Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS).
DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 µl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 µm, 2.1×150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization.
The method was linear over the range 5–400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique.
Conclusions and Clinical Relevance
The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology.
Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women.
116,939 women in the California Teachers Study, aged 22 to 79 years with no history of thyroid cancer at cohort entry, were followed from 1995-1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort).
Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR=0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI<25.0 kg/m2, trend p=0.03) than among overweight or obese women (trend p=0.35; homogeneity-of-trends p=0.03). A similar pattern of risk was observed for recent activity (BMI<25 kg/m2, trend p=0.11; BMI≥25 kg/m2, trend p=0.16; homogeneity-of-trends p=0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood).
Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women.
Physical activity; thyroid cancer; cancer prevention; women; overweight/obesity; Body Mass Index
T cells are important to systemic lupus erythematosus (SLE) disease progression. This study determined the pro-inflammatory potential of T cells within the rare condition juvenile-onset SLE (JSLE).
IL-17A and Th1/Th2-related cytokine concentrations were measured in plasma/serum from JSLE patients (n = 19, n = 11) and HC (n = 18, n = 7). IL17A, RORC, IL23 and IL23R mRNA were measured in peripheral blood mononuclear cells (PBMCs) from JSLE and healthy controls (HC) (n = 12). Th17-associated cytokine expression was analysed in the supernatant of CD3/CD28 activated JSLE (n = 7) and HC (n = 6) PBMCs.
JSLE plasma IL-17A level (21.5 ± 5.2 pg/ml) was higher compared to HC (7.2 ± 2.5 pg/ml, p = 0.028). No differences were found in Th1/Th2 cytokines levels. IL = 17A (p = 0.022), IL-6 (p = 0.028) and IL-21 (p = 0.003) concentrations were increased in supernatants from activated JSLE PBMCs. IL-17 F (p = 0.50) and IL-22 (p = 0.43) were also increased but were not statistically significant. IL17A and IL23 mRNA was significantly higher in JSLE PBMCs (p = 0.018 and p = 0.01).
JSLE T cells have an increased ability to secrete Th17 associated cytokines once activated, which could contribute to the pro-inflammatory disease phenotype seen in these patients.
Juvenile-onset systemic lupus erythematosus; Lupus; IL-17A; Th17
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Children with JIA are at risk of inflammation of the uvea in the eye (uveitis). Overall, 20% to 25% of paediatric uveitis is associated with JIA. Major risk factors for development of uveitis in JIA are oligoarticular pattern of arthritis, an age at onset of arthritis of less than seven years of age, and antinuclear antibody positivity. In the initial stages of mild to moderate inflammation the uveitis is asymptomatic. This has led to current practice of screening all children with JIA for uveitis. Approximately 12% to 38% of patients with JIA develop uveitis in seven years following onset of arthritis. In 30% to 50% of children with JIA-associated uveitis structural complications are present at diagnosis. Furthermore about 50% to 75% of those with severe uveitis will eventually develop visual impairment secondary to ocular complications such as cataract and glaucoma. Defining the severity of inflammation and structural complications in uveitis patients is now possible following Standardised Uveitis Nomenclature (SUN) guidelines, and modified to incorporate the consensus of end point and outcome criteria into the design of randomised trials. Despite current screening and therapeutic options (pre-biologics) 10% to 15% of children with JIA-associated uveitis may develop bilateral visual impairment and certified legally blind. To date, there remains no controlled trial evidence of benefits of biologic therapy.
This study will randomise 154 patients aged 2 to 18 years with active JIA-associated uveitis (despite methotrexate (MTX) treatment for at least 12 weeks). All participants will be treated for 18 months, with follow up of 3 years from randomisation (continuing on MTX throughout). All participants will receive a stable dose of MTX and in addition either adalimumab (20 mg/0.8 ml for patients <30 kg or 40 mg/0.8 ml for patients weighing 30 kg or more, subcutaneous (s/c) injection every 2 weeks based on body weight), or placebo (0.8 ml as appropriate according to body weight) s/c injection every 2 weeks.
