Genome-scale metabolic modeling reveals metabolic trade-offs associated with lipid production in Rhodotorula toruloides.

Rhodotorula toruloides is a non-conventional, oleaginous yeast able to naturally accumulate high amounts of microbial lipids. Constraint-based modeling of R. toruloides has been mainly focused on the comparison of experimentally measured and model predicted growth rates, while the intracellular flux patterns have been analyzed on a rather general level. Hence, the intrinsic metabolic properties of R. toruloides that make lipid synthesis possible are not thoroughly understood. At the same time, the lack of diverse physiological data sets has often been the bottleneck to predict accurate fluxes. In this study, we collected detailed physiology data sets of R. toruloides while growing on glucose, xylose, and acetate as the sole carbon source in chemically defined medium. Regardless of the carbon source, the growth was divided into two phases from which proteomic and lipidomic data were collected. Complemental physiological parameters were collected in these two phases and altogether implemented into metabolic models. Simulated intracellular flux patterns demonstrated the role of phosphoketolase in the generation of acetyl-CoA, one of the main precursors during lipid biosynthesis, while the role of ATP citrate lyase was not confirmed. Metabolic modeling on xylose as a carbon substrate was greatly improved by the detection of chirality of D-arabinitol, which together with D-ribulose were involved in an alternative xylose assimilation pathway. Further, flux patterns pointed to metabolic trade-offs associated with NADPH allocation between nitrogen assimilation and lipid biosynthetic pathways, which was linked to large-scale differences in protein and lipid content. This work includes the first extensive multi-condition analysis of R. toruloides using enzyme-constrained models and quantitative proteomics. Further, more precise kcat values should extend the application of the newly developed enzyme-constrained models that are publicly available for future studies.

Use of behavior change techniques in physical activity programs and services for older adults: findings from a rapid review.

BACKGROUND: Understanding behavior change techniques (BCTs) used in randomized controlled trials (RCTs) of physical activity programs/services for older adults can help us to guide their implementation in real-world settings. PURPOSE: This study aims to: (a) identify the number and type of BCTs used in physical activity programs/services for older adults evaluated in large, good quality RCTs and (b) explore the impact of different BCTs on different outcome domains. METHODS: This is a secondary data analysis of a WHO-commissioned rapid review of physical activity programs/services for older adults. Fifty-six trials testing 70 interventions were coded for the type and number of BCTs present using a published BCT taxonomy. The proportion of positive effects found from physical activity interventions using the most common BCTs was calculated for the outcomes of physical activity, intrinsic capacity, functional ability, social domain, cognitive and emotional functioning, and well-being and quality of life. RESULTS: Thirty-nine of the 93 possible BCTs were identified in the included trials and 529 BCTs in total (mean 7.6, range 2-17). The most common BCTs were "action planning" (68/70 interventions), "instructions on how to perform a behavior" (60/70), "graded tasks" (53/70), "demonstration of behavior" (44/70), and "behavioral practice/rehearsal" (43/70). Interventions that used any of the most common BCTs showed overwhelmingly positive impacts on physical activity and social domain outcomes. CONCLUSION: Consideration of which BCTs are included in interventions and their impact on outcomes can improve the effectiveness and implementation of future interventions. To enable this, providers can design, implement, and evaluate interventions using a BCT taxonomy.

Interventions aimed at modifying health-related behaviors, such as physical activity, are often complex, with numerous components. To better understand interventions' "active ingredients," we conducted a secondary analysis of a World Health Organization (WHO)-commissioned rapid review, using a behavior change technique (BCT) taxonomy. We aimed to classify the number and types of BCTs in physical activity programs for older adults, as identified in randomized controlled trials (RCTs), and examine their impact on outcomes, including physical activity, intrinsic capacity, functional ability, social domain, cognitive and emotional functioning, and well-being. Examining 56 trials testing 70 interventions, we identified 39 out of 93 possible BCTs, totaling 529 instances across interventions. Common BCTs included "action planning," "instructions on how to perform a behavior," "graded tasks," "demonstration of behavior," and "behavioral practice/rehearsal." Interventions using the 10 most common BCTs demonstrated overwhelmingly positive impacts on physical activity and social domain outcomes. However, these BCTs were not consistently present in interventions yielding positive outcomes in other domains, with greater variation in effects. Our study highlights the significance of identifying both BCTs and desired outcomes when designing physical activity interventions. We advocate for the use of a taxonomy in designing and implementing future programs to maximize effectiveness.

Effective fall prevention exercise in residential aged care: an intervention component analysis from an updated systematic review.

