Explore the vast range of titles available.

Background In intensive care, weaning is the term used for the process of withdrawal of mechanical ventilation to enable spontaneous breathing to be re-established. Inspiratory muscle weakness and deconditioning are common in patients receiving mechanical ventilation, especially that of prolonged duration. Inspiratory muscle training could limit or reverse these unhelpful sequelae and facilitate more rapid and successful weaning. Methods This review will involve systematic searching of five electronic databases to allow the identification of randomised trials of inspiratory muscle training in intubated and ventilated patients. From these trials, we will extract available data for a list of pre-defined outcomes, including maximal inspiratory pressure, the duration of the weaning period, and hospital length of stay. We will also meta-analyse comparable results where possible, and report a summary of the available pool of evidence. Discussion The data generated by this review will be the most comprehensive answer available to the question of whether inspiratory muscle training is clinically useful in intensive care. As well as informing clinicians in the intensive care setting, it will also inform healthcare managers deciding whether health professionals with skills in respiratory therapy should be made available to provide this sort of intervention. Through the publication of this protocol, readers will ultimately be able to assess whether the review was conducted according to a pre-defined plan. Researchers will be aware that the review is underway, thereby avoid duplication, and be able to use it as a basis for planning similar reviews.

In the Step Study, the MRKAd5 HIV-1 gag/pol/nef vaccine did not reduce plasma viraemia after infection, and HIV-1 incidence was higher in vaccine-treated than in placebo-treated men with pre-existing adenovirus serotype 5 (Ad5) immunity. We assessed vaccine-induced immunity and its potential contributions to infection risk. To assess immunogenicity, we characterised HIV-specific T cells ex vivo with validated interferon-γ ELISPOT and intracellular cytokine staining assays, using a case–cohort design. To establish effects of vaccine and pre-existing Ad5 immunity on infection risk, we undertook flow cytometric studies to measure Ad5-specific T cells and circulating activated (Ki-67+/BcL-2lo) CD4+ T cells expressing CCR5. We detected interferon-γ-secreting HIV-specific T cells (range 163/106 to 686/106 peripheral blood mononuclear cells) ex vivo by ELISPOT in 77% (258/354) of people receiving vaccine; 218 of 354 (62%) recognised two to three HIV proteins. We identified HIV-specific CD4+ T cells by intracellular cytokine staining in 58 of 142 (41%) people. In those with reactive CD4+ T cells, the median percentage of CD4+ T cells expressing interleukin 2 was 88%, and the median co-expression of interferon γ or tumor necrosis factor α (TNFα), or both, was 72%. We noted HIV-specific CD8+ T cells (range 0·4–1·0%) in 117 of 160 (73%) participants, expressing predominantly either interferon γ alone or with TNFα. Vaccine-induced HIV-specific immunity, including response rate, magnitude, and cytokine profile, did not differ between vaccinated male cases (before infection) and non-cases. Ad5-specific T cells were lower in cases than in non-cases in several subgroup analyses. The percentage of circulating Ki-67+BcL-2lo/CCR5+CD4+ T cells did not differ between cases and non-cases. Consistent with previous trials, the MRKAd5 HIV-1 gag/pol/nef vaccine was highly immunogenic for inducing HIV-specific CD8+ T cells. Our findings suggest that future candidate vaccines have to elicit responses that either exceed in magnitude or differ in breadth or function from those recorded in this trial. National Institute of Allergy and Infectious Diseases, US National Institutes of Health; and Merck Research Laboratories.