This is the first randomised controlled trial that will assess the clinical effectiveness, safety and cost effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis.
Adalimumab; Juvenile idiopathic arthritis; Methotrexate; Ophthalmology; Paediatric; Rheumatology; Safety; Uveitis
Evidence implicating hyperinsulinemia and insulin resistance in the etiology of colorectal cancer suggests that a diet characterized by a high glycemic index and load may increase the risk of this disease, but previous studies have yielded inconsistent results. We assessed the association between intake of total carbohydrates, sugars, fiber, and the glycemic index (GI) and glycemic load (GL) of individual diets, and risk of developing colorectal cancer among 158,800 participants in the Women’s Health Initiative (WHI). We used a GI/GL database developed specifically for the WHI food-frequency questionnaire. Over an average of 7.8 years of follow-up, 1,476 incident cases of colorectal cancer were identified. Cox proportional hazards models were used to estimate the association between dietary factors classified by quintiles and risk of colorectal cancer, with adjustment for covariates. Total carbohydrate intake, glycemic index, glycemic load, and intake of sugars and fiber showed no association with colorectal cancer. Analyses by cancer subsite yielded null results, with the exception of a borderline positive association between glycemic load and rectal cancer (HR for the highest vs. lowest quintile 1.84, 95% confidence interval 0.95–3.56, p for trend 0.05). Analyses stratified by tertiles of body mass index and physical activity showed no evidence of effect modification by these factors. Results of this large study do not support of a role of a diet characterized by a high glycemic index or load in colorectal carcinogenesis in postmenopausal women.
Morbidity and mortality for women with chronic obstructive pulmonary disease (COPD) are increasing, and little is known about gender differences in perception of COPD care.
Surveys were administered to a convenience sample of COPD patients to evaluate perceptions about symptoms, barriers to care, and sources of information about COPD.
Data on 295 female and 273 male participants were analyzed. With similar frequencies, women and men reported dyspnea and rated their health as poor/very poor. Although more women than men reported annual household income <$30,000, no significant gender differences in frequency of health insurance, physician visits, or ever having had spirometry were detected. In adjusted models (1) women were more likely to report COPD diagnostic delay (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.13-2.45, p=0.01), although anxiety (OR 1.83, 95% CI 1.10-3.06, p=0.02) and history of exacerbations (OR 1.60, 95% CI 1.08-2.37, p=0.01) were also significant predictors, (2) female gender was associated with difficulty reaching one's physician (OR 2.54, 95% CI 1.33-4.86, p=0.004), as was prior history of exacerbations (OR 2.25, 95% CI 1.21-4.20, p=0.01), and (3) female gender (OR 2.15, 95% CI 1.10-4.21, p=0.02) was the only significant predictor for finding time spent with their physician as insufficient.
Significant gender-related differences in the perception of COPD healthcare delivery exist, revealing an opportunity to better understand what influences these attitudes and to improve care for both men and women.
Collecting and managing data for clinical and translational research presents significant challenges for clinical and translational researchers, many of whom lack needed access to data management expertise, methods, and tools. At many institutions, funding constraints result in differential levels of research informatics support among investigators. In addition, the lack of widely shared models and ontologies for clinical research informatics and health information technology hampers the accurate assessment of investigators’ needs and complicates the efficient allocation of crucial resources for research projects, ultimately affecting the quality and reliability of research. In this article, we present a model for providing flexible, cost-efficient institutional support for clinical and translational research data management and informatics, the Research Management Team (RMT), and describe our initial experiences with deploying this model at our institution.
