The impact of a UK HIV-1 resistance database for the management and improvement of the clinical care of people living with HIV-1

Background: The introduction of highly active antiretroviral therapies (HAART) in 1996 to treat patients living with the human immunodeficiency virus type 1 (HIV-1), led to dramatic improvements in their mortality and morbidity. However, high levels of adherence to HAART regimens are required and due to the very nature of HIV-1: its high replicative capacity and lack of a proof reading mechanism, drug resistance mutations emerge, which impact on the ability of the drugs to suppress the patient’s circulating viruses. Genotypic resistance testing can determine whether mutations have developed which confer resistance to specific antiretrovirals (ARV) and thus enhance clinical care. Methods: A clinical cohort database was developed to host the demographic, treatment and resistance mutation data for patients living with HIV-1 across the United Kingdom (UK) who had a genotypic resistance test (tests) conducted as part of their clinical care. These data were pooled and interrogated to determine the evolution and dynamics of resistance in targeted sub-groups of patients including treatment-naïve patients; treatment-experienced patients and their potential susceptibility to new ARV drugs; and the evolution of new subtype profiles within the clinical cohort and the impact of this on clinical outcomes. The over-riding aim of each of the studies was to improve the clinical care of patients with HIV-1 infection in the UK. Results: In the treatment-naïve patient cohort (n=380), a resistance prevalence rate of 16.5% was determined. In the treatment-experienced cohort (n=1,786), the resistance prevalence rate was 68.1%. Of those treatment-experienced, 91.3% would be susceptible to the new ARV Etravirine (ETV) and 89.7% to Darunavir (DRV). In the subtype patient cohort (n=1,642), an increase in the prevalence of pure and recombinant non-B subtypes over time was demonstrated and characterised, as well as the identification of polymorphisms specific to non-B subtypes compared to subtype B. Conclusions: The resistance prevalence rate of >10.0% in the treatment-naïve patient cohort supported the need to conduct genotypic resistance tests for all treatment-naïve patients with HIV-1 infection before commencement of HAART in order to ensure the patient was starting on the optimal first-line treatment regimen to control their virus. National and European guidelines were subsequently amended to reflect this requirement. The treatment-experienced patient cohort analyses confirmed the resistance mutations circulating within the treated HIV-1 community which are the source of transmitted resistance to the treatment-naïve patients. Further analyses of the treatment-experienced cohort suggested two new ARVs which were due to be licenced for use with HIV-1 patients would be “theoretically susceptible”, providing further treatment options for these patients with resistance mutations. The subtype patient cohort work determined that subtype characterisation should be introduced as part of clinical care due to the impact of non-B subtypes on the success of genotypic resistance testing, and the different mutational pathways which might occur, leading to resistance in different subtypes. All these studies provided data and evidence of current issues which impacted on the clinical care of patients living with HIV-1 in the UK and influenced changes in guidelines on how best to manage and improve patient care

Delivering sports participation legacies at the grassroots level:the voluntary sports clubs of Glasgow 2014

Voluntary sports clubs (VSCs) provide the primary opportunities for organized community sport in the UK and thus hold the responsibility for delivering on mega-event sports participation legacies. This study presents findings from open-ended questionnaires and interviews conducted in two phases (Phase 1—Spring, 2013; Phase 2—Summer, 2015) with representatives from a sample (n = 39) of VSCs to understand their ability to deliver on the participation legacy goals of London 2012 and the 2014 Commonwealth Games in Glasgow. Thematic analysis of the data outlined three themes where support for VSCs should be placed when planning future mega-events: building VSC capacity, retaining members in the long-term, and promoting general visibility of the VSC throughout the event. Bid teams who hope to use mega-events as catalysts for sports participation increases should direct funding and guidance toward VSCs to ensure they have the tools, knowledge, and capacity to deliver on national sports participation ambitions.</jats:p

'Get fit - keep fit'? Exercise in the female life-cycle in Scotland, 1930-1970

This thesis looks into the complex relationships which women have had with their bodies throughout the twentieth century. It uses oral history evidence, medical sources, and official government material to examine women’s experiences of and access to physical recreation and sport throughout the life-cycle. It argues that despite the official view that throughout the twentieth century women’s sporting bodies were essentially fragile bodies, unsuited to competitive and manly sports, there were a number of alternative discourses available to women during these years. Women who had strong sporting identities, and confidence in their own physical abilities, were able to test the capabilities of their bodies and maintain their exercise participation throughout adolescence, menstruation, pregnancy and during motherhood, despite the advice of state officials, and many doctors, which advised them against participation. This thesis makes a powerful contribution to what at present is a largely uncharted historical landscape of female participation in and experience of physical recreation in Scotland and the UK in the mid-twentieth century. In a global context, it contributes to our understanding of the relationship between the female body and physical activity throughout the physically and culturally guided female life-cycle, and the particular ways in which women interacted with sport and exercise throughout the twentieth century

