Attention deficit hyperactivity disorder (ADHD), autism disorder and intellectual disability (ID) are increasingly identified, and the co-occurrence of these and other social-emotional conditions has raised awareness that treatment of people with multiple diagnoses becomes more complex. Hollingdale and colleagues1 have examined this and begun to identify factors that modify and moderate the cumulative impact on functioning. As...

To assess patient satisfaction and identify associated factors in plastic and hand reconstructive surgery at ALERT Comprehensive Specialised Hospital in Addis Ababa, Ethiopia.

A hospital-based cross-sectional study was conducted from February to March 2023 using a structured questionnaire that incorporated the Patient Satisfaction Questionnaire Short Form and the Outpatient Assessment of healthcare scales. Patient satisfaction was measured using a five-point Likert scale. Descriptive statistics and multivariable logistic regression were employed using Stata V.17.

ALERT Comprehensive Specialised Hospital, Addis Ababa, Ethiopia.

A total of 391 systematically selected adult patients attended the plastic and hand reconstructive surgery outpatient departments.

Overall patient satisfaction and factors influencing satisfaction with surgical services.

Of the 379 respondents (response rate 96.9%), 51.2% were male. The overall patient satisfaction rate was 75.7%. However, 78.6% experienced long waiting times (mean: 2 hours 15 min), 84.4% reported inadequate information provision, and 90.3% indicated that medical care was unaffordable. Significant factors associated with higher satisfaction included age 30–39 years (AOR=2.7; 95% CI 1.09 to 6.83), having laboratory tests ordered (AOR=2.03; 95% CI 1.03 to 4.03) and X-ray/ultrasound imaging (AOR=2.20; 95% CI 1.19 to 4.06). Patients who received care free of charge were less likely to be satisfied compared with those paying out of pocket (AOR=0.23; 95% CI 0.07 to 0.82).

Although overall satisfaction was moderately high, significant dissatisfaction was reported regarding service accessibility, waiting times, communication and affordability. Targeted interventions in these areas are recommended to improve patient-centred care.

The carbon footprint of end-to-end healthcare deliveries by the National Health Service in England totalled 25.0 megatons of carbon dioxide equivalent (CO₂e) in 2019. Optimal and sustainable healthcare can lead to better health outcomes as well as a lower environmental footprint.

To evaluate the potential impact of prevention and effective management of type 2 diabetes mellitus (T2DM) in adults on both the clinical outcomes and greenhouse gas (GHG) emissions in the UK healthcare setting.

We incorporated an environmental module into the existing IQVIA core diabetes model to estimate the impact of improving clinical outcomes on GHG emissions over a lifetime horizon. We assessed two hypothetical scenarios: (1) preventing progression from pre-diabetes to T2DM through diet and exercise versus no intervention and natural disease progression to T2DM; and (2) well-controlled T2DM using interventions with clinical benefit on glycosylated haemoglobin (HbA1c), and renal and cardiovascular outcomes versus uncontrolled T2DM.

Preventing progression to T2DM led to 6.357 additional undiscounted life years and 67% less kg CO₂e emissions compared with subsequent natural progression to T2DM for a person with pre-diabetes over a lifetime (emissions of 9586 kg CO₂e over 37.115 years vs 28 716 kg CO₂e over 30.758 years, respectively). Well-controlled T2DM led to 1.947 additional undiscounted life years and 21% less kg CO₂e emissions per patient over a lifetime compared with uncontrolled T2DM (emissions of 14 545 kg CO₂e over 22.772 years vs 18 516 kg CO₂e over 20.825 years, respectively). In both scenarios, the GHG emission savings were primarily due to reduced emissions related to avoidance of treating complications of T2DM including cardiovascular, renal and eye diseases.

Effective prevention and management of T2DM through implementation of evidence-based clinical guidelines can improve patient outcomes while reducing the healthcare-related environmental impacts.

Minimally invasive endoscopic procedures constitute the cornerstone of first-line treatment for bulbar urethral strictures, although their long-term effectiveness is limited by high recurrence rates. The Optilume drug-coated balloon (DCB) is a novel intervention combining mechanical dilation with localised delivery of paclitaxel to reduce recurrence by inhibiting scar tissue formation. While its efficacy has been demonstrated in patients with recurrent strictures, its potential as a first-line option in treatment-naïve patients remains unexplored. The FIRST-CARE trial aims to assess the efficacy and safety of Optilume DCB compared with standard endoscopic treatment in treatment-naïve patients with bulbar urethral strictures.

