Clinical approach to gastro-oesophageal reflux in idiopathic pulmonary fibrosis

MDIdiopathic pulmonary fibrosis is a progressive condition with limited treatment options and median survival of 3-5 years. Gastro-oesophageal reflux (GOR) has been described in up to 90% of patients. Pulmonary aspiration has been suggested to contribute to IPF, with calls for aggressive antireflux therapy. Whilst medical therapy can usually control acid reflux, surgery may be required to control non-acid refluxate, which may also be harmful if aspirated into the lung. The risks of surgery in the IPF population are significant. There is no validated technique with which to measure aspiration in this group and furthermore, patient attitudes towards the treatment of reflux and aspiration in IPF are unknown. As a result, the population that might benefit from antireflux therapy has yet to be defined. The current study comprised two main aims. The first was to characterise reflux and aspiration in an IPF cohort. The second was to evaluate patient attitudes towards the burden of IPF disease as compared to the burden of antireflux therapy. Methods Symptoms of reflux and lung health were assessed using a panel of structured questionnaires. Oesophageal function and gastro-oesophageal reflux were objectively assessed using manometry and pH-impedance monitoring. A standardised bronchoscopy and bronchoalveolar lavage, with biochemical and cytological analysis, was used to assess pulmonary aspiration. A separate group of individuals with IPF participated in an interview study. Respondents’ own health was evaluated using a visual analogue scale, the EuroQOL-5D -3L survey and a standard gamble utility analysis. Vignettes were constructed to describe mild- and moderate-severity IPF health states and adverse outcomes from medical and surgical antireflux therapy. Patient attitudes towards these four health states were assessed with a ranking exercise and a series of standard gambles. Results pH-impedance monitoring demonstrated supranormal levels of gastro-oesophageal reflux in 22 of 36 study subjects (61%). Eleven subjects had pre-existing evidence of gastro- ii oesophageal reflux and questionnaire assessment suggested GORD in 29% of subjects. Oesophageal manometry identified abnormal oesophageal function in 56%. Supranormal levels of pepsin were detected in bronchoalveolar lavage fluid in 16 subjects. The combination of pepsin quantification and oesophageal monitoring identified a subgroup of subjects with evidence of reflux and aspiration, but there was no correlation between levels of reflux and pepsin concentrations. Cytological staining results correlated poorly with gastro-oesophageal reflux. After formal multidisciplinary review, two patients who participated in the current study have undergone fundoplication. Both have enjoyed a stable disease course since surgery. In the interview study, respondents recorded mean utilities of 0.611 to 0.798 for their own health. Amongst 59 respondents, 38 regarded both IPF health states as preferable to the outcomes of either antireflux therapy outcome; the remainder disagreed. An adverse outcome from antireflux surgery was generally regarded as the worst of the health states. Discussion Oesophageal physiology and BAL fluid analysis may be combined to investigate reflux and aspiration in IPF. The current data suggest that reflux is common and frequently asymptomatic. Aspiration may only be significant in the minority of patients. Oesophageal dysmotility, a relative contra-indication to fundoplication, was evident in the majority of subjects. This is the first report of health state utilities for IPF and demonstrates a disease burden comparable to advanced lung cancer. Opinion was divided as to the relative burden associated with IPF disease and the potential outcomes of antireflux therapy. In conclusion, it remains difficult to identify the IPF patients for whom antireflux surgery might be most beneficial. For a proportion, the risks of such treatment will be prohibitive. The complexity of surgical decisions in this group suggests a requirement for a standard of care that includes a multidisciplinary team, informed by objective aerodigestive physiology and imaging.Knowledge Transfer Partnership in collaboration with Innovate UK. Funding originated largely from the Northern Oesophagogastric Unit, with additional support from the Medical Research Counci

Sudden death in epilepsy: insights from the last 25 years

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with refractory epilepsy, and as such has been a major research focus over the last 25 years. The earliest SUDEP research papers were published in Seizure, as have scores of SUDEP papers since. In this review we discuss the efforts to try and describe the pathophysiological basis of SUDEP, the drive to discover the clinical risk factors that increase the likelihood of SUDEP, and the motivation to increase awareness of SUDEP. These three areas are the prime factors that, when answered, will allow us to better mitigate against SUDEP and help individuals monitor their personal risk. The field has benefited from strong definitions, multinational collaboration, the use of cutting edge genetic analysis, and ensuring that bereaved families are able to take part in research when this is appropriate. Clearly there is much that we do not know and yet, has any area of epilepsy research come so far in the last 25 years

Translation: From bench to brain – Using the visual arts and metaphors to engage and educate

