Digital gamification-based pursed lip breathing exercises driven by Behaviour Change Wheel in patients with COPD: a feasibility trial protocol using pre-post study design

Introduction
Effective chronic obstructive pulmonary disease (COPD) interventions require intensive and repetitive exercises, yet their monotonous nature can reduce adherence. Innovative rehabilitation devices that are safe, user-friendly, engaging and cost-effective are crucial. This study introduces a digital gamification-based approach to pursed lip breathing (PLB) exercises, guided by the Behaviour Change Wheel (BCW) framework. The digital platform transforms traditional PLB into an interactive and enjoyable experience, enhancing motivation and adherence. Using a pre-post study design, this feasibility trial aims to assess the safety, feasibility and acceptability of the digital gamification PLB intervention protocol driven by the BCW framework installed on WeChat (DT-PLB) for home-based COPD management.

Methods and analysis
The methodology of this study is divided into two phases. Phase 1 refers to the development of the DT-PLB system based on research evidence, behavioural analysis from the insight of the BCW and stakeholders’ perspectives, and phase 2 points to present the pre-post trial design for the DT-PLB system consisting of five smartphone-based software interface modules: Ranking, Report, Daily PLB Tasks, Social Community and Mine. Eligible patients with COPD will be recruited from a university hospital in Sichuan Province, Mainland China. The DT-PLB will be conducted in non-hospital settings for patients with COPD for 10 min per session, three times a day on a daily basis for 8 weeks. Data collection will be conducted at two time points: baseline and post-intervention.
Demographic data (eg, age, gender and marital status) will be collected only at baseline. The primary outcome measures in this study will be a series of feasibility outcomes involving participant recruitment and completion of the DT-PLB intervention. Additionally, several clinical outcomes in terms of the effects of the DT-PLB intervention on dyspnoea, exercise capability, quality of life, and pulmonary function index will be evaluated as secondary outcomes.

Ethics and dissemination
This study has received Manchester Metropolitan University ethical approval (REC reference 56631) and the Affiliated Hospital of Southwest Medical University ethical approval (REC reference KY2023105). The findings from DT-PLB will be disseminated widely through peer-reviewed publications, scientific conferences and workshops. If successful, DT-PLB will be directly applied to the Affiliated Hospital of Southwest Medical University to manage PLB exercises.

Trial registration number
NCT06063733.

Leggi
Marzo 2025

The effect of home-based behavioural weight loss combined with pelvic floor muscle training in women seeking weight loss combined with stress urinary incontinence: protocol for a randomised controlled trial

Introduction
Recent guidelines suggest behavioural weight loss (BWL) and pelvic floor muscle training (PFMT) as first-line treatment approaches for women with both obesity and stress urinary incontinence (SUI). However, the optimal therapeutic and management strategies for these populations remain uncertain.

Methods and analysis
This assessor-blinded parallel-group randomised controlled trial aims to compare the efficacy of BWL alone, BWL plus conventional PFMT and BWL plus PFMT with a biofeedback device for women who are overweight or obese experiencing SUI or SUI-predominant mixed urinary incontinence. A total of 120 eligible women will be randomly assigned at a 1:1:1 ratio. All the three groups will be subjected to a 3-month self-supervision intervention after randomisation and will be assessed at baseline, after the 3-month intervention, 6 months after the intervention and 12 months after the intervention. The primary outcome measure is the self-reported severity of urinary incontinence assessed by the International Consultation on Incontinence Questionnaire-Urinary Incontinence short form. The secondary outcomes include weight loss effectiveness, pelvic muscle strength, pelvic floor ultrasound, three-dimensional body posture, adherence to the intervention and questionnaires for symptoms of pelvic organ prolapse, quality of life and sexual function.

Ethics and dissemination
This study has been approved by the Peking Union Medical College Hospital ethics committee (K5504). All results from the study will be submitted to international journals and international conferences.

Trial registration number
This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2400084015).

Leggi
Marzo 2025

TRanscutaneous lImb reCovEry Post-Stroke (TRICEPS): study protocol for a randomised, controlled, multiarm, multistage adaptive design trial

Introduction
Arm weakness after stroke is one of the leading causes of adult-onset disability. Invasive vagus nerve stimulation (VNS) paired with rehabilitation has been shown to improve arm recovery in chronic stroke. Small studies of non-invasive or transcutaneous VNS (tVNS) suggest it is safe and tolerable. However, it is not known whether tVNS paired with rehabilitation is effective in promoting arm recovery in chronic stroke and what the mechanisms of action are.

