Breast cancer worry in higher-risk women offered preventive therapy: a UK multicentre prospective study

PURPOSE: Women's worry about developing breast cancer may influence their decision to use preventive therapy. However, the direction of this relationship has been questioned. We prospectively investigated the relationship between breast cancer worry and uptake of preventive therapy. The socio-demographic and clinical factors associated with high breast cancer worry were also investigated. METHODS: Women at increased risk of developing breast cancer were recruited from clinics across England (n = 408). Participants completed a survey on their breast cancer worry, socio-demographic and clinical factors. Uptake of tamoxifen was recorded at 3 months (n = 258 women, 63.2%). Both primary and sensitivity analyses were conducted using different classifications of low, medium and high worry. RESULTS: 39.5% of respondents reported medium breast cancer worry at baseline and 21.2% reported high worry. Ethnic minority women were more likely to report high worry than white women (OR = 3.02, 95%CI 1.02, 8.91, p = 0.046). Women educated below degree level were more likely to report high worry than those with higher education (OR = 2.29, 95%CI 1.28, 4.09, p = 0.005). No statistically significant association was observed between worry and uptake. In the primary analysis, fewer respondents with medium worry at baseline initiated tamoxifen (low worry = 15.5%, medium = 13.5%, high = 15.7%). In the sensitivity analysis, participants with medium worry reported the highest uptake of tamoxifen (19.7%). CONCLUSIONS: No association was observed between worry and uptake, although the relationship was affected by the categorisation of worry. Standardised reporting of the classification of worry is warranted to allow transparent comparisons across cohorts

Examining Factors in the Research Institute on Addictions Self-Inventory (RIASI): Associations with Alcohol Use and Problems at Assessment and Follow-Up

Impaired driving is a leading cause of alcohol-related deaths and injuries. Rehabilitation or remedial programs, involving assessment and screening of convicted impaired drivers to determine problem severity and appropriate programs, are an important component of society’s response to this problem. Ontario’s remedial program, Back on Track (BOT), involves an assessment process that includes administration of the Research Institute on Addictions Self-Inventory (RIASI) to determine assignment to an education or treatment program. The purpose of this study is to identify factors within the RIASI and examine how factor scores are associated with alcohol use and problem indicators at assessment and six-month follow-up. The sample included 22,298 individuals who completed BOT from 2000 to 2005. Principal component factor analysis with varimax rotation was conducted on RIASI data and an eight factor solution was retained: (1) Negative Affect, (2) Sensation Seeking, (3) Alcohol-Quantity, (4) Social Conformity, (5) High Risk Lifestyle, (6) Alcohol Problems, (7) Interpersonal Competence, and (8) Family History. Regression analyses were conducted to examine associations between factors and alcohol and problem measures obtained at assessment and at follow-up. Most factors, except for Interpersonal Competence, were associated with more alcohol use and problems at assessment. A similar pattern was observed at 6-month follow-up, but interestingly some factors (Negative Affect, Sensation Seeking, Alcohol-Quantity and Family History) predicted fewer days of alcohol use. The Interpersonal Competence factor was associated with significantly lower levels of alcohol use and problems at both assessment and follow-up. This work suggests that the RIASI provides information on several domains that have important relationships with alcohol problem severity and outcomes

Developing theory-based SMS messages to support retention in clinical trials : a mixed methods approach

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This report is independent research supported by the National Institute for Health Research NIHR Advanced Fellowship, Dr Samuel Smith NIHR300588. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. The funders had no role in the design of the study, data collection, analysis, interpretation of data and in the writing of this manuscript. Dr Smith also acknowledges the support of a Yorkshire Cancer Research Fellowship. Prof French is supported by the NIHR Manchester Biomedical Research Centre (IS-BRC1215-20007).Peer reviewedPublisher PD

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

Short survey on aspirin use for cancer prevention among the UK general public

Australian guidance recommends aspirin for colorectal cancer prevention among people aged 50-70 at population risk. The medication could be offered more widely in the future in the UK and other countries. We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We recruited 400 UK respondents aged 50-70 through a market research company to an online survey

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection

Background: chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.Methods: we conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (p<5×10−8) were investigated in additional independent studies, were fine-mapped and putative causal genes identified by gene expression analysis. GWASs of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease among the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWASs).Results: from a GWAS of 9714 cases and 48 471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the human leukocyte antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2203 cases and 17 627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations including blood cell traits, liver biomarkers, infections, gastrointestinal and thyroid-associated diseases, and respiratory disease.Conclusions: novel signals at the FUT2 and mucin loci suggest that mucin fucosylation may be a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention

Maintaining independence in individuals with dementia at home after a fall:a protocol for the UK pilot cluster randomised controlled trial MAINTAIN

