactone form was the predominant species in plasma (>87% of AUC) at all dosages. No drug accumulation was observed on day 4. Clearance was constant with increasing dosage and hematologic toxicities correlated with exposure (p<0.001). A prolonged partial response was observed in one subject with non-small cell lung cancer (NSCLC). Stable disease was noted in patients with small cell lung cancer (SCLC), NSCLC, and duodenal cancer.
AR-67 is a novel, blood stable camptothecin with a predictable toxicity profile and linear pharmacokinetics. The recommended phase II dosage is 7.5mg/m2/day ×5 q 21 days.
Camptothecin analog; cytotoxic therapy; phase I trial; pharmacokinetics; pharmacodynamics
To explore patterns of adherence to guidelines for screening mammography among participants in the Colorado Mammography Project (CMAP) surveillance database.
An algorithm was developed to assess factors associated with adherence to mammography screening guidelines.
Of the 27,778 women ranging from 40–90 years of age included in the analysis, 41.4% were adherent with mammography screening guidelines. According to the model tested in this study, race/ethnicity (Black vs White, OR=0.76, 95% CI=0.64–0.91); educational attainment (high school vs $55,000 vs <$15,000, OR 1.14, 95% CI=1.03–1.26) were statistically significant predictors of adherence to guidelines. A significant interaction between age and family history of breast cancer (BC) was also found. Younger females with a family history of BC were less likely to be adherent than their counterparts without a family history (OR=0.93, 95% CI=0.90–0.96). In general, elderly women were more likely to be adherent compared with the youngest group in this cohort (OR=1.21, 95% CI=1.11–1.33). Inclusion or exclusion of women aged 70 years and older did not change the outcome of the analysis.
Adherence with screening mammography guidelines was found to be associated with women’s personal characteristics including race/ethnicity, age, and family history of BC. In addition, socioeconomic status, as measured by educational level and community economic status, are important predictors of adherence. Efforts to increase adherence may need to be specific to race/ethnic group and age, but the effect of age is mediated by family history of BC and vice versa.
Surveillance; Adherence; Breast Cancer; Mammography; Screening; and Utilization
To examine theory-based selected factors associated with adherence to mammography screening guidelines in a surveillance database.
Data from Colorado Mammography Project (CMAP) from 1994–1998 was extracted and analyzed by using SAS statistical software. Based on the Health Belief Model and Behavioral Model of Health Services Utilization a prediction model was developed to examine the mammography utilization patterns and factors influencing the adherence to screening guidelines.
Out of 27,778 women, 41.4% were adherent with mammography screening guidelines. According to the model tested in this study, race/ethnicity (Black vs White, OR=0.76, 95% CI=0.64–0.91); educational attainment (high school vs < high school, OR= 1.10, 95% CI= 1.04–1.18), college graduate vs < high school (OR=1.33, 95% CI=1.25–1.42); insurance status, (any coverage vs no coverage (OR=1.62, 95% CI=1.25–2.12); and community economic status as defined by median income by zip code of residence ($15,000–$24,999 vs <$15,000, OR=0.84, 95% CI=0.76–0.94; >$55,000 vs <$15,000, OR 1.14, 95% CI=1.03–1.26) were statistically significant predictors of adherence to guidelines. Interaction between age and family history of breast cancer was statically significant. Younger females with a family history of breast cancer were less likely to be adherent than their counterparts without a family history (OR=0.93, 95% CI=0.90–0.96). Inclusion or exclusion of women aged 70 years and older did not change the outcome of the analysis.
The prediction model variables such as race/ethnicity, age and family history of breast cancer, educational level and community economic status, are associated with adherence status. Family history of breast cancer needs to be examined very carefully in future studies as it may play negative role in adherence to screening mammography.
Adherence; Breast Cancer; Mammography; Screening; Health Belief Model; Andersen’s Model
Nearly all studies reporting smoking status collect self-reported data. The objective of this study was to assess sociodemographic characteristics and selected, common smoking-related diseases as predictors of invalid reporting of non-smoking. Valid self-reported smoking may be related to the degree to which smoking is a behavior that is not tolerated by the smoker's social group.
True smoking was defined as having serum cotinine of 15+ng/ml. 1483 "true" smokers 45+ years of age with self-reported smoking and serum cotinine data from the Mobile Examination Center were identified in the third National Health and Nutrition Examination Survey. Invalid non-smoking was defined as "true" smokers self-reporting non-smoking. To assess predictors of invalid self-reported non-smoking, odds ratios (OR) and 95% confidence intervals (CI) were calculated for age, race/ethnicity-gender categories, education, income, diabetes, hypertension, and myocardial infarction. Multiple logistic regression modeling took into account the complex survey design and sample weights.
Among smokers with diabetes, invalid non-smoking status was 15%, ranging from 0% for Mexican-American (MA) males to 22%–25% for Non-Hispanic White (NHW) males and Non-Hispanic Black (NHB) females. Among smokers without diabetes, invalid non-smoking status was 5%, ranging from 3% for MA females to 10% for NHB females. After simultaneously taking into account diabetes, education, race/ethnicity and gender, smokers with diabetes (ORAdj = 3.15; 95% CI: 1.35–7.34), who did not graduate from high school (ORAdj = 2.05; 95% CI: 1.30–3.22) and who were NHB females (ORAdj = 5.12; 95% CI: 1.41–18.58) were more likely to self-report as non-smokers than smokers without diabetes, who were high school graduates, and MA females, respectively. Having a history of myocardial infarction or hypertension did not predict invalid reporting of non-smoking.
Validity of self-reported non-smoking may be related to the relatively slowly progressing chronic nature of diabetes, in contrast with the acute event of myocardial infarction which could be considered a more serious, major life changing event. These data also raise questions regarding the possible role of societal desirability in the validity of self-reported non-smoking, especially among smokers with diabetes, who did not graduate from high school, and who were NHB females.
OBJECTIVE: The purpose of this study was to quantify the validity of self-reported receipt of dental services in 10 categories, using information from dental charts as the "gold standard." METHODS: The Florida Dental Care Study was a prospective cohort study of a diverse sample of adults. In-person interviews were conducted at baseline and at 24 and 48 months following baseline, with telephone interviews at six-month intervals in between. Participants reported new dental visits, reason(s) for the visit(s), and specific service(s) received. For the present study, self-reported data were compared with data from patients' dental charts. RESULTS: Percent concordance between self-report and dental charts ranged from 82% to 100%, while Kappa values ranged from 0.33 to 0.91. Bivariate multiple logistic regressions were performed for each of the service categories, with two outcomes: self-reported service receipt and service receipt determined from the dental chart. Parameter estimate intervals overlapped for each of the four hypothesized predictors of service receipt (age group, sex, "race" defined as non-Hispanic African American vs. non-Hispanic white, and annual household income < 20,000 US dollars vs. > or = 20,000 US dollars), although for five of the 10 service categories, there were differences in conclusions about statistical significance for certain predictors. CONCLUSIONS: The validity of self-reported use of dental services ranged from poor to excellent, depending upon the service type. Regression estimates using either the self-reported or chart-validated measure yielded similar results overall, but conclusions about key predictors of service use differed in some instances. Self-reported dental service use is valid for some, but not all, service types.