Methods and analysis
TRICEPS is a UK multicentre, double-blinded, superiority, parallel-group, three-arm two-stage with an option to select promising arm(s) at 50% accrual, individually randomised, sham-controlled trial. Up to 243 participants will be randomised (1:1:1) using minimisation via a restricted, web-based centralised system. tVNS will be delivered by a movement-activated tVNS system (TVNS Technologies), which delivers stimulation during repetitive task practice. Rehabilitation will consist of repetitive task training for 1 hour a day, 5 days per week for 12 weeks. Participants will be adults with anterior circulation ischaemic stroke between 6 months and 10 years prior with moderate-severe arm weakness. The primary outcome measure will be the change in Upper Limb Fugl-Meyer total motor score at 91 days after the start of treatment. Secondary outcome measures include the Wolf Motor Function Test, the Modified Ashworth Scale to assess spasticity in the affected arm and the Stroke-Specific Quality of Life Scale. A mechanistic substudy including 40 participants will explore the mechanisms of active versus sham tVNS using multimodal MRI and serum inflammatory cytokine levels. Participant recruitment started on 30 November 2023.

Ethics and dissemination
The study has received ethical approval from the Cambridge Central Research Ethics Committee (REC reference: 22/NI/0134). Dissemination of results will be via publications in scientific journals, meetings, written reports and articles in stakeholder publications.

Trial registration number
ISRCTN20221867.

Leggi
Marzo 2025

Study protocol to redefine muscle attenuation cut-offs for better prediction of mortality in patients with cirrhosis: a comprehensive post hoc validation study – a study protocol

Introduction
Myosteatosis, characterised by altered muscle composition detectable by muscle radiodensity attenuation on CT scans, has been associated with increased mortality in patients with cirrhosis. However, standard attenuation cut-offs, derived primarily from oncology populations, may not be appropriate for patients with cirrhosis. This study protocol aims to address this diagnostic gap by validating the Ebadi cut-offs, which are based on a retrospective cohort and have not been extensively validated in a cirrhotic population. The aim of the study is to refine these cut-offs for more accurate prediction of mortality in patients with cirrhosis using two independent patient cohorts (retrospective and prospective).

Methods and analysis
This post hoc validation study analyses muscle weakness cut-offs in patients with cirrhosis using data from two independent cohorts. A total of 1537 patients will be analysed. The study will assess interobserver variability to ensure robust results by analysing random samples of 60 patients from the two cohorts. Statistical methods will be used to determine the accuracy and relevance of current cut-offs in predicting patient mortality. The analysis will also examine the relationship between muscle wasting and clinical outcomes in cirrhosis and the relationship with muscle mass loss.

Ethics and dissemination
Ethical approval for this study has been obtained from the relevant institutional review boards. The results will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals. The results of the study are expected to contribute to improved diagnostic criteria for myosteatosis in cirrhosis, providing clinicians with more tailored and accurate tools for cirrhosis prognosis.

Trial registration number
NCT06593015.

Leggi
Marzo 2025

Knowledge, awareness and perception of Natural Procreative Technology (NaProTechnology) among pharmacy undergraduate students in Nigeria: a pre-post educational video intervention study

Objective
The study assessed the knowledge, awareness and perception of NaProTechnology as well as the effect of an educational video intervention among pharmacy undergraduate students.

Design
The study design was a pre-post educational video intervention using a cross-sectional questionnaire-based survey.

Participants and setting
The study was done among undergraduate students of a school of pharmacy in South-eastern Nigeria.

Intervention and outcome measures
At baseline, the knowledge, awareness and perception of the students were assessed using a 17-item questionnaire: five questions for knowledge, five questions for awareness and seven questions for perception, followed by the administration of an educational video on NaProTechnology which was prepared by one of the authors, a gynaecologist and also an expert in NaProTechnology. A post-intervention survey was done with the same pre-intervention questionnaire to assess the effect of the educational intervention. The correct (knowledge) or positive (awareness and perception) responses for each question were reported as percentages.

