Ambulance clinician use of capillary blood ketone meters to improve emergency hyperglycaemia care: A stepped-wedged controlled, mixed-methods feasibility study.

AIM: To determine whether it was feasible, safe and acceptable for ambulance clinicians to use capillary blood ketone meters for 'high-risk' diabetic ketoacidosis (DKA) recognition and fluid initiation, to inform the need for a full-powered, multi-centre trial. METHODS: Adopting a stepped-wedge controlled design, participants with hyperglycaemia (capillary blood glucose >11.0 mmol/L) or diabetes and unwell were recruited. 'High-risk' DKA intervention participants (capillary blood ketones ≥3.0 mmol/L) received paramedic-led fluid therapy. Participant demographic and clinical data were collated from ambulance and hospital care records. Twenty ambulance and Emergency Department clinicians were interviewed to understand their hyperglycaemia and DKA care experiences. RESULTS: In this study, 388 participants were recruited (Control: n = 203; Intervention: n = 185). Most presented with hyperglycaemia, and incidence of type 1 and type 2 diabetes was 18.5% and 74.3%, respectively. Ketone meter use facilitated 'high-risk' DKA identification (control: 2.5%, n = 5; intervention: 6.5%, n = 12) and was associated with improved hospital pre-alerting. Ambulance clinicians appeared to have a high index of suspicion for hospital-diagnosed DKA participants. One third (33.3%; n = 3) of Control and almost half (45.5%; n = 5) of Intervention DKA participants received pre-hospital fluid therapy. Key interview themes included clinical assessment, ambulance DKA fluid therapy, clinical handovers; decision support tool; hospital DKA management; barriers to hospital DKA care. CONCLUSIONS: Ambulance capillary blood ketone meter use was deemed feasible, safe and acceptable. Opportunities for improved clinical decision making, support and safety-netting, as well as in-hospital DKA care, were recognised. As participant recruitment was below progression threshold, it is recommended that future-related research considers alternative trial designs. CLINICALTRIALS: gov: NCT04940897.

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease: A Randomized, Double-Blind, Multicenter Phase 1 Trial.

BACKGROUND: Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that protects dopamine neurons and improves motor function in animal models of Parkinson's disease (PD). OBJECTIVE: The primary objectives of this study were to assess the safety and tolerability of both CDNF and the drug delivery system (DDS) in patients with PD of moderate severity. METHODS: We assessed the safety and tolerability of monthly intraputamenal CDNF infusions in patients with PD using an investigational DDS, a bone-anchored transcutaneous port connected to four catheters. This phase 1 trial was divided into a placebo-controlled, double-blind, 6-month main study followed by an active-treatment 6-month extension. Eligible patients, aged 35 to 75 years, had moderate idiopathic PD for 5 to 15 years and Hoehn and Yahr score ≤ 3 (off state). Seventeen patients were randomized to placebo (n = 6), 0.4 mg CDNF (n = 6), or 1.2 mg CDNF (n = 5). The primary endpoints were safety and tolerability of CDNF and DDS and catheter implantation accuracy. Secondary endpoints were measures of PD symptoms, including Unified Parkinson's Disease Rating Scale, and DDS patency and port stability. Exploratory endpoints included motor symptom assessment (PKG, Global Kinetics Pty Ltd, Melbourne, Australia) and positron emission tomography using dopamine transporter radioligand [18 F]FE-PE2I. RESULTS: Drug-related adverse events were mild to moderate with no difference between placebo and treatment groups. No severe adverse events were associated with the drug, and device delivery accuracy met specification. The severe adverse events recorded were associated with the infusion procedure and did not reoccur after procedural modification. There were no significant changes between placebo and CDNF treatment groups in secondary endpoints between baseline and the end of the main and extension studies. CONCLUSIONS: Intraputamenally administered CDNF was safe and well tolerated, and possible signs of biological response to the drug were observed in individual patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A systematic review of ambulance service-based randomised controlled trials in stroke.