OBJECTIVE: The effect of fall prevention exercise programmes in residential aged care (RAC) is uncertain. This paper reports on an intervention component analysis (ICA) of randomised controlled trials (RCTs), from an update of a Cochrane review, to develop a theory of features of successful fall prevention exercise in RAC. METHODS: Trial characteristics were extracted from RCTs testing exercise interventions in RAC identified from an update of a Cochrane review to December 2022 (n=32). Eligible trials included RCTs or cluster RCTs in RAC, focusing on participants aged 65 or older, assessing fall outcomes with stand-alone exercise interventions. ICA was conducted on trials with >30 participants per treatment arm compared with control (n=17). Two authors coded trialists' perceptions on intervention features that may have contributed to the observed effect on falls. Inductive thematic analysis was used to identify the key differences between the trials which might account for positive and negative outcomes. RESULTS: 32 RCTs involving 3960 residents including people with cognitive (57%) and mobility (41%) impairments were included. ICA on the 17 eligible RCTs informed the development of a theory that (1) effective fall prevention exercise delivers the right exercise by specifically targeting balance and strength, tailored to the individual and delivered simply at a moderate intensity and (2) successful implementation needs to be sufficiently resourced to deliver structured and supervised exercise at an adequate dose. CONCLUSIONS: This analysis suggests that delivering the right exercise, sufficiently resourced, is important for preventing falls in RAC. This clinical guidance requires confirmation in larger trials.

Exercise Interventions Delivered Through Telehealth to Improve Physical Functioning for Older Adults with Frailty, Cognitive, or Mobility Disability: A Systematic Review and Meta-Analysis.

Introductions: This study assessed the effects of telehealth-delivered exercise interventions on physical functioning for older adults and explored implementation measures related to program delivery. Methods: We conducted a systematic review of studies investigating effects of exercise interventions delivered through telehealth in adults 60+ years of age with frailty, mobility, or cognitive disability on mobility, strength, balance, falls, and quality of life (QoL). Electronic databases (MEDLINE, CINAHL, SPORTSDiscus, and Physiotherapy Evidence Database) were searched from inception until May 2022. Evidence certainty was assessed with Grading of Recommendations, Assessment, Development, and Evaluation and meta-analysis summarized study effects. Results: A total of 11 studies were included, 5 randomized controlled trials, 2 pilot studies, and 4 feasibility studies. The overall certainty of evidence was rated as "low" or "very low." Pooled between-group differences were not statistically significant, but effect sizes suggested that telehealth produced a moderate improvement on mobility (n = 5 studies; standardized mean difference [SMD] = 0.63; 95% confidence interval [CI] = -0.25 to 1.51; p = 0.000, I2 = 86%) and strength (n = 4; SMD = 0.73; 95% CI = -0.10 to 1.56; p = 0.000, I2 = 84%), a small improvement on balance (n = 3; SMD = 0.40; 95% CI = -035 to 1.15; p = 0.012, I2 = 78%), and no effect on QoL. Analysis of implementation measures suggested telehealth to be feasible in this population, given high rates of acceptability and adherence with minimal safety concerns. Discussion: Telehealth may provide small to moderate benefits on a range of physical outcomes and appears to be well received in aged care populations.

Physical activity and injurious falls in older Australian women: adjusted associations and modification by physical function limitation and frailty in the Australian Longitudinal Study on Women's Health.

OBJECTIVES: To investigate associations between leisure-time physical activity (LPA) and injurious falls in older women and explore modification of associations by physical function and frailty. METHODS: Women born during 1946-51 from the Australian Longitudinal Study on Women's Health, injurious falls (self-reported fall with injury and/or medical attention) and self-reported weekly LPA (duration and type). We undertook cross-sectional and prospective analyses using data from 2016 [n = 8,171, mean (SD) age 68 (1)] and 2019 surveys (n = 7,057). Associations were quantified using directed acyclic graph-informed logistic regression and effect modification examined using product terms. RESULTS: Participation in LPA as recommended by World Health Organization (150-300 min/week) was associated with lower odds of injurious falls in cross-sectional (adjusted Odds Ratio (OR) 0.74, 95% CI 0.61-0.90) and prospective analyses (OR 0.75, 95% CI 0.60-0.94). Compared with those who reported no LPA, cross-sectionally, odds of injurious falls were lower in those who reported brisk walking (OR 0.77, 95% CI 0.67-0.89) and vigorous LPA (OR 0.86, 95% CI 0.75-1.00). No significant association was found between different types of LPA and injurious falls prospectively. Only cross-sectionally, physical function limitation and frailty modified the association between LPA and injurious falls, with tendencies for more injurious falls with more activity in those with physical limitation or frailty, and fewer injurious falls with more activity among those without physical function limitation or frailty. CONCLUSION: Participation in recommended levels of LPA was associated with lower odds of injurious falls. Caution is required when promoting general physical activity among people with physical limitation or frailty.

