22 February 2019 In Cancer

PURPOSE: Breast cancer (BC) risk prediction allows systematic identification of individuals at highest and lowest risk. We extend the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk model to incorporate the effects of polygenic risk scores (PRS) and other risk factors (RFs).

METHODS: BOADICEA incorporates the effects of truncating variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM; a PRS based on 313 single-nucleotide polymorphisms (SNPs) explaining 20% of BC polygenic variance; a residual polygenic component accounting for other genetic/familial effects; known lifestyle/hormonal/reproductive RFs; and mammographic density, while allowing for missing information.

RESULTS: Among all factors considered, the predicted UK BC risk distribution is widest for the PRS, followed by mammographic density. The highest BC risk stratification is achieved when all genetic and lifestyle/hormonal/reproductive/anthropomorphic factors are considered jointly. With all factors, the predicted lifetime risks for women in the UK population vary from 2.8% for the 1st percentile to 30.6% for the 99th percentile, with 14.7% of women predicted to have a lifetime risk of >/=17-<30% (moderate risk according to National Institute for Health and Care Excellence [NICE] guidelines) and 1.1% a lifetime risk of >/=30% (high risk).

CONCLUSION: This comprehensive model should enable high levels of BC risk stratification in the general population and women with family history, and facilitate individualized, informed decision-making on prevention therapies and screening.

25 January 2019 In General Health

This study investigated the potential effect of therapeutic doses of acetaminophen (APAP) in combination with light-moderate amounts of alcohol on kidney functions controlling for factors such as hypertension, diabetes and obesity that may predispose the kidney to APAP and/or alcohol toxicity. Secondary analysis of the 2003-2004 National Health and Nutrition Examination Survey data was performed using SAS 9.4. Odds ratios (OR) and 95% confidence intervals (CI) comparing the likelihood that individuals who ingested therapeutic doses of APAP and light-moderate amount of alcohol, compared to those who did not, would have kidney dysfunction were generated from multiple logistics regression models by further controlling for potential predisposing factors namely hypertension, diabetes and obesity. Kidney dysfunction was defined based on self-reports and laboratory examination of serum creatinine (SCr), blood urea nitrogen (BUN), glomerular filtration rate (GFR) and albumin creatinine ratio (ABCR). Statistically significant increased odds of renal dysfunction were noted among respondents who reported use of therapeutic doses of APAP and light-moderate amount of alcohol [OR(95% CI)=1.64(1.28-2.10) self-report, 2.18(1.81-2.63) SCr, 4.60(3.03-7.00) BUN, 3.14(2.42-4.07) GFR, and 1.71(1.36-2.14) ALBCR)] even after adjusting for hypertension, diabetes and obesity [Adjusted OR (95% CI)=1.78 (1.22-2.58) self-report, 2.05 (1.07-3.92) GFR]. The toxic effects of APAP and alcohol on the kidney were hypothesized. The threshold doses at which these effects begin to occur are unknown. The findings of this study suggest that even therapeutic doses of APAP and light-moderate amount of alcohol could be health problematic if consumed concomitantly.

25 January 2019 In Pregnant Women

OBJECTIVES: Fetal alcohol spectrum disorders (FASD) is a worldwide problem. Maternal alcohol consumption is an important risk factor for FASD. It remains unknown which alcohol consumption patterns most strongly predict FASD. The objective of this study was to identify these.

DESIGN: Systematic literature review.

METHODS: We searched in PubMed, PsychINFO, PsycARTICLES, ERIC, CINAHL, Embase and MEDLINE up to August 2018. The query consisted of keywords and their synonyms related to FASD, pregnancy and behaviour. Studies were excluded when not published in English, were reviews or involved non-human subjects. Substantial heterogeneity precluded aggregation or meta-analysis of the data. Instead, data were qualitatively inspected.

RESULTS: In total, 21 studies were eligible for further data analysis. All studies that measured both maternal alcohol drinking behaviours and FASD reported retrospective data on maternal drinking patterns, employing both continuous and categorical measures and exhibiting substantial heterogeneity in measures of alcohol consumption (eg, timing of exposure, quantification of alcohol measure and definition of a standard drink). Study quality improved over time and appeared higher for studies based on active case ascertainment, especially when conducted in schools and when behaviour was assessed through interviews.

CONCLUSIONS: We aimed to identify specific maternal drinking behaviour(s) related to FASD. The state of the literature precludes such conclusions. Evidence-based preventive measures necessitate identifying which prenatal alcohol drinking behaviour(s) are most in need of intervention. Therefore, we formulate three recommendations for future research. First, future studies can optimise the value of the collected dataset through specifying measurements and reporting of maternal drinking behaviours and avoiding categorised measures (nominal or ordinal) whenever possible. Second, samples should not be selected based on FASD status, but instead, FASD status as well as maternal alcohol consumption should both be measured in a general population sample. Finally, we provide 10 reporting guidelines for FASD research.

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