Overtreatment in Prostate Cancer: An Overused Term—Reply

In Reply We appreciate the Letter from Osinski et al regarding our investigation of the overtreatment of prostate cancer among men with limited longevity. We recognize the uncertainties in risk stratification that limit the application of population-based estimates of life expectancy to an individual patient. Given these concerns, it is important to note that in population-based analyses, there will be a minority of patients that drastically outlive their estimated life expectancy and may derive meaningful benefit from treatment. Similarly, there will be men with longer life expectancy that do not live long enough to benefit from treatment. Yet, treatment decisions should be driven by evidence-based factors predicting when the vast majority of patients will or will not benefit from treatment.

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Can Ultra-Hypofractionated Stereotactic Radiation After Radical Prostatectomy Cut Time on Treatment?

Much scholarly ink has been spilled and many an argument made in tumor boards on issues related to salvage radiation (RT) in the event of a biochemical recurrence (BCR) after radical prostatectomy (RP). Before discussing salvage RT, it is important to distinguish it from adjuvant RT: the term adjuvant is used when RT is administered soon after surgery with the prostate-specific antigen (PSA) undetectable in the presence of certain adverse features; alternatively, salvage is defined as the delivery of RT once the PSA is detectable and rising.

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Error in Text

The Letter to the Editor titled “Challenges in Shared Care Research in Hematopoietic Cell Transplant,” published online on May 15, 2025, and in the July 2025 issue, was corrected to fix an error in the text. Specifically, where it previously read “there were fewer responders at day 100 (5%) compared with day 180,” it now correctly reads “there were fewer responders at day 100 (60.5%) compared with day 180.” This article was corrected online.

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Physician Suicide and Associated Features—What Defines a Physician?

To the Editor Makhija et al defined the national incidence of physician suicide and associated features in a well-detailed study of the National Violent Death Reporting System data and death certificates. This is an important problem for the profession, and additional data and insights are valuable. Surprisingly, though, the category of physician was not defined in the article. It would be important to understand who is included in the category of physician or not. In the context of medically trained physicians and individuals eligible to be members of the American Medical Association, the definition of physician would be graduates of medical school or graduates of osteopathic schools in the US or having the international equivalent degrees. However, in the free-text occupations from the decedents’ death certificates (eTable 2 in Supplement 1), although the majority appear to be medically trained physicians, there are professions listed that are not medically trained physicians or are ambiguous as to whether these are all medically trained physicians. The list of ambiguous or non–medically trained physician free-text occupations is below:

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Identifying and reporting modifications to surgical innovation: a systematic review of IDEAL/IDEAL-D studies

Objectives
The Idea, Development, Evaluation, Assessment and Long-term follow-up (IDEAL) framework was designed to improve the quality of surgical research and evaluation of surgical innovation. It has become a widely cited tool for evaluating innovative devices and procedures, yet challenges remain concerning the definition and reporting of incremental innovative modifications, hindering evolution and evaluation of innovations and potentially risking patient safety. This systematic review examined IDEAL studies to identify such modifications and establish recent practices around modification reporting to inform the development of future guidance to facilitate safe, transparent and efficient surgical innovation.

Design
Systematic review and thematic synthesis of studies reporting surgical innovation.

Data sources
Web of Science and Scopus were searched in July 2023 using citation tools to identify studies following the IDEAL framework (citing any of 13 key IDEAL/IDEAL framework publications and guideline papers).

Eligibility criteria
Primary research studies of any design that involved invasive innovative devices or procedures.

Data extraction and synthesis
Study characteristics and verbatim text for all reported modifications, including contextual information, were extracted. Data were analysed and synthesised using thematic synthesis.

Results
Of 1071 records screened, 104 studies published between 2011–2023 were included (n=87 (83.6%) study reports; n=17 (16.3%) protocols). 425 modifications were reported in 76 (73.1%) studies, including modifications to procedures (n=283, 66.6%), devices (n=94, 22.1%) and patient selection (n=48, 11.3%). Procedure/device modifications included technical, non-technical and cessation (conversion to other procedures or abandonment). Modifications were most often reported within IDEAL stage 2a (n=30/44, 68.2%), whereas there was considerable variation across other stages, such as stage 0 (n=2/3, 66%) and stage 2b (n=4/12, 33.3%).

