High dose atorvastatin associated with increased risk of significant hepatotoxicity in comparison to simvastatin in UK GPRD cohort

Background and Aims: Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods: The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results: Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions: The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small

The Relationship Between Collision History and a Computerized Assessment of Visual and Cognitive Skills in a Sample of School Bus Drivers

The objective of this study was to explore whether measures of visual and cognitive performance in a safe computerized driving environment were associated with collision involvement and the cost of collisions in a sample of professional motor vehicle operators. One hundred and nine (109) school bus drivers in a large metropolitan area were asked to take a 15-minute interactive computer-based driving assessment. The skills included visual target identification, scanning in four directions, divided-attention, reaction time, steering smoothness, false positive responses, and evasive maneuvers. An overall score validated in previous research summarized each driver’s performance. Each driver’s collision history over the last three years was then compared to the driving assessment scores. Collision data included collision type, frequency, and damage cost associated with each incident. Drivers with collisions (n = 27) were compared to drivers with no collisions (n = 82). Drivers with collisions had significantly lower overall scanning and steering smoothness scores than drivers without collisions. Drivers with collisions also had significantly higher braking and target false-positive scores, indicating disorientation. The total cost of collisions for the lower 40th percentile test scores was $42,261, whereas the cost for the upper 60th percentile was$10,314. The results indicate that drivers who are prone to become disoriented and overwhelmed in a high-demand computerized assessment were more likely to have had collisions on the road. The relationship between collision cost/incidence and test scores suggests that a sufficiently complex and rapidly paced computerized assessment has utility in identifying drivers who would benefit from remedial training

The Relationship Between Collision History and a Computerized Assessment of Visual and Cognitive Skills in a Sample of School Bus Drivers

The objective of this study was to explore whether measures of visual and cognitive performance in a safe computerized driving environment were associated with collision involvement and the cost of collisions in a sample of professional motor vehicle operators. One hundred and nine (109) school bus drivers in a large metropolitan area were asked to take a 15-minute interactive computer-based driving assessment. The skills included visual target identification, scanning in four directions, divided-attention, reaction time, steering smoothness, false positive responses, and evasive maneuvers. An overall score validated in previous research summarized each driver’s performance. Each driver’s collision history over the last three years was then compared to the driving assessment scores. Collision data included collision type, frequency, and damage cost associated with each incident. Drivers with collisions (n = 27) were compared to drivers with no collisions (n = 82). Drivers with collisions had significantly lower overall scanning and steering smoothness scores than drivers without collisions. Drivers with collisions also had significantly higher braking and target false-positive scores, indicating disorientation. The total cost of collisions for the lower 40th percentile test scores was $42,261, whereas the cost for the upper 60th percentile was$10,314. The results indicate that drivers who are prone to become disoriented and overwhelmed in a high-demand computerized assessment were more likely to have had collisions on the road. The relationship between collision cost/incidence and test scores suggests that a sufficiently complex and rapidly paced computerized assessment has utility in identifying drivers who would benefit from remedial training

The effect of high correlated colour temperature office lighting on employee wellbeing and work performance

BACKGROUND: The effects of lighting on the human circadian system are well-established. The recent discovery of 'non-visual' retinal receptors has confirmed an anatomical basis for the non-image forming, biological effects of light and has stimulated interest in the use of light to enhance wellbeing in the corporate setting. METHODS: A prospective controlled intervention study was conducted within a shift-working call centre to investigate the effect of newly developed fluorescent light sources with a high correlated colour temperature (17000 K) upon the wellbeing, functioning and work performance of employees. Five items of the SF-36 questionnaire and a modification of the Columbia Jet Lag scale, were used to evaluate employees on two different floors of the call centre between February and May 2005. Questionnaire completion occurred at baseline and after a three month intervention period, during which time one floor was exposed to new high correlated colour temperature lighting and the other remained exposed to usual office lighting. Two sided t-tests with Bonferroni correction for type I errors were used to compare the characteristics of the two groups at baseline and to evaluate changes in the intervention and control groups over the period of the study. RESULTS: Individuals in the intervention arm of the study showed a significant improvement in self-reported ability to concentrate at study end as compared to those within the control arm (p < 0.05). The mean individual score on a 5 point Likert scale improved by 36.8% in the intervention group, compared with only 1.7% in the control group. The majority of this improvement occurred within the first 7 weeks of the 14 week study. Substantial within group improvements were observed in the intervention group in the areas of fatigue (26.9%), alertness (28.2%), daytime sleepiness (31%) and work performance (19.4%), as assessed by the modified Columbia Scale, and in the areas of vitality (28.4%) and mental health (13.9%), as assessed by the SF-36 over the study period. CONCLUSION: High correlated colour temperature fluorescent lights could provide a useful intervention to improve wellbeing and productivity in the corporate setting, although further work is necessary in quantifying the magnitude of likely benefits

