Efficacy and Safety of High-Dose TBS on Post-Stroke Upper Extremity Motor Impairment: A Randomized Controlled Trial

Stroke, Ahead of Print. BACKGROUND:Upper extremity (UE) motor function impairment is a major poststroke complication whose recovery remains one of the most challenging tasks in neurological rehabilitation. This study examined the efficacy and safety of the personalized neuroimaging–guided high-dose theta-burst stimulation (TBS) for poststroke UE motor function recovery.METHODS:Patients after stroke with UE motor impairment from a China rehabilitation center were randomly assigned to receive high-dose intermittent TBS (iTBS) to ipsilesional UE sensorimotor network, continuous TBS (cTBS) to contralesional UE sensorimotor network, or sham stimulation, along with conventional therapy for 3 weeks. The primary outcome was the score changes on the Fugl-Meyer assessment-UE from baseline to 1 and 3 weeks. The secondary outcomes included the response rate on Fugl-Meyer assessment-UE scores posttreatment (≥9-point improvement) and score changes in multidimensional scales measuring UE, lower extremity, and activities and participation.RESULTS:From June 2021 to June 2022, 45 participants were randomized and 43 were analyzed. The iTBS and continuous TBS groups showed significantly greater improvement in Fugl-Meyer assessment-UE (mean improvement, iTBS: 10.73 points; continuous TBS: 10.79 points) than the sham group (2.43 points) and exhibited significantly greater response rates on Fugl-Meyer assessment-UE (iTBS, 60.0%; continuous TBS, 64.3%) than the sham group (0.0%). The active groups consistently exhibited superior improvement on the other 2 UE assessments at week 3. However, only the iTBS group showed greater efficacy on 1 lower extremity assessment than the sham group at week 3. Both active groups showed significant improvements in activities and participation assessments.CONCLUSIONS:The study provides evidence for the efficacy and safety of high-dose TBS in facilitating poststroke UE rehabilitation.REGISTRATION:URL:www.chictr.org.cn; Unique identifier: ChiCTR2100047340.

Leggi
Luglio 2024

Protocol for a longitudinal study examining the trajectory of COVID-19, post-COVID, multidimensional disadvantage and health-related quality of life in India: the IndiQol Project

Introduction
The COVID-19 pandemic has raised concerns about the persistence of symptoms after infection, commonly referred to as ‘post-COVID’ or ‘long-COVID’. While countries in high-resource countries have highlighted the increased risk of disadvantaged communities, there is limited understanding of how COVID-19 and post-COVID conditions affect marginalised populations in low-income and middle-income countries. We study the longitudinal patterns of COVID-19, post-COVID symptoms and their impact on the health-related quality of life through the IndiQol Project.

Methods and analysis
The IndiQol Project conducts household surveys across India to collect data on the incidence of COVID-19 and multidimensional well-being using a longitudinal design. We select a representative sample across six states surveyed over four waves. A two-stage sampling design was used to randomly select primary sampling units in rural and urban areas of each State. Using power analysis, we select an initial sample of 3000 household and survey all adult household members in each wave. The survey data will be analysed using limited dependent variable models and matching techniques to provide insights into the impact of COVID-19 pandemic and post-COVID on health and well-being of individuals in India.

Ethics and dissemination
Ethics approval for the IndiQol Project was obtained from the Macquarie University Human Research Ethics Committee in Sydney, Australia and Institutional Review Board of Morsel in India. The project results will be published in peer-reviewed journals. Data collected from the IndiQol project will be deposited with the EuroQol group and will be available to use by eligible researchers on approval of request.

Leggi
Luglio 2024

Evaluating a model of best practice in primary care led post-diagnostic dementia care: feasibility and acceptability findings from the PriDem study

Objectives
To evaluate the feasibility and acceptability of a primary care-based intervention for improving post-diagnostic dementia care and support (PriDem), and implementation study procedures.

Design
A non-randomised, mixed methods, feasibility study.

Setting
Seven general practices from four primary care networks (PCNs) in the Northeast and Southeast of England.

Participants
We aimed to recruit 80 people with dementia (PWD) and 66 carers

Intervention
Clinical Dementia Leads delivered a 12-month intervention in participating PCNs, to develop care systems, build staff capacity and capability, and deliver tailored care and support to PWD and carers.

Outcomes
Recruitment and retention rates were measured. A mixed methods process evaluation evaluated feasibility and acceptability of the intervention and study procedures. Using electronic care records, researchers extracted service use data and undertook a dementia care plan audit, preintervention and postintervention, assessing feasibility of measuring the primary implementation outcome: adoption of personalised care planning by participating general practices. Participants completed quality of life, and service use measures at baseline, 4 and 9 months.

Results
60 PWD (75% of recruitment target) and 51 carers (77% of recruitment target) were recruited from seven general practices across four PCNs. Retention rate at 9 months was 70.0% of PWD and 76.5% of carers. The recruitment approach showed potential for including under-represented groups within dementia. Despite implementation challenges, the intervention was feasible and acceptable, and showed early signs of sustainability. Study procedures were feasible and accessible, although researcher capacity was crucial. Participants needed time and support to engage with the study. Care plan audit procedures were feasible and acceptable.

