Timing of HPV16-E6 antibody seroconversion before OPSCC: findings from the HPVC3 consortium.

BACKGROUND: Human papillomavirus type 16 (HPV16)-E6 antibodies are detectable in peripheral blood before diagnosis in the majority of HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), but the timing of seroconversion is unknown. PATIENTS AND METHODS: We formed the HPV Cancer Cohort Consortium which comprises nine population cohorts from Europe, North America and Australia. In total, 743 incident OPSCC cases and 5814 controls provided at least one pre-diagnostic blood sample, including 111 cases with multiple samples. Median time between first blood collection and OPSCC diagnosis was 11.4 years (IQR = 6-11 years, range = 0-40 years). Antibodies against HPV16-E6 were measured by multiplex serology (GST fusion protein based Luminex assay). RESULTS: HPV16-E6 seropositivity was present in 0.4% of controls (22/5814; 95% CI 0.2% to 0.6%) and 26.2% (195/743; 95% CI 23.1% to 29.6%) of OPSCC cases. HPV16-E6 seropositivity increased the odds of OPSCC 98.2-fold (95% CI 62.1-155.4) in whites and 17.2-fold (95% CI 1.7-170.5) in blacks. Seropositivity in cases was more frequent in recent calendar periods, ranging from 21.9% pre-1996 to 68.4% in 2005 onwards, in those with blood collection near diagnosis (lead time <5 years). HPV16-E6 seropositivity increased with lead time: 0.0%, 13.5%, 23.7%, and 38.9% with lead times of >30 years (N = 24), 20-30 years (N = 148), 10-20 years (N = 228), and <10 years (N = 301 cases) (p-trend < 0.001). Of the 47 HPV16-E6 seropositive cases with serially-collected blood samples, 17 cases seroconverted during follow-up, with timing ranging from 6 to 28 years before diagnosis. For the remaining 30 cases, robust seropositivity was observed up to 25 years before diagnosis. CONCLUSIONS: The immune response to HPV16-driven tumorigenesis is most often detectable several decades before OPSCC diagnosis. HPV16-E6 seropositive individuals face increased risk of OPSCC over several decades.

Chocolate intake and diabetes risk in postmenopausal American women.

BACKGROUND/OBJECTIVES: Recent long-term prospective cohort studies found inverse associations between chocolate consumption and the risk of type 2 diabetes, but provided conflicting evidence on the nature of the association among women. To assess this association in a large cohort of American women. SUBJECTS/METHODS: Multivariable Cox regression was used with the data from 92 678 postmenopausal women in the prospective Women's Health Initiative study. Chocolate intake was assessed by food frequency questionnaire. Incidence of type 2 diabetes was determined by self-report of the first treatment with oral medication or insulin. RESULTS: Among women free of diabetes at baseline, there were 10 804 cases, representing an incidence rate of 11.7% during 13.1 years and 1 164 498 person-years of follow-up. There was no significant linear association between long-term chocolate intake and type 2 diabetes risk, but there was significantly reduced risk at moderate levels of intake. Compared to women who ate 1 oz. of chocolate <1 time per month, those who ate this amount 1-<1.5 times per month, 1.5-<3.5 times per month, 3.5 times per month to <3 times per week and ⩾3 times per week had hazard ratios of 0.97 (95% confidence interval: 0.92, 1.04), 0.92 (0.87, 0.98), 0.93 (0.88, 0.98) and 0.98 (0.92, 1.04) (P for linear trend=0.79). There was only evidence of such inverse associations for women with below-median physical activity (P for interaction <0.0001) and those with age<65 years (P=0.01). CONCLUSIONS: We only found an inverse association between chocolate consumption and type 2 diabetes at moderate levels of consumption in two subgroups of postmenopausal women in the Women's Health initiative cohort.

Pre-existing diabetes and breast cancer prognosis among elderly women.

