A systematic review of compositional data analysis studies examining associations between sleep, sedentary behaviour, and physical activity with health outcomes in adults

This systematic review determined if the composition of time spent in movement behaviours (i.e., sleep, sedentary behaviour (SED), light physical activity, and moderate-to-vigorous physical activity (MVPA)) is associated with health in adults. Five electronic databases were searched in August 2019. Studies were eligible for inclusion if they were peer-reviewed, examined community-dwelling adults, and used compositional data analysis to examine the associations between the composition of time spent in movement behaviours and health outcomes. Eight studies (7 cross-sectional, 1 prospective cohort) of >12 000 unique participants were included. Findings indicated that the 24-h movement behaviour composition was associated with all-cause mortality (1 of 1 analyses), adiposity (4 of 4 analyses), and cardiometabolic biomarkers (8 of 15 analyses). Reallocating time into MVPA from other movement behaviours was associated with favourable changes to most health outcomes and taking time out of SED and reallocating it into other movement behaviours was associated with favourable changes to all-cause mortality. The quality of evidence was very low for all health outcomes. In conclusion, these findings support the notion that the composition of movement across the entire 24-h day matters, and that recommendations for sleep, SED, and physical activity should be combined into a single public health guideline. (PROSPERO registration no.: CRD42019121641.) Novelty The 24-h movement behaviour composition is associated with a variety of health outcomes. Reallocating time into MVPA is favourably associated with health. Reallocating time out of SED is associated with favourable changes to mortality risk

Drawing the answers: Sketching to support free and probed recall by child witnesses and victims with autism spectrum disorder

The success of witness interviews in the criminal justice system depends on the accuracy of information obtained, which is a function of both amount and quality of information. Attempts to enhance witness retrieval such as mental reinstatement of context have been designed with typically developed adults in mind. In this paper, the relative benefits of mental and sketch reinstatement mnemonics are explored with both typically developing children and children with autism. Children watched a crime event video, and their retrieval of event information was examined in free and probed recall phases of a cognitive interview. As expected, typically developing children recalled more correct information of all types than children with autism during free and probed recall phases. Sketching during free recall was more beneficial for both groups in both phases in reducing the amount of incorrect items, but the relative effect of sketching on enhancing retrieval accuracy was greater for children with autism. The results indicate the benefits of choosing retrieval mnemonics that are sensitive to the specific impairments of autistic individuals, and suggest that retrieval accuracy during interviews can be enhanced, in some cases to the same level as that of typically developing individuals

Genetic screening reveals phospholipid metabolism as a key regulator of the biosynthesis of the redox-active lipid coenzyme Q.

Mitochondrial energy production and function rely on optimal concentrations of the essential redox-active lipid, coenzyme Q (CoQ). CoQ deficiency results in mitochondrial dysfunction associated with increased mitochondrial oxidative stress and a range of pathologies. What drives CoQ deficiency in many of these pathologies is unknown, just as there currently is no effective therapeutic strategy to overcome CoQ deficiency in humans. To date, large-scale studies aimed at systematically interrogating endogenous systems that control CoQ biosynthesis and their potential utility to treat disease have not been carried out. Therefore, we developed a quantitative high-throughput method to determine CoQ concentrations in yeast cells. Applying this method to the Yeast Deletion Collection as a genome-wide screen, 30 genes not known previously to regulate cellular concentrations of CoQ were discovered. In combination with untargeted lipidomics and metabolomics, phosphatidylethanolamine N-methyltransferase (PEMT) deficiency was confirmed as a positive regulator of CoQ synthesis, the first identified to date. Mechanistically, PEMT deficiency alters mitochondrial concentrations of one-carbon metabolites, characterized by an increase in the S-adenosylmethionine to S-adenosylhomocysteine (SAM-to-SAH) ratio that reflects mitochondrial methylation capacity, drives CoQ synthesis, and is associated with a decrease in mitochondrial oxidative stress. The newly described regulatory pathway appears evolutionary conserved, as ablation of PEMT using antisense oligonucleotides increases mitochondrial CoQ in mouse-derived adipocytes that translates to improved glucose utilization by these cells, and protection of mice from high-fat diet-induced insulin resistance. Our studies reveal a previously unrecognized relationship between two spatially distinct lipid pathways with potential implications for the treatment of CoQ deficiencies, mitochondrial oxidative stress/dysfunction, and associated diseases

The Challenge of Transparency and Validation in Health Economic Decision Modelling:A View from Mount Hood