Design: Two-arm, randomised, single-blind (participant), investigator-initiated, parallel-group, multicentre clinical trial. Patients: The study will enrol 140 adult male patients with treatment-naïve, single bulbar urethral strictures ≤3 cm in length. Interventions: All patients will undergo the assigned procedure under general anaesthesia with 1.5 g intravenous cefuroxime. Optilume group patients will receive ≥5 min balloon dilation with localised paclitaxel delivery. The control group will receive standard endoscopic treatment (eg, direct visual internal urethrotomy, laser or dilatation). In both groups, a 12–14 French Foley catheter will be left in place for 3–5 days. Primary outcome: Freedom from repeat intervention within 12 months of follow-up. Primary analysis: Time-to-event will be defined from the date of intervention to the date a repeat intervention is decided (indicated and planned) due to confirmed recurrence, with censoring at 12 months. Groups will be compared using Kaplan-Meier survival analysis and the log-rank test. Cox regression and modified Poisson regression will be used to estimate HRs and relative risks.

The trial is approved by the Danish National Committee on Health Research Ethics (2401370) and will be conducted in accordance with the Declaration of Helsinki and principles of Good Clinical Practice. In line with national guidelines, all eligible patients are counselled regarding available treatment options prior to enrolment. Results will be disseminated via peer-reviewed publications and scientific presentations.

NCT06827210.

The term ‘culture of care’ began to be used following the Francis Report in the UK in 2013. This concept involves three dimensions: personal care, leadership care and co-worker care. Personal care focuses on employees’ attitudes and behaviours. Co-worker care relates to a sense of community, and leadership care relates to how employees perceive leaders and managers as caring individuals dedicated to ensuring the well-being of others. Previous studies investigating culture assessment tools used in the healthcare system reported that although organisations are increasingly using culture assessment instruments, there is a focus on assessing safety and quality cultures rather than on caring perspectives. This scoping review aims to map existing studies related to the assessment of culture of care.

This scoping review will be conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews. The search strategy will include four indexed databases (PubMed, EMBASE, Cochrane Library and Latin American and Caribbean Literature in Health Sciences) and additional sources not retrieved with the adopted search strategy. The search strategy will be constructed using the controlled vocabulary in Health Sciences Descriptors, Medical Subject Headings and Emtree. Relevant articles in all languages, without restrictions related to date of publication, will be considered eligible for inclusion. Two independent researchers will select articles based on the inclusion criteria, and a third author will be consulted to establish consensus, if necessary. Data extraction will involve a form with information on the study characteristics, methodological issues and main results from the evidence sources. The extracted data will be analysed using descriptive and content analysis.

Ethics approval is not required, as this review will use data from publicly available bibliographic sources. The results will be disseminated through publications in scientific journals and presentation of the evidence to interested parties.

The protocol was registered in the Open Science Framework (DOI: 10.17605/OSF.IO/U9Q53).

Pain in patients with rheumatoid arthritis (RA) is an unmet clinical need. Targeting joint inflammation with disease-modifying antirheumatic drugs has not resulted in the anticipated reduction in pain for many patients. This can partly be explained by the concept of central sensitisation whereby spinal and supraspinal pathways have a lower threshold of activation, leading to increased perception of pain. Synovial stromal cells, such as fibroblasts, are also thought to play a role through peripheral sensitisation of nerves in the joint. Synovial fibroblasts are known to produce pro-algesic mediators such as interleukin 6 and nerve growth factor at the messenger RNA level. These pro-algesic mediators could activate sensory nerve fibres that send signals from the joint to the spinal cord, thereby driving persistent pain in RA. The purpose of this study is to evaluate which pro-algesic mediators are produced by lining versus sub-lining fibroblasts and whether the level of these mediators correlates with clinical measures of pain in patients with RA.