Cost-effectiveness of physical activity programs and services for older adults: a scoping review.

BACKGROUND: Evidence supporting physical activity for older adults is strongly positive. Implementation and scale-up of these interventions need to consider the value for money. This scoping review aimed to assess the volume of (i) systematic review evidence regarding economic evaluations of physical activity interventions, and (ii) of cost utility analysis (CUA) studies (trial- or model-based) of physical activity interventions for older people. METHODS: We searched five databases (January 2010 to February 2022) for systematic reviews of economic evaluations, and two databases (1976 to February 2022) for CUA studies of physical activity interventions for any population of people aged 60+ years. RESULTS: We found 12 potential reviews, two of which were eligible for inclusion. The remaining 10 reviews included eligible individual studies that were included in this review. All individual studies from the 12 reviews (n = 37) investigated the cost-effectiveness of structured exercise and most showed the intervention was more costly but more effective than no intervention. We identified 27 CUA studies: two investigated a physical activity promotion program and the remainder investigated structured exercise. Most interventions (86%) were more costly but more effective, and the remaining were cost-saving compared to no intervention. CONCLUSIONS: There is a scarcity of reviews investigating the value for money of physical activity interventions for older adults. Most studies investigated structured exercise. Physical activity interventions were generally more effective than no intervention but more costly. As such an intervention could be cost-effective and therefore worthy of wider implementation, but there is a need for more frequent economic evaluation in this field.

R2CHA2DS2-VA Predictsthe Cardiovascular Risk after Carotid Endarterectomy.

BACKGROUND: R2CHA2DS2-VA score has been used to predict short and long-term outcomes in many cardiovascular diseases. This study aims to validate the R2CHA2DS2-VA score as a long-term major adverse cardiovascular events (MACE) predictor after carotid endarterectomy (CEA). Secondary outcomes were also assessed regarding the incidence of all-cause mortality, acute myocardial infarction (AMI), major adverse limb events (MALE), and acute heart failure (AHF). METHODS: From January 2012 to December 2021, patients (n = 205) from a Portuguese tertiary care and referral center that underwent CEA with regional anesthesia (RA) for carotid stenosis (CS) were selected from a previously collected prospective database, and a posthoc analysis was performed. Demographics and comorbidities were registered. Clinical adverse events were assessed 30 days after the procedure and in the subsequent long-term surveillance period. Statistical analysis was performed by the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: Of the patients enrolled, 78.5% were males with a mean age of 70.44 ± 8.9 years. Higher scores of R2CHA2DS2-VA were associated with long-term MACE (adjusted hazard ratio (aHR) 1.390; 95% confidence interval (CI) 1.173-1.647); and mortality (aHR 1.295; 95% CI 1.08-1.545). CONCLUSIONS: This study demonstrated the potential of the R2CHA2DS2-VA score to predict long-term outcomes, such as AMI, AHF, MACE, and all-cause mortality, in a population of patients submitted to carotid endarterectomy.

Economic evaluation of digitally enabled aged and neurological rehabilitation care in the Activity and MObility UsiNg Technology (AMOUNT) trial.

OBJECTIVE: To investigate the trial-based cost-effectiveness of the addition of a tailored digitally enabled exercise intervention to usual care shown to be clinically effective in improving mobility in the Activity and MObility UsiNg Technology (AMOUNT) rehabilitation trial compared to usual care alone. DESIGN: Economic evaluation alongside a pragmatic randomized controlled trial. PARTICIPANTS: 300 people receiving inpatient aged and neurological rehabilitation were randomized to the intervention (n = 149) or usual care control group (n = 151). MAIN MEASURES: Incremental cost effectiveness ratios were calculated for the additional costs per additional person demonstrating a meaningful improvement in mobility (3-point in Short Physical Performance Battery) and quality-adjusted life years gained at 6 months (primary analysis). The joint probability distribution of costs and outcomes was examined using bootstrapping. RESULTS: The mean cost saving for the intervention group at 6 months was AU$2286 (95% Bootstrapped cost CI: -$11,190 to $6410) per participant; 68% and 67% of bootstraps showed the intervention to be dominant (i.e. more effective and cost saving) for mobility and quality-adjusted life years, respectively. The probability of the intervention being cost-effective considering a willingness to pay threshold of AU$50,000 per additional person with a meaningful improvement in mobility or quality-adjusted life year gained was 93% and 77%, respectively. CONCLUSIONS: The AMOUNT intervention had a high probability of being cost-effective if decision makers are willing to pay AU$50,000 per meaningful improvement in mobility or per quality-adjusted life year gained, and a moderate probability of being cost-saving and effective considering both outcomes at 6 months post randomization.