Conclusion
Reporting modifications is imperative for evaluating surgical innovation. However, this review found inconsistent approaches to reporting and describing modifications. Findings will inform the development of a checklist for reporting modifications that aims to complement the IDEAL framework and further promote shared learning, avoiding the repetition of harmful/ineffective modifications and enhancing patient safety.

PROSPERO registration number
CRD42023427704.

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Postthrombectomy Flat-Panel CT Contrast Staining ASPECTS and Functional Outcome Prediction

Stroke, Ahead of Print. BACKGROUND:As indications for and utilization of mechanical thrombectomy continue to expand, there has been an increasing focus on developing improved tools for functional outcome prediction. We aim to evaluate the reliability of utilizing the areas of contrast staining for the Alberta Stroke Program Early Computed Tomography Score (s-ASPECTS) rating in immediate postthrombectomy flat-panel computed tomography and investigate its outcome predictive performance.METHODS:Retrospective analysis of a prospectively collected institutional mechanical thrombectomy database spanning March 2018 to February 2024. s-ASPECTS was calculated. We used ordinal logistic regression models to estimate the relationship between s-ASPECTS and the 90-day modified Rankin Scale and the additional value of these findings to the linear predictor of the MR-PREDICTS tool.RESULTS:One thousand sixty-three patients were included in this study with a mean age of 65±15 years, with 53% being male. s-ASPECTS was independently associated with functional outcomes. s-ASPECTS was observed to have more relevance in the clinical predictive model compared with baseline Alberta Stroke Program Early Computed Tomography Score, as well as to occlusion site and final expanded Thrombolysis in Cerebral Infarction grade. s-ASPECTS was lower among patients with more proximal occlusions, with a lower degree of final reperfusion, with a higher number of passes and longer procedures. The information gathered from flat-panel computed tomography added 18% of new information to MR-PREDICTS, as assessed by the ratio of the variances of the estimated probabilities of good functional outcome with an interobserver consensus score of κ=0.63.CONCLUSIONS:s-ASPECTS was reliably reported and found to be a stronger predictor of outcome compared with baseline Alberta Stroke Program Early Computed Tomography Score, characterizing it as an important prognostic tool for evaluating functional outcomes of patients following mechanical thrombectomy. Further studies are warranted.

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Development and validation of an interpretable machine learning model for predicting Philadelphia chromosome-positive acute lymphoblastic leukaemia using clinical and laboratory parameters: a single-centre retrospective study

Objective
To develop and validate a prediction model of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ALL).

Design
A single-centre retrospective study.

Participants
This study analysed 471 newly diagnosed patients with ALL at the Second Affiliated Hospital of Army Medical University from January 2014 to December 2023.

Methods
Clinical and laboratory parameters were collected, and the important characteristic parameters were selected using BorutaShap. Multiple machine learning (ML) models were constructed and optimised by using the active learning (AL) algorithm. Performance was evaluated using the area under the curve (AUC), comprehensive indicators and decision curve analysis. The interpretability of the model was evaluated by using SHapley Additive Interpretation (SHAP), and external validation was conducted on an independent test cohort.

Results
10 parameters were selected to construct multiple ML models. The CatBoost model integrated with an AL algorithm (CatBoost-AL) was found to be the most effective model for predicting Ph+ALL within the validation data set. This model achieved an AUC of 0.797 (95% CI 0.710 to 0.884), along with sensitivity, specificity and F1 score of 0.667, 0.864 and 0.777, respectively. The prediction performance of CatBoost-AL was further validated with an external testing set, where it maintained a strong AUC of 0.794 (95% CI 0.707 to 0.881). Using SHAP for global interpretability analysis, age, monocyte count, -glutamyl transferase, neutrophil count and alanine aminotransferase were identified as crucial parameters that significantly influence the diagnostic accuracy of CatBoost-AL.