BACKGROUND: The objective of this study was to assess the impact of pre-existing diabetes on breast cancer prognosis. METHODS: Women (n=2833) with centrally confirmed invasive breast cancer in the Women's Health Initiative, who were linked to Medicare claims data (CMS) were followed from the date of breast cancer diagnosis to date of death or 20 September 2013. Information on diabetes was identified through the CMS Chronic Condition Warehouse algorithm. Cox proportional hazard regression was used to estimate adjusted hazard ratios for overall mortality. A competing risks model (proportional subdistribution) model was used to estimate hazard ratios for breast cancer-specific mortality. RESULTS: Women with diabetes were more likely to have factors related to delayed diagnosis (less recent mammograms, and more advanced cancer stage) and were less likely to receive radiation therapy. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR=1.57, 95% CI: 1.23-2.01) and had nonsignificantly increased risk for breast cancer-specific mortality (HR=1.36, 95% CI: 0.86-2.15) before adjustment for factors related to delayed diagnosis and treatment. Adjustment for these factors resulted in a little change in the association of diabetes with overall mortality risk, but further attenuated the point estimate for breast cancer-specific mortality. CONCLUSIONS: Our study provides additional evidence that pre-existing diabetes increases the risk of total mortality among women with breast cancer. Very large studies with data on breast cancer risk factors, screening and diagnostic delays, treatment choices, and the biological influence of diabetes on breast cancer will be needed to determine whether diabetes also increases the risk for breast cancer-specific mortality.

Relationship between diabetes risk and admixture in postmenopausal African-American and Hispanic-American women.

AIMS/HYPOTHESIS: Type 2 diabetes is more prevalent in African-Americans (AFAs) and Hispanic-Americans (HAs) than in European-Americans. We assessed whether continental admixture was correlated with diabetes risk in these high-risk groups. METHODS: We estimated the proportion of sub-Saharan African (AFR), Amerindian (AMI) and European admixture using 92 ancestry-informative marker genotypes in 16,476 AFA and HA women from the Women's Health Initiative. Cox regression models were used to examine the association between admixture and diabetes risk, with and without accounting for socioeconomic status (SES) and adiposity measurements. RESULTS: AFR admixture was significantly associated with diabetes risk in AFA women when adjusting for entry age, neighbourhood SES and BMI or waist/hip ratio (WHR) (all p < 0.0001). In HA women, AMI admixture had significant associations with diabetes risk that remained significant after adjustment for SES and BMI (all p < 0.0005). In both AFAs and HAs, SES showed significant negative associations while BMI or WHR had significant positive associations with diabetes risk, with and without adjustment for genetic admixture. CONCLUSIONS/INTERPRETATION: In AFAs, admixture, SES and BMI/WHR each independently contribute to diabetes risk after accounting for each of the other factors; in HAs, admixture, SES and BMI each independently contribute to diabetes risk after accounting for each of the other factors, whereas admixture is not significantly associated with diabetes risk after accounting for SES and WHR. The findings emphasise the importance of considering both genetic and environmental causes in the aetiology of type 2 diabetes.

Predictors of adherence in the Women's Health Initiative Calcium and Vitamin D Trial.

The authors analyzed data from the Women's Health Initiative (WHI) Calcium and Vitamin D Supplementation Trial (CaD) to learn more about factors affecting adherence to clinical trial study pills (both active and placebo). Most participants (36,282 postmenopausal women aged 50-79 years) enrolled in CaD 1 year after joining either a hormone trial or the dietary modification trial of WHI. The WHI researchers measured adherence to study pills by weighing the amount of remaining pills at an annual study visit; adherence was primarily defined as taking > or = 80% of the pills. The authors in this study examined a number of behavioral, demographic, procedural, and treatment variables for association with study pill adherence. They found that relatively simple procedures (ie, phone contact early in the study [4 weeks post randomization] and direct social contact) later in the trial may improve adherence. Also, at baseline, past pill-use experiences, personal supplement use, and relevant symptoms may be predictive of adherence in a supplement trial.

The effect of conjugated equine oestrogen on diabetes incidence: the Women's Health Initiative randomised trial.

AIMS/HYPOTHESIS: Recent clinical trials have found that the combination of conjugated equine oestrogen (CEO) and medroxyprogesterone has a protective effect on the incidence of type 2 diabetes. To determine the effect of CEO alone on the incidence of diabetes mellitus in postmenopausal women, we analysed the results of the Women's Health Initiative oestrogen-alone trial. METHODS: The Women's Health Initiative is a randomised, double-masked trial comparing the effect of daily 0.625 mg CEO with placebo during 7.1 years of follow-up of 10,739 postmenopausal women who were aged 50-79 years and had previously had a hysterectomy. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin and lipoproteins were measured in an 8.6% random sample of study participants, at baseline and at 1, 3 and 6 years. RESULTS: The cumulative incidence of treated diabetes was 8.3% in the oestrogen-alone group and 9.3% in the placebo group (hazard ratio 0.88, 95% CI 0.77-1.01, p=0.072). During the first year of follow-up, a significant fall in insulin resistance (homeostasis model assessment of insulin resistance) in actively treated women compared with the control subjects (Year 1 baseline between-group difference -0.53) was seen. However, there was no difference in insulin resistance at the 3- or 6-year follow-up. CONCLUSIONS/INTERPRETATION: Postmenopausal therapy with oestrogen alone may reduce the incidence of treated diabetes. The effect is smaller than that seen with oestrogen plus progestin. CEO should not, however, be used with the intention of preventing diabetes, as its well-described adverse effects preclude long-term use for primary prevention.

Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: results from the Women's Health Initiative Hormone Trial.

AIMS/HYPOTHESIS: Studies examining the effect of postmenopausal hormone therapy on concentrations of glucose, insulin and diabetes incidence have been inconclusive, in part because many of the studies were too small. We examined the effect of oestrogen plus progestin on diabetes incidence and insulin resistance. METHODS: The study was a randomised, double-blind trial comparing the effect of daily 0.625 mg conjugated equine oestrogens plus 2.5 mg medroxyprogesterone acetate with that of placebo during 5.6 years of follow-up. The participants were 15,641 postmenopausal women enrolled in the Women's Health Initiative Hormone Trial. These women were aged 50 to 79 and all had an intact uterus. Diabetes incidence was ascertained by self-report of treatment with insulin or oral hypoglycaemic medication. Fasting glucose, insulin, and lipoproteins were measured in a random sample at baseline and at 1 and 3 years. RESULTS: The cumulative incidence of treated diabetes was 3.5% in the hormone therapy group and 4.2% in the placebo group (hazard ratio 0.79, 95% CI 0.67-0.93, p=0.004). There was little change in the hazard ratio after adjustment for changes in BMI and waist circumference. During the first year of follow-up, changes in fasting glucose and insulin indicated a significant fall in insulin resistance in actively treated women compared to the control subjects (Year 1 to baseline between-group difference -0.22+/-0.10, p=0.03). INTERPRETATIONS/CONCLUSION: These data suggest that combined therapy with oestrogen and progestin reduces the incidence of diabetes, possibly mediated by a decrease in insulin resistance unrelated to body size. Future studies of alternative postmenopausal hormone therapy regimens and selective oestrogen agonists and/or antagonists should consider the effects of these regimens on insulin resistance and diabetes.

Measurement characteristics of 2 different self-monitoring tools used in a dietary intervention study.