Effect of sport on health in people aged 60 years and older: a systematic review with meta-analysis.

OBJECTIVES: To summarise evidence of benefits of sport for health among people aged 60+. DESIGN: Systematic review with meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: Medline, CINAHL, SPORTDiscus, the Physiotherapy Evidence Database from inception to April 2021. STUDY SELECTION: RCTs investigating the effect of sport on health-related outcomes in people aged 60+ compared with non-active control. DATA SYNTHESIS AND ANALYSIS: Pooled effect sizes were calculated using random-effect models. Standardised mean differences (SMD), and mean difference (MD) were calculated. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the certainty of the evidence for analyses with ≥3 studies. RESULTS: Nine trials (628 participants) reported in 15 articles were included. Participation in sport improved cardiorespiratory fitness (n=5 trials; SMD=0.43, 95% CI 0.17 to 0.70; low certainty evidence), physical function (n=4; SMD=0.62, 95% CI 0.05 to 1.18; very low certainty evidence), and mental health (n=2; SMD=0.28, 95% CI 0.06 to 0.51) and reduced fat mass (n=6; MD=-0.99 kg, 95% CI -1.75kg to -0.23 kg; low certainty evidence) among older people. We found no significant effects of sport on overall physical activity participation, strength, balance, lean mass and bone mineral density (BMD). One study investigating quality of life reported a positive, but non-significant effect of sport. CONCLUSION: Sport may have a positive impact on health outcomes in people aged 60+. There was uncertainty on the effect of sport on strength, balance, lean mass and BMD. Further research is needed to investigate the optimal type and dose of sport to maximise the long-term benefits among older people.

Impact of physical activity programs and services for older adults: a rapid review.

BACKGROUND: Knowledge of which physical activity programs are most effective for older adults in different sub-populations and contexts is limited. The objectives of this rapid review were to: 1) Overview evidence evaluating physical activity programs/services for older adults; and 2) Describe impact on physical activity, falls, intrinsic capacity (physical domain), functional ability (physical, social, and cognitive/emotional domains), and quality of life. METHODS: We conducted a rapid review of primary studies from 350 systematic reviews identified in a previous scoping review (March 2021: PEDro, MEDLINE, CINAHL, Cochrane Database). For Objective 1, we included intervention studies investigating physical activity programs/services in adults ≥ 60 years. Of these, we included good quality (≥ 6/10 PEDro scale) randomised controlled trials (RCTs) with ≥ 50 participants per group in Objective 2. RESULTS: Objective 1: Of the 1421 intervention studies identified from 8267 records, 79% were RCTs, 87% were in high income countries and 39% were good quality. Objective 2: We identified 87 large, good quality RCTs (26,861 participants). Overall activity promotion, structured exercise and recreation/sport had positive impacts (≥ 50% between-group comparisons positive) across all outcome domains. For overall activity promotion (21 intervention groups), greatest impacts were on physical activity (100% positive) and social outcomes (83% positive). Structured exercise (61 intervention groups) had particularly strong impacts on falls (91% positive), intrinsic capacity (67% positive) and physical functioning (77% positive). Recreation/sport (24 intervention groups) had particularly strong impacts on cognitive/emotional functioning (88% positive). Multicomponent exercise (39 intervention groups) had strong impacts across all outcomes, particularly physical activity (95% positive), falls (90% positive) and physical functioning (81% positive). Results for different populations and settings are presented. CONCLUSION: Evidence supporting physical activity for older adults is positive. We outline which activity types are most effective in different populations and settings.

Economic evaluation of physical activity mass media campaigns across the globe: a systematic review.

BACKGROUND: Physical activity mass media campaigns can deliver physical activity messages to many people, but it remains unclear whether they offer good value for money. We aimed to investigate the cost-effectiveness, cost-utility, and costs of physical activity mass media campaigns. METHODS: A search for economic evaluations (trial- or model-based) and costing studies of physical activity mass media campaigns was performed in six electronic databases (June/2021). The authors reviewed studies independently. A GRADE style rating was used to assess the overall certainty of each modelled economic evaluation. Results were summarised via narrative synthesis. RESULTS: Twenty-five studies (five model-based economic evaluations and 20 costing studies) were included, and all were conducted in high-income countries except for one costing study that was conducted in a middle-income country. The methods and assumptions used in the model-based analyses were highly heterogeneous and the results varied, ranging from the intervention being more effective and less costly (dominant) in two models to an incremental cost of US$130,740 (2020 base year) per QALY gained. The level of certainty of the models ranged from very low (n = 2) to low (n = 3). Overall, intervention costs were poorly reported. CONCLUSIONS: There are few economic evaluations of physical activity mass media campaigns available. The level of certainty of the models was judged to be very low to low, indicating that we have very little to little confidence that the results are reliable for decision making. Therefore, it remains unclear to what extent physical activity mass media campaigns offer good value for money. Future economic evaluations should consider selecting appropriate and comprehensive measures of campaign effectiveness, clearly report the assumptions of the models and fully explore the impact of assumptions in the results. REVIEW REGISTRATION: https://bit.ly/3tKSBZ3.

