Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Conflicting contexts : midwives' interpretation of childbirth through photo elicitation

Introduction: This study seeks to explore midwives' perceptions about childbirth and in particular their beliefs about normality and risk. In the current climate of increasing interventions during labour, it is important to understand the thought processes that impact on midwifery care in order to examine whether these beliefs influence midwifery clinical decision-making. Method: 12 Midwives who worked in a variety of metropolitan hospitals in Sydney, Australia were interviewed about how they care for women during labour. The study utilised an inductive qualitative design using photo elicitation during the interview process. Results: Six themes emerged from the data that clearly indicated midwives felt challenged by working in a system dominated by an obstetric model of care that undermined midwifery autonomy in maintaining normal birth. These themes were: desiring normal, scanning the environment, constructing the context, navigating the way, relinquishing desire and reflecting on reality. Most midwives felt they were unable to practice in the manner they were philosophically aligned to, that is, promoting normal birth, as the medical model restricted their practice. Discussion: The polarised views of childbirth held by midwives and obstetricians do little to enhance normal birth outcomes. Midwives in this study expressed frustration that they were unable to practice midwifery in a way that reflected their belief in normal birth. This, they cite is a result of the oppressive obstetric model prevalent in maternity care facilities in Sydney and the over use of technological interventions during childbirth

Improving health and lives: The Learning Disabilities Public Health Observatory

Purpose – The purpose of this paper is to describe the first 15 months of operation of an innovative specialist national public health observatory for intellectual disability. Design/methodology/approach – The paper provides a narrative account of aims and achievements of the service. Findings – In the first 15 months of operation the observatory has: made available to those involved in commissioning health and social care services, a wealth of information on the health needs of people with intellectual disabilities; identified specific improvements that could viably be made to increase the quality of future information; and begun working with local agencies to support them in making the best use of the available information. Originality/value – People with intellectual disabilities experience significant health inequalities. This paper describes an innovative approach to helping local agencies make the best use of available information in order to commission services that may reduce these inequalities

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.<p></p> Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.<p></p> Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.<p></p> Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.<p></p> Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies

Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Australian Pancreatic Cancer Genome Initiative members: Nam Q. Nguyen, Andrew R. Ruszkiewicz and Chris Worthley of the Royal Adelaide Hospital.Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.International Cancer Genome Consortiu