[Review] Respiratory syncytial virus hospitalization costs, rates, and seasonality in Asia: a systematic review and meta-analysis

This study highlights the significant burden of RSV in Asia, particularly among young children, and highlights substantial variation in seasonality and economic impact across the region. The findings emphasize the need for region-specific RSV data to inform targeted prevention strategies and healthcare resource allocation. High heterogeneity in cost estimates suggests variability in healthcare access and economic conditions, warranting further investigation.

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[Review] Measurable residual disease in hematologic malignancies: a biomarker in search of a standard

Over the past decade, measurable residual disease (MRD) has emerged as a critical tool for detecting and monitoring a variety of cancers, but particularly hematologic malignancies. The rapid adaptation of this novel approach to monitoring disease status is intuitively appealing: it offers significantly greater sensitivity than traditional methods for detecting the small population of malignant cells that persist after treatment, and which are undetectable by standard approaches such as monitoring abnormalities on radiographic scans or assessing morphologic or karyotypic changes from bone marrow sampling.

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Immunomodulatory therapies in community-acquired pneumonia: a protocol for a systematic review and network meta-analysis

Introduction
Community-acquired pneumonia is the leading global cause of infection-related death. A subset of patients with pneumonia develops aberrant immune responses, resulting in harmful inflammation, tissue damage and significant mortality. Immunomodulatory therapies aim to blunt this dysregulated immune response and reduce resultant injury. No consensus exists on the use or impacts of immunomodulatory therapies in the management of community-acquired pneumonia. This protocol describes the methods we will use to undertake a systematic review and network meta-analysis of the effects of immunomodulatory therapies on the mortality of patients with community-acquired pneumonia.

Methods
We will undertake a systematic review and network meta-analysis investigating the use of immunomodulatory therapies in community-acquired pneumonia. Our protocol has been developed and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines and prospectively registered with PROSPERO (CRD42024565301). The primary objectives of this work are to compare the impact of immunomodulatory therapies on 28-day and 90-day mortality in adult patients admitted to hospital with a primary diagnosis of community-acquired pneumonia. The secondary objectives of this work are to identify any differences in the effectiveness of these immunomodulatory therapies in managing community-acquired pneumonia of differing aetiology and severity.
We will conduct a literature search of Medline, Embase, Scopus, Web of Science and Global Health for all relevant articles until 30 June 2024. All observational, interventional and epidemiological studies published in English will be included, and each type of study design will be examined separately. All studies will have their titles and abstracts independently screened by two reviewers, followed by a full article eligibility review and data extraction. A third reviewer will adjudicate any disagreements. Data extracted will include, but not be limited to, the study design, country in which it was undertaken, patient characteristics (eg, age, sex, cause of CAP, severity of CAP), details regarding the immunomodulatory therapy and dosing used and the 28-day and 90-day mortality of each study arm.

Analysis
The risk of bias will be assessed using the Risk of Bias in Non-randomised Studies – of Exposure tool for non-randomised studies and the Cochrane Risk of Bias 2 tool for randomised control trials. The quality of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations for network meta-analysis framework. A quantitative synthesis of data is planned for 28-day and 90-day mortality rates.
We will fit a random-effects network meta-analysis model that includes random effects for between-study heterogeneity and for inconsistency. This will be done using the metafor package for R. We will use a contrast-based approach, modelling estimated treatment effects using reference treatments. In the case of the primary objective, this will be the log odds ratio (OR) of mortality in one treatment compared with another.
Each type of study design will be examined separately. Treatments using the same immunotherapy at different doses may be grouped if appropriate.

Ethical approval and dissemination
This will be a systematic review of published literature; therefore, ethical approval is not required. To ensure communication of our findings, we will publish our results in a peer-reviewed journal and present our findings at appropriate local, national and international meetings.

PROSPERO registration number
CRD42024565301.

