Investigating the relationships between unfavourable habitual sleep and metabolomic traits:evidence from multi-cohort multivariable regression and Mendelian randomization analyses

BACKGROUND: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease.METHODS: We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions.RESULTS: We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures.CONCLUSIONS: Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.</p

Supplemental Material - Variations in policies for accessing elective musculoskeletal procedures in the English National Health Service: A documentary analysis

Supplementary Material for Variations in policies for accessing elective musculoskeletal procedures in the English National Health Service: A documentary analysis by Leila Rooshenas, Sharea Ijaz, Alison Richards, Alba Realpe, Jelena Savovic, Tim Jones, William Hollingworth and Jenny Donovan in Journal of Health Services Research &amp; Policy

Supplemental Material - Variations in policies for accessing elective musculoskeletal procedures in the English National Health Service: A documentary analysis

Supplementary Material for Variations in policies for accessing elective musculoskeletal procedures in the English National Health Service: A documentary analysis by Leila Rooshenas, Sharea Ijaz, Alison Richards, Alba Realpe, Jelena Savovic, Tim Jones, William Hollingworth and Jenny Donovan in Journal of Health Services Research &amp; Policy

A longitudinal study of the associations of children's body mass index and physical activity with blood pressure – dataset

B-Proact1v is a longitudinal study examining changes in children’s physical activity and sedentary behaviours as they progress through primary school. In 2012-2013, 1299 Year 1 children (median age: 6 years) were recruited from 57 schools in greater Bristol, UK (total number of eligible children: 2600; recruitment rate: 50.0%). Following this, data were collected from 1223 Year 4 children (median age: 9 years) from 47 of the original schools between March 2015 and July 2016 (total number of eligible children: 2047; recruitment rate: 59.7%). This included 685 children from the original sample. This dataset represents a subset of the B-Proact1v data to examine the longitudinal associations of children’s body mass index and physical activity with blood pressure. Included in this repository is the dataset and a data dictionary. The dataset includes the variables that underlie the findings in a manuscript entitled ‘A longitudinal study of the associations of children’s body mass index and physical activity with blood pressure’ that has been submitted to PLOS ONE. This dataset has been made available so that future researchers can replicate the study findings using the data. If you wish to use the data for any purpose other than replicating the study findings, please contact the Principal Investigator Professor Russ Jago ([email protected]) to discuss this

B-Proact1v Year 4 & Year 6 Blood Pressure, BMI & PA dataset

B-Proact1v is a longitudinal study examining changes in children’s physical activity and sedentary behaviours as they progress through primary school. In 2012-2013, 1299 Year 1 children (median age: 6 years) were recruited from 57 schools in greater Bristol, UK (total number of eligible children: 2600; recruitment rate: 50.0%). Following this, data were collected from 1223 Year 4 children (median age: 9 years) from 47 of the original schools between March 2015 and July 2016 (total number of eligible children: 2047; recruitment rate: 59.7%). Between March 2017 and July 2018, 50 of the original schools were re-recruited and data collected from 1296 Year 6 children (median age: 11 years). In total, 2132 children participated, of whom 958 participated at one time-point, 662 at two time-points, and 512 at three time-points. This dataset represents a subset of the B-Proact1v data to examine the prospective associations of children’s body mass index and physical activity at age 9 and 11 with blood pressure at age 11. Included in this repository is the dataset and a data dictionary. The dataset includes the variables that underlie the findings in a manuscript entitled ‘Associations of body mass index, physical activity and sedentary time with blood pressure in primary school children from south-west England: a prospective study’ that has been submitted to PLOS ONE. This dataset has been made available so that future researchers can replicate the study findings using the data. If you wish to use the data for any purpose other than replicating the study findings, please contact the Principal Investigator Professor Russ Jago ([email protected]) to discuss this

Data from: Increasing compliance with low tidal volume ventilation in the ICU with two nudge-based interventions: evaluation through intervention time-series analyses

Objectives: Low tidal volume (TVe) ventilation improves outcomes for ventilated patients, and the majority of clinicians state they implement it. Unfortunately, most patients never receive low TVes. ‘Nudges’ influence decision-making with subtle cognitive mechanisms and are effective in many contexts. There have been few studies examining their impact on clinical decision-making. We investigated the impact of 2 interventions designed using principles from behavioural science on the deployment of low TVe ventilation in the intensive care unit (ICU). Setting: University Hospitals Bristol, a tertiary, mixed medical and surgical ICU with 20 beds, admitting over 1300 patients per year. Participants: Data were collected from 2144 consecutive patients receiving controlled mechanical ventilation for more than 1 hour between October 2010 and September 2014. Patients on controlled mechanical ventilation for more than 20 hours were included in the final analysis. Interventions: (1) Default ventilator settings were adjusted to comply with low TVe targets from the initiation of ventilation unless actively changed by a clinician. (2) A large dashboard was deployed displaying TVes in the format mL/kg ideal body weight (IBW) with alerts when TVes were excessive. Primary outcome measure: TVe in mL/kg IBW. Findings: TVe was significantly lower in the defaults group. In the dashboard intervention, TVe fell more quickly and by a greater amount after a TVe of 8 mL/kg IBW was breached when compared with controls. This effect improved in each subsequent year for 3 years. Conclusions: This study has demonstrated that adjustment of default ventilator settings and a dashboard with alerts for excessive TVe can significantly influence clinical decision-making. This offers a promising strategy to improve compliance with low TVe ventilation, and suggests that using insights from behavioural science has potential to improve the translation of evidence into practice.,newalldata_corrected

Data from: Olfactory testing in Parkinson’s disease &amp; REM behavior disorder: a machine learning approach

Objective: We sought to identify an abbreviated test of impaired olfaction, amenable for use in busy clinical environments in prodromal (isolated REM sleep Behavior Disorder (iRBD)) and manifest Parkinson’s. Methods: 890 PD and 313 control participants in the Discovery cohort study underwent Sniffin’ stick odour identification assessment. Random forests were initially trained to distinguish individuals with poor (functional anosmia/hyposmia) and good (normosmia/super-smeller) smell ability using all 16 Sniffin’ sticks. Models were retrained using the top 3 sticks ranked by order of predictor importance. One randomly selected 3-stick model was tested in a second independent Parkinson’s dataset (n=452) and in two iRBD datasets (Discovery n=241; Marburg n=37) before being compared to previously described abbreviated Sniffin’ stick combinations. Results: In differentiating poor from good smell ability, the overall area under the curve (AUC) value associated with the top 3 sticks (Anise, Licorice and Banana) was 0.95 in the development dataset (sensitivity:90%, specificity:92%, PPV:92%, NPV:90%). Internal and external validation confirmed AUCs≥0.90. The combination of 3-stick model determined poor smell and an RBD screening questionnaire score of ≥5, separated iRBD from controls with a sensitivity, specificity, PPV and NPV of 65%, 100%, 100% and 30%. Conclusions: Our 3-Sniffin’-stick model holds potential utility as a brief screening test in the stratification of individuals with Parkinson’s and iRBD according to olfactory dysfunction. Classification of Evidence: This study provides Class III evidence that a 3-Sniffin’-stick model distinguishes individuals with poor and good smell ability and can be used to screen for individuals with iRBD

PROSPERO_registration.pdf, Underlying data for: The impact of the Covid-19 pandemic on suicidal behaviour: a living systematic review protocol

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lsr_fig1.png, Underlying data for: The impact of the Covid-19 pandemic on suicidal behaviour: a living systematic review protocol

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Prisma.pdf, Underlying data for: The impact of the Covid-19 pandemic on suicidal behaviour: a living systematic review protocol

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