Conclusion
An interpretable ML model and online prediction tool were developed to determine whether newly diagnosed patients with ALL are Ph+ALL. The key parameters identified by the optimal model provided a further understanding of Ph+ALL characteristics and were valuable for accurate diagnosis and treatment of Ph+ALL.

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Daily mobility, activity and environmental determinants of stress in ecological momentary assessment (EMA) and GPS studies: a scoping review protocol

Introduction
Stress is omnipresent in our everyday lives and a key risk factor for our physical and mental health. Yet little is known about the impact of geographic life environments, linked to our daily activities and mobility patterns, on our momentary and daily stress levels.
We propose this review to gather evidence on the spatio-temporal determinants of momentary or daily stress in studies using ecological momentary assessment (EMA) or experience sampling methods (ESM) in addition to global positioning systems (GPS) tracking. We will focus on the spatio-temporal definition and modelling of environmental exposures accounting for participant daily activities and mobility patterns and their association with stress.

Methods and analysis
This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework for scoping reviews (2018). We will search the PubMed/Medline, Web of Science, PsycInfo and Scopus databases. We will include papers using EMA or ESM and GPS measuring chronic, daily or momentary stress as an outcome; these methods are also referred to as geographically-explicit ecological momentary assessment.
Articles published from January 2000–June 2025 will be screened. Two independent reviewers will screen titles and abstracts to agree on the inclusion of articles. No geographical or population limitation will be imposed.

Ethics and dissemination
This study is a scoping review based on previously published and publicly available literature. It does not involve the collection of primary data, human participants, or the processing of personal or sensitive information. Therefore, ethical approval is not required in accordance with institutional and international research ethics guidelines. The results will be submitted in peer-reviewed journals and presented at international conferences.

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Prevalence of low-level viremia in the treatment of chronic hepatitis B in China: a systematic review and meta-analysis

Objectives
Low-level viremia (LLV) is a risk factor affecting the prognosis of patients with chronic hepatitis B (CHB). The objective of this study was to systematically assess the prevalence of LLV, thereby providing robust evidence-based medical insights into effective clinical interventions and preventative measures against LLV.

Design
Systematic review and meta-analysis.

Data sources
A comprehensive literature search was conducted across various databases, including China National Knowledge Infrastructure, Wanfang Data (Wanfang), China Science And Technology Journal Database (VIP-CSTJ), China Biology Medicine disc (CBMdisc), PubMed, Embase, Web of Science and the Cochrane Library, spanning from the inception of these databases up to 5 January 2024.

Eligibility criteria
The research type included either a cross-sectional study or a cohort study focusing on the Chinese population, with the outcome being LLV. The languages were limited to both Chinese and English. Studies with any of the following were excluded: subjects with other comorbidities, original articles inaccessible or data unavailable, and duplicate publications.

Data extraction and synthesis
Literature management used EndNote X9.1, and an information extraction table was created using Microsoft Excel to record research information, including first author, year of publication and study type. The prevalence of LLV was assessed via meta-analysis. Meta-analyses were conducted in RStudio using the ‘metaprop ()’ function. Subgroup analysis and sensitivity analysis were used to identify sources of heterogeneity, and funnel plots and AS-Thompson tests were employed to evaluate publication bias.

Results
18 studies, encompassing a total sample of 9773 patients, were included in the analysis. Of these, 3336 patients were identified with LLV. The meta-analysis revealed that the prevalence of LLV among treated CHB patients stands at 33.6% (95% CI 30.2 to 37.0). The antigen status, antiviral treatment regimen (type of drugs and nucleos(t)ide analogues (NAs)), treatment duration, medication adherence and baseline hepatitis B virus DNA levels all affected the prevalence of LLV. Sensitivity analysis further corroborated the stability of these meta-analysis findings. The funnel plot and AS-Thompson test indicated no significant publication bias (t = –0.01, p=0.995).

Conclusions
The prevalence of LLV among CHB patients was established at 33.7% (95% CI 29.8% to 37.6%). Thus, it is imperative for clinical decision-makers to consider the various influencing factors of LLV when formulating treatment plans in order to mitigate any potential adverse outcomes.

