Evaluation of intensive community care services for young people with psychiatric emergencies: study protocol for a multi-centre parallel-group, single-blinded randomized controlled trial with an internal pilot phase.

BACKGROUND: Over 3000 young people under the age of 18 are admitted to Tier 4 Child and Adolescent Mental Health Services (CAMHS) inpatient units across the UK each year. The average length of hospital stay for young people across all psychiatric units in the UK is 120 days. Research is needed to identify the most effective and efficient ways to care for young people (YP) with psychiatric emergencies. This study aims to evaluate the clinical effectiveness and cost-effectiveness of intensive community care service (ICCS) compared to treatment as usual (TAU) for young people with psychiatric emergencies. METHODS: This is a multicentre two-arm randomized controlled trial (RCT) with an internal pilot phase. Young people aged 12 to < 18 considered for admission at participating NHS organizations across the UK will be randomized 1:1 to either TAU or ICCS. The primary outcome is the time to return to or start education, employment, or training (EET) at 6 months post-randomization. Secondary outcomes will include evaluations of mental health and overall well-being and patient satisfaction. Service use and costs and cost-effectiveness will also be explored. Intention-to-treat analysis will be adopted. The trial is expected to be completed within 42 months, with an internal pilot phase in the first 12 months to assess the recruitment feasibility. A process evaluation using visual semi-structured interviews will be conducted with 42 young people and 42 healthcare workers. DISCUSSION: This trial is the first well-powered randomized controlled trial evaluating the clinical and cost-effectiveness of ICCS compared to TAU for young people with psychiatric emergencies in Great Britain. TRIAL REGISTRATION: ISRCTN ISRCTN42999542, Registration on April 29, 2020.

Flow rate accuracy of infusion devices within healthcare settings: a systematic review.

Background: One in five patients admitted to the hospital treated with intravenous (IV) fluid therapy suffer complications due to inappropriate administration. Errors have been reported in 13-84% of the preparation and administration of IV medications. The safe delivery of IV fluids requires precise rate administration. Objectives: This systematic review aims to determine the accuracy of infusion sets and devices and examine the factors that affect the flow rate accuracy of devices. Data Sources and Methods: Six databases (CINAHL, MEDLINE PubMed, EMBASE, Web of Science and Cochrane Database of systematic reviews) were systematically searched. Search terms included infusion pumps, infusion devices, flow rate accuracy, fluid administration rate, gravity-led infusion set and fluid balance. Studies were included if they examined infusion devices' flow rate accuracy and drop rates for fluids or non-oncological drugs. Findings were tabulated and synthesised qualitatively. The quality of the studies was examined based on the design of the studies due to their heterogeneity. Results: Eight studies were included: Four studies were conducted on human subjects in the hospital environment; studies recruited 182 participants between the ages of 18 and 94 years. Two studies examined flow rate accuracy in recruited patients across 509 observations and 2387 drip hours. No trials prospectively assessed the accuracy of infusion pumps in the clinical domain, and no studies were reported on patient safety outcomes. Four studies examined the impact of mechanical and physiological factors on the flow rate accuracies of infusion devices. Height and back pressure simulated vibrating conditions, the viscosity of IV fluid and the positions of patients were reported to have a significant impact on infusion volume and flow rates of infusion devices. Additionally, giving sets that vary from the manufacturer's specifications are reported to increase error percent by 10-20%. Conclusion: Infusion devices are an important source of error in administering IV fluids. Yet, there needs to be more prospective trial data to support their clinical accuracy and the impact on patient outcomes. Future flow variability and accuracy studies should capture their impact on patient safety and clinical outcomes.

