Combination of the lateral-flow immunoassay with multicolor gold nanorod etching for the semi-quantitative detection of digoxin.

We are the first to combine the lateral-flow immunoassay (LFA) with gold nanorod (GNR) etching to achieve a multicolor readout where the color produced was correlated with digoxin concentrations in human serum in the relevant range for therapeutic drug monitoring of 0.5-3.0 ng mL-1.

Care of the older trauma patient following low-energy transfer trauma-highlighting a research void.

BACKGROUND: in high-income countries trauma patients are becoming older, more likely to have comorbidities, and are being injured by low-energy mechanisms. This systematic review investigates the association between higher-level trauma centre care and outcomes of adult patients who were admitted to hospital due to injuries sustained following low-energy trauma. METHODS: a systematic review was conducted in January 2021. Studies were eligible if they reported outcomes in adults admitted to hospital due to low-energy trauma. In the presence of study heterogeneity, a narrative synthesis was pre-specified. RESULTS: three studies were included from 2,898 unique records. The studies' risk of bias was moderate-to-serious. All studies compared outcomes in trauma centres verified by the American College of Surgeons in the USA. The mean/median ages of patients in the studies were 73.4, 74.5 and 80 years. The studies reported divergent results. One demonstrated improved outcomes in level 3 or 4 trauma centres (Observed: Expected Mortality 0.973, 95% CI: 0.971-0.975), one demonstrated improved outcomes in level 1 trauma centres (Adjusted Odds Ratio 0.71, 95% CI: 0.56-0.91), and one demonstrated no difference between level 1 or 2 and level 3 or 4 trauma centre care (adjusted odds ratio 0.91, 95% CI: 0.80-1.04). CONCLUSIONS: the few relevant studies identified provided discordant evidence for the value of major trauma centre care following low-energy trauma. The main implication of this review is the paucity of high-quality research into the optimum care of patients injured in low-energy trauma. Further studies into triage, interventions and research methodology are required.

On-demand nanozyme signal enhancement at the push of a button for the improved detection of SARS-CoV-2 nucleocapsid protein in serum.

We developed an innovative 3D printed casing that incorporates a lateral-flow immunoassay, dehydrated signal enhancement reagents, and a sealed buffer chamber. With only the push of a button for signal enhancement, our device detected the SARS-CoV-2 N-protein in 40 min at concentrations as low as 0.1 ng mL-1 in undiluted serum.

Risk of significant traumatic brain injury in adults with minor head injury taking direct oral anticoagulants: a cohort study and updated meta-analysis.

BACKGROUND: Patients taking direct oral anticoagulants (DOACs) commonly undergo CT head imaging after minor head injury, regardless of symptoms or signs. However, the risk of intracranial haemorrhage (ICH) in such patients is unclear, and further research has been recommended by the UK National Institute for Health and Care Excellence head injury guideline group. METHODS: An observational cohort study was performed in the UK South Yorkshire major trauma centre between 26 June and 3 September 2018. Adult patients taking DOACs with minor head injury were prospectively identified, with case ascertainment supplemented by screening of radiology and ED information technology systems. Clinical and outcome data were subsequently collated from patient records. The primary endpoint was adverse outcome within 30 days, comprising: neurosurgery, ICH or death due to head injury. A previously published meta-analysis was updated with the current results and the findings of other recent studies. RESULTS: 148 patients with minor head injury were included (GCS 15, n=107, 72%; GCS 14, n=41, 28%). Patients were elderly (median 82 years) and most frequently injured from ground level falls (n=142, 96%). Overall risk of adverse outcome was 3.4% (5/148, 95% CI 1.4% to 8.0%). Five patients had ICH, of whom one died within 30 days. One patient was treated with prothrombin complex concentrate but no patient received critical care management or underwent neurosurgical intervention. Updated random effects meta-analysis, including the current results and two further recent studies, showed a weighted overall risk of adverse outcome of 3.2% (n=29/787, 95% CI 2.0% to 4.4%). CONCLUSIONS: The risk of adverse outcome following mild head injury in patients taking DOACs appears low. These findings would support shared patient-clinician decision making, rather than routine imaging, following minor head injury while taking DOACs.

Rapid Diagnostic Test Kit for Point-of-Care Cerebrospinal Fluid Leak Detection.

Cerebrospinal fluid (CSF) leaks can occur when there is communication between the intracranial cavities and the external environment. They are a common and serious complication of numerous procedures in otolaryngology, and if not treated, persistent leaks can increase a patient's risk of developing life-threatening complications such as meningitis. As it is not uncommon for patients to exhibit increased secretions postoperatively, distinguishing normal secretions from those containing CSF can be difficult. Currently, there are no proven, available tests that allow a medical provider concerned about a CSF leak to inexpensively, rapidly, and noninvasively rule out the presence of a leak. The gold standard laboratory-based test requires that a sample be sent to a tertiary site for analysis, where days to weeks may pass before results return. To address this, our group recently developed a semiquantitative, barcode-style lateral-flow immunoassay (LFA) for the quantification of the beta-trace protein, which has been reported to be an indicator of the presence of CSF leaks. In the work presented here, we created a rapid diagnostic test kit composed of our LFA, a collection swab, dilution buffers, disposable pipettes, and instructions. Validation studies demonstrated excellent predictive capabilities of this kit in distinguishing between clinical specimens containing CSF and those that did not. Our diagnostic kit for CSF leak detection can be operated by an untrained user, does not require any external equipment, and can be performed in approximately 20 min, making it well suited for use at the point of care. This kit has the potential to transform patient outcomes.

