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2.
Br Paramed J ; 8(4): 10-20, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38445107

ABSTRACT

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.

3.
Nature ; 619(7970): 572-584, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37468586

ABSTRACT

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.


Subject(s)
Intestines , Single-Cell Analysis , Humans , Cell Differentiation/genetics , Chromatin/genetics , Epithelial Cells/cytology , Epithelial Cells/metabolism , Gene Expression Regulation , Intestinal Mucosa/cytology , Intestines/cytology , Intestines/immunology , Single-Cell Gene Expression Analysis
4.
bioRxiv ; 2023 Jun 11.
Article in English | MEDLINE | ID: mdl-37333362

ABSTRACT

Esophageal adenocarcinoma arises from Barrett's esophagus, a precancerous metaplastic replacement of squamous by columnar epithelium in response to chronic inflammation. Multi-omics profiling, integrating single-cell transcriptomics, extracellular matrix proteomics, tissue-mechanics and spatial proteomics of 64 samples from 12 patients' paths of progression from squamous epithelium through metaplasia, dysplasia to adenocarcinoma, revealed shared and patient-specific progression characteristics. The classic metaplastic replacement of epithelial cells was paralleled by metaplastic changes in stromal cells, ECM and tissue stiffness. Strikingly, this change in tissue state at metaplasia was already accompanied by appearance of fibroblasts with characteristics of carcinoma-associated fibroblasts and of an NK cell-associated immunosuppressive microenvironment. Thus, Barrett's esophagus progresses as a coordinated multi-component system, supporting treatment paradigms that go beyond targeting cancerous cells to incorporating stromal reprogramming.

5.
BMJ Open ; 13(6): e073315, 2023 06 08.
Article in English | MEDLINE | ID: mdl-37290949

ABSTRACT

INTRODUCTION: Patients with episodes of supraventricular tachycardia (SVT), a common heart arrhythmia, are often attended by ambulance services. International guidelines advocate treatment with the Valsalva manoeuvre (VM), but this simple physical treatment has a low success rate, with most patients requiring conveyance to hospital. The Valsalva Assist Device (VAD) is a simple device that might help practitioners and patients perform a more effective VM and reduce the need for patients to be taken to hospital. METHODS AND ANALYSIS: This stepped wedge cluster randomised controlled trial, conducted within a UK ambulance service, compares the current standard VM with a VAD-delivered VM in stable adult patients presenting to the ambulance service with SVT. The primary outcome is conveyance to hospital; secondary outcomes measures include cardioversion rates, duration of ambulance care and number of subsequent episodes of SVT requiring ambulance service care. We plan to recruit approximately 800 patients, to have 90% power to detect an absolute reduction in conveyance rate of 10% (from 90% to 80%) between the standard VM (control) and VAD-delivered VM (intervention). Such a reduction in conveyance would benefit patients, the ambulance service and receiving emergency departments. It is estimated potential savings would pay for devices for the entire ambulance trust within 7 months. ETHICS AND DISSEMINATION: The study has been approved by the Oxford Research Ethics Committee (reference 22/SC/0032). Dissemination will be through peer-reviewed journal publication, presentation at national and international conferences and by the Arrhythmia Alliance, a patient support charity. TRIAL REGISTRATION NUMBER: ISRCTN16145266.


Subject(s)
Tachycardia, Supraventricular , Adult , Humans , Tachycardia, Supraventricular/therapy , Emergency Treatment , Ambulances , Emergency Service, Hospital , Hospitals , Randomized Controlled Trials as Topic
6.
Radiother Oncol ; 184: 109680, 2023 07.
Article in English | MEDLINE | ID: mdl-37105303