OBJECTIVE: To examine the measurement characteristics of 2 self-monitoring tools, a food diary and fat scan, used in the dietary intervention of the Women's Health Trial: Feasibility in Minority Populations study. DESIGN: Comparison of fat intake reported on the self-monitoring tools to a criterion measure of fat intake, specifically the mean of a food frequency questionnaire and a 4-day food record. The main outcome measures were differences in fat grams and correlations between each of the self-monitoring tools and the criterion measure. SUBJECTS/SETTING: Six-month postrandomization data from 313 women aged 50 to 79 years who participated in the intervention group of the Women's Health Trial: Feasibility in Minority Populations study. RESULTS: Both self-monitoring tools underestimated fat intake compared to the criterion measure, the food diary by 9 g and the fat scan by 6 g. The self-monitoring instruments were better than chance at detecting a low-fat dietary pattern, however, and did not differ from each other in their ability to do so. APPLICATIONS/CONCLUSIONS: The self-monitoring tools were modestly precise as measures of fat intake, but neither was sufficiently accurate to be reliable as a sole assessment of dietary adherence. Dietetics professionals are encouraged to assess the measurement properties of self-monitoring tools to use them appropriately in supporting dietary changes.

Differences in eating pattern labels between maintainers and nonmaintainers in the Women's Health Initiative.

OBJECTIVE: To describe how a sample of women in the Women's Health Initiative Dietary Modification Trial (WHIDM) labeled a healthy eating pattern and to compare these labels to their dietary maintenance. DESIGN: Participants completed a food frequency questionnaire and were divided into two maintenance groups, based on the percentage of energy derived from fat in their diets. Individual, semistructured interviews with the same subjects elicited information on labels they use to describe a healthy eating pattern. SUBJECTS/SETTINGS: Subjects were 100 postmenopausal women, 50 to 79 years of age, free of breast and colorectal cancer, and participating in a dietary intervention that consisted of 20% or less energy from fat. MAIN OUTCOME MEASURES: Percentage of energy from fat in the diet and labels used to define a healthy eating pattern. STATISTICAL ANALYSES PERFORMED: Multivariate analysis. RESULTS: The label "consistent/patterned" was a predictor of dietary nonmaintenance (p <.05). IMPLICATIONS: Future studies should use this information to re-educate nonmaintainers on compliance issues.

Bone marrow mobilized with granulocyte colony-stimulating factor in related allogeneic transplant recipients: a study of 29 patients.

We studied whether a short course of granulocyte colony-stimulating factor (G-CSF) administered to normal donors immediately before bone marrow (BM) harvest would shorten time to neutrophil and platelet engraftment in matched related allogeneic BM recipients. Twenty-nine normal donors received 4 consecutive daily subcutaneous injections of G-CSF (median dose, 12.1 microg/kg per day; range, 9.6-15.7 microg/kg per day) immediately before BM harvest. Donors tolerated G-CSF well, with only mild myalgias and arthralgias, and BM was easy to aspirate. The BM harvest contained a median of 5.3 x 10(8) white blood cells (WBCs)/kg (range, 3.1-11.1 x 10(8) WBCs/kg) and 2.5 x 10(6) CD34+ cells per kg (range, 1.5-7.3 x 10(6) CD34+ cells per kg). Median times to neutrophil (18 days [range, 11-30 days] versus 22 days [range, 16-36 days]; P = .05) and platelet (22 days [range, 15-55 days] versus 27 days [range, 18-46 days]; P = .04) engraftment were statistically shorter than those of historical control subjects whose donors had not received G-CSF before BM harvest. However, secondary engraftment-dependent outcomes including red blood cell and platelet transfusions, febrile days, days on antibiotics, days from transplant to hospital discharge, and days in hospital during the first 60 days after transplant were not statistically different from historical control subjects. We conclude that G-CSF administered to normal donors immediately before harvest facilitates BM aspiration, increases the WBC content of the harvest, and hastens neutrophil and platelet engraftment compared with historical control subjects.

Evaluation of a simplified vitamin supplement inventory developed for the Women's Health Initiative.

