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Vasomotor symptoms (hot flushes and night sweats) and other symptoms, including depression, anxiety and panic attacks, are commonly experienced by menopausal women and have been associated with an unfavourable cardiovascular risk profile.To investigate whether presence of menopausal symptoms is associated with the development of cardiovascular disease (CVD).Five electronic databases (Medline, EMBASE and Web of Science) were search until February 17th, 2015 to identify relevant studies. Observational cohort studies or randomised intervention studies were eligible for inclusion if they followed participants prospectively (at least 1 year of follow-up), and reported relevant estimates on the association of any vasomotor symptoms, or other menopausal symptoms, with risk of CVD, coronary heart disease (CHD), or stroke in perimenopausal, menopausal, or postmenopausal women. Data were extracted by two independent reviewers using a pre-designed data collection form. Separate pooled relative risks (RRs) for age and non-established cardiovascular risk factors (e.g., education, ethnicity) adjusted data and for established cardiovascular risk factors and potential mediators-adjusted data (e.g., smoking, body mass index, and hypertension) were calculated.Out of 9,987 initially identified references, ten studies were selected, including 213,976 women with a total of 10,037 cardiovascular disease outcomes. The age and non-established cardiovascular risk factors adjusted RRs) [95% confidence intervals] for development of CHD, Stroke and CVD comparing women with and without any menopausal symptoms were 1.34 [1.13-1.58], 1.30 [0.99-1.70], 1.48 [1.21-1.80] respectively, and the corresponding RRs adjusted for cardiovascular risk factors and potential mediators were 1.18 [1.03-1.35], 1.08 [0.89-1.32], 1.29 [0.98-1.71]. However, these analyses were limited by potential unmeasured confounding and the small number of studies on this topic.Presence of vasomotor symptoms and other menopausal symptoms are generally associated with an increased risk of cardiovascular disease, which is mainly explained by cardiovascular risk factors.

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.

BackgroundPremature birth is the leading cause of neonatal death and second leading in children under 5. Information on outcomes of preterm babies surviving the early neonatal period is sparse although it is considered a major determinant of immediate and long-term morbidity.MethodsSystematic review of studies reporting outcomes for preterm babies in low and middle income settings was conducted using electronic databases, citation tracking, expert recommendations and "grey literature". Reviewers screened titles, abstracts and articles. Data was extracted using inclusion and exclusion criteria, study site and facilities, assessment methods and outcomes of mortality, morbidity, growth and development. The Child Health Epidemiology Reference Group criteria (CHERG) were used to assess quality.FindingsOf 197 eligible publications, few (10.7%) were high quality (CHERG). The majority (83.3%) report on the outcome of a sample of preterm babies at time of birth or admission. Only 16.0% studies report population-based data using standardised mortality definitions. In 50.5% of studies, gestational age assessment method was unclear. Only 15.8% followed-up infants for 2 years or more. Growth was reported using standardised definitions but recommended morbidity definitions were rarely used. The criteria for assessment of neurodevelopmental outcomes was variable with few standardised tools - Bayley II was used in approximately 33% of studies, few studies undertook sensory assessments.ConclusionsTo determine the relative contribution of preterm birth to the burden of disease in children and to inform the planning of healthcare interventions to address this burden, a renewed understanding of the assessment and documentation of outcomes for babies born preterm is needed. More studies assessing outcomes for preterm babies who survive the immediate newborn period are needed. More consistent use of data is vital with clear and aligned definitions of health outcomes in newborn (preterm or term) and intervention packages aimed to save lives and improve health.