Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999-2004

BACKGROUND. Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited. OBJECTIVE. We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20-54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999-2004. METHODS. We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate (MEP), and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS. Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively. The ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77-2.41) for endometriosis, 1.56 (95% CI, 0.93-2.61) for leiomyomata, and 1.71 (95% CI, 1.07-2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19-1.02) for endometriosis, 0.63 (95% CI, 0.35-1.12) for leiomyomata, and 0.59 (95% CI, 0.37-0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed null associations for MEP and MBzP. Associations were similar when we excluded women diagnosed > 7 years before their NHANES evaluation. CONCLUSION. The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies

Butyrate down-regulates CD44 transcription and liver colonisation in a highly metastatic human colon carcinoma cell line

Over-expression of the adhesion molecule CD44 and its splice variants, especially CD44v6, is associated with poor prognosis and metastasis. We aimed at regulating the expression of CD44 in the highly metastatic human colon cancer cell line HM7 and thereby affecting its metastatic ability. HM7 cells show constitutive expression of CD44 standard and variants isoforms, which were significantly down-regulated by treatment with butyrate. Butyrate significantly inhibited transcription of the CD44 gene and abolished epidermal growth factor-mediated up-regulation of the reporter gene luciferase subcloned upstream to the CD44 promoter (−1.1 kb) and transfected to HM7 cells. Nuclear proteins from butyrate-treated cells bound to an epidermal growth factor receptor element motif present in the CD44 promoter. Epidermal growth factor receptor element-site directed mutations eliminated the inducibility of the luciferase reporter gene and did not allowed binding of nuclear proteins harvested from butyrate-treated cells. Butyrate induced CD44 gene repression by specifically interacting with an epidermal growth factor receptor element nuclear transcriptional factor. This interaction affects CD44 transcriptional activity vis-à-vis in vivo metastatic ability of HM7 cells. These results provide additional insight into the anticarcinogenic properties of butyrate

Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients

Ifosfamide and cisplatin cause urinary loss of carnitine, which is a fundamental molecule for energy production in mammalian cells. We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients. Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry. Patients were excluded if they had anaemia or other conditions thought to be causing asthenia. Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life questionnaire. Treatment consisted of oral levocarnitine 4 g daily, for 7 days. Fifty patients were enrolled; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients. In the whole group, baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 (±6.4; standard deviation) and the mean plasma carnitine value was 20.9 μM (±6.8; standard deviation). After 1 week, fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 (±5.4; standard deviation) (P<.001). All patients achieved normal plasma carnitine levels. Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy. In selected patients, levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue. This compound deserves further investigations in a randomised, placebo-controlled study

Health-related quality of life in French adolescents and adults: norms for the DUKE Health Profile

<p>Abstract</p> <p>Background</p> <p>The continual monitoring of population health-related quality of life (HRQoL) with validated instruments helps public health agencies assess, protect, and promote population health. This study aimed to determine norms for the French adolescent and adult general population for the Duke Health Profile (DUKE) questionnaire in a large representative community sample.</p> <p>Methods</p> <p>We randomly selected 17,733 French people aged 12 to 75 years old in 2 steps, by households and individuals, from the National Health Barometer 2005, a periodic population study by the French National Institute for Prevention and Health Education. Quality of life and other data were collected by computer-assisted telephone interview.</p> <p>Results</p> <p>Normative data for the French population were analyzed by age, gender and self-reported chronic disease. Globally, function scores (best HRQoL=100) for physical, mental, social, and general health, as well as perceived health and self-esteem, were 72.3 (SEM 0.2), 74.6 (0.2), 66.8 (0.1), 71.3 (0.1), 71.3 (0.3), 76.5 (0.1), respectively. Dysfunction scores (worst HRQoL=100) for anxiety, depression, pain and disability domains were 30.9 (0.1), 27.6 (0.2), 34.3 (0.3), 3.1 (0.1), respectively.</p> <p>Conclusion</p> <p>The French norms for adolescents and adults for the DUKE could be used as a reference for other studies assessing HRQoL, for specific illnesses, in France and for international comparisons.</p

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

The effects of socioeconomic status and indices of physical environment on reduced birth weight and preterm births in Eastern Massachusetts

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Air pollution and social characteristics have been shown to affect indicators of health. While use of spatial methods to estimate exposure to air pollution has increased the power to detect effects, questions have been raised about potential for confounding by social factors.Methods: A study of singleton births in Eastern Massachusetts was conducted between 1996 and 2002 to examine the association between indicators of traffic, land use, individual and area-based socioeconomic measures (SEM), and birth outcomes ( birth weight, small for gestational age and preterm births), in a two-level hierarchical model.Results: We found effects of both individual ( education, race, prenatal care index) and area-based ( median household income) SEM with all birth outcomes. The associations for traffic and land use variables were mainly seen with birth weight, with an exception for an effect of cumulative traffic density on small for gestational age. Race/ethnicity of mother was an important predictor of birth outcomes and a strong confounder for both area-based SEM and indices of physical environment. The effects of traffic and land use differed by level of education and median household income.Conclusion: Overall, the findings of the study suggested greater likelihood of reduced birth weight and preterm births among the more socially disadvantaged, and a greater risk of reduced birth weight associated with traffic exposures. Results revealed the importance of controlling simultaneously for SEM and environmental exposures as the way to better understand determinants of health.This work is supported by the Harvard Environmental Protection Agency (EPA) Center, Grants R827353 and R-832416, and National Institute for Environmental Health Science (NIEHS) ES-0002

