Low dietary folate intake is associated with several neoplasias, but reports are inconsistent for breast cancer. Additionally, the association of folate with breast cancer estrogen receptor (ER) ...status is not well established.
To determine if dietary intakes of folate, B-vitamins (B2, B6, B12) and methionine are associated with breast cancer risk and ER status in Hispanic, and non-Hispanic White women in the southwestern U.S.
Primary breast cancer cases (n = 2,325) in the 4-Corners region (Arizona, Colorado, New Mexico and Utah), diagnosed between October 1999 and May 2004, were identified through state cancer registries. Controls (n = 2,525) were frequency-matched by ethnicity and age (±5 years). Dietary intake, physical activity and other exposures were assessed using in-person interviews. Risk was assessed through multivariable and multinomial logistic regression with adjustment for relevant covariates.
While there was no overall association with breast cancer, the highest quartile of folate intake was marginally inversely associated with ER- breast cancer (Odds Ratio (OR) = 0.50, 95% CI 0.25-1.00, p for trend = 0.07). Vitamin B12 intake was inversely associated with breast cancer also (OR = 0.73, 95% CI 0.53-1.00, p for trend = 0.06), particularly for the highest quartile of ER+ breast cancer (OR = 0.67, 95% CI 0.46-0.99, p for trend = 0.06), among NHW women (OR = 0.49, 95% CI 0.29-0.81, p for trend = 0.01) and invasive breast cancer (OR = 0.63; 95% CI: 0.42, 0.93, P(trend) = 0.01). Methionine intake was also inversely associated with ER+ breast cancer (OR for 4th quartile = 0.83, 95% CI 0.66-1.03, p for trend = 0.04), primarily among Hispanic women (OR = 0.71, 95% CI 0.47-1.06, and P for trend = 0.02).
Higher intake of folate is marginally associated with a lower risk for ER- breast cancer, and higher intakes of vitamin B-12 and methionine are marginally associated with a lower risk of ER+ breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims:
The concept of a CpG island methylator phenotype (CIMP), especially in microsatellite stable colon cancer, is not accepted universally. We therefore evaluated a large ...population-based sample of individuals with colon cancer and used univariate and multivariate analyses of CIMP with clinicopathologic variables and tumor mutations to determine the biologic relevance of this phenotype.
Methods:
A total of 864 tumors from individuals with colon cancer from Utah and Northern California were evaluated by methylation-specific polymerase chain reaction of CpG islands in
hMLH1, methylated in tumors (MINT) 1, MINT 2, MINT 31, and
CDKN2A (p16). CIMP high was defined as methylation at 2 or more of these loci. The
BRAF V600E mutation was determined by sequencing. Microsatellite instability had been determined previously.
Results:
In a multivariate analysis of microsatellite stable tumors, CIMP high was related significantly to the V600E
BRAF mutation (odds ratio, 39.52; 95% confidence interval, 11.44–136.56),
KRAS2 mutations (odds ratio, 2.22; 95% confidence interval, 1.48–3.34), older age (
P trend = .03), and increased stage (
P trend = .03), and these tumors were less likely to be located in the distal colon (odds ratio, .42; 95% confidence interval, .27–.65). CIMP-high unstable tumors also were more likely to have the V600E
BRAF mutation, be located proximally, and occur in older individuals (in univariate analyses). However, CIMP-high unstable tumors were significantly more likely than their stable counterparts to be
KRAS2 wild type,
TP53 wild type, poorly differentiated, proximally located, occur at lower stages, and have the
BRAF V600E mutation (64.1% vs 17.6%).
Conclusions:
The evaluation of a large, population-based sample strongly supports the biologic relevance of CIMP in colon cancer. However, the presence or absence of microsatellite instability has a major effect on the expression of this phenotype.
The fingers, toes, and tips of the nose and ears have specialised structural and functional features for thermoregulation, and are the most common areas of Raynaud's phenomenon in systemic sclerosis. ...Digital thermal monitoring (DTM) of vascular reactivity assesses Doppler ultrasound hyperemic, low frequency, blood velocity of radial artery and fingertip vascular function. Flow mediated dilation (FMD) is an indirect measure of endothelial function, perfusion, and vasodilator ability. In this study, we investigated the cross-sectional correlation of FMD and DTM variables to inform an optimised noninvasive study of SSc endothelial function. A student's T-test was used to compare means of DTM across binary variables.
Consented SSc registry patients were included in this analysis. The subjects were prepared for FMD and DTM per standardised guidelines. The SSc clinical features were recorded. Spearman's Rank Correlation was used to assess the strength of a relationship FMD and DTM variables.
Thirty-four SSc subjects had FMD and DTM performed on the same day. Relative (0.42, p=<0.02), absolute FMD (0.41, p<0.02), and shear rate (0.32, p<0.07) were weakly, but significantly correlated with the DTM. Reactive hyperemia (-0.44, p=0.000) was weakly inversely, but significantly related with DTM. Baseline diameter and flow were not significantly related to the DTM.
