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Evolving roles and impacts of digital health tools in HIV prevention efforts in Africa: a scoping review protocol

Por: Mpangase · S. H. · Zondi · G. M. · Haffejee · F.
Introduction

With the proliferation of digital technology, the health sector, like other sectors of society, has increasingly adopted digital technologies, resulting in a dynamic landscape where the roles and impacts of digital health tools in different contexts are constantly evolving. This integration of digital technology into the health space has extended into the field of HIV prevention, ushering in new possibilities and challenges. However, review studies documenting the evolving use of digital health tools in HIV prevention are scant, particularly in regions with many low- and middle-income countries, such as in Africa, which have some of the highest HIV prevalence and incidence rates in the world.

Methods and analysis

This scoping review will follow the Joanna Briggs Institute (JBI) 2020 guidelines for methodological rigour and will be reported using Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Review (PRISMA-ScR). Relevant published literature will be searched using a combination of keywords, Boolean terms and Medical Subject Headings in the following databases: CINAHL, Medline, Web of Science, Cochrane Library, Scopus, PubMed, WHO Digital Health ATLAS and Health Source with no date limits for the studies chosen. The Joint United Nations Programme on HIV/AIDS (UNAIDS) website and the reference lists of selected articles will also be used for backward searching, and Google Scholar will be used for forward citation tracking. The search strategy will be formulated following the guidelines provided by the Peer review of Electronic Search Strategies statement for peer assessment of electronic search strategies. Two reviewers will independently assess the references to ensure that they align with the predetermined eligibility criteria. Subsequently, the data from the included studies, published between January 2004 and January 2026, reflecting the period in which digital health innovations have rapidly expanded in Africa, will be extracted and any discrepancies resolved using a third reviewer. Thematic analysis will be used to analyse the data, and the findings will be reported using both tables and figures. The PRISMA-ScR will be followed to report this study’s results. Quality appraisal of the included studies will be done using the mixed methods appraisal tool V.2018.

Ethics and dissemination

This study does not involve human participants and only reviews existing literature in the public domain, and therefore ethical approval was not required. Our intention is to disseminate our research findings through a diverse range of channels, including peer-reviewed journals, conferences and webinars.

Analysis and comparison of the trends in the burden of motor neuron disease in China and worldwide from 1990 to 2021

by Yanan Fu, YuXin Wei, ZiKun Pang, Jie Yang, XinGang Sun

Purpose

This study outlines the changes in the age- and sex-specific burden of motor neuron disease (MND) in China from 1990 to 2021, focusing on the prevalence, incidence, number of disability-adjusted life years and mortality. Additionally, these trends are evaluated in comparison to the Global Burden of Disease data.

Methods

Public data from the Global Burden of Disease database covering the period from 1990 to 2021 were analyzed to explore the burden of motor neuron disease in China and worldwide. Trends in prevalence, incidence, disability-adjusted life years (DALYs) and mortality were examined in the analysis. The average annual percentage change was calculated using Joinpoint, and the relevant 95% confidence intervals (95% CIs) were examined to identify changes in the MND burden over time. Additionally, a thorough comparative analysis was performed to investigate the differences in the MND burden between China and other regions worldwide, considering factors such as age, sex, and time periods.

Results

From 1990 to 2021, the age-standardized incidence rate (ASIR) of motor neuron disease (MND) in China declined from 0.65 per 100,000 to 0.46 per 100,000, whereas the global ASIR decreased slightly from 0.81 per 100,000 to 0.77 per 100,000. In contrast, the age-standardized prevalence rate (ASPR) in China increased from 2.131 per 100,000 to 2.298 per 100,000, whereas the global ASPR decreased slightly from 3.356 per 100,000 to 3.31 per 100,000. The age-standardized mortality rate (ASMR) in China increased from 0.151 per 100,000 to 0.181 per 100,000; the global ASMR also increased from 0.38 per 100,000 to 0.46 per 100,000 during this period. Moreover, the age-standardized disability-adjusted life year (ASDR) rate in China decreased slightly from 7.995 per 100,000 to 7.672 per 100,000, whereas the global ASDR increased from 11.221 per 100,000 to 12.167 per 100,000. The average annual percentage changes (AAPCs) for the ASPR, ASIR, ASDR, and ASMR in China were −1.10%, 0.25%, 0.57%, and −0.14%, respectively. In contrast, the global AAPCs were −0.16%, −0.04%, 0.58%, and 0.26%, respectively. Age and sex played distinct roles in shaping MND burden. The ASIR of MND decreased but then increased for both sexes, remaining higher for males. Its ASPR trends differed: a slight increase in males versus an increase then decrease in females. While the ASMR was consistently higher for males, the DALYs for males started to decrease but surpassed those for females. Global MND rates have remained stable.

