Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials

Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR. Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment. Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients. Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment

When are the hands of healthcare workers positive for methicillin-resistant Staphylococcus aureus?

Hand hygiene is a key component in reducing infection. There are few reports on the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on healthcare workers\u27 (HCWs\u27) hands. The aim of this study was to establish whether HCWs\u27 fingertips were contaminated with MRSA in a clinical hospital setting. The study was conducted in an acute tertiary referral hospital on four MRSA wards that were part of a larger research study on MRSA epidemiology and four other wards not included in the study. The fingertips from all categories of 523 HCWs were sampled on 822 occasions by the imprinting of fingertips on MRSA chromogenic agar plates. The type of hand hygiene agent used, if any, and the immediate prior activity of the HCW were recorded. Overall, 38/822 (5%) fingertips from 523 HCWs were MRSA-positive; 12/194 (6%) after clinical contact, 10/138 (10%) after contact with the patient\u27s environment and 15/346 (4%) after no specific contact. MRSA was recovered on 2/61 (3%) occasions after use of alcohol hand rub, 2/35 (6%) after 4% chlorhexidine detergent, 7/210 (3%) hand washing with soap and water, and 27/493 (5%) when no hand hygiene had been performed. MRSA was recovered from HCWs on seven of the eight wards. MRSA was more frequently present on fingertips on the four non-study wards vs the four MRSA study wards [18/250 (7%), 3/201 (1%), respectively; P\u3c=0.004]. The isolation of MRSA from HCWs\u27 fingertips, including after hand hygiene, indicates that more educational programmes are necessary to improve the quality of hand hygiene to prevent transmission of MRSA

Electronic Structure and Valence Band Spectra of Bi4Ti3O12

The x-ray photoelectron valence band spectrum and x-ray emission valence-band spectra (Ti K _beta_5, Ti L_alpha, O K_alpha) of Bi4Ti3O12 are presented (analyzed in the common energy scale) and interpreted on the basis of a band-structure calculation for an idealized I4/mmm structure of this material.Comment: 6 pages + 7 PostScript figures, RevTex3.0, to be published in Phys.Rev.B52 (Oct.95). Figures also available via anonymous ftp at ftp://ftp.physik.uni-osnabrueck.de/pub/apostnik/BiTiO

Developing an objective indicator of fatigue: An alternative mobile version of the Psychomotor Vigilance Task (m-PVT)

Approximately 20% of the working population report symptoms of feeling fatigued at work. The aim of the study was to investigate whether an alternative mobile version of the ‘gold standard’ Psychomotor Vigilance Task (PVT) could be used to provide an objective indicator of fatigue in staff working in applied safety critical settings such as train driving, hospital staffs, emergency services, law enforcements, etc., using different mobile devices. 26 participants mean age 20 years completed a 25-min reaction time study using an alternative mobile version of the Psychomotor Vigilance Task (m-PVT) that was implemented on either an Apple iPhone 6s Plus or a Samsung Galaxy Tab 4. Participants attended two sessions: a morning and an afternoon session held on two consecutive days counterbalanced. It was found that the iPhone 6s Plus generated both mean speed responses (1/RTs) and mean reaction times (RTs) that were comparable to those observed in the literature while the Galaxy Tab 4 generated significantly lower 1/RTs and slower RTs than those found with the iPhone 6s Plus. Furthermore, it was also found that the iPhone 6s Plus was sensitive enough to detect lower mean speed of responses (1/RTs) and significantly slower mean reaction times (RTs) after 10-min on the m-PVT. In contrast, it was also found that the Galaxy Tab 4 generated mean number of lapses that were significant after 5-min on the m-PVT. These findings seem to indicate that the m-PVT could be used to provide an objective indicator of fatigue in staff working in applied safety critical settings such as train driving, hospital staffs, emergency services, law enforcements, etc

Subjective hunger, gastric upset, and sleepiness in response to altered meal timing during simulated shiftwork