FiND-Pain RA is a multicentre observational study which will recruit 50 patients with seropositive RA who attend the rheumatology department of Guy’s and St Thomas’ Hospital, London, and the Nuffield Orthopaedic Centre, Oxford. Clinical examination, pain-focused patient-reported outcome measures, ultrasound examination and ultrasound-guided synovial biopsy of the knee will be performed. The levels of known and putative pro-algesic mediators will be measured in fibroblasts from the lining and sub-lining layer of the synovium. The location and spatial morphology of sensory nerve fibres and their proximity to lining and sub-lining fibroblasts will be characterised. The primary outcome will be to determine whether the knee pain scores of participants correlate with the level of leukaemia inhibitory factor, a novel putative pain-mediator expressed in sub-lining fibroblasts. The secondary outcomes will be to determine whether other pro-algesic mediators produced by lining or sub-lining fibroblasts correlate with clinical measures of pain and to assess the location and proximity of sensory nerve fibres to lining versus sub-lining fibroblasts.

The study is a sub-study of the PUMIA (Pain Phenotypes and their Underlying Mechanisms in Inflammatory Arthritis) study, which has been approved by the Bromley Research Ethics Committee (REC: 21/LO/0712). The findings of this study will be disseminated through open-access publications, as well as scientific and clinical conferences.

Gram negative bloodstream infections (GN BSI) are a leading cause of mortality worldwide, and antibiotic treatment approaches remain understudied. BALANCE+ is a perpetual Bayesian adaptive platform trial to test multiple treatment questions for hospitalised patients with GN BSI. The vanguard phase objective was to test the feasibility of the main trial.

Adaptive platform trial with five initial domains of investigation, each with open label 1:1 randomisation.

Ten hospitals across four Canadian provinces.

Individuals admitted to hospital with blood cultures yielding Gram negative bacteria.

The five initial domains of investigation included: antibiotic de-escalation versus no de-escalation; oral transition to beta-lactam versus non-beta-lactam treatment; routine versus no routine follow-up blood cultures (FUBCs); central vascular catheter replacement versus retention; and, ceftriaxone versus carbapenem treatment for low risk AmpC organisms.

Domain-specific recruitment rates and protocol adherence.

During the vanguard phase, 719 patients were screened, of whom 563 (78.3%) were eligible, with 179 (31.8%) enrolled into the platform. The platform recruitment rate was 1.37 patients/site-week. Recruitment varied by domain: routine versus no FUBC domain 1.23 patients/site-week; oral beta-lactam versus non-beta-lactam domain 0.48; de-escalation versus no de-escalation domain 0.28; low risk AmpC domain 0.02; catheter replacement versus retention domain 0.01. Domain specific protocol adherence rates were 145/158 (91.8%) for routine versus no routine FUBC, 53/60 (88.3%) for oral beta-lactam versus non-beta-lactam, 26/33 (78.8%) for de-escalation versus no de-escalation, 3/3 (100%) for low risk AmpC, and 0/1 (0%) for line replacement versus retention. There was complete ascertainment of all study outcomes in hospital 170/170 (100%) and near complete ascertainment at 90 days 162/170 (95.3%).

The vanguard phase demonstrated overall trial feasibility by recruitment rate and protocol adherence, with differences across interventions, leading to a transition to the main BALANCE+ platform trial with minimal protocol modifications.

NCT05893147.

Fibrosis is a pathological feature that can occur in a wide range of diseases including diabetes mellitus. We investigated whether in people with type 1 (T1DM) or type 2 diabetes mellitus (T2DM), glycaemia or diabetes-related complications are associated with fibrotic diseases.

Retrospective cohort study using UK Clinical Resource Datalink (CPRD) Aurum and Hospital Episode Statistics.

We included people with prevalent T1DM or T2DM as of 31 December 2015 (recorded in CPRD Aurum), eligible for linkage with Hospital Episode Statistics and followed up for 3 years.

We defined diabetes status using blood/urine biomarkers and complications. In the T2DM cohort, we also investigated exposures of hyperglycaemia, insulin resistance and metformin prescription. Fibrotic condition diagnoses were determined from both primary and secondary care records. Logistic regression analyses were undertaken to understand the strength of association between diabetes status/diabetic complications and fibrotic conditions, respectively.

The T1DM cohort consisted of 9669 people while the T2DM cohort included 504 066 people. In T1DM, we found that albuminuria was associated with lung fibrosis (ORadj: 2.07, 99% CI 1.35 to 2.17), and microvascular complications were associated with atherosclerosis (ORadj: 1.81, 99% CI 1.18 to 2.77) and cardiomyopathy (ORadj 1.53, 99% CI:1.15 to 2.04). In the T2DM cohort, both glycaemia above target and diabetes complications were associated with most fibrotic conditions.

