Operator training requirements and diagnostic accuracy of Fibroscan in routine clinical practice

BACKGROUND: Fibroscan is a quick, non-invasive technique used to measure liver stiffness (kPa), which correlates with fibrosis. To achieve a valid liver stiffness evaluation (LSE) the operator must obtain all the following three criteria: (1) ≥10 successful liver stiffness measurements; (2) IQR/median ratio <0.30 and (3) ≥60% measurement success rate. OBJECTIVES: To assess the operator training requirements and the importance of adhering to the LSE validity criteria in routine clinical practice. METHODS: We retrospectively analysed the LSE validity rates of 2311 Fibroscans performed (1 August 2008 to 31 July 2011) in our tertiary liver outpatients department at the University Hospital Birmingham, UK. The diagnostic accuracy of Fibroscan was assessed in 153 patients, by comparing LSE (valid and invalid) with the modified Ishak fibrosis stage on liver biopsy. RESULTS: Learning curve analysis highlighted that the greatest improvement in validity of LSE rates occurs in the operator’s first 10 Fibroscans, reaching 64.7% validity by the 50th Fibroscan. The correlation between LSE and the fibrosis stage on liver biopsy was superior in patients with a valid LSE (n=97) compared with those with an invalid LSE (n=56) (r(s) 0.577 vs 0.259; p=0.022). Area under receiving operating characteristics for significant fibrosis was greater when LSE was valid (0.83 vs 0.66; p=0.048). Using an LSE cut-off of 8 kPa, the negative predictive value of valid LSE was superior to invalid LSE for the detection of significant (84% vs 71%) and advanced fibrosis (100% vs 93%). CONCLUSIONS: Fibroscan requires minimal operator training (≥10 observed on patients), and when a valid LSE is obtained, it is an accurate tool for excluding advanced liver fibrosis. To ensure the diagnostic accuracy of Fibroscan it is essential that the recommended LSE validity criteria are adhered to in routine clinical practice

The state of play: securities of childhood - insecurities of children

This article is broadly concerned with the positioning of children, both within and outside the subject area of International Relations. It considers the costs of an adult- 5 centric standpoint in security studies and contrasts this with investments made seemingly on behalf of children and their security. It begins by looking at how children and childhoods are constructed and contained - yet also defy categorization - at some cost to their protection. The many competing children and childhoods that are invoked in security discourses and partially sustain their victimcy are then illustrated. It is 10 argued that at their entry point into academia they are essentialized and sentimentalized. Power relations which subvert, yet also rely on children and childhoods can only be disrupted through a reconfiguration of politics and agency which includes an engagement with political literacy on a societal level and acknowledgement of the ubiquitous presence of war in all our live

Daytime variation in hepatitis C virus replication kinetics following liver transplant

Background: There is a growing interest in the role of circadian regulated pathways in disease pathogenesis. Methods: In a cohort of hepatitis C virus (HCV) infected patients undergoing liver transplantation, we observed differences in early viral infection kinetics of the allograft that associated with the time of liver transplant. Results: A higher frequency of subjects transplanted in the morning showed a rebound in viral RNA levels (n=4/6) during the first week post-surgery. In contrast, no viral rebound was observed in seven subjects transplanted in the afternoon. None of the other parameters previously reported to influence viral replication in the post-transplant setting, such as donor age, cold-ischemia time and length of surgery associated with viral rebound. Conclusions: These observation highlights a role for circadian processes to regulate HCV infection of the liver and warrants further investigation

OVERHEATED SECURITY? The Securitisation of Climate Change and the Governmentalisation of Security

Since the mid-2000s, climate change has become one of the defining security issues in political as well as academic debates and amongst others has repeatedly been discussed in the UN Security Council and countless high level government reports in various countries. Beyond the question whether the characterisation as ‘security issue’ is backed up by any robust empirical findings, this begs the question whether the ‘securitisation’ of climate change itself has had tangible political consequences. Moreover, within this research area there is still a lively discussion about which security conceptions apply, how to conceptualise (successful) securitisation and whether it is a (politically and normatively) desirable approach to deal with climate change. The aim of this dissertation is to shed light on these issues and particularly to contribute to a more thorough understanding of different forms or ‘discourses’ of securitisation and their political effects on a theoretical and empirical level. Theoretically, it conceptualises securitisation as resting on different forms of power, which are derived from Michel Foucault’s governmentality lectures. The main argument is that this framework allows me to better capture the ambiguous and diverse variants of securitisation and the ever-changing concept of security as well as to come to a more thorough understanding of the political consequences and powerful effects of constructing issues in terms of security. Empirically, the thesis looks at three country cases, namely the United States, Germany and Mexico. This comparative angle allows me to go beyond the existing literature on the securitisation of climate change that mostly looks at the global level, and to come to a more comprehensive and detailed understanding of different climate security discourses and their political consequences. Concerning the main results, the thesis finds that climate change has indeed been securitised very differently in the three countries and thus has facilitated diverse political consequences. These range from an incorporation of climate change into the defence sector in the US, the legitimisation of far-reaching climate policies in Germany, to the integration of climate change into several civil protection and agricultural insurance schemes in Mexico. Moreover, resting on different forms of power, the securitisation of climate change has played a key role in constructing specific actors and forms of knowledge as legitimate as well as in shaping certain identities in the face of the dangers of climate change. From a normative perspective, neither of these political consequences is purely good or bad but highly ambiguous and necessitates a careful, contextual assessment

Randomised clinical trial: Alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)

Background Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. Aim To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naïve patients with chronic HCV genotype 1 infection. Methods Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy. Results A total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose-dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for &gt;24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension. Conclusions Alisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment-naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon-free combination regimens