This article examines multidisciplinary public engagement projects that bring together developments in psychiatric research and practice with visual art and its use of metaphor. The article focuses on the art exhibition Translation: From bench to brain, which was the basis for further collaborations, illustrating how the learning from the original event influenced subsequent projects. Combining art exhibitions with online documentation and resources, the projects explored not only medical and scientific themes, but also the wider social, cultural and ethical ramifications, specifically aspects of identity, risk and stigma. The activities demonstrate the value of a developmental approach to public engagement as a process, whereby projects build on previous activities and evolving multidisciplinary perspectives, networks and expertise

Polychlorinated biphenyl (PCB) concentrations and profiles in marine mammals from the North Atlantic Ocean

Polychlorinated biphenyls (PCBs) can provide crucial information into the bioaccumulation and biomagnification of POPs in marine mammals. Muscle tissue samples were obtained for detailed PCB congener specific analysis of all 209 PCBs in 11 species of marine mammals stranded across the coast of the UK between 2010 and 2013. At least 145 PCB congeners were found in each individual. The highest concentrations of PCBs were recorded in a killer whale (318 mg/kg lipid) and the highest toxic equivalent in a Risso's dolphin (1687 pg/g TEQ2005 wet). Concentrations of PCBs in the majority of samples exceeded toxic thresholds (9 mg/kg lipid) for marine mammals, highlighting the health risk they face from PCB exposure. Many PCB profiles did not fit typical ‘Aroclor’ signatures, but instead indicated patterns of congeners that are resistant to biotransformation and elimination. However, this study identified a novel PCB signature in a sei whale that has not yet been previously observed in marine mammals. The whale had a PCB profile that included lighter and inadvertent PCB congeners such as PCB 11, suggesting that the main source of exposure was through atmospheric deposition, rather than terrestrial discharges. Seven subsamples were chosen for chiral analysis of PCB 95, 136 and 149. The enantiomer fractions (EFs) of C-PCBs 95 and 149 were non racemic suggesting there may be enantiomer selective metabolism in marine mammals. Although there has been a shift in the literature towards emerging pollutants, this study acts as a stark reminder that PCBs continue to pose a significant risk to wildlife

Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii

We thank the Broad Institute Sequencing Platform for generating the Illumina sequences. We thank Chen-Hsin Yu for helping on the data processing of the phenotypic tests. We acknowledge the South African National Institute for Communicable Diseases’ GERMS-SA surveillance network through which these isolates were originally collected. This project has been funded in whole or in part by the following U.S. Health and Human Services grants from the National Institute of Allergy and Infectious Diseases: U19 AI110818 (Broad Institute), R01 AI93257 (J.R.P.), R01 AI73896 (J.R.P.), and R01 AI025783 (T.G.M.). R.A.F. was supported by the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The content is solely our responsibility and does not necessarily represent the official views of the funders. The use of product names in this manuscript does not imply their endorsement by the U.S. Department of Health and Human Services. The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the CDC.Peer reviewedPublisher PD

Further development and feasibility randomised controlled trial of a digital programme for adolescent depression, MoodHwb: study protocol

Introduction: A digital programme, MoodHwb, was codesigned with young people experiencing or at high risk of depression, parents/carers and professionals, to provide support for young people with their mood and well-being. A preliminary evaluation study provided support for the programme theory and found that MoodHwb was acceptable to use. This study aims to refine the programme based on user feedback, and to assess the acceptability and feasibility of the updated version and study methods. Methods and analysis: Initially, this study will refine MoodHwb with the involvement of young people, including in a pretrial acceptability phase. This will be followed by a multicentre feasibility randomised controlled trial comparing MoodHwb plus usual care with a digital information pack plus usual care. Up to 120 young people aged 13–19 years with symptoms of depression and their parents/carers will be recruited through schools, mental health services, youth services, charities and voluntary self-referral in Wales and Scotland. The primary outcomes are the feasibility and acceptability of the MoodHwb programme (including usage, design and content) and of trial methods (including recruitment and retention rates), assessed 2 months postrandomisation. Secondary outcomes include potential impact on domains including depression knowledge and stigma, help-seeking, well-being and depression and anxiety symptoms measured at 2 months postrandomisation. Ethics and dissemination: The pretrial acceptability phase was approved by the Cardiff University School of Medicine Research Ethics Committee (REC) and the University of Glasgow College of Medicine, Veterinary and Life Sciences REC. The trial was approved by Wales NHS REC 3 (21/WA/0205), the Health Research Authority(HRA), Health and Care Research Wales (HCRW), university health board Research and Development (R&D) departments in Wales, and schools in Wales and Scotland. Findings will be disseminated in peer-reviewed open-access journals, at conferences and meetings, and online to academic, clinical, and educational audiences and the wider public. Trial registration number ISRCTN12437531

The Family Nurse Partnership to reduce maltreatment and improve child health and development in young children: the BB:2 6 routine data-linkage follow-up to earlier RCT

