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Non-native trees profoundly alter the structure and resilience of native forest ecosystems through direct or indirect effects on ecosystem processes, e.g. by altering invertebrate communities, but such effects are poorly understood in New Zealand. We sampled adjacent stands of the non-native tree Douglas fir (Pseudotsuga menziesii) and native beech (Nothofagaceae) forests and tested whether the overall invertebrate communities varied across forest types. We then assessed whether natural enemies, both trophic-generalist predators and more trophic-specialist parasitoids, differed across forest types. We found a trend for lower overall invertebrate family diversity in Douglas fir plantations compared to native beech forests. Parasitoid abundance was lower in Douglas fir forests compared to native beech forests, although we could not tease apart whether these effects were due to differences in forest age, forest type, or a combination of these factors. Our findings suggest that there are subtle shifts in invertebrate community composition from native forests to non-native forests, and that trophic specialisation might play a key role in determining which natural enemies can inhabit non-native forests in New Zealand. Nevertheless, our small sample size calls for further exploration of these patterns. [ABSTRACT FROM AUTHOR]

The integration of ethics in engineering education has largely been focused at the curriculum design level. The authors posit that this integration be done at the accreditation level and investigate how ethics may be more extensively incorporated in the documentation of a particular engineering accreditation body's qualification standards. The paper proceeds, by means of a narrative review, to justify an expanded conception of the teaching of ethics within engineering education. It builds a synthesis of contrasting conceptual approaches to the teaching of ethics within engineering and proposes a conceptual framework to guide both regulators and educators to identify and engage with different elements of the ethics across the curriculum within an engineering programme. The South African case study provides a context to engage with existing policy formulation around programme accreditation and to demonstrate the application of the proposed conceptual framework across the graduate attributes so to indicate how ethics might be more comprehensively integrated within a programme. This demonstrates that ethics needs to be repositioned at the centre of the preparation of engineers, rather than at the periphery. The expected consequence of this integration is the more extensive incorporation of ethics within and across accredited engineering programmes. [ABSTRACT FROM AUTHOR]

Introduction: Although the direct oral anticoagulant rivaroxaban is recommended for stroke prevention in patients with non-valvular atrial fibrillation based on Phase III clinical trials, there is still a need for additional safety data from everyday clinical practice. The ROSE study was initiated to collect further information on the safety and utilisation of rivaroxaban in a broader range of patient groups in routine clinical practice. Methods and results: The ROSE study was conducted in hospitals in England and Wales. Consenting adults with non-valvular atrial fibrillation newly started on rivaroxaban were eligible and followed up for 12 weeks. Data was derived through secondary use of medical records. The primary outcome was major bleeding within gastrointestinal, urogenital and intracranial sites. A total of 4846 patients were enrolled in the study September 2013 to January 2016, 965 of which were treated with rivaroxaban for non-valvular atrial fibrillation. The median age in the rivaroxaban non-valvular atrial fibrillation cohort was 76 years, 53.6% were male. The median HAS-BLED score was 2 and the median CHA2DS2-VASc score was 4. The risk of major bleeding within each of the primary sites of gastrointestinal, urogenital and intracranial during the 12 week observation period was low (0.2%; n = 2). The risk of major bleeding in all sites was 1.0% (n = 10) at a rate of 5.5 events per 100 patient years. Conclusion: In terms of the primary outcome risk of major bleeding within gastrointestinal, urogenital and intracranial sites during the 12 week observation period, the risk estimates in the non-valvular atrial fibrillation rivaroxaban user population were low (<1%), and consistent with risk estimated from clinical trial data and in routine clinical practice. [ABSTRACT FROM AUTHOR]

The article presents the study which examines how patient's weight is incorporated in the existing health care systems that requires an accurate measurement to ensure positive patient outcome. It explains that the risk of complications and adverse outcomes increases when the patients are not weighed in the prescribing high risk medicines (HRM). It recommends that patient weight must be a mandatory element for the admission process for compliance monitoring.

Background: Following the expansion of the European Union, there has been a large influx of Central and East European (CEE) migrants to the UK. CEE men who have sex with men (MSM) represent a small minority within this population that are none-the-less important to capture in sexual health research among the CEE migrant community. This paper examines the feasibility of recruiting CEE MSM for a survey of sexual behaviour in London using respondent driven sampling (RDS), via gay websites and in GUM clinics. Methods: We sought CEE MSM to start RDS chain referral among GUM clinic attendees, our personal contacts and at gay events and venues in central London. We recruited CEE MSM (n = 485) via two popular websites for gay men in Britain (March-May 2009) and at two central London GUM clinics (n = 51) (July 2008-March 2009). Results: We found seventeen men who knew other CEE MSM in London and agreed to recruit contacts into the study. These men recruited only three men into the study, none of whom recruited any further respondents, and RDS was abandoned after 7 months (July 2008-January 2009). Half of the men that we approached to participate in RDS did not know any other CEE MSM in London. Men who agreed to recruit contacts for RDS were rather more likely to have been in the UK for more than one year (94.1% vs 70.0%, p = 0.052). Men recruited through gay websites and from GUM clinics were similar. Conclusions: The Internet was the most successful method for collecting data on sexual risk behaviour among CEE MSM in London. CEE MSM in London were not well networked. RDS may also have failed because they did not fully understand the procedure and/or the financial incentive was not sufficient motivation to take part. [ABSTRACT FROM AUTHOR]

Background: Since May 2004, ten Central and Eastern European (CEE) countries have joined the European Union, leading to a large influx of CEE migrants to the United Kingdom (UK). The SALLEE project (sexual attitudes and lifestyles of London's Eastern Europeans) set out to establish an understanding of the sexual lifestyles and reproductive health risks of CEE migrants. CEE nationals make up a small minority of the population resident in the UK with no sampling frame from which to select a probability sample. There is also difficulty estimating the socio-demographic and geographical distribution of the population. In addition, measuring self-reported sexual behaviour which is generally found to be problematic, may be compounded among people from a range of different cultural and linguistic backgrounds. This paper will describe the methods adopted by the SALLEE project to address these challenges. Methods: The research was undertaken using quantitative and qualitative methods: a cross-sectional survey of CEE migrants based on three convenience samples (recruited from community venues, sexual health clinics and from the Internet) and semi-structured in-depth interviews with a purposively selected sample of CEE migrants. A detailed social mapping exercise of the CEE community was conducted prior to commencement of the survey to identify places where CEE migrants could be recruited. A total of 3,005 respondents took part in the cross-sectional survey, including 2,276 respondents in the community sample, 357 in the clinic sample and 372 in the Internet sample. 40 in-depth qualitative interviews were undertaken with a range of individuals, as determined by the interview quota matrix. Discussion: The SALLEE project has benefited from using quantitative research to provide generalisable data on a range of variables and qualitative research to add in-depth understanding and interpretation. The social mapping exercise successfully located a large number of CEE migrants for the community sample and is recommended for other migrant populations, especially when little or no official data are available for this purpose. The project has collected timely data that will help us to understand the sexual lifestyles, reproductive health risks and health service needs of CEE communities in the UK. [ABSTRACT FROM AUTHOR]

