Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium.

BACKGROUND: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. PATIENTS AND METHODS: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. RESULTS: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. CONCLUSION: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Breast-feeding and risk of epithelial ovarian cancer.

PURPOSE: Evidence suggests that breast-feeding may decrease the risk of epithelial ovarian cancer but it is not clear whether there is a relationship with duration of breast-feeding, patterns of breast-feeding, or particular histological subtypes of ovarian cancer. We sought to investigate these issues in detail. METHODS: Data from participants in a population-based study of ovarian cancer in western Washington State, USA (2002-2007) who had had at least one birth (881 cases and 1,345 controls) were used to assess relations between patterns of breast-feeding and ovarian cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Women who ever breast-fed had a 22 % reduction in risk of ovarian cancer compared with those who never breast-fed (OR = 0.78, 95% CI 0.64-0.96) and risk reduction appeared greater with longer durations of feeding per child breast-fed (OR = 0.56, 95% CI 0.32-0.98 for 18 months average duration breast-feeding versus none). Introduction of supplementary feeds did not substantially alter these effects. The overall risk reduction appeared greatest for the endometrioid and clear cell subtypes (OR per month of average breast-feeding per child breast-fed = 0.944, 95% CI 0.903-0.987). CONCLUSIONS: Among women who have had the opportunity to breast-feed, ever breast-feeding and increasing durations of episodes of breast-feeding for each breast-fed child are associated with a decrease in the risk of ovarian cancer independent of numbers of births, which may be strongest for the endometrioid subtype.

Tagging single-nucleotide polymorphisms in candidate oncogenes and susceptibility to ovarian cancer.

Low-moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) known to be involved in OC development. Thirty-four tagging SNPs in these genes were genotyped in approximately 1800 invasive OC cases and 3000 controls from population-based studies in Denmark, the United Kingdom and the United States. We found no evidence of disease association for SNPs in BRAF, KRAS, ERBB2 and PIK3CA when OC was considered as a single disease phenotype; but after stratification by histological subtype, we found borderline evidence of association for SNPs in KRAS and BRAF with mucinous OC and in ERBB2 and PIK3CA with endometrioid OC. For NMI, we identified a SNP (rs11683487) that was associated with a decreased risk of OC (unadjusted P(dominant)=0.004). We then genotyped rs11683487 in another 1097 cases and 1792 controls from an additional three case-control studies from the United States. The combined odds ratio was 0.89 (95% confidence interval (CI): 0.80-0.99) and remained statistically significant (P(dominant)=0.032). We also identified two haplotypes in ERBB2 associated with an increased OC risk (P(global)=0.034) and a haplotype in BRAF that had a protective effect (P(global)=0.005). In conclusion, these data provide borderline evidence of association for common allelic variation in the NMI with risk of epithelial OC.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Hybrid tree frogs: vocalizations of males and selective phonotaxis of females.

Male hybrids of reciprocal crosses between gray and pinewoods tree frogs (Hyla chtysoscelis x H. femoralis) that were raised to sexual maturity in the laboratory produced distinctive vocalizations. Hybrid females preferred the calls of hybrids to calls of gray tree frogs and also chose synthetic calls with a pulse repetition rate typical of the hybrids in preference to calls with a rate typical of pinewoods tree frogs.

Final report and recommendations from the National Notifiable Diseases Working Group.

UNLABELLED: The National Notifiable Diseases Working Group performed a ranking of 48 communicable diseases to assist with determining priorities for national surveillance. The WG offers six specific recommendations relating to the addition or deletion of communicable diseases from the list of nationally notifiable diseases. KEY RECOMMENDATIONS: 1. Clostridium difficile-associated diarrhea, paralytic shellfish poisoning, and invasive listeriosis are recommended for addition to the Nationally Notifiable Disease List. 2. New proposals for diseases not recommended for national notification include hepatitis E, HTLV-1, and HTLV-2. 3. Dengue virus infection should be deleted from the Nationally Notifiable Disease List. (Dengue hemorrhagic fever should continue to be reported.) 4. Classic Creutzfeld-Jacob disease ranked well below the threshold for inclusion; however, it should be retained on the list because surveillance of classic CJD is key to effective surveillance of new variant disease and because consulted provinces and territories strongly favoured its retention. 5. Several diseases that ranked near the borderline for reporting should be retained on the list as follows: a. a. brucellosis, because although it does not rank highly on the basis of its endemic pattern it is a category B biological warfare agent; b. laboratory-confirmed influenza because it forms part of a functional and working surveillance approach; c group B streptococcal infection because alternative hospital-based surveillance systems do not yet capture a significant proportion fo cases. 6. Transfusion-transmitted infections were unrankable by the current system. 7. The approach to reporting dengue hemorrhagic fever, plague, West Nile virus infections, and other viral hemorrhagic fevers should be made congruent with the approach for other notifiable diseases (see Discussion). 8. The feasibility and utility of national reporting for communicable diseases that have very high incidence and low severity (e.g. chickenpox, norovirus) should be carefully considered, especially when it leads to little or no case-by-case data reported by health authorities. The WG recommends that these diseases be placed under surveillance but that case-by-case reporting not be required at the national level. Alternative approaches to tracking trends could include enumerating outbreaks in the case of norovirus or the use of sentinel surveillance, laboratory surveillance, or physician billing events in the case of varicella.