Introduction: Individuals with dementia face an increased risk of falls. Falls can cause a decline in the individual’s overall functionality. All types of falls, including those that do not result in injury, can lead to psychosocial consequences, such as diminished confidence and a fear of falling. Projections indicate a rising trend in dementia diagnoses, implying an increase in fall incidents. Yet, there is a lack of evidence to support interventions for people living with dementia who have fallen. Our objective is to test the feasibility of a falls intervention trial for people with dementia. Method and analysis: This is a UK-based two-arm pilot cluster randomised controlled trial. In this study, six collaborating sites, which form the clusters, will be randomly allocated to either the intervention arm or the control arm (receiving treatment as usual) at a 1:1 ratio. During the 6 month recruitment phase, each cluster will enrol 10 dyads, comprising 10 individuals with dementia and their respective carers, leading to a total sample size of 60 dyads. The primary outcomes are the feasibility parameters for a full trial (ie, percentage consented, follow-up rate and cost framework). Secondary outcomes include activities of daily living, quality of life, fall efficacy, mobility, goal attainment, cognitive status, occurrence of falls, carer burden and healthcare service utilisation. Outcome measures will be collected at baseline and 28 weeks, with an additional assessment scheduled at 12 weeks for the healthcare service utilisation questionnaire. An embedded process evaluation, consisting of interviews and observations with participants and healthcare professionals, will explore how the intervention operates and the fidelity of study processes. Ethics and dissemination: The study was approved by the NHS and local authority research governance and research ethics committees (NHS REC reference: 23/WA/0126). The results will be shared at meetings and conferences and will be published in peer-reviewed journals. Trial registration number: ISRCTN16413728

A Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints: the COSGROVE study.

BACKGROUND: Fetal growth restriction refers to a fetus that does not reach its genetically predetermined growth potential. It is well-recognized that growth-restricted fetuses are at increased risk of both short- and long-term adverse outcomes. Systematic evaluation of the evidence from clinical trials of fetal growth restriction is often difficult because of variation in the outcomes that are measured and reported. The development of core outcome sets for fetal growth restriction studies would enable future trials to measure similar meaningful outcomes. OBJECTIVE: The purpose of this study was to develop core outcome sets for trials of prevention or treatment of fetal growth restriction. STUDY DESIGN: This was a Delphi consensus study. A comprehensive literature review was conducted to identify outcomes that were reported in studies of prevention or treatment of fetal growth restriction. All outcomes were presented for prioritization to key stakeholders (135 healthcare providers, 68 researchers/academics, and 35 members of the public) in 3 rounds of online Delphi surveys. A priori consensus criteria were used to reach agreement on the final outcomes for inclusion in the core outcome set at a face-to-face meeting with 5 healthcare providers, 5 researchers/academics, and 6 maternity service users. RESULTS: In total, 22 outcomes were included in the final core outcome set. These outcomes were grouped under 4 domains: maternal (n=4), fetal (n=1), neonatal (n=12), and childhood (n=5). CONCLUSION: The Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints study identified a large number of potentially relevant outcomes and then reached consensus on those factors that, as a minimum, should be measured and reported in all future trials of prevention or treatment of fetal growth restriction. This will enable future trials to measure similar meaningful outcomes and to ensure that findings from different studies can be compared and combined

Strategies to self-manage side-effects of adjuvant endocrine therapy among breast cancer survivors : an umbrella review of empirical evidence and clinical guidelines

Purpose: Side-effects of adjuvant endocrine therapy (AET) are common in breast cancer survivors, and can affect adherence to treatment. We synthesised the evidence for strategies to self-manage these side-effects. Methods: We searched for systematic reviews and clinical guidelines on self-management strategies for AET side-effects (arthralgia, fatigue, hot flashes, gastrointestinal discomfort, nausea, vulvovaginal symptoms, and sleep disturbance). We searched oncology organisation’s websites and eight databases (Inception-November 2020). Screening, data extraction and quality assessment were completed independently in duplicate. PROSPERO: 2019CRD4201914001. Results: We identified 33 systematic reviews and 18 clinical guidelines. 21% of reviews were high quality, and the average quality score for guidelines was 44%. Evidence for most strategies was absent or weak. There was consensus from a low-quality review and multiple guidelines to recommend moisturisers, gels and lubricants for vulvovaginal symptoms. Evidence was weak for physical activity for self-managing most symptoms, although two high-quality reviews indicated yoga and aerobic exercise could reduce fatigue. Primary research was often biased by weak and underpowered study designs. Eleven reviews did not report information on adverse events. Conclusions: Most self-management strategies for breast cancer survivors experiencing side-effects from AET lack evidence. Primary research is needed using high-quality well-powered designs focusing on implementable strategies. Implications for Cancer Survivors: Patients and clinicians should be aware that although the risk of harm is low for these self-management strategies, the likelihood of benefit is often unclear. Women should consider moisturisers, gels or lubricants for self-managing vulvovaginal symptoms, and yoga or aerobic exercise for alleviating fatigue