Obesity is associated with impaired health-related quality of life (QoL) and reduced productivity; less is known about the effect of dietary factors. This study investigated how dietary behaviors, physical activity, and Body Mass Index (BMI) relate to weight-specific QoL and work productivity. The study was conducted in 31 small blue-collar and service industry worksites in Seattle. Participants were 747 employees (33.5% non-White). Measures included self-reported servings of fruits and vegetables, dietary behaviors such as fast food consumption, Godin free-time physical activity scores, measured height and weight, Obesity and Weight Loss Quality of Life (OWLQOL) scores, and Work Limitations Questionnaire (WLQ) scores. Baseline data were analyzed using linear mixed models separately for men (n=348) and women (n=399), since gender modified the effects. BMI was negatively associated with OWLQOL in both women (p<0.001) and men (p<0.001). The linear effect estimate for OWLQOL score associated with one-category increase in BMI was 30% (95% CI: 25%, 44%) for women and 14% (95% CI: 10%, 17%) for men. BMI was positively associated with productivity loss only in women (exp(slope)=1.46, 95% CI: 1.02, 2.11, p=0.04). Eating while doing another activity was negatively associated with OWLQOL scores in men (p=0.0006, independent of BMI) and with productivity in women (p=0.04, effect diminished when adjusting for BMI). Fast food meals were associated with decreased productivity for men (p=0.038, independent of BMI). Results suggest the obesogenic dietary behaviors and higher BMI are associated with decreased QoL and productivity variously in women and men.
Dietary behaviors; Obesity; Quality of Life; Work productivity
•ER and ERR transcription levels were unaffected in Marisa cornuarietis exposed to 17β-estradiol or 4-tert-Octylphenol.•The mollusc ER protein interacts with the phytoestrogen genistein in transfected HEK-293 cells.•The mollusc ERR protein interacts weakly with bisphenol-A in transfected HEK-293 cells.•The mollusc ER protein binds to the vertebrate consensus estrogen response element (ERE) sequence.
Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10−6 M for Gen and >10−5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and bisphenol A, respectively) would do otherwise.
Mollusc; Estrogen receptor; Estrogen-related receptor; Gene transcription; Estrogen; Exposure
Lifestyle-based interventions, which typically promote various behavioral modification strategies, can serve as a setting for evaluating specific behaviors and strategies thought to promote or hinder weight loss. The aim of this study was to test the associations of self-monitoring (self-weighing, food journal completion) and eating-related (dietary intake, diet-related weight-control strategies, and meal patterns) behaviors with weight loss in a sample of postmenopausal overweight-to-obese women enrolled in a 12-month dietary weight loss intervention. Changes in body weight and adoption of self-monitoring and eating-related behaviors were assessed in 123 participants. Generalized linear models tested associations of these behaviors with 12-month weight change after adjusting for potential confounders. Mean percent weight loss was 10.7%. In the final model, completing more food journals was associated with a greater % weight loss (interquartile range, 3.7% greater weight loss; p<0.0001) while skipping meals (4.3% lower weight loss; p<0.05) and eating out for lunch (at least once a week, 2.5% lower weight loss; p<0.01) were associated with a lower amount of weight loss. These findings suggest that a greater focus on dietary self-monitoring, home-prepared meals, and consuming meals at regular intervals may improve 12-month weight loss among postmenopausal women enrolled in a dietary weight loss intervention.
Women; behavioral strategies; eating behaviors; weight loss
Numerous environmental pressures have precipitated long-term population reductions of many insect species. Population declines in aerially foraging insectivorous birds have also been detected, but the cause remains unknown partly because of a dearth of long-term monitoring data on avian diets. Chimney swifts (Chaetura pelagica) are a model aerial insectivore to fill such information gaps because their roosting behaviour makes them easy to sample in large numbers over long time periods. We report a 48-year-long (1944–1992) dietary record for the chimney swift, determined from a well-preserved deposit of guano and egested insect remains in Ontario (Canada). This unique archive of palaeo-environmental data reflecting past chimney swift diets revealed a steep rise in dichlorodiphenyltrichloroethane (DDT) and metabolites, which were correlated with a decrease in Coleoptera remains and an increase in Hemiptera remains, indicating a significant change in chimney swift prey. We argue that DDT applications decimated Coleoptera populations and dramatically altered insect community structure by the 1960s, triggering nutritional consequences for swifts and other aerial insectivores.
aerial insectivores; dichlorodiphenyltrichloroethane; diet reconstruction; guano
To examine the association of objectively measured participation in low levels of physical activity with incident type 2 diabetes.