Canadian street youth: correlates of sexual risk-taking activity.

The purpose of this study was to develop a national perspective on the sexual activity of street youth in Canada and to determine the correlates of risky sexual behavior according to street youth's link to the street. Five categories of street youth (sex industry workers, heavy drug and/or alcohol users, young offenders, homeless and unemployed) ages 15 to 20 years were recruited in 1988 from 10 Canadian urban centers to participate in a 45-minute structured interview focusing on knowledge and attitudes regarding sexually transmitted diseases (STD)/human immunodeficiency virus, current sexual practices, sexual and STD history, demographic background, alcohol/drug use and relationship with parents and peers. Data from the survey were also compared with findings from more than 15,000 non-street youth adolescents surveyed in the same year with the use of parallel questionnaires. Of 712 street youth surveyed (391 males, mean age 17.3 years; 321 females, mean age 16.8 years), the majority were sexually active (95% males, 93% females) and 22% reported at least one previous STD (16% males, 30% females). The lowest STD rates were in unemployed males (5%) and the highest (68%) in female sex industry workers. STD/human immunodeficiency virus high risk behaviors were frequent with 47% of males and 41% of females having had at least 10 different partners, 73% of males and 75% of females inconsistently using condoms and 22% of males and 24% of females participating in anal intercourse. Even among sex industry workers more than 40% used condoms inconsistently.(ABSTRACT TRUNCATED AT 250 WORDS)

Cohorting of infants with respiratory syncytial virus.

During two winter periods (1994-1995 and 1995-1996), nasopharyngeal aspirates were obtained from infants and young children with an acute respiratory illness, after initial assessment in an area with six cubicles which serves as an admissions unit. Aspirates were sent for rapid diagnostic testing. Respiratory syncytial virus (RSV) positive patients were cohorted into two six-bedded bays on the paediatric wards. Over the two successive winter periods studied, 347 RSV positive patients were assigned to the cohort. No nosocomial infections were identified during the first winter; in the second, two were identified. Cohorting at admission eased clinical management, with one area used for high-dependency care and cubicles being freed for children with other infectious diseases. Nosocomial infection was minimized.

Hospital response protocols for child sexual abuse and sexually transmitted diseases in children.

Hospitals are significant portals of entry to the health care system for children who have been sexually abused. Hospital staff have the opportunity to investigate, intervene in and prevent the cycle of abuse. Accordingly, several Canadian hospitals have standardized responses to meet the needs of the sexually abused child; however, the prevalence of protocols and the degree of standardization across the country have not been documented. A survey of hospitals in Canada indicated that 46% of hospitals that treated children had a response protocol for child sexual abuse and only 17% had a response protocol for sexually transmitted diseases in children. Protocols were more likely to be in place in hospitals that were accredited, specialized in paediatrics, were designated as teaching facilities for medicine, nursing and social work, and had more than 200 beds. In hospitals without protocols, staff were often not convinced of their need or desirability.

Urine testing for Chlamydia trachomatis and hassle-free follow-up is acceptable to street youth.

