The complex polyploid genome architecture of sugarcane.

Sugarcane, the world's most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype ('monoploid') representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.

An introduction to the sources, fate, occurrence and effects of endocrine disrupting chemicals released into the environment.

Many classes of compounds are known or suspected to disrupt the endocrine system of vertebrate and invertebrate organisms. This review of the sources and fate of selected endocrine disrupting chemicals (EDCs) in the environment includes classes of compounds that are "legacy" contaminants, as well as contaminants of emerging concern. EDCs included for discussion are organochlorine compounds, halogenated aromatic hydrocarbons, brominated flame retardants, per- and polyfluoroalkyl substances, alkylphenols, phthalates, bisphenol A and analogues, pharmaceuticals, drugs of abuse and steroid hormones, personal care products, and organotins. An exhaustive survey of the fate of these contaminants in all environmental media (e.g., air, water, soil, biota, foods and beverages) is beyond the scope of this review, so the priority is to highlight the fate of EDCs in environmental media for which there is a clear link between exposure and endocrine effects in humans or in biota from other taxa. Where appropriate, linkages are also made between the fate of EDCs and regulatory limits such as environmental quality guidelines for water and sediments and total daily intake values for humans.

Methods for the analysis of endocrine disrupting chemicals in selected environmental matrixes.

Endocrine disrupting chemicals (EDCs) are heterogenous in structure, chemical and physical properties, and their capacity to partition into various environmental matrixes. In many cases, these chemicals can disrupt the endocrine systems of vertebrate and invertebrate organisms when present at very low concentrations. Therefore, sensitive and varied analytical methods are required to detect these compounds in the environment. This review summarizes the analytical methods and instruments that are most used to monitor for EDCs in selected environmental matrixes. Only those matrixes for which there is a clear link between exposures and endocrine effects are included in this review. Also discussed are emerging methods for sample preparation and advanced analytical instruments that provide greater selectivity and sensitivity.

Effects of endocrine disrupting chemicals on gonad development: Mechanistic insights from fish and mammals.

Over the past century, evidence has emerged that endocrine disrupting chemicals (EDCs) have an impact on reproductive health. An increased frequency of reproductive disorders has been observed worldwide in both wildlife and humans that is correlated with accidental exposures to EDCs and their increased production. Epidemiological and experimental studies have highlighted the consequences of early exposures and the existence of key windows of sensitivity during development. Such early in life exposures can have an immediate impact on gonadal and reproductive tract development, as well as on long-term reproductive health in both males and females. Traditionally, EDCs were thought to exert their effects by modifying the endocrine pathways controlling reproduction. Advances in knowledge of the mechanisms regulating sex determination, differentiation and gonadal development in fish and rodents have led to a better understanding of the molecular mechanisms underlying the effects of early exposure to EDCs on reproduction. In this manuscript, we review the key developmental stages sensitive to EDCs and the state of knowledge on the mechanisms by which model EDCs affect these processes, based on the roadmap of gonad development specific to fish and mammals.

Impacts of endocrine disrupting chemicals on reproduction in wildlife and humans.

Endocrine disrupting chemicals (EDCs) are ubiquitous in aquatic and terrestrial environments. The main objective of this review was to summarize the current knowledge of the impacts of EDCs on reproductive success in wildlife and humans. The examples selected often include a retrospective assessment of the knowledge of reproductive impacts over time to discern how the effects of EDCs have changed over the last several decades. Collectively, the evidence summarized here within reinforce the concept that reproduction in wildlife and humans is negatively impacted by anthropogenic chemicals, with several altering endocrine system function. These observations of chemicals interfering with different aspects of the reproductive endocrine axis are particularly pronounced for aquatic species and are often corroborated by laboratory-based experiments (i.e. fish, amphibians, birds). Noteworthy, many of these same indicators are also observed in epidemiological studies in mammalian wildlife and humans. Given the vast array of reproductive strategies used by animals, it is perhaps not surprising that no single disrupted target is predictive of reproductive effects. Nevertheless, there are some general features of the endocrine control of reproduction, and in particular, the critical role that steroid hormones play in these processes that confer a high degree of susceptibility to environmental chemicals. New research is needed on the implications of chemical exposures during development and the potential for long-term reproductive effects. Future emphasis on field-based observations that can form the basis of more deliberate, extensive, and long-term population level studies to monitor contaminant effects, including adverse effects on the endocrine system, are key to addressing these knowledge gaps.

Men's experiences of radiotherapy treatment for localized prostate cancer and its long-term treatment side effects: a longitudinal qualitative study.

