Haemoglobin vesicles (HbVs) (product name, NMU-HbVs [Nara Medical University-Haemoglobin Vesicles]), which contain purified human haemoglobin encapsulated within liposomes, have been developed as a potential alternative to blood transfusions in emergency situations. A previous phase I study examined doses up to 100 mL in 11 healthy volunteers. Here, we describe the protocol for a phase Ib study, wherein we will evaluate the safety and pharmacokinetics of NMU-HbV in healthy Japanese adults.

This single-centre, open-label, dose-escalation study will enrol 16 healthy volunteers divided into four cohorts. Planned doses are 100 mL for cohorts 1 and 2, 200 mL for cohort 3 and 400 mL for cohort 4, with infusion rates gradually increasing to a maximum of 5.0 mL/min. The primary endpoint will be safety, which will be assessed as the incidence of adverse events within 14 days and significant clinical changes within 72 hours after administration. Safety evaluations will include subjective symptoms, vital signs, electrocardiograms and laboratory test results compared with the baseline. The secondary endpoint will be pharmacokinetics, which will be assessed as changes in NMU-HbV concentration immediately after infusion until day 4 to determine the maximum blood concentration, time to reach the maximum blood concentration, area under the blood concentration-time curve and elimination half-life. This study will provide data on the safety and pharmacokinetic profiles of NMU-HbV at doses up to 400 mL. The findings are expected to support the further development of NMU-HbV as a viable alternative to emergency transfusions.

The study protocol was approved by the Institutional Review Board of Nara Medical University on 10 December 2024. Dissemination plans include publishing in peer-reviewed scientific journals and presentation at international conferences.

Japan Registry of Clinical Trials (jRCT2051240249). Registered on 27 January 2025 (https://jrct.mhlw.go.jp/en-latest-detail/jRCT2051240249).

Values and preferences are key determinants of optimal care, and variability in patient values and preferences often dictates differences in patient management. Clinicians’ views of patients’ values and preferences may differ across cultural aspects and stage of training, but the extent to which this is the case remains uncertain. One key value and preference issue is the trade-off between quantity and quality of life, and this issue is particularly prominent among patients with dementia. We therefore propose to investigate the extent to which physicians’ perceptions of optimal management for patients living with advanced dementia may differ due to cross-cultural factors and stage of medical training.

We will conduct a sequential explanatory mixed-methods study (QUAN -> qual). First, we will administer paper-based or electronic surveys during educational sessions, conferences and rounds to medical students, residents and physicians in ten countries, either in person or online. Following that, a qualitative inquiry, guided by the findings of the quantitative study and the principles of the interpretive description design, will inform an in-depth exploration of the predictive factors identified in the quantitative data analysis.

The Hamilton Integrated Research Ethics Board at McMaster University has approved this study (approval number 2024-17651). We will disseminate our findings in peer-reviewed publications and present results at conferences as oral and poster presentations.

Sleep problems are an escalating global health concern, with prevalence estimates ranging from 8.3% to 45%. Physicians are disproportionately affected, with rates around 44% compared with 36% in the general population. In Bangladesh, reported rates range from 32% to 58%, with physicians being particularly vulnerable. Poor sleep among physicians is strongly linked to burnout, medical errors and increased mental health risks. Despite these serious implications, existing evidence from Bangladesh remains fragmented and inconsistent, limiting its utility for health policy and workforce interventions. This review therefore seeks to generate reliable pooled prevalence estimates and identify key determinants of sleep problems among Bangladeshi physicians.

The research team will search the PubMed, Scopus, Web of Science, EMBASE, PsycInfo, ProQuest Medical, CINAHL, Google Scholar and BanglaJOL electronic and regional databases following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines for published studies from inception until 1 August 2025, using truncated and phrase-searched keywords, relevant medical subject headings and citation chaining from grey literature. Observational cross-sectional studies published within the predefined timeframe, using validated assessment tools, and published in English or other major international languages will be prioritised for inclusion. Review papers, case reports, case series, intervention studies, commentaries, preprints, meeting abstracts, protocols, unpublished articles and letters will be excluded. Two independent reviewers will screen the retrieved papers using the Rayyan web-based application, with any disagreements resolved by a third reviewer. Quantitative estimates of sleep problems, including prevalence, duration, quality and associated risk factors among Bangladeshi physicians will be extracted. A narrative synthesis and meta-analysis will be performed to assess the pooled prevalence using a random effects meta-analysis model. Forest and funnel plots will be generated for visualisation. Heterogeneity will be assessed using the I² statistic, with sensitivity or subgroup analysis conducted as required. The quality of included studies will be evaluated using Joanna Briggs Institute critical appraisal tools for observational study designs. All statistical analysis will be conducted using Jamovi V2.7.6, R V4.3.2 ‘meta’ packages and GraphPad Prism V9.0.2.