Well-being as a Function of Person-Country Fit in Human Values

It is often assumed that incongruence between individuals’ values and those of their country is distressing, but the evidence has been mixed. Across 29 countries, the present research investigated whether well-being is higher if people’s values match with those of people living in the same country or region. Using representative samples, we find that person-country and person-region value congruence predict six well-being measures (e.g., emotional well-being, relationship support; N = 54,673). Crucially, however, value type moderates whether person-country fit is positively or negatively associated with well-being. People who value self-direction, stimulation, and hedonism more and live in countries and regions where people on average share these values report lower well-being. In contrast, people who value achievement, power, and security more and live in countries and regions where people on average share these values, report higher well-being. Additionally, we find that people who moderately value stimulation report the highest well-being

Appraising and applying evidence about a diagnostic test during a performance-based assessment

BACKGROUND: The practice of Evidence-based Medicine requires that clinicians assess the validity of published research and then apply the results to patient care. We wanted to assess whether our soon-to-graduate medical students could appraise and apply research about a diagnostic test within a clinical context and to compare our students with peers trained at other institutions. METHODS: 4(th )year medical students who previously had demonstrated competency at probability revision and just starting first-year Internal Medicine residents were used for this research. Following an encounter with a simulated patient, subjects critically appraised a paper about an applicable diagnostic test and revised the patient's pretest probability given the test result. RESULTS: The medical students and residents demonstrated similar skills at critical appraisal, correctly answering 4.7 and 4.9, respectively, of 6 questions (p = 0.67). Only one out of 28 (3%) medical students and none of the 15 residents were able to correctly complete the probability revision task (p = 1.00). CONCLUSIONS: This study found that most students completing medical school are able to appraise an article about a diagnostic test but few are able to apply the information from the article to a patient. These findings raise questions about the clinical usefulness of the EBM skills possessed by graduating medical students within the area of diagnostic testing

Personal values and involvement in problem behaviors among Bahamian early adolescents: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Few studies, particularly in developing countries, have explored the relationship between adolescents and parental values with adolescent problem behaviors. The objectives of the study are to (1) describe adolescents' personal values, their problem behaviors, and the relationships thereof according to gender and (2) examine the relationship between parental values, adolescent values, and adolescents' problem behaviors among sixth-grade students and one of their parents.</p> <p>Methods</p> <p>The data used in these analyses were from the baseline assessment of a school-based HIV risk reduction intervention being conducted and evaluated among sixth grade students and one of their parents across 9 elementary schools in The Bahamas. Personal values were measured by the Portrait Values Questionnaire (PVQ). Seven reported problem behaviors were queried from the students, which included physical fight with a friend, drank alcohol, beer, or wine, smoked a cigarette, pushed or carried any drugs, carried a gun, knife, screwdriver or cutlass to use as a weapon, had sex and used marijuana or other illicit drugs over the past 6 months. Multilevel modeling for binary data was performed to estimate the associations between adolescent and parental values and adolescent problem behaviors.</p> <p>Results</p> <p>Among 785 students, 47% of the students reported at least one problem behavior. More boys (54%) reported having one or more problem behaviors than girls (41%, p < 0.01). Boys compared to girls expressed a higher level of self-enhancement (means score: 36.5 vs. 35.1; p = 0.03), while girls expressed a higher level of self-transcendence (42.3 vs. 40.7; p = 0.03). The results of multilevel modeling indicates that boys with a higher level of self-enhancement and girls with a higher level of openness to change and a lower level of conservation were more likely to report engagement in problem behaviors. Only two parental values (self-transcendence and conservation) were low or modestly correlated with youth' values (openness to change and self-enhancement). Parental-reported values documented limited association on adolescents' reported values and behaviors.</p> <p>Conclusion</p> <p>In designing interventions for reducing adolescents' problem behaviors, it may be important to understand the values associated with specific problem behaviors. Further exploration regarding lack of association between adolescent and parental values and problem behaviors is needed.</p

A web-based library consult service for evidence-based medicine: Technical development

BACKGROUND: Incorporating evidence based medicine (EBM) into clinical practice requires clinicians to learn to efficiently gain access to clinical evidence and effectively appraise its validity. Even using current electronic systems, selecting literature-based data to solve a single patient-related problem can require more time than practicing physicians or residents can spare. Clinical librarians, as informationists, are uniquely suited to assist physicians in this endeavor. RESULTS: To improve support for evidence-based practice, we have developed a web-based EBM library consult service application (LCS). Librarians use the LCS system to provide full text evidence-based literature with critical appraisal in response to a clinical question asked by a remote physician. LCS uses an entirely Free/Open Source Software platform and will be released under a Free Software license. In the first year of the LCS project, the software was successfully developed and a reference implementation put into active use. Two years of evaluation of the clinical, educational, and attitudinal impact on physician-users and librarian staff are underway, and expected to lead to refinement and wide dissemination of the system. CONCLUSION: A web-based EBM library consult model may provide a useful way for informationists to assist clinicians, and is feasible to implement