PURPOSE: To investigate men's experiences of receiving external-beam radiotherapy (EBRT) with neoadjuvant Androgen Deprivation Therapy (ADT) for localized prostate cancer (LPCa) in the ProtecT trial. METHODS: A longitudinal qualitative interview study was embedded in the ProtecT RCT. Sixteen men with clinically LPCa who underwent EBRT in ProtecT were purposively sampled to include a range of socio-demographic and clinical characteristics. They participated in serial in-depth qualitative interviews for up to 8 years post-treatment, exploring experiences of treatment and its side effects over time. RESULTS: Men experienced bowel, sexual, and urinary side effects, mostly in the short term but some persisted and were bothersome. Most men downplayed the impacts, voicing expectations of age-related decline, and normalizing these changes. There was some reticence to seek help, with men prioritizing their relationships and overall health and well-being over returning to pretreatment levels of function. Some unmet needs with regard to information about treatment schedules and side effects were reported, particularly among men with continuing functional symptoms. CONCLUSIONS: These findings reinforce the importance of providing universal clear, concise, and timely information and supportive resources in the short term, and more targeted and detailed information and care in the longer term to maintain and improve treatment experiences for men undergoing EBRT.

Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease.

BACKGROUND: Falls are a common complication of Parkinson's disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson's disease. METHODS: This is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson's motor and non-motor symptoms, quality of life and cost-effectiveness. DISCUSSION: This trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson's disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population. TRIAL REGISTRATION: REC reference: 19/SW/0043. EudraCT: 2018-003219-23. ISCRTN: 41639809 (registered 16/04/2019). ClinicalTrials.gov Identifier: NCT04226248 PROTOCOL AT TIME OF PUBLICATION: Version 7.0, 20th January 2021.

Modelling the lifetime cost-effectiveness of radical prostatectomy, radiotherapy and active monitoring for men with clinically localised prostate cancer from median 10-year outcomes in the ProtecT randomised trial.

BACKGROUND: Optimal management strategies for clinically localised prostate cancer are debated. Using median 10-year data from the largest randomised controlled trial to date (ProtecT), the lifetime cost-effectiveness of three major treatments (radical radiotherapy, radical prostatectomy and active monitoring) was explored according to age and risk subgroups. METHODS: A decision-analytic (Markov) model was developed and informed by clinical input. The economic evaluation adopted a UK NHS perspective and the outcome was cost per Quality-Adjusted Life Year (QALY) gained (reported in UK£), estimated using EQ-5D-3L. RESULTS: Costs and QALYs extrapolated over the lifetime were mostly similar between the three randomised strategies and their subgroups, but with some important differences. Across all analyses, active monitoring was associated with higher costs, probably associated with higher rates of metastatic disease and changes to radical treatments. When comparing the value of the strategies (QALY gains and costs) in monetary terms, for both low-risk prostate cancer subgroups, radiotherapy generated the greatest net monetary benefit (£293,446 [95% CI £282,811 to £299,451] by D'Amico and £292,736 [95% CI £284,074 to £297,719] by Grade group 1). However, the sensitivity analysis highlighted uncertainty in the finding when stratified by Grade group, as radiotherapy had 53% probability of cost-effectiveness and prostatectomy had 43%. In intermediate/high risk groups, using D'Amico and Grade group > = 2, prostatectomy generated the greatest net monetary benefit (£275,977 [95% CI £258,630 to £285,474] by D'Amico and £271,933 [95% CI £237,864 to £287,784] by Grade group). This finding was supported by the sensitivity analysis. Prostatectomy had the greatest net benefit (£290,487 [95% CI £280,781 to £296,281]) for men younger than 65 and radical radiotherapy (£201,311 [95% CI £195,161 to £205,049]) for men older than 65, but sensitivity analysis showed considerable uncertainty in both findings. CONCLUSION: Over the lifetime, extrapolating from the ProtecT trial, radical radiotherapy and prostatectomy appeared to be cost-effective for low risk prostate cancer, and radical prostatectomy for intermediate/high risk prostate cancer, but there was uncertainty in some estimates. Longer ProtecT trial follow-up is required to reduce uncertainty in the model. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

Socioeconomic position and suicidal behaviour in rural Sri Lanka: a prospective cohort study of 168,000+ people.