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[Articles] Global outbreaks of respiratory syncytial virus infections from 1960 to 2025: a systematic review and meta-analysis

RSV outbreaks have contributed significantly to global morbidity since the 1960s, with increasing reports over time. While the CFRs have decreased, they remain high in certain subgroups based on age, genotype, and outbreak setting. The pooled attack rate remains substantial, particularly in healthcare settings involving RSV-B genotypes and among immunosuppressed populations. This meta-analysis underscores the importance of targeted vaccination and treatment strategies for controlling RSV outbreaks worldwide in the future.

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Assessing the experimental EuroQol toddler and infant populations (EQ-TIPS) descriptive system: a protocol integrating discrete choice experiment (DCE) surveys in instrument development

Introduction
The experimental EuroQol Toddler and Infant Populations (EQ-TIPS) instrument is currently under development as a health-related quality of life (HRQoL) measure for toddlers and infants aged 0–36 months. Using this protocol, researchers can conduct surveys with discrete choice experiments (DCEs) that examine the key properties of HRQoL instruments, specifically whether severity aligns with preferences across each attribute and the extent to which attributes influence choices. To demonstrate this protocol, we will conduct two waves of DCE surveys using different choice tasks and a common scenario (a 1-month health episode for a 1-year-old child).

Methods and analysis
In the first wave (a general population sample of 400 Australian adults; 14 kaizen tasks each), respondents will view a single EQ-TIPS-five-level (v3.0) profile for each task and be asked to make a series of choices that sequentially alleviate the child’s health problems. Using this exploratory evidence, we will assess whether EQ-TIPS severity aligns with preferences and the extent to which each attribute level influences choices (ie, main effects). In the second wave (1000 Australian adults; 28 paired comparisons), respondents will see two EQ-TIPS profiles for each task and be asked to choose between them. Using this confirmatory evidence, we will compare the main effects and their uncertainty by wave. For each DCE, we will estimate a main-effects conditional logit model and test for differences in effects using cluster bootstrap techniques. As sensitivity analyses, we will evaluate the effects of task sequence, attribute order and sample size on uncertainty in each wave.

Ethics and dissemination
The independent review board at Includovate evaluated the application for ethical clearance and approved the study on 19 February 2025. To disseminate our findings, we will prepare multiple manuscripts for publication in peer-reviewed journals and present highlights at scientific meetings, such as the EuroQol Plenary Meeting and the International Academy of Health Preference Research.

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ProVag: the effect of oral probiotics on the vaginal microbiota composition in women receiving medical assisted reproduction in a Dutch fertility clinic – protocol of a randomised, placebo-controlled, double-blind study

Introduction
Differences in the profile of the vaginal microbiota (VMB) have been associated with pregnancy rates after medical assisted reproduction (MAR) such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Monitoring the VMB profile of IVF patients creates an opportunity to identify the best window for IVF treatment and embryo transfer. The ReceptIVFity test is a predictive test that assesses the chances of becoming pregnant in women undergoing IVF treatment based on the VMB composition. A VMB profile dominated by beneficial strains, most notably Lactobacillus species, is associated with increased pregnancy chances. However, to date, limited evidence is available on the effect of active modification strategies to facilitate the modulation of the VMB profile to help restore a VMB dominated by Lactobacillus species.

Methods and analysis
This is a randomised, placebo-controlled, double-blind intervention study. The study will involve 1:1 randomisation to one of the two arms: oral probiotic or placebo. Vaginal and rectal swabs will be collected at intake and 4, 6 and 8 weeks after the start of the treatment. Our objective is to determine if oral probiotic treatment improves the VMB profile of IVF patients from a low to a medium/high ReceptIVFity score, compared with placebo treatment. Secondary outcomes are: the potential of the bacterial strains in the oral probiotic to be detected in the vaginal tract and/or in the gut, and if the treatment leads to an increased ongoing pregnancy rate after IVF.

Ethics and dissemination
Ethical approval was obtained by the local medical ethical review committee at the Maastricht University Medical Centre. Findings from this study will be published in a peer-reviewed scientific journal and presented at one or more scientific conferences.

Trial registration number
CCMO NL81210.068.22, registered 25 September 2023.