OBJECTIVE: To evaluate whether street youth would use a sexually transmitted disease (STD) screening program involving non-nominal, noninvasive testing of urine for Chlamydia trachomatis with hassle-free follow-up and partner self-notification. DESIGN: Cross-sectional pilot study in six centres frequented by street youth 13 to 25 years of age in the Regional Municipality of Ottawa-Carleton. INTERVENTIONS: A structured, non-nominal face-to-face interview using an 88-item questionnaire was administered by a trained research assistant. Immediate feedback was provided to participants about specific individual risk reduction strategies for high risk life styles. Each street youth provided a urine sample that was tested non-nominally for C trachomatis by polymerase chain reaction (PCR). A single dose of azithromycin therapy was provided to participants who tested positive, each of whom was requested to encourage recent sexual partners to come forward for testing and treatment. RESULTS: One hundred and sixty-three street youth were recruited (98 males and 65 females [male to female ratio 1.5:1]) over the four months of the study. The mean ages of participants were males 18.3+/-2.50 years and females 16.7+/-2.02 years. Ninety-two per cent (146) of all participants were sexually active and 99% of the sexually active youth (145 of 146) submitted urine samples. Urine samples were positive in 12 (8.2%) participants (seven males, five females), all of whom were asymptomatic. All those who tested positive were recruited from a single site (site specific rate 13.6%). Overall, only 25% of those tested returned spontaneously for test results; however, nine of 12 participants with positive results were treated due to investigator vigilance in locating the youth. Street youth partner self-notification resulted in five additional street youth requesting testing and treatment. CONCLUSIONS: Street youth participated in a STD testing program when a street friendly program and noninvasive methods were used. Although more expensive, urine PCR testing increased program acceptance by street youth compared with previous local results. Detection of C trachomatis was high in this hard-to-reach population. There is a need to address further the problem of poor return rates for results and treatment, as well as low rates of partner notification.

The use of Apple Macintosh computers and Hypercard in teaching physiology laboratories.

A network of Apple Macintosh computers has been integrated into existing undergraduate physiology laboratories. Hypercard software programs replace the traditional laboratory handout; the text contains a number of buttons linked to cards that provide additional information on a particular subject. This additional information includes theory, the use of various instruments, expected results, and details on how to perform data analysis. This system of information layering allows students to work independently, at their own pace, and allows them to learn as much or as little as they consider necessary. Each computer is interfaced with a MacLab/4 data-acquisition unit, which permits the computer screen to display a four-channel chart recorder or a two-channel oscilloscope.

The Canadian Paediatric Surveillance Program: Beyond collecting numbers.

Traditionally, anecdotal data and retrospective case reports have been used for insight into the natural history, epidemiology and case management of rare diseases. This lack of information has often resulted in delayed recognition and diagnosis of rare diseases, increasing the risk of complications or death of children. Furthermore, the study of rare condiions has been hampered by the need to generate sufficient numbers to enable meaningful analysis and interpretation, a need that requires data collection from a large population. The Canadian Paediatric Surveillance Program (CPSP) was established in 1996 to contribute to the improvement of the health of children and youth by national surveillance and research into uncommon paediatric diseases and conditions. The CPSP provides the mechanism to enable the prospective collection of national epidemiological data on such diseases and conditions. After five years, has the CPSP risen to meet expectations? Is it based on scientific evidence? The CPSP has revealed itself to be a very sensitive surveillance tool, providing invaluable longitudinal, epidemiological information for public health decision-makers. The present paper reviews how the different communicable diseases on the CPSP monthly reporting form stand the test of the 1998 priority criteria for diseases under national surveillance set by Canada's Advisory Committee on Epidemiology.

High-risk STD/HIV behavior among college students.

The current sexually transmitted disease (STD) epidemic in adolescents has led to concern about the potential for spread of the human immunodeficiency virus (HIV). In 1988, a total of 5514 students in first-year community college and university classrooms across Canada were surveyed to assess STD/HIV-related knowledge, attitudes, and risk behavior. The students' mean age was 19.7 years; the male-to-female ratio was 1:1.4. Students knew more about HIV/acquired immunodeficiency syndrome than other STDs. Of the 74.3% of the men and 68.9% of the women who were coitally active, 14.3% of the men and 18.6% of the women had participated in anal intercourse and 5.5% reported a previous STD. Only 24.8% of the men and 15.6% of the women always used a condom during sexual intercourse. Among the 21.3% of the men and 8.6% of the women with 10 or more partners, regular condom use was reported in only 21% and 7.5%, respectively. In this subgroup, anal intercourse was practiced by 26.9% of the men and 34.8% of the women, and previous STD was reported by 10.6% and 24.2%, respectively. Factors associated with not using a condom included number of sexual partners, embarrassment about condom purchase, difficulty discussing condom use with a partner, use of oral contraceptives, insufficient knowledge of HIV/STDs, and the belief that condoms interfere with sexual pleasure. These factors are potentially amenable to change. Effective, behaviorally focused educational programs are needed to improve condom use and reduce STD/HIV risk.