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

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

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

A cell model for conditional profiling of androgen-receptor-interacting proteins.

Partial androgen insensitivity syndrome (PAIS) is associated with impaired male genital development and can be transmitted through mutations in the androgen receptor (AR). The aim of this study is to develop a cell model suitable for studying the impact AR mutations might have on AR interacting proteins. For this purpose, male genital development relevant mouse cell lines were genetically modified to express a tagged version of wild-type AR, allowing copurification of multiprotein complexes under native conditions followed by mass spectrometry. We report 57 known wild-type AR-interacting proteins identified in cells grown under proliferating and 65 under nonproliferating conditions. Of those, 47 were common to both samples suggesting different AR protein complex components in proliferating and proliferation-inhibited cells from the mouse proximal caput epididymus. These preliminary results now allow future studies to focus on replacing wild-type AR with mutant AR to uncover differences in protein interactions caused by AR mutations involved in PAIS.Peer Reviewe

Pre-Meal Whey Protein Alters Postprandial Insulinemia by Enhancing β-Cell Function and Reducing Insulin Clearance in T2D

CONTEXT: Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on β-cell function and insulin kinetics remains unclear. OBJECTIVE: To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and β-cell function. METHODS: This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and β-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured. RESULTS: β-cell function was 40% greater after WP (P = .001) and was accompanied with a -22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (-1.5 mmol/L and -16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133). CONCLUSION: In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in β-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further β-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146 Website link: www.isrctn.com/ISRCTN17563146

"We also deserve help during the pandemic": The effect of the COVID-19 pandemic on foreign domestic workers in Hong Kong.

The coronavirus disease 2019 (COVID-19) pandemic poses particular challenges for migrant workers around the world. This study explores the unique experiences of foreign domestic workers (FDWs) in Hong Kong, and how COVID-19 impacted their health and economic wellbeing. Interviews with FDWs (n = 15) and key informants (n = 3) were conducted between May and August 2020. FDWs reported a dual-country experience of the pandemic, where they expressed concerns about local transmission risks as well as worries about their family members in their home country. Changes to their current work situation included how their employers treated them, as well as their employment status. FDWs also cited blind spots in the Hong Kong policy response that also affected their experience of the pandemic, including a lack of support from the Hong Kong government. Additional support is needed to mitigate the particularly negative effects of the pandemic on FDWs

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

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

The Clinical Application of Mealtime Whey Protein for the Treatment of Postprandial Hyperglycaemia for People With Type 2 Diabetes: A Long Whey to Go

© Copyright © 2020 Smith, Bowden Davies, Stevenson and West. Mitigating postprandial hyperglycaemic excursions may be effective in not only enhancing glycaemic control for people with type 2 diabetes but also reducing the onset of diabetes-related complications. However, there are growing concerns over the long-term efficacy of anti-hyperglycaemic pharmacotherapies, which coupled with their rising financial costs, underlines the need for further non-pharmaceutical treatments to regulate postprandial glycaemic excursions. One promising strategy that acutely improves postprandial glycaemia for people with type 2 diabetes is through the provision of mealtime whey protein, owing to the slowing of gastric emptying and increased secretion of insulin and the incretin peptides. The magnitude of this effect appears greater when whey protein is consumed before, rather than with, a meal. Herein, this dietary tool may offer a simple and inexpensive strategy in the management of postprandial hyperglycaemia for people with type 2 diabetes. However, there are insufficient long-term studies that have investigated the use of mealtime whey protein as a treatment option for individuals with type 2 diabetes. The methodological approaches applied in acute studies and outcomes reported may also not portray what is achievable long-term in practice. Therefore, studies are needed to refine the application of this mealtime strategy to maximize its clinical potential to treat hyperglycaemia and to apply these long-term to address key components of successful diabetes care. This review discusses evidence surrounding the provision of mealtime whey protein to treat postprandial hyperglycaemia in individuals with type 2 diabetes and highlights areas to help facilitate its clinical application