Beyond Cost Per Use: Exploring Multivariable E-Resource Assessment

The converging pressures of dwindling budgets, increasing subscription costs, and shifting user expectations has intensified the impact of collection management decision making. Assessing e-resource subscriptions is an integral part of any library’s collection management process, though it is especially important in academic environments. While cost per use (CPU) can be a straightforward and informative measure to consider, that lone data point might not reveal the true value of an e-resource. This paper outlines a multifaceted assessment strategy that considers the various merits of an e-resource, such as supporting accreditation, providing access to material not easily obtained through resource-sharing channels, discoverability, platform ease of use, and the quality of vendor support or responsiveness. Incorporating CPU data into a more holistic rubric might require additional time and energy, but the resulting decisions to renew or discontinue subscriptions will be more nuanced and compatible with a library’s underlying commitment to curating distinctive and accessible e-resource collections. While the proposed rubric is not a panacea, it is an inherently flexible tool that can be customized at the local level to help libraries define and articulate their priorities, analyze value as a multifaceted concept, and strategically invest their collection budgets into resources that resonate with long-term goals and needs

Pharyngeal Oxygen Delivery Device Sustains Manikin Lung Oxygenation Longer Than High-Flow Nasal Cannula

PURPOSE: Hypoxemia during a failed airway scenario is life threatening. A dual-lumen pharyngeal oxygen delivery device (PODD) was developed to fit inside a traditional oropharyngeal airway for undisrupted supraglottic oxygenation and gas analysis during laryngoscopy and intubation. We hypothesized that the PODD would provide oxygen as effectively as high-flow nasal cannula (HFNC) while using lower oxygen flow rates. METHODS: We compared oxygen delivery of the PODD to HFNC in a preoxygenated, apneic manikin lung that approximated an adult functional residual capacity. Four arms were studied: HFNC at 20 and 60 liters per minute (LPM) oxygen, PODD at 10 LPM oxygen, and a control arm with no oxygen flow after initial preoxygenation. Five randomized 20-minute trials were performed for each arm (20 trials total). Descriptive statistics and analysis of variance were used with statistical significance of RESULTS: Mean oxygen concentrations were statistically different and decreased from 97% as follows: 41 ± 0% for the control, 90 ± 1% for HFNC at 20 LPM, 88 ± 2% for HFNC at 60 LPM, and 97 ± 1% (no change) for the PODD at 10 LPM. CONCLUSION: Oxygen delivery with the PODD maintained oxygen concentration longer than HFNC in this manikin model at lower flow rates than HFNC

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study)

Abstract Background Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson’s Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. Methods The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology – Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. Trial registration ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0

Beta-blocker Therapy and Clinical Outcomes in Patients with Moderate COPD and Heightened Cardiovascular Risk:An Observational Sub-study of SUMMIT

Rationale: Cardiovascular disease is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD). Although beta-blockers can be used safely in COPD, concerns remain regarding safety and efficacy interactions in patients using concomitant inhaled long-acting beta-agonists. Objectives: To compare the differential effects of long-acting beta agonist or inhaled corticosteroid use on clinical outcomes in patients with heightened cardiovascular risk treated and not treated with beta-blockers. Methods: We examined data from 16,485 participants in the Study to Understand Mortality and MorbidITy in COPD (SUMMIT) who were randomized to once daily inhaled fluticasone furoate (FF), vilanterol (VI), their combination (FF/VI), or placebo and examined the associations between treatment allocation and lung function, COPD exacerbations, cardiovascular events, and all-cause mortality stratified by baseline beta-blocker therapy. Results: Baseline beta-blocker therapy was used by 31% (n=5,159) of SUMMIT participants. There was no evidence of an interaction between baseline beta-blocker therapy and the association between inhaled treatments and FEV1 at 3 months (p=0.27), 6 months (p=0.14), or 12 months (p=0.33). The placebo-adjusted mean difference in post-bronchodilator FEV1 at 3 months in the VI alone group was 58 mL [95% confidence interval (CI) 38, 78] in those taking baseline beta-blocker therapy, and 51 mL [95%CI 38, 65], in those not taking baseline beta-blocker therapy. The placebo-adjusted mean difference in post-bronchodilator FEV1 at 3 months in the FF/VI group was 85 mL [95%CI 65, 105] in those taking baseline beta-blocker therapy, and 68 mL [95%CI 54, 82] in those not taking baseline beta-blocker therapy. Overall, there was no evidence of interactions by randomized treatment, including VI alone or in combination with FF, for COPD exacerbations (p=0.18), cardiovascular composite events (p=0.33), and all-cause mortality (p=0.41). Conclusions: There is no evidence to suggest that baseline beta-blocker therapy reduces the respiratory benefits or increases the cardiovascular risk of inhaled long-acting beta-agonists in patients with COPD and heightened cardiovascular risk. Clinical trial registered with ClinicalTrials.gov (NCT01313676

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

Measles Virus C Protein Impairs Production of Defective Copyback Double-Stranded Viral RNA and Activation of Protein Kinase R

Measles virus (MV) lacking expression of C protein (C(KO)) is a potent activator of the double-stranded RNA (dsRNA)-dependent protein kinase (PKR), whereas the isogenic parental virus expressing C protein is not. Here, we demonstrate that significant amounts of dsRNA accumulate during C(KO) mutant infection but not following parental virus infection. dsRNA accumulated during late stages of infection and localized with virus replication sites containing N and P proteins. PKR autophosphorylation and stress granule formation correlated with the timing of dsRNA appearance. Phospho-PKR localized to dsRNA-containing structures as revealed by immunofluorescence. Production of dsRNA was sensitive to cycloheximide but resistant to actinomycin D, suggesting that dsRNA is a viral product. Quantitative PCR (qPCR) analyses revealed reduced viral RNA synthesis and a steepened transcription gradient in C(KO) virus-infected cells compared to those in parental virus-infected cells. The observed alterations were further reflected in lower viral protein expression levels and reduced C(KO) virus infectious yield. RNA deep sequencing confirmed the viral RNA expression profile differences seen by qPCR between C(KO) mutant and parental viruses. After one subsequent passage of the C(KO) virus, defective interfering RNA (DI-RNA) with a duplex structure was obtained that was not seen with the parental virus. We conclude that in the absence of C protein, the amount of PKR activator RNA, including DI-RNA, is increased, thereby triggering innate immune responses leading to impaired MV growth