Economic evaluations of fall prevention exercise programs: a systematic review.

OBJECTIVE: To investigate cost-effectiveness and costs of fall prevention exercise programmes for older adults. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Web of Science, Scopus, National Institute for Health Research Economic Evaluation Database, Health Technology Assessment database, Tufts Cost-Effectiveness Analysis Registry, Research Papers in Economics and EconLit (inception to May 2022). ELIGIBILITY CRITERIA FOR STUDY SELECTION: Economic evaluations (trial-based or model-based) and costing studies investigating fall prevention exercise programmes versus no intervention or usual care for older adults living in the community or care facilities, and reporting incremental cost-effectiveness ratio (ICER) for fall-related outcomes or quality-adjusted life years (QALY, expressed as cost/QALY) and/or intervention costs. RESULTS: 31 studies were included. For community-dwelling older adults (21 economic evaluations, 6 costing studies), results ranged from more effective and less costly (dominant) interventions up to an ICER of US$279 802/QALY gained and US$11 986/fall prevented (US$ in 2020). Assuming an arbitrary willingness-to-pay threshold (US$100 000/QALY), most results (17/24) were considered cost-effective (moderate certainty). The greatest value for money (lower ICER/QALY gained and fall prevented) appeared to accrue for older adults and those with high fall risk, but unsupervised exercise appeared to offer poor value for money (higher ICER/QALY). For care facilities (two economic evaluations, two costing studies), ICERs ranged from dominant (low certainty) to US$35/fall prevented (moderate certainty). Overall, intervention costs varied and were poorly reported. CONCLUSIONS: Most economic evaluations investigated fall prevention exercise programmes for older adults living in the community. There is moderate certainty evidence that fall prevention exercise programmes are likely to be cost-effective. The evidence for older adults living in care facilities is more limited but promising. PROSPERO REGISTRATION NUMBER: PROSPERO 2020 CRD42020178023.

A scoping review of physical activity interventions for older adults.

BACKGROUND: To inform implementation and future research, this scoping review investigates the volume of evidence for physical activity interventions among adults aged 60+. Our research questions are: (1) what is the evidence regarding interventions designed to increase total physical activity in adults aged 60+ years, in accordance with three of the four strategic objectives of GAPPA (active societies, active environments, active people); (2) what is the current evidence regarding the effectiveness of physical activity programmes and services designed for older adults?; and (3) What are the evidence gaps requiring further research? METHODS: We searched PEDro, MEDLINE, CINAHL and Cochrane from 1 January 2010 to 1 November 2020 for systematic reviews and meta-analyses of physical activity interventions in adults aged 60+. We identified interventions designed to: (1) increase physical activity; and (2) deliver physical activity programmes and services in home, community or outpatient settings. We extracted and coded data from eligible reviews according to our proposed framework informed by TIDieR, Prevention of Falls Network Europe (PROFANE), and WHO's International Classification of Functioning, Disability and Health (ICF). We classified the overall findings as positive, negative or inconclusive. RESULTS: We identified 39 reviews of interventions to increase physical activity and 342 reviews of programmes/services for older adults. Interventions were predominantly structured exercise programmes, including balance strength/resistance training, and physical recreation, such as yoga and tai chi. There were few reviews of health promotion/coaching and health professional education/referral, and none of sport, workplace, sociocultural or environmental interventions. Fewer reported outcomes of total physical activity, social participation and quality of life/well-being. We noted insufficient coverage in diverse and disadvantaged samples and low-middle income countries. CONCLUSIONS: There is a modest but growing volume of evidence regarding interventions designed to increase total physical activity in older adults, although more interventional studies with long term follow-up are needed, particularly for GAPPA 1. Active Societies and GAPPA 2. Active Environments. By comparison, there is abundant evidence for GAPPA 3. specific programmes and services, but coverage of sport and workplace interventions, and diverse samples and settings is lacking. Comprehensive reviews of individual studies are now needed as well as research targeting neglected outcomes, populations and settings.

Nanoparticles for Targeted Brain Drug Delivery: What Do We Know?

