Coagulation initiated on herpesviruses

Herpesviruses have been previously correlated to vascular disease and shown to cause thrombogenic and atherogenic changes to host cells. Herein we show that even in the absence of cells, purified cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) can initiate thrombin production. Functional assays demonstrated that purified HSV-1 and HSV-2 provide the necessary phospholipid (proPL) for assembling the coagulation factors Xa and Va into prothrombinase, which is responsible for generating thrombin. These observations are consistent with our earlier studies involving CMV. The presence of proPL on all three herpesviruses was confirmed directly by flow cytometry and electron microscopy by using annexin V and factor Va, respectively, as proPL-specific probes. Of equal importance, we found that CMV, HSV-1, and HSV-2 were also able to facilitate factor Xa generation from the inactive precursor factor X, but only when factor VII/VIIa and Ca²⁺ were present. Monoclonal antibodies specific for tissue factor (TF), the coagulation initiator, inhibited this factor X activation and, furthermore, enabled identification of TF antigen on each virus type by flow cytometry and electron microscopy. Collectively, these data show that CMV, HSV-1, and HSV-2 can initiate the generation of thrombin by having essential proPL and TF activities on their surface. Unlike the normal cellular source, the viral activity is constitutive and, therefore, not restricted to sites of vascular injury. Thus cell-independent thrombin production may be the earliest event in vascular pathology mediated by herpesviruses.     

Roadmap for the development of the University of North Carolina at Chapel Hill Genitourinary OncoLogy Database—UNC GOLD

BackgroundThe management of genitourinary malignancies requires a multidisciplinary care team composed of urologists, medical oncologists, and radiation oncologists. A genitourinary (GU) oncology clinical database is an invaluable resource for patient care and research. Although electronic medical records provide a single web-based record used for clinical care, billing, and scheduling, information is typically stored in a discipline-specific manner and data extraction is often not applicable to a research setting. A GU oncology database may be used for the development of multidisciplinary treatment plans, analysis of disease-specific practice patterns, and identification of patients for research studies. Despite the potential utility, there are many important considerations that must be addressed when developing and implementing a discipline-specific database.Methods and materialsThe creation of the GU oncology database including prostate, bladder, and kidney cancers with the identification of necessary variables was facilitated by meetings of stakeholders in medical oncology, urology, and radiation oncology at the University of North Carolina (UNC) at Chapel Hill with a template data dictionary provided by the Department of Urologic Surgery at Vanderbilt University Medical Center. Utilizing Research Electronic Data Capture (REDCap, version 4.14.5), the UNC Genitourinary OncoLogy Database (UNC GOLD) was designed and implemented.ResultsThe process of designing and implementing a discipline-specific clinical database requires many important considerations. The primary consideration is determining the relationship between the database and the Institutional Review Board (IRB) given the potential applications for both clinical and research uses. Several other necessary steps include ensuring information technology security and federal regulation compliance; determination of a core complete dataset; creation of standard operating procedures; standardizing entry of free text fields; use of data exports, queries, and de-identification strategies; inclusion of individual investigators' data; and strategies for prioritizing specific projects and data entry.ConclusionsA discipline-specific database requires a buy-in from all stakeholders, meticulous development, and data entry resources to generate a unique platform for housing information that may be used for clinical care and research with IRB approval. The steps and issues identified in the development of UNC GOLD provide a process map for others interested in developing a GU oncology database.     

We are the experts: people with asthma talk about their medicine information needs

People with chronic illness are being encouraged to become more involved in their care. For this, they need to be well informed about their medicines, and more written medicines information is becoming available. However, there is little data about its effectiveness and impact. This study examined the patient perspective of medicines information through focus groups of people with asthma. Most participants actively sought medicines information from a variety of professional and lay sources. There were some positive experiences but many examples of partial or total information failure. Individualised information was valued and medicine leaflets were generally seen as less helpful than face-to-face advice. Some felt strongly that patients with long experience should be involved in the development of medicine information leaflets. We conclude that medicine information leaflets do not currently meet the needs of users and that people who take medicines should be involved in their development and testing.     

Home Food Environment Changes and Dietary Intake during an Adolescent Behavioral Weight Loss Intervention Differ by Food Security Status

Behavioral weight loss (BWL) for pediatric obesity includes guidance on improving the home food environment and dietary quality; yet food insecurity presents barriers to making these changes. This study examined if home food environment, dietary quality, energy intake, and body weight changes during adolescent obesity treatment differed by food security status, and if changes in the home food environment were associated with changes in dietary quality and energy intake by food security status. Adolescents (n = 82; 13.7 ± 1.2 years) with obesity participated in a 4-month BWL treatment. Food insecurity, home food environment (Home Food Inventory [HFI]), dietary quality (Healthy Eating Index [HEI]), energy intake, and body mass index (BMI) were assessed at baseline and post-treatment. A reduced obesogenic home food environment and improved dietary quality were observed for food secure (ps < 0.01), but not insecure households (ps > 0.05) (mean difference, HFI: −6.6 ± 6.4 vs. −2.4 ± 7.4; HEI: 5.1 ± 14.4 vs. 2.7 ± 17.7). Energy intake and BMI decreased for adolescents in food secure and insecure households (ps < 0.03) (mean difference; energy intake: −287 ± 417 vs. −309 ± 434 kcal/day; BMI: −1.0 ± 1.4 vs. −0.7 ± 1.4). BWL yielded similar reductions in energy intake and body weight yet did not offer the same benefits for improved dietary quality and the home food environment for adolescents with food insecurity.     