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Outcomes of patient and public involvement in the development of the Cognitive Decline after Brain Radiosurgery (CoDe B-Rad) study: refining the research question and methodology

Objectives
Patient and public involvement (PPI) was sought in the development of the protocol for the Cognitive Decline after Brain Radiosurgery (CoDe B-Rad) study, which aims to identify potential side effects of stereotactic radiosurgery (SRS). PPI served to refine the research question and methodology.

Design
PPI.

Setting
PPI conducted online with people based in the UK. The CoDe B-Rad study is running in regional National Health Service tertiary care in the UK and is currently nearing recruitment completion.

Participants
Patients and carers with lived experiences of brain radiotherapy. Contributors were identified through national charities.

Procedures
Initial focus groups were planned, but participation proved challenging. Instead, online questionnaires, one-to-one discussions and participation in support groups were completed.

Results
All contributors experienced changes to their cognition and/or quality of life (QoL) after radiotherapy. Quantifying the side effects of SRS and minimising them were identified as a research gap. Discussion group participation proved challenging. PPI plans were altered to accommodate the physical and mental needs of contributors. It was decided to combine the Montreal Cognitive Assessment along with European Organisation for Research and Treatment in Cancer QLQ-C30 and BN20 to capture cognitive status and QoL of patients with brain metastases and meningiomas after SRS. Patients/carers recommended for sessions to be restricted to 30 min and testing to be offered face-to-face, online, in hospital or at patients’ homes. Coproduction was not achievable with our patient population but that did not diminish the input of contributors nor the impact it had on designing the study protocol.

Conclusions
In cancer research, diligent considerations are required to ensure the suitability of involvement methods for this vulnerable population. Flexibility and adaptability of draft PPI plans are essential to achieve meaningful contributions. The protocol of the ongoing CoDe B-Rad study was positively shaped by people with lived experiences of brain radiotherapy.

Trial registration number
NCT06466720 (CoDe B-Rad study).

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Palliative care communication between patients with intellectual disabilities and hospice staff: a Conversation Analysis pilot study

Introduction
Communication challenges are among the main barriers for people with intellectual disabilities in accessing palliative care. They include inadequate skills among staff and difficulties with confirming understanding and around the presentation and assessment of symptoms. In-depth analysis of interactions between people with an intellectual disability and staff may shed light on these communicative challenges as well as facilitators. However, no studies have closely analysed the interactions between people with an intellectual disability and professionals within palliative care settings.

Methods and analysis
This protocol describes a pilot study assessing the feasibility and acceptability of conducting a Conversation Analysis study involving video-recording palliative care conversations between people with intellectual disabilities and professionals.
Three conversations between patients with an intellectual disability, their companions and palliative care staff will be video recorded in a UK hospice. Recordings will be transcribed and analysed using Conversation Analysis. Communication phenomena of interest and worth further exploration will be identified in collaboration with key stakeholders.

Ethics and dissemination
The study received a favourable opinion by a UK research ethics committee in February 2025. All participants must provide informed consent to take part in the study. It will be carefully assessed that potential participants with an intellectual disability have capacity to consent to take part. Accessible study information materials for participants with an intellectual disability are available (ie, easy-read and video).
Study findings will be disseminated in academic papers and conference presentations. Progress and findings will also be shared via social media and with relevant groups of people with intellectual disabilities, family carers, service providers and academics.

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Development and validation of critical appraisal tool for individual participant data meta-analysis: protocol for a modified e-Delphi study

Introduction
Individual participant data meta-analysis (IPD-MA) is regarded as the gold standard for evidence synthesis. However, diverse recommendations and guidance on its conduct exist, and there is no consensus-based tool for the critical appraisal of a completed IPD-MA. We aim to close this gap by systematically identifying quality items and developing and validating a critical appraisal checklist for IPD-MA.