The blood-brain barrier (BBB) is a barrier that separates the blood from the brain tissue and possesses unique characteristics that make the delivery of drugs to the brain a great challenge. To achieve this purpose, it is necessary to design strategies to allow BBB passage, in order to reach the brain and target the desired anatomic region. The use of nanomedicine has great potential to overcome this problem, since one can modify nanoparticles with strategic molecules that can interact with the BBB and induce uptake through the brain endothelial cells and consequently reach the brain tissue. This review addresses the potential of nanomedicines to treat neurological diseases by using nanoparticles specially developed to cross the BBB.

Digitally enabled aged care and neurological rehabilitation to enhance outcomes with Activity and MObility UsiNg Technology (AMOUNT) in Australia: A randomised controlled trial.

BACKGROUND: Digitally enabled rehabilitation may lead to better outcomes but has not been tested in large pragmatic trials. We aimed to evaluate a tailored prescription of affordable digital devices in addition to usual care for people with mobility limitations admitted to aged care and neurological rehabilitation. METHODS AND FINDINGS: We conducted a pragmatic, outcome-assessor-blinded, parallel-group randomised trial in 3 Australian hospitals in Sydney and Adelaide recruiting adults 18 to 101 years old with mobility limitations undertaking aged care and neurological inpatient rehabilitation. Both the intervention and control groups received usual multidisciplinary inpatient and post-hospital rehabilitation care as determined by the treating rehabilitation clinicians. In addition to usual care, the intervention group used devices to target mobility and physical activity problems, individually prescribed by a physiotherapist according to an intervention protocol, including virtual reality video games, activity monitors, and handheld computer devices for 6 months in hospital and at home. Co-primary outcomes were mobility (performance-based Short Physical Performance Battery [SPPB]; continuous version; range 0 to 3; higher score indicates better mobility) and upright time as a proxy measure of physical activity (proportion of the day upright measured with activPAL) at 6 months. The dataset was analysed using intention-to-treat principles. The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000936628). Between 22 September 2014 and 10 November 2016, 300 patients (mean age 74 years, SD 14; 50% female; 54% neurological condition causing activity limitation) were randomly assigned to intervention (n = 149) or control (n = 151) using a secure online database (REDCap) to achieve allocation concealment. Six-month assessments were completed by 258 participants (129 intervention, 129 control). Intervention participants received on average 12 (SD 11) supervised inpatient sessions using 4 (SD 1) different devices and 15 (SD 5) physiotherapy contacts supporting device use after hospital discharge. Changes in mobility scores were higher in the intervention group compared to the control group from baseline (SPPB [continuous, 0-3] mean [SD]: intervention group, 1.5 [0.7]; control group, 1.5 [0.8]) to 6 months (SPPB [continuous, 0-3] mean [SD]: intervention group, 2.3 [0.6]; control group, 2.1 [0.8]; mean between-group difference 0.2 points, 95% CI 0.1 to 0.3; p = 0.006). However, there was no evidence of a difference between groups for upright time at 6 months (mean [SD] proportion of the day spent upright at 6 months: intervention group, 18.2 [9.8]; control group, 18.4 [10.2]; mean between-group difference -0.2, 95% CI -2.7 to 2.3; p = 0.87). Scores were higher in the intervention group compared to the control group across most secondary mobility outcomes, but there was no evidence of a difference between groups for most other secondary outcomes including self-reported balance confidence and quality of life. No adverse events were reported in the intervention group. Thirteen participants died while in the trial (intervention group: 9; control group: 4) due to unrelated causes, and there was no evidence of a difference between groups in fall rates (unadjusted incidence rate ratio 1.19, 95% CI 0.78 to 1.83; p = 0.43). Study limitations include 15%-19% loss to follow-up at 6 months on the co-primary outcomes, as anticipated; the number of secondary outcome measures in our trial, which may increase the risk of a type I error; and potential low statistical power to demonstrate significant between-group differences on important secondary patient-reported outcomes. CONCLUSIONS: In this study, we observed improved mobility in people with a wide range of health conditions making use of digitally enabled rehabilitation, whereas time spent upright was not impacted. TRIAL REGISTRATION: The trial was prospectively registered with the Australian New Zealand Clinical Trials Register; ACTRN12614000936628.

Evidence on physical activity and osteoporosis prevention for people aged 65+ years: a systematic review to inform the WHO guidelines on physical activity and sedentary behaviour.