ABSTRACT

BACKGROUND AND PURPOSE: Cardiac arrhythmia is a recognised potential complication of thoracic radiotherapy, but the responsible cardiac substructures for arrhythmogenesis have not been identified. Arrhythmogenic tissue is commonly located in the pulmonary veins (PVs) of cardiology patients with arrhythmia, however these structures are not currently considered organs-at-risk during radiotherapy planning. A standardised approach to their delineation was developed and evaluated. MATERIALS AND METHODS: The gross and radiological anatomy relevant to atrial fibrillation was derived from cardiology and radiology literature by a multidisciplinary team. A region of interest and contouring instructions for radiotherapy computed tomography scans were iteratively developed and subsequently evaluated. Radiation oncologists (n = 5) and radiation technologists (n = 2) contoured the PVs on the four-dimensional planning datasets of five patients with locally advanced lung cancer treated with 1.8-2.75 Gy fractions. Contours were compared to reference contours agreed by the researchers using geometric and dosimetric parameters. RESULTS: The mean dose to the PVs was 35% prescription dose. Geometric and dosimetric similarity of the observer contours with reference contours was fair, with an overall mean Dice of 0.80 ± 0.02. The right superior PV (mean DSC 0.83 ± 0.02) had better overlap than the left (mean DSC 0.80 ± 0.03), but the inferior PVs were equivalent (mean DSC of 0.78). The mean difference in mean dose was 0.79 Gy ± 0.71 (1.46% ± 1.25). CONCLUSION: A PV atlas with multidisciplinary approval led to reproducible delineation for radiotherapy planning, supporting the utility of the atlas in future clinical radiotherapy cardiotoxicity research encompassing arrhythmia endpoints.


Subject(s)
Pulmonary Veins , Humans , Pulmonary Veins/diagnostic imaging , Radiotherapy Planning, Computer-Assisted/methods , Heart , Tomography, X-Ray Computed/methods , Arrhythmias, Cardiac , Organs at Risk
7.
Sci Adv ; 9(3): eadd1166, 2023 01 20.
Article in English | MEDLINE | ID: mdl-36662860

ABSTRACT

Although literature suggests that resistance to TNF inhibitor (TNFi) therapy in patients with ulcerative colitis (UC) is partially linked to immune cell populations in the inflamed region, there is still substantial uncertainty underlying the relevant spatial context. Here, we used the highly multiplexed immunofluorescence imaging technology CODEX to create a publicly browsable tissue atlas of inflammation in 42 tissue regions from 29 patients with UC and 5 healthy individuals. We analyzed 52 biomarkers on 1,710,973 spatially resolved single cells to determine cell types, cell-cell contacts, and cellular neighborhoods. We observed that cellular functional states are associated with cellular neighborhoods. We further observed that a subset of inflammatory cell types and cellular neighborhoods are present in patients with UC with TNFi treatment, potentially indicating resistant niches. Last, we explored applying convolutional neural networks (CNNs) to our dataset with respect to patient clinical variables. We note concerns and offer guidelines for reporting CNN-based predictions in similar datasets.


Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/complications , Tumor Necrosis Factor Inhibitors/therapeutic use , Inflammation/complications , Biomarkers
8.
Br Paramed J ; 7(2): 8-15, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36451710

ABSTRACT

Background: Following the emergence of COVID-19, there have been local and national changes in the way emergency medical service (EMS) staff respond to and treat patients in out-of-hospital cardiac arrest (OHCA). The views of EMS staff on the impact of COVID-19 and management of OHCA have not previously been explored. This study aimed to explore the views of staff, with a specific focus on communication during resuscitation, resuscitation procedures and the perception of risk. Methods: A qualitative phenomenological enquiry was conducted. A purposive sample of n = 20 participants of various clinical grades was selected from NHS EMS providers in the United Kingdom. Data were collected using semi-structured interviews, transcribed verbatim and inductive thematic analysis was applied. Results: Three main themes emerged which varied according to clinical grade, location and guidelines.Decision making: Staff generally felt supported to make best-interest termination of resuscitation decisions. Staff made informed decisions to compromise on recommended levels of personal protective equipment (PPE), since it felt impractical in the pre-hospital context, to improve communication or to reduce delays to care.Service pressures: Availability of operational staff and in-hospital capacity were reduced. Staff felt pressure and disconnect from the continuous updates to clinical guidelines which resulted in organisational change fatigue.Moral injury: The emotional impacts of prolonged and frequent exposure to failed resuscitation attempts and patient death caused many staff to take time away from work to recover. Conclusion: This qualitative study is the first known to explore staff views on the impacts of COVID-19 on OHCA resuscitation, which found positive outcomes but also negative impacts important to inform EMS systems. Staff felt that COVID-19 created delays to the delivery of resuscitation, which were multi-faceted. Staff developed new ways of working to overcome the barriers of impractical PPE. There was little impact on resuscitation procedures. Moving forwards, EMS should consider how to limit organisational change and better support the ongoing emotional impacts on staff.

