Association between intravenous fluid administration and endothelial glycocalyx shedding in humans: a systematic review.

INTRODUCTION: Several studies have demonstrated associations between greater rate/volume of intravenous (IV) fluid administration and poorer clinical outcomes. One postulated mechanism for harm from exogenous fluids is shedding of the endothelial glycocalyx (EG). METHODS: A systematic review using relevant search terms was performed using Medline, EMBASE and Cochrane databases from inception to October 2023. Included studies involved humans where the exposure was rate or volume of IV fluid administration and the outcome was EG shedding. The protocol was prospectively registered on PROSPERO: CRD42021275133. RESULTS: The search yielded 450 articles, with 20 articles encompassing 1960 participants included in the review. Eight studies were randomized controlled clinical trials. Half of studies examined patients with sepsis and critical illness; the remainder examined perioperative patients or healthy subjects. Almost all reported blood measurements of soluble EG components; one study used in vivo video-microscopy to estimate EG thickness. Four of 10 sepsis studies, and 9 of 11 non-sepsis studies, found a positive relationship between IV fluid rate/volume and measures of EG shedding. CONCLUSIONS: A trend toward an association between IV fluid rate/volume and EG shedding was found in studies of stable patients, but was not consistently observed among studies of septic and critically ill patients.

Critical Illness Outside the Intensive Care Unit: Research Challenges in Emergency and Prehospital Settings.

Patients with acute critical illness require prompt interventions, yet high-quality evidence supporting many investigations and treatments is lacking. Clinical research in this setting is challenging due to the need for immediate treatment and the inability of patients to provide informed consent. Attempts to obtain consent from surrogate decision-makers can be intrusive and lead to unacceptable delays to treatment. These problems may be overcome by pragmatic approaches to study design and the use of supervised waivers of consent, which is ethical and appropriate in situations where there is high risk of poor outcome and a paucity of proven effective treatment.

A snapshot on a journey from frustration to readiness-A qualitative pre-implementation exploration of readiness for technology adoption in Public Health Protection in Ireland.

In an era of emergent infectious disease, the timely and efficient management of disease outbreaks is critical to public health protection. Integrated technologies for case and incident management (CIM) collect real-time health intelligence for decision making in Public Health. In Ireland, a Public Health reform program is preparing for implementation of a health information system for health protection. Project implementers seek to document and understand the readiness and willingness of future users to adopt the new system, prior to system procurement and implementation. Qualitative key informant interviews were conducted (n = 8) with Public Health personnel from a single regional department of Public Health representing medical, nursing, disease surveillance and administrative roles, at managerial and staff levels. A qualitative thematic analysis was performed. Participants were frustrated by weaknesses in the current practice of CIM and were ready and willing to adopt a digital CIM system if it met their needs. However, they were frustrated by lack of clear timelines. We identified 7 enablers and 3 barriers to readiness and willingness to adopt a CIM system. 'Newness of the workforce' was the main enabler of readiness and willingness, while 'lack of knowledge and familiarity with system' was the main barrier to readiness and willingness. Experiences during the COVID-19 pandemic gave a clear understanding of the problems and need for a digital CIM system and the reform program facilitated a culture of change, readying the workforce for the new health information system. New members of the Public Health departments are a likely ready and eager cohort for adoption of a modern, 'fit for purpose' CIM system and the execution of implementation will likely determine how ready and willing the wider network of departments will be to adopt a national CIMS.

Taipan snake venom time has high sensitivity for lupus anticoagulants in non-anticoagulated, triple positive antiphospholipid syndrome patients.

INTRODUCTION: Dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) are the mainstay assays in lupus anticoagulant (LA) detection yet they have limitations, particularly in relation to interferences and specificity. The recently validated Taipan snake venom time (TSVT) screening with ecarin time (ET) confirmatory assays overcome many of those limitations due to the innate specificity engendered from direct prothrombin activation, and insensitivity to the effects of vitamin K antagonists (VKA). The present study aimed to further evidence diagnostic utility of TSVT/ET by performing them in samples from 116 nonanticoagulated patients with established triple-positive antiphospholipid syndrome (APS). METHODS: Samples were identified in three expert centres who performed dRVVT, APTT and solid phase antiphospholipid antibody assays with reagents from a variety of manufacturers. All samples additionally received TSVT/ET analysis using standardised reagents. RESULTS: Ninety seven of 116 (83.6%) were dRVVT- and APTT-positive, 85/97 (87.6%) of which were TSVT/ET-positive, 9/116 (7.8%) were dRVVT-positive only, 6 of which were TSVT/ET-positive, and 10/116 (8.6%) were APTT-positive only, 5 of which were TSVT/ET-positive. 96/116 TSVT/ET-positivity returned a high sensitivity for LA of 82.8%. Low coefficients of determination revealed weak relationships between LA potency and anticardiolipin and anti-ß2-glycoprotein I antibody titres for all three LA assays. CONCLUSIONS: TSVT/ET has high sensitivity for the clinically significant LA found in triple positive APS patients. TSVT/ET can establish multiple LA assay positivity in nonanticoagulated patients negative for one of dRVVT or APTT, and is the only assay pairing insensitive to VKAs, the recommended anticoagulation for APS.

Practical Considerations for the Use of the Rapid AcuStar® ADAMTS13 Activity Assay in the Diagnosis of Acute Thrombotic Thrombocytopenic Purpura (TTP).

Introduction: Conventional practice in the management of acute TTP entails empirical treatment of suspected cases whilst awaiting confirmatory ADAMTS13 deficiency testing. Rapid ADAMTS13 assays offer increased accessibility and rapid diagnostics. The new automated HemosIL AcuStar® ADAMTS13 assay has seen increasing use among UK TTP Specialist Centres alongside the traditional ELISA method to confirm severe ADAMTS13 deficiency. Methods: A multi-centre retrospective case-control study was performed to review patients demonstrating discrepant ADAMTS13 activity results measured using rapid (AcuStar®) and ELISA assays in parallel from September 2019 to December 2021. Cases were compared with a cohort of suspected TTP patients exhibiting no difference in assay results and in relation to their presenting characteristics and pre-test probability of a diagnosis of TTP. Results: Where the clinical index of suspicion for TTP was high at presentation, acute TTP was confirmed using the AcuStar® assay < 0.2 IU/dL and subsequently < 10 IU/dL by ELISA with zero incidence of discrepancy. For patients with low clinical suspicion of acute TTP, a discrepancy between the AcuStar® and ELISA assay results was observed in 2% of cases; 5-10 IU/dL in AcuStar®, confirmed as >20 IU/dL by ELISA. A concurrent cancer diagnosis or sepsis was observed in 40% of discrepant cases. Conclusions: Where acute TTP is strongly suspected, there is a good correlation between the rapid AcuStar® ADAMTS13 assay and the conventional ELISA assay. Where the clinical suspicion of acute TTP is low, caution should be exercised in the interpretation of the ADAMTS13 activity using the AcuStar® assay. Accurate interpretation requires robust ADAMTS13 testing algorithms to be incorporated into diagnostic pathways.