Shiftworkers report eating during the night when the body is primed to sleep. This study investigated the impact of altering food timing on subjective responses. Healthy participants (n = 44, 26 male, age Mean ± SD = 25.0 ± 2.9 years, BMI = 23.82 ± 2.59kg/m2) participated in a 7-day simulated shiftwork protocol. Participants were randomly allocated to one of three eating conditions. At 00:30, participants consumed a meal comprising 30% of 24 h energy intake (Meal condition; n = 14, 8 males), a snack comprising 10% of 24 h energy intake (Snack condition; n = 14; 8 males) or did not eat during the night (No Eating condition; n = 16, 10 males). Total 24 h individual energy intake and macronutrient content was constant across conditions. During the night, participants reported hunger, gut reaction, and sleepiness levels at 21:00, 23:30, 2:30, and 5:00. Mixed model analyses revealed that the snack condition reported significantly more hunger than the meal group (p < 0.001) with the no eating at night group reporting the greatest hunger (p < 0.001). There was no difference in desire to eat between meal and snack groups. Participants reported less sleepiness after the snack compared to after the meal (p < 0.001) or when not eating during the night (p < 0.001). Gastric upset did not differ between conditions. A snack during the nightshift could alleviate hunger during the nightshift without causing fullness or increased sleepiness.Charlotte C Gupta, Stephanie Centofanti, Jillian Dorrian , Alison M Coates, Jacqueline M Stepien, David Kennaway, Gary Wittert, Leonie Heilbronn, Peter Catcheside, Manny Noakes, Daniel Coro, Dilushi Chandrakumar and Siobhan Bank

It’s not just what you eat but when: The impact of eating a meal during simulated shift work on driving performance

Published online: 13 Oct 2016.Shiftworkers have impaired performance when driving at night and they also alter their eating patterns during nightshifts. However, it is unknown whether driving at night is influenced by the timing of eating. This study aims to explore the effects of timing of eating on simulated driving performance across four simulated nightshifts. Healthy, non-shiftworking males aged 18-35 years (n = 10) were allocated to either an eating at night (n = 5) or no eating at night (n = 5) condition. During the simulated nightshifts at 1730, 2030 and 0300 h, participants performed a 40-min driving simulation, 3-min Psychomotor Vigilance Task (PVT-B), and recorded their ratings of sleepiness on a subjective scale. Participants had a 6-h sleep opportunity during the day (1000-1600 h). Total 24-h food intake was consistent across groups; however, those in the eating at night condition ate a large meal (30% of 24-h intake) during the nightshift at 0130 h. It was found that participants in both conditions experienced increased sleepiness and PVT-B impairments at 0300 h compared to 1730 and 2030 h (p < 0.001). Further, at 0300 h, those in the eating condition displayed a significant decrease in time spent in the safe zone (p < 0.05; percentage of time within 10 km/h of the speed limit and 0.8 m of the centre of the lane) and significant increases in speed variability (p < 0.001), subjective sleepiness (p < 0.01) and number of crashes (p < 0.01) compared to those in the no eating condition. Results suggest that, for optimal performance, shiftworkers should consider restricting food intake during the night.Charlotte C. Gupta, Jill Dorrian, Crystal L. Grant, Maja Pajcin, Alison M. Coates, David J. Kennaway, Gary A. Wittert, Leonie K. Heilbronn, Chris B. Della Vedova, and Siobhan Bank

How much is left in your "sleep tank"? Proof of concept for a simple model for sleep history feedback