PURPOSE: Lower socioeconomic position (SEP) is associated with an increased risk of suicidal behaviour in high income countries, but this association is not established in low- and middle-income countries (LMIC). METHODS: We investigated the association of SEP with suicidal behaviour in a prospective cohort study of 168,771 Sri Lankans followed up for episodes of attempted suicide and suicide. SEP data were collected at baseline at the household and individual level at the start of the follow-up period. We used multilevel Poisson regression models to investigate the association of SEP at community, household and individual levels with attempted suicide/suicide. RESULTS: Lower levels of asset ownership [IRR (95% CI) suicide 1.74 (0.92, 3.28); attempted suicide 1.67 (1.40, 2.00)] and education [suicide 3.16 (1.06, 9.45); attempted suicide 2.51 (1.70, 3.72)] were associated with an increased risk of suicidal behaviour. The association of these measures of SEP and attempted suicide was stronger in men than women. Individuals living in deprived areas [1.42 (1.16, 1.73)] and in households with a young female head of household [1.41 (1.04, 1.93)] or a temporary foreign migrant [1.47 (1.28, 1.68)] had an elevated risk of attempted suicide. Farmers and daily wage labourers had nearly a doubling in risk of attempted suicide compared to other occupations. CONCLUSIONS: Improved employment opportunities, welfare and mental health support services, as well as problem-solving skills development, may help support individuals with poorer education, farmers, daily wage labourers, individuals in young female-headed households and temporary foreign migrant households.

Comparison of patient (POEM), observer (EASI, SASSAD, TIS) and corneometry measures of emollient effectiveness in children with eczema: findings from the COMET feasibility trial.

BACKGROUND: Eczema affects around 20% of children, but multiple different outcome measures have hampered research into the effectiveness of different treatments. OBJECTIVES: To compare the change in scores and correlations within and between five measures of eczema severity: Patient-Orientated Eczema Measure (POEM), Eczema Area and Severity Index (EASI), Six Area, Six Sign Atopic Dermatitis (SASSAD), Three Item Severity (TIS) and skin hydration (corneometry). METHODS: Data from a feasibility trial that randomized young children with eczema to one of four emollients were used. Participants were followed for 3 months (84 days). Descriptive statistics (by emollient over time) and Spearman's correlation coefficients comparing scores at each time point and absolute change (between adjacent time points) for each outcome measure were calculated. RESULTS: In total, 197 children, mean ± SD age 21·7 ± 12·8 months, were randomized. POEM and TIS appeared to capture a range of eczema severity at baseline, but only POEM had close approximation to normal distribution. Mean POEM, EASI, SASSAD and TIS scores improved month by month, with POEM showing the greatest sensitivity (effect size 0·42). Correlations within POEM, EASI, SASSAD and TIS were moderate to good, decreasing over time. Correlations between measures were strongest for EASI, SASSAD and TIS. By contrast, corneometry scores were more variable, correlated less well over time and were poorly correlated with the other measures. CONCLUSIONS: Except for corneometry, all measures appear to change in relation to emollient use over time and correlate well with themselves. POEM demonstrated the greatest range of scores at baseline and change in eczema severity over the first 28 days.

Interventions to reduce the impact of unemployment and economic hardship on mental health in the general population: a systematic review.

BACKGROUND: Job loss, debt and financial difficulties are associated with increased risk of mental illness and suicide in the general population. Interventions targeting people in debt or unemployed might help reduce these effects. METHOD: We searched MEDLINE, Embase, The Cochrane Library, Web of Science, and PsycINFO (January 2016) for randomized controlled trials (RCTs) of interventions to reduce the effects of unemployment and debt on mental health in general population samples. We assessed papers for inclusion, extracted data and assessed risk of bias. RESULTS: Eleven RCTs (n = 5303 participants) met the inclusion criteria. All recruited participants were unemployed. Five RCTs assessed 'job-club' interventions, two cognitive behaviour therapy (CBT) and a single RCT assessed each of emotional competency training, expressive writing, guided imagery and debt advice. All studies were at high risk of bias. 'Job club' interventions led to improvements in levels of depression up to 2 years post-intervention; effects were strongest among those at increased risk of depression (improvements of up to 0.2-0.3 s.d. in depression scores). There was mixed evidence for effectiveness of group CBT on symptoms of depression. An RCT of debt advice found no effect but had poor uptake. Single trials of three other interventions showed no evidence of benefit. CONCLUSIONS: 'Job-club' interventions may be effective in reducing depressive symptoms in unemployed people, particularly those at high risk of depression. Evidence for CBT-type interventions is mixed; further trials are needed. However the studies are old and at high risk of bias. Future intervention studies should follow CONSORT guidelines and address issues of poor uptake.

Diffusion-weighted magnetic resonance imaging for residual and recurrent cholesteatoma: a systematic review and meta-analysis.

