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Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.
Phase 2a randomised, placebo-controlled, double-blinded, trial.
Hospitals in Canada, Turkey and the USA.
A total of 61 subjects with moderate-to-severe COVID-19.
Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.
The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.
At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2 ≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.
In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.
Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual’s body image can inform obesity prevention and management. This study’s objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension.
Research visits were completed in local research clinics in respective countries.
Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country).
Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg.
Most women and men from the USA and Seychelles had ‘Perceived minus Actual weight status Discrepancy’ scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size.
This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people’s perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.
Knowledge models inform organizational behavior through the logical association of documentation processes, definitions, data elements, and value sets. The development of a well-designed knowledge model allows for the reuse of electronic health record data to promote efficiency in practice, data interoperability, and the extensibility of data to new capabilities or functionality such as clinical decision support, quality improvement, and research. The purpose of this article is to describe the development and validation of a knowledge model for healthcare-associated venous thromboembolism prevention. The team used FloMap, an Internet-based survey resource, to compare metadata from six healthcare organizations to an initial draft model. The team used consensus decision-making over time to compare survey results. The resulting model included seven panels, 41 questions, and 231 values. A second validation step included completion of an Internet-based survey with 26 staff nurse respondents representing 15 healthcare organizations, two electronic health record vendors, and one academic institution. The final knowledge model contained nine Logical Observation Identifiers Names and Codes panels, 32 concepts, and 195 values representing an additional six panels (groupings), 15 concepts (questions), and the specification of 195 values (answers). The final model is useful for consistent documentation to demonstrate the contribution of nursing practice to the prevention of venous thromboembolism. by Özgür İlke Ulusoy, Nidambur Vasudev Ballal, Rajkumar Narkedamalli, Nuran Ulusoy, Krishna Prasad Shetty, Alexander Maniangat Luke
This study aimed to evaluate the dislodgement resistance and structural changes of different mineral trioxide aggregate cements (MTA) like Pro-Root MTA, Ortho MTA, and Retro MTA after exposure to sodium hypochlorite (NaOCl), NaOCl-Ethylenediaminetetraacetic acid (EDTA), 1-hydroxyethylidene-1, 1-bisphosphonate (Dual Rinse HEDP), and NaOCl-Maleic acid (MA). The root canal spaces of 150 dentine slices were obturated using tricalcium silicate cements and divided into 3 groups (n = 50): Group1: ProRoot MTA, Group2: Retro MTA, and Group3: Ortho MTA. The samples in each group were further subdivided into four experimental (n = 10) and one control groups (n = 10): 2.5% NaOCl-17% EDTA, Dual Rinse HEDP, 2.5% NaOCl-7% Maleic acid, 2.5% NaOCl, distilled water (control). The dislodgement resistance and structural changes of cements were measured. Use of DR HEDP resulted in higher dislodgement resistance compared to17% EDTA and 7% MA in the samples obturated with Ortho MTA and Pro-Root MTA (pby Jake V. Hinton, Calvin M. Fletcher, Luke A. Perry, Noah Greifer, Jessica N. Hinton, Jenni Williams-Spence, Reny Segal, Julian A. Smith, Christopher M. Reid, Laurence Weinberg, Rinaldo Bellomo
BackgroundPlatelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown.
MethodsWe conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005–2021 across 58 sites were included. The primary outcome was operative mortality.
ResultsOf 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P Conclusion
In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting.