This non-invasive study of SSc endothelial function suggests that macrocirculation (including relative and absolute FMD, shear rate, and peak hyperemia) and microcirculatory thermoregulation (characterised by DTM) are significantly correlated, thus warrants further prospective study.
Dietary Na recommendations are expressed as absolute amounts (mg/d) rather than as Na density (mg/kcal). Our objective was to determine whether the strength of the relationship of Na intake with ...blood pressure (BP) varied with energy intake. The DASH (Dietary Approaches to Stop Hypertension)-Sodium trial was a randomized feeding trial comparing 2 diets (DASH and control) and 3 levels of Na density. Participants with pre- or stage 1 hypertension consumed diets for 30 days in random order; energy intake was controlled to maintain body weight. This secondary analysis of 379 non-Hispanic black and white participants used mixed-effects models to assess the association of Na and energy intakes with BP. The relationships between absolute Na and both systolic and diastolic BP varied with energy intake. BP rose more steeply with increasing Na at lower energy intake than at higher energy intake (P interaction<0.001). On the control diet with 2300 mg Na, both systolic and diastolic BP were higher (3.0 mm Hg; 95% confidence interval, 0.2–5.8; and 2.7 mm Hg; 95% confidence interval, 1.0–4.5, respectively) among those with lower energy intake (higher Na density) than among those with higher energy intake (lower Na density). The association of Na with systolic BP was stronger at lower levels of energy intake in both blacks and whites (P<0.001). The association of Na and diastolic BP varied with energy intake only among blacks (P=0.001). Sodium density should be considered as a metric for expressing dietary Na recommendations.
The BRAF V600E mutation has been associated with microsatellite instability and the CpG island methylator phenotype (CIMP) in colon cancer. We evaluated a large population-based sample of individuals ...with colon cancer to determine its relationship to survival and other clinicopathologic variables. The V600E BRAF mutation was seen in 5% (40 of 803) of microsatellite-stable tumors and 51.8% (43 of 83) of microsatellite-unstable tumors. In microsatellite-stable tumors, this mutation was related to poor survival, CIMP high, advanced American Joint Committee on Cancer (AJCC) stage, and family history of colorectal cancer odds ratio, 4.23; 95% confidence interval (95% CI), 1.65-10.84. The poor survival was observed in a univariate analysis of 5-year survival (16.7% versus 60.0%; P < 0.01); in an analysis adjusted for age, stage, and tumor site hazard rate ratio (HRR), 2.97; 95% CI, 2.05-4.32; in stage-specific, age-adjusted analyses for AJCC stages 2 to 4 (HRR, 4.88, 3.60, and 2.04, respectively); and in Kaplan-Meier survival estimates for AJCC stages 2 to 4 (P < 0.01 for all three stages). Microsatellite-unstable tumors were associated with an excellent 5-year survival whether the V600E mutation was present or absent (76.2% and 75.0%, respectively). We conclude that the BRAF V600E mutation in microsatellite-stable colon cancer is associated with a significantly poorer survival in stages 2 to 4 colon cancer but has no effect on the excellent prognosis of microsatellite-unstable tumors.
To estimate the association between habitus measures and pelvic floor support and symptoms in primiparous women 1 year after term vaginal delivery.
In this cross-sectional study including women ...enrolled at seven academic and community sites, we assessed pelvic floor support, weight, height, waist circumference, and percent fat using air displacement plethysmography and participants completed questionnaires, all at one year postpartum. We tested the association of quintiles of habitus measure, including body mass index (BMI), waist circumference, percent body fat, and waist/height ratio, with the primary outcomes: anatomic support, dichotomized as maximal vaginal descent less than 0 cm (better support) compared with 0 cm or more (worse support) per the pelvic organ prolapse quantification examination and symptom burden (positive with bothersome symptoms in two or more of six symptom domains), and on five secondary outcomes. The sample size provides 90% power to detect odds ratios (ORs) of 1.78 or greater between women at mean compared with mean+1 SD of habitus measure.
Of 592 participants, 55 (9.3%) demonstrated worse support and 321 (54.2%) symptom burden. In multivariable analyses, habitus measures were not significantly associated with anatomic support or, except for the highest waist/height ratio quintile, with symptom burden. Compared with women in the first quintile of each habitus measure, those in most higher quintiles demonstrated elevated odds of moderate to severe urinary incontinence (UI); increased odds for stress urinary incontinence (SUI) were mainly limited to the highest quintile. After adjusting for percent body fat, the increased odds for BMI on SUI (OR 2.47, 95% CI 1.43-4.28) were no longer significant (OR 1.38, 95% CI 0.54, 3.51).