RESEARCH DESIGN AND METHODS
The study population included participants free of diabetes and cardiovascular disease at baseline (n = 1,826) who participated in a follow-up examination. Generalized estimating equations were used to examine the association of steps per day with incident diabetes.
During 5 years of follow-up, 243 incident cases of diabetes were identified. When compared with participants in the lowest quartile of steps per day (<3,500 steps), participants in the upper three quartiles of steps per day had lower odds for diabetes, consistent with a threshold effect. Contrasting the three upper quartiles with the lowest quartile, the odds ratio of diabetes was 0.71 (95% CI 0.51–0.98).
Modest levels of physical activity are associated with a lower risk of incident diabetes, compared with lower levels of activity.
Neighborhood characteristics, such as healthy food availability, have been associated with consumption of healthy food. Little is known about the influence of the local food environment on other dietary choices, such as the decision to consume organic food. We analyzed the associations between organic produce consumption and demographic, socioeconomic and neighborhood characteristics in 4,064 participants aged 53–94 in the Multi-Ethnic Study of Atherosclerosis using log-binomial regression models. Participants were classified as consuming organic produce if they reported eating organic fruits and vegetables either “sometimes” or “often or always”. Women were 21% more likely to consume organic produce than men (confidence interval [CI]: 1.12–1.30), and the likelihood of organic produce consumption was 13% less with each additional 10 years of age (CI: 0.84–0.91). Participants with higher education were significantly more likely to consume organic produce (prevalence ratios [PR] were 1.05 with a high school education, 1.39 with a bachelor's degree and 1.68 with a graduate degree, with less than high school as the reference group [1.00]). Per capita household income was marginally associated with produce consumption (p = 0.06), with the highest income category more likely to consume organic produce. After adjustment for these individual factors, organic produce consumption was significantly associated with self-reported assessment of neighborhood produce availability (PR: 1.07, CI: 1.02–1.11), with an aggregated measure of community perception of the local food environment (PR: 1.08, CI: 1.00–1.17), and, to a lesser degree, with supermarket density (PR: 1.02: CI: 0.99–1.05). This research suggests that both individual-level characteristics and qualities of the local food environment are associated with having a diet that includes organic food.
There is an emerging consensus that protected areas are key in reducing adverse land-cover change, but their efficacy remains difficult to quantify. Many previous assessments of protected area effectiveness have compared changes between sets of protected and unprotected sites that differ systematically in other potentially confounding respects (e.g. altitude, accessibility), have considered only forest loss or changes at single sites, or have analysed changes derived from land-cover data of low spatial resolution. We assessed the effectiveness of protection in reducing land-cover change in Important Bird Areas (IBAs) across Africa using a dedicated visual interpretation of higher resolution satellite imagery. We compared rates of change in natural land-cover over a c. 20-year period from around 1990 at a large number of points across 45 protected IBAs to those from 48 unprotected IBAs. A matching algorithm was used to select sample points to control for potentially confounding differences between protected and unprotected IBAs. The rate of loss of natural land-cover at sample points within protected IBAs was just 42% of that at matched points in unprotected IBAs. Conversion was especially marked in forests, but protection reduced rates of forest loss by a similar relative amount. Rates of conversion increased from the centre to the edges of both protected and unprotected IBAs, but rates of loss in 20-km buffer zones surrounding protected IBAs and unprotected IBAs were similar, with no evidence of displacement of conversion from within protected areas to their immediate surrounds (leakage).
To evaluate long-term change in fruit and vegetable intake following a group randomized trial of worksites.