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Randomised controlled trial comparing low doses of aspirin in the prevention of pre-eclampsia (ASAPP): a study protocol

Introduction
Pre-eclampsia (PEC) is a morbid and potentially lethal complication of pregnancy and is more common in women with risk factors such as hypertension, diabetes, autoimmune disease, kidney disease or multifetal pregnancies. Low dose aspirin (ASA) is currently the only prophylactic therapy known to decrease PEC in this patient population. However, currently, there is no prospective literature comparing various low-dose ASA formulations in the risk reduction of PEC. In the USA, the currently available low-dose ASA is over-the-counter and found in 81 mg tablets. Therefore, when clinicians initiate low-dose ASA therapy, they may prescribe one or two tablets of 81 mg per day without comparative evidence to guide their decision. Our objective is to prospectively compare pregnant patients on 81 mg vs 162 mg of ASA and determine a possible dose response in the prevention of PEC.

Methods and analysis
We designed a pragmatic phase 3 prospective randomised open label blinded-end point clinical trial with parallel assignment between two groups of pregnant people at high risk for PEC, as defined by the US Preventive Services Task Force and American College of Obstetricians and Gynecologists (ACOG). The primary outcome is the incidence of preterm (

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Developing a core outcome set for gender-affirming healthcare in transgender and gender diverse adults in Sweden using the Delphi approach: a study protocol

Introduction
Despite an increasing amount of research related to gender-affirming treatment (GAT) outcomes among transgender and gender-diverse (TGD) people (ie, people who experience discomfort or distress in the misalignment between their gender and sex assigned at birth) in recent years, the evidence base for current recommendations is suboptimal. One contributing factor is the heterogeneity in the outcomes and outcome measures used. This study seeks to address this challenge by developing a foundational core outcome set (COS) to be used for TGD adults receiving GAT in Sweden.

Methods
Recommendations from the Core Outcome Measures in Effectiveness Trials initiative will be used to address this aim in four phases. Phase 1, an umbrella review of peer-reviewed literature and international guidelines in GAT will be conducted to identify relevant outcomes. In phase 2, we will solicit input from TGD individuals through the review of patient and interest organisations’ reports and an anonymous survey to identify outcomes of personal significance. In phase 3, using the Delphi method, 2–3 rounds of assessment will be conducted where researchers, healthcare professionals, policy-makers and TGD adults rate the identified outcomes by perceived importance. In phase 4, a consensus meeting will convene representatives from all stakeholder groups to finalise the COS.

Analysis
The results of this study will consist of a COS for GAT regarding TGD adults in Sweden. Participant survey responses will be evaluated using interpretive analysis to identify core outcomes. During each of the Delphi rounds, Likert-type scale ratings will be aggregated for outcomes to advance or be eliminated in each round.

Ethics and dissemination
The study has received ethical approval by the Swedish Ethical Review Authority (Umeå medicine department, Registration number: 2024-04672-01). The results of this study will be published open-access and disseminated through TGD interest organisations and a Swedish research network for gender dysphoria.

Trial registration number
COMET registration number 3223.

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Investigating the relationship between Pfkelch13 mutations and response to artemisinin-based treatment for uncomplicated falciparum malaria: a protocol for a systematic review and individual patient data meta-analysis

Introduction
Artemisinin-based combination therapies (ACTs) remain the WHO-recommended treatment for uncomplicated Plasmodium falciparum malaria. However, the emergence and spread of artemisinin resistance (ART-R) threatens ACT efficacy. ART-R is phenotypically expressed as delayed parasite clearance, which can facilitate ACT partner drug resistance. ART-R has been causally linked to specific mutations in the Pfkelch13 gene.