BACKGROUND: Diagnosis and management of recurrent or residual cholesteatoma can be problematic. Diffusion-weighted imaging magnetic resonance imaging (MRI) sequences have been used for follow-up of such lesions. More recent non-echoplanar imaging (non-EPI) sequences are thought to be superior to older echoplanar imaging (EPI) sequences. OBJECTIVE OF REVIEW: Evaluate whether diffusion-weighted magnetic resonance imaging is useful in the diagnosis of recurrent or residual cholesteatoma. TYPE OF REVIEW: Systematic review and meta-analysis. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane Database were searched, with no limits on date or language. STUDY SELECTION: Adults or children who had previously undergone tympanomastoid surgery by any method with confirmation of recurrence/residual disease by second-look/revision surgery. EVALUATION METHODS: Two reviewers independently reviewed studies. Data extracted on 11 domains and rechecked. DATA SYNTHESIS: Statistical analysis with SPSS. RESULTS: A total of 575 studies were identified of which 27 met the inclusion criteria. These covered 727 patient episodes. For EPI studies: sensitivity (sd) 71.82 (24.5), specificity (sd) 89.36 (13.4), PPV (sd) 93.36 (8.1) and NPV (sd) 73.36 (15.8). For non-EPI studies: sensitivity 89.79 (12.1), specificity (sd) 94.57 (5.8), PPV (sd) 96.50 (4.2) and NPV 80.46 (20.2). Improved sensitivity of non-EPI sequences reached significance (P = 0.02). CONCLUSIONS: Diffusion-weighted MRI is both sensitive and specific for the detection of recurrent or residual cholesteatoma following ear surgery. Non-EPI techniques are superior to EPI techniques.

The Patient-Oriented Eczema Measure in young children: responsiveness and minimal clinically important difference.

BACKGROUND: The Patient-Oriented Eczema Measure (POEM) has been recommended as the core patient-reported outcome measure for trials of eczema treatments. Using data from the Choice of Moisturiser for Eczema Treatment randomized feasibility study, we assess the responsiveness to change and determine the minimal clinically important difference (MCID) of the POEM in young children with eczema. METHODS: Responsiveness to change by repeated administrations of the POEM was investigated in relation to change recalled using the Parent Global Assessment (PGA) measure. Five methods of determining the MCID of the POEM were employed; three anchor-based methods using PGA as the anchor: the within-patient score change, between-patient score change and sensitivity and specificity method, and two distribution-based methods: effect size estimate and the one half standard deviation of the baseline distribution of POEM scores. RESULTS: Successive POEM scores were found to be responsive to change in eczema severity. The MCID of the POEM change score, in relation to a slight improvement in eczema severity as recalled by parents on the PGA, estimated by the within-patient score change (4.27), the between-patient score change (2.89) and the sensitivity and specificity method (3.00) was similar to the one half standard deviation of the POEM baseline scores (2.94) and the effect size estimate (2.50). CONCLUSIONS: The Patient-Oriented Eczema Measure as applied to young children is responsive to change, and the MCID is around 3. This study will encourage the use of POEM and aid in determining sample size for future randomized controlled trials of treatments for eczema in young children.

Parental suicide attempt and offspring educational attainment during adolescence in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort.

BACKGROUND: Few studies have investigated the impact of parental suicide attempt (SA) on offspring outcomes other than mental health. We investigated the association of parental SA with offspring educational attainment in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHOD: Parental SA was prospectively recorded from pregnancy until the study children were 11 years old. National school test results (ages 11-16 years) were obtained by record linkage. Multilevel regression models quantified the association between parental SA and offspring outcomes. RESULTS: Data were available for 6667 mother-child and 3054 father-child pairs. Adolescents whose mothers had attempted suicide were less likely than their peers to achieve the expected educational level by age 14 years [adjusted odds ratio (aOR) 0.63, 95% confidence interval (CI) 0.41-0.95] in models controlling for relevant confounders, including parental education and depression. At age 16 years, adolescents whose mothers had attempted suicide were less likely to obtain the expected educational level (five or more qualifications at grade A*-C) (aOR 0.66, 95% CI 0.43-1.00) in models controlling for relevant confounders and parental education; however, after additionally controlling for maternal depression the results were consistent with chance (aOR 0.74, 95% CI 0.48-1.13). Findings in relation to paternal SA were consistent with those of maternal SA but power was limited due to lower response rate amongst fathers. CONCLUSIONS: Maternal SA was associated with diminished educational performance at age 14 years. Educational attainment during adolescence can have substantial effect on future opportunities and well-being and these offspring may benefit from interventions.

Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka.

Measuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self-reported pesticide exposure.