Methods and analysis
This study will comprise three phases, as follows:
Phase 1: a systematic methodology review to identify potential checklist domains and items; this will be conducted according to the Cochrane methods for systematic reviews and reported following the Preferred Reporting Items for Systematic Reviews and Meta-analysis 2020 guidance. We will include studies that address methodological guides and essential statistical requirements for IPD-MA. We will use the proposed items to prepare a preliminary checklist for the e-Delphi study.
Phase 2: at least two rounds of an e-Delphi survey will be conducted among panels with expertise in IPD-MA research, consensus development, healthcare providers, journal editors, healthcare policymakers, patients and public partners from diverse geographic locations with experience in IPD-MA. Participants will use Qualtrics software to rate items on a 5-point Likert scale. The Wilcoxon matched signed rank test will estimate response stability across rounds. Consensus on including an item will be achieved if ≥75% of the panel rates the item as ‘strongly agree’ or ‘agree’ and items will be excluded if ≥75% rates it as ‘strongly disagree’ or ‘disagree’. A convenience sample of 10 reviewers with experience in conducting an IPD-MA will pilot-test the checklist to provide practical feedback that will be used to refine the checklist.
Phase 3: critical appraisal checklist validation: to improve confidence in the tool’s uptake, a subset of the e-Delphi participants and graduate students of epidemiology and biostatistics will conduct content validity and reliability testing, respectively, per the Consensus-based Standards for the Selection of Health Measurement Instruments.

Ethics and dissemination
Ethics approval has been obtained from the Western University Health Science Research Ethics Board in Canada. The validated checklist will be published in a peer-reviewed open-access journal and shared across the networks of this study’s steering committee, Cochrane IPD-MA group and the institutions’ social media platforms.

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Effects of potassium-enriched salt substitutes on blood pressure in Iranian hypertensive patients: the protocol for a randomised, double-blind controlled trial

Introduction
Potassium-enriched salt substitutes have favourable effects on blood pressure, but it has not been tested in Iran. The present protocol is a double-blinded, randomised-controlled trial designed to investigate the effects of potassium-enriched salt substitutes on blood pressure in Iranian hypertensive patients.

Methods and analysis
The primary objectives are to determine the effects on systolic and diastolic blood pressure at 3 months and 6 months. The secondary objectives are to assess the effects on serum levels of potassium, sodium, urea and creatinine; the urinary ratio of sodium to potassium; participants’ attitudes toward the use of salt or salt substitutes; the recurrence of hypertensive crisis; and the occurrence and/or reoccurrence of strokes, transient ischaemic attack and cardiovascular accidents. Eligible individuals will receive the usual salt (100% sodium chloride) in the control group or salt substitute (70% sodium chloride and 30% potassium chloride) in the intervention group. A total of 500 hypertensive participants aged 40–65 years will be recruited and randomised to intervention or control groups. Potassium-enriched salt substitution in Iran will be considered to improve CVD complications and prevent deaths. Continuous and categorical baseline characteristics will be tested using the independent t-test and 2 test. The effect of the intervention on primary and secondary outcomes will be assessed using the intention-to-treat method and two-way mixed ANOVA models.

Ethics and dissemination
This study has been approved by Alborz University of Medical Sciences (0-0-103-6369) and has received ethics approval (IR.ABZUMS.REC.1402.293). We will publish our study findings for peer-reviewed publications, conference presentations and digital stories.

Trial registration number
IRCT20240121060757N1.

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Comparing non-ischaemic heart preservation (NIHP) with ischaemic static cold storage of donor hearts in adult cardiac transplantation: study protocol for a randomised controlled trial

Introduction
Ischaemia–reperfusion (I/R) injury remains a major challenge in heart transplantation, with mortality risk increasing significantly when allograft ischaemic time exceeds 4 hours. Non-ischaemic heart preservation (NIHP), using continuous hypothermic perfusion, has shown promise in preliminary studies for reducing I/R injury and improving outcomes. This randomised controlled trial aims to compare NIHP with standard static cold storage (SCS) in adult heart transplantation.