Conclusions
The PriDem model is an acceptable and feasible intervention. A definitive study is warranted to fully inform dementia care policy and personalised dementia care planning guidance. Successful strategies to support inclusion of PWD and their carers in future research were developed.

Trial registration number
ISRCTN11677384.

Leggi
Luglio 2024

Post-traumatic stress disorder symptoms following exposure to acute psychological trauma in children aged 8-16 years in South Africa: protocol for the Sinethemba longitudinal study

Introduction
Children exposed to trauma are vulnerable to developing post-traumatic stress disorder (PTSD) and other adverse mental health outcomes. In low-and middle-income countries (LMICs), children are at increased risk of exposure to severe trauma and co-occurring adversities. However, relative to high-income countries, there is limited evidence of the factors that predict good versus poor psychological recovery following trauma exposure in LMIC children, and the role of caregiver support in these high-adversity communities.

Methods and analysis
We will conduct a longitudinal, observational study of 250 children aged 8–16 years and their caregivers in South Africa, following child exposure to acute trauma. Dyads will be recruited from community hospitals following a potentially traumatic event, such as a motor vehicle accident or assault. Potential participants will be identified during their hospital visit, and if they agree, will subsequently be contacted by study researchers. Assessments will take place within 4 weeks of the traumatic event, with 3-month and 6-month follow-up assessments. Participants will provide a narrative description of the traumatic event and complete questionnaires designed to give information about social and psychological risk factors. Child PTSD symptoms will be the primary outcome, and wider trauma-related mental health (depression, anxiety, behavioural problems) will be secondary outcomes. Regression-based methods will be used to examine the association of psychosocial factors in the acute phase following trauma, including caregiver support and responding, with child PTSD and wider mental health outcomes.

Ethics and dissemination
Ethical approvals have been granted by Stellenbosch University and the University of Bath, with additional approvals to recruit via hospitals and healthcare clinics being granted by the University of Cape Town, the Department of Health and the City of Cape Town. Study findings will be disseminated via publication in journals, workshops for practitioners and policy-makers, and public engagement events.

Leggi
Luglio 2024

Effectiveness of telerehabilitation in patients with post-COVID-19: a systematic review and meta-analysis of randomised controlled trials

Objective
To assess the effects of telerehabilitation on clinical symptoms, physical function, psychological function and quality of life (QoL) in patients with post-COVID-19.

Design
Systematic review and meta-analysis of randomised controlled trials (RCTs).

Data sources
PubMed, Web of Science, Embase and Cochrane Library were searched for publications from 1 January 2020 to 17 April 2024.

Eligibility criteria
RCTs investigating the effects of telerehabilitation in patients with post-COVID-19 were included. The outcomes of interest encompassed clinical symptoms, physical function, psychological function and QoL. Only studies reported in English were included.

Data extraction and synthesis
Two reviewers independently extracted data and evaluated the risk of bias. Statistical analysis was conducted using Review Manager V.5.3, employing mean difference (MD) with a 95% CI, and the corresponding P value was used to ascertain the treatment effect between groups. Heterogeneity was quantified using the I2 statistic. The quality of evidence was assessed by GRADE.

Results
16 RCTs (n=1129) were included in this systematic review, 15 of which (n=1095, 16 comparisons) were included in the meta-analysis. The primary pooled analysis demonstrated that, compared with no rehabilitation or usual care, telerehabilitation can improve physical function (measured by 30 s sit-to-stand test [6 RCTs, n=310, MD=1.58 stands, 95% CI 0.50 to 2.66; p=0.004]; 6 min walking distance [6 RCTs, n=324, MD=76.90 m, 95% CI 49.47 to 104.33; p

Leggi
Luglio 2024

Efficacy of MRI-guided rTMS for post-traumatic stress disorder by modulating amygdala activity: study protocol for a randomised controlled trial

Introduction
Post-traumatic stress disorder (PTSD) is a prevalent and severe psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex provides limited relief for symptoms of PTSD. This study will be conducted to validate the efficacy of MRI-guided rTMS in targeting the sites most closely associated with the amygdala for patients with PTSD. We hypothesise that the intervention will improve clinical symptoms by decreasing amygdala activity in patients.

Methods and analysis
A randomised, double-blind, sham-controlled trial will be conducted. Forty-eight eligible patients with PTSD will be randomly assigned to receive either active or sham MRI-guided rTMS for 10 consecutive days after the initial MRI scans. MRI scans will be recollected at the end of the intervention. Clinical assessments will be performed at baseline, treatment day 5, treatment day 10, and 2 weeks, 4 weeks, 8 weeks after completion of the intervention to monitor changes in clinical symptoms. The primary assessment outcome is the change in PTSD symptoms between baseline and treatment day 10, as measured by the PTSD Checklist for DSM-5. Repeated measures analysis of variance will be performed using statistical software SPSS V.26.0. The significance level will be set at 0.05.

