A Randomised trial of anti-GM-CSF Otilimab in severe COVID-19 pneumonia (OSCAR).

Abstract BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of coronavirus disease 2019 (COVID-19). METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure, and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (N=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8, 11.4; p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2, 33.1; p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (N=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3, 11.2; p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CCL17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.

Co-developing patient and family engagement indicators for health system improvement with healthcare system stakeholders: a consensus study.

OBJECTIVE: To develop a set of patient and family engagement indicators (PFE-Is) for measuring engagement in health system improvement for a Canadian provincial health delivery system through an evidence-based consensus approach. DESIGN: This mixed-method, multiphase project included: (1) identification of existing measures of patient and family engagement through a review of the literature and consultations with a diverse provincial council of patients, caregivers, community members and researchers. The Public and Patient Engagement Evaluation Tool (PPEET) was selected; (2) consultations on relevance, acceptability and importance with patient and family advisors, and staff members of Alberta Health Services' Strategic Clinical Networks. This phase included surveys and one-on-one semi-structured interviews aimed to further explore the use of PPEET in this context. Findings from the survey and interviews informed the development of PFE-Is; (3) a Delphi consensus process using a modified RAND/UCLA Appropriateness Method to identify and refine a core set of PFE-Is. PARTICIPANTS: The consensus panel consisted of patients, family members, community representatives, clinicians, researchers and healthcare leadership. RESULTS: From an initial list of 33 evidence-based PFE-Is identified, the consensus process yielded 18 final indicators. These PFE-Is were grouped into seven themes: communication, comfort to contribute, support needed for engagement, impact and influence of engagement initiative, diversity of perspectives, respectful engagement, and working together indicators. CONCLUSIONS: This group of final patient, family and health system leaders informed indicators can be used to measure and evaluate meaningful engagement in health research and system transformation. The use of these metrics can help to improve the quality of patient and family engagement to drive health research and system transformation.

Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.

Palliative and end-of-life care in intensive care units in low- and middle-income countries: A systematically constructed scoping review.

PURPOSE: Death is common in intensive care units, and integrating palliative care enhances outcomes. Most research has been conducted in high-income countries. The aim is to understand what is known about the type and topics of research on the provision of palliative care within intensive care units in low- and middle-income countries MATERIALS AND METHODS: Scoping review with nine databases systematically searched for literature published in English on palliative care in intensive care units in low- and middle- income settings (01/01/1990 to 31/05/2021). Two reviewers independently checked search results and extracted textual data, which were analyzed and represented as themes. RESULTS: Thirty papers reported 19 empirical studies, two clinical case reports and six discussion papers. Papers originated from Asia and Africa, primarily using observational designs and qualitative approaches, with no trials or other robust evaluative or comparative studies. No studies directly sought data from patients or families. Five areas of research focus were identified: withholding and withdrawing treatment; professional knowledge and skills; patient and family views; culture and context; and costs of care. CONCLUSIONS: Palliative care in intensive care units in low-and middle-income countries is understudied. Research focused on the specific needs of intensive care in low- and middle-income countries is required to ensure optimal patient outcomes.

Safety and Immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India.

BACKGROUND: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. METHODS: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. FINDINGS: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34·9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36·36%), 4/12 (33·33%), 10/10 (100·00%) and 8/10 (80·00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. INTERPRETATION: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

Study on PCM Assisted Constant Temperature Water Heating System

Spread of novel coronavirus across the globe creates panic situations internationally. Major challenge of this pandemic situation is the absence of a specific treatment or vaccine for curing the disease. As per published report of WHO, temperature above 55 ° C is potentially kill Corona virus. This study focuses on design a water heating system that could provide water above the required temperature with minimal input power even during the off-sunshine hours. The thermal performance of Phase Change Material (PCM) integrated solar water heating system providing water temperature above 56 ° C both during the day and the off sunshine hours has been discussed in this present study. The phase change behaviour of paraffin-wax-6035 confined within a copper tube of 100 mm diameter and 1000 mm length and 1 mm thickness, has been studied using CFD analysis. The analysis is carried out for three different cases viz. conventional solar water heating system, modified solar water heating system integrated with bare PCM tube and finned PCM tube of 1 mm fin thickness. The thermal storage capacity of solar water heater is compared based on the thermal storage capacity factor which is calculated to be 1.1149 & 1.1586 for bare PCM tube and finned PCM tube case, respectively with respect to the conventional solar water heater.