Conclusion

The prevalence, incidence, DALYs and mortality of motor neuron disease in China decreased between 1990 and 2021, suggesting a relative decrease in the total burden of MND in the country. Age influences the burden of MND, with a higher occurrence incidence in children and middle-aged individuals; the prevalence of MND is highest in the younger population, whereas MND-related mortality is the highest within the middle-aged and senior populations. Compared with females, males are more likely to be affected by MND and have a greater likelihood of death. Given the rapid population aging in China, MND is expected to remain a significant public health issue.

Efficacy of sequential denosumab after teriparatide for 6 months compared with denosumab monotherapy in reducing risk of osteoporotic fractures in patients with new fractures: a multicentre randomised controlled trial (STAND study) protocol

Por: Chi · Y. · Zhu · Y. · Yuan · J. · Pang · Q. · Cui · L. · Jiang · Y. · Jiajue · R. · Liu · W. · Wang · O. · Li · M. · Xing · X. · Li · H. · Xie · G. · Wu · Y. · Xia · W.
Introduction

Osteoporosis (OP) is a systemic skeletal disorder that increases fragility and susceptibility to fractures. Despite the availability of teriparatide for the treatment of patients with acute fractures with better efficacy, its long-term daily injection and high cost limit its broader use among a wider patient population, especially for those living in low- and middle-income countries. This study aims to evaluate the efficacy of a novel sequential treatment with teriparatide daily for 6 months followed by denosumab every 6 months for another 18 months, in comparison with denosumab monotherapy every 6 months for 24 months, in reducing the risk of fractures in patients with newly diagnosed osteoporotic fractures. The study will also explore the possible difference between two sequential treatments (shifting to denosumab treatment at 6 or 12 months) in their effect on increasing bone mineral density (BMD).

Methods and analysis

This study is designed as a multicentre, open-label, randomised controlled trial among 2478 patients with newly diagnosed osteoporotic fractures from 58 hospitals across China. Participants will be randomly assigned in a 10:10:1 ratio to three treatment groups: 24 months of denosumab monotherapy, early sequential treatment (teriparatide for 6 months followed by denosumab for 18 months) and late sequential treatment (teriparatide for 12 months followed by denosumab for 12 months). The primary outcome is the incidence of vertebral fractures over 24 months of treatment. Secondary outcomes include changes in BMD at the lumbar spine, total hip and femoral neck, changes in bone turnover markers (β-carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 N-terminal propeptide), treatment adherence and cost-effectiveness. Follow-up assessments are scheduled at 3, 6, 9, 12, 18 and 24 months post-randomisation for primary and secondary outcomes, and biannually afterwards for the primary outcome.

Ethics and dissemination

The study protocol has been registered on ClinicalTrials.gov and has received ethical approval from the Peking Union Medical College Hospital Medical Science Research Ethics Committee (1-22PJ939). The findings will be disseminated through peer-reviewed scientific journals.

Trial registration number

NCT05866029.

Symptomatic changes and influencing factors following manipulation under anaesthesia in patients with adhesive capsulitis of shoulder: a protocol for a prospective cohort study

Por: Wang · Y. · Pang · J. · Shi · Y.
Introduction

Adhesive capsulitis of the shoulder is a common shoulder disease. With the ageing population, the incidence of adhesive capsulitis has been rising year by year, posing a significant threat to the quality of life of middle-aged and elderly individuals. As one of the main means of treating adhesive capsulitis, manipulation under anaesthesia (MUA) can achieve good clinical results while maintaining high economic benefits. The purpose of this study is to investigate the prognostic factors and the longitudinal recovery trajectory of patients, so as to provide a basis for the precise treatment of MUA.

Methods and analysis

The study is a longitudinal prospective cohort study with a 12-month follow-up. A trajectory analysis model (latent growth curve modelling) will be used to observe the recovery changes of adhesive capsulitis patients. Linear mixed-effects models will be employed to analyse the prognostic factors of adhesive capsulitis.

