Adjuvant endocrine therapy after breast cancer: a qualitative study of factors associated with adherence.

INTRODUCTION: Despite evidence of the efficacy of adjuvant endocrine therapy (AET) in reducing the risk of recurrence and mortality after treatment for primary breast cancer, adherence to AET is suboptimal. This study aimed to explore factors that influence adherence and nonadherence to AET following breast cancer to inform the development of supportive interventions. METHODS: Interviews were conducted with 32 women who had been prescribed AET, 2-4 years following their diagnosis of breast cancer. Both adherers (n=19) and nonadherers (n=13) were recruited. The analysis was conducted using the Framework approach. RESULTS: Factors associated with adherence were as follows: managing side effects including information and advice on side effects and taking control of side effects, supportive relationships, and personal influences. Factors associated with nonadherence were as follows: burden of side effects, feeling unsupported, concerns about long-term AET use, regaining normality, including valuing the quality of life over length of life, and risk perception. CONCLUSION: Provision of timely information to prepare women for the potential side effects of AET and education on medication management strategies are needed, including provision of timely and accurate information on the efficacy of AET in reducing breast cancer recurrence and on potential side effects and ways to manage these should they arise. Trust in the doctor-patient relationship and clear patient pathways for bothersome side effects and concerns with AET are important. Training and education on AET for GPs should be considered alongside novel care pathways such as primary care nurse cancer care review and community pharmacist follow-up

Visualising Conversation Structure across Time: Insights into Effective Doctor-Patient Consultations

Effective communication between healthcare professionals and patients is critical to patients’ health outcomes. The doctor/patient dialogue has been extensively researched from different perspectives, with findings emphasising a range of behaviours that lead to effective communication. Much research involves self-reports, however, so that behavioural engagement cannot be disentangled from patients’ ratings of effectiveness. In this study we used a highly efficient and time economic automated computer visualisation measurement technique called Discursis to analyse conversational behaviour in consultations. Discursis automatically builds an internal language model from a transcript, mines the transcript for its conceptual content, and generates an interactive visual account of the discourse. The resultant visual account of the whole consultation can be analysed for patterns of engagement between interactants. The findings from this study show that Discursis is effective at highlighting a range of consultation techniques, including communication accommodation, engagement and repetition

Adjuvant endocrine therapy after breast cancer: A qualitative study of factors associated with adherence

Introduction : Despite evidence of the efficacy of Adjuvant Endocrine Therapy (AET) in reducing the risk of recurrence and mortality after treatment for primary breast cancer, adherence to AET is suboptimal. This study aimed to explore factors that influence adherence and non-adherence to adjuvant endocrine therapy (AET) following breast cancer to inform the development of supportive interventions. Methods: Interviews were conducted with 32 women who had been prescribed AET, 2-4 years following their diagnosis of breast cancer,. Both adherers (n=19) and non-adherers (n=13) were recruited. The analysis was conducted using the Framework approach. Results: Factors associated with adherence were: Managing side effects including information and advice on side effects, and taking control of side effects, Supportive relationships, and Personal influences. Factors associated with non-adherence were: Burden of side effects, Feeling unsupported, Concerns about long term AET use, Re-gaining normality, including valuing quality of life over length of life, and Risk perception Conclusions: Provision of timely information to prepare women for the potential side effects of AET and education on medication management strategies are needed, including provision of timely and accurate information on the efficacy of AET in reducing breast cancer recurrence, and on potential side effects and ways to manage these should they arise. . Trust in the doctor-patient relationship and clear patient pathways for bothersome side effects and concerns with AET are important. Training and education around AET for GPs should be considered alongside novel care pathways such as primary care nurse cancer care review, and community pharmacist follow-up

Attitudes of the autism community to early autism research

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as: use of ‘at-risk’ language; communicating study findings to parents; and the future perspective of enrolled infants when they reach adulthood. The current study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism, and practitioners in health and education settings across eleven European countries. Survey respondents (n=2317) were positively disposed towards early autism research and there was significant overlap in their priorities for the field, and preferred language to describe infant research participants. However there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase ‘at-risk’ to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Concordant association of insulin degrading enzyme gene (IDE) variants with IDE mRNA, abeta, and alzheimer's disease.

Background: The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD). Methodology/Principal findings: We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8), fold-increase = 2.12,); the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003). Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2)-C (p = 0.006) and HepG2 (p = 0.02) cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879), we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011) and total measured plasma Abeta levels (b = -0.130, p = 0.009). Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03), and the eleven IDE haplotypes (global p = 0.02) also showed significant association. Conclusions: Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Ass40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs) strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Pharmacy students’ self-reported attitudes, beliefs and behaviours about communicating with patients, measured over time

Background: Pharmacy students receive training to effectively communicate with patients about their medications.Objectives: A theory-based approach (Communication Accommodation Theory [CAT]) was used to investigate the impact of communication skills' tutorials on Pharmacy students' self-reported attitudes, beliefs and behaviours in patient communication.Methods: Final year Pharmacy students completed an online, 30-item, patient-centred communication survey at three points in time, before and after attending three CAT-based tutorials (Survey #1 and Survey #2). Survey #3 was distributed six to twelve months into students' intern training year (post-graduation). Differences between participants' responses over time were measured and analysed.Results: Response rates were 78% for Survey #1, 84% for Survey #2, and 28% for Survey #3. Further analysis indicated that Survey #3 respondents were not statistically different from the larger sample size. Key areas changed from baseline (Survey #1) to post tutorials (Survey #2) and were sustained well into Pharmacy students' intern year (Survey #3).Conclusions: This novel research indicated growing awareness and retention of key communication behaviours over time