Objectives: To compare the characteristics of a self-selected, convenience sample of men who have sex with men (MSM) recruited through the internet with MSM drawn from a national probability survey in Great Britain. Methods: The internet sample (n = 2065) was recruited through two popular websites for homosexual men in Great Britain in May and June 2003. This sample was compared with MSM (n = 117) from the National Survey of Sexual Attitudes and Lifestyles (Natsal), a probability sample survey of adults resident in Great Britain conducted between May 1999 and February 2001. Results: No significant differences were observed between the samples on a range of sociodemographic and behavioural variables (p>0.05). However, men from the internet sample were younger (p<0.001) and more likely to be students (p = 0.001), but less likely to live in London (p = 0.001) or report good health (p = 0.014). Although both samples were equally likely to report testing for HIV, men from the internet sample were more likely to report a sexually transmitted infection in the past year (16.9% v 4.8%, adjusted odds ratio 4.14, 95% CI 1.76 to 9.74; p = 0.001), anal intercourse (76.9% v 63.3%; p = 0.001) and unprotected anal intercourse in the past 3 months (45% v 36.6%; p = 0.064). Conclusions: The internet provides a means of recruiting a self-selected, convenience sample of MSM whose social and demographic characteristics are broadly similar to those of MSM drawn from a national probability survey. However, estimates of high-risk sexual behaviour based on internet convenience samples are likely to overestimate levels of sexual risk behaviour in the wider MSM population. [ABSTRACT FROM AUTHOR]

The Engineering Education Research Network in Africa (EERN-Africa) was created to enable connections between practitioners and researchers with a shared interest in African engineering education contexts. Recognising the importance of developing an African voice in the engineering education research space, the EERN-Africa community has interacted in a dynamic and dialogic way with our own teaching and research practices across diverse African contexts, with an ethical commitment to democratic and inclusive community-building. The objective of this paper is to reflect on the current status of the Community of Practice (CoP), and the challenges and opportunities in sustaining and growing the CoP. A collaborative analysis of perspectives on this emerging identity is presented, using an Appreciative Inquiry (AI) methodology and drawing on collective written reflections and discussions. Six broad themes on the value that the CoP has for both individuals and the group were identified: networking, capacity development, emotional support, impact on professional identity, social and environmental impact, and breaking borders. This paper contributes an approach for collaborative capacity-building in EER through a virtual CoP, underpinned by the spirit of ubuntu. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were: (i) to determine the factors associated with HRQOL at baseline in our cohort, and (ii) to evaluate if there are differences in baseline HRQOL measures by antiretroviral treatment. Methods: The Short Form 36 (SF-36) was administered between 2006 and 2010 among members of the United States HIV Natural History Study cohort (NHS), and participants who completed the SF-36 were included in the study. Physical component summary (PCS) and mental component summary (MCS) scores were computed based on standard algorithms. Multivariate linear regression models were constructed for PCS and MCS to estimate the association between selected variables and HRQOL scores. Results: Antiretroviral therapy (ART) was not independently associated with HRQOL scores. Factors associated with PCS were CD4+ count < 200 cells/mm3 (β = -5.84, 95% CI: -7.63, -4.06), mental comorbidity (β = -2.82, 95% CI: -3.79, -1.85), medical comorbidity (β = -2.51, 95% CI: -3.75, -1.27), AIDS diagnosis (β = -2.38, 95% CI: -3.79, -0.98). Others were gender, military rank, marital status, and age. Factors independently associated with MCS were CD4+ count < 200 cells/mm3 (β = -1.93, 95% CI: -3.85, -0.02), mental comorbidity (β = -6.25, 95% CI: -7.25, -5.25), age (β = 0.37, 95% CI: 0.14, 0.60), and being African American (β = 1.55, 95% CI: 0.63, 2.47). Conclusion: Among military active duty and beneficiaries with HIV, modifiable factors associated with HRQOL measures included advanced HIV disease, and mental or medical comorbidity. Addressing these factors may improve quality of life of HIV-infected individuals in the NHS cohort. [ABSTRACT FROM AUTHOR]

Focuses on the gene mapping of primary congenital lymphedema to the 5q35.3 region. Evidences suggesting a major locus in 5q35.3; Manifestations of lymphedema; Probability of heterogeneity for primary lymphedema.

Abstract: Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64–1.89) or in Linxian (OR=1.47, 95%CI=0.70–3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79–1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC. [Copyright &y& Elsevier]

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited myocardial disorder associated with arrhythmias, heart failure, and sudden death. To date, mutations in four genes encoding major desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2, and desmoglein-2) have been implicated in the pathogenesis of ARVD/C. We screened 77 probands with ARVD/C for mutations in desmocollin-2 (DSC2), a gene coding for a desmosomal cadherin. Two heterozygous mutations—a deletion and an insertion—were identified in four probands. Both mutations result in frameshifts and premature truncation of the desmocollin-2 protein. For the first time, we have identified mutations in desmocollin-2 in patients with ARVD/C, a finding that is consistent with the hypothesis that ARVD/C is a disease of the desmosome. [ABSTRACT FROM AUTHOR]

Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer's disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is common amongst those with type 2 diabetes (T2DM). Alanine aminotransferase (ALT) is known to correlate with levels of liver inflammation and fibrosis. Recent data from our audit programme showed promising reductions in ALT with dapagliflozin. Our aim was to test the same hypothesis, that canagliflozin may improve ALT levels in patients with T2DM, therefore possibly providing benefit in NAFLD. Methods: Data were extracted from the ABCD nationwide audit programme and then stratified into 4 groups based on gender and elevated or normal baseline ALT levels using gender specific references ranges (Prati et al). Baseline and follow-up ALT measurements in the 12-month (6-18months) period were required as a minimum. Data were analysed using Stata 16. Results: 730 datasets were included with mean (±SD) age 61.3yrs (±10.8), 60.1% male, 76% Caucasian (where known), BMI 32.5kg/m2 (±6.5), baseline HbA1c 8.9% (±1.6%) and weight 97.6kg (±22.2) and were broadly similar across all 4 sub-groups. For the entire population, median ALT decreased by 3U/L (95% CI -2, -3; P<0.01). Both male and female subgroups with normal ALT at baseline showed no significant change in ALT. In those with raised ALT at baseline (female ≥19U/L; male ≥30U/L) a change in ALT of -8U/L (95% CI -6, -9U/L; P<0.001) in men and -4U/L in women (95% CI -2, -5; P<0.05). Kruskal-Wallis test confirmed the difference between all groups was significant to P<0.01. No statistically significant correlation was noted between change in weight and change in ALT, which may suggest a weight-loss independent mechanism. Conclusion: Our data show that ALT decreases with canagliflozin, similar to that demonstrated with dapagliflozin. This decrease is greatest in those with elevated baseline levels. Weight-loss is not a predictor of change in ALT suggesting a potential weight-loss independent mechanism. Disclosure: T.S.J. Crabtree: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. D.K. Sennik: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. A. Bickerton: None. K.H. Darzy: None. P. Winocour: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Napp Pharmaceuticals, Sanofi. M.L. Cull: None. A. Strzelecka: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. I.W. Gallen: None. M. Yadagiri: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is recognized as one of the greatest global public health challenges. There is increasing consensus that optimal disease modification using pharmaceuticals may best be achieved earlier in the disease continuum before symptoms occur. However, more needs to be understood about what outcomes are meaningful to potential participants in clinical trials within this preventative paradigm and how people make trade‐offs between risks and benefits. The Electronic Person‐Specific Outcome Measure (ePSOM) programme is developing an app to capture person‐specific outcomes and preferences in clinical trials. Objective: As one phase in the ePSOM programme, this study explored what matters when developing new treatments to prevent AD and how trade‐offs are made between risks and benefits, from three perspectives. Design: Focus groups were conducted with people living with memory problems (n = 21) and healthy volunteers (n = 10), and telephone interviews with health and social care professionals (n = 10). Differences and overlap between the three groups were explored. Results: Outcomes that matter lie in five key domains in relation to what matters in everyday life: Everyday Functioning; Relationships and Social Connections; Enjoying Life; Sense of Identity; and Alleviating  Symptoms. Insights were gained into the significance of reducing the risk of developing dementia with drugs and the processes of weighing up risks versus benefits. Discussion and conclusions: The key domains identified are being used to inform the next stage of the ePSOM programme which is to develop a survey to be distributed nationally in the UK to explore these issues further. [ABSTRACT FROM AUTHOR]

In the ABCD nationwide liraglutide audit the impact of liraglutide on HbA1c was found to lessen with increasing duration of diabetes (abstract 1038-P, ADA 2012). We were interested to examine the relationship between change in HbA1c and duration of diabetes in response to canagliflozin in real clinical use in the ABCD nationwide canagliflozin audit. By December 2018 the audit had accumulated data on 972 canagliflozin treated patients of whom there were 604 with baseline HbA1c ≥ 7% and follow-up HbA1c (mean ± SD age 60.3 ± 11.1 year, BMI 33.7 ± 6.7 kg/m2, 62% male, median (IQR) diabetes duration 6.0 (2.6-11) year). By 1st return to clinic after commencing canagliflozin at median (IQR) 4.1 (3.0-6.1) months, mean ± SD HbA1c fell by 0.91 ± 1.2%, from 9.2 ± 1.5 to 8.3 ± 1.3% (p<0.001). Patients with duration of diabetes data (n=434) were divided into 3 groups: 0-5, 6-10, >10 years with mean ± SD baseline HbA1c 9.1 ± 1.6, 9.2 ± 1.5 and 9.3 ± 1.3% respectively (p=0.62). The mean ± SD falls in HbA1c for the 3 groups were 0.87 ± 1.3%, 0.88 ± 1.2%, and 0.86 ± 1.2%, respectfully (p=0.99) (Figure). There was thus no relationship between duration of diabetes and fall in HbA1c in this audit of canagliflozin in real clinical use in the UK. This result contrasts with that from the ABCD liraglutide audit and is in keeping with the differing modes of action of liraglutide and canagliflozin. Disclosure: R.E.J. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. A. Bickerton: Employee; Self; MyWay Digital Health. K. Thong: None. M. Yadagiri: None. M.L. Cull: None. M.C. Wyres: None. P. Winocour: None. K.H. Darzy: None. A. Strzelecka: None. S.G. Gohil: None. A. Gallagher: Speaker's Bureau; Self; Novo Nordisk A/S. I.W. Gallen: None. Funding: Association of British Clinical Diabetologists [ABSTRACT FROM AUTHOR]

Background: Previous studies have noted significant gender difference in the risk of liver cancer among hepatitis B chronic infection patients. Some indicated that it might be due to lifestyle-related differences. This paper tests whether or not such a gender discrepancy among the chronic hepatitis B population is confounded by lifestyle and environment related exposures. Methods: We retrieved a sample of 1863 participants from a prospective cohort in Haimen City, China in 2003. Liver disease severity was categorized as “normal”, “mild”, “moderate”, and “severe” based on a clinical diagnosis. Lifestyle and environmental exposures were measured by questionnaires. We used factor analysis and individual variables to represent lifestyle and environmental exposures. We applied the cumulative logit models to estimate the effect of gender on liver disease severity and how it was impacted by lifestyle and environmental exposures. Results: Gender and HBeAg positivity were independent risk factors for more severe liver disease. Compared to females, males were 2.08 times as likely to develop more severe liver disease (95% CI: 1.66–2.61). Participants who were HBeAg positivite were 2.19 times (95% CI: 1.61–2.96) as likely to develop more severe liver disease compared to those who were negative. Controlling for lifestyle and environmental exposures did not change these estimations. Conclusions: Males in the HBV infected population have an increased risk of severe liver disease. This gender effect is independent of the lifestyle and environmental exposures addressed in this study. Our findings support the hypothesis that gender discrepancies in HCC risk are attributable to intrinsic differences between males and females. [ABSTRACT FROM AUTHOR]

The global burden of hepatocellular carcinoma (HCC; primary liver cancer) is increasing. HCC is often unaccompanied by clear symptomatology, causing patients to be unaware of their disease. Moreover, effective treatment for those with advanced disease is lacking. As such, effective surveillance and early detection of HCC are essential. However, current screening and surveillance guidelines are not being fully implemented. Some at-risk populations fall outside of the guidelines, and patients who are screened are often not diagnosed at an early enough stage for treatment to be effective. From March 17 to 19, 2015, the Hepatitis B Foundation sponsored a workshop to identify gaps and limitations in current approaches to the detection and treatment of HCC and to define research priorities and opportunities for advocacy. In this Commentary, we summarize areas for further research and action that were discussed throughout the workshop to improve the recognition of liver disease generally, improve the recognition of liver cancer risk, and improve the recognition that screening for HCC makes a life-saving difference. Participants agreed that primary prevention of HCC relies on prevention and treatment of viral hepatitis and other underlying etiologies. Earlier diagnosis (secondary prevention) needs to be substantially improved. Areas for attention include increasing practitioner awareness, better definition of at-risk populations, and improved performance of screening approaches (ultrasound, biomarkers for detection, risk stratification, targeted therapies). The heterogeneous nature of HCC makes it unlikely that a single therapeutic agent will be universally effective. Medical management will benefit from the development of new, targeted treatment approaches. [ABSTRACT FROM AUTHOR]

Describes the experiences of supportive groups for the relatives of patients with dementia in London, England. Evaluation on the adequacy of inpatient resources for demented patients; Benefits of support groups; Common themes discussed in the group.

