The study by Goto et al screened adolescents across Ukraine for mental health consequences of war.1 These adolescents had a range of exposures to the Russian invasion beginning in early 2022 and completed self-report symptom questionnaires. Prior studies cited in the article suggested that children and adolescents may be especially vulnerable to war-related mental health problems. Given the difficulties of conducting research during ongoing hostilities, this study’s efforts to collect and systematically evaluate a large research...

Music-based training programmes, such as learning how to play an instrument or sing in a choir, have been suggested as potential interventions for promoting healthy brain ageing in older adults at risk of cognitive decline because of their ability to enhance cognitive functions and potentially promote neuroplasticity. However, there is limited empirical evidence in older adults at risk of dementia, especially that evaluates both piano and singing interventions and their effects on cognition and neuroplasticity. In this protocol, we outline a study to assess the efficacy of keyboard and singing music training programmes on reducing cognitive decline and other outcomes in older adults with Mild Cognitive Impairment (MCI).

This randomised, single-blind, controlled, parallel-group trial aims to enrol 432 individuals with MCI from the community in Sydney, Australia. Participants are randomly allocated to participate in either keyboard lessons, singing lessons or a film discussion control group once a week for 3 months. The primary objective is to assess the effectiveness of two music training programmes (keyboard and choral singing) for enhancing verbal memory after 3 months compared with control. Additionally, we will examine how these music-based interventions affect other aspects of cognition, mood, sleep, overall well-being, markers of brain plasticity and blood biomarkers of Alzheimer’s disease and neurodegeneration. Tertiary objectives are to identify factors that impact the success of the interventions, such as participation rates, engagement levels and key demographic and clinical features. Outcomes are collected at baseline and at 3 and 9 months. The primary endpoint analysis will include all randomised participants to estimate the treatment effect using intention-to-treat principles. Primary and secondary outcomes will be analysed using linear mixed models and effect size measures will be calculated.

This study will be the first robust, randomised controlled trial to assess the potential and relative value of music engagement for cognitive decline in high-risk MCI individuals, as well as broader effects on other markers of mental health, well-being and neurodegeneration. Co-designed with implementation in mind, the music interventions can potentially be delivered within memory clinic or community settings.

The Sydney University Human Research Ethics Committee (2023-026) has approved this protocol. The trial findings will be shared through conferences, publications and media.

Australian and New Zealand Clinical Trials Registry (ACTRN12623000407695), Registered 21/04/2023 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385552

2.02 29/11/2024.

Since 2018, WHO has endorsed the use of whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex isolates to detect drug-resistant tuberculosis (DR-TB). This endorsement was based on the assumption that a faster and more detailed description of the resistance profile would improve treatment prescription for DR-TB by healthcare providers, and hence the treatment outcomes of patients. Nonetheless, this assumption has not been tested in routine clinical practice and different scenarios. In Brazil, WGS is not routinely used for the diagnosis of DR-TB, having been carried out in only a few centres for research purposes. With this trial, we will evaluate whether a WGS-based drug-resistance report improves treatment adequacy in patients with pulmonary DR-TB, compared with the current standard-of-care diagnostic methods used in the state of São Paulo, Brazil.

We will conduct a non-randomised controlled clinical trial with two arms to compare the intervention group (ie, individuals receiving a WGS-based report) with a historical control group (i.e., individuals who received resistance diagnostics based on the standard of care of conventional genotyping and phenotyping techniques). The primary outcome will be the proportion of patients whose treatment scheme was adequate based on complete resistance profile determined by WGS and/or phenotypic drug-susceptibility testing (pDST). Other secondary outcomes will also be considered. The target sample size is 88 eligible patients per group. The intervention group will be prospectively recruited over 18 months and the control group will be composed of patients diagnosed with pulmonary DR-TB up to 2 years before the start of the trial. To ensure comparability, isolates from the control group will undergo WGS retrospectively, and pDST will be performed retrospectively in both groups. This clinical trial will take place in six medical centres for the treatment of DR-TB in the state of São Paulo. This study is intended to support the implementation of the WGS in the routine diagnosis of DR-TB in the state of São Paulo.

Ethical approval was obtained from the Human Research Committee of the Institute of Biomedical Sciences, University of São Paulo, Brazil (CAAE: 79497924.1.1001.5467). Study results will be published in peer-reviewed journals and disseminated to policymakers and stakeholders.

