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.

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.

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.

Consumption of prunes as a source of dietary fiber in men with mild hypercholesterolemia.

Forty-one free-living adult men with mild hypercholesterolemia (5.2-7.5 mmol/L) voluntarily participated in an 8-wk crossover study designed to determine the effect of prunes as a source of fiber on plasma cholesterol and on fecal output and bile acid concentration. During the prune period, subjects supplemented their usual diets with 12 prunes (100 g; 6 g dietary fiber) daily. Plasma low-density-lipoprotein cholesterol was significantly lower after the prune period (3.9 mmol/L) than after the grape-juice-control period (4.1 mmol/L). Fecal bile acid concentration of lithocholic acid was significantly lower after the prune period (0.95 mg bile acid/g dry wt stool) than after the grape-juice-control period (1.20 mg bile acid/g dry wt stool). Both fecal wet and dry weights were approximately 20% higher after the prune period than after the grape-juice-control period. Total bile acids (mg/72 h) did not significantly differ between experimental periods.

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.

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.

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.

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.

[The lytic activity of Yersinia pestis phage P 3d serovar]. / Liticheskaia aktivnost' faga Yersinia pestis P 3-go serovara.

The lytic activity of plague phage II, serovar 3, with respect to 1,800 bacterial strains has been studied: 760 Yersinia pestis strains, 262 Y. pseudotuberculosis strains, 252 Y. enterocolitica strains, 166 Escherichia coli strains, 90 Shigella strains and 270 strains of other species. The phage has been found to lyse 81.8% of Y. pestis strains, 1 Y. pseudotuberculosis strain and 1 Y. enterocolitica strain. The representatives of other 19 bacterial species have proved to be resistant to the phage. Though having a wide range of action within Y. pestis, the phage does not lyse most of the strains of the causative agent of plague, isolated in certain natural foci. This fact offers promise for using the phage for the differentiation of Y. pestis.

[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.

[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.

[Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit intoxication]. / Detoksitsiruiushchee deistvie antibiotikov i ikh éffektivnost' pri éksperimental'noi chume na stadii vyrazhennoi intoksikatsii.

The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent).