The predictive value of quantitative nucleic acid amplification detection of Clostridium difficile toxin gene for faecal sample toxin status and patient outcome.

BACKGROUND: Laboratory diagnosis of Clostridium difficile infection (CDI) remains unsettled, despite updated guidelines. We investigated the potential utility of quantitative data from a nucleic acid amplification test (NAAT) for C. difficile toxin gene (tg) for patient management. METHODS: Using data from the largest ever C. difficile diagnostic study (8853 diarrhoeal samples from 7335 patients), we determined the predicative value of C. difficile tgNAAT (Cepheid Xpert C.diff) low cycle threshold (CT) value for patient toxin positive status, CDI severity, mortality and CDI recurrence. Reference methods for CDI diagnosis were cytotoxicity assay (CTA) and cytotoxigenic culture (CTC). RESULTS: Of 1281 tgNAAT positive faecal samples, 713 and 917 were CTA and CTC positive, respectively. The median tgNAAT CT for patients who died was 25.5 vs 27.5 for survivors (p = 0.021); for toxin-positivity was 24.9 vs 31.6 for toxin-negative samples (p<0.001) and for patients with a recurrence episode was 25.6 vs 27.3 for those who did not have a recurrent episode (p = 0.111). Following optimal cut-off determination, low CT was defined as ≤25 and was significantly associated with a toxin-positive result (P<0.001, positive predictive value 83.9%), presence of PCR-ribotype 027 (P = 0.025), and mortality (P = 0.032). Recurrence was not associated with low CT (p 0.111). CONCLUSIONS: Low tgNAAT CT could indicate CTA positive patients, have more severe infection, increased risk of mortality and possibly recurrence. Although, the limited specificity of tgNAAT means it cannot be used as a standalone test, it could augment a more timely diagnosis, and optimise management of these at-risk patients

Restorative sleep predicts the resolution of chronic widespread pain: results from the EPIFUND study

PublishedJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tVersion of record of article published in Rheumatology (Oxford). 2008 Dec; 47(12): 1809–1813. Published online 2008 Oct 7. doi: 10.1093/rheumatology/ken389OBJECTIVES: Poor sleep is associated with chronic widespread pain (CWP). Conversely, good-quality sleep may play a role in the resolution of pain symptoms. Sleep is a multidimensional construct, comprising a number of diverse components. The aims of the current study were to examine the hypotheses that: (i) good sleep quality would predict the resolution of CWP, (ii) restorative sleep would predict the resolution of CWP and (iii) that these relationships would be independent of confounding psychological factors. METHODS: Subjects in a population-based prospective study completed a pain questionnaire at baseline from which subjects with CWP were identified. Baseline sleep was measured using the Estimation of Sleep Problems Scale which measures sleep onset, maintenance, early wakening and restorative sleep. The questionnaire also contained scales examining psychosocial status. Subjects were followed up 15 months later and pain status was assessed. RESULTS: A total of 1061 subjects reported CWP at baseline of whom 679 (75% of eligible subjects) responded at follow-up. Of those, a total of 300 (44%) no longer satisfied criteria for CWP. Univariate analysis revealed that three of the four sleep components were associated with the resolution of CWP: rapid sleep onset, odds ratio (OR) = 1.7, 95% CI 1.2, 2.5; absence of early wakening, OR = 1.6, 95% CI 1.1, 2.4; and restorative sleep, OR = 2.7, 95% CI 1.5, 4.8. After adjusting for the effect of psychosocial factors, which may have confounded the relationship, only restorative sleep (OR = 2.0, 95% CI 1.02, 3.8) was associated. CONCLUSIONS: Self-reported restorative sleep was independently associated with the resolution of CWP and return to musculoskeletal health.This study was funded by the Arthritis Research Campaign, Grant number: 1755

Promoting healthy weight in primary school children through physical activity and nutrition education: a pragmatic evaluation of the CHANGE! randomised intervention study

Background: This pragmatic evaluation investigated the effectiveness of the Children’s Health, Activity and Nutrition: Get Educated! (CHANGE!) Project, a cluster randomised intervention to promote healthy weight using an educational focus on physical activity and healthy eating. Methods: Participants (n = 318, aged 10–11 years) from 6 Intervention and 6 Comparison schools took part in the 20 weeks intervention between November 2010 and March/April 2011. This consisted of a teacher-led curriculum, learning resources, and homework tasks. Primary outcome measures were waist circumference, body mass index (BMI), and BMI z-scores. Secondary outcomes were objectively-assessed physical activity and sedentary time, and food intake. Outcomes were assessed at baseline, at post-intervention (20 weeks), and at follow-up (30 weeks). Data were analysed using 2-level multi-level modelling (levels: school, student) and adjusted for baseline values of the outcomes and potential confounders. Differences in intervention effect by subgroup (sex, weight status, socio-economic status) were explored using statistical interaction. Results: Significant between-group effects were observed for waist circumference at post-intervention (β for intervention effect =−1.63 (95% CI = −2.20, -1.07) cm, p<0.001) and for BMI z-score at follow-up (β=−0.24 (95% CI = −0.48, -0.003), p=0.04). At follow-up there was also a significant intervention effect for light intensity physical activity (β=25.97 (95% CI = 8.04, 43.89) min, p=0.01). Interaction analyses revealed that the intervention was most effective for overweight/obese participants (waist circumference: β=−2.82 (95% CI = −4.06, -1.58) cm, p<0.001), girls (BMI: β=−0.39 (95% CI = −0.81, 0.03) kg/m2, p=0.07), and participants with higher family socioeconomic status (breakfast consumption: β=8.82 (95% CI = 6.47, 11.16), p=0.07). Conclusions: The CHANGE! intervention positively influenced body size outcomes and light physical activity, and most effectively influenced body size outcomes among overweight and obese children and girls. The findings add support for the effectiveness of combined school-based physical activity and nutrition interventions. Additional work is required to test intervention fidelity and the sustained effectiveness of this intervention in the medium and long term

Epidemiology of foot complaints in systemic lupus erythematosus

Foot complaints are common in inflammatory arthropathies such as rheumatoid arthritis and cause considerable disability. However, little is known about the nature and extent of foot complaints in systemic lupus erythematosus (SLE) as highlighted by a recent systematic review [1]. We set out to explore the clinical features and symptoms of foot involvement among people with SLE from the patients' perspective

Adiposity, fitness, health-related quality of life and the reallocation of time between children’s school day activity behaviours: a compositional data analysis

Sedentary time (ST), light (LPA), and moderate-to-vigorous physical activity (MVPA) constitute the range of school day activity behaviours. This study investigated whether the composition of school activity behaviours was associated with health indicators, and the predicted changes in health when time was reallocated between activity behaviours. Accelerometers were worn for 7-days between October and December 2010 by 318 UK children aged 10-11, to provide estimates of school day ST, LPA, and MVPA. BMI z-scores and percent waist-to-height ratio were calculated as indicators of adiposity. Cardiorespiratory fitness (CRF) was assessed using the 20-m Shuttle Run Test. The PedsQLTM questionnaire was completed to assess psychosocial and physical health-related quality of life (HRQL). Log-ratio multiple linear regression models predicted health indicators for the mean school day activity composition, and for new compositions where fixed durations of time were reallocated from one activity behaviour to another, while the remaining behaviours were unchanged. The school day activity composition significantly predicted adiposity and CRF (p=0.04-0.002), but not HRQL. Replacing MVPA with ST or LPA around the mean activity composition predicted higher adiposity and lower CRF. When ST or LPA were substituted with MVPA, the relationships with adiposity and CRF were asymmetrical with favourable, but smaller predicted changes in adiposity and CRF than when MVPA was replaced. Predicted changes in HRQL were negligible. The school day activity composition significantly predicted adiposity and CRF but not HRQL. Reallocating time from ST and LPA to MVPA is advocated through comprehensive school physical activity promotion approaches

Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

This is the final version of the article. Available from Wiley via the DOI in this record.BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, β = 0.023, P = 0.01; highest, β = 0.021, P = 0.02), Digit Vigilance Task (lowest, β = 0.009, P = 0.05; highest, β = 0.01, P = 0.02) and Power of Attention (lowest, β = 0.017, P = 0.02; highest, β = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, β = 0.021, P = 0.02; highest, β = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.This work was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals Foundation Trust and Newcastle University (AG). The Newcastle 85+ Study has been funded by the Medical Research Council, Biotechnology and Biological Sciences Research Council and the Dunhill Medical Trust. Additional work has also been funded by the British Heart Foundation, Unilever Corporate Research, Newcastle University and National Health Service (NHS) North of Tyne (Newcastle Primary Care Trust). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service, UK. We acknowledge the operational support of NHS North of Tyne, the local general practitioners and their staff, the research nurses, laboratory technicians, data management and clerical team, as well as many colleagues for their expert advice. Thanks are due especially to the study participants

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A review of assessment methods for river hydromorphology

The work leading to this paper has received funding for the EU’s FP7 under Grant Agreement No. 282656 (REFORM

Eleanor Davies and the New Jerusalem

Eleanor Davies was a great believer in historical moments. In her first work—A Warning to the Dragon and All His Angels of 1625-she told readers that “The Lord is at the Dore.”1 This immanence of God made her watchful and purposeful, reading the signs in her daily life, counting days, weeks, and years because she believed that Christ would come again. His arrival had been predestined from the beginning of the world: “from the going forth of the Commandement, which is the beginning of the Creation to the building of the New Jerusalem, the second comming of Messiah, the Prince the Sonne of God, it shall be Seaven Weekes or Seaven Moneths.”2 For Davies, time was elastic, but history was absolute. What the biblical prophets (in this case Ezekiel) said would come to pass, really would come to pass, but their promises were oracular; they had complete authority but were also elusive. Davies accepted this. She knew that she was living in the latter days, but when it came to God’s final judgment, “the daye and houre knoweth no man.”3 God could not be known as such and what she called knowledge was a spiritual transformation that took place when “He powreth out his Spirit upon his hand-maidens,” like herself.4 This essay uses A Warning to the Dragon and Davies’ works of the 1630s and 1640s to examine her theology