U1111-1308-4669.

To assess the comparative effectiveness of educational interventions in neurological disease for healthcare workers and students.

Systematic review.

Medline, Embase and Cochrane through to 1 June 2025.

Studies evaluating neurological disease educational interventions with a comparator group (observational cohort/randomised controlled trial (RCT)) were included.

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted (PROSPERO: CRD42023461838). Knowledge acquisition and educational methodologies were collected from each study. Study outcomes were classified using the Kirkpatrick and Kirkpatrick four-level model (learner reaction, knowledge acquisition, behavioural change, clinical outcome).¹ Risk of bias was assessed using the Newcastle-Ottawa scale for non-randomised studies and the Cochrane Risk of Bias tool for RCTs.^{2 3}

A total of 67 studies involving 4728 participants were included. Of these, 36 were RCTs, and 31 were observational studies. Virtual interventions were the most common (67.2%, n=45 studies), primarily targeting either medical students (46.3%, n=31 studies) or specialists (40.3%, n=27 studies). Overall, 70.1% (n=47) of studies demonstrated outcomes in favour of the intervention. However, few studies used K&K level 3/4 outcomes, with two studies evaluating behaviour change (level 3) and three assessing clinical outcomes (level 4 combined with other levels). No study exclusively assessed level 4 outcomes. Meta-analysis of 22 RCTs with calculable standardised mean differences (SMDs) (n=1748) showed a significant benefit of interventions (SMD 0.75, 95% CI 0.22 to 1.27, p=0.0056).

This review highlights a growing body of research particularly focusing on virtual techniques, specialist audiences and treatment-oriented content. Few studies assessed changes in practice or patient care. Non-specialists remain underrepresented. Future studies should prioritise assessing the clinical impact of educational interventions within non-specialist audiences.

Cardiovascular autonomic neuropathy (CAN) is a serious, untreatable complication of diabetes that contributes to excess cardiovascular mortality and morbidity. CAN is associated with increased fibrosis and inflammation, possibly driven by increased sympathetic activity and overactive mineralocorticoid receptors (MRs). These may represent a potential therapeutic target. MR antagonists (MRAs) improve autonomic function in non-diabetic diseases, and finerenone, a non-steroidal MRA, has demonstrated promising results in managing diabetic kidney disease and cardiovascular complications, suggesting its potential as a novel therapy for early-stage CAN. This trial aims to evaluate whether daily administration of finerenone can modify the disease progression of early-stage CAN.

This trial is a two-centre, double-blind, parallel-group, 1:1 randomised, placebo-controlled study evaluating the effect of 78 weeks of intervention with finerenone or placebo on early-stage CAN in 100 individuals with type 2 diabetes in Denmark. The primary endpoint is the between-group difference in the expiration:inspiration ratio of the cardiovascular autonomic reflex tests (CARTs). Secondary endpoints are the between-group differences in the remaining CARTs, heart rate variability measures and fibrosis markers. Treatment effects on other forms of neuropathy and related pathological mechanisms will be explored.

The study complies with the Declaration of Helsinki and the International Counsil for Harmonisation good clinical practice guidelines, with ethics approval obtained from the Danish Medical Research Ethics Committee. All participants will provide written informed consent. Due to the risk of hyperkalaemia associated with finerenone, safety will be closely monitored throughout the study. Findings will be disseminated through peer-reviewed publications, conference presentations and clinical trial registries. A lay summary will be provided to participants on study completion.

ClinicalTrials.gov: NCT06906081; registration date: 25 March 2025. Clinical Trials Information System: EUCT no. 2024-516597-30-00; registration date: 3 September 2024.

Global health initiatives (GHIs) have played a significant role in expanding access to healthcare worldwide, particularly in maternal health. For instance, many regions in sub-Saharan Africa have seen a notable rise in the availability of skilled birth attendants. However, despite these gains in access, maternal mortality rates in low-income and middle-income countries within the African Region remain alarmingly high. Although GHIs have invested heavily in maternal health, there is limited evidence regarding their effects on the quality of maternal healthcare, an essential factor influencing maternal outcomes. The WHO has developed quality standards for maternal and newborn care to guide all stakeholders in delivery of care for mothers. These include evidence-based practices for managing childbirth complications, efficient health information systems, appropriate referral mechanisms, respectful and dignified treatment of patients, emotional support, well-trained and motivated healthcare providers and a conducive physical environment. These standards serve as a framework for improving and assessing the quality of maternal and newborn services. Despite significant funding and technical guidance aimed at enhancing care quality, there remains a lack of robust data on how GHIs have influenced the quality of maternal health services. To address this evidence gap, we conducted a scoping review to gather and analyse existing evidence on the effects of GHIs on maternal care quality in Sub-Saharan Africa. This report presents the findings from that review.