Background Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance antidepressants (m-ADM) can prevent relapse, whereas, r psychological help can help them recover from depression in the longterm. A recently developed treatment, mindfulness-based cognitive therapy (MBCT), shows potential as a brief group program for people with recurring depression.. This trial asks the policy research question; is MBCT with support to taper/discontinue antidepressant medication (MBCT-TS) superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant medication (ADM) usage, (d) (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? An explanatory research question also asks whether an increase in mindfulness skills is the key mechanism of change. The design is a single-blind, parallel randomized controlled trial examining MBCT-TS versus m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT-TS with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. Results Depressive relapse/recurrence over two years is the primary outcome variable. Analyses will be conducted following CONSORT standards and overseen by the trial's Data Monitoring and Safety Committee. Initial analyses will be conducted on an intention-to-treat basis, with subsequent analyses being per protocol. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre-and post-treatment and a qualitative study of service users' views and experiences. Conclusions If the results of our exploratory trial are extended to this definitive trial, MBCT-TS will be established as an alternative approach to maintenance antidepressants for people with a history of recurrent depression. The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: An estimated one million people worldwide die each year from complications of chronic hepatitis B infection (CHB), including liver cancer. A disproportionate number of infections and deaths occur in China. The incidence and mortality of liver cancer in Haimen City is among the highest in China, and in the world. A multi-year citywide campaign was aimed at eliminating hepatitis B virus (HBV) infection and significantly reducing the number of liver cancer deaths due to CHB in Haimen City, China.Methods: Strategies included a public health information campaign targeting the 1.03 million city residents; specialized health education for leaders and providers to increase adoption of evidence-based HBV management protocols; establishment of health care infrastructure and management systems; and increased prevention and care delivery to key subpopulations (especially pregnant women).Results: The project developed and deployed broad-reaching public awareness and health education tools and modules to 280,000 households and at community-based events. More than 90% of targeted healthcare providers and 80% of the community leaders/government officials attended educational seminars during the project period (1,441 health care providers; 1,883 local government officials). A centralized registration and management system for pregnant women was developed and instituted, 100% of pregnant women were enrolled (5,407 women over one year), and all infants born to HBV-infected mothers received one dose of HBIG and the first dose of HBV vaccine by 24 hours of birth.Conclusions: Lessons from the implementation phase of the project include the importance of: gaining early and ongoing support from the local government and health bureau for success in reaching the targeted populations; and having project management by a local, experienced, and trusted health expert to navigate implementation and relationships, and help develop culturally and linguistically appropriate materials. [ABSTRACT FROM AUTHOR]

Hypermethylation of the promoter of the tumor suppressor gene, adenomatous polyposis coli (APC), occurs in various malignancies, including hepatocellular carcinoma (HCC). However, reports on the specificity of the methylation of the APC gene for HCC have varied. To gain insight into how these variations occur, bisulfite PCR sequencing was performed to analyze the methylation status of both sense and antisense strands of the APC gene in samples of HCC tissue, matched adjacent non-HCC liver tissue, hepatitis, cirrhosis, and normal liver tissues. DNA derived from fetal liver and 12 nonhepatic normal tissue was also examined. These experiments revealed liver-specific, antisense strand-biased CpG methylation of the APC gene and suggested that, although methylation of the antisense strand of the APC gene exists in normal liver and other non-HCC disease liver tissue, methylation of the sense strand of the APC gene occurs predominantly in HCC. To determine the effect of the DNA strand on the specificity of the methylated APC gene as a biomarker for HCC detection, quantitative methylation-specific PCR assays for sense and antisense strand DNA were developed and performed on DNA isolated from HCC (n = 58), matched adjacent non-HCC (n = 58), cirrhosis (n = 41), and hepatitis (n = 39). Receiver operating characteristic curves were constructed. With the cutoff value set at the limit of detection, the specificity of sense and antisense strand methylation was 84% and 43%, respectively, and sensitivity was 67.2% and 72.4%, respectively. This result demonstrated that the identity of the methylated DNA strand impacted the specificity of APC for HCC detection. Interestingly, methylation of the sense strand of APC occurred in 40% of HCCs from patients with serum AFP levels less than 20 ng/mL, suggesting a potential role for APC as a biomarker to complement AFP in HCC screening. [ABSTRACT FROM AUTHOR]

Aims Recent immunohistochemical studies observed the loss of plakoglobin (PG) from the intercalated disc (ID) as a hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), suggesting a final common pathway for this disease. However, the underlying molecular processes are poorly understood. Methods and results We have identified novel mutations in the desmosomal cadherin desmocollin 2 (DSC2 R203C, L229X, T275M, and G371fsX378). The two missense mutations (DSC2 R203C and T275M) have been functionally characterized, together with a previously reported frameshift variant (DSC2 A897fsX900), to examine their pathogenic potential towards PG's functions at the ID. The three mutant proteins were transiently expressed in various cellular systems and assayed for expression, processing, localization, and binding to other desmosomal components in comparison to wild-type DSC2a protein. The two missense mutations showed defects in proteolytic cleavage, a process which is required for the functional activation of mature cadherins. In both cases, this is thought to cause a reduction of functional DSC2 at the desmosomes in cardiac cells. In contrast, the frameshift variant was incorporated into cardiac desmosomes; however, it showed reduced binding to PG. Conclusion Despite different modes of action, for all three variants, the reduced ability to provide a ligand for PG at the desmosomes was observed. This is in agreement with the reduced intensity of PG at these structures observed in ARVC patients. [ABSTRACT FROM AUTHOR]