OBJECTIVE: To evaluate the accuracy of a simplified inventory procedure for assessing nutrient intake from vitamin and mineral supplements. DESIGN: Participants brought their supplements to a clinic. An interviewer conducted the supplement inventory procedure, which consisted of recording data on the type of multiple vitamin and single supplements used. For the multiple vitamins, the interviewer recorded the exact dose for a subset of nutrients (vitamin C, calcium, selenium). For other nutrients, we imputed the dose in multiple vitamins. The dose of all single supplements was recorded. Labels of the supplements were photocopied and we transcribed the exact nutrient label data for the criterion measure. Spearman correlation coefficients were used to assess precision of nutrient intakes from the simplified inventory compared to the criterion measure. SETTING/SUBJECTS: Data are from 104 adult vitamin supplement users in Washington state. RESULTS: Correlation coefficients between nutrient intake estimated from the simplified inventory compared to the criterion measure were high (0.8-1.0) for those nutrients (vitamin C, calcium, selenium) for which the interviewer recorded the exact dose contained in multiple vitamins. However, for nutrients for which imputations were made regarding dose in multiple vitamins, correlation coefficients ranged from good (0.8 for vitamin E) to poor (0.3 for iron). CONCLUSIONS: The simplified inventory is rapid (4-5 min) and practical for large-scale studies. The precision of nutrient estimates using this procedure was variable, although excellent for the subset of nutrients for which the dose was recorded exactly. This study illustrates many of the challenges of collecting high quality supplement data.

(n-3) fatty acid supplementation in moderately hypertriglyceridemic adults changes postprandial lipid and apolipoprotein B responses to a standardized test meal.

The effects of (n-3) fatty acids on the postprandial state were investigated by monitoring the alimentary responses to identical test meals fed to adults [n = 11; fasting triacylglycerol (TG) 2.55 +/- 0.24 mmol/L; mean +/- SEM] after a self-selected diet baseline period (BLP) and then after a 6-wk (n-3) fatty acid period (FOP) [ approximately 5.2 g (n-3) fatty acids] and a 6-wk control oil period (COP) administered in random order. Samples were drawn immediately prior to the test meal (time 0) and then hourly from 2 to 6 h postmeal. Postprandial plasma triacylglycerol (TG) and TG-rich lipoprotein (TRL) TG apo B48, and B100 absolute concentrations were significantly lower after FOP than after COP or BLP, while plasma cholesterol was unchanged. Normalizing the results as increments over time 0 eliminated the diet effect on all but plasma TG. Time remained a significant effect for plasma TG, TRL TG, and TRL TC. Finally, only absolute TRL B48 and absolute and incremental plasma TG concentrations displayed significant time-diet interactions. These results suggest that postprandial TRL apo B reductions are likely caused by (n-3) fatty acid suppression of both hepatic and intestinal apoB secretion/synthesis. Altered TRL metabolism, i.e. changes in postprandial TG, cholesterol, apo B48, and increase in LDL particle size, may represent an additional mechanism for the reduced heart disease risk associated with fish [(n-3) fatty acid] consumption.

Measurement characteristics of the Women's Health Initiative food frequency questionnaire.

PURPOSE: The Women's Health Initiative (WHI) is the largest research program ever initiated in the United States with a focus on diet and health. Therefore, it is important to understand and document the measurement characteristics of the key dietary assessment instrument: the WHI food frequency questionnaire (FFQ). METHODS: Data are from 113 women screened for participation in the WHI in 1995. We assessed bias and precision of the FFQ by comparing the intake of 30 nutrients estimated from the FFQ with means from four 24-hour dietary recalls and a 4-day food record. RESULTS: For most nutrients, means estimated by the FFQ were within 10% of the records or recalls. Precision, defined as the correlation between the FFQ and the records and recalls, was similar to other FFQs. Energy adjusted correlation coefficients ranged from 0.2 (vitamin B12) to 0.7 (magnesium) with a mean of 0.5. The correlation for percentage energy from fat (a key measure in WHI) was 0.6. Vitamin supplement use was common. For example, almost half of total vitamin E intake was obtained from supplements. Including supplemental vitamins and minerals increased micronutrient correlation coefficients, which ranged from 0.2 (thiamin) to 0.8 (vitamin E) with a mean of 0.6. CONCLUSIONS: The WHI FFQ produced nutrient estimate, that were similar to those obtained from short-term dietary recall and recording methods. Comparison of WHI FFQ nutrient intake measures to independent and unbiased measures, such as doubly labeled water estimates of energy expenditure, are needed to help address the validity of the FFQ in this population.

