Microglial activation in normal-appearing brain regions of patients with cerebral glioma: a cross-sectional study

Background

Translocator protein (TSPO) is overexpressed mainly in activated microglia under disease conditions. [¹¹C]-(R)PK11195 is a radioligand for TSPO widely applied in PET studies. Previously we have found upregulated TSPO in neoplastic cells and its correlation with malignant transformation in human gliomas using [¹¹C]-(R)PK11195 PET and neuropathological assessment. We aimed to investigate TSPO expression and microglial activation in normal-appearing brain regions of patients with glioma.

Antimicrobial resistance in hospital wastewater in Scotland: a cross-sectional metagenomics study

BackgroundAntimicrobial resistance (AMR) is a global health crisis. It is well established that hospital wastewater can contain organisms that are on the WHO priority list of antibiotic-resistant organisms. We aimed to use metagenomics to study whether the abundances of resistance genes in hospital wastewater reflects clinical activity within the hospital.MethodsHospital wastewater was collected over a 24-h period in June, 2017 from multiple collection points representing different specialties within a tertiary hospital site in Scotland, UK and simultaneously from community sewage works. High throughput shotgun sequencing was done using Illumina HiSeq4000. Sequence reads were assigned taxonomically and to the AMR genes in the ResFinder database. The measured AMR gene abundances were correlated to hospital antimicrobial usage in defined daily doses per 100 occupied bed-days, mean patient length of stay in hospital, mean patient age per hospital collection point, and resistance levels in clinical isolates.Findings1047 bacterial genera and 174 different AMR genes were detected across all samples. Microbiota composition and AMR gene abundance and diversity varied between each collection point and AMR gene abundance was higher in hospital wastewater than in community influent. The composition of AMR genes correlated with microbiota composition (Procrustes analysis, p=0·002). Increased antimicrobial consumption at a class level was associated with higher AMR gene abundance within that class in hospital wastewater (incidence rate ratio 2·80, 95% CI 1·2–6·5, p=0·016). Prolonged mean patient length of stay was associated with higher total AMR gene abundance in hospital wastewater (2·05, 1·39–3·01, p=0·0003). No overall association was found between resistance in clinical isolates at an antimicrobial class level and AMR gene abundance in hospital wastewater.InterpretationAntimicrobial usage is a major driver of AMR gene outflow from hospitals into the sewage environment. The positive relationship between length of stay and AMR gene abundance is consistent with prolonged admission being a risk factor for carriage and infection with resistant microorganisms. Our findings show that hospital wastewater does reflect inpatient activity. With further evaluation this method might represent a useful surveillance tool to monitor hospital AMR gene outflow and guide environmental policy on AMR.FundingAcademy of Medical Sciences.     

Comparative prognostic value of myocardial strain derived from DENSE CMR: the British Heart Foundation MR-MI study

Background

Infarct size assessed early after acute ST-segment elevation myocardial infarction (STEMI) can overestimate the true extent of infarction, limiting its usefulness as a prognostic biomarker. Myocardial strain derived from displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) provides information on myocardial contractility with high precision and accuracy. We hypothesised that the prognostic value of peak circumferential strain is higher than infarct size.

Role of CLEC-2-driven platelet activation in the pathogenesis of toxic liver damage

Background

Toxic liver injury from drugs including paracetamol is the main cause of acute liver failure in developed countries. The mechanisms that drive irreversible liver failure are poorly understood; platelets could have an important role in this process given their roles beyond haemostasis, including liver regeneration. Ligation of the platelet receptor CLEC-2 with its cognate ligand podoplanin (PDPN) powerfully activates platelets; we sought to investigate the role of CLEC-2 in the pathogenesis of acute liver failure.

Effects of phosphodiesterase-5 inhibition with sildenafil on calcium waves in cardiac myocytes

Background

Diastolic Ca²⁺ waves in cardiac myocytes lead to arrhythmias by inducing delayed after-depolarisations. Waves occur when sarcoplasmic reticulum (SR) content reaches a threshold level. The phosphodiesterase-5 inhibitor, sildenafil, is antiarrhythmic in mammalian myocardial ischaemia models, and in rat myocytes it reduces Ca²⁺ transient amplitude and SR Ca²⁺ content. We sought to determine effects of sildenafil on propensity to Ca²⁺ waves in the large mammal.