Objectives This study aimed to assess the economic credentials of a workplace-delivered intervention to reduce sitting time among desk-based workers. Methods We performed within-trial cost-efficacy analysis and long-term cost-effectiveness analysis (CEA) and recruited 231 desk-based workers, aged 24-65 years, across 14 worksites of one organization. Multicomponent workplace-delivered intervention was compared to usual practice. Main outcome measures including total device-measured workplace sitting time, body mass index (BMI), self-reported health-related quality of life (Assessment of Quality of Life-8D, AQoL-8D), and absenteeism measured at 12 months. Results Compared to usual practice, the intervention was associated with greater cost (AU$431/person), benefits in terms of reduced workplace sitting time [-46.8 minutes/8-hour workday, 95% confidence interval (CI): -69.9- -23.7] and increased workplace standing time (42.2 minutes/8-hour workday, 95% CI 23.8-60.6). However, there were no significant benefits for BMI [0.148 kg/m^2 (95% CI-1.407-1.703)], QoL-8D [-0.006 (95% CI -0.074-0.063)] and absenteeism [2.12 days (95% CI -2.01-6.26)]. The incremental cost-efficacy ratios (ICER) ranged from AU$9.94 cost/minute reduction in workplace sitting time to AU$13.37/minute reduction in overall sitting time. CEA showed the intervention contributed to higher life year (LY) gains [0.01 (95% CI 0.009-0.011)], higher health-adjusted life year (HALY) gains [0.012 (95% CI 0.0105 - 0.0135)], and higher net costs [AU$344 (95% CI $331-358)], with corresponding ICER of AU$34 443/LY and AU$28 703/HALY if the intervention effects were to be sustained for five-years. CEA results were sensitive to assumptions surrounding intervention-effect decay rate and discount rate. Conclusions The intervention was cost-effective over the lifetime of the cohort when scaled up to the national workforce and provides important evidence for policy-makers and workplaces regarding allocation of resources to reduce workplace sitting.

Background The online BeUpstanding™ program is an eight-week workplace-delivered intervention for desk-based workers to raise awareness of the benefits of sitting less and moving more and build a supportive culture for change. A workplace representative (the “champion”) delivers the program, which includes a workshop where teams collectively choose their sit less/move more strategies. A toolkit provides the champion with a step-by-step guide and associated resources to support program uptake, delivery, and evaluation. Here we report on the main findings from the Australian national implementation trial of BeUpstanding. Methods Recruitment (12/06/2019 to 30/09/2021) was supported by five policy and practice partners, with desk-based work teams from across Australia targeted. Effectiveness was measured via a single arm, repeated-measures trial. Data were collected via online surveys, toolkit analytics, and telephone calls with champions. The RE-AIM framework guided evaluation, with adoption/reach (number and characteristics); effectiveness (primary: self-reported workplace sitting time); implementation (completion of core components; costs); and, maintenance intentions reported here. Linear mixed models, correcting for cluster, were used for effectiveness, with reach, adoption, implementation, and maintenance outcomes described. Results Of the 1640 website users who signed-up to BeUpstanding during the recruitment period, 233 were eligible, 198 (85%) provided preliminary consent, and 118 (50.6%) champions consented and started the trial, with 94% ( n  = 111 champions) completing. Trial participation was from across Australia and across industries, and reached 2,761 staff, with 2,248 participating in the staff survey(s): 65% female; 64% university educated; 17% from a non-English speaking background. The program effectively changed workplace sitting (-38.5 [95%CI -46.0 to -28.7] minutes/8-hour workday) and all outcomes targeted by BeUpstanding (behaviours and culture), with small-to-moderate statistically-significant effects observed. All participating teams ( n  = 94) completed at least 5/7 core steps; 72.4% completed all seven. Most champions spent $0 (72%) or >$0-$5 (10%) per team member; most (67/70 96%) intended to continue or repeat the program. Conclusions BeUpstanding can be adopted and successfully implemented by a range of workplaces, reach a diversity of staff, and be effective at creating a supportive culture for teams of desk-based workers to sit less and move more. Learnings will inform optimisation of the program for longer-term sustainability. Trial registration ACTRN12617000682347.

Background. Human immunodeficiency virus (HIV)–infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown. Methods. Twelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996–2000), middle (2001–2005), and modern (2006–2010) eras. Results. Among 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61–1.47) for HCV, 0.95 (.40–2.26) for HBV, and 1.52 (.46–5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy. Conclusions. Despite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients.