Background The short-term effectiveness (to 24 months post partum) of a preventative home-visiting intervention, the Family Nurse Partnership, was previously assessed in the Building Blocks trial (BB:0–2). Objectives The objectives were to establish the medium-term effectiveness of the Family Nurse Partnership in reducing maltreatment and improving maternal health (second pregnancies) and child health, developmental and educational outcomes (e.g. early educational attendance, school readiness); to explore effect moderators and mediators; and to describe the costs of enhancing usually provided health and social care with the Family Nurse Partnership. Design Children and their mothers from an existing trial cohort were followed up using routine data until the child was 7 years of age. Setting This study was set in 18 partnerships between local authorities and health-care organisations in England. Participants The participants were mothers [and their firstborn child(ren)] recruited as pregnant women aged ≤ 19 years, in local authority Family Nurse Partnership catchment areas, at < 25 weeks’ gestation, able to provide consent and able to converse in English. Participants mandatorily withdrawn (e.g. owing to miscarriage) from the BB:0–2 trial were excluded. Interventions The intervention comprised up to a maximum of 64 home visits by specially trained family nurses from early pregnancy until the firstborn child was 2 years of age, plus usually provided health and social care support. The comparator was usual care alone. Main outcome measures The primary outcome measure was child-in-need status recorded at any time during follow-up. The secondary outcomes were as follows: (1) referral to social services, child protection registration (plan), child-in-need categorisation, looked-after status, recorded injuries and ingestions at any time during follow-up; (2) early child care and educational attendance, school readiness (Early Years Foundation Stage Profile score) and attainment at Key Stage 1; and (3) health-care costs. Data sources The following data sources were used: maternally reported baseline and follow-up data (BB:0–2), Hospital Episode Statistics data (NHS Digital), social care and educational data (National Pupil Database) and abortions data (Department of Health and Social Care). Results There were no differences between study arms in the rates of referral to social services, being registered as a child in need, receiving child protection plans, entering care or timing of first referral for children subsequently assessed as in need. There were no differences between study arms in rates of hospital emergency attendance, admission for injuries or ingestions, or in duration of stay for admitted children. Children in the Family Nurse Partnership arm were more likely to achieve a good level of development at reception age (school readiness), an effect strengthened when adjusting for birth month. Differences at Key Stage 1 were not statistically different, but, after adjusting for birth month, children in the Family Nurse Partnership arm were more likely to reach the expected standard in reading. Programme effects were greater for boys (Key Stage 1: writing); children of younger mothers (Key Stage 1: writing, Key Stage 1: mathematics); and children of mothers not in employment, education or training at study baseline (Key Stage 1: writing). There were no differences between families who were part of the Family Nurse Partnership and those who were not for any other outcome. The differences between study arms in resource use and costs were negligible

A nurse-led home-visitation programme for first-time mothers in reducing maltreatment and improving child health and development (BB:2-6): longer-term outcomes from a randomised cohort using data-linkage

Objectives Measure effectiveness of family nurse partnership (FNP) home-visiting programme in reducing maltreatment and improving maternal health and child health, developmental and educational outcomes; explore effect moderators, mediators; describe costs. Design Follow-up of BB:0–2 trial cohort (ISRCTN:23019866) up to age 7 years in England using record linkage. Participants 1618 mothers aged 19 years or younger and their firstborn child(ren) recruited to BB:0–2 trial at less than 25 weeks gestation and not mandatorily withdrawn from trial or opted out. Intervention families were offered up to a maximum of 64 home visits by specially trained nurses from pregnancy until firstborn child was 2 years old, plus usually provided health and social care support. Comparator was usual care alone. Outcome measures Primary outcome: state-verified child-in-need status recorded at any time during follow-up. Secondary outcomes: referral to social services, child protection registration (plan), child-in-need categorisation, looked-after status, recorded injuries and ingestions any time during follow-up, early childcare and educational attendance, school readiness and attainment at key stage 1 (KS1), healthcare costs. Results Match rates for 1547 eligible children (1517 singletons, 15 sets of twins) were 98.3% (NHS Digital) and 97.4% (National Pupil Database). There was no difference between study arms in the proportion of children being registered as in need (adjusted OR 0.98, 95% CI 0.74 to 1.31), or for any other measure of maltreatment. Children in the FNP arm were more likely to achieve a good level of development at reception age (school readiness) (adjusted OR 1.24, 95% CI 1.01 to 1.52). After adjusting for birth month, children in FNP arm were more likely to reach the expected standard in reading at KS1 (adjusted OR 1.26, 95% CI 1.02 to 1.57). We found no trial arm differences for resource use and costs. Conclusions FNP did not improve maltreatment or maternal outcomes. There was evidence of small advantages in school readiness and attainment at KS1