Photofission-Based, Nuclear Material Detection: Technology Demonstration

The Idaho National Engineering and Environmental Laboratory (INEEL), the Los Alamos National Laboratory (LANL), and the Advanced Research and Applications Corporation (ARACOR) [Sunnyvale, California] performed a photonuclear technology demonstration for shielded nuclear material detection during August 21–22, 2002, at the LANL TA-18 facility. The demonstration used the Pulsed Photonuclear Assessment Technique (PPAT) that focused on the application of a photofission-based, nuclear material detection method as a viable complement to the ARACOR Eagle inspection platform. The Eagle is a mobile and fully operational truck and cargo inspection system that uses a 6-MeV electron accelerator to perform real-time radiography. This imaging is performed using an approved “radiation-safe” or “cabinet safe” operation relative to the operators, inspectors, and any stowaways within the inspected vehicles. While the PPAT has been primarily developed for active interrogation, its neutron detection system also maintains a complete and effective passive detection capability

Realizing the promise of population biobanks: a new model for translation

The promise of science lies in expectations of its benefits to societies and is matched by expectations of the realisation of the significant public investment in that science. In this paper, we undertake a methodological analysis of the science of biobanking and a sociological analysis of translational research in relation to biobanking. Part of global and local endeavours to translate raw biomedical evidence into practice, biobanks aim to provide a platform for generating new scientific knowledge to inform development of new policies, systems and interventions to enhance the public’s health. Effectively translating scientific knowledge into routine practice, however, involves more than good science. Although biobanks undoubtedly provide a fundamental resource for both clinical and public health practice, their potentiating ontology—that their outputs are perpetually a promise of scientific knowledge generation—renders translation rather less straightforward than drug discovery and treatment implementation. Biobanking science, therefore, provides a perfect counterpoint against which to test the bounds of translational research. We argue that translational research is a contextual and cumulative process: one that is necessarily dynamic and interactive and involves multiple actors. We propose a new multidimensional model of translational research which enables us to imagine a new paradigm: one that takes us from bench to bedside to backyard and beyond, that is, attentive to the social and political context of translational science, and is cognisant of all the players in that process be they researchers, health professionals, policy makers, industry representatives, members of the public or research participants, amongst others

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The state of the art of central venous catheter care in the intensive care unit of a tertiary hospital; A quality initiative and call to action

Introduction The acute central venous catheter (CVC) is the most common vascular access device found in the intensive care unit (ICU). Appropriate CVC tip termination, device patency along with minimizing the number of CVC dressing changes are evidence-based interventions proven to reduce central line-associated blood-stream infections. Study Objectives The objectives of our quality initiative (QI) were to assess: 1. The quality of the securement device. 2. Documentation of insertion and management of the CVC. 3. CVC tip termination from an x-ray. Methods Using a convenient sample we performed a clinical audit using a statewide electronic quality system; Governance, Evidence, Knowledge and Outcome (GEKO). A case report form was devised and underpinned with face validity and relevant current literature. We selected a pragmatic sample of 50 patients. Results The mean age was 60 +/- 14.7 years and the male gender accounted for 60% of our study population. Five-lumen CVCs were inserted in 80% of patients with 84% of CVCs located on the patient's right side. Over 50% were inserted high up in the internal jugular (IJ) vein. 100% of CVCs were sutured in place. The edges of the dressings were loose in 40% with an additional border fixation found in 68%. Our specific CVC clinical information system portal was completed in 86% of patients. However, all required fields were not completed in 86%. Over 50% of the CVC tip termination was descriptively identified. Consequently, we performed an inter-class correlation to measure CVC tip agreement amongst a vascular access expert, ICU consultant and interventional radiologist with moderate agreement at 0.57. Conclusion(s) As a result of our QI a re-evaluation of CVC insertion care and maintenance occurred. New securement strategies have been implemented and reevaluated. Additionally, the ECG method may be a better empiric method for confirming CVC tip termination.No Full Tex

Muscle growth and anabolism in intensive care survivors (GAINS 2.0): Protocol for a multi-centre randomised; placebo controlled clinical trial of nandrolone in deconditioned adults recovering from critical illness.

BackgroundIntensive care patients can experience significant long-term impairment in mobility and function caused by their critical illness. A potential contributory factor apart from critical illness polymyoneuropathy is the low levels of anabolic hormones in these patients. Testosterone levels in critically ill patients are extremely low, even in the latter recovery phase. A potential solution to critical illness myopathy may be to provide anabolic support in addition to standard care (early physiotherapy) to further improve gains in strength.Research questionThis project aims to test whether a synthetic testosterone (nandrolone) improves muscle strength in ICU survivors compared to placebo.MethodsGAINS 2.0 is a multicentre, randomised, double blinded placebo-controlled trial which will allocate ICU patients in a 1:1 ratio to nandrolone compared to placebo which commenced recruitment in July 2023. Adult patients admitted to the ICU, receiving nutrition for a minimum of 24 hours with an ICU stay of at least 5 days, or patients with significant weakness as result of their ICU stay (such that they are unable to mobilise independently) will be eligible to participate. Sample size will be 54 patients. Patients will be randomised to receive nandrolone 100mg (males) / 50mg(females) weekly for 3 weeks in addition to standard care. The co-primary outcomes are the time to walking with one person assisting (Intensive Care Mobility scale = 8 or more, in days from randomisation), change in muscle strength measured by the Medical Research Council (MRC) muscle strength sum score from enrolment to hospital discharge and number of days out of hospital up to day 90 post-discharge. Secondary outcomes are grip strength measured by hand-held dynamometry. SF-36 scores (quality of life and functional domains), and days to return to work, for those working pre-ICU, will be collected via a 3-month phone follow-up.ConclusionsA previous pilot feasibility trial showed that nandrolone is safe and feasible. We hypothesize nandrolone will improve muscle strength and physical functioning at hospital discharge and at follow-up. The results of this trial may have significant interest to clinicians and patients considering the large and increasing number of patients surviving intensive care but with physical impairment. This trial may have significant implications on lowering hospital costs and daily adjusted life years.Trial registryanzctr.org.au; No.: ACTRN12623000729628 URL: anzctr.org.au