Are the flow rate of infusion devices accurate in fluid administration? Background/Why was this study done? Nearly all patients in healthcare settings undergo treatment with fluid therapy that is administered through a vein. Inaccurate intravenous fluid administration causes patient harm. However, very little information in the literature explains how precisely intravenous fluid is administered. What did the researchers do? We reviewed the literature on flow rate accuracies of specific infusion devices and examined the factors that affect the flow rate accuracies of intravenous fluid administered to patients. What did the researchers find? We found that the flow rate accuracies of infusion devices vary greatly, and they are often affected by physiological and mechanical factors. However, the precise impact of this on patients' clinical outcomes is not often reported, representing a significant knowledge gap. What do the findings mean? We conclude that there is an urgent need to improve the reporting and precision of intravenous fluid rate administration and to understand how this impacts patient safety and clinical outcomes.

Integrated virtual screening and molecular dynamics simulation revealed promising drug candidates of p53-MDM2 interaction.

In the vast majority of malignancies, the p53 tumor suppressor pathway is compromised. In some cancer cells, high levels of MDM2 polyubiquitinate p53 and mark it for destruction, thereby leading to a corresponding downregulation of the protein. MDM2 interacts with p53 via its hydrophobic pocket, and chemical entities that block the dimerization of the protein-protein complex can restore p53 activity. Thus far, only a few chemical compounds have been reported as potent arsenals against p53-MDM2. The Protein Data Bank has crystallogaphic structures of MDM2 in complex with certain compounds. Herein, we have exploited one of the complexes in the identification of new p53-MDM2 antagonists using a hierarchical virtual screening technique. The initial stage was to compile a targeted library of structurally appropriate compounds related to a known effective inhibitor, Nutlin 2, from the PubChem database. The identified 57 compounds were subjected to virtual screening using molecular docking to discover inhibitors with high binding affinity for MDM2. Consequently, five compounds with higher binding affinity than the standard emerged as the most promising therapeutic candidates. When compared to Nutlin 2, four of the drug candidates (CID_140017825, CID_69844501, CID_22721108, and CID_22720965) demonstrated satisfactory pharmacokinetic and pharmacodynamic profiles. Finally, MD simulation of the dynamic behavior of lead-protein complexes reveals the stability of the complexes after a 100,000 ps simulation period. In particular, when compared to the other three leads, overall computational modeling found CID_140017825 to be the best pharmacological candidate. Following thorough experimental trials, it may emerge as a promising chemical entity for cancer therapy.

Evaluation of Mental Health First Aid from the Perspective Of Workplace End UseRs-EMPOWER: protocol of cluster randomised trial phase.

BACKGROUND: Mental Health First Aid (MHFA) is a mental health intervention that teaches people how to identify, understand and help someone who may be experiencing a mental health issue. Reviews of the implementation of MHFA found between 68 and 88% of trained Mental Health First Aiders had used their skills when in contact with someone experiencing mental health difficulties. Reviews evaluating the impact of MHFA suggest positive outcomes. However, to date, there has been no systematic, rigorous evaluation of the impact of MHFA on recipients of the intervention, the organisations providing it and the cost-effectiveness of MHFA overall. This trial will evaluate the effectiveness and cost-effectiveness of MHFA. METHODS: The study is a multi-centred, two-arm clustered randomised controlled trial. Organisations will be randomly allocated to the control or intervention (estimated sample size 800 recipients). The intervention is the standard MHFA intervention provided by Mental Health First Aid England (MHFAE). The control condition will be organisations having a brief consultation from MHFAE on promoting mental health and well-being in the workplace. The primary outcome is health seeking behaviour, measured using the Actual Help Seeking Questionnaire, at 6 months' follow-up. Data collection will be undertaken at baseline (T0), post-intervention-up to 3 months (T1), at 6 months (T2), 12 months (T3) and 24 months (T4). The primary analysis will be conducted on those participants who receive MHFA, a per protocol analysis. DISCUSSION: The study is the first to evaluate the effect of MHFA in the workplace on employees with direct and indirect experience of the intervention, when compared with usual practice. Being also the first to assess, systematically, the social impact of MHFA and investigate its cost-effectiveness adds to the originality of the study. The study promises to yield important data, as yet unknown, regarding the effectiveness, cost-effectiveness, implementation issues, and the sustainability of MHFA in the workplace. TRIAL REGISTRATION: Clinicaltrials.gov NCT04311203 . Registered on 17 March 2020.