Medium-sized blue-collar businesses in the Seattle metropolitan area were recruited. Intake was assessed using serial cross-sectional samples of current workforce at 3 time points. The multilevel 18-month intervention involved partnership with the companies. Long-term follow-up was at 4.4 years postbaseline. Statistical analysis used general linear models, adjusting for worksite random effects.
Initially, 45 worksites were randomized, with 29 agreeing to participate in a new study. Fruits and vegetable intake increased, with larger sustained changes in the intervention worksites, resulting in a long-term differential change of 0.25 servings per day, 95% confidence interval (0.09 to 0.40).
Intervention sustained small effects at 4 years, including 2 years with no contact. Although effects were not large, this low-intensity intervention approach could provide an important public health model.
Intervention evaluation studies; behavior change persistence; food; fruits and vegetables; long-term effects
To define inactive disease (ID) and clinical remission (CR), and delineate variables that can be used to measure ID/CR in childhood-onset systemic lupus erythematosus (cSLE).
Delphi questionnaires were sent to an international group of pediatric rheumatologists. Respondents provided information about variables to be used in future algorithms to measure ID/CR. The usefulness of these variables was assessed in 35 children in ID and 31 children with minimally active lupus (MAL).
While ID reflects cSLE status at a specific point in time, CR requires the presence of ID for ≥ 6 months and considers treatment. There was consensus that patients in ID/CR can have ≤ 2 mild non-limiting symptoms (i.e. fatigue, arthralgia, headaches or myalgia) but not Raynaud’s phenomenon, chest pain, or objective physical signs of cSLE; ANA positivity and ESR elevation can be present. CBC, renal function testing, and complement C3 all must be within the normal range. Based on consensus, only damage-related laboratory or clinical findings of cSLE are permissible with ID. The above parameters were suitable to differentiate children with ID/CR from those with MAL (area under the receiver operating characteristic curve > 0.85). Disease activity scores with or without the physician global assessment of disease activity and patient symptoms were well suited to differentiate children with ID from those with MAL.
Consensus has been reached on common definitions of ID/CR with cSLE and relevant patient characteristics with ID/CR. Further studies must assess the usefulness of the data-driven candidate criteria for ID in cSLE.
lupus; childhood-onset SLE; SLE; pediatric SLE; juvenile SLE; remission; inactive disease; children; cSLE
Recent research has identified self-monitoring behaviors as important strategies for both initial weight loss and weight loss maintenance, but relatively little is known about adopters and non-adopters of these behaviors. To test our hypothesis that key characteristics distinguish adopters from non-adopters, we examined the demographic characteristics and eating behaviors (e.g. restrained, uncontrolled, emotional and binge eating) associated with more frequent compared to less frequent use of these behaviors. Baseline demographic characteristics and eating behaviors, as well as, 12-month self-monitoring behaviors (i.e. self-weighing, food journaling, calorie counting) were assessed in 123 postmenopausal women enrolled in a dietary weight-loss intervention. Logistic regression models were used to test associations of self-monitoring use with demographic characteristics and eating behaviors. Non-Whites, compared to non-Hispanic Whites, were less likely to count calories regularly (adjusted OR: 0.36–95% CI: 0.13–0.97, p<0.05), controlling for intervention arm and baseline BMI. Participants with a college degree or higher education were less likely to self-weigh daily (adjusted OR: 0.30, 95% CI: 0.13–0.67, p≤0.01) compared to individuals who attended some college or less. Those with higher baseline binge eating scores were less likely to count calories (adjusted OR: 0.84, 95% CI: 0.73–0.97, p≤0.01) compared to participants with lower binge eating scores. In summary, use of diet-related self-monitoring behaviors varied by race/ethnicity, education, and binge eating score in postmenopausal women who completed a year-long dietary weight loss intervention. Improved recognition of groups less likely to self monitor may be helpful in promoting these behaviors in future interventions.
