Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data.

Background: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies.

Methods: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.

PROTOCOL: Behavioral, information and monetary interventions to reduce energy consumption in households: A "living" systematic review.

This is the protocol for a Campbell systematic review. The objectives are as follows: Our proposed systematic review and meta-analysis will integrate the evidence available from all sources to answer the following questions: (1) to what extent can information, behavioral and monetary interventions reduce energy consumption of households in residential buildings? (average treatment effect of interventions) (2) what is the relative effectiveness of interventions? (account for heterogeneity in treatment effects across and within studies) (3) how effective are combinations of different interventions?

Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies.

Background: There is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studies on the efficacy, safety, and underlying mechanism of action of TAAR1 agonism for psychosis.

Exploring the use and impact of the Australian living guidelines for the clinical care of people with COVID-19: where to from here?

Objectives: The Australian National COVID-19 Clinical Evidence Taskforce has been developing, maintaining, and disseminating living guidelines and decision support tools (clinical flowcharts) for the care of people with suspected or confirmed COVID-19 since 2020. Living guidelines, a form of living evidence, are a relatively new approach; hence, more work is required to determine how to optimize their use to inform practice, policy, and decision-making and to explore implementation, uptake, and impact implications. An update of an earlier impact evaluation was conducted to understand sustained awareness and use of the guidelines; the factors that facilitate the widespread adoption of the guidelines and to explore the perceived strengths and opportunities for improvement of the guidelines.

New living evidence resource of human and non-human studies for early intervention and research prioritisation in anxiety, depression and psychosis.

In anxiety, depression and psychosis, there has been frustratingly slow progress in developing novel therapies that make a substantial difference in practice, as well as in predicting which treatments will work for whom and in what contexts. To intervene early in the process and deliver optimal care to patients, we need to understand the underlying mechanisms of mental health conditions, develop safe and effective interventions that target these mechanisms, and improve our capabilities in timely diagnosis and reliable prediction of symptom trajectories. Better synthesis of existing evidence is one way to reduce waste and improve efficiency in research towards these ends.

Changes in dispensing of medicines proposed for re-purposing in the first year of the COVID-19 pandemic in Australia.

Background: Since COVID-19 was first recognised, there has been ever-changing evidence and misinformation around effective use of medicines. Understanding how pandemics impact on medicine use can help policymakers act quickly to prevent harm. We quantified changes in dispensing of common medicines proposed for "re-purposing" due to their perceived benefits as therapeutic or preventive for COVID-19 in Australia.

Perspectives of patients, family members, health professionals and the public on the impact of COVID-19 on mental health.

Background: The coronavirus (COVID-19) pandemic has seen a global surge in anxiety, depression, post-traumatic stress disorder (PTSD), and stress.

Aims: This study aimed to describe the perspectives of patients with COVID-19, their family, health professionals, and the general public on the impact of COVID-19 on mental health.

Methods: A secondary thematic analysis was conducted using data from the COVID-19 COS project.

Awareness, value and use of the Australian living guidelines for the clinical care of people with COVID-19: an impact evaluation.

Background And Objective: The Australian National COVID-19 Clinical Evidence Taskforce is developing living, evidence-based, national guidelines for treatment of people with COVID-19. These living guidelines are updated each week. We undertook an impact evaluation to understand the extent to which health professionals providing treatment to people with COVID 19 were aware of, valued and used the guidelines, and the factors that enabled or hampered this.

Living Systematic Reviews.

Systematic reviews are difficult to keep up to date, but failure to do so leads to poor review currency and accuracy. "Living systematic review" (LSR) is an approach that aims to continually update a review, incorporating relevant new evidence as it becomes available. LSRs may be particularly important in fields where research evidence is emerging rapidly, current evidence is uncertain, and new research may change policy or practice decisions.

Rapid and Living Guidance for COVID-19.

In their article, Qaseem and colleagues reported how the American College of Physicians responded to the urgent need for guidance during the COVID-19 pandemic by producing living, rapid practice points. The editorialists discuss the challenges of developing high-quality, up-to-date evidence-based recommendations and how rapid and living reviews and guidelines are important additions to the tools we have available to translate research evidence into improved health outcomes.

Core Outcome Measures for Trials in People With Coronavirus Disease 2019: Respiratory Failure, Multiorgan Failure, Shortness of Breath, and Recovery.

Objectives: Respiratory failure, multiple organ failure, shortness of breath, recovery, and mortality have been identified as critically important core outcomes by more than 9300 patients, health professionals, and the public from 111 countries in the global coronavirus disease 2019 core outcome set initiative. The aim of this project was to establish the core outcome measures for these domains for trials in coronavirus disease 2019.

Design: Three online consensus workshops were convened to establish outcome measures for the four core domains of respiratory failure, multiple organ failure, shortness of breath, and recovery.

Core Outcomes Set for Trials in People With Coronavirus Disease 2019.