This study followed the enhanced six-stage framework for scoping reviews developed by Arksey and O’Malley. We included both peer-reviewed and grey literature such as reports and policy documents that addressed the impact of GHIs on maternal health services in sub-Saharan Africa between 2010 and 2024. Sources in all languages were considered. A defined set of inclusion and exclusion criteria guided the screening process. The selected studies underwent qualitative synthesis and descriptive analysis and were visually represented where appropriate. This review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

The search yielded only five quantitative studies, depicting the limited evidence on this critical subject. The studies showed that GHIs had varied effects on quality of care for mothers. These effects included improved readiness of facilities to provide care, improved prenatal-postnatal processes, increased provider knowledge, active management of labour and a decrease in mortality rates in some instances such as Uganda and Zambia. However, there was limited or no improvement in clinical practices, patient experiences and satisfaction with care. Additionally, the studies did not focus on the multidimensional aspects of quality of care as guided by WHO’s comprehensive standards for quality of maternal health services, highlighting a major gap identified throughout this review.

While the limited studies available showed some improvements in specific care quality indicators, there remain significant gaps in the knowledge around how GHIs affect care quality comprehensively. Additionally, the identified studies highlighted significant challenges as a key gap to achieving the intended outcomes and sustaining the gains made during programme implementation. To have a more in-depth understanding of GHIs and their impact on quality of care, it is important to align programme implementation and assessments with comprehensive frameworks such as WHO’s multidimensional quality model. Further, there is a need to adopt iterative, context-sensitive interventions that provide a comprehensive approach to quality of care. The information gathered will be used to inform subsequent studies on the effects of GHIs on quality of care of maternal health services in Uganda and contribute to the development of maternal healthcare policies.

Ovarian cancer remains a significant clinical challenge due to its aggressive nature and high mortality rate. Tumour-infiltrating lymphocytes (TILs) play a critical role in the tumour microenvironment, influencing treatment response and patient survival across various cancer types, including ovarian cancer. A systematic review is warranted to consolidate evidence on TILs as prognostic biomarkers in ovarian cancer, with the goals of integrating them into clinical practice to enhance patient outcomes. This study aims to assess the prognostic significance of TILs in ovarian cancer.

A comprehensive literature search will be conducted across multiple databases, including PubMed, Embase, Web of Science, Scopus, Cochrane Library, CINAHL, ScienceDirect and LILACS. No restrictions regarding publication date or language will be applied. Original studies evaluating the role of TILs in women with ovarian cancer will be considered for inclusion. Two independent authors will screen titles and abstracts, and any discrepancies will be resolved through discussion with a third author. The risk of bias in included studies will be assessed using the Quality in Prognosis Studies (QUIPS) tool. Data synthesis will be performed using R software (V.4.3.1).

This study reviews the published data; thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal.

CRD42024543955.

This project aims to comprehensively examine the incidence of suicidality, individual and population characteristics, and health pathways, for a cohort of Australian veterans using linked administrative data.

The cohort will comprise veterans who are clients of the Department of Veterans’ Affairs (DVA) residing in Queensland between 1 January 2017 and 31 December 2022. People currently serving in the Australian Defence Force, Australian Federal Police personnel, other DVA clients who are not veterans (eg, eligible dependents), and clients currently known to DVA who have requested that their data not be disclosed for research will be excluded. This cohort will be linked to DVA administrative data, the Queensland Hospital Admitted Patients Data Collection (QHAPDC), Queensland Hospital Non-Admitted Patients Data Collection, Emergency Data Collection (EDC), Consumer Integrated Mental Health and Addiction Application (CIMHAA), Queensland Death Register, National Death Index, Medicare Benefits Schedule, Centrelink (Data Over Multiple Individual Occurrences) database and Pharmaceutical Benefits Scheme. These data will be linked for a period of at least 1-year preindex and postindex contact with DVA, such that the entire study period is expected to encompass at least 1 January 2016 to 31 December 2023.