Weight loss; postmenopausal; women; demographic; psychosocial; behaviors; diet
Here, high-throughput sequencing was employed to reveal the highly diverse bacterial populations present in 62 Irish artisanal cheeses and, in some cases, associated cheese rinds. Using this approach, we revealed the presence of several genera not previously associated with cheese, including Faecalibacterium, Prevotella, and Helcococcus and, for the first time, detected the presence of Arthrobacter and Brachybacterium in goats' milk cheese. Our analysis confirmed many previously observed patterns, such as the dominance of typical cheese bacteria, the fact that the microbiota of raw and pasteurized milk cheeses differ, and that the level of cheese maturation has a significant influence on Lactobacillus populations. It was also noted that cheeses containing adjunct ingredients had lower proportions of Lactococcus species. It is thus apparent that high-throughput sequencing-based investigations can provide valuable insights into the microbial populations of artisanal foods.
Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo.
This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200mg, and 70 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine.
Regression analysis showed no significant difference between either modafinil group (200 or 400mg) and placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period (p=0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p=0.003), between those having the top quartile of compliance (>85% urines modafinil +, N=36), and the lower three quartiles of modafinil 200 and 400mg groups (N=106).
Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication.
Methamphetamine; Substance-Related Disorders; drug therapy [subheading]; Modafinil; Medication Adherence; Attention Deficit Hyperactivity Disorders
The daily administered dose of progestin in continuous-combined estrogen-progestin therapy is provided to counteract the proliferative effect of estrogen on the postmenopausal endometrium. However, there remains some uncertainty as to whether use of such a combined regimen, over the long-term, is associated with an altered risk of endometrial cancer. We pooled data from four population-based case-control studies of endometrial cancer in western Washington State. Cases, ages 45–74, were diagnosed between 1985 and 2005. Using logistic regression with adjustment for confounding factors, women who had exclusively used continuous-combined estrogen-progestin therapy (90 endometrial cancer cases, 227 controls) were compared to women who had never used any type of hormone therapy (774 cases, 1116 controls). Associations with duration and recency of use were evaluated overall and within strata defined by body mass index. Long-term use of continuous-combined estrogen-progestin therapy (≥10 years) was associated with a reduced risk of endometrial cancer (OR=0.37, 95% CI: 0.21–0.66). This association was most pronounced in women with a body mass index ≥30 kg/m2 (OR=0.19, 95% CI: 0.05–0.68). Associations did not differ according to recency of use. These results suggest that long duration of use of continuous-combined estrogen-progestin therapy is associated with a reduced risk of endometrial cancer risk.
endometrial cancer; hormone therapy; estrogen; progestin; body mass index
Snacking may play a role in weight control. The associations of timing and frequency of snacking with observed weight change and nutrient intake were assessed in an ancillary study to a 12-month randomized controlled trial in Seattle, WA. Overweight-to-obese postmenopausal women (n=123) enrolled in the two dietary weight loss arms from 2007–2008 with complete data at 12-months were included in these analyses. Generalized linear models were used to test the associations between snacking and weight loss (%) and nutrient intake at the 12-month time point. Participants were on average 58 years old and mainly non-Hispanic White (84%). Ninety-seven percent reported ≥ 1 snack/day. Weight loss (%) was significantly lower among mid-morning (10:30am–11:29am) snackers (7.0%, 95% CI 4.3, 9.7) compared to non-mid-morning snackers (11.4%, 95% CI 10.2, 12.6; p value: 0.004). A higher proportion of mid-morning snackers reported more than 1 snack/day (95.7%), compared to afternoon (82.8%) and evening (80.6%) snackers, though differences were not statistically significant. Women who reported ≥2 snacks/day vs. ≤ 1 snack/day had higher fiber intake (p=0.027). Afternoon snackers had higher fruit and vegetable intake compared to non-afternoon-snackers (p=0.035). These results suggest that snack meals can be a source for additional fruits, vegetables, and fiber-rich foods; however, snacking patterns might also reflect unhealthy eating habits and impede weight loss progress. Future dietary weight loss interventions should evaluate the effects of timing, frequency, and quality of snacks on weight loss.
snacking; weight loss; women; nutrient intake
Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk.
