Phthalates have been found in many personal care and industrial products, but have not previously been reported in food purchased in the United States. Phthalates are ubiquitous synthetic compounds ...and therefore difficult to measure in foods containing trace levels. Phthalates have been associated with endocrine disruption and developmental alteration.
Our goals were to report concentrations of phthalates in U.S. food for the first time, specifically, nine phthalates in 72 individual food samples purchased in Albany, New York, and to compare these findings with other countries and estimate dietary phthalate intake.
A convenience sample of commonly consumed foods was purchased from New York supermarkets. Methods were developed to analyze these foods using gas chromatography-mass spectroscopy. Dietary intakes of phthalates were estimated as the product of the food consumption rate and concentration of phthalates in that food.
The range of detection frequency of individual phthalates varied from 6% for dicyclohexyl phthalate (DCHP) to 74% for di-2-ethylhexyl phthalate (DEHP). DEHP concentrations were the highest of the phthalates measured in all foods except beef where di-n-octyl phthalate (DnOP) was the highest phthalate found, with pork having the highest estimated mean concentration of any food group (mean 300 ng/g; maximum, 1,158 ng/g). Estimated mean adult intakes ranged from 0.004 μg/kg/day for dimethyl phthalate (DMP) to 0.673 μg/kg/day for DEHP.
Phthalates are widely present in U.S. foods. While estimated intakes for individual phthalates in this study were more than an order of magnitude lower than U.S. Environmental Protection Agency reference doses, cumulative exposure to phthalates is of concern and a more representative survey of U.S. foods is indicated.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Background
Several studies have reported that haemophilia carriers have a bleeding tendency independent of factor activity. However, investigations have been fraught with methodological concerns. The ...ATHNdataset houses the largest data set of haemophilia carriers in the world. We undertook an analysis of haemophilia carriers in this data set using methodologies that characterize bleeding symptoms in carriers.
Aim
Determine the proportion of haemophilia carriers who have a normal bleeding score (BLS) and factors that affect the BLS.
Methods
The ATHNdataset was queried for haemophilia carriers with a documented BLS. Collected data included demographics, ISTH‐BAT score, factor activity level, type of haemophilia (A or B), genotype and geographic residence.
Results
Nine hundred twenty‐two haemophilia carriers in the ATHNdataset reported a BLS. When adjusted for age, 74% reported a normal score. Logistic regression identified age, factor activity level, ethnicity and region of residence as risk factors for an abnormal score.
Conclusions
The majority of haemophilia carriers (74%) in the ATHNdataset had a normal BLS, including the majority (59%) with factor activity levels < 40 IU/dl. Conversely, 24% of haemophilia carriers with a factor activity level >40 IU/dl reported an abnormal BLS. These results are consistent with previous studies of haemophilia carriers. Additional investigation is needed to determine why a majority of haemophilia carriers with low factor activity levels report normal BLSs while a significant minority of haemophilia carriers with normal activity levels report abnormal BLSs.
OBJECTIVES/GOALS: To determine predictors of mortality in non-severe hemophilia A (NSHA) patients. METHODS/STUDY POPULATION: The ATHNdataset was used to identify NSHA patients who have authorized the ...sharing of their demographic and clinical information for research. Factors examined included race, ethnicity, hemophilia severity, Hepatitis B, Hepatitis C and HIV infections. A mortality rate was calculated for each factors examined. The relative risk of death between patients in different categories of the factors was assessed by using the ratio of these mortality rates. To adjust for the effects of all of the studied factors with mortality, a multivariate analysis was performed using logistic regression. All hypothesis testing was two-tailed, with a significance level of .05. RESULTS/ANTICIPATED RESULTS: A total of 6,606 NSHA patients were followed for an average of 8.5 years. During 56,064 person years of observation, 136 (2.1%) NSHA patients died; 20% of deaths were malignancy-related. Mortality rates were similar across racial group. Hispanic patients were 60% less likely to die than non-Hispanic patients (p = 0.006). Patients with Hepatitis C infection and HIV infection were 7 times as likely to die compared to those without infections (p<0.001). After adjusting for the effects of all examined factors in a multivariate analysis, patients with hepatitis C and HIV infection remain significantly associated with increased mortality at 6.1 times and 3.6 times the risk, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Despite significant improvement in the therapeutic approaches for infectious diseases, Hepatitis C and HIV infections remain strong predictors of mortality in this NSHA cohort. CONFLICT OF INTEREST DESCRIPTION: N/A.