BACKGROUND: Treatment for stroke is time-dependent, and ambulance services play a vital role in the early recognition, assessment and transportation of stroke patients. Innovations which begin in ambulance services to expedite delivery of treatments for stroke are developing. However, research delivery in ambulance services is novel, developing and not fully understood. AIMS: To synthesise literature encompassing ambulance service-based randomised controlled interventions for acute stroke with consideration to the characteristics of the type of intervention, consent modality, time intervals and issues unique to research delivery in ambulance services. Online searches of MEDLINE, EMBASE, Web of Science, CENTRAL and WHO IRCTP databases and hand searches identified 15 eligible studies from 538. Articles were heterogeneous in nature and meta-analysis was partially available as 13 studies reported key time intervals, but terminology varied. Randomised interventions were evident across all points of contact with ambulance services: identification of stroke during the call for help, higher dispatch priority assigned to stroke, on-scene assessment and clinical interventions, direct referral to comprehensive stroke centres and definitive care delivery at scene. Consent methods ranged between informed patient, waiver and proxy modalities with country-specific variation. Challenges unique to the prehospital setting comprise the geographical distribution of ambulance resources, low recruitment rates, prolonged recruitment phases, management of investigational medicinal product and incomplete datasets. CONCLUSION: Research opportunities exist across all points of contact between stroke patients and ambulance services, but randomisation and consent remain novel. Early collaboration and engagement between trialists and ambulance services will alleviate some of the complexities reported. REGISTRATION NUMBER: PROSPERO 2018CRD42018075803.

Challenges and Experiences in Multicenter Prehospital Stroke Research: Narrative Data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial-2 (RIGHT-2).

BACKGROUND: Ambulance services are increasingly research active and the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) is the largest United Kingdom (UK) ambulance-based randomized controlled trial in stroke. We explore the complexities and challenges encountered during RIGHT-2. METHODS: Five hundred and sixteen of 1487 paramedics from eight UK ambulance services serving 54 comprehensive or primary stroke care centers screened and consented 1149 patients presenting within 4 h of FAST-positive stroke and with systolic blood pressure >120 mmHg; participants were randomized to treatment with transdermal glyceryl trinitrate versus sham patch in the ambulance. KEY FINDINGS: Working with multiple ambulance services demanded flexibility in the trial protocol to overcome variation in operating procedures to ensure deliverability. Many paramedics are novice researchers, and research concepts and practices are emerging including consent strategies in emergency stroke care. Regional variation in hospital participation and hours/days of operation presented paramedics with additional considerations prior to patient recruitment. The working hours of hospital research staff often do not reflect the 24/7 nature of ambulance work, which challenged deliverability until trial processes became fully embedded. Management of investigational medicinal product between ambulance stations, in-transit when on ambulance vehicles and on handover at hospital, necessitated an in-depth review to maintain accountability. CONCLUSION: RIGHT-2 demonstrated that although there are significant practical challenges to conducting multicenter ambulance-based research in a time-dependent environment, careful planning and management facilitated delivery. Lessons learned here will help inform the design and conduct of future ambulance-based trials.

Peripherally Infused Norepinephrine to Avoid Central Venous Catheter Placement in a Medical Intensive Care Unit: A Pilot Study.

BACKGROUND: Reducing central venous catheter (CVC) utilization can reduce complications in the intensive care unit (ICU). While norepinephrine (NE) is traditionally administered via a CVC, lower concentrations may be safely administered via peripheral intravenous (PIV) lines. OBJECTIVE: We aimed to describe the implementation of a pilot protocol utilizing PIVs to administer a low-dose and lower-concentration NE, review the number of CVCs avoided, and evaluate any adverse events. METHODS: In a quaternary medical intensive care unit (MICU), from March 1, 2019, to February 29, 2020, we reviewed charts for CVC placement and adverse events from the pNE infusion. We also measured unit-level CVC utilization in all MICU patients and assessed the change in utilization associated with the peripheral norepinephrine (pNE) protocol. RESULTS: Over a 1-year period, 87 patients received a pNE infusion. Overall, 44 patients (51%) never required CVC placement during their MICU stay. Three patients (3%) experienced adverse events, none of which were documented as serious and or required antidote for treatment. Implementation of the protocol was associated with a decrease in the number of patients at the unit level who received CVCs, even if they did not receive pNE. CONCLUSION AND RELEVANCE: In this small pilot study, we pragmatically demonstrated that pNE is safe and may reduce the need for CVC placement. This information can be used to aid in pNE protocol development and implementation at other institutions, but further research should be done to confirm the safety of routine use of pNE in clinical practice.