by Lakmini Kosgahakumbura, Jayani Gamage, Luke P. Robertson, Taj Muhammad, Björn Hellman, Ulf Göransson, Prabath Jayasinghe, Chamari Hettiarachchi, Paco Cárdenas, Sunithi Gunasekera
Sri Lanka is a biodiversity hotspot and one of the richest geographical locations of marine sponges in the Indian ocean. However, the most extensive taxonomical study on Sri Lankan sponge biodiversity dates back ~100 years and only a limited number of studies have been conducted on sponge natural products. In the current study, 35 marine sponge specimens (collected from 16 sponge habitats around Sri Lanka) were identified, microfractionated and evaluated for antibacterial and anticancer assays. In total, 30 species were characterized, of which 19 species gave extracts with antibacterial and/or cytotoxic activities. Microfractionated organic extract of Aciculites orientalis gave the most potent antibacterial activity against Staphylococcus aureus and strongest lymphoma cell toxicity was exhibited by the organic extract of Acanthella sp. Guided by the molecular ion peaks in the bioactive fractions, large-scale extraction of Stylissa massa led to the isolation of three bromopyrrole alkaloids, sceptrin, hymenin and manzacidin A/C. Of these, sceptrin exhibited broad spectrum antibacterial activity against both Escherichia coli and S. aureus (MIC of 62.5 μM against both species). Based on natural product literature, seven promising species were identified as understudied. Their further exploration may lead to the discovery of structurally novel compounds.Non-compliance with COVID-19 infection prevention and control (IPC) is one of the global public health problems particularly among those frontline healthcare workers. However, there are no detailed investigations on COVID-19 IPC compliance among healthcare workers in conflict-affected settings. The objective of this research was to assess compliance with COVID-19 IPC measures and determine the factors associated with it among healthcare providers in Ethiopian governmental hospitals affected by conflict.
A cross-sectional study was carried out within institutional settings.
The study was conducted in three public hospitals located in northeastern Ethiopia during the period of March to April 2022.
Simple random sampling technique was used to select 325 healthcare workers after proportional allocation was made to each public hospital.
The primary outcome was non-compliance with COVID-19 IPC. A multivariable logistic regression analysis was employed to identify factors associated with the lack of adherence to the COVID-19 IPC protocol.
Nearly half (150, 46.2%) of the healthcare workers had non-compliance with COVID-19 IPC protocol. Absence of hand washing soap (adjusted OR (AOR)=2.99; 95% CI 2.46 to 5.76), workload (AOR=2.25; 95% CI 1.33 to 3.84), disruption in the supply of piped water (AOR=1.82; 95% CI 1.11 to 2.99), did not undergo training in COVID-19 IPC (AOR=2.85; 95% CI 1.85 to 4.84), absence of COVID-19 IPC guidelines (AOR=2.14; 95% CI 1.11 to 4.13) and chewing khat (AOR=2.3; 95% CI 1.32 to 3.72) were determinant factors for non-compliance.
The magnitude of non-compliance with COVID-19 IPC was high. Hospital managers and federal ministry of health should provide regular training on COVID-19 IPC, continuous piped water and personal protective facilities for healthcare workers. Ultimately, improving the security situation in the area would help improve COVID-19 IPC compliance among healthcare workers in these and other similar conflict-affected settings.
Implementation of enhanced recovery pathways (ERPs) has resulted in improved patient-centred outcomes and decreased costs. However, there is a lack of high-level evidence for many ERP elements. We have designed a randomised, embedded, multifactorial, adaptive platform perioperative medicine (REMAP Periop) trial to evaluate the effectiveness of several perioperative therapies for patients undergoing complex abdominal surgery as part of an ERP. This trial will begin with two domains: postoperative nausea/vomiting (PONV) prophylaxis and regional/neuraxial analgesia. Patients enrolled in the trial will be randomised to arms within both domains, with the possibility of adding additional domains in the future.
In the PONV domain, patients are randomised to optimal versus supraoptimal prophylactic regimens. In the regional/neuraxial domain, patients are randomised to one of five different single-injection techniques/combination of techniques. The primary study endpoint is hospital-free days at 30 days, with additional domain-specific secondary endpoints of PONV incidence and postoperative opioid consumption. The efficacy of an intervention arm within a given domain will be evaluated at regular interim analyses using Bayesian statistical analysis. At the beginning of the trial, participants will have an equal probability of being allocated to any given intervention within a domain (ie, simple 1:1 randomisation), with response adaptive randomisation guiding changes to allocation ratios after interim analyses when applicable based on prespecified statistical triggers. Triggers met at interim analysis may also result in intervention dropping.