A natural experimental evaluation of the effect of universal infant free school meals on key stage 1 pupil's dietary intake in northeast England: a pilot study

BackgroundIn 2013, a government-commissioned review of school food recommended that all key stage 1 pupils in England should receive free school meals. In 2014, Universal Infant Free School Meals (UIFSM) were implemented, costing £450 million. There has been no evaluation of this policy change on pupil's diets. We assessed the effect of UIFSM on pupil's lunch and total daily intake.MethodsWe used cross-sectional surveys in 2008–09 (before) and 2017–18 (after UIFSM) in two primary schools in Newcastle (school A in most deprived ward; school B in least deprived ward) and a validated, prospective 4-day food diary. All pupils (4–7 years) were eligible to participate with written parental consent (2008–09: n=112; 2017–18 n=84). A linear regression model explored the effect of year, school, level of deprivation (pupil postcode), and the interactions between these factors on mean change in percent energy non-milk extrinsic sugars (%E NMES), calcium, yoghurt, and cake; analyses were adjusted for gender. Ethical approval for this study was granted by Newcastle University.FindingsAt lunchtime, we found evidence of a decrease in pupils mean ENMES before and after UIFSM (mean change –4·6% [95% CI –6·3 to –2·9]), which was reflected in total daily intake (–3·8% [–5·2 to –2·7]). We found a year and school interaction on mean calcium: pupils in School B had a similar mean intake before and after UIFSM; in school A, calcium intake had increased (difference between schools in calcium change –120 mg [95% CI –179 to –62]); no evidence was found of an effect in total daily intake. After UIFSM, mean portions of yoghurt decreased in school B and increased in school A (–0·25 portions [–0·46 to –0·04]); mean portions of cake increased in School B and remained similar in school A (0·23 [0·43–0·42]).InterpretationWithin the limitations of this study (repeat cross-sectional survey; only two schools) there is evidence that UIFSM contributed to a reduction in ENMES. Schools should consider implementation of healthier policies (eg, removing the daily cake choice).FundingDepartment of Health and Social Care's Policy Research Programme (Public Health Research Consortium), Newcastle University.     

Barriers to treatment of mental health problems for Palestinian people in refugee camps in Jordan: a cross-sectional study

Background

About 2·1 million Palestinians live in Jordan, and 370?000 Palestinians live in Jordanian refugee camps. Conflict in their country of origin, poverty, unemployment, and squalid camp conditions are some of the environmental factors that render Palestine refugees susceptible to mental health problems. The aim of this study was to identify the barriers that contribute to the treatment gap in mental health-care services for Palestinian refugees in the Baqa'a refugee camp north of Amman, Jordan.

“The Mould that Changed the World”: a quantitative and qualitative evaluation of knowledge and behavioural change in children in the UK following participation in a musical about antimicrobial resistance

BackgroundA primary school musical—“The Mould that Changed the World”—was developed as a unique public engagement strategy to combat antimicrobial resistance (AMR) by engaging children in the story of the discovery of antibiotics, the risks of drug-resistant infections, and the importance of prudent antibiotic use.MethodsThe musical intervention was implemented in two UK primary schools. Parental consent was obtained for all participating children. All 182 participating children, aged 9–11 years, were given an online questionnaire in the classroom before rehearsals began and at 2 weeks after performance with a 6-month evaluation in one school. The effect of the musical was analysed using generalised linear models to control for confounding factors. For the qualitative evaluation, 15 participating children were selected randomly from each school to take part in semi-structured focus groups (n=5 per group) before rehearsals began and 2 weeks after performance. This study was approved by the University of Edinburgh research governance office as an evaluation of an intervention.FindingsConsistent with other intervention studies, knowledge gain was shown with children being more likely to answer questions on key messages of the musical correctly 2 weeks after performance (n=161) compared with the pre-rehearsal questionnaire (n=180; odds ratio 4·63 [95% CI 2·46–9·31], p<0·0001 for knowledge that bacteria can become resistant to antibiotics; 3·26 [1·75–6·32], p=0·00014 for knowledge that antibiotic resistant infections can be life threatening; 2·16 [1·39–3·38], p=0·00059 for knowledge that prudent use of antibiotics will halt rise of antibiotic resistant infections). Long-term knowledge gain was shown by a consistent level of correct answers on key messages between 2 weeks (response rate 95%, n=89) and 6 months after the musical (response rate 71%, n=67). Following the musical children participating in the focus groups (n=30) articulated a greater understanding of AMR and the risks of antibiotic overuse. They discussed intention to minimise personal antibiotic use and influence attitudes to antibiotics in their family and friends.InterpretationAlthough only evaluated in two schools, this study shows that initiatives such as musical theatre can improve both short-term and long-term knowledge in children. It shows a hitherto infrequently reported change in attitude and intention to behaviour change in children at an influential age for health beliefs. This unique public health tool has the potential for national roll-out in primary schools across the UK.FundingBritish Society of Antimicrobial Chemotherapy.     