What are the demographic and clinical differences between those older adults with traumatic brain injury who receive a neurosurgical intervention to those that do not? A systematic literature review with narrative synthesis.

OBJECTIVES: This review aimed to identify the demographic and clinical differences between those older adults admitted directly under neurosurgical care and those that were not, and whether EMS clinicians could use these differences to improve patient triage. METHODS: The authors searched for papers that included older adults who had suffered a TBI and were either admitted directly under neurosurgical care or were not. Titles and abstracts were screened, shortlisting potentially eligible papers before performing a full-text review. The Newcastle-Ottawa Scale was used to assess the risk of bias. RESULTS: A total of nine studies were eligible for inclusion. A high abbreviated injury score head, Marshall score or subdural hematoma greater than 10 mm were associated with neurosurgical care. There were few differences between those patients who did and did not receive neurosurgical intervention. CONCLUSIONS: Absence of guidelines and clinician bias means that differences between those treated aggressively and conservatively observed in the literature are fraught with bias. Further work is required to understand which patients would benefit from an escalation of care and whether EMS can identify these patients so they are transported directly to a hospital with the appropriate services on-site.

A prospective, matched comparison of ultra-low and standard-dose computed tomography for assessment of renal colic.

OBJECTIVE: To determine the diagnostic accuracy of ultra-low-dose computed tomography (ULDCT) compared with standard-dose CT (SDCT) in the evaluation of patients with clinically suspected renal colic, in addition to secondary features (hydroureteronephrosis, perinephric stranding) and additional pathological entities (renal masses). PATIENTS AND METHODS: A prospective, comparative cohort study was conducted amongst patients presenting to the emergency department with signs and symptoms suggestive of renal or ureteric colic. Patients underwent both SDCT and ULDCT. Single-blinded review of the image sets was performed independently by three board-certified radiologists. RESULTS: Among 21 patients, the effective radiation dose was lower for ULDCT [mean (SD) 1.02 (0.16) mSv] than SDCT [mean (SD) 4.97 (2.02) mSv]. Renal and/or ureteric calculi were detected in 57.1% (12/21) of patients. There were no significant differences in calculus detection and size estimation between ULDCT and SDCT. A higher concordance was observed for ureteric calculi (75%) than renal calculi (38%), mostly due to greater detection of calculi of <3 mm by SDCT. Clinically significant calculi (≥3 mm) were detected by ULDCT with high specificity (97.6%) and sensitivity (100%) compared to overall detection (specificity 91.2%, sensitivity 58.8%). ULDCT and SDCT were highly concordant for detection of secondary features, while ULDCT detected less renal cysts of <2 cm. Inter-observer agreement for the ureteric calculi detection was 93.9% for SDCT and 87.8% for ULDCT. CONCLUSION: ULDCT performed similarly to SDCT for calculus detection and size estimation with reduced radiation exposure. Based on this and other studies, ULDCT should be considered as the first-line modality for evaluation of renal colic in routine practice.

Second Harmonic Generation Spectroscopy of Membrane Probe Dynamics in Gram-Positive Bacteria.

Bacterial membranes are complex mixtures with dispersity that is dynamic over scales of both space and time. To capture adsorption onto and transport within these mixtures, we conduct simultaneous second harmonic generation (SHG) and two-photon fluorescence measurements on two different gram-positive bacterial species as the cells uptake membrane-specific probe molecules. Our results show that SHG not only can monitor the movement of small molecules across membrane leaflets but also is sensitive to higher-level ordering of the molecules within the membrane. Further, we show that the membranes of Staphylococcus aureus remain more dynamic after longer times at room temperature in comparison to Enterococcus faecalis. Our findings provide insight into the variability of activities seen between structurally similar molecules in gram-positive bacteria while also demonstrating the power of SHG to examine these dynamics.

Patient and clinician factors associated with prehospital pain treatment and outcomes: cross sectional study.