Country profile:sport and physical activity policy in Scotland

As a result of the successful devolution referendum in 1997 and the passing of the Scotland Act 1998, several legislative powers were devolved from the Government of the United Kingdom to the new Scottish Parliament including responsibility for sport, health and education. In consideration of this initial constitutional change, and subsequent amendments to taxation and welfare, this country profile provides an overview of how sport is organised and governed in Scotland, including the evolving trends in sport and physical activity policy. The aim is to analyse sport and physical activity policy in Scotland and to explore the wider social, political and economic challenges that impact upon its successful enactment. The profile begins with a historical evaluation of sport in Scotland and the key policy developments that have shaped it across the 20th and 21st century. This is followed by an evaluation of the current politics, structure and funding of sport in Scotland. In building upon those evaluations, three significant and inter-connected contemporary issues in Scottish sport are critically analysed. Whilst there are other relevant contemporary issues worthy of critique, we contend that (1) mega sport event legacies; (2) equality and inequality in sports participation and, (3) health inequalities are the most relevant to the Scottish Governments wider policy agenda and the role of sport and physical activity within it. Finally, a summary of the key findings is presented alongside recommendations for future research in sport and physical activity in Scotland

Enablers and barriers in ultra-running: a comparison of male and female ultra-runners

Female participation rates in ultra-running is considerably lower than that of males, but the reasons for this are not fully understood. In this study, online questionnaire responses were collected from ultra-runners taking part in the Scottish Jedburgh 3 Peaks ultra and Highland Fling race. One-to-one-semi-structured phone interviews were conducted with a subset of runners to further explore themes from questionnaire responses. Similar experiences among male and female ultra-runners were identified. Enablers were: wanting a challenge, nature/outdoors, and the friendliness of the ultra-community. The main barrier was training time. Qualitative responses suggested negotiation-efficacy was important for factoring in training around work and family commitments, and although a greater proportion of males had dependants compared to females, female participation was considerably lower than males. This may be due to the historical influences of traditional gender roles however this effect may be diminishing as female participation in Scottish ultra-races appears to be increasing

Country profile : sport and physical activity policy in Scotland

As a result of the successful devolution referendum in 1997 and the passing of the Scotland Act 1998, several legislative powers were devolved from the Government of the United Kingdom to the new Scottish Parliament including responsibility for sport, health and education. In consideration of this initial constitutional change, and subsequent amendments to taxation and welfare, this country profile provides an overview of how sport is organised and governed in Scotland, including the evolving trends in sport and physical activity policy. The aim is to analyse sport and physical activity policy in Scotland and to explore the wider social, political and economic challenges that impact upon its successful enactment. The profile begins with a historical evaluation of sport in Scotland and the key policy developments that have shaped it across the 20th and 21st century. This is followed by an evaluation of the current politics, structure and funding of sport in Scotland. In building upon those evaluations, three significant and inter-connected contemporary issues in Scottish sport are critically analysed. Whilst there are other relevant contemporary issues worthy of critique, we contend that (1) mega sport event legacies; (2) equality and inequality in sports participation and, (3) health inequalities are the most relevant to the Scottish Governments wider policy agenda and the role of sport and physical activity within it. Finally, a summary of the key findings is presented alongside recommendations for future research in sport and physical activity in Scotland

Validity of the iPhone M7 Motion Coprocessor to Estimate Physical Activity During Structured and Free-Living Activities in Healthy Adults

Modern smartphones such as the iPhone contain an integrated accelerometer, which can be used to measure body movement and estimate the volume and intensity of physical activity. Objectives: The primary objective was to assess the validity of the iPhone to measure step count and energy expenditure during laboratory-based physical activities. A further objective was to compare free-living estimates of physical activity between the iPhone and the ActiGraph GT3X+ accelerometer. Methods: Twenty healthy adults wore the iPhone 5S and GT3X+ in a waist-mounted pouch during bouts of treadmill walking, jogging, and other physical activities in the laboratory. Step counts were manually counted, and energy expenditure was measured using indirect calorimetry. During two weeks of free-living, participants (n = 17) continuously wore a GT3X+ attached to their waist and were provided with an iPhone 5S to use as they would their own phone. Results: During treadmill walking, iPhone (703 ± 97 steps) and GT3X+ (675 ± 133 steps) provided accurate measurements of step count compared with the criterion method (700 ± 98 steps). Compared with indirect calorimetry (8 ± 3 kcal·min−1), the iPhone (5 ± 1 kcal·min−1) underestimated energy expenditure with poor agreement. During free-living, the iPhone (7,990 ± 4,673 steps·day−1) recorded a significantly lower (p

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results

HIV-1 drug-resistance patterns among patients on failing treatment in a large number of European countries

Background: Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy. Methods: The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries. Genotypic resistance was interpreted using the ANRS algorithm. Phenotypic resistance was predicted using the Virco geno- to phenotype system. Results: 80.7% of the sequences included at least one drug-resistance mutation. Mutations were found for NRTIs (73.5%), NNRTIs (48.5%), and protease inhibitors (35.8%). Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. Among NRTIs, resistance was most frequently predicted for lamivudine. About half of all sequences had reduced susceptibility for NNRTIs. Resistance to most boosted protease inhibitors was found in &lt; 25%. No sequence had resistance to all currently available drugs. Conclusion: Levels of resistance among patients with therapy failure were high. The patterns of resistance reflect resistance to drugs available for a longer time. Fully suppressive regimens can be designed even for the most mutated HIV because boosted protease inhibitors have remained active against most circulating viruses and new drug classes have become available.</p