We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of four population-based endometrial cancer case-control studies of women 45–74 years of age (1,712 cases and 2,134 controls) during 1985–2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews.
Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14–0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree.
In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.
To develop widely acceptable preliminary criteria of global flare for childhood-onset SLE (cSLE).
Pediatric rheumatologists (n=138) rated a total of 358 unique patient profiles (PP) with information about the cSLE flare descriptors (cSLE-FD) from two consecutive visits: patient global assessment of well-being, physician global assessment of disease activity (MD-global), health-related quality of life, anti-dsDNA antibodies, disease activity index score, protein/creatinine (P/C) ratio, complement levels and ESR. Based on 2996 rater responses about the course of cSLE (baseline vs. follow-up) the accuracy (sensitivity, specificity, area under the receiver operating characteristic curve) of candidate flare criteria was assessed. An international consensus conference was held to rank these candidate flare criteria as per the ACR-recommendations for the development and validation of criteria sets.
The highest ranked candidate criteria considered absolute changes (Δ) of the SLEDAI or BILAG, MD-global, P/C ratio, and ESR; Flare scores can be calculated [0.5 × ΔSLEDAI + 0.45 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR], where values ≥ 1.04 are reflective of a flare. Similarly, BILAG-based flare scores [0.4 × ΔBILAG + 0.65 × ΔP/C ratio + 0.5 × ΔMD-global + 0.02 × ΔESR] of ≥ 1.15 were diagnostic of a flare. Flare scores increase with flare severity.
Consensus has been reached on preliminary criteria for global flares in cSLE. Further validation studies are needed to confirm the usefulness of the cSLE flare criteria in research and for clinical care.
lupus; childhood-onset SLE; SLE; pediatric SLE; juvenile SLE; flare; criteria; children; cSLE
The food frequency questionnaire approach to dietary assessment is ubiquitous in nutritional epidemiology research. Food records and recalls provide approaches that may also be adaptable for use in large epidemiologic cohorts, if warranted by better measurement properties. The authors collected (2007–2009) a 4-day food record, three 24-hour dietary recalls, and a food frequency questionnaire from 450 postmenopausal women in the Women’s Health Initiative prospective cohort study (enrollment, 1994–1998), along with biomarkers of energy and protein consumption. Through comparison with biomarkers, the food record is shown to provide a stronger estimate of energy and protein than does the food frequency questionnaire, with 24-hour recalls mostly intermediate. Differences were smaller and nonsignificant for protein density. Food frequencies, records, and recalls were, respectively, able to “explain” 3.8%, 7.8%, and 2.8% of biomarker variation for energy; 8.4%, 22.6%, and 16.2% of biomarker variation for protein; and 6.5%, 11.0%, and 7.0% of biomarker variation for protein density. However, calibration equations that include body mass index, age, and ethnicity substantially improve these numbers to 41.7%, 44.7%, and 42.1% for energy; 20.3%, 32.7%, and 28.4% for protein; and 8.7%, 14.4%, and 10.4% for protein density. Calibration equations using any of the assessment procedures may yield suitable consumption estimates for epidemiologic study purposes.
bias (epidemiology); biological markers; diet; energy intake; epidemiologic methods; measurement error; nutrition assessment
To explore the association of baseline co-worker social support with follow-up measures of health care use and sickness absence.
Data were obtained on 1,240 employees from 33 worksites, through Promoting Activity and Changes in Eating, a group randomized weight maintenance trial. Co-worker social support, health care utilization, and absenteeism were assessed via a self-reported questionnaire. Generalized Estimating Equations were employed using STATA version 10.
Higher baseline co-worker social support was significantly associated with a greater number of doctors’ visits (p = 0.015). Co-worker social support was unrelated to number of hospitalizations, emergency room visits, or absenteeism.
The relationship between co-worker social support and health care utilization and absenteeism is complex and uncertain. Future studies should measure more specific outcomes, incorporate important mediating variables, and distill how social networks influence these outcomes.