Results
There were 410 and 350 students in the pre- and post-intervention surveys, respectively, with a relatively equal number of males and females. The majority were between 18 and 29 years old. The average proportion of the participants with correct responses on the knowledge assessment of NaProTechnology was 13.2% and 75.7% in the pre- and post-intervention surveys, respectively (p

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Marzo 2025

An NRF2/β3-Adrenoreceptor Axis Drives a Sustained Antioxidant and Metabolic Rewiring Through the Pentose-Phosphate Pathway to Alleviate Cardiac Stress

Circulation, Ahead of Print. BACKGROUND:Cardiac β3-adrenergic receptors (ARs) are upregulated in diseased hearts and mediate antithetic effects to those of β1AR and β2AR. β3AR agonists were recently shown to protect against myocardial remodeling in preclinical studies and to improve systolic function in patients with severe heart failure. However, the underlying mechanisms remain elusive.METHODS:To dissect functional, transcriptional, and metabolic effects, hearts and isolated ventricular myocytes from mice harboring a moderate, cardiac-specific expression of a humanADRB3transgene (β3AR-Tg) and subjected to transverse aortic constriction were assessed with echocardiography, RNA sequencing, positron emission tomography scan, metabolomics, and metabolic flux analysis. Subsequently, signaling and metabolic pathways were further investigated in vivo in β3AR-Tg and ex vivo in neonatal rat ventricular myocytes adenovirally infected to express β3AR and subjected to neurohormonal stress. These results were complemented with an analysis of single-nucleus RNA-sequencing data from human cardiac myocytes from patients with heart failure.RESULTS:Compared with wild-type littermates, β3AR-Tg mice were protected from hypertrophy after transaortic constriction, and systolic function was preserved. β3AR-expressing hearts displayed enhanced myocardial glucose uptake under stress in the absence of increased lactate levels. Instead, metabolomic and metabolic flux analyses in stressed hearts revealed an increase in intermediates of the pentose-phosphate pathway in β3AR-Tg, an alternative route of glucose utilization, paralleled with increased transcript levels of NADPH-producing and rate-limiting enzymes of the pentose-phosphate pathway, without fueling the hexosamine metabolism. The ensuing increased content of NADPH and of reduced glutathione decreased myocyte oxidant stress, whereas downstream oxidative metabolism assessed by oxygen consumption was preserved with higher glucose oxidation in β3AR-Tg mice after transaortic constriction compared with wild type, together with increased mitochondrial biogenesis. Unbiased transcriptomics and pathway analysis identified NRF2 (NFE2L2) as an upstream transcription factor that was functionally verified in vivo and in β3AR-expressing cardiac myocytes, where its translocation and nuclear activity were dependent on β3AR activation of nitric oxide synthase and nitric oxide production through S-nitrosation of the NRF2-negative regulator Keap1.CONCLUSIONS:Moderate expression of cardiac β3AR, at levels observed in human cardiac myocardium, exerts metabolic and antioxidant effects through activation of the pentose-phosphate pathway and NRF2 pathway through S-nitrosation of Keap1, thereby preserving myocardial oxidative metabolism, function, and integrity under pathophysiological stress.

Leggi
Marzo 2025

An NRF2/β3-Adrenoreceptor Axis Drives a Sustained Antioxidant and Metabolic Rewiring Through the Pentose-Phosphate Pathway to Alleviate Cardiac Stress

Circulation, Ahead of Print. BACKGROUND:Cardiac β3-adrenergic receptors (ARs) are upregulated in diseased hearts and mediate antithetic effects to those of β1AR and β2AR. β3AR agonists were recently shown to protect against myocardial remodeling in preclinical studies and to improve systolic function in patients with severe heart failure. However, the underlying mechanisms remain elusive.METHODS:To dissect functional, transcriptional, and metabolic effects, hearts and isolated ventricular myocytes from mice harboring a moderate, cardiac-specific expression of a humanADRB3transgene (β3AR-Tg) and subjected to transverse aortic constriction were assessed with echocardiography, RNA sequencing, positron emission tomography scan, metabolomics, and metabolic flux analysis. Subsequently, signaling and metabolic pathways were further investigated in vivo in β3AR-Tg and ex vivo in neonatal rat ventricular myocytes adenovirally infected to express β3AR and subjected to neurohormonal stress. These results were complemented with an analysis of single-nucleus RNA-sequencing data from human cardiac myocytes from patients with heart failure.RESULTS:Compared with wild-type littermates, β3AR-Tg mice were protected from hypertrophy after transaortic constriction, and systolic function was preserved. β3AR-expressing hearts displayed enhanced myocardial glucose uptake under stress in the absence of increased lactate levels. Instead, metabolomic and metabolic flux analyses in stressed hearts revealed an increase in intermediates of the pentose-phosphate pathway in β3AR-Tg, an alternative route of glucose utilization, paralleled with increased transcript levels of NADPH-producing and rate-limiting enzymes of the pentose-phosphate pathway, without fueling the hexosamine metabolism. The ensuing increased content of NADPH and of reduced glutathione decreased myocyte oxidant stress, whereas downstream oxidative metabolism assessed by oxygen consumption was preserved with higher glucose oxidation in β3AR-Tg mice after transaortic constriction compared with wild type, together with increased mitochondrial biogenesis. Unbiased transcriptomics and pathway analysis identified NRF2 (NFE2L2) as an upstream transcription factor that was functionally verified in vivo and in β3AR-expressing cardiac myocytes, where its translocation and nuclear activity were dependent on β3AR activation of nitric oxide synthase and nitric oxide production through S-nitrosation of the NRF2-negative regulator Keap1.CONCLUSIONS:Moderate expression of cardiac β3AR, at levels observed in human cardiac myocardium, exerts metabolic and antioxidant effects through activation of the pentose-phosphate pathway and NRF2 pathway through S-nitrosation of Keap1, thereby preserving myocardial oxidative metabolism, function, and integrity under pathophysiological stress.

