A multivariant recall-by-genotype study of the metabolomic signature of BMI

OBJECTIVE: This study estimated the effect of BMI on circulating metabolites in young adults using a recall‐by‐genotype study design. METHODS: A recall‐by‐genotype study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low versus high genetic liability for higher BMI defined by a genetic risk score (GRS). Regression analyses were performed to investigate associations between BMI GRS group and relative abundance of 973 metabolites. RESULTS: After correction for multiple testing, 29 metabolites were associated with BMI GRS group. Bilirubin was among the most strongly associated metabolites, with reduced levels measured in individuals in the high‐BMI GRS group (β = −0.32, 95% CI: −0.46 to −0.18, Benjamini‐Hochberg adjusted p = 0.005). This study observed associations between BMI GRS group and the levels of several potentially diet‐related metabolites, including hippurate, which had lower mean abundance in individuals in the high‐BMI GRS group (β = −0.29, 95% CI: −0.44 to −0.15, Benjamini‐Hochberg adjusted p = 0.008). CONCLUSIONS: Together with existing literature, these results suggest that a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging

The Effect of Pre-Analytical Conditions on Blood Metabolomics in Epidemiological Studies

Serum and plasma are commonly used in metabolomic-epidemiology studies. Their metabolome is susceptible to differences in pre-analytical conditions and the impact of this is unclear. Participant-matched EDTA-plasma and serum samples were collected from 37 non-fasting volunteers and profiled using a targeted nuclear magnetic resonance (NMR) metabolomics platform (n = 151 traits). Correlations and differences in mean of metabolite concentrations were compared between reference (pre-storage: 4 °C, 1.5 h; post-storage: no buffer addition delay or NMR analysis delay) and four pre-storage blood processing conditions, where samples were incubated at (i) 4 °C, 24 h; (ii) 4 °C, 48 h; (iii) 21 °C, 24 h; and (iv) 21 °C, 48 h, before centrifugation; and two post-storage sample processing conditions in which samples thawed overnight (i) then left for 24 h before addition of sodium buffer followed by immediate NMR analysis; and (ii) addition of sodium buffer, then left for 24 h before NMR profiling. We used multilevel linear regression models and Spearman’s rank correlation coefficients to analyse the data. Most metabolic traits had high rank correlation and minimal differences in mean concentrations between samples subjected to reference and the different conditions tested, that may commonly occur in studies. However, glycolysis metabolites, histidine, acetate and diacylglycerol concentrations may be compromised and this could bias results in association/causal analyses

Effectiveness and cost-effectiveness of a group-based pain self-management intervention for patients undergoing total hip replacement: Feasibility study for a randomized controlled trial

Background: Total hip replacement (THR) is a common elective surgical procedure and can be effective for reducing chronic pain. However, waiting times can be considerable. A pain self-management intervention may provide patients with skills to more effectively manage their pain and its impact during their wait for surgery. This study aimed to evaluate the feasibility of conducting a randomized controlled trial to assess the effectiveness and cost-effectiveness of a group-based pain self-management course for patients undergoing THR.Methods: Patients listed for a THR at one orthopedic center were posted a study invitation pack. Participants were randomized to attend a pain self-management course plus standard care or standard care only. The lay-led course was delivered by Arthritis Care and consisted of two half-day sessions prior to surgery and one full-day session after surgery. Participants provided outcome and resource-use data using a diary and postal questionnaires prior to surgery and one month, three months and six months after surgery. Brief telephone interviews were conducted with non-participants to explore barriers to participation.Results: Invitations were sent to 385 eligible patients and 88 patients (23%) consented to participate. Interviews with 57 non-participants revealed the most common reasons for non-participation were views about the course and transport difficulties. Of the 43 patients randomized to the intervention group, 28 attended the pre-operative pain self-management sessions and 11 attended the post-operative sessions. Participant satisfaction with the course was high, and feedback highlighted that patients enjoyed the group format. Retention of participants was acceptable (83% of recruited patients completed follow-up) and questionnaire return rates were high (72% to 93%), with the exception of the pre-operative resource-use diary (35% return rate). Resource-use completion rates allowed for an economic evaluation from the health and social care payer perspective.Conclusions: This study highlights the importance of feasibility work prior to a randomized controlled trial to assess recruitment methods and rates, barriers to participation, logistics of scheduling group-based interventions, acceptability of the intervention and piloting resource use questionnaires to improve data available for economic evaluations. This information is of value to researchers and funders in the design and commissioning of future research.Trial registration: Current Controlled Trials ISRCTN52305381. © 2014 Wylde et al.; licensee BioMed Central Ltd

