Self-reported medication side effects in an older cohort living independently in the community - the Melbourne Longitudinal Study on Health Ageing (MELSHA) : cross-sectional analysis of prevalence and risk factors

Background Medication side effects are an important cause of morbidity, mortality and costs in older people. The aim of our study was to examine prevalence and risk factors for self-reported medication side effects in an older cohort living independently in the community.Methods The Melbourne Longitudinal Study on Healthy Ageing (MELSHA), collected information on those aged 65 years or older living independently in the community and commenced in 1994. Data on medication side effects was collected from the baseline cohort (n = 1000) in face-to-face baseline interviews in 1994 and analysed as cross-sectional data. Risk factors examined were: socio-demographics, health status and medical conditions; medication use and health service factors. Analysis included univariate logistic regression to estimate unadjusted risk and multivariate logistic regression analysis to assess confounding and estimate adjusted risk.Results Self-reported medication side effects were reported by approximately 6.7% (67/1000) of the entire baseline MELSHA cohort, and by 8.5% (65/761) of those on medication. Identified risk factors were increased education level, co-morbidities and health service factors including recency of visiting the pharmacist, attending younger doctors, and their doctor\u27s awareness of their medications. The greatest increase in risk for medication side effects was associated with liver problems and their doctor\u27s awareness of their medications. Aging and gender were not risk factors.Conclusion Prevalence of self-reported medication side effects was comparable with that reported in adults attending General Practices in a primary care setting in Australia. The prevalence and identified risk factors provide further insight and opportunity to develop strategies to address the problem of medication side effects in older people living independently in the community setting. <br /

Explaining the willingness of public professionals to implement new policies: A policy alienation framework

Nowadays, many public policies focus on economic values, such as efficiency and client choice. Public professionals often show resistance to implementing such policies. We analyse this problem using an interdisciplinary approach. From public administration, we draw on the policy alienation concept, which consists of five dimensions: strategic powerlessness, tactical powerlessness, operational powerlessness, societal meaninglessness and client meaninglessness. These are considered as factors that influence the willingness of professionals to implement policies (change willingness - a concept drawn from the change management literature). We test this model in a survey among 478 Dutch healthcare professionals implementing a new reimbursement policy. The first finding was that perceived autonomy (operational powerlessness) significantly influenced change willingness, whereas strategic and tactical powerlessness were not found to be significant. Second, both the meaninglessness dimensions proved highly significant. We conclude that clarifying the value of a policy is important in getting professionals to willingly implement a policy, whereas their participation on the strategic or tactical levels seems less of a motivational factor. These insights help in understanding why public professionals embrace or resist the implementation of particular policies. Points for practitioners Policymakers develop public policies which, nowadays, tend to focus strongly on economic values, such as increasing efficiency or offering citizens the opportunity to choose among suppliers of public services. Public professionals, who have to implement these policies, are often reluctant to do so. This study shows that the causes of this resistance are unlikely to be found in the lack of influence these professionals have in the shaping of the policy at the national or organizational level. Rather, professionals might resist implementing policies because they do not see them as meaningful for society, or for their own clients. Therefore, policymakers should focus on this perceived meaninglessness and adopt ways to counter this, for example by intensively communicating the value associated with a policy

Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on similar to 4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.Peer reviewe

Functional Analysis of a Breast Cancer-Associated FGFR2 Single Nucleotide Polymorphism Using Zinc Finger Mediated Genome Editing

The authors thank Barts Charity for funding and Breast Cancer Campaign for funding the Barts Breast Tissue Bank

A two-stage association study identifies methyl-CpG-binding domain protein 2 gene polymorphisms as candidates for breast cancer susceptibility

Genome-wide association studies for breast cancer have identified over 40 single-nucleotide polymorphisms (SNPs), a subset of which remains statistically significant after genome-wide correction. Improved strategies for mining of genome-wide association data have been suggested to address heritable component of genetic risk in breast cancer. In this study, we attempted a two-stage association design using markers from a genome-wide study (stage 1, Affymetrix Human SNP 6.0 array, cases=302, controls=321). We restricted our analysis to DNA repair/modifications/metabolism pathway related gene polymorphisms for their obvious role in carcinogenesis in general and for their known protein–protein interactions vis-à-vis, potential epistatic effects. We selected 22 SNPs based on linkage disequilibrium patterns and high statistical significance. Genotyping assays in an independent replication study of 1178 cases and 1314 controls were attempted using Sequenom iPLEX Gold platform (stage 2). Six SNPs (rs8094493, rs4041245, rs7614, rs13250873, rs1556459 and rs2297381) showed consistent and statistically significant associations with breast cancer risk in both stages, with allelic odds ratios (and P-values) of 0.85 (0.0021), 0.86 (0.0026), 0.86 (0.0041), 1.17 (0.0043), 1.20 (0.0103) and 1.13 (0.0154), respectively, in combined analysis (N=3115). Of these, three polymorphisms were located in methyl-CpG-binding domain protein 2 gene regions and were in strong linkage disequilibrium. The remaining three SNPs were in proximity to RAD21 homolog (S. pombe), O-6-methylguanine-DNA methyltransferase and RNA polymerase II-associated protein 1. The identified markers may be relevant to breast cancer susceptibility in populations if these findings are confirmed in independent cohorts

Impact of endophyte inoculation on the morphological identity of cultivars of Lolium perenne (L) and Festuca arundinacea (Schreb.)

Publication history: Accepted - 9 April 2020; Published online - 5 May 2020Grass endophytes have been shown to confer enhanced environmental resilience to symbiont cultivars with reports of modified growth. If inoculating with an endophyte (E+) made an accession morphologically distinct from its registered endophyte free (E−) accession, there could be protection and ownership issues for testing authorities and breeders. This study investigated if, in official Plant Breeders Rights (PBR) field trials, the morphological characteristics of E+and E− accessions of perennial ryegrass and tall fescue cultivars were sufficiently modified to designate them as mutually distinct and also distinct from their definitive accessions (Def), held by the testing authorities. Testing perennial ryegrass on 17 characters at 2 sites generated 48,960 observations and for tall fescue on 9 characters at 1 site, 12,960 observations (each for 3 accessions of 4 cultivars × 60 plants × 2 growing cycles). Distinctness required a p < 0.01 difference in a single character from the combined over years analysis (COYD). A few significant differences were recorded between E− and E+accessions. Cultivar Carn E+ was smaller than Carn E− for Infloresence Length (p < 0.01) in both years but COYD analysis (p < 0.05) was insufficient to declare distinctiveness. Overall, the number of observed differences between E−/E+ accessions was less or similar to the number expected purely by chance. In contrast, comparisons between Def and E− or E+ accessions showed a number of significant differences that were substantially more numerous than expected by chance. These results showed no conclusive evidence of endophyte inclusion creating false PBR distinctions but unexpectedly, several E− and E+ accessions were distinguished from their official definitive stock.This study was jointly funded by the EU Community Plant Variety Office, Angers, France and Euroseeds, Brussels, Belgium

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition