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1.
Int J Nurs Stud ; 153: 104732, 2024 May.
Article En | MEDLINE | ID: mdl-38493656

BACKGROUND: Compassion is critical to the provision of high-quality healthcare and is foregrounded internationally as an issue of contemporary concern. Paid care experience prior to nurse training has been suggested as a potential means of improving compassion, which has been characterised by the values and behaviours of care, compassion, competence, communication, courage, and commitment. There is however a dearth of evidence to support the effectiveness of prior care experience as a means of improving compassion in nursing. OBJECTIVE: To explore the impact of paid prior care experience on the values and behaviours of pre-registration nursing students indicated as characterising compassionate care. DESIGN: Longitudinal mixed methods design employing a modified concurrent triangulation strategy, comprising two work packages. Work package 1 was qualitative, and work package 2 adopted a concurrent embedded strategy with a dominant quantitative component. Research is reported in accordance with the Good Reporting of a Mixed Methods Study framework. SETTING(S): Three United Kingdom universities. PARTICIPANTS: Pre-registration nursing students attending one of three universities, and individuals who had previously participated in a Health Education England paid prior care experience pilot. Participant numbers at time point 1 were questionnaires n = 220, telephone interviews n = 10, and focus groups n = 8. METHODS: Work package 1 consisted of longitudinal semi-structured telephone interviews. Work package 2 comprised validated online questionnaires measuring emotional intelligence, compassion satisfaction and fatigue, resilience, psychological empowerment, and career commitment (as proxies of compassionate values and behaviours), and focus groups. Qualitative data were thematically analysed. Quantitative data were analysed via Analysis of Variance in SPSS v 26. RESULTS: Qualitative findings suggest that prior care experience has both positive and negative effects on students' compassionate values and behaviours, however positive effects do not extend to qualification. No statistically significant differences were found in any of the quantitative outcome measures between participants with and without paid prior care experience. A statistically significant increase in compassion fatigue was identified in both groups of participants post-qualification. Paid prior care experience did not prevent participants from experiencing reality shock on becoming a student or on qualification. CONCLUSIONS: There is insufficient evidence of longitudinal beneficial impact to recommend paid prior care experience as an effective intervention to foster nursing students' compassionate values and behaviours. These findings do not support mandating a period of paid care experience as a prerequisite for entry into nurse education. REGISTRATION: N/A. Tweetable abstract Insufficient evidence of longitudinal beneficial impact to recommend prior care experience as an effective intervention to foster nursing student compassion @PriorCareExp @Sarah_F_R.


Empathy , Students, Nursing , Students, Nursing/psychology , Humans , Longitudinal Studies , Female , Male , United Kingdom , Adult , Young Adult
2.
Health Technol Assess ; 28(3): 1-120, 2024 Jan.
Article En | MEDLINE | ID: mdl-38343036

Background: Containment (e.g. physical restraint and seclusion) is used frequently in mental health inpatient settings. Containment is associated with serious psychological and physical harms. De-escalation (psychosocial techniques to manage distress without containment) is recommended to manage aggression and other unsafe behaviours, for example self-harm. All National Health Service staff are trained in de-escalation but there is little to no evidence supporting training's effectiveness. Objectives: Objectives were to: (1) qualitatively investigate de-escalation and identify barriers and facilitators to use across the range of adult acute and forensic mental health inpatient settings; (2) co-produce with relevant stakeholders an intervention to enhance de-escalation across these settings; (3) evaluate the intervention's preliminary effect on rates of conflict (e.g. violence, self-harm) and containment (e.g. seclusion and physical restraint) and understand barriers and facilitators to intervention effects. Design: Intervention development informed by Experience-based Co-design and uncontrolled pre and post feasibility evaluation. Systematic reviews and qualitative interviews investigated contextual variation in use and effects of de-escalation. Synthesis of this evidence informed co-design of an intervention to enhance de-escalation. An uncontrolled feasibility trial of the intervention followed. Clinical outcome data were collected over 24 weeks including an 8-week pre-intervention phase, an 8-week embedding and an 8-week post-intervention phase. Setting: Ten inpatient wards (including acute, psychiatric intensive care, low, medium and high secure forensic) in two United Kingdom mental health trusts. Participants: In-patients, clinical staff, managers, carers/relatives and training staff in the target settings. Interventions: Enhancing de-escalation techniques in adult acute and forensic units: Development and evaluation of an evidence-based training intervention (EDITION) interventions included de-escalation training, two novel models of reflective practice, post-incident debriefing and feedback on clinical practice, collaborative prescribing and ward rounds, practice changes around admission, shift handovers and the social and physical environment, and sensory modulation and support planning to reduce patient distress. Main outcome measures: Outcomes measured related to feasibility (recruitment and retention, completion of outcome measures), training outcomes and clinical and safety outcomes. Conflict and containment rates were measured via the Patient-Staff Conflict Checklist. Clinical outcomes were measured using the Attitudes to Containment Measures Questionnaire, Attitudes to Personality Disorder Questionnaire, Violence Prevention Climate Scale, Capabilities, Opportunities, and Motivation Scale, Coercion Experience Scale and Perceived Expressed Emotion in Staff Scale. Results: Completion rates of the proposed primary outcome were very good at 68% overall (excluding remote data collection), which increased to 76% (excluding remote data collection) in the post-intervention period. Secondary outcomes had high completion rates for both staff and patient respondents. Regression analyses indicated that reductions in conflict and containment were both predicted by study phase (pre, embedding, post intervention). There were no adverse events or serious adverse events related to the intervention. Conclusions: Intervention and data-collection procedures were feasible, and there was a signal of an effect on the proposed primary outcome. Limitations: Uncontrolled design and self-selecting sample. Future work: Definitive trial determining intervention effects. Trial registration: This trial is registered as ISRCTN12826685 (closed to recruitment). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/101/02) and is published in full in Health Technology Assessment; Vol. 28, No. 3. See the NIHR Funding and Awards website for further award information. Context: Conflict (a term used to describe a range of potentially unsafe events including violence, self-harm, rule-breaking, medication refusal, illicit drug and alcohol use and absconding) in mental health settings causes serious physical and psychological harm. Containment interventions which are intended to minimise harm from violence (and other conflict behaviours) such as restraint, seclusion and rapid tranquilisation can result in serious injuries to patients and, occasionally, death. Involvement in physical restraint is the most common cause of serious physical injury to National Health Service mental health staff in the United Kingdom. Violence to staff results in substantial costs to the health service in sickness and litigation payments. Containment interventions are also expensive (e.g. physical restraint costs mental health services £6.1 million and enhanced observations £88 million per annum). Despite these harms, recent findings indicate containment interventions such as seclusion and physical restraint continue to be used frequently in mental health settings. Clinical trials have demonstrated that interventions can reduce containment without increasing violence and other conflict behaviours (e.g. verbal aggression, self-harm). Substantial cost-savings result from reducing containment use. De-escalation, as an intervention to manage aggression and potential violence without restrictive practices, is a core intervention. 'De-escalation' is a collective term for a range of psychosocial techniques designed to reduce distress and anger without the need to use 'containment' interventions (measures to prevent harm through restricting a person's ability to act independently, such as physical restraint and seclusion). Evidence indicates that de-escalation involves ensuring conditions for safe intervention and effective communication are established, clarifying and attempting to resolve the patient's concern, conveyance of respect and empathy and regulating unhelpful emotions such as anxiety and anger. Despite featuring prominently in clinical guidelines and training policy domestically and internationally and being a component of mandatory National Health Service training, there is no evidence-based model on which to base training. A systematic review of de-escalation training effectiveness and acceptability conducted in 2015 concluded: (1) no model of training has demonstrated effectiveness in a sufficiently rigorous evaluation, (2) the theoretical underpinning of evaluated models was often unclear and (3) there has been inadequate investigation of the characteristics of training likely to enhance acceptability and uptake. Despite all National Health Service staff being trained in de-escalation there have been no high-quality trials evaluating the effectiveness and cost-effectiveness of training. Feasibility studies are needed to establish whether it is possible to conduct a definitive trial that can determine the clinical, safety and cost-effectiveness of this intervention.


Mental health hospitals are stressful places for patients and staff. Patients are often detained against their will, in places that are noisy, unfamiliar and frightening. Violence and self-injury happen quite frequently. Sometimes staff physically restrain patients or isolate patients in locked rooms (called seclusion). While these measures might sometimes be necessary to maintain safety, they are psychologically and physically harmful. To help reduce the use of these unsafe measures, staff are trained in communication skills designed to reduce anger and distress without using physical force. Professionals call these skills 'de-escalation'. Although training in de-escalation is mandatory, there is no good evidence to say whether it works or not, or what specific techniques staff should be trained in. The Enhancing de-escalation techniques in adult acute and forensic units: Development and evaluation of an evidence-based training intervention (EDITION) project aimed to develop and evaluate a de-escalation training programme informed by research evidence. We interviewed over one hundred people who either worked in or received treatment in a mental health hospital. These people were clear that the training should target key sources of interpersonal and environmental stress that prevent de-escalation from working. We also reviewed all the scientific studies on de-escalation and training, aiming to identify the elements of training that are most likely to increase use of de-escalation. Then, in partnership with current mental health service users and clinical staff, we developed the training programme. Training was delivered to more than 270 staff working in 10 different wards in mental health hospitals. We measured rates of violence, self-injury and use of physical restraint and seclusion 8 weeks before staff received training and 16 weeks after they received training (24 weeks of data collection in total). Analysis of these data showed that these unsafe events were occurring significantly less frequently after training than they were before training, which raised the possibility that the training was helping to reduce harm.


Aggression , State Medicine , Adult , Humans , Feasibility Studies , United Kingdom , Surveys and Questionnaires
4.
ANZ J Surg ; 94(1-2): 96-102, 2024 Feb.
Article En | MEDLINE | ID: mdl-38291008

BACKGROUND: Although modern Australian healthcare systems provide patient-centred care, the ability to predict and prevent suboptimal post-procedural outcomes based on patient demographics at admission may improve health equity. This study aimed to identify patient demographic characteristics that might predict disparities in mortality, readmission, and discharge outcomes after either an operative or non-operative procedural hospital admission. METHODS: This retrospective cohort study included all surgical and non-surgical procedural admissions at three of the four major metropolitan public hospitals in South Australia in 2022. Multivariable logistic regression, with backwards selection, evaluated association between patient demographic characteristics and outcomes up to 90 days post-procedurally. RESULTS: 40 882 admissions were included. Increased likelihood of all-cause, post-procedure mortality in-hospital, at 30 days, and 90 days, were significantly associated with increased age (P < 0.001), increased comorbidity burden (P < 0.001), an emergency admission (P < 0.001), and male sex (P = 0.046, P = 0.03, P < 0.001, respectively). Identification as ATSI (P < 0.001) and being born in Australia (P = 0.03, P = 0.001, respectively) were associated with an increased likelihood of 30-day hospital readmission and decreased likelihood of discharge directly home, as was increased comorbidity burden (P < 0.001) and emergency admission (P < 0.001). Being married (P < 0.001) and male sex (P = 0.003) were predictive of an increased likelihood of discharging directly home; in contrast to increased age (P < 0.001) which was predictive of decreased likelihood of this occurring. CONCLUSIONS: This study characterized several associations between patient demographic factors present on admission and outcomes after surgical and non-surgical procedures, that can be integrated within patient flow pathways through the Australian healthcare system to improve healthcare equity.


Patient Discharge , Patient Readmission , Humans , Male , South Australia/epidemiology , Australia , Retrospective Studies , Hospitals, Public , Risk Factors , Demography
5.
Intern Med J ; 53(7): 1261-1264, 2023 07.
Article En | MEDLINE | ID: mdl-37401652

Computers are an integral component of modern hospitals. Mouse clicks are currently inherent to this use of computers. However, mouse clicks are not instantaneous. These clicks may be associated with significant costs. Estimated costs associated with 10 additional clicks per day for 20 000 staff exceed AU$500 000 annually. Workflow modifications that increase clicks should weigh the potential benefits of such changes against these costs. Future investigation of strategies to reduce low-value clicks may provide an avenue for health care savings.


Computers , Delivery of Health Care , Humans , Time Factors , Workflow
6.
ANZ J Surg ; 93(9): 2119-2124, 2023 09.
Article En | MEDLINE | ID: mdl-37264548

BACKGROUND: This study aimed to examine the performance of machine learning algorithms for the prediction of discharge within 12 and 24 h to produce a measure of readiness for discharge after general surgery. METHODS: Consecutive general surgery patients at two tertiary hospitals, over a 2-year period, were included. Observation and laboratory parameter data were stratified into training, testing and validation datasets. Random forest, XGBoost and logistic regression models were evaluated. Each ward round note time was taken as a different event. Primary outcome was classification accuracy of the algorithmic model able to predict discharge within the next 12 h on the validation data set. RESULTS: 42 572 ward round note timings were included from 8826 general surgery patients. Discharge occurred within 12 h for 8800 times (20.7%), and within 24 h for 9885 (23.2%). For predicting discharge within 12 h, model classification accuracies for derivation and validation data sets were: 0.84 and 0.85 random forest, 0.84 and 0.83 XGBoost, 0.80 and 0.81 logistic regression. For predicting discharge within 24 h, model classification accuracies for derivation and validation data sets were: 0.83 and 0.84 random forest, 0.82 and 0.81 XGBoost, 0.78 and 0.79 logistic regression. Algorithms generated a continuous number between 0 and 1 (or 0 and 100), representing readiness for discharge after general surgery. CONCLUSIONS: A derived artificial intelligence measure (the Adelaide Score) successfully predicts discharge within the next 12 and 24 h in general surgery patients. This may be useful for both treating teams and allied health staff within surgical systems.


Artificial Intelligence , Patient Discharge , Humans , Algorithms , Machine Learning , Logistic Models
9.
Nurse Educ Today ; 120: 105625, 2023 Jan.
Article En | MEDLINE | ID: mdl-36427453

OBJECTIVES: Compassion in nursing and interventions to support it are of international relevance and concern. Prior care experience as a prerequisite for entry into pre-registration nurse education is suggested as a means of improving compassion. The impact of prior care experience has not been comprehensively reviewed, therefore the potential effectiveness of prior care experience as a means of improving compassion is unknown. The scoping review question was 'What is known about the impact of care experience prior to commencing pre-registration nurse education and training?' The primary objective was to scope and synthesise existing literature relating to the topic and ascertain key themes pertaining to impact. A secondary objective was to appraise literature, to contextualise findings and assess the state and stage of knowledge and research in the area. DESIGN: The review was guided by Arksey and O'Malley's methodological framework and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews Checklist. DATA SOURCES: Health sciences databases CINAHL, Medline and PubMed. METHODS: Databases were searched in February 2019, updated August 2021. Data (study characteristics, findings, methodological observations) were extracted from papers meeting inclusion criteria (including peer-reviewed empirical papers with English language, electronic full-text available) and findings thematically analysed. RESULTS: Forty-five papers from 14 countries were included. The majority (64.4 %) were published in Europe (31.1 % in the United Kingdom) between 2010 and 2021 (69 %), 60 % from 2013. Four qualitative themes (compassionate care, commitment, competence and communication) describe the impact of prior care experience, which was variable. CONCLUSIONS: Evidence to support the effectiveness of prior care experience as a prerequisite for entry into nurse education to improve compassion, is inconsistent and insufficient. The literature displays methodological limitations and conclusions should be interpreted in light of these caveats. Recommendations are made for future research, to improve quality and comparability.


Clinical Competence , Education, Nursing , Humans , Educational Status , United Kingdom , Europe
11.
J Adv Model Earth Syst ; 14(6): e2021MS002889, 2022 Jun.
Article En | MEDLINE | ID: mdl-35864945

A new configuration of the Community Earth System Model (CESM)/Community Atmosphere Model with full chemistry (CAM-chem) supporting the capability of horizontal mesh refinement through the use of the spectral element (SE) dynamical core is developed and called CESM/CAM-chem-SE. Horizontal mesh refinement in CESM/CAM-chem-SE is unique and novel in that pollutants such as ozone are accurately represented at human exposure relevant scales while also directly including global feedbacks. CESM/CAM-chem-SE with mesh refinement down to ∼14 km over the conterminous US (CONUS) is the beginning of the Multi-Scale Infrastructure for Chemistry and Aerosols (MUSICAv0). Here, MUSICAv0 is evaluated and used to better understand how horizontal resolution and chemical complexity impact ozone and ozone precursors over CONUS as compared to measurements from five aircraft campaigns, which occurred in 2013. This field campaign analysis demonstrates the importance of using finer horizontal resolution to accurately simulate ozone precursors such as nitrogen oxides and carbon monoxide. In general, the impact of using more complex chemistry on ozone and other oxidation products is more pronounced when using finer horizontal resolution where a larger number of chemical regimes are resolved. Large model biases for ozone near the surface remain in the Southeast US as compared to the aircraft observations even with updated chemistry and finer horizontal resolution. This suggests a need for adding the capability of replacing sections of global emission inventories with regional inventories, increasing the vertical resolution in the planetary boundary layer, and reducing model biases in meteorological variables such as temperature and clouds.

12.
BMC Public Health ; 22(1): 827, 2022 04 25.
Article En | MEDLINE | ID: mdl-35468747

BACKGROUND: Resilience is central to positive mental health and well-being especially when faced with adverse events. Factors such as exercise, location, sleep, mental health, and personality are moderators and mediators of resilience. However, the impact of these factors on resilience during severe adverse events are unknown. The present study examined how the COVID-19 pandemic affected resilience and its moderators and mediators by investigating whether there was a difference in resilience and quality of life between people with varying levels of exercise, including those who changed their exercise levels pre and during a COVID-19-related lockdown, and whether location affected the relationship between levels of exercise and resilience and quality of life. METHODS: Following ethical approval, a cross-sectional online survey capturing data on self-reported key moderators and mediators of resilience before and during the COVID-19 lockdown imposed on the 23rd March 2020 in the UK was distributed via social media and completed over a three week time period during July 2020 via a self-selecting sample of the general population (N = 85). The key moderators and mediators of resilience the survey assessed were exercise, location, life-orientation, mental health, and sleep quality. All data were self-reported. RESULTS: Participants' exercise intensity level increased as resilience increased (F(2,82) = 4.22, p = .003: Wilks' lambda = .82, partial n2 = 0.09). The relationship between exercise, and resilience and quality of life was independent of sleep and mental health status pre-lockdown (p = .013, p = .027 respectively). In the face of the COVID-19 pandemic, this relationship was dependent on mental health but not sleep quality (p = <.001 for resilience p = .010 for quality of life). There were no statistically significant differences between participants living in urban or rural locations. CONCLUSION: Exercise is strongly correlated to resilience and during a pandemic such as COVID-19 it becomes a mechanism in which to moderate resilience. The relationship between exercise and resilience is supported by this study. The influence that a pandemic had on mental health is mediated by its effect on quality of life.


COVID-19 , Resilience, Psychological , COVID-19/epidemiology , Communicable Disease Control , Cross-Sectional Studies , Humans , Pandemics , Quality of Life , United Kingdom/epidemiology
13.
Methods Mol Biol ; 2410: 3-25, 2022.
Article En | MEDLINE | ID: mdl-34914040

The COVID-19 pandemic of 2020-2021 has highlighted the importance of vaccines and vaccination in human health. The pandemic has resulted in social distancing, travel restrictions, decreased trade, high unemployment, commodity price decline, and financial stress that has impacted the global economy. Since December 2020, a massive vaccination campaign is undergoing in every country on the planet to protect against SARS-CoV-2. Vaccination is the cheapest health-care interventions that can save more lives than any other drugs or therapies. Some of the common diseases of the twentieth century including smallpox and polio are seldom reported due to intense vaccination programs that eradicated it. Smallpox is completely eradicated globally; whereas, polio is confined to only a couple of countries. Vaccination has not only improved the health of man but also improved food security by preventing diseases in farm animals and aquacultured fish. Awareness of the principles of immunology and novel vaccines has led to effective vaccination strategies. Climate change could lead to generation of new strains of infectious microorganisms that would require development of novel vaccines. Recent years have seen the increase in incidence of brain-eating amoeba and flesh-eating bacteria (necrotizing fasciitis). There are no vaccines for these diseases. Though vaccination programs have eradicated several diseases and increased the quality of life, there are several diseases that have no effective vaccines. Currently there are no vaccines for cancer, neurodegenerative diseases, autoimmune diseases, as well as infectious diseases like tuberculosis, AIDS, and parasitic diseases including malaria. Spontaneous evolution of pathogenic microorganisms may lead to pandemics that impact the health of not only humanity but also other animals. Hence, the challenge to vaccinologists is the development of novel vaccines and vaccination strategies within limited time period and using minimum resources. In addition, the vaccine developed should be administered globally within a short duration so as to prevent generation of pathogenic variants more lethal than the parent strain.


Vaccination , Vaccines , Animals , COVID-19 , Humans , Pandemics , Quality of Life , Vaccine Development
14.
J Affect Disord ; 285: 10-21, 2021 04 15.
Article En | MEDLINE | ID: mdl-33618056

BACKGROUND: There is emerging evidence that physical activity can have beneficial effects on anxiety. A comprehensive synthesis of the evidence of the anxiolytic effects of physical activity from randomised controlled trials (RCTs) in children and young people (CYP) is warranted. METHODS: A search of 13 databases was conducted to identify RCTs testing the effects of physical activity on anxiety symptoms in children and young people (up to 25 years). Screening, data extraction and risk of bias assessment (using the Cochrane Collaboration tool for assessing risk of bias) were independently undertaken by two study authors. The primary analysis used a random effects model to compare the effect of physical activity interventions to no intervention or minimal intervention control conditions on state anxiety, assessed using validated, self-report measures. RESULTS: Of the 3590 articles retrieved, 22 RCTs were included, with nine included in the primary meta-analysis. The overall standardised mean difference was 0.54 (95% CI -0.796, -0.28), representing a moderate improvement in state anxiety, compared to no intervention or minimal intervention control conditions. Physical activity was also found to produce significantly superior effects on state anxiety when compared to a time and attention-controlled group. LIMITATIONS: The studies are of low quality overall, and there are a limited number of studies included in the meta-analyses therefore limiting the precision of results. CONCLUSIONS: Physical activity may be a useful approach to addressing anxiety symptoms in children and young people, however, further trials of clinical populations are required to determine the effectiveness of physical activity as a treatment of anxiety disorders.


Anxiety Disorders , Anxiety , Adolescent , Anxiety/therapy , Anxiety Disorders/therapy , Bias , Child , Exercise , Humans
15.
Int J Ment Health Nurs ; 30(1): 300-316, 2021 Feb.
Article En | MEDLINE | ID: mdl-32876391

This paper presents, as part of a larger mixed-methods design, a study generating a theoretical understanding of issues pertinent to the quality of mental health care in the KSA from the perspective of those using services. Semi-structured interviews were undertaken with thirty service users admitted to inpatient psychiatric wards, using an interview guide developed by the researchers, based on relevant literature. Findings from the thematic analysis showed five themes: (1) The hospital as a prison: a custody versus care dilemma, (2) quality of interactions between staff and service users, (3) quality of services, (4) staff qualities and (5) suggestions for achieving quality of care. A theoretical model drawing upon Donabedian Health Care Model for Evaluating quality of care and the Andersen Behavioural Model of Health Service Use is evident from the data. Structural aspects of care include staff experience and qualifications and key enablers around social and financial support, service users' health needs and status and the physical infrastructure and ward rules. These drive processes of care based upon robust rates of interaction between staff and service users and appear central to quality of mental health care in KSA. Quality of mental health care in KSA is manifested by a therapeutic ethos with a high degree of interaction between professional carers and service users, with the former being highly educated, competent, compassionate, with a high degree of self-awareness, and specialized in mental health. We have uncovered elements of Fanon and Azoulay's 'Cultural Originality' as well as contemporary examples of Goffman's mortification of the self.


Mental Health Services , Mental Health , Humans , Psychiatric Department, Hospital , Qualitative Research , Saudi Arabia
16.
PLoS One ; 15(12): e0242536, 2020.
Article En | MEDLINE | ID: mdl-33301441

Retinoic acid (RA) has been shown to improve epithelial and endothelial barrier function and development and even suppress damage inflicted by inflammation on these barriers through regulating immune cell activity. This paper thus sought to determine whether RA could improve baseline barrier function and attenuate TNF-α-induced barrier leak in the human bronchial epithelial cell culture model, 16HBE14o- (16HBE). We show for the first time that RA increases baseline barrier function of these cell layers indicated by an 89% increase in transepithelial electrical resistance (TER) and 22% decrease in 14C-mannitol flux. A simultaneous, RA-induced 70% increase in claudin-4 attests to RA affecting the tight junctional (TJ) complex itself. RA was also effective in alleviating TNF-α-induced 16HBE barrier leak, attenuating 60% of the TNF-α-induced leak to 14C-mannitol and 80% of the leak to 14C-inulin. Interleukin-6-induced barrier leak was also reduced by RA. Treatment of 16HBE cell layers with TNF-α resulted in dramatic decrease in immunostaining for occludin and claudin-4, as well as a downward "band-shift" in occludin Western immunoblots. The presence of RA partially reversed TNF-α's effects on these select TJ proteins. Lastly, RA completely abrogated the TNF-α-induced increase in ERK-1,2 phosphorylation without significantly decreasing the TNF-driven increase in total ERK-1,2. This study suggests RA could be effective as a prophylactic agent in minimizing airway barrier leak and as a therapeutic in preventing leak triggered by inflammatory cascades. Given the growing literature suggesting a "cytokine storm" may be related to COVID-19 morbidity, RA may be a useful adjuvant for use with anti-viral therapies.


Bronchi/drug effects , Respiratory Mucosa/drug effects , Tretinoin/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Anti-Inflammatory Agents/pharmacology , Bronchi/cytology , Bronchi/metabolism , Cell Line , Humans , Inflammation/drug therapy , Inflammation/metabolism , Permeability/drug effects , Respiratory Mucosa/cytology , Respiratory Mucosa/metabolism , Tight Junctions/drug effects , Tight Junctions/metabolism
17.
Biosci Rep ; 40(10)2020 10 30.
Article En | MEDLINE | ID: mdl-32985670

The human bronchial epithelial cell line, 16HBE14o- (16HBE), is widely used as a model for respiratory epithelial diseases and barrier function. During differentiation, transepithelial electrical resistance (TER) increased to approximately 800 Ohms × cm2, while 14C-d-mannitol flux rates (Jm) simultaneously decreased. Tight junctions (TJs) were shown by diffusion potential studies to be anion-selective with PC1/PNa = 1.9. Transepithelial leakiness could be induced by the phorbol ester, protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), and the proinflammatory cytokine, tumor necrosis factor-α (TNF-α). Basal barrier function could not be improved by the micronutrients, zinc, or quercetin. Of methodological significance, TER was observed to be more variable and to spontaneously, significantly decrease after initial barrier formation, whereas Jm did not significantly fluctuate or increase. Unlike the strong inverse relationship between TER and Jm during differentiation, differentiated cell layers manifested no relationship between TER and Jm. There was also much greater variability for TER values compared with Jm. Investigating the dependence of 16HBE TER on transcellular ion conductance, inhibition of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel with GlyH-101 produced a large decrease in short-circuit current (Isc) and a slight increase in TER, but no significant change in Jm. A strong temperature dependence was observed not only for Isc, but also for TER. In summary, research utilizing 16HBE as a model in airway barrier function studies needs to be aware of the complexity of TER as a parameter of barrier function given the influence of CFTR-dependent transcellular conductance on TER.


Bronchi/cytology , Cell Line/pathology , Epithelial Cells/physiology , Respiratory Mucosa/cytology , Cell Culture Techniques , Cell Differentiation/physiology , Cell Line/drug effects , Cell Membrane Permeability/drug effects , Cell Membrane Permeability/physiology , Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Electric Impedance , Epithelial Cells/drug effects , Glycine/analogs & derivatives , Glycine/pharmacology , Humans , Hydrazines/pharmacology , Mannitol/metabolism , Respiratory Tract Diseases/pathology , Tight Junctions/drug effects , Tight Junctions/metabolism
18.
Trials ; 21(1): 715, 2020 Aug 14.
Article En | MEDLINE | ID: mdl-32795364

BACKGROUND: Mental Health First Aid (MHFA) is a mental health intervention that teaches people how to identify, understand and help someone who may be experiencing a mental health issue. Reviews of the implementation of MHFA found between 68 and 88% of trained Mental Health First Aiders had used their skills when in contact with someone experiencing mental health difficulties. Reviews evaluating the impact of MHFA suggest positive outcomes. However, to date, there has been no systematic, rigorous evaluation of the impact of MHFA on recipients of the intervention, the organisations providing it and the cost-effectiveness of MHFA overall. This trial will evaluate the effectiveness and cost-effectiveness of MHFA. METHODS: The study is a multi-centred, two-arm clustered randomised controlled trial. Organisations will be randomly allocated to the control or intervention (estimated sample size 800 recipients). The intervention is the standard MHFA intervention provided by Mental Health First Aid England (MHFAE). The control condition will be organisations having a brief consultation from MHFAE on promoting mental health and well-being in the workplace. The primary outcome is health seeking behaviour, measured using the Actual Help Seeking Questionnaire, at 6 months' follow-up. Data collection will be undertaken at baseline (T0), post-intervention-up to 3 months (T1), at 6 months (T2), 12 months (T3) and 24 months (T4). The primary analysis will be conducted on those participants who receive MHFA, a per protocol analysis. DISCUSSION: The study is the first to evaluate the effect of MHFA in the workplace on employees with direct and indirect experience of the intervention, when compared with usual practice. Being also the first to assess, systematically, the social impact of MHFA and investigate its cost-effectiveness adds to the originality of the study. The study promises to yield important data, as yet unknown, regarding the effectiveness, cost-effectiveness, implementation issues, and the sustainability of MHFA in the workplace. TRIAL REGISTRATION: Clinicaltrials.gov NCT04311203 . Registered on 17 March 2020.


First Aid , Mental Health , Workplace , England , Humans , Multicenter Studies as Topic , Quality of Life , Randomized Controlled Trials as Topic
19.
Health Technol Assess ; 23(47): 1-176, 2019 09.
Article En | MEDLINE | ID: mdl-31524133

BACKGROUND: There is currently insufficient evidence for the clinical effectiveness and cost-effectiveness of psychological therapies for post-stroke depression. OBJECTIVE: To evaluate the feasibility of undertaking a definitive trial to evaluate the clinical effectiveness and cost-effectiveness of behavioural activation (BA) compared with usual stroke care for treating post-stroke depression. DESIGN: Parallel-group, feasibility, multicentre, randomised controlled trial with nested qualitative research and a health economic evaluation. SETTING: Acute and community stroke services in three sites in England. PARTICIPANTS: Community-dwelling adults 3 months to 5 years post stroke who are depressed, as determined by the Patient Health Questionnaire-9 (PHQ-9) or the Visual Analogue Mood Scales 'Sad' item. Exclusions: patients who are blind and/or deaf, have dementia, are unable to communicate in English, do not have mental capacity to consent, are receiving treatment for depression at the time of stroke onset or are currently receiving psychological intervention. RANDOMISATION AND BLINDING: Participants were randomised (1 : 1 ratio) to BA or usual stroke care. Randomisation was conducted using a computer-generated list with random permuted blocks of varying sizes, stratified by site. Participants and therapists were aware of the allocation, but outcome assessors were blind. INTERVENTIONS: The intervention arm received up to 15 sessions of BA over 4 months. BA aims to improve mood by increasing people's level of enjoyable or valued activities. The control arm received usual care only. MAIN OUTCOME MEASURES: Primary feasibility outcomes concerned feasibility of recruitment to the main trial, acceptability of research procedures and measures, appropriateness of baseline and outcome measures, retention of participants and potential value of conducting the definitive trial. Secondary feasibility outcomes concerned the delivery of the intervention. The primary clinical outcome 6 months post randomisation was the PHQ-9. Secondary clinical outcomes were Stroke Aphasic Depression Questionnaire - Hospital version, Nottingham Leisure Questionnaire, Nottingham Extended Activities of Daily Living, Carer Strain Index, EuroQol-5 Dimensions, five-level version and health-care resource use questionnaire. RESULTS: Forty-eight participants were recruited in 27 centre-months of recruitment, at a recruitment rate of 1.8 participants per centre per month. The 25 participants randomised to receive BA attended a mean of 8.5 therapy sessions [standard deviation (SD) 4.4 therapy sessions]; 23 participants were allocated to usual care. Outcome assessments were completed by 39 (81%) participants (BA, n = 18; usual care, n = 21). Mean PHQ-9 scores at 6-month follow-up were 10.1 points (SD 6.9 points) and 14.4 points (SD 5.1 points) in the BA and control groups, respectively, a difference of -3.8 (95% confidence interval -6.9 to -0.6) after adjusting for baseline PHQ-9 score and centre, representing a reduction in depression in the BA arm. Therapy was delivered as intended. BA was acceptable to participants, carers and therapists. Value-of-information analysis indicates that the benefits of conducting a definitive trial would be likely to outweigh the costs. It is estimated that a sample size of between 580 and 623 participants would be needed for a definitive trial. LIMITATIONS: Target recruitment was not achieved, although we identified methods to improve recruitment. CONCLUSIONS: The Behavioural Activation Therapy for Depression after Stroke trial was feasible with regard to the majority of outcomes. The outstanding issue is whether or not a sufficient number of participants could be recruited within a reasonable time frame for a definitive trial. Future work is required to identify whether or not there are sufficient sites that are able to deliver the services required for a definitive trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12715175. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 47. See the NIHR Journals Library website for further project information.


Approximately one-third of stroke patients experience depression, which can have negative effects on recovery and quality of life (QoL). Currently, we do not have sufficient evidence to indicate which psychological interventions are effective and affordable to the NHS for treating post-stroke depression. We aimed to determine whether or not it is feasible to conduct a future large-scale study to evaluate a psychological intervention, called behavioural activation (BA) therapy, for treating post-stroke depression. BA aims to improve mood by identifying what stroke patients enjoy doing and helping them to undertake these activities. BA can be used with all stroke patients with depression, including people with cognitive or communication difficulties. We recruited 48 post-stroke patients who had suffered a stroke between 3 months and 5 years previously. People with dementia or significant aphasia were excluded. Participants were divided into two groups at random. About half of the participants received BA over a 4-month period and the other half did not. Participants received all other available care. After 6 months, participants completed questionnaires about their mood, activity level and QoL. We also interviewed 16 participants and 10 carers about their views on the actual research process and therapy. Although we were able to recruit participants to the study, we recruited fewer than the original target of 72 participants owing to delays in starting recruitment. However, we have identified ways to improve participant recruitment in a future study. We found that it was feasible to deliver BA, and the therapy was found to be acceptable to participants, carers and therapists. The results indicate that the benefits of conducting a large-scale future study would outweigh the costs. However, the main consideration will be whether or not we could identify enough stroke services able to run the study for a long enough period to recruit the large number of participants required.


Cognitive Behavioral Therapy/methods , Depression/etiology , Stroke/psychology , Adult , Aged , Aged, 80 and over , Depression/therapy , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Stroke/complications , Surveys and Questionnaires , Treatment Outcome
20.
J Hand Surg Am ; 44(7): 620.e1-620.e7, 2019 Jul.
Article En | MEDLINE | ID: mdl-31280820

Total wrist arthrodesis, fusion of the carpus to the radius, is a well-established and commonly performed procedure for the management of pancarpal degenerative arthritis, trauma, and other severe diseases of the wrist. A well-known complication of this is radiocarpal nonunion, with a rate of 4.4%. Commonly, bone grafting is done at the time of the surgery using local bone, iliac crest bone graft, or cancellous allograft bone. The Synthes Reamer-Irrigator-Aspirator (RIA) is a flexible reamer originally designed as a single-pass intramedullary reamer that can be used in reaming of long bone fractures prior to insertion of an intramedullary nail. Recently, its use has been expanding to the harvesting of bone graft. We present a case study of 2 patients who had total wrist arthrodesis after severe trauma to the wrist resulting in severe bone loss, in whom we used an RIA to obtain bone graft, and both patients went on to union. The first patient is a 17-year-old male who sustained a blast injury from a firework resulting in a mangling injury to the wrist with soft tissue and severe bone loss of his carpus. After being treated with multiple debridements with an external fixator, he was definitively treated with a wrist fusion with RIA bone graft. He went on to osseous union by his 4-month follow-up. Our second patient is a 53-year-old woman who sustained a gunshot wound to the wrist resulting in massive bone loss of the distal radius. After being initially treated with multiple debridements and external fixation, she was treated with a wrist fusion with RIA bone graft and went on to osseous fusion by her 3-month follow-up. Neither patient had complications from the RIA procedure.


Arthrodesis/instrumentation , Blast Injuries/surgery , Bone Transplantation/instrumentation , Wounds, Gunshot/surgery , Wrist Injuries/surgery , Adolescent , Blast Injuries/diagnostic imaging , Blast Injuries/etiology , Female , Humans , Male , Middle Aged , Therapeutic Irrigation/instrumentation , Wounds, Gunshot/diagnostic imaging , Wrist Injuries/diagnostic imaging , Wrist Injuries/etiology
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