9.
BMC Emerg Med ; 22(1): 184, 2022 11 23.
Article in English | MEDLINE | ID: mdl-36418963

ABSTRACT

BACKGROUND: Head injury (HI) in older adults due to low-energy falls result in a substantial number of emergency department (ED) attendances. However, mortality associated with minor HI is very low. Reducing conveyance to hospital is important for older adults and is a priority for the National Health Service (NHS). Therefore, paramedics are required to make accurate decisions regarding conveyance to the ED. This study used routine data and semi-structured interviews to explore the factors that influence paramedic decision-making when considering whether to convey an adult aged 65 years and over with a minor HI to the ED. METHODS: Semi-structured telephone interviews were completed with ten UK paramedics from a single EMS (ambulance) provider organisation. Interviews explored the factors influencing the paramedics' conveyance decision-making in adults aged 65 years and over with a minor HI. Data were initially analysed inductively to develop a thematic framework. A retrospective analysis of ambulance service data was also completed to determine the scope and scale of the issue in Southwest England. An in-depth audit of 100 conveyed patient records was used to determine the proportion of patients conveyed to the ED who met National Institute for Health and Care Excellence (NICE) and Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidelines. RESULTS: In 2019 South Western Ambulance Service NHS Foundation Trust (SWASFT) attended 15,650 emergency calls to patients aged 65 and over with minor HI, with 70.5% conveyed to ED. 81% of conveyed patients met NICE and JRCALC guideline criteria for conveyance, with the remainder conveyed due to wound care or other medical concerns. The framework developed from the interviews comprised four themes: resources; patient factors; consequences; paramedic factors. Important factors included: the patient's social situation; guidelines; clinical support availability; the history and presentation of the patient; risk. CONCLUSION: This study examined paramedic conveyance decisions for older people with minor HI. It identified multiple influencing factors, highlighting the complex nature of these decisions, and may serve as a basis for developing an intervention to safely decrease ED conveyance in this patient group.


Subject(s)
Craniocerebral Trauma , State Medicine , Humans , Aged , Retrospective Studies , Allied Health Personnel , Craniocerebral Trauma/therapy , Emergency Service, Hospital
10.
OTA Int ; 5(3): e166, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36425092

ABSTRACT

Middle to distal-third clavicular shaft fractures are commonly treated with precontoured anterior plating. Some surgeons use mini-fragment plate fixation and position these plates on the anterior clavicle. Recent studies demonstrated the advantages of anterior clavicle plating, including a possible biomechanical advantage with cantilever bending forces and less subsequent implant removal. The insertion and positioning of anteriorly based clavicle plates requires the release of a portion of the anterior deltoid origin from the lateral clavicle. The purpose of this study is to evaluate the anatomy of the deltoid in relation to the clavicle and to determine the percentage of the deltoid origin released to place modern anterior precontoured plates. Methods: Six right and 4 left cadaver shoulders were dissected, each from separate cadaveric specimens (6 male and 4 female). All measurements were made with digital calipers. The length of the clavicle was measured from the acromioclavicular joint to the sternoclavicular joint. The length of deltoid origin on the lateral clavicle was measured from the acromioclavicular joint to the most medial attachment of the deltoid on the clavicle. Percentage of clavicle with deltoid origin was subsequently calculated. Results: The average length of the cadaveric clavicles was 164.4 mm with a range from 134.3 to 178.1 mm. The average amount of deltoid origin on the clavicle was 58.7 mm with a range from 43.4 to 69 mm. On average 35.5% of the clavicle had deltoid origin, with a range from 30.2% to 38.8%. Conclusion: On average, 35.5% of the clavicular osseous anatomy contains deltoid origin. This should be taken into consideration when performing anterior plating for clavicle fractures. With a significant portion of deltoid origin elevated, surgeons may consider altering postoperative protocols until some interval healing has occurred to this anterior head of the deltoid.