Available online 07 May 2018Technology-supported methods for sleep recording are becoming increasingly affordable. Sleep history feedback may help with fatigue-related decision making - Should I drive? Am I fit for work? This study examines a "sleep tank" model (SleepTank™), which is analogous to the fuel tank in a car, refilled by sleep, and depleted during wake. Required inputs are sleep period time and sleep efficiency (provided by many consumer-grade actigraphs). Outputs include suggested hours remaining to "get sleep" and percentage remaining in tank (Tank%). Initial proof of concept analyses were conducted using data from a laboratory-based simulated nightshift study. Ten, healthy males (18-35y) undertook an 8h baseline sleep opportunity and daytime performance testing (BL), followed by four simulated nightshifts (2000 h-0600 h), with daytime sleep opportunities (1000 h-1600 h), then an 8 h night-time sleep opportunity to return to daytime schedule (RTDS), followed by daytime performance testing. Psychomotor Vigilance Task (PVT) and Karolinska Sleepiness Scale were performed at 1200 h on BL and RTDS, and at 1830 h, 2130 h 0000 h and 0400 h each nightshift. A 40-minute York Driving Simulation was performed at 1730 h, 2030 h and 0300 h on each nightshift. Model outputs were calculated using sleep period timing and sleep efficiency (from polysomnography) for each participant. Tank% was a significant predictor of PVT lapses (p < 0.001), and KSS (p < 0.001), such that every 5% reduction resulted in an increase of two lapses, or one point on the KSS. Tank% was also a significant predictor of %time in the Safe Zone from the driving simulator (p = 0.001), such that every 1% increase in the tank resulted in a 0.75% increase in time spent in the Safe Zone. Initial examination of the correspondence between model predictions and performance and sleepiness measures indicated relatively good predictive value. Results provide tentative evidence that this "sleep tank" model may be an informative tool to aid in individual decision-making based on sleep history.Jillian Dorrian, Steven Hursh, Lauren Waggoner, Crystal Grant, Maja Pajcin, Charlotte Gupta, Alison Coates, David Kennaway, Gary Wittert, Leonie Heilbronn, Chris Della Vedova, Siobhan Bank

Healthcare Staff Wellbeing, Burnout, and Patient Safety: A Systematic Review

Objective To determine whether there is an association between healthcare professionals’ wellbeing and burnout, with patient safety. Design Systematic research review. Data Sources PsychInfo (1806 to July 2015), Medline (1946 to July 2015), Embase (1947 to July 2015) and Scopus (1823 to July 2015) were searched, along with reference lists of eligible articles. Eligibility Criteria for Selecting Studies Quantitative, empirical studies that included i) either a measure of wellbeing or burnout, and ii) patient safety, in healthcare staff populations. Results Forty-six studies were identified. Sixteen out of the 27 studies that measured wellbeing found a significant correlation between poor wellbeing and worse patient safety, with six additional studies finding an association with some but not all scales used, and one study finding a significant association but in the opposite direction to the majority of studies. Twenty-one out of the 30 studies that measured burnout found a significant association between burnout and patient safety, whilst a further four studies found an association between one or more (but not all) subscales of the burnout measures employed, and patient safety. Conclusions Poor wellbeing and moderate to high levels of burnout are associated, in the majority of studies reviewed, with poor patient safety outcomes such as medical errors, however the lack of prospective studies reduces the ability to determine causality. Further prospective studies, research in primary care, conducted within the UK, and a clearer definition of healthcare staff wellbeing are needed. Implications This review illustrates the need for healthcare organisations to consider improving employees’ mental health as well as creating safer work environments when planning interventions to improve patient safety

Children’s participation in school grounds developments: creating a place for education that promotes children’s social inclusion

Abstract This paper advances the idea that &lsquo;education for the social inclusion of children&rsquo; is similar but different to &lsquo;inclusive education&rsquo; as it has come to be understood and used by some authors and UK government documents. &lsquo;Inclusive education&rsquo; tends to carry an inward emphasis on the participation of children in the education system (with discussions on school culture, transitions, truancy, exclusion rates, underachievement, and school leaving age). In contrast, education for the promotion of children&rsquo;s social inclusion requires an outward emphasis on children's participation in 'mainstream' society while they are still children. The latter emphasis is seen to be lacking in educational policy discourse in Scotland though a recent shift in policy towards education for active citizenship is noted. Examples are provided to show how many policy statements enact a limitation on the scope for education to promote children&rsquo;s social inclusion by emphasising children&rsquo;s deficits as social actors and focussing on the &lsquo;condition&rsquo; of social exclusion. The paper draws on an empirical study of children&rsquo;s participation in changing school grounds in Scotland. The analysis shows how the enclosure of learning in books, classrooms and normative curricula was challenged. Learning from school grounds developments was constructed relationally and spatially but the scope of what was to be learned was often delineated by adults. The paper closes with a discussion of how education that promotes the social inclusion of children will benefit from seeing both children and adults as current though partial citizens and utilising socio-spatial opportunities for the generation of uncertain curricula through their shared and/or differentiated participation