Within the T1DM population, no consistent association between diabetes status and all fibrotic diseases was observed. More research is required to understand whether the association between diabetes complications and fibrotic diseases is due to shared risk factors or whether glycaemia in T2DM may be influenced by fibrotic pathology.

To examine trends in preconception and pregnancy cardiometabolic risk factors and conditions, pregnancy and birth complications, obstetric interventions, and the impact of COVID-19, and to forecast future disease burden.

A multi-centre retrospective cohort study.

A large hospital network with three maternity hospitals serving ethnically diverse populations in Melbourne, Australia.

Pregnant women who gave birth between 2016 and 2022.

Trends in cardiometabolic conditions, birth complications and obstetric interventions.

Over 7 years, 63 232 women were included, of whom 40% were nulliparous, and 60.9% were born overseas from 167 countries. From 2016–2022, maternal age (30.2–31.3 years), obesity (21.0%–26.2%), gestational diabetes mellitus (GDM) (15.9%–28.1%) and caesarean delivery (28.5%–37.6%) increased, while average gestational weight gain, premature births and special care admissions declined from 12.6–11.6 kg, 6.3%–4.9% and 24.2%–14.1%, respectively; and was statistically significant (p

Prepregnancy and pregnancy cardiometabolic risk factors and conditions, pregnancy and birth complications, and obstetric interventions increased markedly over 7 years. Despite this, offspring complications, including special care admissions, stillbirths and prematurity, decreased, while pregnancy complications peaked during COVID-19. GDM is forecasted to increase to 43.0% by 2028, posing an unsustainable health and economic burden that necessitates urgent public health initiatives.

To meet the elevated nutritional requirements of very low birthweight (

This is a three-arm, pragmatic, multicentre, double-blind, randomised clinical trial of 615 human milk–fed infants born either (1) ≤1250 g or (2)

Ethical approval was obtained from Clinical Trials Ontario (CTO) and local research ethics boards that are not CTO members. Study findings will be disseminated to clinicians at seminars and conferences and in peer-reviewed publications.

NCT05308134.

The TRAjectory of knee heaLth in runners (TRAIL) study is a prospective cohort study investigating the long-term knee health trajectories of runners with and without a heightened osteoarthritis risk. This study aims to describe the recruitment results and baseline characteristics of the TRAIL cohort.

Runners aged 18–50 years and running ≥3 times and ≥10 km per week on average in the past 6 months were eligible. Participants were recruited via running podcasts, running clubs and social media between July 2020 and August 2023. Data were collected at study enrolment and at a face-to-face baseline testing session, which occurred a median of 33 weeks (IQR 18 to 86 weeks) after enrolment. Follow-up data collection is ongoing.

Out of 462 runners who completed an online registration form, 268 runners enrolled, of which 135 had a history of knee surgery (46% females) and 133 were non-surgical controls (50% females). 60% of the surgery group had undergone anterior cruciate ligament reconstruction, 33% meniscus and/or cartilage surgery, and 7% other knee surgery. 54 participants previously enrolled were unable to continue in the study before attending baseline data collection. Of the 214 runners who remained in the study and attended baseline data collection, 108 had a history of knee surgery (49% females) and 106 did not have a history of knee surgery (51% females).

Participants will be followed for 10 years through ongoing patient-reported outcomes and continuous monitoring of training loads using wearable devices. At baseline, 4- and 10-year follow-up, knee MRI and knee-health patient-reported outcomes will be collected to evaluate structural and symptomatic knee osteoarthritis progression. Data will inform guidelines for safe running practices and rehabilitation post-knee surgery.

This review aims to map oral health plans, programmes and policies worldwide in countries with universal health coverage.