Automation of Biomarker Preconcentration, Capture, and Nanozyme Signal Enhancement on Paper-Based Devices.

Infectious diseases remain one of the leading causes of deaths in developing countries because of a lack of basic sanitation, healthcare clinics, and centralized laboratories. Paper-based rapid diagnostic tests, such as the lateral-flow immunoassay (LFA), provide a promising alternative to the traditional laboratory-based tests; however, they typically suffer from having a poor sensitivity. Biomarker preconcentration and signal enhancement are two common methods to improve the sensitivity of paper-based assays. While effective, these methods often require multiple liquid handling steps which are not ideal for use by untrained personnel in a point-of-care setting. Our lab previously discovered the phenomenon of an aqueous two-phase system (ATPS) separating on paper, which allowed for the seamless integration of concentration and detection of biomarkers on the LFA. In this work, we have extended the functionality of an ATPS separating on paper to automate the sequential delivery of signal enhancement reagents in addition to concentrating biomarkers. The timing of reagent delivery was controlled by changing the initial composition of the ATPS. We applied this technology to automate biomarker concentration and nanozyme signal enhancement on the LFA, resulting in a 30-fold improvement in detection limit over the conventional LFA when detecting Escherichia coli, all while maintaining a single application step.

Point-of-Care Cerebrospinal Fluid Detection.

OBJECTIVE: A cerebrospinal fluid leak is one of the most serious complications in otolaryngology. It may occur as a result of injury to the skull base, typically traumatic or iatrogenic. While the presence of a leak is often discerned in the emergent setting, distinguishing normal secretions from those containing cerebrospinal fluid can be difficult during postoperative visits in the clinic. As most current laboratory-based assays are labor intensive and require several days to result, we aim to develop a more user-friendly and rapid point-of-care cerebrospinal fluid detection device. STUDY DESIGN: Our laboratory developed a barcode-style lateral-flow immunoassay utilizing antibodies for beta-trace protein, a protein abundant in and specific for cerebrospinal fluid, with a concentration of 1.3 mg/L delineating a positive result. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Tests with known concentrations of resuspended beta-trace protein and the contents of discarded lumbar drains (presumed to contain cerebrospinal fluid) were performed to validate our novel device. RESULTS: Our results demonstrate the ability of our device to semiquantitatively identify concentrations of beta-trace protein from 0.3-90 mg/L, which is within the required range to diagnose a leak, thus making beta-trace protein an excellent target for rapid clinical detection. CONCLUSION: Herein we detail the creation and initial validation of the first point-of-care cerebrospinal fluid detection device. This device is a feasible method to more efficiently and cost-effectively identify cerebrospinal fluid leaks, minimize costs, and improve patient outcomes.

Why Do People Choose Emergency and Urgent Care Services? A Rapid Review Utilizing a Systematic Literature Search and Narrative Synthesis.

OBJECTIVES: Rising demand for emergency and urgent care services is well documented, as are the consequences, for example, emergency department (ED) crowding, increased costs, pressure on services, and waiting times. Multiple factors have been suggested to explain why demand is increasing, including an aging population, rising number of people with multiple chronic conditions, and behavioral changes relating to how people choose to access health services. The aim of this systematic mapping review was to bring together published research from urgent and emergency care settings to identify drivers that underpin patient decisions to access urgent and emergency care. METHODS: Systematic searches were conducted across Medline (via Ovid SP), EMBASE (via Ovid), The Cochrane Library (via Wiley Online Library), Web of Science (via the Web of Knowledge), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; via EBSCOhost). Peer-reviewed studies written in English that reported reasons for accessing or choosing emergency or urgent care services and were published between 1995 and 2016 were included. Data were extracted and reasons for choosing emergency and urgent care were identified and mapped. Thematic analysis was used to identify themes and findings were reported qualitatively using framework-based narrative synthesis. RESULTS: Thirty-eight studies were identified that met the inclusion criteria. Most studies were set in the United Kingdom (39.4%) or the United States (34.2%) and reported results relating to ED (68.4%). Thirty-nine percent of studies utilized qualitative or mixed research designs. Our thematic analysis identified six broad themes that summarized reasons why patients chose to access ED or urgent care. These were access to and confidence in primary care; perceived urgency, anxiety, and the value of reassurance from emergency-based services; views of family, friends, or healthcare professionals; convenience (location, not having to make appointment, and opening hours); individual patient factors (e.g., cost); and perceived need for emergency medical services or hospital care, treatment, or investigations. CONCLUSIONS: We identified six distinct reasons explaining why patients choose to access emergency and urgent care services: limited access to or confidence in primary care; patient perceived urgency; convenience; views of family, friends, or other health professionals; and a belief that their condition required the resources and facilities offered by a particular healthcare provider. There is a need to examine demand from a whole system perspective to gain better understanding of demand for different parts of the emergency and urgent care system and the characteristics of patients within each sector.