Understanding the impact of a new public health approach to end-of-life care: a qualitative study of a community led intervention

Background

Social isolation is recognised for its substantial impact on mortality, ranking above many established public health threats. The end of life can compound this problem; with escalating acute care costs due to poor social support and rising numbers of deaths, new solutions are needed. Examples of peers providing social support exist within end-of-life care but have not been well characterised. We aimed to understand the impacts and facilitative processes of a home visiting intervention.

Long-term consequences of young patients undergoing endoscopic sphincterotomy: a cohort study

Background

An estimated 15% of the UK population has gallstones. Gallstones in the biliary tree can result in complications such as cholangitis and pancreatitis, which have high morbidity and mortality rates. To prevent such complications, patients can undergo endoscopic sphincterotomy. In our centre, an initial study was undertaken in 2002 to examine outcomes of endoscopic sphincterotomy in patients under the age of 50 years. The aim of our current project was to examine the long-term outcomes until Nov 30, 2015.

Barriers and facilitators to sitting less at work in different organisations: a qualitative study

Background

Long-term sitting is associated with increased risks of chronic disease and premature mortality. Since workplaces contribute to a large proportion of daily sitting time, reducing sitting in the workplace is a relevant public health objective. To develop effective interventions, factors that can influence reduced sitting behaviour at work must be understood. This study aimed to explore these barriers and facilitators and determine how they might differ by organisation type.

Introduction of standardised tobacco packaging and minimum excise tax on in the UK: a prospective study

BackgroundStandardised packaging for factory made and roll your own tobacco was implemented in the UK in May, 2017, alongside a minimum excise tax for factory made products. As other jurisdictions attempt to implement standardised packaging, the tobacco industry continues to suggest that it would be counterproductive, in part by leading to falls in price due to commoditisation. Here, we assess the impact of the introduction of these policies on the UK tobacco market.MethodsWe did a prospective study of UK commercial electronic point-of-sale data from 11 constituent geographic areas. The main outcomes were changes in sales volumes, volume-weighted real prices, and tobacco industry revenue. These were assessed using trend estimation from generalised additive mixed models. Products distributed to less than 10% of stores were excluded for sample design reasons; nevertheless, the analysis included an estimated 91% of the UK tobacco market products. The study did not require ethical approval.Findings107 572 monthly observations of products from May, 2015, to April,2018were included in the analysis. Introduction of standardised packaging and a minimum excise tax was associated with a doubling of the rate of sales decline. The most marked change in sales volumes was among the cheapest factory-made brands, where substantial sales growth stopped and prices rose markedly (prices increased by 0·035 p for the cheapest factory-made brands compared with 0·016 p across all factory-made brands and a 0·004 p increase across all products from May, 2015, to April, 2018). There was no evidence of commoditisation as market segmentation (price differentiation and different price trajectories for premium and lower priced products) continued. Company monthly net revenues declined from GBP £231 million (95% CI £222 million to £240 million) in May, 2015, to £192 million (£182 million to £201 million) in April, 2018.InterpretationThe concurrently introduced policies of standardised packaging and minimum excise tax were associated with declining tobacco sales and tobacco industry revenue, which might underpin the tobacco industry's opposition to the policies. Prices at the end of the period were higher than the at the start, implying no long-term price falls. A minimum excise tax might limit the tobacco industry's ability to keep low-priced tobacco, which is popular with young and disadvantaged smokers, available. The complementary introduction of standardised packaging and the minimum excise tax meant effects could not be distinguished statistically.FundingCancer Research UK and British Heart Foundation (grant number C27260/A23168).     