Ethics and dissemination
Ethical approval has been obtained from the Ethics Committee of Xijing Hospital in Xi’an, China (KY20222176-X-1), and the trial has been registered on ClinicalTrials.gov. The findings of this trial will be disseminated at academic conferences or published in peer-reviewed scientific journals.

Trial registration number
NCT05544110.

Leggi
Luglio 2024

Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol

Introduction
Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia’s hepatitis C elimination targets.

Methods and analysis
A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models.

Ethics and dissemination
The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals.

Trial registration number
NCT05016609.

Trial progression
The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

Leggi
Luglio 2024

Aggressive hydration with lactated Ringers solution versus plasma solution for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (ALPS study): protocol for a multicentre, double-blind, randomised controlled trial

Introduction
Endoscopic retrograde cholangiopancreatography (ERCP) plays an indispensable role in treating pancreato-biliary diseases but carries a risk of post-ERCP pancreatitis (PEP). Despite advances in the prevention strategies, prevention of PEP remains imperfect, necessitating more refined hydration methods. This study investigates the effectiveness of lactated Ringer’s solution versus plasma solution in preventing PEP.

Method and analysis
This multicentre, double-blind, randomised controlled trial, will be initiated by the investigator-sponsor, and conducted in three tertiary centres in South Korea. The aim of this study is to assess the effectiveness of hydration in preventing PEP in patients with naïve papillae. It will target patients with naïve papillae, focusing on those at medium to high risk of PEP. Patients aged ≤18 years and those with serious comorbidities, acute/chronic pancreatitis and various other medical conditions will be excluded. Eligible participants will be randomly assigned into two arms in equal numbers: (1) PEP prevention using lactated Ringer’s solution and (2) PEP prevention using plasma solution. The primary outcome of this study will be the occurrence of PEP, and secondary outcomes will be additional risk factors and potential adverse events related to ERCP. With a total enrolment of 844 patients, the study will be able to detect significant differences between the intervention arms.

Ethics and dissemination
Ethical approval is obtained from each institution (Asan Medical Centre, 2023-0382; Seoul National University Hospital, H-2302-05-1404; Samsung Medical Centre, SMC 2023-02-001-009). All participants provided informed consent following clear explanation of the study procedures. The results of the study will be disseminated in peer-reviewed journals and research conferences.

Trial registration number
NCT05832047.

Protocol version
Ver 4.1 (2023).

Leggi
Luglio 2024

Fatigue and physical activity in post-CABG patients: the parallel mediation model of kinesiophobia and self-efficacy : a prospective multicentre and cross-sectional study in China

Objectives
The objective of this study was to investigate how kinesiophobia and self-efficacy explain the relationship between fatigue and physical activity (PA) in post-coronary artery bypass grafting (post-CABG) patients over the age of 45.

Design
A prospective multicentre and cross-sectional study.

Setting
The study was conducted in four public tertiary hospitals in China.

Participants
A total of 1278 patients who underwent CABG surgery were selected from the case pool, with their surgeries occurring between 3 and 19 months prior to selection. Out of 1038 patients who met the inclusion criteria and were invited to participate in the study, 759 patients agreed to participate and complete the questionnaire. Ultimately, 376 questionnaires were deemed eligible and included in the analysis.

Primary and secondary outcome measures
The questionnaire included the following scales: the Chinese version of the Multidimensional Fatigue Inventory (MFI-20), the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart), the Cardiac Exercise Self-Efficacy Instrument (CESEI) and the International Physical Activity Questionnaire-Long (IPAQ-L). A serial mediation model was used to test whether the association between fatigue and PA was mediated by kinesiophobia and self-efficacy, in the overall sample and subsamples defined by age.

Results
The results confirmed that fatigue was directly (95% CI (–5.73 to –3.02)) associated with PA. Higher kinesiophobia (95% CI (–0.16 to –0.05)) or lower PA self-efficacy (95% CI (–0.11 to –0.02)) were parallel pathways through which higher fatigue impediment reduced PA levels. In both subgroups, the street pathways of kinesiophobia and self-efficacy were altered. In the age, 45–60 years group, kinesiophobia (Boot 95% CI (–0.19 to–0.05)) was a mediator of fatigue on PA levels, while in the 61–75 years age group, self-efficacy (Boot 95% CI (–0.17 to –0.04)) was a mediator of fatigue on PA levels.

Conclusions
A clear relationship between fatigue and PA was mediated by both kinesiophobia and self-efficacy. Furthermore, our findings highlight the importance of adapting the intervention according to the age of the patients, mainly by reducing patients’ kinesiophobia in patients aged 45–60 years and increasing patients’ self-efficacy in patients aged 61–75 years. It may be possible to improve PA levels in post-CABG patients over 45 years of age by eliminating kinesiophobia and increasing self-efficacy.

Leggi
Luglio 2024

Improving Outcomes After Post–Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation

Circulation, Ahead of Print. This scientific statement presents a conceptual framework for the pathophysiology of post–cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post–cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post–cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post–cardiac arrest brain injury.

Leggi
Giugno 2024