Study protocol for an evaluation of the effectiveness of 'care bundles' as a means of improving hospital care and reducing hospital readmission for patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic Obstructive Pulmonary Disease is one of the commonest respiratory diseases in the United Kingdom, accounting for 10% of unplanned hospital admissions each year. Nearly a third of these admitted patients are re-admitted to hospital within 28 days of discharge. Whilst there is a move within the NHS to ensure that people with long-term conditions receive more co-ordinated care, there is little research evidence to support an optimum approach to this in COPD. This study aims to evaluate the effectiveness of introducing standardised packages of care i.e. care bundles, for patients with acute exacerbations of COPD as a means of improving hospital care and reducing re-admissions. METHODS / DESIGN: This mixed-methods evaluation will use a controlled before-and-after design to examine the effect of, and costs associated with, implementing care bundles for patients admitted to hospital with an acute exacerbation of COPD, compared with usual care. It will quantitatively measure a range of patient and organisational outcomes for two groups of hospitals - those who deliver care using COPD care bundles, and those who deliver care without the use of COPD care bundles. These care bundles may be provided for patients with COPD following admission, prior to discharge or at both points in the care pathway. The primary outcome will be re-admission to hospital within 28 days of discharge, although the study will additionally investigate a number of secondary outcomes including length of stay, total bed days, in-hospital mortality, costs of care and patient / carer experience. A series of nested qualitative case studies will explore in detail the context and process of care as well as the impact of COPD bundles on staff, patients and carers. DISCUSSION: The results of the study will provide information about the effectiveness of care bundles as a way of managing in-hospital care for patients with an acute exacerbation of COPD. Given the number of unplanned hospital admissions for this patient group and their rate of subsequent re-admission, it is hoped that this evaluation will make a timely contribution to the evidence on care provision, to the benefit of patients, clinicians, managers and policy-makers. TRIAL REGISTRATION: International Standard Randomised Controlled Trials - ISRCTN13022442 - 11 February 2015.

Variation between hospitals in inpatient admission practices for self-harm patients and its impact on repeat presentation.

PURPOSE: Self-harm patient management varies markedly between hospitals, with fourfold differences in the proportion of patients who are admitted to a medical or psychiatric inpatient bed. The current study aimed to investigate whether differences in admission practices are associated with patient outcomes (repeat self-harm) while accounting for differences in patient case mix. METHODS: Data came from the National Self-Harm Registry Ireland. A prospective cohort of 43,595 self-harm patients presenting to hospital between 2007 and 2012 were included. As well as conventional regression analysis, instrumental variable (IV) methods utilising between hospital differences in rates of hospital admission were used in an attempt to gain unbiased estimates of the association of admission with risk of repeat self-harm. RESULTS: The proportion of self-harm patients admitted to a medical bed varied from 10 to 74 % between hospitals. Conventional regression and IV analysis suggested medical admission was not associated with risk of repeat self-harm. Psychiatric inpatient admission was associated with an increased risk of repeat self-harm in both conventional and IV analyses. This increased risk persisted in analyses stratified by gender and when restricted to self-poisoning patients only. CONCLUSIONS: No strong evidence was found to suggest medical admission reduces the risk of repeat self-harm. Models of health service provision that encourage prompt mental health assessment in the emergency department and avoid unnecessary medical admission of self-harm patients appear warranted. Psychiatric inpatient admission may be associated with a heightened risk of repeat self-harm in some patients, but these findings could be biased by residual confounding and require replication.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP).

BACKGROUND: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. METHODS: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50-69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. RESULTS: Among randomised practices, 271 (68%) in the intervention arm (198,114 men) and 302 (78%) in the control arm (221,929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). CONCLUSIONS: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Telephone versus face-to-face clinics for the management of new rhinology referrals: a retrospective cohort study.

OBJECTIVE: This study aimed to compare outcomes of telephone and face-to-face consultations for new rhinology referrals and discuss the wider use of telemedicine in rhinology. METHOD: This was a retrospective cohort study of new rhinology referrals seen in either a telephone or face-to-face clinic. Primary outcome was the proportion of patients given a definitive outcome at initial appointment (discharged or added to waiting list) versus those requiring follow up. RESULTS: A total of 137 patients (70 telephone, 67 face-to-face) were included. A total of 45 of 67 patients (67 per cent) undergoing a face-to-face consultation received a definitive outcome following initial review, versus 11 of 70 (16 per cent) telephone patients. Of 70 telephone patients 57 (81 per cent) were followed up face-to-face for examination. CONCLUSION: The role of telephone clinics in the assessment of new rhinology referrals is currently limited by the lack of clinical examination. Further research on developing remote assessment pathways that incorporate asynchronous review of recorded examinations are needed before telemedicine can become established within the rhinology clinic.