Socioeconomic inequalities in risk of small for gestational age birth in primiparous and multiparous women: analysis of a population-based cohort in the south of England

Background

Small for gestational age (SGA) babies have increased risk of later morbidity. Birth of the first child is a life-changing event that affects biology, behaviour, and social circumstances. We aimed to examine socioeconomic inequalities in SGA risk, and explore potential mediators and effect modification by parity.

The effectiveness of epigallocathechin-3-gallate for treatment of human papillomavirus-driven epithelial neoplasms: a preclinical study

Background

Epigallocathechin-3-gallate (EGCG), the major bioactive polyphenol in green tea, has anticarcinogenic properties in vitro and in vivo. Several recent reports have shown that EGCG affects the expression of human papillomavirus (HPV)-encoded E6 and E7, two oncoproteins required for HPV-driven oncogenesis. Here, we aimed to explore the effects of EGCG on keratinocyte proliferation and differentiation, in addition to HPV18 replication, in a three-dimensional organotypic raft culture system.

Heart function and structure during the first year of haemodialysis treatment: Cardiac Uraemic Fibrosis Detection in Dialysis Patients,an observational prospective study

Background

Patients with end-stage renal disease undergoing haemodialysis are at high risk of sudden cardiac death. Advanced renal disease is associated with cardiac hypertrophy, which increases risk of life-threatening arrhythmias. Using a new MRI technique, T1 mapping, and the blood biomarker brain natriuretic peptide (BNP), we aimed to measure changes in function and structure of the heart muscle during the first year of haemodialysis treatment in the Cardiac Uraemic Fibrosis Detection in Dialysis Patients study.

Mental health need: use of administrative data and record linkage to inform mental health policy and practice

Background

With mental ill-health on the rise globally, it is crucial to investigate whether the needs of individuals with mental ill-health are fully addressed. Attempts to measure negative consequences of unmet needs have been limited by the use of cross-sectional study designs or self-report measures. We aimed to investigate the interplay between perceived mental ill-health and unmet need in relation to mental health on a population level.

Role of stabilin-1 in chronic liver tissue injury and repair

Background

Organ fibrosis is a major cause of global mortality. Few medical therapies are available to treat this condition. We have previously demonstrated increased expression of stabilin-1 at sites of chronic liver disease. Using models of chronic liver injury, we aimed to elucidate the role of stabilin-1 during fibrosis and repair.

Mapping alcohol and tobacco tax interventions for health in the UK: a qualitative framework analysis

BackgroundAlcohol and tobacco use undermine population health, generating substantial costs. Increasing price is an effective means to reduce consumption and tax is a key harm reduction tool. In the UK, alcohol and tobacco tax are managed within fiscal policy, which does not necessarily prioritise health promotion. We aimed to map the objectives and options for alcohol and tobacco tax change in the UK, including the potential for greater coordination to improve health.MethodsWe did five semi-structured interviews with ten participants selected for their expertise in alcohol or tobacco tax policy. Interviews occurred in pairs (ie, one alcohol and one tobacco expert in each interview) to elicit comparison between substances and were supported by a rapid literature review of tax options. Participants were from government, arms-length governmental organisations, and advocacy groups. Informed by a rapid literature review, comparative framework analysis of alcohol and tobacco tax policy objectives, options, and factors pertaining to coordination between tobacco and alcohol was done.FindingsParticipants raised common health objectives (reducing consumption, harm, inequalities) and fiscal objectives (raising revenue, mitigating societal costs). Drawing on options identified in the rapid review, participants discussed common tax options to achieve these objectives: tax rate increases (sudden rises, annual increases, minimum thresholds), changing tax structures (taxing products differently, tax proportional to harm), levies (taxing retailers and manufacturers), and revenue hypothecation (for prevention or treatment of addiction, local services). Participants were positive about policy exchange across alcohol and tobacco and modelling the combined effect of tax changes, but uncertain about formally linking tax policy across substances.InterpretationRaising tax is often considered to improve health by making products less affordable, but a tax regime that raises additional revenue can support prevention and treatment services and mitigate the social and economic costs of consumption. An unresolved issue for policy debate is who should pay this revenue and how revenue would be maintained if the health objective of falling consumption were met. Although more input from fiscal policymakers would deepen findings, our rapid review and interview approach facilitated discussion across alcohol and tobacco, and use of the framework approach ensured consistent analysis.FundingNational Institute of Health Research Public Health Research programme.