OBJECTIVE: We aimed to identify how patient (age, sex, condition) and paramedic factors (sex, role) affected prehospital analgesic administration and pain alleviation. METHODS: We used a cross-sectional design with a 7-day retrospective sample of adults aged 18 years or over requiring primary emergency transport to hospital, excluding patients with Glasgow Coma Scale below 13, in two UK ambulance services. Multivariate multilevel regression using Stata 14 analysed factors independently associated with analgesic administration and a clinically meaningful reduction in pain (≥2 points on 0-10 numerical verbal pain score [NVPS]). RESULTS: We included data on 9574 patients. At least two pain scores were recorded in 4773 (49.9%) patients. For all models fitted there was no significant relationship between analgesic administration or pain reduction and sex of the patient or ambulance staff. Reduction in pain (NVPS ≥2) was associated with ambulance crews including at least one paramedic (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.14 to 2.04, p < 0.01), with any recorded pain score and suspected cardiac pain (OR 2.2, 95% CI 1.02 to 4.75). Intravenous morphine administration was also more likely where crews included a paramedic (OR 2.82, 95% CI 1.93 to 4.13, P < 0.01), attending patients aged 51 to 64 years (OR 2.04, 95% CI 1.21 to 3.45, p = 0.01), in moderate to severe (NVPS 4-10) compared with lower levels of pain for any clinical condition group compared with the reference condition. CONCLUSION: There was no association between patient sex or ambulance staff sex or grade and analgesic administration or pain reduction.

Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest: The PRINCESS Randomized Clinical Trial.

Importance: Therapeutic hypothermia may increase survival with good neurologic outcome after cardiac arrest. Trans-nasal evaporative cooling is a method used to induce cooling, primarily of the brain, during cardiopulmonary resuscitation (ie, intra-arrest). Objective: To determine whether prehospital trans-nasal evaporative intra-arrest cooling improves survival with good neurologic outcome compared with cooling initiated after hospital arrival. Design, Setting, and Participants: The PRINCESS trial was an investigator-initiated, randomized, clinical, international multicenter study with blinded assessment of the outcome, performed by emergency medical services in 7 European countries from July 2010 to January 2018, with final follow-up on April 29, 2018. In total, 677 patients with bystander-witnessed out-of-hospital cardiac arrest were enrolled. Interventions: Patients were randomly assigned to receive trans-nasal evaporative intra-arrest cooling (n = 343) or standard care (n = 334). Patients admitted to the hospital in both groups received systemic therapeutic hypothermia at 32°C to 34°C for 24 hours. Main Outcomes and Measures: The primary outcome was survival with good neurologic outcome, defined as Cerebral Performance Category (CPC) 1-2, at 90 days. Secondary outcomes were survival at 90 days and time to reach core body temperature less than 34°C. Results: Among the 677 randomized patients (median age, 65 years; 172 [25%] women), 671 completed the trial. Median time to core temperature less than 34°C was 105 minutes in the intervention group vs 182 minutes in the control group (P < .001). The number of patients with CPC 1-2 at 90 days was 56 of 337 (16.6%) in the intervention cooling group vs 45 of 334 (13.5%) in the control group (difference, 3.1% [95% CI, -2.3% to 8.5%]; relative risk [RR], 1.23 [95% CI, 0.86-1.72]; P = .25). In the intervention group, 60 of 337 patients (17.8%) were alive at 90 days vs 52 of 334 (15.6%) in the control group (difference, 2.2% [95% CI, -3.4% to 7.9%]; RR, 1.14 [95% CI, 0.81-1.57]; P = .44). Minor nosebleed was the most common device-related adverse event, reported in 45 of 337 patients (13%) in the intervention group. The adverse event rate within 7 days was similar between groups. Conclusions and Relevance: Among patients with out-of-hospital cardiac arrest, trans-nasal evaporative intra-arrest cooling compared with usual care did not result in a statistically significant improvement in survival with good neurologic outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT01400373.

Factors affecting quality of life in patients experiencing facial disfigurement due to surgery for head and neck cancer.