Ethics and dissemination

Ethical approval was obtained from the Institutional Review Board of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (approval number: 2025-1707-047-02), following ethical guidelines and standard reporting practices. The research findings will be disseminated through presentations at both regional and global medical conferences.

Trial registration number

ChiCTR2500100645.

Impact of physical activity on sleep in adults recovering from substance use disorders: a protocol for an N-of-1 observational study

Por: Thal · S. · Richardson · C. · McVeigh · J. · Thompson · C. · Wan · P. · Pang · B. · Riddell · H. · Bright · S. · Clarke · J. · Myers · B.
Introduction

Sleep impairments are prevalent among individuals recovering from substance use disorders (SUDs) and are associated with poorer treatment outcomes and increased relapse risk. Physical activity (PA) is known to enhance sleep in general populations, but its day-to-day effects on sleep during SUD recovery remain underexplored, especially across different recovery stages.

Methods and Analysis

In this observational n-of-1 study, we aim to examine within-person associations between daily PA and sleep quality in three groups of individuals at varying stages of substance use recovery (early treatment, continuing care and long-term recovery). A substudy will validate the agreement between two wearable sleep-monitoring devices. A total of 90 participants (30 per recovery group) from Western Australia will complete daily ecological momentary assessments and wear the SENS Motion sensor and/or Withings Sleep Analyzer over a 30-day period. Outcomes include device-derived sleep and PA measures, self-reported affect, craving, well-being and recovery outcomes. Multilevel models will explore within-person and between-person associations. This study will generate individualised evidence on associations between PA and sleep to inform tailored SUD care. It will also assess the feasibility of using wearable sleep monitors in real-world SUD recovery settings. Results may support the future development of just-in-time adaptive intervention procedures.

Ethics and Dissemination

The study was approved by the Human Research Ethics Committee of Curtin University (HRE2025-0379). Findings will be shared through peer-reviewed publications and conference presentations, with lay summaries provided to treatment facilities and interested participants to support translation into community and service settings.

Trial registration number

ACTRN12625000835448.

Prevalence and determinants of underweight and overweight/obesity among Ghanaian children: a cross-sectional study using DHS data in Ghana

Por: Dam · K. M. · Alhassan · P. D. A. · Addai · J. · Apanga · S. · Adjei-Mensah · E. · Sienso · B. A. · Boakye · G. · Bawa · A. W. · Tamal · C. · Seneadza · N. A. H. · Abdul-Mumin · A. · Nuertey · B. D.
Background

There is a global rise in the burden of childhood obesity, increasing the risk of early onset adult obesity. Most developing countries face the double burden of malnutrition; overnutrition as overweight/obesity and undernutrition.

Objectives

To determine the current burden and determinants of childhood thinness, overweight and obesity using national survey data.

Design

Data from a cross-sectional survey conducted in 2022 were used.

Setting

Data from the seventh Demographic Health Survey conducted in Ghana were used.

Participants

The participants included 4417 children ≤59 months.

Method

The seventh Ghana Demographic Health Survey in 2022 employed a two-stage stratified cluster sampling design, selecting 618 clusters to create a nationally representative sample. Weight and height were measured using the SECA 874U scale and Shorrboard, respectively. Children’s heights were measured recumbent (24 months). Multivariate logistic regression was used to assess the relationship between thinness and obesity, as well as the independent factors.

Outcome variable

The outcome variable was obesity, determined by a WHZ of >+2SD.

Results

The weighted prevalence of overweight/obesity and thinness in children under 5 years is 9.9% and 5.2%, respectively. Children who were overweight or obese had a mean age of 23.11 months, those who were thin or severely thin had a lower mean age of 21.02 months, and those with normal nutritional status were relatively older, with a mean age of 28.41 months. The Upper West, Northeast and Northern regions had the lowest densities of obesity. In the multivariate logistic regression model, children residing in Ashanti, Oti, Northern, North East and Upper East regions had significantly reduced odds of being obese compared with those in the Ahafo region. The average haemoglobin for those overweight/obese was 10.8 g/dL, and 10.7 g/dL for those who were normal and marginally reduced, 10.5 g/dL for those who were thin.

