Flexible piecewise linear model for investigating dose-response relationship in meta-analysis: Methodology, examples, and comparison.

OBJECTIVES: Dose-response meta-analysis (DRMA) is widely employed in establishing the potential dose-response relationship between continuous exposures and disease outcomes. However, there is no valid DRMA method readily for discrete exposures, especially when the possible dose-response trend not likely to be linear. We proposed a piecewise linear DRMA model as a solution to this issue. METHODS: We illustrated the methodology of piecewise linear model in both one-stage DRMA approach and two-stage DRMA approach. The method by testing the equality of slopes of each piecewise was employed to judge if there is "piecewise effect" against a simple linear trend. We then used sleep (continuous exposure) and parity (discrete exposure) data as examples to illustrate how to apply the model in DRMA using the Stata code attached. We also empirically compared the slopes of piecewise linear model with simple linear as well as restricted cubic spline model. RESULTS: Both one-stage and two-stage piecewise linear DRMA model fitted well in our examples, and the results were similar. Obvious "piecewise effects" were detected in both the two samples by the method we used. In our example, the new model showed a better fitting effect and practical, reliable results compared to the simple linear model, while similar results for to restricted cubic spline model. CONCLUSION: Piecewise linear function is a valid and straightforward method for DRMA and can be used for discrete exposures, especially when the simple linear function is under fitted. It represents a superior model to linear model in DRMA and may be an alternative model to the nonlinear model.

Effects of dance on cognitive function among older adults: a protocol for systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is characterized by problems in thinking, memory, language, and judgment that are greater than cognitive changes in normal aging. Considering the unprecedented growth of the older adult population and the projected increase in the prevalence of cognitive impairment, it is imperative to find effective strategies to improve or maintain cognitive function in older adults. The objective of this review is to summarize the effects of dance versus any other control group on cognitive function, physical function, adverse events, and quality of life in older adults. METHOD: We will search the following databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify the randomized controlled trials (RCTs) evaluating the effects of dance on cognitive function among older adults. Also, we will search http://apps.who.int/trialsearch , clinicaltrials.gov and conference abstracts to identify ongoing and unpublished studies. There will be no restrictions on language, date, or journal of publication. Reviewers will independently and in duplicate screen for eligible studies using pre-defined criteria. Data extraction from eligible studies will be performed independently and in duplicate. The Cochrane risk of bias tool will be used to assess the risk of bias of studies. Our primary outcome of interest is cognitive function, more specifically the executive function domain. We will include other domains as well such as processing speed and reaction time. Secondary outcomes of interest are physical function. The secondary outcomes also include adverse events including falls and quality of life. We will use Review Manager (RevMan 5.3) to pool the effect of dance for each outcome where possible. Results will be presented as relative risks along with 95% confidence intervals for dichotomous outcomes and as mean differences, or standardized mean differences along with 95% confidence intervals, for continuous outcomes. We will assess the certainty of the evidence using the GRADE approach and present findings in a Summary of Findings table. DISCUSSION: This systematic review, to our best knowledge the first-ever, will synthesize the available evidence on the effects of dance on cognitive function among older people. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017057138.

Early Exercise in Critically Ill Youth and Children, a Preliminary Evaluation: The wEECYCLE Pilot Trial.

OBJECTIVES: To determine the feasibility of conducting a full trial evaluating the efficacy of early mobilization using in-bed cycling as an adjunct to physiotherapy, on functional outcomes in critically ill children. DESIGN: Single center, pilot, randomized controlled trial. SETTING: Twelve-bed tertiary care, medical-surgical PICU at McMaster Children's Hospital, Hamilton, ON, Canada. PATIENTS: Children 3-17 years old who were limited to bed-rest with an expected PICU stay of at least 48 hours. Patients were excluded if they were at their baseline level of function, already mobilizing out of bed or expected to do so within 24 hours. INTERVENTIONS: Patients were randomized in a 2:1 ratio to early mobilization using in-bed cycling in addition to usual care physiotherapy (cycling arm) or to usual care physiotherapy alone (control). Usual care was according to institutional practice guidelines. The primary outcome was feasibility and safety. MEASUREMENTS AND MAIN RESULTS: Thirty patients were enrolled (20 to the cycling and 10 to control) over a 12-month period, at a 93.7% consent rate. The median (interquartile range) time from PICU admission to mobilization was 1.5 days (1-3) in the cycling arm and 2.5 days (2-7) in the control arm. Total duration of mobilization therapy in PICU was 210 (152-380) and 136 minutes (42-314 min) in cycling and control arms, respectively. Total number of PICU days mobilized was 5.0 (3-6) with cycling and 2.5 (2-4.8) with usual care. No adverse events occurred in either arm. The main threat to feasibility of mobilization was the availability of physiotherapists or research personnel. CONCLUSIONS: Early mobilization is safe and feasible in the PICU. In-bed cycling may facilitate greater duration and intensity of mobilization, in critically ill children. A full-scale randomized controlled trial is warranted to evaluate the efficacy of this intervention on PICU-acquired morbidities and functional outcomes in this population.

Cyclic hypoxia does not alter RAD51 expression or PARP inhibitor cell kill in tumor cells.

Solid tumors contain regions of chronic and cyclic hypoxia. Chronic hypoxia can downregulate RAD51 and sensitize cells to PARP inhibition. Herein, we show that RAD51 expression, cell survival and toxicity to PARP inhibition is not affected under cyclic hypoxic conditions. This suggests that PARP inhibition may be selectively toxic in tumor sub-regions associated with chronic hypoxia.