THE CONTRIBUTION OF ELBOW EXTENSION TO WRIST SPEED IN CRICKET FAST BOWLERS

The purpose of this modelling study was to assess the sensitivity of wrist joint speed to systematic manipulations of empirical elbow joint flexion-extension kinematic profiles. The joint kinematic profiles of 12 cricket fast bowlers were entered into a Forward Kinematic Model and the elbow joint kinematic profiles were subsequently amplified to elicit wrist speed changes. An amplification factor of zero decreased wrist speed by a mean of 8.6% (± 6.9%), whereas an amplification factor of two increased speed by a mean of 8.8% (± 7.1%). An opposite relationship was found for two participants who extended the elbow joint prior to release and it is proposed that an internally rotated humerus will displace the wrist joint posteriorly when the elbow joint is extending

Tracking TCRß sequence clonotype expansions during antiviral therapy using high-throughput sequencing of the hypervariable region

To maintain a persistent infection viruses such as hepatitis C virus (HCV) employ a range of mechanisms that subvert protective T cell responses. The suppression of antigen-specific T cell responses by HCV hinders efforts to profile T cell responses during chronic infection and antiviral therapy. Conventional methods of detecting antigen-specific T cells utilize either antigen stimulation (e.g., ELISpot, proliferation assays, cytokine production) or antigen-loaded tetramer staining. This limits the ability to profile T cell responses during chronic infection due to suppressed effector function and the requirement for prior knowledge of antigenic viral peptide sequences. Recently, high-throughput sequencing (HTS) technologies have been developed for the analysis of T cell repertoires. In the present study, we have assessed the feasibility of HTS of the TCRβ complementarity determining region (CDR)3 to track T cell expansions in an antigen-independent manner. Using sequential blood samples from HCV-infected individuals undergoing antiviral therapy, we were able to measure the population frequencies of &gt;35,000 TCRβ sequence clonotypes in each individual over the course of 12 weeks. TRBV/TRBJ gene segment usage varied markedly between individuals but remained relatively constant within individuals across the course of therapy. Despite this stable TRBV/TRBJ gene segment usage, a number of TCRβ sequence clonotypes showed dramatic changes in read frequency. These changes could not be linked to therapy outcomes in the present study; however, the TCRβ CDR3 sequences with the largest fold changes did include sequences with identical TRBV/TRBJ gene segment usage and high junction region homology to previously published CDR3 sequences from HCV-specific T cells targeting the HLA-B*0801-restricted 1395HSKKKCDEL1403 and HLA-A*0101-restricted 1435ATDALMTGY1443 epitopes. The pipeline developed in this proof of concept study provides a platform for the design of future experiments to accurately address the question of whether T cell responses contribute to SVR upon antiviral therapy. This pipeline represents a novel technique to analyze T cell dynamics in situations where conventional antigen-dependent methods are limited due to suppression of T cell functions and highly diverse antigenic sequences

The prevalence of hepatitis C virus among people of South Asian origin in Glasgow: results from a community based survey and laboratory surveillance

Background South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. Methods A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. Results In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. Conclusions South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted.</p

Estimating Population Abundance with a Mixture of Physical Capture and PIT Tag Antenna Detection Data

The inclusion of passive interrogation antenna (PIA) detection data has promise to increase precision of population abundance estimates (Nˆ ). However, encounter probabilities are often higher for PIAs than for physical capture. If the difference is not accounted for, Nˆ may be biased. Using simulations, we estimated the magnitude of bias resulting from mixed capture and detection probabilities and evaluated potential solutions for removing the bias for closed capture models. Mixing physical capture and PIA detections (pdet) resulted in negative biases in Nˆ . However, using an individual covariate to model differences removed bias and improved precision. From a case study of fish making spawning migrations across a stream-wide PIA (pdet ≤ 0.9), the coefficient of variation (CV) of Nˆ declined 39%–82% when PIA data were included, and there was a dramatic reduction in time to detect a significant change in Nˆ . For a second case study, with modest pdet (≤0.2) using smaller PIAs, CV (Nˆ ) declined 4%–18%. Our method is applicable for estimating abundance for any situation where data are collected with methods having different capture–detection probabilities