AIM:: to explore the factors affecting quality of life in patients who experience facial disfigurement resulting from surgical treatment for head and neck cancer. BACKGROUND:: the number of people diagnosed with head and neck cancers has been rising over the past 30 years. This, combined with the improved survivorship of cancer patients, has led to a need to understand how these patients adapt to the physical, social and emotional toll of cancer and facial disfigurement and how these affect quality of life. METHODOLOGY:: a systematic search of four nursing and psychological-focused databases was undertaken using pertinent keywords. FINDINGS:: following a thematic analysis, four main themes and one subtheme emerged; changes within the self, social support; social reintegration; and help from healthcare professionals, which had the subtheme of information. CONCLUSION:: facial disfigurement has a significant effect on patients' quality of life. Nurses are ideally placed to identify, inform and support patients and their family and friends.

Using a risk assessment tool for parastomal hernia prevention.

All patients with a stoma are at risk of developing some degree of parastomal herniation given enough follow-up time. Based on current evidence, preventive measures are strongly advised to minimise the incidence of a parastomal hernia forming. This article explores the evidence for consistency in care and management of parastomal hernia, focusing on the development of a risk assessment tool, taking into consideration the patient's and the nurse's perspective.

Celebrating advancing practice.

Julia Williams, Senior Lecturer-Adult Nursing, Postgraduate Diploma Programme Lead, Buckinghamshire New University, julia.williams@bucks.ac.uk.

Supporting the psychological needs of teenagers and young adults during cancer treatment: a literature review.

BACKGROUND: The developmental period of the teenage years and young adulthood can be a challenging time for most. Experiencing a diagnosis of cancer during this time inevitably presents further challenges and concerns. Identifying such issues can help to provide better ways of understanding the patients' experience and their needs, offering nurses insight to enhance care and support for teenagers and young adults (TYAs) undergoing cancer treatments. AIM: To explore the literature regarding the psychological issues faced by TYAs during cancer treatment to inform nursing practice. METHOD: A systematic search of electronic databases was conducted using predetermined search terms which yielded relevant articles. Applying an inclusion and exclusion criteria identified six articles that were deemed appropriate to explore the focus question. RESULTS: A thematic analysis identified three main themes and five sub-themes: anxieties about treatment, concerns regarding the impact on life (feeling restricted and different, the benefits of being sick, facing uncertainty) and coping strategies (positive thinking and problem solving, support). CONCLUSION: Teenagers and young adults face a unique set of psychological concerns and challenges during cancer treatment, resulting in the development of specific coping strategies. These strategies should be promoted by nurses, ensuring patients are supported throughout their cancer journey.

The Kock pouch reconsidered: an alternative surgical technique.

The psychological impact stoma surgery can have on an individual is well documented within the literature (White and Hunt, 1997; Borwell, 2009; Williams, 2005; Brown, 2005). For many years, surgeons have explored and developed innovations in surgical techniques, in particular restorative procedures with a view of preventing permanent stoma formation; ileal anal pouch (IAP) now being the surgical procedure of choice for treatment of ulcerative colitis (UC) and familial adenomatous polyposis (FAP). However, high morbidity rates are associated with pouch longevity (Castillo et al 2005; Nessar and Wu, 2012) and once removed can lead to a high-output ileostomy with risks of electrolyte imbalance and malabsorption. This then creates the dilemma of whether the Kock pouch (KP) should be offered as a surgical option. This article offers a historical perspective of the KP and its place in the surgical management of UC and FAP. This article also presents results from a recent audit funded by the Ileostomy Association (IA), highlighting how patients manage their KP and the importance of maintaining bowel control and being free of an incontinent stoma as a means of coming to terms with their condition.

'Family members screaming for help makes it very difficult to don PPE'. A qualitative study on UK ambulance staff experiences of infection prevention and control practices during the COVID-19 pandemic.

