Telaprevir or boceprevir based therapy for chronic hepatitis C infection: Development of resistance-associated variants in treatment failure

The use of triple-therapy, pegylated-interferon, ribavirin and either of the first generation hepatitis C virus (HCV) protease inhibitors telaprevir or boceprevir, is the new standard of care for treating genotype 1 chronic HCV. Clinical trials have shown response rates of around 70–80%, but there is limited data from the use of this combination outside this setting. Through an expanded access programme, we treated 59 patients, treatment naïve and experienced, with triple therapy. Baseline factors predicting treatment response or failure during triple therapy phase were identified in 58 patients. Thirty seven (63.8%) of 58 patients had undetectable HCV RNA 12 weeks after the end of treatment. Genotype 1a (p = 0.053), null-response to previous treatment (p = 0.034), the rate of viral load decline after 12 weeks of previous interferon-based treatment (p = 0.033) were all associated with triple-therapy failure. The most common cause of on-treatment failure for telaprevir-based regimens was the development of resistance-associated variants (RAVs) at amino acids 36 and/or 155 of HCV protease (p = 0.027) whereas in boceprevir-based regimens mutations at amino acid 54 were significant (p = 0.015). SVR12 rates approaching 64% were achieved using triple therapy outside the clinical trial setting, in a patient cohort that included cirrhotics.

Embracing difference and the deferral of self-government: a critical analysis of the framing and practice of contemporary peace building

This thesis analyses how dominant policy approaches to peacebuilding have moved away from a single and universalised understanding of peace to be achieved through a top-down strategy of democratisation and economic liberalisation, prevalent at the beginning of 1990s. Instead, throughout the 2000s, peacebuilders have increasingly adopted a commitment to cultivating a bottom-up and hybrid peace building process that is context-sensitive and intended to be more respectful of the needs and values of post-war societies. The projects of statebuilding in Kosovo and, to a lesser extent, in Bosnia are examined to illustrate the shift. By capturing this shift, I seek to argue that contemporary practitioners of peace are sharing the sensibility of the theoretical critics of liberalism. These critics have long contended that post-war societies cannot be governed from ‘above’ and have advocated the adoption of a bottom-up approach to peacebuilding. Now, both peace practitioners and their critics share the tendency to embrace difference in peacebuilding operations, but this shift has failed to address meaningfully the problems and concerns of post-conflict societies. The conclusion of this research is that, drawing on the assumption that these societies are not capable of undertaking sovereign acts because of their problematic inter-subjective frames, the discourses of peacebuilding (in policy-making and academic critique) have increasingly legitimised an open-ended role of interference by external agencies, which now operate from ‘below’. Peacebuilding has turned into a long-term process, in which international and local actors engage relationally in the search for ever-more emancipatory hybrid outcomes, but in which self-government and self-determination are constantly deferred. Processes of emphasising difference have thus denied the political autonomy of post-war societies and have continuously questioned the political and human equality of these populations in a hierarchically divided world.

Starting antidepressant use: a qualitative synthesis of UK and Australian data

Objective To explore people's experiences of starting antidepressant treatment. Design Qualitative interpretive approach combining thematic analysis with constant comparison. Relevant coding reports from the original studies (generated using NVivo) relating to initial experiences of antidepressants were explored in further detail, focusing on the ways in which participants discussed their experiences of taking or being prescribed an antidepressant for the first time. Participants 108 men and women aged 22–84 who had taken antidepressants for depression. Setting Respondents recruited throughout the UK during 2003–2004 and 2008 and 2012–2013 and in Australia during 2010–2011. Results People expressed a wide range of feelings about initiating antidepressant use. People's attitudes towards starting antidepressant use were shaped by stereotypes and stigmas related to perceived drug dependency and potentially extreme side effects. Anxieties were expressed about starting use, and about how long the antidepressant might begin to take effect, how much it might help or hinder them, and about what to expect in the initial weeks. People worried about the possibility of experiencing adverse effects and implications for their senses of self. Where people felt they had not been given sufficient time during their consultation information or support to take the medicines, the uncertainty could be particularly unsettling and impact on their ongoing views on and use of antidepressants as a viable treatment option. Conclusions Our paper is the first to explore in-depth patient existential concerns about start of antidepressant use using multicountry data. People need additional support when they make decisions about starting antidepressants. Health professionals can use our findings to better understand and explore with patients’ their concerns before their patients start antidepressants. These insights are key to supporting patients, many of whom feel intimidated by the prospect of taking antidepressants, especially during the uncertain first few weeks of treatment.