Conclusion

Regional disparities, maternal nutritional status, socioeconomic conditions and unsafe water sources were significant determinants of child nutrition outcomes. These findings call for targeted, multipronged interventions that integrate maternal-child nutrition, safe water, sanitation and regional context.

Global, regional, and national burden of endometriosis among women of reproductive age, 1990–2021: Insights from the global burden of disease study 2021

by Jun Zhang, Mengduan Pang, Ling Li, Chuanjia Guo

Background

Endometriosis is a common gynecological disorder among women of reproductive age worldwide. This study aims to examine global patterns of endometriosis disease burden among reproductive-aged women and to evaluate its correlation with socioeconomic development indices.

Methods

This study conducted a comprehensive analysis of endometriosis disease burden using epidemiological parameters from the Global Burden of Disease (GBD) 2021 database, including incidence rates, prevalence rates, Disability-Adjusted Life Years (DALYs), and corresponding age-standardized rates. Through stratified analyses at global, regional, and national levels, we systematically evaluated the disease burden patterns among reproductive-aged women and performed correlation analysis with socioeconomic development indices.

Results

We found that the highest incidence of endometriosis among women of reproductive age globally occurs in the 20–24 age group, with an incidence rate of 399.49 per 100,000 in 1990 and 304.31 per 100,000 in 2021. The results show that the global disease burden of endometriosis is mainly influenced by population size, followed by epidemiological changes. Compared to countries with a medium Social Development Index (SDI), the disease burden of endometriosis in low and high SDI regions fluctuated significantly from 1990 to 2021. In most countries with SDI values between 0.2 and 0.6, the burden of endometriosis showed a gradual decline.

Conclusion

Endometriosis remains a significant public health issue for women of reproductive age globally. Although the global disease burden of endometriosis among women of reproductive age showed a slight decline from 1990 to 2021, the disease burden continues to fluctuate in certain regions and countries. In light of the differences in the disease burden of endometriosis across regions and countries, regionalized disease management strategies are expected to be developed in the future.

Relationships Between Job Engagement and Self‐Efficacy, Perceived Organisational Support and Perceived Job Security for Newly Recruited Nurses: A Cross‐Sectional Study

ABSTRACT

Aims

To examine the relationships among perceived organisational support, perceived job security, self-efficacy and job engagement among newly recruited nurses and the mediating role of perceived job security and self-efficacy in the relationship between perceived organisational support and job engagement.

Design

Cross-sectional study.

Methods

This study employed a multicentre cross-sectional survey design and used the Perceived Job Security Scale, General Self-Efficacy Scale, Perceived Organisational Support Scale and Job Engagement Scale to survey 536 newly recruited nurses (from September 2023 to April 2024). Structural equation modelling was used to test the effects of perceived organisational support, perceived job security and self-efficacy on job engagement.

Results

In the study model, perceived organisational support, perceived job security and self-efficacy all directly affect job engagement among newly recruited nurses. Additionally, perceived organisational support can be used to predict job engagement through self-efficacy and perceived job security.

Conclusion

Perceived organisational support, job security and self-efficacy are positive predictors of job engagement among newly recruited nurses. Furthermore, perceived job security and self-efficacy mediate the relationship between perceived organisational support and job engagement.

Impact

Newly recruited nurses, as key agents in clinical nursing practice, play a crucial role in reducing nursing errors and improving work efficiency. The results of this study show that perceived organisational support, perceived job security and self-efficacy positively predict job engagement among newly recruited nurses. Clinical nursing managers and educators should assist newly recruited nurses in enhancing their perceived organisational support to foster job engagement by bolstering their perceived job security and self-efficacy.

Reporting Method

This study adhered to the STROBE guidelines.

Patient or Public Contributions

No patient or public contribution.

Three infections, one fight: an implementation study to map needle prevalence and evaluate HIV, syphilis and hepatitis C prevention interventions in Regina, Saskatchewan - a protocol

Por: Eaton · A. D. · Rowe · M. W. · Varghese · S. M. · House · H. · Pang · N. · Kwan · S. · Ford · P. · Reddy · V. D. · Acoose · T. · Littleford · J. · Lang · K. · Foreman · E. S. · Sasakamoose · J. · Pandey · M. · Medeiros · P. · Loutfy · M. R. · Grace · D. · Brennan · D. J. · Zhao · K. · Shuper
Introduction

Saskatchewan is facing a public health crisis driven by high rates of HIV, syphilis and hepatitis C virus (HCV) infections, particularly among people who use drugs. Injection drug use is a major contributor to these syndemic infections, exacerbated by structural barriers such as stigma, poverty and limited culturally safe healthcare. Innovative, community-informed approaches are urgently needed to improve prevention, testing and linkage to care.