Background: Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM) can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. We need to develop psychological therapies that prevent depressive relapse/recurrence. A recently developed treatment, Mindfulness-based Cognitive Therapy (MBCT, see http://www.mbct.co.uk) shows potential as a brief group programme for people with recurring depression. In two studies it has been shown to halve the rates of depression recurring compared to usual care. This trial asks the policy research question, is MBCT superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and, secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant (ADM) usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? An explanatory research question asks is an increase in mindfulness skills the key mechanism of change? Methods/Design: The design is a single blind, parallel RCT examining MBCT vs. m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT plus ADM-tapering with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care. Depressive relapse/recurrence over two years is the primary outcome variable. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre/post-treatment and a qualitative study of service users' views and experiences. Discussion: If the results of our exploratory trial are extended to this definitive trial, MBCT will be established as an alternative approach to maintenance anti-depressants for people with a history of recurrent depression. The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches. Trial registration number: ISRCTN26666654 [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the clinical expression of adenosine monophosphate-activated protein kinase (AMPK) gene mutations (PRKAG2) in adenosine monophosphate (AMP) kinase disease based on 12 years follow-up of known mutation carriers and to define the prevalence of PRKAG2 mutations in hypertrophic cardiomyopathy (HCM). Background: Adenosine monophosphate-activated protein kinase gene mutations cause HCM with Wolff-Parkinson-White syndrome and conduction disease. Methods: Clinical evaluation of 44 patients with known AMP kinase disease was analyzed. Mutation analysis of PRKAG2 was performed by fluorescent single-strand confirmation polymorphism analysis and direct sequencing of abnormal conformers in 200 patients with HCM. Results: Only one additional mutation was identified. The mean age at clinical diagnosis in the 45 gene carriers was 24 years (median 20 years, range 9 to 55 years). Symptoms of palpitation, dypspnea, chest pain, or syncope were present in 31 (69%) gene carriers; 7 (15%) complained of myalgia and had clinical evidence of proximal myopathy. Skeletal muscle biopsy showed excess mitochondria and ragged red fibers with minimal glycogen accumulation. Disease penetrance defined by typical electrocardiogram abnormalities was 100% by age 18 years. Thirty-two of 41 adults (78%) had left ventricular hypertrophy (LVH) on echocardiography, and progressive LVH was documented during follow-up. Survival was 91% at a mean follow-up of 12.2 years. Progressive conduction disease required pacemaker implantation in 17 of 45 (38%) at a mean age of 38 years. Conclusions: The AMP kinase disease is uncommon in HCM and is characterized by progressive conduction disease and cardiac hypertrophy and includes extracardiac manifestations such as a skeletal myopathy, consistent with a systemic metabolic storage disease. Defects in adenosine triphosphate utilization or in specific cellular substrates, rather than mere passive deposition of amylopectin, may account for these clinical features. [ABSTRACT FROM AUTHOR]

Chronic infection with hepatitis B virus (HBV) is associated with the majority of hepatocellular carcinoma (HCC). The diagnosis of HCC is usually made in the late stages of the disease, when treatment options are limited and prognosis is poor. We therefore have developed a method of glycoproteomic analysis in an attempt to discover serum markers that can assist in the early detection of HBV-induced liver cancer. Briefly, a comparative method for analysis of oligosaccharides released from serum glycoproteins and for recovery and identification of proteins with aberrant glycosylation, as a function of cancer diagnosis, is described. The model we have used is the woodchuck (Marmota monax), which shares similarities in the glycosylation pattern associated with liver proteins in human HCC. In this report, we show that woodchucks diagnosed with HCC have dramatically higher levels of serum- associated core a-1,6-linked fucose, as compared with woodchucks without a diagnosis of HCC. The coupling of this methodology with 2D gel proteomics has permitted the identification of several glycoproteins with altered glycosylation as a function of cancer. One such glycoprotein, Golgi Protein 73 (GP73), was found to be elevated and hyperfucosylated in animals with HCC. Further, the study showed GP73 to be elevated in the serum of people with a diagnosis of 11CC, providing a validation of our approach. The potential of this technology for biomarker discovery and the implications of increased levels of GP73 in liver cancer are discussed. [ABSTRACT FROM AUTHOR]

The identification of mechanisms that prevent infection with human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) would facilitate the development of an effective AIDS vaccine. In time-course experiments, protection against detectable superinfection with homologous wild-type SIV was achieved within 21 days of inoculation with live attenuated SIV, prior to the development of detectable anti-SIV humoral immunity. Partial protection against superinfection was achieved within 10 days of inoculation with live attenuated SIV, prior to the development of detectable anti-SIV humoral and cellular immunity. Furthermore, co-inoculation of live attenuated SIV with wild-type SIV resulted in a significant reduction in peak virus loads compared to controls that received wild-type SIV alone. These findings imply that innate immunity or non-immune mechanisms are a significant component of early protection against superinfection conferred by inoculation with live attenuated SIV. [Copyright &y& Elsevier]

Comments on the article "Trends in the treatment of ductal carcinoma in situ (DCIS) of the breast" by N.N. Baxter et al. published in the "Journal of the National Cancer Institute" in 2004. Failure to take into consideration changes in radiation therapy; Objection to the description of complete excision without radiation therapy as 'undertreatment'; Authors' preference for least aggressive treatments.

To determine whether attenuated simian immunodeficiency virus (SIV) vaccines confer protection against superinfection via secondary cellular immune responses, we searched for markers of immune activation following rechallenge. Productive infection with either attenuated SIVmacC8 or wild-type SIVmacJ5 resulted in a transient increase in T-lymphocyte CD25 and Mafa-DR expression. A pronounced increase in the frequency of FAS+ CD8+ lymphocytes was observed following SIVmacJ5 infection only. A transient increase in lymphocytes positive for intracellular IFN-γ and IL-4 was observed following primary infection with either virus. In contrast, lymphocytes positive for intracellular IL-2 were reduced. Following SIVmacJ5 challenge of SIVmacC8-infected vaccinees, no evidence of detectable superinfection was obtained. Rechallenge of vaccinees did not alter the frequency of activated peripheral T-lymphocytes, perturb cytokine profiles, or generate an anamnestic antibody response. These data do not support the hypothesis that protection conferred by live attenuated SIV is mediated by the induction of vigorous T-cell responses upon rechallenge. [Copyright &y& Elsevier]

Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of hepatocellular carcinoma (HCC), with disease progression occurring relentlessly over many years. The diagnosis of HCC usually occurs at late stages in the disease when there are few effective treatment options and the prognosis for patients with HCC is very poor. The long latency period, together with clearly identified at risk populations, provide opportunities for earlier detection that will allow more timely and effective treatment of this devastating cancer. We are using a proteomic approach to test the hypothesis that changes in the amount of certain serum polypeptides, or changes in their post-translational modifications, can be used to predict the onset of HCC. Advances in the standardization of two dimensional gel electrophoresis (2DE) coupled with computerized image analysis now permit the reproducible resolution of thousands of polypeptides per run. Serum polypeptides from individuals at different stages in the disease continuum are being resolved by 2DE to identify those that change with disease progression. Polypeptides found by this method can be further characterized by mass spectrometry. In addition, the potential for changes in the glycan structure of certain polypeptides to serve as a marker for disease progression can be explored. The proteomic approach is expected to liberate us from the need to "cherry pick" or guess the best biomarkers and let the data tell us which are the best indicators of disease. Information may also be gleaned about the pathobiology of the disease process. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) commonly co-exists with type 2 diabetes. Alanine aminotransferase (ALT) levels are known to correlate, to some degree, with liver inflammation. Methods: All data submitted to the ABCD nationwide empagliflozin audit programme were included if they had relevant baseline and follow-up data and were then stratified by baseline ALT for two analyses: 1) using gender-specific reference ranges; 2) by normal (<30U/L), mildly raised (30-59 U/L) and very raised levels (twice male reference limit, ≥60 U/L). Data were analysed using non-parametric methods due to skew using Stata SE 16. Results: 6510 datasets were included with mean(±SD) age 60.0yrs(±10.4), 61.2% male, BMI 34.2kg/m2(±6.5), HbA1c 9.3%(±1.6) and weight 98.4kg(±21.23). For the entire population, median ALT changed by -4 U/L (95% CI -4, -4; P<0.01). When stratified, in both analyses, all groups showed significant changes in ALT from baseline. These are shown in Figure 1. Conclusion: Our data demonstrate changes in ALT associated with empagliflozin use. Decreases of a significantly greater magnitude are noted in those with raised ALT at baseline. Empaglifozin may provide benefit in NAFLD. Disclosure: T. S. J. Crabtree: Other Relationship; Self; Novo Nordisk, Sanofi. J. Elliott: Advisory Panel; Self; Abbott, Speaker's Bureau; Self; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk. A. Bickerton: None. I. W. Gallen: None. K. Dhatariya: Speaker's Bureau; Self; Novo Nordisk. M. L. Cull: None. A. Evans: None. S. M. Phillips: None. R. E. Ryder: Other Relationship; Self; Novo Nordisk. Funding: Boehringer Ingelheim [ABSTRACT FROM AUTHOR]

Background: Data previously presented from our audit programme showed that sodium-glucose co-transporter 2 inhibitors (SGLT2s) remain equally effective at reducing HbA1c irrespective of duration of diabetes. This analysis was performed to establish if the same held true for empagliflozin. Methods: Data extracted from the ABCD nationwide empagliflozin audit was stratified into groups based on duration of diabetes: group 1 (<5yrs; n=2320), group 2 (≥5yrs, <10yrs; n=1516), group 3 (≥10yrs; n=2224). Data was analysed using paired t-tests and ANOVA in Stata 16. Results: 6060 datasets were included with mean (±SD) age 59.5yrs (±10.4), 61.1% male, 86% Caucasian (where known), BMI 33.2kg/m2 (±7.2), baseline HbA1c 9.2% (±1.6%) and weight 98.1kg (±21.0). These were broadly similar across all 3 sub-groups apart from age, which understandably increased with duration of diabetes (group 1 57.7yrs±10.8 v group 3 62.0yrs±9.7). Decreases in HbA1c (%) from baseline were observed in all groups, greatest in group 1 (-1.27%; 95% CI -1.19%, -1.35%) and least pronounced in group 3 (-0.9%; 95% CI -0.83%, -0.97%). ANOVA showed significant differences amongst the groups for HbA1c change (P<0.001) but not for weight, BMI or blood pressure. Further analysis has demonstrated no significant difference between HbA1c reductions in group 1 and 2 (P=0.79) but very significant differences (P<0.001) between both groups 1 and 2 and group 3, suggesting the change in response occurs at around the 10 year mark. Conclusions: This analysis demonstrates statistically significant differences in the magnitude of HbA1c change (due to empagliflozin use) in those with shorter v longer durations of diabetes, appearing to occur after 10 years. Although the pattern is generally comparable to other SGLT2s the statistical significance is likely to have been increased from previous data due to a larger sample. The clinical significance of such minor differences in effect is not clear. Disclosure: T.S.J. Crabtree: None. K. Adamson: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. A.M. Robinson: None. M. Atkin: Speaker's Bureau; Self; AstraZeneca, Napp Pharmaceuticals. D.S. Morris: None. D.M. Williams: None. J.W. Stephens: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Napp Pharmaceuticals, Novo Nordisk A/S. D.K. Sennik: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. M.L. Cull: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. [ABSTRACT FROM AUTHOR]