Background: During the first wave of the COVID-19 pandemic in the UK, ambulance staff continued to deliver direct patient care whilst simultaneously adapting to a considerable escalation in evolving infection prevention and control (IPC) practices. Aim: To enable learning to benefit future planning, this qualitative article aims to describe ambulance staff's experiences of this rapid escalation of IPC practices. Method: Three online surveys were presented during the acceleration, peak, and deceleration phases of the pandemic's first wave in the UK (2020). Overall, 18 questions contributed 14,237 free text responses that were examined using inductive thematic analysis at both descriptive and interpretive levels. Findings: Many participants lacked confidence in policies related to the use of personal protective equipment (PPE) because of perceived inadequate supporting evidence, confusing communication, and low familiarity with items. Compliance with policy and confidence in PPE use were further influenced by discomfort, urgency, and perceptions of risk. Various suggestions were made to improve IPC practices within the work environment, including reducing unnecessary exposure through public education and remote triage improvements. Discussion: Some participants' poor experiences of escalating IPC practices were shared with health care workers studied in other environments and in previous epidemics, emphasising the need for lessons to be learnt. PPE should be developed with consideration of ambulance staff's unique working environment and regular familiarisation training could be beneficial. Pragmatic, evidence-based, clearly communicated policies implemented with sufficient resources may protect staff and facilitate them to maintain standards of care delivery during a pandemic.

The SEE-IT Trial: emergency medical services Streaming Enabled Evaluation In Trauma: a feasibility randomised controlled trial.

BACKGROUND: Use of bystander video livestreaming from scene to Emergency Medical Services (EMS) is becoming increasingly common to aid decision making about the resources required. Possible benefits include earlier, more appropriate dispatch and clinical and financial gains, but evidence is sparse. METHODS: A feasibility randomised controlled trial with an embedded process evaluation and exploratory economic evaluation where working shifts during six trial weeks were randomised 1:1 to use video livestreaming during eligible trauma incidents (using GoodSAM Instant-On-Scene) or standard care only. Pre-defined progression criteria were: (1) ≥ 70% callers (bystanders) with smartphones agreeing and able to activate live stream; (2) ≥ 50% requests to activate resulting in footage being viewed; (3) Helicopter Emergency Medical Services (HEMS) stand-down rate reducing by ≥ 10% as a result of live footage; (4) no evidence of psychological harm in callers or staff/dispatchers. Observational sub-studies included (i) an inner-city EMS who routinely use video livestreaming to explore acceptability in a diverse population; and (ii) staff wellbeing in an EMS not using video livestreaming for comparison to the trial site. RESULTS: Sixty-two shifts were randomised, including 240 incidents (132 control; 108 intervention). Livestreaming was successful in 53 incidents in the intervention arm. Patient recruitment (to determine appropriateness of dispatch), and caller recruitment (to measure potential harm) were low (58/269, 22% of patients; 4/244, 2% of callers). Two progression criteria were met: (1) 86% of callers with smartphones agreed and were able to activate livestreaming; (2) 85% of requests to activate livestreaming resulted in footage being obtained; and two were indeterminate due to insufficient data: (3) 2/6 (33%) HEMS stand down due to livestreaming; (4) no evidence of psychological harm from survey, observations or interviews, but insufficient survey data from callers or comparison EMS site to be confident. Language barriers and older age were reported in interviews as potential challenges to video livestreaming by dispatchers in the inner-city EMS. CONCLUSIONS: Progression to a definitive RCT is supported by these findings. Bystander video livestreaming from scene is feasible to implement, acceptable to both 999 callers and dispatchers, and may aid dispatch decision-making. Further assessment of unintended consequences, benefits and harm is required. TRIAL REGISTRATION: ISRCTN 11449333 (22 March 2022). https://www.isrctn.com/ISRCTN11449333.

The Influence of Size on the Intracranial Distribution of Biomedical Nanoparticles Administered by Convection-enhanced Delivery in Minipigs.