Methods and analysis

This study will implement a rapid assessment and response system in Regina, Saskatchewan, Canada, integrating geospatial mapping of community needle prevalence with pop-up interventions. Needle hotspot maps will be used to guide the deployment of community-based pop-up events offering point-of-care testing for HIV, syphilis and HCV, alongside education on pre-exposure prophylaxis (PrEP) and postexposure prophylaxis (PEP). A convergent participatory mixed-methods design will be used to evaluate feasibility, acceptability and effectiveness, guided by the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Quantitative data will assess changes in knowledge of PrEP and PEP, satisfaction with the intervention and report new diagnoses and participant demographics descriptively. A qualitative substudy will include 30 participants and will explore experiences with the intervention, barriers to care and perceptions of service delivery.

Ethics and dissemination

Ethical approval has been obtained from the research ethics board of the Saskatchewan Health Authority (#24–91). Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. This study may provide a model of community-based geospatial testing and education that could be scaled up and adapted elsewhere.

Registration

Open Science Framework https://doi.org/10.17605/OSF.IO/HVK3B

Feasibility of implementing a non-invasive self-sampling method for saliva specimens that can be used for the diagnosis of respiratory infections among paediatric patients in the Tshwane District, South Africa: a study protocol

Por: Nxele · S. · Dlangalala · T. · Gxekwa · N. V. · Ramatsokotla · S. · Musekiwa · A. · Kgatle · M. M. · Hatchett · D. B. · Shin · A. · Tu · W.-c. · Robertson · I. H. · Su · X. · Berthier · E. · Thongpang · S. · Theberge · A. B. · Mashamba-Thompson · T. P.
Introduction

Effective community-based disease management is essential for public health. In low- and middle-income countries, sustainable strategies for timely diagnosis and treatment are a research priority. This study aims to assess the feasibility of a non-invasive saliva self-sampling method, paired with digitally linked molecular point-of-care diagnostics, for detecting respiratory infections among paediatric patients in the Tshwane District, South Africa.

Methods and analysis

A field study will be conducted at Steve Biko Academic Hospital to compare saliva collection using the CandyCollect lollipop device and standard mouth swabs. The spiral groove of the lollipop device captures pathogens, which are stored in DNA/RNA preservation media and later analysed using quantitative PCR and commercially available rapid antigen tests. The multiplex respiratory pathogen panel, based on TaqMan real-time PCR technology, targets key paediatric pathogens including Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, respiratory syncytial virus (RSV) and influenza A/B. Nucleic acids will be extracted using standard viral extraction kits and analysed following manufacturer protocols. Internal controls will be included in each qPCR run, and samples with CT values below defined thresholds will be considered positive. Rapid antigen tests will detect common pathogens such as influenza A/B, RSV and SARS-CoV-2 for comparative analysis. User experience and acceptability will be assessed via child-friendly and caregiver surveys following sample collection. The study will be implemented in two phases: diagnostic performance evaluation and user feedback assessment. The protocol is aligned with the Standard Protocol Items: Recommendations for Interventional Trials 2013 checklist.

Ethics and dissemination

Ethical approval has been granted by the University of Pretoria (509/2023) and the Gauteng Department of Health (GP_202406_032). The study is registered in the Pan African Clinical Trial Registry (PACTR202411743094783). Findings will be disseminated through peer-reviewed journals, conferences and stakeholder briefings. The study complies with South Africa’s Protection of Personal Information Act. Data collection is scheduled from November 2024 to February 2025, with project completion expected within 1 year.

Trial registration number

Pan African Clinical Trial Registry (PACTR202411743094783).

“Sandwiched Individuals” Exploring the Push and Pull Factors Influencing Retention Among Mid‐Career Nurses: An Integrative Review

ABSTRACT

Aim

To systematically analyse international empirical literature and establish a comprehensive understanding of the push and pull factors influencing retention and turnover among mid-career nurses.

Design

An integrative review.