This review will synthesise evidence from existing published literature. While completing the findings, the findings will be submitted to an international peer-reviewed journal and disseminated through conferences, policy forums and stakeholders’ networks to inform future research and interventions.

CRD420251123294.

Economic evaluations are essential for informing healthcare resource allocation. When conducted from a societal perspective, they may include productivity costs such as paid and unpaid productivity losses for patients and their caregivers. Although several methods exist to measure and value productivity costs, there is limited methodological consensus on which methods should be used. This scoping review aims to synthesise existing methods for measuring and valuing patient and caregiver productivity costs.

This review will follow the Arksey and O’Malley framework, enhanced by subsequent methodological guidance from Levac and the Joanna Briggs Institute. The six stages include identifying the research question; identifying relevant studies; selecting studies; charting the data; collating, summarising and reporting the results; and consultation. We will search MEDLINE, Embase and EconLit from 1996 to July 2025. Eligible sources will include peer-reviewed literature that reports methods for the measurement or valuation of productivity costs related to paid or unpaid work among patients or caregivers. Screening and data extraction will be conducted independently by two reviewers. Extracted data will include types of productivity costs, instruments used, valuation approaches, as well as recommendations on preferred measurement and valuation methods. Results will be synthesised thematically and reported using the Preferred Reporting Items for Systematic Review and Meta-Analysis for Scoping Reviews checklist.

Ethics approval is not required as this review will rely exclusively on publicly available literature and does not involve human participants or the use of primary data. The findings will first be shared with Canada’s Drug Agency as a report and then disseminated through peer-reviewed publication and academic presentations to inform future research and practice.

This protocol has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/FK9D4).

Neonatal haemochromatosis, considered to be a gestational alloimmune liver disease (NH-GALD), is a rare but serious disease that results in fulminant hepatic failure. The recurrence rate of NH-GALD in a subsequent infant of a mother with an affected infant is 70%–90%. Recently, antenatal maternal high-dose intravenous immunoglobulin (IVIG) therapy has been reported as being effective for preventing recurrence of NH-GALD in a subsequent infant. However, no clinical trial has been conducted to date.

This is a multicentre open-label, single-arm study of antenatal maternal high-dose IVIG therapy in pregnant women with a history of documented NH in a previous offspring. The objective of this study is to evaluate the efficacy and safety of antenatal maternal high-dose IVIG therapy in preventing or reducing the severity of alloimmune injury to the fetal liver.

The clinical trial is being performed in accordance with the Declaration of Helsinki. The trial protocol was approved by the Clinical Research Review Board at four hospitals. Before enrolment, written informed consent would be obtained from eligible pregnant women. The results are expected to be published in a scientific journal.

28 October 2024, V.8.0.

jRCT1091220353.

Alzheimer’s disease (AD) impacts over 55 million individuals worldwide and remains the leading cause of dementia (60–70% of cases). By 2050, South and Southeast Asia are projected to have an older adult population more than double, bearing a major share of Alzheimer’s disease burden. This will exert a heavy strain on healthcare systems, particularly in resource-limited countries where support and infrastructure are already stretched. Despite this, no review has yet explored the regional epidemiology and associated risk factors in this context. Thus, this study protocol outlines to synthesise prevailing evidence from these densely populated regions, particularly low- and middle-income nations within South and Southeast Asia.

This review will include studies that reported epidemiological characteristics including prevalence, age of onset, mortality, and risk factors of AD and related dementias comprising in South and Southeast Asian regions. Studies published in any language from inception to date will be extracted from PubMed, Scopus, CINAHL, EMBASE and APA PsycNet, following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We will also search grey literature sources and screen the reference lists of the articles selected for full-text review to identify additional relevant studies. Observational studies including case–control, cohort, and cross-sectional designs reporting desired outcomes will be included and appraised for quality assessment with the modified Newcastle-Ottawa Scale (mNOS). The included articles will be appraised by two independent reviewers, with a third resolving any conflicts. Pooled estimates of prevalence, age of onset and mortality will be analysed using random effect meta-analysis (REML) model. Associated risk factors, including modifiable and non-modifiable will be narratively synthesised. Forest plots will be used to visualise the findings, and heterogeneity across the included studies will be assessed using the I² and Cochrane’s Q statistics. Potential publication bias will be assessed using a funnel plot along with the Begg’s and Egger’s tests. Sensitivity and subgroup analyses will also be conducted to assess the robustness of pooled estimates and to explore potential sources of heterogeneity. Statistical analysis will be conducted using Rstudio (v.4.3.2) and GraphPad Prism V.9.0.2.

The systematic review is focused on the analysis of secondary data from published literature; thus, no ethical approval will be needed. The protocol will follow international standard guidelines, findings will be reported in a reputed journal and disseminated through (inter)national conferences, webinars and key stakeholders to inform policy, research and AD management strategies.

CRD 420251047105.