Habitus in primiparous patients at 1 year postpartum was not associated with anatomic support or symptom burden. Habitus was more associated with moderate to severe UI than mild UI. The association of higher BMI with SUI was attenuated by fitness, reflected by fat percentage.
Example of the creation of a standardized regular expression by REDEx.
•REDEx accurately extracted weight from outpatient primary care notes.•Extracted values were reliable (highly correlated with ...values from structured field).•Unique values (2 per individual per year) were identified.•This method can reduce missing/mistimed values in cohort identification.•REDEx is flexible and can be retrained to textual expressions.
Bodyweight related measures (weight, height, BMI, abdominal circumference) are extremely important for clinical care, research and quality improvement. These and other vitals signs data are frequently missing from structured tables of electronic health records. However they are often recorded as text within clinical notes. In this project we sought to develop and validate a learning algorithm that would extract bodyweight related measures from clinical notes in the Veterans Administration (VA) Electronic Health Record to complement the structured data used in clinical research.
We developed the Regular Expression Discovery Extractor (REDEx), a supervised learning algorithm that generates regular expressions from a training set. The regular expressions generated by REDEx were then used to extract the numerical values of interest.
To train the algorithm we created a corpus of 268 outpatient primary care notes that were annotated by two annotators. This annotation served to develop the annotation process and identify terms associated with bodyweight related measures for training the supervised learning algorithm. Snippets from an additional 300 outpatient primary care notes were subsequently annotated independently by two reviewers to complete the training set. Inter-annotator agreement was calculated.
REDEx was applied to a separate test set of 3561 notes to generate a dataset of weights extracted from text. We estimated the number of unique individuals who would otherwise not have bodyweight related measures recorded in the CDW and the number of additional bodyweight related measures that would be additionally captured.
REDEx’s performance was: accuracy=98.3%, precision=98.8%, recall=98.3%, F=98.5%. In the dataset of weights from 3561 notes, 7.7% of notes contained bodyweight related measures that were not available as structured data. In addition 2 additional bodyweight related measures were identified per individual per year.
Bodyweight related measures are frequently stored as text in clinical notes. A supervised learning algorithm can be used to extract this data. Implications for clinical care, epidemiology, and quality improvement efforts are discussed.
We describe Raynauds phenomenon (RP), potential very early diagnosis of systemic sclerosis (VEDOSS), and systemic sclerosis (SSc) in Veterans deployed in support of Post-9/11 operations. We sought to ...describe the military occupation specialty, clinical features, and vasodilator use across the three diagnoses.
Individual Veterans medical records were assessed for RP (ICD-9443.0), VEDOSS with swelling of hands (ICD-9729.81) and RP (ICD-9443.0), and SSc (ICD-9710.1). The distribution of sociodemographic, military service branch, job classification, vasodilator use, and comorbidities were examined across the three classifications of disease. The chi-squared test and Fisher's exact compared frequency of these categorical variables. Logistic regression assessed the likelihood of characteristics of the three classifications.
In this population of 607,665 individual Veteran medical records, 857 had RP, 45 met possible VEDOSS criteria, and 71 had a diagnosis of SSc. The majority of RP, potential VEDOSS and SSc cases were white males. Those in craftworks, engineering or maintenance, and healthcare had a greater likelihood of RP. Less than half of RP and VEDOSS patients were on vasodilators. The most common comorbidities in this population were the diagnostic code for pain (highest in the potential VEDOSS group 81.6%), followed by depression in all groups.
This is a unique Veteran population of predominately-male patients. Our data suggests that vasodilator medications are potentially being under-utilized for RP and potential VEDOSS. Our data highlights mood and pain management as an important aspect of SSc care.
Summary Background and aims Gastrointestinal manifestations in systemic sclerosis (SSc) can influence the nutritional status of patients. Our objective was to examine whether nutritional status was ...associated with symptoms captured by the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract Questionnaire (GIT 2.0). Methods A series of 24 University of Utah SSc Center patients were assessed using the MUST, SGA, and GIT 2.0. A single evaluator administered the nutrition assessment and gastrointestinal symptom questionnaire. Results Nine patients were assessed at moderate to high risk of malnutrition using the Malnutrition Universal Screening Tool (MUST) and 12 patients with moderate to severe malnutrition using Subjective Global Assessment (SGA). Neither MUST nor SGA status was associated with duration of disease. Soilage, social function and emotional subscores were associated with SGA nutritional status. Clinically significant differences in Total GIT 2.0 score, reflux, distention/bloating, soilage, diarrhea, social function and emotional well-being were observed across levels of nutritional status. Conclusions Clinically significant differences in gastrointestinal tract symptoms were observed across levels of nutritional status in patients with varying severity of SSc. These two clinically utilized tools, the SGA and the GIT 2.0, appear to be complementary in the evaluation of SSc patients.
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