Hemophilia A is characterized by unpredictable spontaneous bleeds and chronic comorbidities. However, limited data exists at the national level into detailed management patterns related to patient ...clinical characteristics, representative real‐world dosing and treatment frequency, and costs. To assess and characterize the US severe hemophilia A (SHA) population, including subgroups of patients, in terms of clinical and demographic characteristics, healthcare resource utilization received at hemophilia treatment centers (HTCs), and projected annual costs of treatment utilizing data from the ATHNdataset of the American Thrombosis and Hemostasis Network (ATHN). Adult male people with SHA (PwSHA) (FVIII < 1%) were identified in the ATHNdataset between January 2013 and September 2019. This retrospective cohort study described patients’ demographic and clinical characteristics, clinical history, as well as the HTC‐related health resource utilization (HRU), treatment utilization, and projected annual treatment costs of US PwSHA received over the most recent year. Results are reported for the overall population and for three mutually exclusive subpopulations of patients: PwSHA with a history of and/or current inhibitors, PwSHA without a history of inhibitors but with (or a history of) one or more transfusion‐transmitted infections (hepatitis B virus HBV, hepatitis C virus HCV, or human immunodeficiency virus HIV), and PwSHA without a history of inhibitors or of transfusion‐transmitted infections (HBV, HCV, or HIV). Of the overall PwSHA cohort (N = 3677), there was a high prevalence of HCV (24.1%) and HIV (13.7%), while the prevalence of HBV (4.9%) was lower. Note that 20.5% of PwSHA overall currently or ever had FVIII inhibitors. On average, PwSHA had 2.8 total HTC visits per year, including 0.9 comprehensive care visits, 1.1 telephone contact visits, 0.5 office visits, and 0.1 surgeries or other procedures. However, 23.3% of PwSHA were not seen at an HTC, and 33.8% of PwSHA did not have a comprehensive care visit during their most recent year of data. HTC‐related HRU was similar between the overall cohort and across the patient subpopulations, although PwSHA and inhibitors had more frequent HTC visits (a mean of 3.6 visits annually vs. 2.5–2.8 in the other groups). Using reported treatment frequency and dosing, estimated mean annual hemophilia treatment costs varied by treatment and across the three subpopulations: extended half‐life factor product ($893,609–934,301 by subpopulation), standard half‐life factor product ($798,700–930,812), plasma‐derived factor product ($613,220–801,061), and non‐factor product treatment ($765,289—833,240). This study summarized recent sociodemographic and clinical characteristics, HTC‐related HRU, and HA treatments and projected costs among adult PwSHA, including among key subpopulations of PwSHA. PwSHA experience substantial clinical and resource burden on a chronic basis, despite the care coordination efforts of ATHN‐affiliated HTCs. These findings motivate further exploration of the drivers of resource utilization, observed differences across subpopulations and other disparities, and ongoing monitoring of clinical and treatment burden in the face of an evolving care landscape.