11.
Dev Psychobiol ; 64(8): e22340, 2022 12.
Article in English | MEDLINE | ID: mdl-36426796

ABSTRACT

Recent scholarship has highlighted the importance of understanding relations between hormones, rather than studying hormones in isolation. Considering neuroendocrine coupling, or the coordination of hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axis hormones over time, is one way to investigate how systems governing stress responsiveness and pubertal development covary during critical periods. To date, however, most work has considered hormone coupling cross-sectionally. The current study investigated neuroendocrine coupling in a longitudinal sample from the Northeastern United States. Youth (N = 437, 53% male, 90% White) provided saliva samples for analysis of diurnal hormone activity at ages 9 (three samples per day across 3 days) and 12 (one sample per day on the same weekday for 4 weeks). At both timepoints, samples collected 30-min after waking were assayed for cortisol, dehydroepiandrosterone (DHEA), and testosterone. Multilevel growth modeling was used to determine how levels of morning cortisol changed in tandem with DHEA and testosterone. Morning cortisol-DHEA coupling varied by child sex, as males' cortisol-DHEA diminished over time, especially among pubertally advanced males. Females, in contrast, demonstrated strengthening cortisol-DHEA coupling over time, especially more pubertally advanced females. Morning cortisol-testosterone coupling did not vary by sex or pubertal status, demonstrating strengthening associations between ages 9 and 12. The current findings contribute to the literature on hormone coupling across development and expand this work into an earlier developmental phase than previously investigated.


Subject(s)
Hydrocortisone , Hypothalamo-Hypophyseal System , Female , Humans , Adolescent , Child , Male , Infant, Newborn , Pituitary-Adrenal System , Testosterone , Dehydroepiandrosterone
12.
Astrobiology ; 22(11): 1310-1329, 2022 11.
Article in English | MEDLINE | ID: mdl-36112369

ABSTRACT

At a Mars analog site in Utah, we tested two science operation methods for data acquisition and decision-making protocols: a scenario where the tactical day is preplanned, but major adjustments may still be made before plan delivery; and a scenario in which the sol path must largely be planned before a given tactical planning day and very few adjustments to the plan may be made. The goal was to provide field-tested insight into operations planning for rover missions where science operations must facilitate the efficient choice of sampling locations at a site relevant to searching for habitability and biosignatures. Results of the test indicate that preplanning sol paths did not result in a sol cost savings nor did it improve science return or optimal biologically relevant sample collection. In addition because facies variations in an environment can be subtle and evident only at scales below orbital resolution, acquiring systematic observations is crucial. We also noted that while spectral data provided insight into the chemical components as a whole at this site, they did not provide a guide to targets for which the traverse should be altered. Finally, strategic science planning must include a special effort to account for terrain.


Subject(s)
Exobiology , Mars , Exobiology/methods , Extraterrestrial Environment , Goals , Strategic Planning
13.
Trials ; 23(1): 677, 2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35978361

ABSTRACT

BACKGROUND: Approximately 75,000 people fracture a hip each year in the UK. This painful injury can be devastating-with a high associated mortality rate-and survivors likely to be more dependent and less mobile. Pain relief at the scene of injury is known to be inadequate. Intravenous morphine is usually given by paramedics, but opioids are less effective for dynamic pain and can cause serious side effects, including nausea, constipation, delirium and respiratory depression. These may delay surgery, require further treatment and worsen patient outcomes. We completed a feasibility study of paramedic-provided fascia iliaca compartment block (FICB), testing the intervention, trial methods and data collection. The study (RAPID) demonstrated that a full trial was feasible. In this subsequent study, we aim to test safety, clinical and cost-effectiveness of paramedic-provided FICB as pain relief to patients with suspected hip fracture in the prehospital environment. METHODS: We will conduct a pragmatic multi-centre individually randomised parallel-group trial, with a 1:1 allocation between usual care (control) and FICB (intervention). Hospital clinicians in five sites (paired ambulance services and receiving hospitals) in England and Wales will train 220 paramedics to administer FICB. The primary outcome is change in pain score from pre-randomisation to arrival at the emergency department. One thousand four hundred patients are required to find a clinically important difference between trial arms in the primary outcome (standardised statistical effect ~ 0.2; 90% power, 5% significance). We will use NHS Digital (England) and the SAIL (Secure Anonymised Information Linkage) databank (Wales) to follow up patient outcomes using routine anonymised linked data in an efficient study design, and questionnaires to capture patient-reported outcomes at 1 and 4 months. Secondary outcomes include mortality, length of hospital stay, job cycle time, prehospital medications including morphine, presence of hip fracture, satisfaction, mobility, and NHS costs. We will assess safety by monitoring serious adverse events (SAEs). DISCUSSION: The trial will help to determine whether paramedic administered FICB is a safe, clinically and cost-effective treatment for suspected hip fracture in the pre-hospital setting. Impact will be shown if and when clinical guidelines either recommend or reject the use of FICB in routine practice in this context. TRIAL REGISTRATION: ISRCTN15831813 . Registered on 22 September 2021.


Subject(s)
Analgesia , Hip Fractures , Nerve Block , Allied Health Personnel , Analgesia/methods , Cost-Benefit Analysis , Fascia , Hip Fractures/surgery , Humans , Morphine/adverse effects , Multicenter Studies as Topic , Nerve Block/adverse effects , Nerve Block/methods , Pain/drug therapy , Randomized Controlled Trials as Topic
14.
Emerg Med J ; 39(11): 826-832, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35914922

ABSTRACT

BACKGROUND: Birth before arrival at hospital (BBA) is associated with unfavourable perinatal outcomes and increased mortality. An important risk factor for mortality following BBA is hypothermia, and emergency medical services (EMS) providers are well placed to provide warming strategies. However, research from the UK suggests that EMS providers (paramedics) do not routinely record neonatal temperature following BBA. This study aimed to determine the proportion of cases in which neonatal temperature is documented by paramedics attending BBAs in the South West of England and to explore the barriers to temperature measurement by paramedics. METHODS: A two-phase multi-method study. Phase I involved an analysis of anonymised data from electronic patient care records between 1 February 2017 and 31 January 2020 in a single UK ambulance service, to determine 1) the frequency of BBAs attended and 2) the percentage of these births where a neonatal temperature was recorded, and what proportion of these were hypothermic. Phase II involved interviews with 20 operational paramedics from the same ambulance service, to explore their experiences of, and barriers and facilitators to, neonatal temperature measurement and management following BBA. RESULTS: There were 1582 'normal deliveries' attended by paramedics within the date range. Neonatal temperatures were recorded in 43/1582 (2.7%) instances, of which 72% were below 36.5°C. Data from interviews suggested several barriers and potential facilitators to paramedic measurement of neonatal temperature. Barriers included unavailable or unsuitable equipment, prioritisation of other care activities, lack of exposure to births, and uncertainty regarding responsibilities and roles. Possible facilitators included better equipment, physical prompts, and training and awareness-raising around the importance of temperature measurement. CONCLUSIONS: This study demonstrates a lack of neonatal temperature measurement by paramedics in the South West following BBA, and highlights barriers and facilitators that could serve as a basis for developing an intervention to improve neonatal temperature measurement.


Subject(s)
Emergency Medical Services , Emergency Medical Technicians , Pregnancy , Infant, Newborn , Female , Humans , Ambulances , Temperature , Allied Health Personnel , Emergency Medical Technicians/education , Emergency Medical Services/methods , Hospitals
15.
Nurs Educ Perspect ; 43(6): E88-E90, 2022.
Article in English | MEDLINE | ID: mdl-35853132

ABSTRACT

ABSTRACT: End-of-life (EOL) education in baccalaureate nursing degree programs is critical to prepare nurses to care for patients and families with complex physical and psychosocial needs at the EOL. This quantitative descriptive study examines the current state of EOL education in baccalaureate nursing programs across the United States. Results of this study show that nurse educators continue to use strategies to provide this education; however, the amount and frequency of content delivered require improvement, and support for faculty development is needed.


Subject(s)
Education, Nursing, Baccalaureate , Hospice and Palliative Care Nursing , Humans , United States , Faculty, Nursing , Curriculum , Death
16.
Mov Disord ; 37(8): 1683-1692, 2022 08.
Article in English | MEDLINE | ID: mdl-35702056

ABSTRACT

BACKGROUND: Dystonia is an understudied motor feature of Parkinson's disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. OBJECTIVE: The objective of this study was to investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in patients with PD with and without dystonia. METHODS: We examined the prevalence and distribution of dystonia in patients with PD undergoing deep brain stimulation surgery.  During surgery, we recorded intracranial electrophysiology from the motor cortex and directional electrodes in the subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia. RESULTS: Dystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0 ± 3.3 and 4.2 ± 2.9 Hz peak frequencies for hand and foot movements, respectively). Patients with PD with dystonia during deep brain stimulation surgery displayed greater M1 beta power at rest and STN low-frequency power during movements versus those without dystonia. CONCLUSIONS: Spectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low-frequency synchronization, especially in patients with PD with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Deep Brain Stimulation , Dystonia , Dystonic Disorders , Parkinson Disease , Subthalamic Nucleus , Dystonia/etiology , Humans , Subthalamic Nucleus/physiology
18.
Biomacromolecules ; 23(5): 2150-2159, 2022 05 09.
Article in English | MEDLINE | ID: mdl-35468284

ABSTRACT

This study examined poly(glycerol-1,8-octanediol-sebacate) (PGOS) copolymers with low-level substitution of O (1,8-octanediol) for G (glycerol) units (G/O ratios 0.5:0.5, 0.66:0.33, 0.75:0.25, 0.8:0.2, and 0.91:0.09) prepared in bulk by immobilized Candida antarctica Lipase B (N435) catalysis. The central question explored was the extent that exchanging less than half of poly(glycerol sebacate) (PGS) glycerol units with 1,8-octanediol can be used as a strategy to fine-tune biomaterial properties. Synthesized copolymers having G/O ratios of 0.66:0.33, 0.75:0.25, 0.8:0.2, and 0.91:0.09 have similar molecular weights, where Mw varied from 52,800 to 63,800 g/mol, Mn varied from 5100 to 6450 g/mol, and DM (molecular mass dispersity, Mw/Mn) values were also similar (8.4-11.4). All of the copolymers were branched, and dendritic glycerol units reached 11% for PGOS-0.91:0.09:1.0. Analysis of DSC second heating scans revealed that copolymers with higher 1,8-octanediol contents have relatively higher Tm and ΔHf values. Over the copolymer compositional range studied herein, Tm and ΔHf values varied from 5.3 to 21.1 °C and 8.0 to 23.1 J/g, respectively. Stress-strain curves of PGOS copolymers cured at 140 °C for 48 h exhibited either a unimodal, bimodal, or trimodal response to tensile loading. Varying G/O from 10:1 to 2:1 resulted in significant increases in the peak stress (0.26-4.01 MPa), preyield modulus (0.65-62.59 MPa), failure to strain (64-110%), and failure toughness (0.1-0.56 MPa). This demonstrates that altering the G/O ratio over a narrow compositional range provides biomaterials with widely different yet tunable mechanical properties. Further investigation of PGOS-0.75:0.25:1.0 films revealed that varying the cure conditions from 120 to 160 °C for periods of 24-72 h provides access to biomaterials with a failure strain range from 15 to 224% and Young's modulus from 1.17 to 10.85 MPa. Hence, using the dual variables of compositional variation and changes in cure conditions provides an exciting platform for PGS analogues to optimize material-tissue interactions. Increased contents of 1,8-octanediol slowed in vitro degradation. Slowed degradation of PGOS relative to PGS will be valuable for use in slower healing wounds.


Subject(s)
Biocompatible Materials , Glycerol , Catalysis , Decanoates , Lipase
19.
Health Technol Assess ; 26(21): 1-158, 2022 04.
Article in English | MEDLINE | ID: mdl-35426781