Leggi
Marzo 2025

Polygenic Risk Score for the Efficacy of Clopidogrel in Patients With Minor Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the CHANCE Trial

Stroke, Ahead of Print. BACKGROUND:Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is recommended for secondary prevention in patients with a minor stroke or transient ischemic attack. However, the effectiveness of DAPT can be significantly influenced by genetic variations. This study aimed to estimate the impact of multiple single-nucleotide polymorphisms across various genes on DAPT efficacy using polygenic risk score (PRS).METHODS:In this post hoc analysis, we included 2905 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), which enrolled a total of 5170 patients in China between October 2009 and July 2012. The primary outcome was new stroke within 90 days. Sixteen single-nucleotide polymorphisms across 7 genes involved in clopidogrel metabolism were selected for PRS development. PRS were calculated by summing single-nucleotide polymorphisms from each individual. The Cox proportional-hazards regression model was utilized to estimate the hazard ratio (HR) and 95% CIs of PRS. The predictive value of PRS was estimated by C statistic and compared with a previously validated model.RESULTS:The elevated PRSs were associated with an increased risk of new stroke within 90 days (Ptrend=0.01). The efficacy of DAPT versus aspirin alone in preventing 1-year composite vascular events was significantly different between patients with low (adjusted HR, 0.47 [95% CI, 0.31–0.71]) and high PRSs (adjusted HR, 0.84 [95% CI, 0.60–1.18];Pinteraction=0.03). In patients receiving DAPT, higher PRSs were associated with increased risk of new stroke and composite vascular events at 90 days (adjusted HR per SD increase was 1.51 [95% CI, 1.15–1.99]) and at 1 year (adjusted HR per SD increase was 1.34 [95% CI, 1.08–1.67]). The C statistic for predicting 90-day new stroke using the PRS developed in this study was 0.57 (95% CI, 0.52–0.62), compared with 0.52 (95% CI, 0.48–0.55) for the ABCD-GENE score.CONCLUSIONS:Using PRS integrating multiple genes may enhance the precision of secondary prevention strategies for patients with minor stroke or transient ischemic attack in the short and long term.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT00979589.

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Marzo 2025

Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohns disease: post hoc analysis of the RISK study

Background
One in three children with Crohn’s disease develop perianal fistula complications (PFCs), among the most disturbing and difficult-to-treat disease-related complications. Retrospective evidence suggests PFCs may be preventable.

Objective
We aimed to determine if early antitumour necrosis factor-alpha (anti-TNF) therapy prevents PFC development in a well-characterised prospective cohort of paediatric patients with Crohn’s disease who were free from PFC at enrolment.

Design
RISK was a multicentre inception cohort of children newly diagnosed with Crohn’s disease. We included all patients who had never experienced PFCs 30 days after study enrolment. We conducted nearest-neighbour propensity score-matched triad analyses. Matching was performed to balance patient characteristics across three mutually exclusive treatment groups based on therapy prior to either PFC development or the end of the observation period.

Results
Among 873 patients without perianal fistula, 447 matched patients were included (149 per treatment group). The presence of non-penetrating perianal lesions (large skin tags, ulcers and/or fissures) was significantly associated with PFC development, with 4-fold greater odds of PFC (OR 4.08, 95% CI (95% CI) 1.70 to 9.78; p=0.0016). Early anti-TNF therapy was associated with an 82% decrease in the odds of PFC (OR 0.18, 95% CI 0.05 to 0.66; p=0.01). Among those with perianal lesions, anti-TNF therapy was associated with 94% reduced odds of PFC development (OR 0.055, 95% CI 0.006 to 0.50; p=0.010). No other treatment group was associated with reduced risk of PFC.