The core protocol and domain-specific appendices were approved by the University of Pittsburgh Institutional Review Board. A waiver of informed consent was obtained for this trial. Trial results will be announced to the public and healthcare providers once prespecified statistical triggers of interest are reached as described in the core protocol, and the most favourable interventions will then be implemented as a standardised institutional protocol.
by Luke Bracegirdle, Matthew Stubbs, Rezaur Rahman, Alexander I. R. Jackson, Helmi C. Burton-Papp, Robert Chambers, Sanjay Gupta, Michael P. W. Grocott, Ahilanandan Dushianthan
BackgroundCOVID-19 placed immense strain on healthcare systems, necessitating innovative responses to the surge of critically ill patients, particularly those requiring mechanical ventilation. In this report, we detail the establishment of a dedicated critical care prone positioning team at University Hospital Southampton in response to escalating demand for prone positioning during the initial wave of the pandemic.
MethodsThe formation of a prone positioning team involved meticulous planning and collaboration across disciplines to ensure safe and efficient manoeuvrers. A comprehensive training strategy, aligned with national guidelines, was implemented for approximately 550 staff members from a diverse background. We surveyed team members to gain insight to the lived experience.
ResultsA total of 78 full-time team members were recruited and successfully executed over 1200 manoeuvres over an eight-week period. Our survey suggests the majority felt valued and expressed pride and willingness to participate again should the need arise.
ConclusionThe rapid establishment and deployment of a dedicated prone positioning team may have contributed to both patient care and staff well-being. We provide insight and lessons that may be of value for future respiratory pandemics. Future work should explore objective clinical outcomes and long-term sustainability of such services.
The critical care nursing workforce is in crisis, with one-third of critical care nurses worldwide intending to leave their roles. This paper aimed to examine the problem from a wellbeing perspective, offering implications for research, and potential solutions for organisations.
Discursive/Position paper.
The discussion is based on the nursing and wellbeing literature. It is guided by the authors' collaborative expertise as both clinicians and researchers. Data were drawn from nursing and wellbeing peer-reviewed literature, such as reviews and empirical studies, national surveys and government and thinktank publications/reports.
Critical care nurses have been disproportionately affected by the COVID-19 pandemic with studies consistently showing critical care nurses to have the worst psychological outcomes on wellbeing measures, including depression, burnout and post-traumatic stress disorder (PTSD). These findings are not only concerning for the mental wellbeing of critical care nurses, they also raise significant issues for healthcare systems/organisations: poor wellbeing, increased burnout and PTSD are directly linked with critical care nurses intending to leave the profession. Thus, the wellbeing of critical care nurses must urgently be supported. Resilience has been identified as a protective mechanism against the development of PTSD and burnout, thus offering evidence-based interventions that address resilience and turnover have much to offer in tackling the workforce crisis. However, turnover data must be collected by studies evaluating resilience interventions, to further support their evidence base. Organisations cannot solely rely on the efficacy of these interventions to address their workforce crisis but must concomitantly engage in organisational change.
We conclude that critical care nurses are in urgent need of preventative, evidence-based wellbeing interventions, and make suggestions for research and practice.
Background
Public health nurse home visiting is a promising approach for addressing the complex needs of families at risk of child maltreatment. The Colorado Nurse Support Program advances service provision by using evidence-based practices to provide tailored assessment and intervention to low-income, primiparous, and multiparous families with children under 18 years of age identified as high risk by county human service systems.
Objectives
This study aimed to test the effects of the Nurse Support Program on child protective services case characteristics between Nurse Support Program families and a demographically comparable reference group of families and evaluate changes in parenting outcomes from pre- to postprogram involvement for Nurse Support Program families.
Methods
We used a matched comparison group quasi-experimental design in which families in the Nurse Support Program (n = 48) were compared to families (n = 150) who were identified using administrative data from Colorado’s Comprehensive Child Welfare Information System. Outcomes were child protective case characteristics (child protection referrals, open assessments, founded assessments, open cases, and children’s placement in out-of-home care) and parenting outcomes.
Results
Nurse Support Program families were less likely to have a child protection case opened or have their child placed in out-of-home care. There were no significant between-group differences in child protection referrals, open assessments, or founded assessments. Families in the Nurse Support Program showed improvements in parenting outcomes over time.
Discussion
Findings suggest that the Nurse Support Program is a successful public health nurse home-visiting approach to promote positive parenting and family preservation among families with complex needs. Implementing tailored public health nurse home-visiting programs, such as the Nurse Support Program, should continue to be evaluated and supported to mitigate the public health risk of child maltreatment. 
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