This protocol describes a scoping review that will follow the Joanna Briggs Institute methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review checklist, guided by the PCC framework: Population—countries with universal health coverage (78 globally recognised); Concept—oral health plans, programmes and policies; Context—integration into health systems. Searches will be conducted in MEDLINE (PubMed), Scopus, Web of Science, Embase, Health System Evidence and Epistemonikos, with no restrictions on date, language or study type. Grey literature will be accessed through Google Scholar, OpenThesis and the Brazilian Digital Library of Theses and Dissertations. Official documents from ministries of health and international bodies, including the WHO and the International Monetary Fund, will also be reviewed. Two independent reviewers will screen titles and abstracts; a third will resolve disagreements. Eligible records will undergo full-text review. Data will be extracted into predefined categories reflecting health system components: population, structure, services, governance and oral health indicators. Results will be presented using tables, charts and figures to illustrate strategies and innovations.

This review does not involve primary data collection and does not require ethical approval. Results will be disseminated through a peer-reviewed publication and presentations at academic conferences and scientific events.

Open Science Framework (DOI 10.17605/OSF.IO/RCP8N).

The development of effective vaccines targeting human papillomavirus (HPV) has significantly contributed to disease prevention, highly relevant in immunosuppressed patients who have higher incidence of HPV-related cancers than their non-immunosuppressed counterparts. However, the acceptance and uptake of the HPV vaccine among immunosuppressed individuals pose unique challenges. Immunocompromised patients’ acceptance of the HPV vaccine is influenced by multifaceted factors, including concerns about safety and effectiveness, interactions with immunosuppressive medications and uncertainties due to their compromised immunity. This systematic review aims to identify the main factors influencing HPV vaccine acceptance among immunosuppressed patients.

A comprehensive search strategy will be executed across databases such as MEDLINE/PubMed, Embase, Scopus, Web of Science, ScienceDirect, Latin American and Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature and Cochrane Database. The review will encompass the three WHO-endorsed HPV vaccines (quadrivalent, bivalent and nonavalent) and will consider studies related to HPV vaccines and their administration. The scope includes study focusing on immunosuppressed patients who received organ transplants, cancer treatments or are HIV-positive. No temporal restrictions will be applied, and searches will be conducted until December 2025. Observational studies, including retrospective/prospective cohorts, case–control and cross-sectional studies, reporting factors influencing HPV vaccination in immunosuppressed populations will be included. Studies with overlapping patient populations will be excluded. Data extraction will include study details, demographics, vaccine type, risk/protective factors, outcomes and medical history. Validation and cross-verification will ensure data accuracy. Risk of bias will be assessed using ROBINS-I (Risk Of Bias In Non-randomised Studies of Interventions), and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will rate evidence certainty. Meta-analysis, guided by Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, will employ fixed/random-effects models, assessing heterogeneity using I² statistics.

This research will analyse previously published data, so ethical approval is not required. The results of the systematic review will be submitted for publication in a peer-reviewed journal.

CRD42023452537.

To investigate the prognostic value of the Subgroups for Targeted Treatment (STarT) Screening Tool adapted for concussion (STarT-C) on persistent symptoms and disability at 6–9 months following mild traumatic brain injury (mTBI).

Secondary analysis of two prospective studies: an observational cohort study in New Zealand and usual care control arm of a clinical trial in Canada (ClinicalTrials.gov Registry (NCT04704037)).

Participants in the New Zealand cohort were recruited from concussion clinics (five sites) and those in the Canadian cohort were recruited from emergency departments/urgent care centres (eight sites).

New Zealand participants (n=93, median age 37 years, 60% women) were assessed at median=6 weeks post-injury (T1) and 6 months later (T2). Canadian participants (n=223, median age 38 years, 56% women) were assessed at median=2 weeks (T1) and 6 months later (T2).

Symptoms at T2 were assessed using the validated Rivermead Postconcussion Symptoms Questionnaire (RPQ) and disability using the WHO Disability Assessment Schedule 2.0 12-item Interview.

In linear regression analyses, the STarT-C predicted symptom burden (R²=18–36%) and disability (R²=15–18%) at T2 in both cohorts. While the additional prognostic value over and above baseline variables was substantial (delta R² 8–40%), the additional prognostic value over the RPQ at T1 was variable and generally lower (delta R²=1–9%).

The STarT-C—a brief screening tool—predicted persistent symptoms and disability in adults following mTBI. The incremental prognostic value of the STarT-C over the RPQ may be variable, but regardless, the tool may be useful for identifying those at risk of prolonged recovery who may benefit from early psychological intervention.

Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a debilitating chronic illness that affects the central nervous and immune systems, causing core symptoms of extreme fatigue, post-exertional malaise, cognitive issues and sleep disturbance. With reported higher online use than in other chronic illnesses, people with ME/CFS are often housebound and isolated and may struggle to maintain social relationships. Due to a lack of biomarkers, the illness is often contested, causing invalidation and stigma for those affected. This study aims to broaden the knowledge on how people with ME/CFS gain online connections and whether and how these connections integrate into and impact their everyday life.

Qualitative interviews will be conducted with adults aged over 18 years with a diagnosis or self-diagnosis of ME or CFS (n=20–25). A semi-structured topic guide will be used to interview participants and explore online connections and relationships between these and everyday life with ME/CFS. Interviews will be recorded and transcribed verbatim. Data will be thematically analysed to gain in-depth insight into this largely unexplored topic.

The study has ethical approval from the University of Birmingham (reference: RN_1722-Jun2024), and informed written consent will be provided by all participants. Findings will be published in peer-reviewed journals and disseminated to advocacy organisations and health professionals seeking to offer remote support for people with ME/CFS and their families. This study will provide crucial insight into online use and how it can guide the formulation of management plans for people who may currently receive no support from health professionals at all.

Secondary and tertiary renal hyperparathyroidism (RHPT) are common sequelae of chronic kidney disease and are associated with worse patient mortality and quality of life. Clinical guidelines remain lacking with regard to recommendations for using intraoperative parathyroid hormone (IOPTH) during surgery for RHPT. A prospective randomised study will help evaluate the role of IOPTH in guiding surgery for secondary and tertiary RHPT.

Intraoperative parathyroid hormone monitoring to guide surgery in renal hyperparathyroidism is a pragmatic, multicentre, five-arm, parallel-group, patient-blinded and outcome assessor-blinded prospective pilot trial used to evaluate the feasibility of performing a definitive trial. Eligible participants include adult patients diagnosed with secondary or tertiary hyperparathyroidism who are candidates for subtotal or total parathyroidectomy. Consenting patients will be randomly assigned, through central allocation, in a 1:1:1:1:1 fashion to undergo surgery with IOPTH monitoring (four experimental arms: postexcision IOPTH samples taken at 10, 15, 20 or 25 min) or to undergo surgery without IOPTH monitoring (control arm). The primary feasibility objective is to estimate the percentage of eligible patients that are randomised: ≥70% proceed; 50–69% modify protocol before proceeding;

Ethics approval was obtained from the Hamilton Integrated Research Ethics Board. Pilot trial results will be shared widely through local, national and international academic and clinical networks and will be disseminated through conference presentations and publication in peer-reviewed journals.

NCT06542315, registered on 6 August 2024.

The prevalence of women with primary dysmenorrhoea is high and negatively impacts physical and mental health. The intense cyclic episodes of pain generate central nervous system dysfunctional processing. In this sense, strategies focused on the central nervous system are important to re-establish normal functioning. Home-based self-administered transcranial direct current stimulation (tDCS) emerges as a strategy to modulate dysfunctional brain areas and improve the symptoms. This protocol aims to evaluate the effects of home-based self-administered tDCS for pain, premenstrual symptoms, physical performance, quality of life, electroencephalography and patient global impression in women affected by primary dysmenorrhoea.

This is a single-centre, parallel, randomised, double-blinded clinical trial protocol. 40 women affected by primary dysmenorrhoea will be randomised into two groups (active-tDCS or sham-tDCS). Then, 20 consecutive sessions of home-based self-administered tDCS will be performed. The assessments will occur at five time points: baseline, after the 20th sessions, at the first, second and third cycles after tDCS interventions (follow-ups). Primary outcome will be pain according to visual analogue scale. Quality of life, premenstrual symptoms screening, depression, anxiety, physical performance, electroencephalography and participants’ satisfaction will be the secondary outcomes. A mixed analysis of variance will calculate the effect of stimulation.

The study was approved by the ethics committee of the Federal University of Rio Grande do Norte (No. 6.037.756) and registered in the Brazilian Clinical Trials Registry (n° RBR-747k8vb). Participants may withdraw at any time without penalty. Free support will be available from the lead researcher if needed. All procedures will follow Good Clinical Practice and international ethical standards.

https://ensaiosclinicos.gov.br/rg/RBR-747k8vb