BACKGROUND: Various physical activity interventions for prevention and treatment of osteoporosis have been designed and evaluated, but the effect of such interventions on the prevention of osteoporosis in older people is unclear. The aim of this review was to investigate the association between physical activity and osteoporosis prevention in people aged 65 years and above. METHODS: A systematic review was conducted and searches for individual studies were conducted in PubMed (January 2010 to March 2020) and for systematic reviews were conducted in PubMed, Embase, CINAHL and SPORTDiscus (January 2008 to July 2020). Records were screened according to the following eligibility criteria: i) population: adults aged 65 years and older; ii) exposure: greater volume, duration, frequency, or intensity of physical activity; iii) comparison: no physical activity or lesser volume, duration, frequency, or intensity of physical activity; iv) outcome: osteoporosis related measures (e.g., bone mineral density). The methodological quality of included studies was assessed and meta-analysis summarised study effects. The GRADE approach was used to rate certainty of evidence. RESULTS: We included a total of 59 studies, including 12 observational studies and 47 trials. Within the included trials, 40 compared physical activity with no intervention controls, 11 compared two physical activity programs, and six investigated different doses of physical activity. Included studies suggest that physical activity interventions probably improve bone health among older adults and thus prevent osteoporosis (standardised effect size 0.15, 95% CI 0.05 to 0.25, 20 trials, moderate-certainty evidence, main or most relevant outcome selected for each of the included studies). Physical activity interventions probably improve lumbar spine bone mineral density (standardised effect size 0.17, 95% CI 0.04 to 0.30, 11 trials, moderate-certainty evidence) and may improve hip (femoral neck) bone mineral density (standardised effect size 0.09, 95% CI - 0.03 to 0.21, 14 trials, low-certainty evidence). Higher doses of physical activity and programs involving multiple exercise types or resistance exercise appear to be most effective. Typical programs for which significant intervention impacts were detected in trials were undertaken for 60+ mins, 2-3 times/week for 7+ months. Observational studies suggested a positive association between long-term total and planned physical activity on bone health. CONCLUSIONS: Physical activity probably plays a role in the prevention of osteoporosis. The level of evidence is higher for effects of physical activity on lumbar spine bone mineral density than for hip. Higher dose programs and those involving multiple exercises and resistance exercises appear to be more effective.

Paracetamol versus placebo for knee and hip osteoarthritis.

BACKGROUND: Paracetamol (acetaminophen) is vastly recommended as the first-line analgesic for osteoarthritis of the hip or knee. However, there has been controversy about this recommendation given recent studies have revealed small effects of paracetamol when compared with placebo. Nonetheless, past studies have not systematically reviewed and appraised the literature to investigate the effects of this drug on specific osteoarthritis sites, that is, hip or knee, or on the dose used. OBJECTIVES: To assess the benefits and harms of paracetamol compared with placebo in the treatment of osteoarthritis of the hip or knee. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, AMED, CINAHL, Web of Science, LILACS, and International Pharmaceutical Abstracts to 3 October 2017, and ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) portal on 20 October 2017. SELECTION CRITERIA: We included randomised controlled trials comparing paracetamol with placebo in adults with osteoarthritis of the hip or knee. Major outcomes were pain, function, quality of life, adverse events and withdrawals due to adverse events, serious adverse events, and abnormal liver function tests. DATA COLLECTION AND ANALYSIS: Two review authors used standard Cochrane methods to collect data, and assess risk of bias and quality of the evidence. For pooling purposes, we converted pain and physical function (Western Ontario and McMaster Universities Osteoarthritis Index function) scores to a common 0 (no pain or disability) to 100 (worst possible pain or disability) scale. MAIN RESULTS: We identified 10 randomised placebo-controlled trials involving 3541 participants with hip or knee osteoarthritis. The paracetamol dose varied from 1.95 g/day to 4 g/day, and the majority of trials followed participants for three months only. Most trials did not clearly report randomisation and concealment methods and were at unclear risk of selection bias. Trials were at low risk of performance, detection, and reporting bias.At 3 weeks' to 3 months' follow-up, there was high-quality evidence that paracetamol provided no clinically important improvements in pain and physical function. Mean reduction in pain was 23 points (0 to 100 scale, lower scores indicated less pain) with placebo and 3.23 points better (5.43 better to 1.02 better) with paracetamol, an absolute reduction of 3% (1% better to 5% better, minimal clinical important difference 9%) and relative reduction of 5% (2% better to 8% better) (seven trials, 2355 participants). Physical function improved by 12 points on a 0 to 100 scale (lower scores indicated better function) with placebo and was 2.9 points better (0.95 better to 4.89 better) with paracetamol, an absolute improvement of 3% (1% better to 5% better, minimal clinical important difference 10%) and relative improvement of 5% (2% better to 9% better) (7 trials, 2354 participants).High-quality evidence from eight trials indicated that the incidence of adverse events was similar between groups: 515/1586 (325 per 1000) in the placebo group versus 537/1666 (328 per 1000, range 299 to 360) in the paracetamol group (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.92 to 1.11). There was less certainty (moderate-quality evidence) around the risk of serious adverse events, withdrawals due to adverse events, and the rate of abnormal liver function tests, due to wide CIs or small event rates, indicating imprecision. Seventeen of 1480 (11 per 1000) people treated with placebo and 28/1729 (16 per 1000, range 8 to 29) people treated with paracetamol experienced serious adverse events (RR 1.36, 95% CI 0.73 to 2.53; 6 trials). The incidence of withdrawals due to adverse events was 65/1000 participants in with placebo and 77/1000 (range 59 to 100) participants with paracetamol (RR 1.19, 95% CI 0.91 to 1.55; 7 trials). Abnormal liver function occurred in 18/1000 participants treated with placebo and 70/1000 participants treated with paracetamol (RR 3.79, 95% CI 1.94 to 7.39), but the clinical importance of this effect was uncertain. None of the trials reported quality of life.Subgroup analyses indicated that the effects of paracetamol on pain and function did not differ according to the dose of paracetamol (3.0 g/day or less versus 3.9 g/day or greater). AUTHORS' CONCLUSIONS: Based on high-quality evidence this review confirms that paracetamol provides only minimal improvements in pain and function for people with hip or knee osteoarthritis, with no increased risk of adverse events overall. Subgroup analysis indicates that the effects on pain and function do not differ according to the dose of paracetamol. Due to the small number of events, we are less certain if paracetamol use increases the risk of serious adverse events, withdrawals due to adverse events, and rate of abnormal liver function tests.Current clinical guidelines consistently recommend paracetamol as the first-line analgesic medication for hip or knee osteoarthritis, given its low absolute frequency of substantive harm. However, our results call for reconsideration of these recommendations.