This study received ethical approval from the Departments of Defence and Veterans’ Affairs Human Research Ethics Committee (HREC; Project ID: 556-23), and the Australian Institute of Health and Welfare HREC (Project ID: EO2024/1/1461). This project also received Public Health Act approval (File reference: PHA 556-23). The project was ratified by the University of Queensland HREC (Project ID: 2024/HE002153). The findings of this project will be disseminated via a publicly available report, presentations and peer-reviewed publications.

Body image dissatisfaction (BID) is relatively common in Chinese female undergraduates. This study aims to explore the reasons for BID among female undergraduates to develop effective early intervention strategies.

A qualitative research approach was used through semi-structured interviews, allowing for an in-depth understanding of the experiences of participants.

The study was conducted from April 2024 to November 2024 at Yibin University in Sichuan province, China.

The study involved 25 female undergraduates with an average age of 19.8±1.3 years. These participants were selected to provide rich qualitative data about their experiences and views regarding BID.

The participants showed a high level of BID, and the thematic analysis revealed five overarching themes regarding the causes of BID among female undergraduates: (1) individual factors; (2) media factors; (3) family factors; (4) peer factors; and (5) overall societal impact.

The thematic analysis revealed that dissatisfaction with body image among female undergraduates is a multidimensional issue influenced by various factors, including individual and sociocultural elements. The conclusion emphasises the necessity of strengthening comprehensive intervention measures to address these influencing factors.

Intensive care units (ICUs) exposes both patients and families to an unfamiliar/stressful environment, featuring the urgency for enhanced end-of-life (EoL) care within ICUs.1 2 The emotional burden of EoL decisions can intensify the needs of bereaved families, leading to decreased quality of life,...

Older adults are particularly vulnerable to climate-related stressors such as extreme heat, food and water insecurity and displacement, all of which can worsen existing health conditions. This is further compounded by age-related physiological changes, pre-existing health conditions and social factors like isolation and limited mobility. With a growing population of older adults in low-income and middle-income countries, their vulnerability to climate change becomes a critical global public health issue and yet is understudied and needs urgent and comprehensive action. This study aims to investigate how climate seasonality impacts the health, well-being and socioeconomic conditions of older adults in rural communities of Kenya.

This formative qualitative study will use a combination of 40 in-depth interviews with older adults and key informant interviews with 20 health workers and 12 policy-makers to provide a comprehensive understanding of the impacts of climate seasonality on the health, well-being and socioeconomic conditions of older adults in rural communities of Busia and Kilifi Counties in Kenya. These counties were selected for the study due to their history of significant flooding and heat stress events. Study participants will be purposively selected for the interviews. A thematic approach will be employed in data analysis using NVivo V.14 software.

This study received ethical approval from the Medical College of Wisconsin Institutional Review Board, Institutional Scientific Ethics Review Committee at Africa International University and National Commission for Science, Technology and Innovation, Kenya. The study outputs will reflect the views and experiences of older adults, health workers and policy-makers. The findings will be disseminated to the scientific community through conferences and peer-reviewed publications and to the older adults, health workers, communities and policy-makers through videos and dissemination meetings, and policy briefs. The findings will deepen understanding of how climate seasonality is experienced by older people and shape strategies for resilience and adaptation.

This study aimed to determine the association between diabetes mellitus (DM) medication use and glycaemic control.

This was a retrospective diabetes registry-based cohort study.

Singapore.

Patients aged 18 and above with incident DM in the SingHealth Diabetes Registry from 2013 to 2020 were included. The entire study period included a 1 year baseline period, a 1 year observation period and a 3 month outcome period.

Drug use was measured using the proportion of days covered (PDC), and the changes in glycated haemoglobin (HbA1c) between the outcome and baseline periods were assessed. The associations between baseline HbA1c and PDC ≥0.80 and between PDC and change in HbA1c were analysed using logistic regression and the Kruskal–Wallis test, respectively.

