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Effects of (2<i>R</i>,6<i>R</i>)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice

by Todd M. Hillhouse, Kaitlyn J. Partridge, Patrick I. Garrett, Sarah C. Honeycutt, Joseph H. Porter

Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52- and 56-degree hot plate test and acetic acid writhing) and pain-depressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1–32 mg/kg) failed to produce antinociception in the 52- and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2–32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.

Cost-effectiveness of a radio intervention to stimulate early childhood development: protocol for an economic evaluation of the SUNRISE trial in Burkina Faso

Por: Palmer · T. · Clare · A. · Fearon · P. · Head · R. · Hill · Z. · Kagone · B. · Kirkwood · B. · Manu · A. · Skordis · J. · on behalf of the SUNRISE team
Introduction

Approximately 250 million children under 5 years of age are at risk of poor development in low-income and middle-income countries. However, existing early childhood development (ECD) interventions can be expensive, labour intensive and challenging to deliver at scale. Mass media may offer an alternative approach to ECD intervention. This protocol describes the planned economic evaluation of a cluster-randomised controlled trial of a radio campaign promoting responsive caregiving and opportunities for early learning during the first 3 years of life in rural Burkina Faso (SUNRISE trial).

Methods and analysis

The economic evaluation of the SUNRISE trial will be conducted as a within-trial analysis from the provider’s perspective. Incremental costs and health outcomes of the radio campaign will be compared with standard broadcasting (ie, ‘do nothing’ comparator). All costs associated with creating and broadcasting the radio campaign during intervention start-up and implementation will be captured. The cost per child under 3 years old reached by the intervention will be calculated. Incremental cost-effectiveness ratios will be calculated for the trial’s primary outcome (ie, incremental cost per SD of cognitive gain). A cost-consequence analysis will also be presented, whereby all relevant costs and outcomes are tabulated. Finally, an analysis will be conducted to assess the equity impact of the intervention.

Ethics and dissemination

The SUNRISE trial has ethical approval from the ethics committees of the Ministry of Health, Burkina Faso, University College London and the London School of Hygiene and Tropical Medicine. The results of the economic evaluation will be disseminated in a peer-reviewed journal and presented at a relevant international conference.

Trial registration number

The SUNRISE trial was registered with ClinicalTrials.gov on 19 April 2019 (identifier: NCT05335395).

Pancreatic quantitative sensory testing to predict treatment response of endoscopic therapy or surgery for painful chronic pancreatitis with pancreatic duct obstruction: study protocol for an observational clinical trial

Por: Phillips · A. E. · Afghani · E. · Akshintala · V. S. · Benos · P. Y. · Das · R. · Drewes · A. M. · Easler · J. · Faghih · M. · Gabbert · C. · Halappa · V. · Khashab · M. A. · Olesen · S. S. · Saloman · J. L. · Sholosh · B. · Slivka · A. · Wang · T. · Yadav · D. · Singh · V. K.
Introduction

Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP.

Methods and analysis

This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction. Primary outcome: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment.

Ethics and dissemination

The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies.

Trial registration number

NCT04996628.

Comprehensive quality assessment for aphasia rehabilitation after stroke: protocol for a multicentre, mixed-methods study

Por: Harvey · S. · Stone · M. · Zingelman · S. · Copland · D. A. · Kilkenny · M. F. · Godecke · E. · Cadilhac · D. A. · Kim · J. · Olaiya · M. T. · Rose · M. L. · Breitenstein · C. · Shrubsole · K. · OHalloran · R. · Hill · A. J. · Hersh · D. · Mainstone · K. · Mainstone · P. · Unsworth · C. A
Introduction

People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments.

Methods and analysis

This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4).

Ethics and dissemination

Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women’s Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families.

Identifying provider, patient and practice factors that shape long-term opioid prescribing for cancer pain: a qualitative study of American and Australian providers

Por: Fereydooni · S. · Lorenz · K. · Azarfar · A. · Luckett · T. · Phillips · J. L. · Becker · W. · Giannitrapani · K.
Introduction

Prescribing long-term opioid therapy is a nuanced clinical decision requiring careful consideration of risks versus benefits. Our goal is to understand patient, provider and context factors that impact the decision to prescribe opioids in patients with cancer.

Methods

We conducted a secondary analysis of the raw semistructured interview data gathered from 42 prescribers who participated in one of two aligned concurrent qualitative studies in the USA and Australia. We conducted a two-part analysis of the interview: first identifying all factors influencing long-term prescribing and second open coding-related content for themes.

Results

Factors that influence long-term opioid prescribing for cancer-related pain clustered under three key domains (patient-related, provider-related and practice-related factors) each with several themes. Domain 1: Patient factors related to provider–patient continuity, patient personality, the patient’s social context and patient characteristics including racial/ethnic identity, housing and socioeconomic status. Domain 2: Provider-related factors centred around provider ‘personal experience and expertise’, training and time availability. Domain 3: Practice-related factors included healthcare interventions to promote safer opioid practices and accessibility of quality alternative pain therapies.

Conclusion

Despite the differences in the contexts of the two countries, providers consider similar patient, provider and practice-related factors when long-term prescribing opioids for patients with cancer. Some of these factors may be categorised as cognitive biases that may intersect in an already disadvantaged patient and exacerbate disparities in the treatment of their pain. A more systematic understanding of these factors and how they impact the quality of care can inform appropriate interventions.

Retinoid orphan receptor gamma t (rorγt) promotes inflammatory eosinophilia but is dispensable for innate immune-mediated colitis

by Alvaro Torres-Huerta, Katelyn Ruley-Haase, Theodore Reed, Antonia Boger-May, Derek Rubadeux, Lauren Mayer, Arpitha Mysore Rajashekara, Morgan Hiller, Madeleine Frech, Connor Roncagli, Cameron Pedersen, Mary Catherine Camacho, Lauren Hollmer, Lauren English, Grace Kane, David L. Boone

Inflammatory bowel diseases (IBD) result from uncontrolled inflammation in the intestinal mucosa leading to damage and loss of function. Both innate and adaptive immunity contribute to the inflammation of IBD and innate and adaptive immune cells reciprocally activate each other in a forward feedback loop. In order to better understand innate immune contributions to IBD, we developed a model of spontaneous 100% penetrant, early onset colitis that occurs in the absence of adaptive immunity by crossing villin-TNFAIP3 mice to RAG1-/- mice (TRAG mice). This model is driven by microbes and features increased levels of innate lymphoid cells in the intestinal mucosa. To investigate the role of type 3 innate lymphoid cells (ILC3) in the innate colitis of TRAG mice, we crossed them to retinoid orphan receptor gamma t deficient (Rorγt-/-) mice. Rorγt-/- x TRAG mice exhibited markedly reduced eosinophilia in the colonic mucosa, but colitis persisted in these mice. Colitis in Rorγt-/- x TRAG mice was characterized by increased infiltration of the intestinal mucosa by neutrophils, inflammatory monocytes, macrophages and other innate cells. RNA and cellular profiles of Rorγt-/- x TRAG mice were consistent with a lack of ILC3 and ILC3 derived cytokines, reduced antimicrobial factors, increased activation oof epithelial repair processes and reduced activation of epithelial cell STAT3. The colitis in Rorγt-/- x TRAG mice was ameliorated by antibiotic treatment indicating that microbes contribute to the ILC3-independent colitis of these mice. Together, these gene expression and cell signaling signatures reflect the double-edged sword of ILC3 in the intestine, inducing both proinflammatory and antimicrobial protective responses. Thus, Rorγt promotes eosinophilia but Rorγt and Rorγt-dependent ILC3 are dispensable for the innate colitis in TRAG mice.

REST: a preoperative tailored sleep intervention for patients undergoing total knee replacement - feasibility study for a randomised controlled trial

Por: Bertram · W. · Penfold · C. · Glynn · J. · Johnson · E. · Burston · A. · Rayment · D. · Howells · N. · White · S. · Wylde · V. · Gooberman-Hill · R. · Blom · A. · Whale · K.
Objectives

To test the feasibility of a randomised controlled trial (RCT) of a novel preoperative tailored sleep intervention for patients undergoing total knee replacement.

Design

Feasibility two-arm two-centre RCT using 1:1 randomisation with an embedded qualitative study.

Setting

Two National Health Service (NHS) secondary care hospitals in England and Wales.

Participants

Preoperative adult patients identified from total knee replacement waiting lists with disturbed sleep, defined as a score of 0–28 on the Sleep Condition Indicator questionnaire.

Intervention

The REST intervention is a preoperative tailored sleep assessment and behavioural intervention package delivered by an Extended Scope Practitioner (ESP), with a follow-up phone call 4 weeks postintervention. All participants received usual care as provided by the participating NHS hospitals.

Outcome measures

The primary aim was to assess the feasibility of conducting a full trial. Patient-reported outcomes were assessed at baseline, 1-week presurgery, and 3 months postsurgery. Data collected to determine feasibility included the number of eligible patients, recruitment rates and intervention adherence. Qualitative work explored the acceptability of the study processes and intervention delivery through interviews with ESPs and patients.

Results

Screening packs were posted to 378 patients and 57 patients were randomised. Of those randomised, 20 had surgery within the study timelines. An appointment was attended by 25/28 (89%) of participants randomised to the intervention. Follow-up outcomes measures were completed by 40/57 (70%) of participants presurgery and 15/57 (26%) postsurgery. Where outcome measures were completed, data completion rates were 80% or higher for outcomes at all time points, apart from the painDETECT: 86% complete at baseline, 72% at presurgery and 67% postsurgery. Interviews indicated that most participants found the study processes and intervention acceptable.

Conclusions

This feasibility study has demonstrated that with some amendments to processes and design, an RCT to evaluate the clinical and cost-effectiveness of the REST intervention is feasible.

Trial registration number

ISRCTN14233189.

Exploring the feasibility and acceptance of an optimised physiotherapy approach for lateral elbow tendinopathy: a qualitative investigation within the OPTimisE trial

Por: Bateman · M. · Saunders · B. · Cooper · K. · Littlewood · C. · Hill · J. C.
Objectives

To explore the acceptability of an optimised physiotherapy (OPTimisE) intervention for people with lateral elbow tendinopathy (LET) and feasibility of comparing it to usual care in a randomised controlled trial.

Design

Semistructured interviews, analysed using thematic analysis and mapped onto the COM-B model of behaviour change.

Setting

Conducted as part of the OPTimisE Pilot & Feasibility randomised controlled trial within physiotherapy departments in the United Kingdom National Health Service.

Participants

17 patients with LET (purposively sampled to provide representativeness based on age, sex, ethnicity, deprivation index and treatment allocation) and all 8 physiotherapists involved as treating clinicians or site principal investigators.

Results

Four themes were identified. First, participants reported the OPTimisE intervention as acceptable. Second, differences between the OPTimisE intervention and usual care were identified, including the use of an orthosis, holistic advice/education including modifiable risk factors, forearm stretches, general upper body strengthening and a more prescriptive exercise-dosing regimen. Third, participants provided feedback related to the trial resources, which were viewed positively, but identified language translation as a need. Fourth, feedback related to trial processes identified the need for changes to outcome collection and reduction of administrative burden. From the perspective of adopting the OPTimisE intervention, we found evidence that participants were able to change their behaviour. Considering the findings through the lens of the COM-B model, the intervention is likely to be deliverable in practice and the trial can be delivered at scale with some additional support for physiotherapists.

Conclusions

Overall, the OPTimisE intervention was found to be different to usual care and acceptable to patients and physiotherapists. The study highlighted the need to refine trial processes and resources prior to a full-scale trial, to reduce administrative burden, increase support for physiotherapists, improve return rate of outcome questionnaires and provide language translation.

Trial registration number

ISRCTN database 19 July 2021. https://www.isrctn.com/ISRCTN64444585.

Assessing the acceptability of, adherence to and preference for a dual prevention pill (DPP) for HIV and pregnancy prevention compared to oral pre-exposure prophylaxis (PrEP) and oral contraception taken separately: protocols for two randomised, controlle

Por: Friedland · B. A. · Mgodi · N. M. · Palanee-Phillips · T. · Mathur · S. · Plagianos · M. G. · Bruce · I. V. · Lansiaux · M. · Murombedzi · C. · Musara · P. · Dandadzi · A. · Reddy · K. · Ndlovu · N. · Zulu · S. K. · Shale · L. R. · Zieman · B. · Haddad · L. B.
Introduction

Oral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, uptake and persistence have been low among southern African women. A dual prevention pill (DPP) that combines PrEP with oral contraception (OC) may increase PrEP use and better meet women’s sexual and reproductive health needs. We will gauge the DPP’s acceptability in two cross-over clinical trials.

Methods and analysis

PC952 (Zimbabwe) and PC953 (South Africa) will compare acceptability, adherence and preference for an over-encapsulated DPP versus PrEP and OCs taken separately. HIV-negative, non-pregnant cisgender females in Johannesburg, South Africa (n=96, 16–40 years) and Harare, Zimbabwe (n=30, 16–24 years) will be randomised 1:1 to the order of regimens—DPP or two separate tablets—each used for three 28-day cycles, followed by a 6-month choice period in South Africa. Monthly clinic visits include HIV and pregnancy testing; safety assessments and risk reduction and adherence counselling. We will assess adherence (monthly) based on tenofovir diphosphate drug levels in dried blood spots and by self-report. We will evaluate acceptability (monthly) and preference (end of cross-over) via computer-assisted self-interviewing and in-depth interviews with a subset of participants. Data collection started in September 2022 and ended in January 2024.

Ethics and dissemination

PC952 was approved by the Ministry of Health and Child Care, Medical Research Council, Research Council and Medicines Control Authority of Zimbabwe; the Chitungwiza City Health Ethics Committee; and the Joint Research Ethics Committee for the University of Zimbabwe Faculty of Medicine and Health Sciences and Parirenyatwa Group of Hospitals. PC953 was approved by the South African Health Products Regulatory Authority and the University of the Witwatersrand’s Human Research Ethics Committee. The Population Council IRB approved both studies. We will disseminate results in open-access journals, clinical trials registries, and at local and international meetings and conferences.

Trial registration numbers

NCT04778514, NCT04778527.

Do they stay, or do they go? Children presenting to five emergency departments across New South Wales, Australia with acute burn injuries: a retrospective review

Por: Phillips · W. · Southern · E. · Cattell · C. · Owens · P. · Jaques · M. · Melbourne · G. · Kezhekkekara · S. · Frost · S. A.
Objective

The overall objective of the study was to describe the disposition status of children presenting with a burn injury to five emergency departments (ED) across New South Wales (NSW), Australia.

Design

A retrospective study design was used to review routinely collected ED data.

Setting

Study sites included five acute hospitals across NSW, Australia.

Participants

During the 5-year study period between 1 January 2015 to 31 December 2020, there were 5213 paediatric burn injury presentations.

Results

The mean age of burn injury presentations was 24 months (Inter-Quartile-Range (IQR) 12–84), of which 57% (2951/5213) were males. The most common presentation time was between 16:00 and 23:59 hours (63%, 3297/5213), and the median time spent in the ED was 3 hours (IQR 1–4). The majority (80%, 4196/5213) of the burn injuries presentations did not require hospital admission. The most common principal diagnoses were ‘Burn body region unspecified’ (n=1916) and ‘Burn of wrist and hand’ (n=1060).

Conclusion

Most children who presented to the hospital with a burn injury were not admitted. Often the details of these burns were poorly recorded and a complete picture of the true burden of burn injury in children, especially the ongoing care given outside the acute hospital setting, is missing. This information is crucial, as it would inform future models of care as the paradigm shifts rapidly towards primary, ambulatory and outpatient models of care.

Design and content validation of a checklist about infection‐prevention performance of intensive care nurses in simulation‐based scenarios

Abstract

Objective

To design, develop and validate a new tool, called NEUMOBACT, to evaluate critical care nurses' knowledge and skills in ventilator-associated pneumonia (VAP) and catheter-related bacteraemia (CRB) prevention through simulation scenarios involving central venous catheter (CVC), endotracheal suctioning (ETS) and mechanically ventilated patient care (PC) stations.

Background

Simulation-based training is an excellent way for nurses to learn prevention measures in VAP and CRB.

Design

Descriptive metric study to develop NEUMOBACT and analyse its content and face validity that followed the COSMIN Study Design checklist for patient-reported outcome measurement instruments.

Methods

The first version was developed with the content of training modules in use at the time (NEUMOBACT-1). Delphi rounds were used to assess item relevance with experts in VAP and CRB prevention measures, resulting in NEUMOBACT-2. Experts in simulation methods then assessed feasibility, resulting in NEUMOBACT-3. Finally, a pilot test was conducted among 30 intensive care unit (ICU) nurses to assess the applicability of the evaluation tool in clinical practice.

Results

Seven national experts in VAP and CRB prevention and seven national simulation experts participated in the analysis to assess the relevance and feasibility of each item, respectively. After two Delphi rounds with infection experts, four Delphi rounds with simulation experts, and pilot testing with 30 ICU nurses, the NEUMOBACT-FINAL tool consisted of 17, 26 and 21 items, respectively, for CVC, ETS and PC.

Conclusion

NEUMOBACT-FINAL is useful and valid for assessing ICU nurses' knowledge and skills in VAP and CRB prevention, acquired through simulation.

Relevance for Clinical Practice

Our validated and clinically tested tool could facilitate the transfer of ICU nurses' knowledge and skills learning in VAP and CRB prevention to critically ill patients, decreasing infection rates and, therefore, improving patient safety.

Patient or Public Contribution

Experts participated in the Delphi rounds and nurses in the pilot test.

Implementation of rapid genomic sequencing in safety-net neonatal intensive care units: protocol for the VIrtual GenOme CenteR (VIGOR) proof-of-concept study

Por: D'Gama · A. M. · Hills · S. · Douglas · J. · Young · V. · Genetti · C. A. · Wojcik · M. H. · Feldman · H. A. · Yu · T. W. · G Parker · M. · Agrawal · P. B. · VIGOR Network · Agrawal · Allcroft · Bhandari · Cantu · DGama · Douglas · Feldman · Genetti · Hills · Honrubia · Kritzer · Parke
Introduction

Rapid genomic sequencing (rGS) in critically ill infants with suspected genetic disorders has high diagnostic and clinical utility. However, rGS has primarily been available at large referral centres with the resources and expertise to offer state-of-the-art genomic care. Critically ill infants from racial and ethnic minority and/or low-income populations disproportionately receive care in safety-net and/or community settings lacking access to state-of-the-art genomic care, contributing to unacceptable health equity gaps. VIrtual GenOme CenteR is a ‘proof-of-concept’ implementation science study of an innovative delivery model for genomic care in safety-net neonatal intensive care units (NICUs).

Methods and analysis

We developed a virtual genome centre at a referral centre to remotely support safety-net NICU sites predominantly serving racial and ethnic minority and/or low-income populations and have limited to no access to rGS. Neonatal providers at each site receive basic education about genomic medicine from the study team and identify eligible infants. The study team enrols eligible infants (goal n of 250) and their parents and follows families for 12 months. Enrolled infants receive rGS, the study team creates clinical interpretive reports to guide neonatal providers on interpreting results, and neonatal providers return results to families. Data is collected via (1) medical record abstraction, (2) surveys, interviews and focus groups with neonatal providers and (3) surveys and interviews with families. We aim to examine comprehensive implementation outcomes based on the Proctor Implementation Framework using a mixed methods approach.

Ethics and dissemination

This study is approved by the institutional review board of Boston Children’s Hospital (IRB-P00040496) and participating sites. Participating families are required to provide electronic written informed consent and neonatal provider consent is implied through the completion of surveys. The results will be disseminated via peer-reviewed publications and data will be made accessible per National Institutes of Health (NIH) policies.

Trial registration number

NCT05205356/clinicaltrials.gov.

Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis

Por: Bruorton · M. · Donnelley · M. · Goddard · T. · OConnor · A. · Parsons · D. · Phillips · J. · Carson-Chahhoud · K. · Tai · A.
Introduction

Cystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry (XV) is a novel form of X-ray imaging that can generate lung ventilation data through the breathing cycle. XV technology has been validated in multiple animal models, including the β-ENaC mouse model of CF lung disease. It has since been assessed in early-phase clinical trials in adult human subjects; however, there is a paucity of data in the paediatric cohort, including in CF. The aim of this pilot study was to investigate the feasibility of performing a single-centre cohort study in paediatric patients with CF and in those with normal lungs to demonstrate the appropriateness of proceeding with further studies of XV in these cohorts.

Methods and analysis

This is a cross-sectional, single-centre, pilot study. It will recruit children aged 3–18 years to have XV lung imaging performed, as well as paired pulmonary function testing. The study will aim to recruit 20 children without CF with normal lungs and 20 children with CF. The primary outcome will be the feasibility of recruiting children and performing XV testing. Secondary outcomes will include comparisons between XV and current assessments of pulmonary function and structure.

Ethics and dissemination

This project has ethical approval granted by The Women’s and Children’s Hospital Human Research Ethics Committee (HREC ID 2021/HRE00396). Findings will be disseminated through peer-reviewed publication and conferences.

Trial registration number

ACTRN12623000109606.

Association of Long COVID with mental health disorders: a retrospective cohort study using real-world data from the USA

Por: Zhang · Y. · Chinchilli · V. M. · Ssentongo · P. · Ba · D. M.
Objectives

Mental health disorders (MHD) rank third for US adult hospitalisations. Given the substantial prevalence of ‘Long COVID’ in SARS-CoV-2 survivors, this study aims to assess its association with increased MHD risk using extensive real-world data.

Design

A retrospective cohort study with propensity score matching was conducted. We used the International Classification of Diseases, 10th Revision codes to identify individuals with Long COVID status and COVID-19 histories. Multivariable stratified Cox proportional hazards regression analysis was conducted to determine the association of Long COVID status with MHD.

Setting

Data were sourced from the TriNetX database, spanning records from 1 October 2021 to 16 April 2023.

Participants

Two distinct cohorts were established: one comprising individuals diagnosed with Long COVID and another comprising individuals with no history of Long COVID or COVID-19. At the start of the study, none of the participants had a recorded MHD.

Primary and secondary outcome measures

The main outcome of interest was a composite diagnosis of MHD. Secondary outcomes were individual mental health conditions.

Results

The study included 43 060 control participants without Long COVID and 4306 Long COVID participants, demonstrating well-balanced distribution across all covariates. After adjusting for 4 demographic factors and 10 comorbidities, Long COVID was associated with MHD (adjusted HR, aHR 2.60; 95% CI 2.37 to 2.85). In subgroup analysis, Long COVID was associated with major depression disorder (aHR 3.36; 95% CI 2.82 to 4.00) and generalised anxiety disorder (aHR 3.44; 95% CI 2.99 to 3.96).

Conclusions

In this retrospective large real-world cohort study, Long COVID was associated with an increased risk of incident MHD. The MHD impact is significant considering the vast number of patients with Long COVID. Enhanced MHD screening among COVID-19 survivors should be a priority.

Protocol of a 12-week eHealth programme designed to reduce concerns about falling in community-living older people: Own Your Balance randomised controlled trial

Por: Lim · M. L. · Perram · A. · Radford · K. · Close · J. · Draper · B. · Lord · S. R. · Anstey · K. J. · O'Dea · B. · Ambrens · M. · Hill · T.-Y. · Brown · A. · Miles · L. · Ngo · M. · Letton · M. · van Schooten · K. S. · Delbaere · K.
Introduction

Concerns about falling (CaF) are common in older people and have been associated with avoidance of activities of daily life. Exercise designed to prevent falls can reduce CaF, but the effects are usually short-lived. Cognitive behavioural therapy (CBT) can reduce CaF for longer but is not readily available in the community and unlikely to prevent falls. A multidomain intervention that combines CBT, motivational interviewing and exercise could be the long-term solution to treat CaF and reduce falls in older people with CaF. This paper describes the design of a randomised controlled trial to test the effectiveness of two different 12 week self-managed eHealth programmes to reduce CaF compared with an active control.

Methods

A total of 246 participants (82 per group) aged 65 and over, with substantial concerns about falls or balance will be recruited from the community. They will be randomised into: (1) myCompass-Own Your Balance (OYB) (online CBT programme) intervention or (2) myCompass-OYB plus StandingTall intervention (an eHealth balance exercise programme), both including motivational interviewing and online health education or (3) an active control group (online health education alone). The primary outcome is change in CaF over 12 months from baseline of both intervention groups compared with control. The secondary outcomes at 2, 6 and 12 months include balance confidence, physical activity, habitual daily activity, enjoyment of physical activity, social activity, exercise self-efficacy, rate of falls, falls health literacy, mood, psychological well-being, quality of life, exercise self-efficacy, programme adherence, healthcare use, user experience and attitudes towards the programme. An intention-to-treat analysis will be applied. The healthcare funder’s perspective will be adopted for the economic evaluation if appropriate.

Ethics and dissemination

Ethical approval was obtained from the South Eastern Sydney Local Health District Human Research Ethics Committee (2019/ETH12840). Results will be disseminated via peer-reviewed journals, local and international conferences, community events and media releases.

Trial registration number

ACTRN12621000440820.

A strengths‐based qualitative exploration of critical care nurses' reasons for remaining in critical care

Abstract

Aims

Globally, the nursing shortage is a growing concern. Much of the research on retention of nurses focuses on the experience of those who left positions. In this study, we set out to listen to critical care nurses (CCRNs) who have chosen to remain in their positions to understand the factors retaining them in critical care.

Design

This interpretive descriptive study was guided by the following research question: ‘what factors influence CCRN's decision to continue to work in critical care?’

Methods

Digitally recorded interviews and a focus group were conducted between July 2022 and January 2023 using a semi-structured, strengths-based interview guide with CCRNs from three critical care units at a tertiary hospital in a city in a central Canadian province. Transcribed interviews were analysed using open, axial and selective coding and constant comparative analysis.

Results

Twenty-two CCRNs participated in interviews and three in a focus group. The theme of Respect, demonstrated through the interconnected concepts of Working to Full Scope, Team, Rotations and Compensation was identified. Working to Full Scope was described as providing nursing care aligned with how each nurse envisions what nursing is. Being part of a Team led by strong nurse leaders that provides opportunities and supports the sharing of their perspectives was also found. Respect was also found to be demonstrated through Rotations that recognize that work is one part of these nurses' lives. Compensation that reflects the increased education, knowledge and skills required in critical care was the final concept of Respect.

Conclusion

Organizations should focus their efforts across the identified concepts to demonstrate Respect for CCRNs and retain them.

Implications for Practice

The findings of this study provide ways to support the retention of CCRNs.

Impact

This research will have an impact on nursing leaders by providing tangible ways to retain CCRNs.

Reporting Method

Reporting of this work was guided by the Standards for Reporting Qualitative Research.

Patient or Public Contribution

No patient or public contribution.

Struggling in the dehumanized world of COVID—An exploratory mixed‐methods study of frontline healthcare workers' experiences

Abstract

Aim

To explore healthcare workers' experiences of the changed caring reality during the COVID-19 pandemic in Sweden.

Design

An online fully mixed-methods design.

Methods

A web-based self-reported questionnaire with fixed and open-ended answers collected data from March to April 2021, analysed in three steps. First, free-text questions were analysed by qualitative content analysis. Then quantitative linear regression analyses using models covering stress and coping mechanisms were conducted. Finally, a meta-inference of qualitative and quantitative data emerged a new comprehensive understanding. The COREQ guidelines were used for reporting.

Results

Meta-inferenced results of quantitative and qualitative findings show the pandemic was a traumatic experience for healthcare workers. Main theme; When work became a frightening experience in a dehumanized reality, comprised four themes: Entering unprepared into a frightful, incomprehensible world; Sacrificing moral values and harbouring dilemmas in isolation; Lack of clear management; and Reorient in togetherness and find meaning in a changed reality. Qualitative results comprised four categories; Working in a dehumanized world; Living in betrayal of ones' own conscience; Lack of structure in a chaotic time and Regaining vitality together. Subdimensions comprehensibility and meaningfulness were associated significantly with post-traumatic stress disorder in multiple regression analysis. In multiple regression analysis, sense of coherence was the most prominent coping strategy.

Conclusions

Forcing oneself to perform beyond one's limit, sacrificing moral values and lacking management was a traumatic experience to healthcare workers during the pandemic. Reorienting as a way of coping was possible in togetherness with colleagues. There is an urgency of interventions to meet the needs among healthcare workers who took on a frontline role during the COVID-19 pandemic and to prevent mental health illness in future crisis.

Patient or Public Contribution

No patient or public contribution.

Summary

The pandemic outbreak exposed frontline healthcare workers to unparallelled stress shown as negative for their mental health in several meta-analyses and systematic reviews. In-depth understanding on experiences and how symptoms of post-traumatic stress disorder relate to coping mechanisms have been scarcely explored. This study contributes to understanding on healthcare workers' experiences and the relation between lower sense of coherence and increased risk of developing symptoms of post-traumatic stress disorder.

Implications for Practice/Policy

This study might guide how to prepare for resilience in future emergencies.

Nurse‐led clinics in primary health care: A scoping review of contemporary definitions, implementation enablers and barriers and their health impact

Abstract

Aims

To define nurse-led clinics in primary health care, identify barriers and enablers that influence their successful implementation, and understand what impact they have on patient and population health outcomes.

Background

Nurse-led clinics definitions remain inconsistent. There is limited understanding regarding what enablers and barriers impact successful nurse-led clinic implementation and their impact on patient health care.

Design

Scoping review using narrative synthesis.

Methods

PubMed, MEDLINE, Web of Science, Scopus, CINAHL and PsycINFO were searched to identify nurse-led clinic definitions and models of care between 2000 and 2023. Screening and selection of studies were based on eligibility criteria and methodological quality assessment. Narrative synthesis enabled to communicate the phenomena of interest and follows the PRISMA for Scoping Reviews (PRISMA-ScR) checklist.

Results

Among the 36 identified studies, key principles of what constitutes nurse-led clinics were articulated providing a robust definition. Nurse-led clinics are, in most cases, commensurate with standard care, however, they provide more time with patients leading to greater satisfaction. Enablers highlight nurse-led clinic success is achieved through champions, partners, systems, and clear processes, while barriers encompass key risk points and sustainability considerations.

Conclusion

The review highlights several fundamental elements are central to nurse-led clinic success and are highly recommended when developing interventional nurse-led strategies. Nurse-led clinics within primary health care seek to address health care through community driven, health professional and policy supported strategies. Overall, a robust and contemporary definition of nurse-led care and the clinics in which they operate is provided.

Relevance to Clinical Practice

The comprehensive definition, clear mediators of success and the health impact of nurse-led clinics provide a clear framework to effectively build greater capacity among nursing services within primary health care. This, in addition, highlights the need for good health care policy to ensure sustainability.

Patient or Public Contribution

No Patient or Public Contribution.

Exploring hospital mealtime experiences of older inpatients, caregivers and staff using photovoice methods

Abstract

Aim

To gather and understand the experience of hospital mealtimes from the perspectives of those receiving and delivering mealtime care (older inpatients, caregivers and staff) using photovoice methods to identify touchpoints and themes to inform the co-design of new mealtime interventions.

Methods

This study was undertaken on acute care wards within a single metropolitan hospital in Brisbane, Australia in 2019. Photovoice methods involved a researcher accompanying 21 participants (10 older patients, 5 caregivers, 4 nurses and 2 food service officers) during a mealtime and documenting meaningful elements using photographs and field notes. Photo-elicitation interviews were then undertaken with participants to gain insight into their experience. Data were analysed using inductive thematic analysis, involving a multidisciplinary research team including a consumer.

Results

Themes were identified across the three touchpoints: (1) preparing for the meal (the juggle, the anticipation), (2) delivering/receiving the meal (the rush, the clutter and the wait) and (3) experiencing the meal (the ideal, pulled away and acceptance). Despite a shared understanding of the importance of meals and shared vision of ‘the ideal’ mealtime, generally this was a time of tension, missed cares and dissatisfaction for staff, patients and caregivers. There was stark contrast in some aspects of mealtime experience, with simultaneous experiences of ‘the rush’ (staff) and ‘the wait’ (patients and caregivers). There was an overwhelming sense of acceptance and lack of control over change from all.

Conclusions

This study identified themes during hospital mealtimes which have largely gone unaddressed in the design of mealtime interventions to date. This research may provide a framework to inform the future co-design of mealtime interventions involving patients, caregivers and multidisciplinary staff, centred around these key touchpoints.

Practice Implications

Mealtimes are experienced differently by patients, caregivers, nurses and food service officers across three key touchpoints: preparing for, delivering/receiving and experiencing the meal. Improving mealtime experiences therefore necessitates a collaborative approach, with co-designed mealtime improvement programs that include specific interventions focusing each touchpoint. Our data suggest that improvements could focus on reducing clutter, clarifying mealtime roles and workflows and supporting caregiver involvement.

Impact

What problem did the study address?

Mealtimes are the central mechanism to meet patients' nutritional needs in hospital; however, research consistently shows that many patients do not eat enough to meet their nutritional requirements and that they often do not receive the mealtime assistance they require. Interventions to improve hospital mealtimes have, at best, shown only modest improvements in nutritional intake and mealtime care practices. Gaining deeper insight into the mealtime experience from multiple perspectives may identify new opportunities for improvement.

What were the main findings?

Patients, caregivers and staff have shared ideals of comfort, autonomy and conviviality at mealtimes, but challenges of complex teamwork and re-prioritisation of mealtimes in the face of prevailing power hierarchies make it difficult to achieve this ideal. There are three discrete touchpoints (preparing for, delivering/receiving and experiencing the meal) that require different approaches to improvement. Our data suggests a need to focus improvement on reducing clutter, clarifying mealtime roles and workflows and supporting caregivers.

Where and on whom will the research have an impact?

The research provides a framework for multidisciplinary teams to begin co-designing improvements to mealtime care to benefit patients, caregivers and staff, while also providing a method for researchers to understand other complex care situations in hospital.

Reporting Method

This manuscript is written in adherence with the Standards for Reporting Qualitative Research.

Patient or Public Contribution

Patients and caregivers were involved in the conception and design of the study through their membership of the hospital mealtime reference group. A consumer researcher (GP) was involved in the team to advise on study conduct (i.e. recruitment methods and information), data analysis (i.e. coding transcripts), data interpretation (i.e. review and refinement of themes) and manuscript writing (i.e. review and approval of final manuscript).

Presence of keel bone damage in laying hens, pullets and roosters of local chicken breeds

by Lisa Jung, Sonja Hillemacher, Inga Tiemann, Mascha Lepke, Dirk Hinrichs

In commercial laying hens, keel bone damage (KBD) is a severe health and welfare problem leading to pain, reduced mobility and decreased laying performance. Flocks of all production systems and hybrid lines can be affected. KBD is a multifactorial welfare issue and, among other factors, associated with a high laying performance which negatively affects the calcium deposit in the medullary bones. Therefore, mature hens of local breeds with much lower egg production than commercial hybrids may be expected to show less or even no keel bone damage. This study evaluates (i) the prevalence of KBD in local breeds, (ii) the difference in type and level of damages, and (iii) if roosters and pullets are also affected. In total, we palpated 343 mature hens, 40 pullets, and 18 roosters of 13 different local breeds and one commercial hybrid. The animals were kept on eight different farms in free-range or floor-housing systems. Our results showed that on average 44.2% of mature hens per local breed were affected by KBD (range: 11.1%-84.7%). We found deviation of less than 1 cm in 26.9%, deviations of more than 1 cm in 6.4% and palpable fractures in 23.8% of the mature hens of local breeds. The tip was damaged in 23.6% of the mature hens. Also, pullets and roosters were affected by KBD. Finally, we found that KBD also occurs in local breeds. Therefore, we conclude that even the low laying performance of local breeds does not prevent them from the occurrence of KBD.KBD in local breeds may rather be associated with genetics (breed) as well as management and housing. Thus, breeders of local breeds should include bone health as a selection trait. Owners of local breeds should also pay attention to the condition of the keel and ought to be trained about preventive measures.
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