Because of the blood-brain barrier (BBB), successful drug delivery to the brain has long been a key objective for the medical community, calling for pioneering technologies to overcome this challenge. Convection-enhanced delivery (CED), a form of direct intraparenchymal microinfusion, shows promise but requires optimal infusate design and real-time distribution monitoring. The size of the infused substances appears to be especially critical, with current knowledge being limited. Herein, we examined the intracranial administration of polyethylene glycol (PEG)-coated nanoparticles (NPs) of various sizes using CED in groups of healthy minipigs (n = 3). We employed stealth liposomes (LIPs, 130 nm) and two gold nanoparticle designs (AuNPs) of different diameters (8 and 40 nm). All were labeled with copper-64 for quantitative and real-time monitoring of the infusion via positron emission tomography (PET). NPs were infused via two catheters inserted bilaterally in the putaminal regions of the animals. Our results suggest CED with NPs holds promise for precise brain drug delivery, with larger LIPs exhibiting superior distribution volumes and intracranial retention over smaller AuNPs. PET imaging alongside CED enabled dynamic visualization of the process, target coverage, timely detection of suboptimal infusion, and quantification of distribution volumes and concentration gradients. These findings may augment the therapeutic efficacy of the delivery procedure while mitigating unwarranted side effects associated with nonvisually monitored delivery approaches. This is of vital importance, especially for chronic intermittent infusions through implanted catheters, as this information enables informed decisions for modulating targeted infusion volumes on a catheter-by-catheter, patient-by-patient basis.

The COVID-19 ambulance response assessment (CARA) study: a national survey of ambulance service healthcare professionals' preparedness and response to the COVID-19 pandemic.

Background: The COVID-19 pandemic placed significant demand on the NHS, including ambulance services, but it is unclear how this affected ambulance service staff and paramedics in other clinical settings (e.g. urgent and primary care, armed services, prisons). This study aimed to measure the self-perceived preparedness and impact of the first wave of the pandemic on paramedics' psychological stress and perceived ability to deliver care. Methods: Ambulance clinicians and paramedics working in other healthcare settings were invited to participate in a three-phase sequential online survey during the acceleration (April 2020), peak (May 2020) and deceleration (September/October 2020) phases of the first wave of COVID-19 in the United Kingdom. Recruitment used social media, Trust internal bulletins and the College of Paramedics' communication channels, employing a convenience sampling strategy. Data were collected using purposively developed open- and closed-ended questions and the validated general health questionnaire-12 (GHQ-12). Data were analysed using multi-level linear and logistic regression models. Results: Phase 1 recruited 3717 participants, reducing to 2709 (73%) by phase 2 and 2159 (58%) by phase 3. Participants were mostly male (58%, n = 2148) and registered paramedics (n = 1992, 54%). Mean (standard deviation) GHQ-12 scores were 16.5 (5.2) during phase 1, reducing to 15.2 (6.7) by phase 3. A total of 84% of participants (n = 3112) had a GHQ-12 score ≥ 12 during the first phase, indicating psychological distress. Participants that had higher GHQ-12 scores were feeling unprepared for the pandemic, and reported a lack of confidence in using personal protective equipment and managing cardiac arrests in confirmed or suspected COVID-19 patients. Conclusions: Most participants reported psychological distress, the reasons for which are multi-factorial. Ambulance managers need to be aware of the risks to staff mental health and take action to mitigate these, to support staff in the delivery of unscheduled, emergency and urgent care under these additional pressures.

Research priorities for the management of major trauma: an international priority setting partnership with the James Lind Alliance.

OBJECTIVE: The objective of this study is to determine research priorities for the management of major trauma, representing the shared priorities of patients, their families, carers and healthcare professionals. DESIGN/SETTING: An international research priority-setting partnership. PARTICIPANTS: People who have experienced major trauma, their carers and relatives, and healthcare professionals involved in treating patients after major trauma. The scope included chest, abdominal and pelvic injuries as well as major bleeding, multiple injuries and those that threaten life or limb. METHODS: A multiphase priority-setting exercise was conducted in partnership with the James Lind Alliance over 24 months (November 2021-October 2023). An international survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second international survey asked respondents to prioritise the research questions. A final shortlist of 19 questions was taken to a stakeholder workshop, where consensus was reached on the top 10 priorities. RESULTS: A total of 1572 uncertainties, submitted by 417 respondents (including 132 patients and carers), were received during the initial survey. These were refined into 53 unique indicative questions, of which all 53 were judged to be true uncertainties after reviewing the existing evidence. 373 people (including 115 patients and carers) responded to the interim prioritisation survey and 19 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions. CONCLUSIONS: The top 10 research priorities for major trauma include patient-centred questions regarding pain relief and prehospital management, multidisciplinary working, novel technologies, rehabilitation and holistic support. These shared priorities will now be used to guide funders and teams wishing to research major trauma around the globe.