Of 184 646 unique patients in the registry from 2013 to 2020, 36 314 met the inclusion and exclusion criteria and were included in the analysis. The median PDC for any DM drug, oral DM drugs and insulin during the observation period was 20.3%, 16.8% and 0%, respectively. Those who had good glycaemic control at baseline were less likely to receive DM drugs and those with poor baseline glycaemic control or missing baseline HbA1c were more likely to be consistent users (PDC >80%) (px 10^-16).

The relationship between DM drug use and glycaemic control is complex and non-monotonic. Higher PDC for any DM drug and oral DM drugs during the observation period was significantly associated with clinically relevant HbA1c improvements.

To assess factors associated with the adoption of the WHO Package of Essential Non-Communicable Diseases (PEN) Protocol 1 at primary healthcare (PHC) facilities in Nepal after healthcare workers received training.

Cross-sectional study.

PHC facilities across various provinces in Nepal.

A total of 180 healthcare workers trained in PEN, recruited from a random selection of 105 basic healthcare facilities.

The adoption of PEN Protocol 1 components: blood pressure measurement, blood glucose screening, 10-year cardiovascular disease (CVD) risk assessment using WHO/International Society of Hypertension risk charts and body mass index (BMI) assessment. Factors associated with protocol adoption were assessed using generalised estimating equations for ORs.

Among participants, 100% reported measuring blood pressure, while 56% measured blood sugar, 28% assessed CVD risk and 27% assessed BMI. The adoption of the CVD risk prediction chart was positively associated with the availability of amlodipine (adjusted OR (aOR) 3.00; 95% CI 1.09 to 8.27). The adoption of BMI assessment was positively associated with access to a stadiometer (aOR 3.23; 95% CI 1.26 to 8.30) and a glucometer (aOR 3.07; 95% CI 1.12 to 8.40), and negatively associated with lack of motivation/inertia of previous practice (aOR 0.60; 95% CI 0.42 to 0.87) and environmental factors such as lack of time and resources (aOR 0.57; 95% CI 0.37 to 0.89). Blood glucose level measurements were positively associated with being at a PHC centre (aOR 7.34; 95% CI 2.79 to 19.3) and the availability of metformin (OR 2.40; 95% CI 1.08 to 5.29).

Adoption of PEN Protocol 1 varied by component and was influenced by resource availability, provider motivation and system barriers. Addressing these factors is key to optimising implementation in low-resource settings.

Many patients with tuberculosis (TB) suffer from a huge economic burden, even though TB services are often provided free of charge at the point of care. Costs can create significant barriers, hindering patients’ access to TB treatment. These costs include direct medical costs (such as consultation fees), direct non-medical costs (such as transportation costs) and indirect costs (such as wages foregone). This systematic review aims to synthesise the best available evidence on economic evaluations of patient-cost studies on self-administered treatment (SAT) for drug-sensitive TB compared with facility-based directly observed treatment, short-course (FB DOTS), globally.

We will conduct a systematic review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and search PubMed, Academic Search Complete, Scopus, CINAHL Plus (EBSCO) and Google Scholar for articles published up to 2025, without date restrictions. Eligible studies must be full or partial (cost analyses without effectiveness data) economic evaluations conducted globally, comparing SAT to FB DOTS regarding TB patient costs. Grey literature will be included. Exclusion criteria include studies not reporting patient costs between SAT and FB DOTS, and non-economic evaluations (non-original research). Two independent reviewers will conduct the screening, data extraction and quality assessment. A quality assessment will be performed using the Consolidated Health Economic Evaluation Reporting Standards statement, the Consensus on Health Economic Criteria checklist and the ROBINS-I tool.

Ethics approval is not required for this systematic review because it does not use individual patient data. Instead, we will use publicly available economic evaluation research studies. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals.

CRD42024591221.

Cardiovascular (CV) disease is the leading cause of morbidity and mortality globally. Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor of major adverse cardiovascular events. Patients without prior myocardial infarction (MI) or stroke but with established risk factors and elevated LDL-C may benefit from intensive lipid-lowering therapy (LLT); however, the size and potential healthcare burden of this population globally are not known. The benefits of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in these patients, are currently being studied in the phase 3 Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke (VESALIUS-CV) trial. To characterise the high-risk pre–CV-event (VESALIUS-CV–like) individuals in the real world, an observational study is being conducted across multiple countries.