Association of Maternal Smoking With Child Cotinine Levels

INTRODUCTION: Our aim was to understand the strength of association between parental smoking and child environmental tobacco smoke (ETS) exposure in order to inform the development of future tobacco control policies. ETS was measured using child cotinine levels below the active smoking threshold. METHODS: Participants were drawn from the Avon Longitudinal Study of Parents and Children and included 3,128 participants at age 7 years and 1,868 participants at age 15 years. The primary outcome was cotinine levels of nonsmoking children, to investigate the relationship between maternal smoking and child cotinine levels. The secondary outcome was cotinine levels of all individuals to investigate the relationship between child smoking and child cotinine levels. Maternal and child smoking behavior was assessed by self-report questionnaire. We adjusted for several sociodemographic variables. RESULTS: We found an association between maternal smoking and child cotinine at age 7 years (mean cotinine = 1.16ng/ml serum, ratio of geometric means = 3.94, 95% CI = 2.86–5.42) and at age 15 years (mean cotinine = 0.94ng/ml serum, ratio of geometric means = 5.26, 95% CI = 3.06–9.03), after adjustment for potential confounders. CONCLUSIONS: The magnitude of this association for children whose mothers were heavy smokers was comparable with the quantity of half the levels of cotinine observed among children who were irregular (i.e., nonweekly) active smokers, and it was greater than five times higher than that seen in nonsmoking children whose mothers didn’t smoke. This provides further evidence for the importance of public health interventions to reduce smoking exposure in the home

Palliative Care for a Mentally Incompetent End Stage Renal Failure Patient: Why Is It Important?

People with intellectual disabilities are among the most disadvantaged groups in society. Here we report a mentally incompetent end stage renal failure (ESRF) patient with frequent emergency visits who made a significant improvement in symptoms control and reduction in casualty visits after introduction of renal palliative care service. Multidisciplinary approach would be useful in this case

Finding My Way: Protocol of a randomised controlled trial evaluating an internet self-help program for cancer-related distress

Background\ud \ud A cancer diagnosis elicits greater distress than any other medical diagnosis, and yet very few studies have evaluated the efficacy of structured online self-help therapeutic programs to alleviate this distress. This study aims to assess the efficacy over time of an internet Cognitive Behaviour Therapy (iCBT) intervention (‘Finding My Way’) in improving distress, coping and quality of life for individuals with a recent diagnosis of early stage cancer of any type.\ud \ud Methods/Design\ud \ud The study is a multi-site Randomised Controlled Trial (RCT) seeking to enrol 188 participants who will be randomised to either the Finding My Way Intervention or an attention-control condition. Both conditions are delivered online; with 6 modules released once per week, and an additional booster module released one month after program-completion. Participants complete online questionnaires on 4 occasions: at baseline (immediately prior to accessing the modules); post-treatment (immediately after program-completion); then three and six months later. Primary outcomes are general distress and cancer-specific distress, with secondary outcomes including Health-Related Quality of Life (HRQoL), coping, health service utilisation, intervention adherence, and user satisfaction. A range of baseline measures will be assessed as potential moderators of outcomes. Eligible participants are individuals recently diagnosed with any type of cancer, being treated with curative intent, aged over 18 years with sufficient English language literacy, internet access and an active email account and phone number. Participants are blinded to treatment group allocation. Randomisation is computer generated and stratified by gender.\ud \ud Discussion\ud \ud Compared to the few prior published studies, Finding My Way will be the first adequately powered trial to offer an iCBT intervention to curatively treated patients of heterogeneous cancer types in the immediate post-diagnosis/treatment period. If found efficacious, Finding My Way will assist with overcoming common barriers to face-to-face therapy in a cost-effective and accessible way, thus helping to reduce distress after cancer diagnosis and consequently decrease the cancer burden for individuals and the health system.\ud \ud Trial registration\ud \ud Australian New Zealand Clinical Trials Registry ACTRN12613000001​796 16.10.1