Data Sources

PubMed, Web of Science, Scopus, EMBASE (Ovid), and CINAHL (EBSCO) were searched for studies published between January 2001 and November 2024.

Methods

An integrative literature review was conducted following the five-step process outlined by Whittemore and Knafl. Articles were screened by title, abstract, and full text based on predefined inclusion and exclusion criteria. The quality of eligible studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Data were extracted and synthesised narratively, and the findings were presented according to the socio-ecological framework.

Results

A total of 1930 studies were identified, with 14 included for analysis: 10 qualitative, 3 quantitative, and 1 mixed-methods study. Guided by the socio-ecological framework, four themes and 10 subthemes emerged: (1) Intrapersonal (professional knowledge/skills, health issues, work-family balance); (2) Interpersonal (professional collaborative relationships, supervisor support); (3) Organisational (organisational characteristics, work characteristics, career development); and (4) Societal (salary/benefits, Social/governmental recognition).

Conclusion

This review reveals the heterogeneity of research on this topic and confirms previous findings. It identifies certain push-and-pull factors common to nurses across all stages of their careers. However, mid-career nurses face unique challenges, including more complex healthcare demands, declining health status, growing family caregiving responsibilities, unclear organisational roles, underutilisation of professional skills, career stagnation, and limitations on salary growth. These findings highlight the need for tailored retention strategies for mid-career nurses.

Implications for the Profession

A “one-size-fits-all” retention strategy does not meet the needs of all nurses. To improve nurse retention rates, it is essential to address the shifting demands and priorities that arise as nurses reassess and transition through different career stages. For mid-career nurses, acknowledging and valuing their expertise and capabilities, providing sufficient resources, and fostering a supportive work environment that promotes career development may be effective strategies for retaining these experienced professionals.

Reporting Method

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Patient or Public Contribution

No Patient or Public Contribution.

Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study: a protocol for a multicentre phase 1 safety trial of melatonin to augment therapeutic hypothermia for moderate/severe hypoxic ischaemic encephalopathy

Por: Pang · R. · Macneil · A. · Wadke · A. · Jaami · Y. · Marlow · N. · Standing · J. F. · Dehbi · H.-M. · Tranter · P. · Robertson · N. J. · on behalf of the ACUMEN Consortium · Allegaert · Becher · Boardman · Boylan · Cowan · Dehbi · Foran · Hunt · Jaami · Kendall · MacNeil · Mahaveer
Introduction

Neonatal death and later disability remain common sequelae of hypoxic-ischaemic encephalopathy (HIE) despite the now standard use of therapeutic hypothermia (HT). New therapeutic approaches to brain protection are required. Melatonin is an indolamine hormone with free-radical scavenging, antiapoptotic, anti-inflammatory and gene regulatory neuroprotective properties, which has extensive preclinical evidence of safety and efficacy. Pharmacokinetic (PK) data suggest it is necessary to reach melatonin levels of 15–30 mg/L within 6–8 hours of hypoxia-ischaemia for brain protection. We developed a novel Good Manufacturing Practice (GMP) grade melatonin in ethanol 50 mg/mL solution for intravenous use. In preclinical studies, ethanol is an adjuvant excipient with additional neuroprotective benefit; optimised dosing protocols can achieve therapeutic melatonin levels while limiting blood alcohol concentrations (BACs).

Methods and analysis

The Acute High Dose Melatonin for Encephalopathy of the Newborn (ACUMEN) Study is a first-in-human, international, multicentre, phase 1 safety study of intravenous melatonin in babies with moderate/severe HIE receiving HT. Sixty babies will be studied over two phases: a dose escalation study including four dose levels to establish the recommended phase 2 dose (RP2D), followed by a 6-month cohort expansion study of RP2D to further characterise PKs and affirm safety. Participants will receive a 2-hour intravenous infusion of melatonin within 6 hours of birth, followed by five maintenance doses every 12 hours to cover the period of HT. Plasma melatonin and BACs will be monitored. The RP2D will be based on the attainment of therapeutic melatonin levels while limiting BACs and the frequency of dose-limiting events (DLEs). A Bayesian Escalation with Overdose Control approach will be used to estimate the risk of DLE per dose level, with a target level of

Ethics and dissemination

Approval has been given by the London Central National Health Service Health Research Authority Ethics Committee (25/LO/0170) and UK Clinical Trials Authorisation from the Medicines and Healthcare products Regulatory Agency. Separate approvals have been sought in Ireland and Australia. Dissemination will be via peer-reviewed journals, conference presentations, public registries and plain language summaries for parent/legal guardian(s), in accordance with national requirements.

Trial registration number

ISRCTN61218504. EU CT: 2025-520538-49-00.

Protocol version

Publication based on the UK protocol V.3.0, 08 May 2025

Effect of electrical stimulation on functional recovery of lower limbs in patients after anterior cruciate ligament surgery: a systematic review and meta-analysis

Por: Shan · W. · Zheng · T. · Zhang · J. · Pang · R.
Objectives

This study aimed to summarise the existing literature about enhancing muscle strength, lower limb function and self-reported function by electrical stimulation (ES) relative to conventional physical therapy following anterior cruciate ligament reconstruction (ACLR), and to assess the comprehensive treatment effects of ES via meta-analysis.

Design

Systematic review, meta-analysis.

Methods

This study systematically searched five electronic databases (PubMed, Web of Science, Scopus, Embase and Chinese National Knowledge Infrastructure), covering records from their inception until February 2024, adhering to a predefined search strategy. Two independent reviewers extracted and synthesised the relevant data using RevMan software (V.5.3). Due to identified heterogeneity, a random-effects model was applied for the meta-analysis. The meta-analysis calculated the effect sizes concerning lower limb function outcomes as standardised mean differences (SMD) with 95% CIs. The methodological quality of the included studies was assessed by the Physiotherapy Evidence Database scale.

Results

A total of 15 studies involving 1583 patients (between the ages of 15 and 50 years) were included. Meta-analysis results indicated that the ES group could improve the lower limb comprehensive function compared with the control group (CG) based on four clinical tests: the muscle strength (SMD=0.55, 95% CI 0.14 to 0.95, p=0.008, I2=74%), the range of motion (SMD=1.10, 95% CI 0.40 to 1.79, p=0.002, I2=89%), the Lysholm scale (SMD=1.05, 95% CI 0.36 to 1.73, p=0.003, I2=91%) and the visual analogue scale (SMD=0.87, 95% CI 0.38 to 1.37, p=0.006, I2=75%). However, there were no significant differences between the CG and the ES group in terms of leg circumference (SMD=0.61, 95% CI –0.78 to 2.00, p=0.39, I2=87%).

Conclusions

Adjunctive ES has the potential to enhance early-phase ACLR rehabilitation outcomes, particularly by improving muscle strength, lower limb function and self-reported function, despite the use of different ES modalities.

PROSPERO registration number

CRD42024549752.

Methods of assessment of diabetic retinopathy in low- and middle-income countries: a protocol for scoping review

Por: Kousha · O. · Gil · L. C. · Panggalo · I. · Blaikie · A. · Ellis · J.
Introduction

Globally, over a hundred million people are estimated to suffer from diabetic retinopathy (DR), which is a major complication of diabetes mellitus (DM). The prevalence of DM is projected to increase from the current 537 million by almost 50%, to 783 million by 2045. As a result, DR is one of the fastest rising causes of preventable blindness. Three out of four people suffering from DM live in low- and middle-income countries (LMICs), where resources for both diagnosis and treatment are lacking. There has been a reduction in the rate of blindness from DR in high-income countries, while an opposite trend has been noted in LMICs, contributing to this massive morbidity burden. This scoping review aims to ascertain the methods used to assess DR in LMICs.

Methods and analysis

The scoping review will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Review (PRISMA-ScR) guidelines and the Arksey and O’Malley (2005) methodology framework. A systematic search of peer-reviewed literature will be carried out for all papers up to 15 May 2025 by identifying studies from electronic databases, including Embase, Medline and CENTRAL (Cochrane Library). A hand search of the associated reference lists of included studies and grey literature will also be conducted. The identified studies will be screened based on agreed eligibility (inclusion/exclusion) criteria by two independent reviewers, with any disagreements resolved via arbitration from a third reviewer. The data will be thematically summarised according to different aspects of DR assessment methods, and key findings will be elicited. The key findings will provide a comprehensive and clear understanding of the assessment methods used to identify DR in LMICs.

Ethics and dissemination

Ethical approval was not sought for this work as only publicly available information is used. The results will be disseminated through a peer-reviewed publication, conference presentations and meetings with stakeholders.

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