Men with hemophilia were initially thought to be protected from cardiovascular disease (CVD), but it is now clear that atherothrombotic events occur. The primary objective of the CVD in Hemophilia ...study was to determine the prevalence of CVD and CVD risk factors in US older men with moderate and severe hemophilia and to compare findings with those reported in age-comparable men in the Atherosclerosis Risk in Communities (ARIC) cohort. We hypothesized if lower factor levels are protective from CVD, we would see a difference in CVD rates between more severely affected and unaffected men. Beginning in October 2012, 200 patients with moderate or severe hemophilia A or B (factor VIII or IX level ≤ 5%), aged 54 to 73 years, were enrolled at 19 US hemophilia treatment centers. Data were collected from patient interview and medical records. A fasting blood sample and electrocardiogram (ECG) were obtained and assayed and read centrally. CVD was defined as any angina, any myocardial infarction by ECG or physician diagnosis, any self-reported nonhemorrhagic stroke or transient ischemic attack verified by physicians, or any history of coronary bypass graft surgery or coronary artery angioplasty. CVD risk factors were common in the population. Compared with men of similar age in the ARIC cohort, patients with hemophilia had significantly less CVD (15% vs 25.8%; P < .001). However, on an individual patient level, CVD events occur and efforts to prevent cardiovascular events are warranted. Few men were receiving secondary prophylaxis with low-dose aspirin, despite published opinion that it can be used safely in this patient population.
•CV risk factors are common in older men with hemophilia.•Although older men with hemophilia have less CV disease than comparable unaffected men, CV events do occur and require treatment.
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Sternal precautions are intended to prevent complications after median sternotomy, but little data exist to support the consensus recommendations. To better characterize the forces on the sternum ...that can occur during everyday events, we conducted a prospective nonrandomized study of 41 healthy volunteers that evaluated the force exerted during bench press resistance exercise and while sneezing. A balloon-tipped esophageal catheter, inserted through the subject's nose and advanced into the thoracic cavity, was used to measure the intrathoracic pressure differential during the study activities. After the 1 repetition maximum (1-RM) was assessed, the subject performed the bench press at the following intensities, first with controlled breathing and then with the Valsalva maneuver: 40% of 1-RM (low), 70% of 1-RM (moderate), and 1-RM (high). Next, various nasal irritants were used to induce a sneeze. The forces on the sternum were calculated according to a cylindrical model, and a 2-tailed paired t test was used to compare the mean force exerted during a sneeze with the mean force exerted during each of the 6 bench press exercises. No statistically significant difference was found between the mean force from a sneeze (41.0 kg) and the mean total force exerted during moderate-intensity bench press exercise with breathing (41.4 kg). In conclusion, current guidelines and recommendations limit patient activity after a median sternotomy. Because these patients can repeatedly withstand a sneeze, our study indicates that they can withstand the forces from more strenuous activities than are currently allowed.
We designed a study to measure the functional capacity requirements of firefighters to aid in the development of an occupation-specific training program in cardiac rehabilitation; 23 healthy male ...firefighters with no history of heart disease completed a fire and rescue obstacle course that simulated 7 common firefighting tasks. They wore complete personal protective equipment and portable metabolic instruments that included a data collection mask. We monitored each subject's oxygen consumption (VO2 ) and working heart rate, then calculated age-predicted maximum heart rates (220 − age) and training target heart rates (85% of age-predicted maximum heart rate). During performance of the obstacle course, the subjects' mean working heart rates and peak heart rates were higher than the calculated training target heart rates ( t22 = 5.69 working vs target, p <0.001 and t22 = 15.14 peak vs target, p <0.001). These findings, with mean results for peak VO2 (3,447 ml/min) and metabolic equivalents (11.9 METs), show that our subjects' functional capacity greatly exceeded that typically attained by patients in traditional cardiac rehabilitation programs (5 to 8 METs). In conclusion, our results indicate the need for intense, occupation-specific cardiac rehabilitation training that will help firefighters safely return to work after a cardiac event.
Introduction: Obesity is associated with endothelial dysfunction, hemostatic and fibrinolytic disturbances. The relationship between obesity and elevated Von Willebrand Factor (VWF) is complex and ...not fully elucidated. There is a significant knowledge gap regarding the impact of BMI on VWF levels. Given the proinflammatory effect associated with abdominal obesity, we hypothesized that there would be an increased prevalence of obesity among individuals with Low VWF (LVWF) compared to Type 1 Von Willebrand Disease (T1VWD) in the ATHN (American Thrombosis and Hemostasis Network) dataset.