Conclusion
Early anti-TNF therapy prevents perianal fistula development, especially among patients at increased risk.

Leggi
Marzo 2025

Nurse retention in peri- and post-COVID-19 work environments: a scoping review of factors, strategies and interventions

Objectives
The COVID-19 pandemic highlighted the deterioration of nurses’ working conditions and a growing global nursing shortage. Little is known about the factors, strategies and interventions that could improve nurse retention in the peri- and post-COVID-19 period. An improved understanding of strategies that support and retain nurses will provide a foundation for developing informed approaches to sustaining the nursing workforce. The aim of this scoping review is to investigate and describe the (1) factors associated with nurse retention, (2) strategies to support nurse retention and (3) interventions that have been tested to support nurse retention, during and after the COVID-19 pandemic.

Design
Scoping review.

Data sources
This scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. MEDLINE, Embase, CINAHL and Scopus databases were searched on 17 April 2024. The search was limited to a publication date of ‘2019 to present’.

Eligibility criteria
Qualitative, quantitative, mixed-methods and grey literature studies of nurses (Registered Nurse (RN), Licenced Practical Nurse (LPN), Registered Practical Nurse (RPN), Publlic Health Nurse (PHN), including factors, strategies and/or interventions to support nurse retention in the peri- and post-COVID-19 period in English (or translated into English), were included. Systematic reviews, scoping reviews and meta-syntheses were excluded, but their reference lists were hand-screened for suitable studies.

Data extraction and synthesis
The following data items were extracted: title, journal, authors, year of publication, country of publication, setting, population (n=), factors that mitigate intent to leave (or other retention measure), strategies to address nurse retention, interventions that address nurse retention, tools that measure retention/turnover intention, retention rates and/or scores. Data were evaluated for quality and synthesised qualitatively to map the current available evidence.

Results
Our search identified 130 studies for inclusion in the analysis. The majority measured some aspect of nurse retention. A number of factors were identified as impacting nurse retention including nurse demographics, safe staffing and work environments, psychological well-being and COVID-19-specific impacts. Nurse retention strategies included ensuring safe flexible staffing and quality work environments, enhancing organisational mental health and wellness supports, improved leadership and communication, more professional development and mentorship opportunities, and better compensation and incentives. Only nine interventions that address nurse retention were identified.

Conclusions
Given the importance of nurse retention for a variety of key outcomes, it is imperative that nursing leadership, healthcare organisations and governments work to develop and test interventions that address nurse retention.

Leggi
Marzo 2025

Randomised controlled trial of LGBTQ-affirmative cognitive-behavioural therapy for sexual minority womens minority stress, mental health and hazardous drinking: Project EQuIP protocol

Introduction
Sexual minority women represent one of the highest-risk groups for hazardous drinking and comorbid mental health problems (eg, depression, anxiety). Research has identified cognitive (eg, expectations of rejection), affective (eg, emotion dysregulation) and behavioural (eg, avoidant coping) pathways through which minority stress (eg, stigma) places sexual minority women at disproportionate risk of hazardous drinking and comorbid depression/anxiety; yet no evidence-based interventions have been tested to address these pathways in this population. This article describes the design of Project EQuIP (Empowering Queer Identities in Psychotherapy), a randomised controlled trial of a transdiagnostic lesbian, gay, bisexual, transgender, queer (LGBTQ)-affirmative cognitive-behavioural therapy intervention (CBT) designed to improve minority stress coping and reduce sexual minority women’s hazardous drinking and mental health comorbidities.

Methods and analysis
This two-arm randomised controlled trial, funded by the National Institute on Alcohol Abuse and Alcoholism, has two objectives: (1) test the efficacy of 10 sessions of LGBTQ-affirmative CBT compared with 10 sessions of supportive counselling for sexual minority women in the community (anticipated n=450) who report hazardous alcohol use and meet criteria for a Diagnostic and Statistical Manual of Mental Disorders – 5 diagnosis of a depression or anxiety disorder and (2) examine psychosocial mechanisms and demographic factors as potential mediators and moderators, respectively, of the treatment-outcome relationship. This study’s primary outcome is change in the proportion of heavy drinking days. Secondary outcomes are changes in depressive and anxious symptoms.

Ethics and dissemination
The Yale University Human Subjects Committee reviewed and approved the research protocol. Results of this study will be disseminated to researchers and practitioners through peer-review publications and conference presentations, and directly to study participants.

Trial registration number
Registered on 17 August 2022 (ClinicalTrials.gov identifier: NCT05509166).

Leggi
Marzo 2025