Introduction: Alanine transaminase (ALT) is an important marker for Nonalcoholic Fatty Liver Disease (NAFLD), and its levels are reduced following treatment with SGLT2i. However, how raised ALT levels and hence NAFLD affects HbA1c response to SGLT2i is not known. Methods: Data for this study was obtained from the ABCD nationwide audits of patients with type 2 diabetes started on SGLT2i. We used a gradient boosting machine learning algorithm (GBM) to identify if ALT is an important predictor of glycaemic response to SGLT2i. The results of the GBM model were confirmed using linear regression analysis where the absolute drop in HbA1c was modelled as a dependent variable with baseline ALT as independent variable adjusted for relevant covariates. Results: We studied 9,609 patients initiated on Empagliflozin (n=5061), Dapagliflozin (n=3711) or Canagliflozin (n=837). The mean age of the study population was 59(±10.3), 62% male with a mean weight of 96.6(±18.8), baseline eGFR 81(±11) and baseline HbA1c 9.06% (±1.62). At a median 5.8 months follow-up, the mean HbA1c drop was 0.81% and was similar in all three types of SGLT2i. The drop in HbA1c was 0.62%, 0.78% and 1.01% in 1st 2nd and 3rd quartiles of baseline ALT, respectively (P-Anova <0.0001). In the GBM analysis the important predictors of glycaemic response were baseline weight (relative influence (RI)=71%), and baseline HbA1c (RI= 7.2%), baseline ALT (RI= 5.6%) baseline creatinine (RI= 4.9%). The model accuracy was 0.73 (0.71-0.75) and area under the curve was 0.83. In the linear regression model, higher baseline ALT was associated with a larger drop in HbA1c (beta=0.007, P<0.0001) after adjustments for baseline weight, weight loss, baseline HbA1c, and duration of diabetes. Conclusion: Higher baseline ALT levels are associated with a more significant SGLT2 induced HbA1c drop and SGLT2 inhibitors and are likely to be more effective in those with NAFLD. Disclosure: H. Deshmukh: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. D.K. Sennik: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. K. Adamson: None. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose linked transporter 2 inhibitors (SGLT2s) are currently favoured for their tolerability, cardiovascular benefit and renal protective effects. However, due to their mechanism of action, they are only licensed for use in those with preserved renal function at baseline. Previous analyses with other drugs in the class showed potential benefits even when used in those with estimated glomerular filtration rate (eGFR) below licensed level. Methods: Data was extracted from the ABCD nationwide empagliflozin audit and then stratified into groups, as follows, based on baseline eGFR (mL/min/1.73m2): CKD1 (n=2900, eGFR≥90), CKD2 (n=2753, eGFR<90, eGFR≥60), CKD3a (n=210, eGFR<60, eGFR≥45) and CKD3b+ (n=17, eGFR<45). Data was analysed using paired t-tests and ANOVA in Stata 16. Results: 5880 datasets were included with mean (±SD) age 59.5yrs (±10.4), 61.1% male, 86% Caucasian (where known), BMI 33.1kg/m2 (±6.6), HbA1c 9.17% (±1.61) and median duration diabetes 7.3 years (2.2-12.1 IQR) and were broadly similar across groups apart from age: those with more impaired renal function being generally older (CKD1 55.4yrs±9.5 v CKD3b+ 69.6yrs±8.5) with a longer duration diabetes with median (IQR) in CKD1 6.6yrs (1.8-10.9) v CKD3b+ 14.5yrs (8.9-17.3). Reductions in HbA1c, weight and BMI occurred in all groups (P<0.005); reductions in HbA1c were of a smaller magnitude as eGFR declined (ANOVA P<0.01). Changes in systolic (SBP) and diastolic blood pressure (DBP) were significant in those in CKD1- CKD3a but not in CKD3b+ (SBP +2.6mmHg, 95% CI +14.9, -9.6). eGFR was observed to decrease in CKD1 and CKD2 (CKD1 eGFR -2.1mL/min/1.73m2, CI 95% -1.8, -2.3). Conclusion: The use of empagliflozin at eGFR<45mL/min/1.73m2 may still confer HbA1c improvement (although perhaps of lower magnitude) and weight loss, though SBP and DBP reduction may be limited. More evidence is needed regarding its use at lower levels of eGFR. Disclosure: T.S.J. Crabtree: None. K. Adamson: None. A. Bickerton: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. A.M. Robinson: None. M. Atkin: Speaker's Bureau; Self; AstraZeneca, Napp Pharmaceuticals. D.S. Morris: None. D.M. Williams: None. J.W. Stephens: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Napp Pharmaceuticals, Novo Nordisk A/S. D.K. Sennik: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. M.L. Cull: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. M. Yadagiri: None. I.W. Gallen: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S. [ABSTRACT FROM AUTHOR]

Introduction: We investigated characteristics and treatment outcomes of patients treated with empagliflozin in a large-scale audit of routine clinical practice in the UK. Methods: Data was obtained from the Association of British Clinical Diabetologists Nationwide Empagliflozin Audit. Between December 2014 to September 2018, multiple sites submitted data through 10 major centers on 1947 patients with at least one follow-up visit after empagliflozin initiation. Results: Baseline characteristics of patients were, mean±SD, age 59.9±9.9 years, diabetes duration 6.4±5.4 years, HbA1c 9.41±1.43%, weight 99.6±20.8 years, BMI 33.6±9.1 kg/m2and 62.1% were male. Proportion of use of empagliflozin 25mg (vs. 10mg), GLP-1 receptor agonist, and insulin were 63.7%, 13.7% and 20.1%, respectively. There were 44.9%, 49.9%, 5.1% and 0.1% of patients with eGFR>90, 60-89, 45-59 and <45 ml/min/1.73m2, respectively. By 26 weeks, treatment with empagliflozin was associated with, mean±SD, HbA1c reduction of 1.35±1.49% (p<0.0001), weight reduction of 3.6±5.1 kg (p<0.0001) and systolic blood pressure reduction of 5±14 mmHg (p<0.0001). Conclusions: An audit of empagliflozin use in the UK revealed poorly controlled diabetes being frequently encountered in practice in contrast to randomized clinical trials. There was a preponderance of empagliflozin 25mg dose use, disproportionate prescribing to men rather than women, and frequent co-prescription with GLP-1 receptor agonists and insulin. The audit showed excellent adherence to prescribing guidelines in relation to avoiding empagliflozin use in patients with eGFR<45 ml/min/1.73m2. There was similar treatment efficacy with empaglilfozin as was seen in clinical trials. Disclosure: K. Thong: None. J. Chung-Wah-Cheong: None. M. Yadagiri: None. M.L. Cull: None. A. Bickerton: Employee; Self; MyWay Digital Health. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. H. Reid: None. D.S. Morris: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NAPP Pharmaceuticals Limited, Novo Nordisk A/S, Sanofi-Aventis. M. Atkin: Advisory Panel; Self; NAPP Pharmaceuticals Limited. Consultant; Self; My mHealth. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. A.M. Robinson: Advisory Panel; Self; Takeda UK. D.M. Williams: None. J.W. Stephens: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, NAPP Pharmaceuticals Limited. K. Adamson: None. I.W. Gallen: None. R.E. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. Funding: Association of British Clinical Diabetologists [ABSTRACT FROM AUTHOR]