Clinical and economic analysis of allogeneic peripheral blood progenitor cell transplants: a Canadian perspective.

Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 microg/kg/day) (group 1) and 20 mobilized with 10 microg/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 x 10(6) CD34+/kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34,643 vs $37,354) but the mean overall cost for both groups was similar at 100 days ($46,334 vs $46,083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT.

[Enhancement of treatment efficacy in experimental plague by the sequential administration of antibiotics]. / Povyshenie éffektivnosti lecheniia éksperimental'noi chumy putem posledovatel'nogo vvedeniia antibiotikov.

It was shown that the use of ampicillin, azlocillin or polymyxin 24 or 96 hours after the plague infection at the background of the every-day use of rifampicin in the doses protecting only 30 per cent of the animals from death provided 80-100-percent survival of the animals. With the every-day use of ampicillin, azlocillin or polymyxin in succession with rifampicin there was observed a 3-fold increases in the survival of the albino mice as compared to those exposed to an analogous dose of rifampicin alone. A decrease in the number of administrations of the above drugs and an increase in the intervals between the administration also resulted in a significant rise of the animal survival in comparison with that after the every-day use of a similar dose of rifampicin.

Dietary fiber.

Most of our understanding of the physiologic effects of dietary fiber are derived from studies in adults. These investigations have indicated the potential problems with fiber consumption are most likely to occur if isolated polysaccharides or nonpurified fiber supplements are consumed excessively. Such problems include intestinal obstruction and significant reductions in nutrient availability. Inclusion of foods that contain dietary fiber such as fruits, vegetables, beans, and whole-grain products is unlikely to result in complications for most individuals. Young children may need to consume smaller servings of these foods than adults; however, their inclusion in the diet is an important part of meeting dietary recommendation for fiber intake. Excess consumption of fiber-supplemented foods (e.g., bran cereals) should be monitored to avoid appetite suppression that could limit selection of foods to maintain a balanced diet.

Diabetes mellitus--a priority health care issue for women.

Diabetes occurs in more than 13 million persons in the United States, and approximately 60% of the new cases are diagnosed in women. This review examines health issues related to women with diabetes mellitus. The following issues are discussed in the review. The prevalence of diabetes is higher in Native-American, black, and Hispanic women than in white women. Women with upper-body obesity are at risk for developing non-insulin-dependent diabetes mellitus (NIDDM) and women with diabetes are at risk for developing heart disease. Diabetes, obesity, and heart disease are all modifiable by nutrition. White women with diabetes derive approximately 40% of energy from fat, which is 10% greater than the national goal. Women with a history of gestational diabetes are at risk for developing NIDDM. Women with insulin-dependent diabetes mellitus (IDDM) are at high risk of developing complications in pregnancy, and pregnancy outcomes improve with preconceptual counseling. Women with IDDM are at risk for developing eating disorders, although not to a greater extent than the nondiabetic population. Women with diabetes are at risk for developing endometrial cancer. Both IDDM and NIDDM prevention clinical trials are in progress, although none target women specifically. Dietetics practitioners are encouraged to use local and national diabetes resources.

[A method of sequential administration of antibiotics in preventive treatment of experimental plague in albino mice]. / Metod posledovatel'nogo vvedeniia antibiotikov v predupreditel'nom lechenii éksperimental'noi chumy belykh myshei.

Combination of a betalactam antibiotic (ampicillin or azlocillin) or polymyxin B with rifampicin were studied with their administration in succession at various intervals in an experimental model of plague infection of albino mice. It was shown that when the administration of the betalactams or polymyxin B preceded the administration of rifampicin, the efficacy of the preventive therapy considerably increased. The time of the intervals was noted to be of importance and should be predetermined for every subsequent administration.