ABSTRACT

BACKGROUND: When a cardiac arrest occurs, cardiopulmonary resuscitation should be started immediately. However, there is limited evidence about the best approach to airway management during cardiac arrest. OBJECTIVE: The objective was to determine whether or not the i-gel® (Intersurgical Ltd, Wokingham, UK) supraglottic airway is superior to tracheal intubation as the initial advanced airway management strategy in adults with non-traumatic out-of-hospital cardiac arrest. DESIGN: This was a pragmatic, open, parallel, two-group, multicentre, cluster randomised controlled trial. A cost-effectiveness analysis accompanied the trial. SETTING: The setting was four ambulance services in England. PARTICIPANTS: Patients aged ≥ 18 years who had a non-traumatic out-of-hospital cardiac arrest and were attended by a participating paramedic were enrolled automatically under a waiver of consent between June 2015 and August 2017. Follow-up ended in February 2018. INTERVENTION: Paramedics were randomised 1 : 1 to use tracheal intubation (764 paramedics) or i-gel (759 paramedics) for their initial advanced airway management and were unblinded. MAIN OUTCOME MEASURES: The primary outcome was modified Rankin Scale score at hospital discharge or 30 days after out-of-hospital cardiac arrest, whichever occurred earlier, collected by assessors blinded to allocation. The modified Rankin Scale, a measure of neurological disability, was dichotomised: a score of 0-3 (good outcome) or 4-6 (poor outcome/death). The primary outcome for the economic evaluation was quality-adjusted life-years, estimated using the EuroQol-5 Dimensions, five-level version. RESULTS: A total of 9296 patients (supraglottic airway group, 4886; tracheal intubation group, 4410) were enrolled [median age 73 years; 3373 (36.3%) women]; modified Rankin Scale score was known for 9289 patients. Characteristics were similar between groups. A total of 6.4% (311/4882) of patients in the supraglottic airway group and 6.8% (300/4407) of patients in the tracheal intubation group had a good outcome (adjusted difference in proportions of patients experiencing a good outcome: -0.6%, 95% confidence interval -1.6% to 0.4%). The supraglottic airway group had a higher initial ventilation success rate than the tracheal intubation group [87.4% (4255/4868) vs. 79.0% (3473/4397), respectively; adjusted difference in proportions of patients: 8.3%, 95% confidence interval 6.3% to 10.2%]; however, patients in the tracheal intubation group were less likely to receive advanced airway management than patients in the supraglottic airway group [77.6% (3419/4404) vs. 85.2% (4161/4883), respectively]. Regurgitation rate was similar between the groups [supraglottic airway group, 26.1% (1268/4865); tracheal intubation group, 24.5% (1072/4372); adjusted difference in proportions of patients: 1.4%, 95% confidence interval -0.6% to 3.4%], as was aspiration rate [supraglottic airway group, 15.1% (729/4824); tracheal intubation group, 14.9% (647/4337); adjusted difference in proportions of patients: 0.1%, 95% confidence interval -1.5% to 1.8%]. The longer-term outcomes were also similar between the groups (modified Rankin Scale: at 3 months, odds ratio 0.89, 95% confidence interval 0.69 to 1.14; at 6 months, odds ratio 0.91, 95% confidence interval 0.71 to 1.16). Sensitivity analyses did not alter the overall findings. There were no unexpected serious adverse events. Mean quality-adjusted life-years to 6 months were 0.03 in both groups (supraglottic airway group minus tracheal intubation group difference -0.0015, 95% confidence interval -0.0059 to 0.0028), and total costs were £157 (95% confidence interval -£270 to £583) lower in the tracheal intubation group. Although the point estimate of the incremental cost-effectiveness ratio suggested that tracheal intubation may be cost-effective, the huge uncertainty around this result indicates no evidence of a difference between groups. LIMITATIONS: Limitations included imbalance in the number of patients in each group, caused by unequal distribution of high-enrolling paramedics; crossover between groups; and the fact that participating paramedics, who were volunteers, might not be representative of all paramedics in the UK. Findings may not be applicable to other countries. CONCLUSION: Among patients with out-of-hospital cardiac arrest, randomisation to the supraglottic airway group compared with the tracheal intubation group did not result in a difference in outcome at 30 days. There were no notable differences in costs, outcomes and overall cost-effectiveness between the groups. FUTURE WORK: Future work could compare alternative supraglottic airway types with tracheal intubation; include a randomised trial of bag mask ventilation versus supraglottic airways; and involve other patient populations, including children, people with trauma and people in hospital. TRIAL REGISTRATION: This trial is registered as ISRCTN08256118. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and supported by the NIHR Comprehensive Research Networks and will be published in full in Health Technology Assessment; Vol. 26, No. 21. See the NIHR Journals Library website for further project information.