Introduction: We investigated clinical parameters that are potentially associated with improved empagliflozin treatment response. Methods: We obtained data from a large-scale audit of empagliflozin use in the UK. We analyzed the association between patients' baseline age, HbA1c, weight, diabetes duration, alanine aminotransferase (ALT), sex, chronic kidney disease (CKD) stage, empagliflozin dose (25 vs. 10mg), use of GLP-1RAs and use of insulin with HbA1c and weight changes at 26 weeks of treatment. Results: Among 1436 patients, HbA1c reduced by, mean[95% CI], 1.35%[1.27,1.42] (p<0.0001) from a baseline of, mean±SD, 9.41±1.41%. Among 1381 patients, weight reduced by 3.6 kg[3.3,3.9] (p<0.0001) from a baseline of 100.2±20.7 kg. Results of univariate analyses are shown in Table 1. In multivariate analysis, higher baseline HbA1c (p<0.0001), lower CKD stage (p=0.002) and higher ALT (log transformed)(p=0.02) were associated with greater HbA1c reduction. Higher baseline weight (p<0.001) and non-insulin use (p<0.0001) were associated with greater weight reduction. Conclusion: As expected, HbA1c reduction was associated with baseline HbA1c and background renal function, while weight reduction was associated with baseline weight. The interactions between HbA1c reduction and ALT levels, and weight reduction with insulin treatment status warrant further investigations. Disclosure: K. Thong: None. J. Chung-Wah-Cheong: None. M. Yadagiri: None. M.L. Cull: None. A. Bickerton: Employee; Self; MyWay Digital Health. S.M. Phillips: None. A. Evans: None. D.K. Sennik: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. A. Rohilla: None. H. Reid: None. D.S. Morris: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NAPP Pharmaceuticals Limited, Novo Nordisk A/S, Sanofi-Aventis. M. Atkin: Advisory Panel; Self; NAPP Pharmaceuticals Limited. Consultant; Self; My mHealth. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. A.M. Robinson: Advisory Panel; Self; Takeda UK. D.M. Williams: None. J.W. Stephens: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, NAPP Pharmaceuticals Limited. I.W. Gallen: None. K. Adamson: None. R.E. Ryder: Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Bioquest. Funding: Association of British Clinical Diabetologists [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQOL) is a patient-centered outcome measure used in assessing the individual's overall functional health status but studies looking at HRQOL as a predictive tool are few. This work examines whether summary scores of HRQOL are predictive of all-cause hospitalization in the US Military HIV Natural History Study (NHS) cohort.Methods: The Short Form 36 (SF-36) was administered between 2006 and 2010 to 1711 NHS cohort members whose hospitalization records we had also obtained. Physical component summary scores (PCSS) and mental component summary scores (MCSS) were computed based on standard algorithms. Terciles of PCSS and MCSS were generated with the upper terciles (higher HRQOL) as referent groups. Proportional hazards multivariate regression models were used to estimate the hazard of hospitalization for PCSS and MCSS separately (models 1 and 2, respectively) and combined (model 3).Results: The hazard ratios (HR) of hospitalization were respectively 2.12 times (95% CI: 1.59-2.84) and 1.59 times (95% CI: 1.19-2.14) higher for the lower and middle terciles compared to the upper PCSS tercile. The HR of hospitalization was 1.33 times (95% CI: 1.02-1.73) higher for the lower compared to the upper MCSS tercile. Other predictors of hospitalization were CD4 count < 200 cells/mm3 (HR = 2.84, 95% CI: 1.96, 4.12), CD4 count 200-349 cells/mm3 (HR = 1.67, 95% CI: 1.24, 2.26), CD4 count 350-499 cells/mm3 (HR = 1.41, 95% CI: 1.09, 1.83), plasma viral load > 50 copies/mL (HR = 1.82, 95% CI: 1.46, 2.26), and yearly increment in duration of HIV infection (HR = 0.94, 95% CI: 0.93, 0.96) (model 3).Conclusion: After controlling for factors associated with hospitalization among those with HIV, both PCSS and MCSS were predictive of all-cause hospitalization in the NHS cohort. HRQOL assessment using the SF-36 may be useful in stratifying hospitalization risk among HIV-infected populations. [ABSTRACT FROM AUTHOR]

Background: Depression is a common and distressing mental health problem that is responsible for significant individual disability and cost to society. Medication and psychological therapies are effective for treating depression and maintenance anti-depressants (m-ADM) can prevent relapse. However, individuals with depression often express a wish for psychological help that can help them recover from depression in the long-term. A recently developed treatment, mindfulness-based cognitive therapy (MBCT), shows potential as a brief group program for people with recurring depression.This trial asks the policy research question; is MBCT with support to taper/discontinue antidepressant medication (MBCT-TS) superior to m-ADM in terms of: a primary outcome of preventing depressive relapse/recurrence over 24 months; and secondary outcomes of (a) depression free days, (b) residual depressive symptoms, (c) antidepressant medication (ADM) usage, (d) psychiatric and medical co-morbidity, (e) quality of life, and (f) cost effectiveness? An explanatory research question also asks whether an increase in mindfulness skills is the key mechanism of change.The design is a single-blind, parallel randomized controlled trial examining MBCT-TS versus m-ADM with an embedded process study. To answer the main policy research question the proposed trial compares MBCT-TS with m-ADM for patients with recurrent depression. Four hundred and twenty patients with recurrent major depressive disorder in full or partial remission will be recruited through primary care.Results: Depressive relapse/recurrence over two years is the primary outcome variable. Analyses will be conducted following CONSORT standards and overseen by the trial's Data Monitoring and Safety Committee. Initial analyses will be conducted on an intention-to-treat basis, with subsequent analyses being per protocol. The explanatory question will be addressed in two mutually informative ways: quantitative measurement of potential mediating variables pre- and post-treatment and a qualitative study of service users' views and experiences.Conclusions: If the results of our exploratory trial are extended to this definitive trial, MBCT-TS will be established as an alternative approach to maintenance antidepressants for people with a history of recurrent depression. The process studies will provide evidence about the effective components which can be used to improve MBCT and inform theory as well as other therapeutic approaches.Trial Registration: Trial registered 7 May 2009; ISRCTN26666654. [ABSTRACT FROM AUTHOR]

Research has found that populations with low socioeconomic status (SES) and minority populations have greater access to small corner markets and less access to supermarkets than high-SES and Caucasian populations. This represents a significant difference in the farm-to-fork continuum that these populations experience. This research examined whether differential retail access to foods results in different food safety risks at the retail level for consumers with different demographics. U.S. Census Bureau census tracts with high African American, Asian, Hispanic, Caucasian, low-SES, and high-SES populations were identified in Philadelphia, PA. Approximately 60 retail food establishments were sampled in each census tract category from June 2008 to June 2010. Food samples collected at stores included milk, eggs, lunchmeat, sandwiches, and ready-to-eat (RTE) fresh fruit, greens, and herbs, when available. With the exception of milk and eggs, only food that had been handled and/or prepared at the retail level was sampled. Food samples were tested for temperature, aerobic plate count, coliforms, fecal coliforms, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. The results indicated that internal egg temperatures were higher in samples from low-SES census tracts than in eggs from Caucasian census tracts, and eggs were more often found unrefrigerated in markets in low-SES and Asian census tracts. Milk samples from markets in Hispanic and low-SES census tracts had higher aerobic plate counts than high-SES census tract samples. Sandwiches from markets in high-SES census tracts had higher coliform counts than sandwiches from markets in all other census tract categories. Markets in Asian census tracts had a higher incidence of fecal coliform contamination on sandwiches than markets in Caucasian census tracts. Fecal coliforms were present in a percentage of RTE greens from markets in all census tracts except African American, with the highest percentages of RTE greens positive for fecal coliforms in low-SES (100%), Asian (71.4%), and Caucasian (45.5%) markets. [ABSTRACT FROM AUTHOR]