Transparency in health economic decision modelling is important for engendering confidence in the models and in the reliability of model-based cost-effectiveness analyses. The Mount Hood Diabetes Challenge Network has taken a lead in promoting transparency through validation with biennial conferences in which diabetes modelling groups meet to compare simulated outcomes of pre-specified scenarios often based on the results of pivotal clinical trials. Model registration is a potential method for promoting transparency, while also reducing the duplication of effort. An important network initiative is the ongoing construction of a diabetes model registry (https://www.mthooddiabeteschallenge.com). Following the 2012 International Society for Pharmacoeconomics and Outcomes Research and the Society of Medical Decision Making (ISPOR-SMDM) guidelines, we recommend that modelling groups provide technical and non-technical documentation sufficient to enable model reproduction, but not necessarily provide the model code. We also request that modelling groups upload documentation on the methods and outcomes of validation efforts, and run reference case simulations so that model outcomes can be compared. In this paper, we discuss conflicting definitions of transparency in health economic modelling, and describe the ongoing development of a registry of economic models for diabetes through the Mount Hood Diabetes Challenge Network, its objectives and potential further developments, and highlight the challenges in its construction and maintenance. The support of key stakeholders such as decision-making bodies and journals is key to ensuring the success of this and other registries. In the absence of public funding, the development of a network of modellers is of huge value in enhancing transparency, whether through registries or other means

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

Multicentre pilot randomised clinical trial of early in-bed cycle ergometry with ventilated patients.

Introduction: Acute rehabilitation in critically ill patients can improve post-intensive care unit (post-ICU) physical function. In-bed cycling early in a patient\u27s ICU stay is a promising intervention. The objective of this study was to determine the feasibility of recruitment, intervention delivery and retention in a multi centre randomised clinical trial (RCT) of early in-bed cycling with mechanically ventilated (MV) patients. Methods: We conducted a pilot RCT conducted in seven Canadian medical-surgical ICUs. We enrolled adults who could ambulate independently before ICU admission, within the first 4 days of invasive MV and first 7 days of ICU admission. Following informed consent, patients underwent concealed randomisation to either 30 min/day of in-bed cycling and routine physiotherapy (Cycling) or routine physiotherapy alone (Routine) for 5 days/week, until ICU discharge. Our feasibility outcome targets included: accrual of 1-2 patients/month/site; \u3e80% cycling protocol delivery; \u3e80% outcomes measured and \u3e80% blinded outcome measures at hospital discharge. We report ascertainment rates for our primary outcome for the main trial (Physical Function ICU Test-scored (PFIT-s) at hospital discharge). Results: Between 3/2015 and 6/2016, we randomised 66 patients (36 Cycling, 30 Routine). Our consent rate was 84.6 % (66/78). Patient accrual was (mean (SD)) 1.1 (0.3) patients/month/site. Cycling occurred in 79.3% (146/184) of eligible sessions, with a median (IQR) session duration of 30.5 (30.0, 30.7) min. We recorded 43 (97.7%) PFIT-s scores at hospital discharge and 37 (86.0%) of these assessments were blinded. Discussion: Our pilot RCT suggests that a future multicentre RCT of early in-bed cycling for MV patients in the ICU is feasible. Trial registration number: NCT02377830

Health related quality of life outcomes following surgery and/or radiation for patients with potentially unstable spinal metastases.

Currently there is no prospective pain and health related quality of life (HRQOL) data of patients with potentially unstable spinal metastases who were treated with surgery ± radiation or radiation alone.An international prospective cohort multicenter study of patients with potentially unstable spinal metastases, defined by a SINS score 7 to 12, treated with surgery ± radiation or radiotherapy alone was conducted. HRQOL was evaluated with the numeric rating scale (NRS) pain score, the SOSGOQ2.0, the SF-36, and the EQ-5D at baseline and 6, 12, 26, and 52 weeks after treatment.A total of 136 patients were treated with surgery ± radiotherapy and 84 with radiotherapy alone. At baseline, surgically treated patients were more likely to have mechanical pain, a lytic lesion, a greater median Spinal Instability Neoplastic score, vertebral compression fracture, lower performance status, HRQOL, and pain scores. From baseline to 12 weeks post-treatment, surgically treated patients experienced a 3.0-point decrease in NRS pain score (95% CI -4.1 to -1.9, p.001), and a 12.7-point increase in SOSGOQ2.0 score (95% CI 6.3-19.1, p.001). Patients treated with radiotherapy alone experienced a 1.4-point decrease in the NRS pain score (95% CI -2.9 to 0.0, p=.046) and a 6.2-point increase in SOSGOQ2.0 score (95% CI -2.0 to 14.5, p=.331). Beyond 12 weeks, significant improvements in pain and HRQOL metrics were maintained up to 52-weeks follow-up in the surgical cohort, as compared with no significant changes in the radiotherapy alone cohort.Patients treated with surgery demonstrated clinically and statistically significant improvements in pain and HRQOL up to 1-year postsurgery. Treatment with radiotherapy alone resulted in improved pain scores, but these were not sustained beyond 3 months and HRQOL outcomes demonstrated nonsignificant changes over time. Within the SINS potentially unstable group, distinct clinical profiles were observed in patients treated with surgery or radiotherapy alone