Correction of linoleic acid deficiency in cystic fibrosis

To identify evidence of essential fatty acid deficiency, we screened 64 patients with cystic fibrosis by analyzing total lipid extracts from plasma. Forty-three had an abnormal linoleate (18:2) level (less than 26%). Thirteen deficient patients (aged 10-24 yr) ingested for 1 yr 7% of their total calories as linoleate derived from a daily supplement of Microlipid. Five deficient patients (aged 10-37 yr) served as controls. Plasma and erythrocyte fatty acid composition were monitored by gas chromatography of total lipid extracts seven times during the twelve month period. Prostaglandins E2 and F2 alpha and their 15 keto 13, 14 dihydrometabolite, 6-keto F1 alpha, and thromboxane B2 were measured by radioimmunoassay. Sweat tests, oxygen saturation, growth indices, clinical severity scores, compliance, and possible side effects from taking Microlipid were followed. Results showed that oral supplementation with Microlipid can significantly increase plasma and erythrocytes % 18:2. One compliant patient died during the study and had normal tissue 18:2 levels. Nine of 13 patients gained more weight while taking Microlipid than in the previous year. No significant changes in sweat electrolytes, clinical scores, or oxygen saturation were found during the study year. Prostaglandin metabolites prostaglandin E2 showed an upward trend in supplemented patients, compared to controls. Prostaglandin F2 alpha remained unchanged over 1 yr but showed a trend significantly downward over the final 6 months in supplemented patients. We conclude that linoleate deficiency can be corrected with daily Microlipid supplements and that correction may alter prostaglandin metabolism.     

A cost-analysis of adopting a healthful diet in a family-based obesity treatment program

OBJECTIVE: To assess dietary costs during a family-based pediatric obesity intervention. DESIGN: Families were randomized to one of two groups. Dietary and cost data were collected from a parent or child using three 24-hour recalls: at baseline, 6 months, and 12 months. SUBJECTS: Thirty-one families with an obese 8- to 12-year-old child entered treatment, with complete dietary data provided from 20 families. INTERVENTION: The 20-week behavior modification intervention emphasized increasing diet nutrient-density. Families attended group and individual sessions or group sessions. MAIN OUTCOME MEASURES: Energy intake; percent of energy from protein, fat, and carbohydrate; servings and percent servings from food groups classified by nutrient density; and daily food costs. STATISTICAL ANALYSES PERFORMED: Mixed analyses of variance, with group as the between-subject factor, and time as the within-subject factor. RESULTS: No significant effect of group was found in any analyses. Significant decreases in percent overweight were observed at 6 and 12 months for children (-10.0+/-8.7 and -8.0+/-10.3, respectively) (mean+/-standard deviation) and parents (-6.7+/-10.3 and -5.3+/-14.1). Energy intake for parents and children combined significantly decreased from baseline (1,881+/-462) to 6 months (1,412+/-284), and 1 year (1,338+/-444). Servings from low-nutrient-dense foods significantly decreased from baseline (34.7+/-16.2) to 6 months (16.0+/-8.6) and 1 year (18.6+/-9.2), causing a significant increase in diet nutrient density. Dietary cost did not change at 6 months, but significantly decreased from baseline to 1 year ($6.77+/-2.41 to $5.04+/-1.80). Cost per 1,000 kcal did not significantly change. APPLICATIONS/CONCLUSIONS: Adopting a lower-energy, nutrient-dense diet did not increase dietary costs over time. Consequently, cost should not be a barrier in the adoption of a healthful diet.     

Official warnings on thromboembolism risk with oral contraceptives fail to inform users adequately

Following the 1995 "pill scare" relating to the risk of venous thrombosis from taking second- or third-generation oral contraceptives, the Committee on Safety of Medicines (CSM) withdrew their earlier recommended restrictions on the use of third-generation pills and published recommended wording to be used in patient information leaflets. However, the effectiveness of this wording has not been tested. An empirical study (with 186 pill users, past users, and non-users) was conducted to assess understanding, based on this wording, of the absolute and relative risk of thrombosis in pill users and in pregnancy. The results showed that less than 12% of women in the (higher education) group fully understood the absolute levels of risk from taking the pill and from being pregnant. Relative risk was also poorly understood, with less than 40% of participants showing full understanding, and 20% showing no understanding. We recommend that the CSM revisit the wording currently provided to millions of women in the UK.     

Transvaginal ultrasonographic cervical measurement as a predictor of successful labor induction

OBJECTIVE: Our purpose was to compare transvaginal cervical measurement and the Bishop score as indicators of duration of labor and successful induction of labor at term.Study Design: This prospective observational study recruited women with singleton gestations scheduled for induction of labor at > or =37 weeks. Transvaginal ultrasonographic measurement of cervical length was performed and the Bishop score was determined, each by operators masked to the other measurement. Data were collected on parity, gestational age, mode of delivery, induction agent, induction-to-delivery interval, Bishop score, and cervical length measurement. RESULTS: A total of 77 women were analyzed. Vaginal delivery occurred in 69%. Both Bishop score and cervical length showed linear correlation with duration of labor (R(2) = 0.43, P <. 001; R(2) = 0.48, P <.001; respectively). Women with cervical length <3.0 cm had shorter labors (P <.001) and were more likely to be delivered vaginally (P <.001). Women with a Bishop score >4 also had shorter labors and were more likely to be delivered vaginally, with similar P values. A logistic regression model identified cervical length and parity as the only independent predictors of vaginal delivery. CONCLUSIONS: Both ultrasonographically measured cervical length and Bishop score predict duration of labor and likelihood of vaginal delivery. However, only cervical length and parity were independent predictors of mode of delivery.