This retrospective cohort study will use a common protocol and an analytical common data model approach to characterise VESALIUS-CV–like individuals in the real world across different geographical regions and healthcare settings. The study period will be from 2010 to 2022, subject to data availability in study sites. Patients aged 50 years and older at high risk of CV disease but without prior MI or stroke will be included in this study. VESALIUS-CV–like individuals are defined through a combination of the following: (1) one diagnosis of coronary artery disease, cerebrovascular disease, peripheral artery disease or diabetes with microvascular complications or chronic insulin use; (2) an elevated LDL-C measurement and (3) other high-risk factors. The objectives of this study are to estimate the prevalence of VESALIUS-CV–like individuals, describe their characteristics and care pathways and estimate their incidence rates of CV events and healthcare costs. The prevalence of VESALIUS-CV–like individuals will be expressed as annual prevalence; patient characteristics at index date will be presented using summary statistics; care pathways will be summarised as LLT prescription across time; and the incidence of defined CV events will be expressed as events per person-years as well as at certain time periods. Healthcare costs will be presented as CV-related costs in different time periods.

Approvals of the study protocol were obtained from relevant local ethics and regulatory frameworks for each participating database. The results of the study will be submitted to peer-reviewed scientific publications and presented at scientific conferences.

Chronic inflammatory skin diseases, despite low mortality, significantly impair quality of life (QoL). Up to 80% of patients with dermatological conditions experience severe itch and poor sleep, as well as related mental health challenges such as anxiety and depression. The relationship between skin diseases and mental health highlights the challenges that doctors face in treating these conditions. Existing psychotherapeutics, such as mindfulness training, cognitive behavioural therapy and acceptance and commitment therapy, are widely used and effective in the treatment of mental health illnesses. However, there is limited evidence on the application of such interventions in dermatology, and most mental health apps lack robust clinical evaluation. We report the design of a randomised controlled trial to evaluate the efficacy and implementation of a mobile app containing dermatology-specified psychotherapeutic strategies in reducing QoL burden.

English-speaking patients aged 16 years and older with psoriasis, eczema or chronic urticaria will be recruited and randomised into the intervention arm (psychotherapeutic application) or active control group (Healthy365 app, a general wellness application managed by the Singapore Health Promotion Board). This allows a comparative assessment of app-usage-specific outcomes while preserving the blinding of all participants. The primary outcome is the change in the Dermatology Life Quality Index (DLQI) score from baseline to week 8. Secondary outcomes include physician-assessed disease severity at weeks 8 and 16 relative to baseline, differences in other patient-reported measures at weeks 8, 16 and 32, self-reported treatment adherence and initiation/escalation of systemic medications. To understand how patients engage with the app, we will evaluate the implementation process, focusing on key measures such as engagement, satisfaction and willingness to pay. Statistical analysis will be carried out on an intention-to-treat basis, and missing data will be analysed using last observation carried forward.

All participants will receive both verbal and written study information that aligns with Good Clinical Practice guidelines. Ethical approval has been obtained from the National Healthcare Group’s Domain Specific Review Board (reference number: 2022/00751). Results will be disseminated via publication in a relevant journal. Data will be available from the corresponding author on reasonable request.

NCT06702293.

Chronic limb-threatening ischaemia (CLTI) represents a severe and debilitating condition characterised by inadequate blood supply to the extremities, leading to acute and persistent pain, ulceration and a heightened risk of limb loss. Patients with CLTI often experience chronic pain that significantly impairs their quality of life. The pain experienced by patients with CLTI can be complex and challenging to manage, requiring a refined approach to balance analgesic efficacy with potential adverse pharmacological effects and pre-existing, competing comorbidities. This systematic review protocol aims to explore, critically assess and compare the effectiveness and safety of different pharmacological and locoregional analgesic approaches for managing pain occurring secondary to CLTI.

The methods will be performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Five electronic databases will be searched. At least two reviewers will perform study screening, data extraction and quality assessments. Any disagreements will be arbitrated by an additional independent reviewer. Randomised studies, observational cohort studies and case series consisting of four or more patients will be included. Grey literature will be excluded. The primary outcome will be the effectiveness of analgesia. Secondary outcomes will include adverse effects of analgesia and functional outcomes. Where the data allow, appropriate quantitative synthesis methods will be pursued.

This systematic review will not involve primary data collection; thus, no ethical approval is required. The results will be disseminated in a peer-reviewed publication and presented at conferences.

CRD42024561800