Objectives: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019.

Design: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries.

International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019.

Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials.

Towards a new model for producing evidence-based guidelines: a qualitative study of current approaches and opportunities for innovation among Australian guideline developers.

Many organisations in Australia undertake systematic reviews to inform development of evidence-based guidelines or would like to do so. However, the substantial resources required to produce systematic reviews limit the feasibility of evidence-based approaches to guideline development. We are working with Australian guideline developers to design, build and test systems that make creating evidence-based guidelines easier and more efficient.

Recruiting people with HIV to an online self-management support randomised controlled trial: barriers and facilitators.

Unlabelled: Background Recruitment of people to randomised trials of online interventions presents particular challenges and opportunities. The aim of this study was to evaluate factors associated with the recruitment of people with HIV (PWHIV) and their doctors to the HealthMap trial, a cluster randomised trial of an online self-management program.

Methods: Recruitment involved a three-step process.

Routine versus Targeted Viral Load Strategy among Patients Starting Antiretroviral in Hanoi, Vietnam.

Introduction: HIV viral load (VL) testing is recommended by the WHO as the preferred method for monitoring patients on antiretroviral therapy (ART). However, evidence that routine VL (RVL) monitoring improves clinical outcomes is lacking.

Methods: We conducted a prospective, randomized controlled trial of RVL monitoring every six months versus a targeted VL (TVL) strategy (routine CD4 plus VL testing if clinical or immunological failure) in patients starting ART between April 2011 and April 2014 at Bach Mai Hospital in Hanoi.

Performance of a Novel Low-Cost, Instrument-Free Plasma Separation Device for HIV Viral Load Quantification and Determination of Treatment Failure in People Living with HIV in Malaysia: a Diagnostic Accuracy Study.

HIV viral load (VL) testing is the recommended method for monitoring the response of people living with HIV and receiving antiretroviral therapy (ART). The availability of standard plasma VL testing in low- and middle-income countries (LMICs), and access to this testing, are limited by the need to use fresh plasma. Good specimen collection methods for HIV VL testing that are applicable to resource-constrained settings are needed.

The systematic development of a complex intervention: HealthMap, an online self-management support program for people with HIV.

Background: Despite persistent calls for HIV care to adopt a chronic care approach, few HIV treatment services have been able to establish service arrangements that prioritise self-management. To prevent cardiovascular and other chronic disease outcomes, the HealthMap program aims to enhance routine HIV care with opportunities for self-management support. This paper outlines the systematic process that was used to design and develop the HealthMap program, prior to its evaluation in a cluster-randomised trial.

Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial.

Disulfiram (DSF) was well tolerated and activated viral transcription (cell-associated unspliced (CA-US) and plasma human immunodeficiency virus (HIV) RNA) in a phase II dose-escalation trial in HIV+ antiretroviral therapy (ART)-suppressed participants. Here, we investigated whether exposure to DSF and its metabolites predicted these changes in HIV transcription. Participants were administered 500 (N = 10), 1,000 (N = 10), or 2,000 (N = 10) mg of DSF for 3 consecutive days.

Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1.

Objective(s): To determine whether variation in cell-associated unspliced (CA-US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis.

Methods: Prospective observational study of HIV-infected individuals on ART. Blood was collected on three occasions and CA-US HIV RNA and mRNA of the circadian-locomotor-output-cycles-kaput (CLOCK)-associated genes quantified by real time PCR.

The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial.

Background: Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment.

Methods: In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia.

Living systematic review: 1. Introduction-the why, what, when, and how.

Systematic reviews are difficult to keep up to date, but failure to do so leads to a decay in review currency, accuracy, and utility. We are developing a novel approach to systematic review updating termed "Living systematic review" (LSR): systematic reviews that are continually updated, incorporating relevant new evidence as it becomes available. LSRs may be particularly important in fields where research evidence is emerging rapidly, current evidence is uncertain, and new research may change policy or practice decisions.

Time from HIV diagnosis to commencement of antiretroviral therapy as an indicator to supplement the HIV cascade: Dramatic fall from 2011 to 2015.

Introduction: The HIV care cascade is increasingly used to evaluate HIV treatment programs at the population level. However, the cascade indicators lack the ability to show changes over time, which reduces their utility to guide health policy. Alternatives have been proposed but are complex or result in a delay in results.

No adverse safety or virological changes 2 years following vorinostat in HIV-infected individuals on antiretroviral therapy.

Objective: To determine the long-term effects of vorinostat on safety and virological parameters in HIV-infected individuals on suppressive antiretroviral therapy (ART).

Design: Prospective longitudinal observational extended follow-up of 20 HIV-infected individuals on ART previously enrolled in a clinical trial of daily vorinostat 400 mg for 14 days. Extended follow-up included visits at 6, 12, 18 and 24 months postenrolment in the initial clinical trial.