Methods and analysis
The trial is a prospective, open-label, multicentre, single-blinded, randomised controlled trial including 66 adult heart transplant recipients across four Swedish hospitals. Participants will be randomised into 1:1 ratio to NIHP or SCS preservation groups and undergo a 12-month follow-up period. The primary outcome is 1-year survival free from acute cellular rejection or retransplantation. Secondary outcomes include quality of life, I/R injury markers, graft function and adverse events. Substudies will evaluate renal function using MRI and continuously monitor physical activity and heart rhythm via wearable devices. Analysis will follow intention-to-treat principles, with time-to-event analysis using Cox proportional hazard models and Kaplan-Meier estimates.

Ethics and dissemination
The study has been approved by the Swedish Ethical Review Authority. It will be conducted according to the Declaration of Helsinki and relevant local and international regulations. Results will be published in peer-reviewed journals following Consolidated Standards of Reporting Trials guidelines.

Trial registration number
NCT04066127.

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Brain-Body Interactions in Ischemic Stroke: VNS Reprograms Microglia and FNS Enhances Cerebellar Neuroprotection

Stroke, Ahead of Print. Stroke significantly impacts mortality and long-term disability, necessitating effective rehabilitation strategies to enhance recovery. This review examines the roles of vagus nerve stimulation (VNS) and fastigial nucleus stimulation (FNS) in facilitating ischemic stroke recovery through brain-body interactions. VNS enhances ischemic stroke recovery by reprogramming microglia from proinflammatory (M1) to neuroprotective (M2) phenotypes, reducing neuroinflammation and promoting tissue repair via neurotrophic factors. It has shown promise in clinically improving chronic upper limb deficits when combined with rehabilitation therapies. Conversely, FNS provides cerebellar-mediated neuroprotection by mainly mitigating excitotoxic damage and inflammatory responses independent of cerebral blood flow alterations, as evidenced by preclinical models of middle cerebral artery occlusion. By integrating VNS-driven immunomodulation with FNS-mediated excitotoxicity suppression, this review highlights their synergistic potential to improve rehabilitation outcomes for ischemic stroke survivors. Biomarker-guided protocols: VNS for cortical/subcortical ischemic deficits and FNS for cerebellar network recovery are advocated to address postischemic disability via anti-inflammatory rewiring, neuroplasticity enhancement, and cerebellar-thalamocortical circuit stabilization. Critical gaps remain in hemorrhagic stroke, where FNS’s excitotoxicity suppression may destabilize clots, necessitating subtype-specific safety validations.

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Randomised trial of home sleep apnoea testing compared to in-lab polysomnography for the evaluation of obstructive sleep apnoea in children: rationale and study protocol

Introduction
Obstructive sleep apnoea (OSA) affects 1–5% of the paediatric population, including 55–90% of children with Down syndrome (DS), and has been associated with negative effects on neurocognitive development, cardiovascular health, immune development and quality of life. In-lab attended polysomnography (PSG) is currently the gold standard for the diagnosis of OSA in children, but it poses challenges due to the burden on families and limited testing facilities. Home sleep apnoea testing (HSAT), an unattended sleep test done at home, is an accepted alternative for adults but lacks sufficient evidence to be used clinically for the evaluation of OSA in children. HSAT may be especially beneficial for children with DS or others with sensory issues or those who struggle with sleeping in a laboratory setting overnight.

Methods and analysis
This single-centre trial compares HSAT to PSG for the diagnosis of OSA in children, including those with DS. The trial will enrol 317 children 5–12 years old, including approximately 100 with DS. The primary outcome is the diagnostic accuracy of HSAT compared with PSG for OSA evaluated through ROC. Secondary outcomes include the agreement between HSAT and PSG for therapeutic decision-making and comparison of preference and acceptability of HSAT versus PSG. This trial seeks to evaluate HSAT as an alternative diagnostic tool for paediatric OSA, potentially expanding testing options for clinicians and families.

Ethics and dissemination
This study has been approved by the Institutional Review Board at Children’s Hospital of Philadelphia (#21–0 19 533). Informed consent will be obtained from all participants, and no identifiable data will be reported.

Trial registration number
NCT05382754.

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