Methods: A retrospective review of de-identified patients included in the ATHN dataset as of March 2018 was performed. The dataset was queried for all patients with a diagnosis of “T1VWD,” who were over 18 years of age when labs were drawn and when BMI was recorded, who had VWF Ristocetin cofactor (RCO) levels <50 IU/dL and who had BMI entered within 24 months of the date of lab entry. Subjects were categorized with VWF RCO ≤30% as T1VWD and 30-50% as LVWF. We used the NIH definitions for BMI (BMI<18.5, underweight; 18.5-24.9, normal; 25-29.9, overweight; 30-39.9, obese; BMI >40, extremely obese).
Results: Of the 6939 patients with T1VWD in the ATHN dataset, 4754 patients had VWF RCO <50%, 1019 were above the age of 18, resulting in 548 evaluable subjects with BMI and laboratory metrics. There were 186 patients in the T1VWD cohort, and 362 patients in the LVWF cohort, with a Female:Male ratio >3:1 (Table 1). BMI was treated as a continuous measurement and on bivariate analysis there was not a statistically significant difference (p=0.593), with mean BMI 28.2 (17.2-52) in T1VWD and 28.6 (15.3-55.4) in LVWF. Prevalence of obesity (BMI ≥30) was not significantly different between cohorts (T1VWF 32% vs. LVWF 36%, p=0.345, Table 1). The prevalence of obesity by age (18-39, 40-59, >60 years) was similar among both cohorts with the exception of a larger proportion of obese individuals over the age of 60 in the LVWF cohort (63% vs 25%). Mean FVIII level for LVWF cohort was significantly higher compared to that for T1VWD cohort (80% vs. 53%; p<0.001). In addition, extremely obese patients had an elevated mean FVIII level compared to overweight patients (81% vs. 60%; p=0.041, Table 2).
Among individuals with BMI≥30, there were increased rates for Black race (p=0.013), and Medicaid and Medicare rates (p=0.028) when compared to non-obese individuals (Table 3). While rates of obesity are known to vary regionally, no conclusions could be drawn as there was disproportionate geographic clustering in states with well-established hemophilia treatment centers.
Conclusions: Our analysis identified that 34.8% of adults categorized as VWD in the ATHN data set are obese, with similar prevalence among T1VWD and LVWF. This finding, coupled with associated race, ethnic and socioeconomic risk factors can help prioritize prevention and weight management as a critical component of the comprehensive care model. Increasing degree of obesity may be associated with elevated FVIII, and should be studied prospectively in larger cohorts and the potential impact on cardiovascular risk. Limitations of this analysis include incomplete laboratory data, lack of longitudinal laboratory data, unknown potential confounders including pregnancy or medication effect, and non-uniform geographic distribution of patients. Further research is needed to evaluate the impact of obesity on bleeding phenotype, bleeding related complications, and management practices, as well as the effects of weight change on VWF and FVIII levels.
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Schaefer:Siemens: Research Funding; Stago: Research Funding.
Purpose To quantify the impact of ignoring misclassification of a response variable and measurement error in a covariate on statistical power, and to develop software for sample size and power ...analysis that accounts for these flaws in epidemiologic data. Methods A Monte Carlo simulation-based procedure is developed to illustrate the differences in design requirements and inferences between analytic methods that properly account for misclassification and measurement error to those that do not in regression models for cross-sectional and cohort data. Results We found that failure to account for these flaws in epidemiologic data can lead to a substantial reduction in statistical power, over 25% in some cases. The proposed method substantially reduced bias by up to a ten-fold margin compared to naive estimates obtained by ignoring misclassification and mismeasurement. Conclusions We recommend as routine practice that researchers account for errors in measurement of both response and covariate data when determining sample size, performing power calculations, or analyzing data from epidemiological studies.
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