Smoking as a Risk Factor for the Development of Periimplant Diseases.

BACKGROUND: Risk factors associated with periimplant disease have been exhaustively explored in many studies. However, despite the high incidence of smokers in the general population, it is still unclear whether smoking is a risk factor for the development of periimplant diseases. PURPOSE: The aim of this review was to analyze all pertinent literature, including systematic reviews, clinical trials, and long-term follow-up, to evaluate smoking as a real risk factor for periimplant diseases. MATERIAL AND METHODS: A comprehensive search was conducted on MEDLINE through PubMed database of the US National Library of Medicine, for articles published until March 2018. All searches were performed using medical subject headings or free-text words. After screening, data extraction, and duplicate removal from 972 found articles, 19 were included in this review. RESULTS: The influence of smoking on the healing process around implants has been explored for potential disruption of the healing process and periimplant disease development. Despite the discussed results in many studies, most of the analyzed literature shows a scientific basis to determine smoking as a risk factor for periimplant disease development, considering that smoking increases the susceptibility to periimplant disease. However, future studies excluding confounding factors need to be performed. CONCLUSION: This review showed that smoking is a real risk factor that increases the likelihood of development of periimplant disease.

Genetic and Environmental Contributions to Sleep Quality and Low Back Pain: A Population-Based Twin Study.

OBJECTIVE: The aim of the study was to estimate the extent to which the co-occurrence of poor sleep quality and low back pain is due to the same genetic and/or environmental risk factors or due to a causal association. METHODS: Cross-sectional data on sleep quality (Pittsburgh Sleep Quality index) and low back pain were collected in a population-based sample of adult twins (N = 2134) registered with the Murcia Twin Registry. Bivariate analysis and structural equation modeling were used. RESULTS: The phenotypic correlation between sleep quality and low back pain was 0.23 (95% confidence interval [CI] = 0.17-0.28). The best-fitting bivariate model included additive genetic and unique environmental factors. Genetic factors accounted for 26% (95% CI = 10-40) and 34% (95% CI = 25-43) of the variability of low back pain and sleep quality, respectively. The correlation between the genetic factors underlying each trait was rG of 0.33 (95% CI = 0.03-0.66), and this overlap of genetic factors explained 42.5% of the phenotypic correlation. On the other hand, nonshared environmental factors of each variable were only fairly correlated rE of 0.19 (95% CI = 0.06-0.31), although this overlap explained 57.5% of the phenotypic correlation. In addition, twins in monozygotic pairs with poorer sleep quality presented more often with low back pain than their co-twins (ρ^ = 0.25, p < .0001). CONCLUSIONS: The data are compatible with a causal effect of sleep quality on low back pain (or the reverse effect), because the correlations between the genetic and unique environmental factors for each trait were significant and there was a significant correlation between the monozygotic twins' difference scores. Apart from environmental factors that affect both characteristics, there are many individual-specific events that influence low back pain but differ from those influencing sleep quality.