BACKGROUND: Cardiac arrest is a serious medical emergency in which the heartbeat and breathing stop suddenly. Every year in the UK, a large number of patients (around 123 per 100,000) suffer a cardiac arrest outside hospital. Only 7­9% of these patients survive to leave hospital. The best initial treatment in cardiac arrest is cardiopulmonary resuscitation (commonly known as CPR), during which it is vital to give chest compressions and maintain a clear airway. Two main techniques are used to keep the airway clear: tracheal intubation (inserting a breathing tube into the windpipe) and a supraglottic airway device (a newer device that is inserted less deeply and sits just above the voicebox). Both techniques are used routinely by paramedics in the UK when treating a cardiac arrest, but there is no evidence about which technique is best. The AIRWAYS-2 trial aimed to find out whether or not a supraglottic airway device is better than tracheal intubation. WHO PARTICIPATED AND WHAT WAS INVOLVED?: Paramedics from four UK ambulance services were put into one of two groups at random. One group was randomly chosen to use tracheal intubation and the other group was randomly chosen to use a supraglottic airway device at all adult cardiac arrests they attended for approximately 2 years. Paramedics were able to apply their clinical judgement and use a different device if they felt that this would be best for the patient. A total of 1523 paramedics took part and enrolled 9296 patients. Following cardiac arrest, a patient's recovery was assessed as good or poor (including patients who did not survive). WHAT DID THE TRIAL FIND?: A similar percentage of patients in both groups had a good recovery. There was no evidence to suggest that the supraglottic airway device was any better than tracheal intubation for treating a cardiac arrest.


Subject(s)
Cardiopulmonary Resuscitation , Out-of-Hospital Cardiac Arrest , Adult , Aged , Airway Management , Child , Cost-Benefit Analysis , Female , Humans , Intubation, Intratracheal/methods , Male , Out-of-Hospital Cardiac Arrest/therapy , Quality of Life , Quality-Adjusted Life Years
20.
Emerg Med J ; 39(7): 540-546, 2022 Jul.
Article in English | MEDLINE | ID: mdl-34764186

ABSTRACT

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug used to prevent bleeding. It was introduced as an intervention for post-traumatic haemorrhage across emergency medical services (EMS) in the UK during 2012. However, despite strong evidence of effectiveness, prehospital TXA administration rates are low. This study used the theoretical domains framework (TDF) to identify barriers and facilitators to the administration of TXA to trauma patients by EMS providers (paramedics) in the UK. METHODS: Interviews were completed with 18 UK paramedics from a single EMS provider organisation. A convenience sampling approach was used, and interviews continued until thematic saturation was reached. Semistructured telephone interviews explored paramedics' experiences of administering TXA to trauma patients, including identifying whether or not patients were at risk of bleeding. Data were analysed inductively using thematic analysis (stage 1). Themes were mapped to the theoretical domains of the TDF to identify behavioural theory-derived barriers and facilitators to the administration of TXA to trauma patients (stage 2). Belief statements were identified and assessed for importance according to prevalence, discordance and evidence base (stage 3). RESULTS: Barriers and facilitators to paramedics' administration of TXA to trauma patients were represented by 11 of the 14 domains of the TDF. Important barriers included a lack of knowledge and experience with TXA (Domain: Knowledge and Skills), confusion and restrictions relating to the guidelines for TXA administration (Domain: Social/professional role and identity), a lack of resources (Domain: Environmental context and resources) and difficulty in identifying patients at risk of bleeding (Domain: Memory, attention and decision processes). CONCLUSIONS: This study presents a behavioural theory-based approach to identifying barriers and facilitators to the prehospital administration of TXA to trauma patients in the UK. It identifies multiple influencing factors that may serve as a basis for developing an intervention to increase prehospital administration of TXA.


Subject(s)
Antifibrinolytic Agents , Emergency Medical Services , Tranexamic Acid , Allied Health Personnel , Antifibrinolytic Agents/therapeutic use , Hemorrhage/drug therapy , Humans , Qualitative Research , Tranexamic Acid/therapeutic use
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