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.

Post awakening salivary cortisol secretion and trait well-being: The importance of sample timing accuracy

Indices of post awakening cortisol secretion (PACS), include the rise in cortisol(cortisol awakening response: CAR) and overall cortisol concentrations (e.g. area under the curve with reference to ground: AUCg) in the first 30—45 min. Both are commonly investigated in relation to psychosocial variables. Although sampling within the domestic setting is ecologically valid, participant non-adherence to the required timing protocol results in erroneous measurement of PACS and this may explain discrepancies in the literature linking these measures to trait well-being (TWB). We have previously shown that delays of little over 5 min(between awakening and the start of sampling) to result in erroneous CAR estimates. In this study, we report for the first time on the negative impact of sample timing inaccuracy (verified by electronic-monitoring) on the efficacy to detect significant relationships between PACS and TWB when measured in the domestic setting.Healthy females (N = 49, 20.5 ± 2.8 years) selected for differences in TWB collected saliva samples (S1—4) on 4 days at 0, 15, 30, 45 min post awakening, to determine PACS. Adherence to the sampling protocol was objectively monitored using a combination of electronic estimates of awakening (actigraphy) and sampling times (track caps).Relationships between PACS and TWB were found to depend on sample timing accuracy. Lower TWB was associated with higher post awakening cortisol AUCg in proportion to the mean sample timing accuracy (p < .005). There was no association between TWB and the CAR even taking into account sample timing accuracy. These results highlight the importance of careful electronic monitoring of participant adherence for measurement of PACS in the domestic setting. Mean sample timing inaccuracy, mainly associated with delays of >5 min between awakening and collection of sample 1 (median = 8 min delay), negatively impacts on the sensitivity of analysis to detect associations between PACS and TWB.

How women use and experience western herbal practice for distress: implications for health care and self-management approaches.

Introduction: In the UK, common mental health disorders account for one in five of all work days lost, and cost employers £25bn each year. Herbal medicine has been shown to potentially be of use for mental distress, including conditions like anxiety. In 2008, 35% of British adults surveyed claimed to have used herbal medicine at some stage, the majority of whom were women. However, there is little research into how the users of western herbal medicine (WHM) experience the practice of herbal medicine, or how these experiences may change over time. Our research is studying women in the south-east of the UK who are suffering from distress (either as a primary complaint, or associated with another condition) who are seeking the services of a herbalist who practices WHM. Aim: To investigate the experiences of western herbal practice by women who are suffering with distress. Methods: The study is using semi-structured interviews of around thirty women, to elicit patient narratives at two time points. Thematic analysis is being used to consider how distressed women perceive and experience their distress, their reasons for using WHM, what contribution the women perceive the consultation and treatment with WHM may or may not make to their wellbeing, and whether their experiences change over time. Currently, sixteen women have been interviewed, and a preliminary thematic analysis has commenced. Results: Preliminary finding suggest that not only do women internalise their distress, but that they are surprisingly isolated in how they deal with it, whilst some also express social embarrassment about their experiences. The women perceived that their distress is not always considered seriously from their medical practitioners’ point of view. These women are drawn to herbalists not only in a search for effective treatment, but also to be given time to have their story heard, to form a collaborative relationship, and to attempt to regain some control of their life. The herbal treatment is valued due to its perceived naturalness, and reduced risk of adverse side effects. Nevertheless, WHM is just one of a number of self-care strategies that women utilise to help manage their distress. Discussion: Effective treatment is not only dependent upon the herbs, but also upon an effective therapeutic relationship. Feeling that the herbalist hears their story, provides a treatment plan that is individually tailored to the patient, and is available (even outside of the consultation) are all important in helping to establish this relationship.