IntroductionDespite being an important period for the development of movement behaviours (physical activity, sedentary behaviour and sleep), few interventions commencing prior to preschool have been trialled. The primary aim of this trial is to assess the 12-month efficacy of the Let’s Grow mHealth intervention, designed to improve the composition of movement behaviours in children from 2 years of age. Let’s Grow is novel in considering composition of movement behaviours as the primary outcome, using non-linear dynamical approaches for intervention delivery, and incorporating planning for real-world implementation and scale-up from its inception.Methods and analysisA randomised controlled trial will test the effects of the 12-month parental support mHealth intervention, Let’s Grow, compared with a control group that will receive usual care plus electronic newsletters on unrelated topics for cohort retention. Let’s Grow will be delivered via a purpose-designed mobile web application with linked SMS notifications. Intervention content includes general and movement-behaviour specific parenting advice and incorporates established behaviour change techniques. Intervention adherence will be monitored by app usage data. Data will be collected from participants using 24-hour monitoring of movement behaviours and parent report at baseline (T0), mid-intervention (T1; 6 months post baseline), at intervention conclusion (T2; 12 months post baseline) and 1-year post intervention (T3; 2 years post baseline). The trial aims to recruit 1100 families from across Australia during 2021. In addition to assessment of efficacy, an economic evaluation and prospective scalability evaluation will be conducted.Ethics and disseminationThe study was approved by the Deakin University Human Ethics Committee (2020-077). Study findings will be disseminated through publication in peer-reviewed journals, presentation at scientific and professional conferences, and via social and traditional media.Trial registration numberACTRN12620001280998; U1111-1252-0599.

The web-based BeUpstanding Champion Toolkit was developed to support work teams in addressing the emergent work health and safety issue of excessive sitting. It provides a step-by-step guide and associated resources that equip a workplace representative-the champion-to adopt and deliver the 8-week intervention program (BeUpstanding) to their work team. The evidence-informed program is designed to raise awareness of the benefits of sitting less and moving more, build a supportive culture for change, and encourage staff to take action to achieve this change. Work teams collectively choose the strategies they want to implement and promote to stand up, sit less, and move more, with this bespoke and participative approach ensuring the strategies are aligned with the team's needs and existing culture. BeUpstanding has been iteratively developed and optimized through a multiphase process to ensure that it is fit for purpose for wide-scale implementation. The study aimed to describe the current version of BeUpstanding, and the methods and protocol for a national implementation trial. The trial will be conducted in collaboration with five Australian workplace health and safety policy and practice partners. Desk-based work teams from a variety of industries will be recruited from across Australia via partner-led referral pathways. Recruitment will target sectors (small business, rural or regional, call center, blue collar, and government) that are of priority to the policy and practice partners. A minimum of 50 work teams will be recruited per priority sector with a minimum of 10,000 employees exposed to the program. A single-arm, repeated-measures design will assess the short-term (end of program) and long-term (9 months postprogram) impacts. Data will be collected on the web via surveys and toolkit analytics and by the research team via telephone calls with champions. The Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework will guide the evaluation, with assessment of the adoption/reach of the program (the number and characteristics of work teams and participating staff), program implementation (completion by the champion of core program components), effectiveness (on workplace sitting, standing, and moving), and maintenance (sustainability of changes). There will be an economic evaluation of the costs and outcomes of scaling up to national implementation, including intervention affordability and sustainability. The study received funding in June 2018 and the original protocol was approved by institutional review board on January 9, 2017, with national implementation trial consent and protocol amendment approved March 12, 2019. The trial started on June 12, 2019, with 48 teams recruited as of December 2019. The implementation and multimethod evaluation of BeUpstanding will provide the practice-based evidence needed for informing the potential broader dissemination of the program. Australian New Zealand Clinical Trials Registry ACTRN12617000682347; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372843&isReview=true. DERR1-10.2196/15756.