Methods and analysis
The systematic review and associated meta-analysis aim to determine the correlation between Pfkelch13 (alleles present in the Kelch13 gene region of the P. falciparum parasite) genotypes and clinical and parasitological response to ACTs from a globally representative data set pooling individual patient data (IPD) from eligible published and unpublished studies. The eligibility criteria include Pfkelch13 genotyping results at baseline complemented by individually linked parasitological and clinical assessments following artemisinin-based treatment. The data will be curated, standardised and analysed using this proposed statistical analysis plan (SAP), adhering to PRISMA-IPD (PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Our SAP will apply hierarchical modelling to assess the effect of the P. falciparum parasite Pfkelch13 mutations on parasite clearance half-life and therapeutic efficacy across different regions. This will include study sites as random effects in the model and potential predictors such as age, sex, baseline parasite load and other potential effect modifiers as fixed effects. This analysis will enhance the understanding of the influence of Pfkelch13 mutations on malaria treatment outcomes.

Ethics and dissemination
Data were obtained with informed consent and ethical approvals from the relevant countries and were pseudonymised before curation in the Infectious Diseases Data Observatory (IDDO)/WorldWide Antimalarial Resistance Network (WWARN) repository. Data ownership remains with contributors. This IPD meta-analysis met the Oxford Tropical Research Ethics Committee criteria for waiving ethical review, as it is a secondary analysis of existing pseudonymised data. The resulting peer-reviewed publication and conference proceedings will help strengthen and enhance the efficiency of ART-R surveillance and response and support policy decisions.

PROSPERO registration number
CRD42019133366.

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Cutaneous non-volar melanoma dermoscopy and histopathology correlation: a systematic review protocol

Introduction
Dermoscopy has a proved validity in the diagnosis of cutaneous melanoma, which is one of the most aggressive forms of skin cancer. Although some studies have demonstrated a relationship between specific dermoscopic and pathologic melanoma features, there is no solid evidence allowing reliable conclusions. This study will evaluate the evidence regarding this association.

Methods and analysis
Observational studies eligible for our systematic review will enrol adults with histological cutaneous non-volar melanoma diagnosis and with dermoscopy image analysis. We will search the following databases: PubMed, Embase, Web of Science, MEDLINE and Cochrane Library. We will not impose any language or date restrictions. Outcomes of interest include the association of at least one of the melanoma dermoscopy features (irregular pigmentation, blue-white veil, atypical network, multicomponent pattern, atypical dots and/or globules, regression, peripheral tan structureless area, negative network, shiny white structures, atypical vessels and streaks/pseudopods), with melanoma Breslow index or other histopathology characteristics (melanoma subtype, mitotic index and presence of ulceration). Two reviewers will independently screen and search results, extract data from eligible studies and assess risk of bias. The evidence derived by this study will elucidate the possible link between melanoma dermoscopy and histopathology. If we could predict melanoma thickness based on dermoscopy, we would be able to anticipate melanoma treatment with impact on survival.

Ethics and dissemination
Ethical approval is not required because this is a literature-based study. It will be published in scientific Pubmed indexed open access journals to ensure its accessibility.

PROSPERO registration number
CRD42024564919.

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Community-based rehabilitation approach in older adult population: a scoping review protocol

Introduction
The global population of individuals aged 60 years and older is growing rapidly, presenting multiple complex challenges, including frailty, cognitive decline, functional impairments, multimorbidity and polypharmacy. Consequently, addressing the rehabilitation needs of this age group poses significant difficulties in today’s world. There is some evidence that community-based rehabilitation approaches can meet the unique rehabilitation needs of older individuals. Therefore, this scoping review aims to explore the application of community-based rehabilitation approaches for the older adult population.

Methods and analysis
This scoping review will follow the methodological framework outlined by Arksey and O’Malley. The search will be conducted using academic databases, including PubMed, ScienceDirect, Embase, CINAHL and Web of Science, with the search terms ‘community-based rehabilitation,’ ‘aged,’ ‘older,’ ‘elder’ and ‘geriatric’. Additionally, Google Scholar will be used to identify relevant literature. Publications in English from inception to January 2025 that explicitly address community-based rehabilitation programmes for older adults will be eligible. Inclusion criteria encompass studies reporting on CBR interventions, outcomes or implementation targeting older adults with disabilities or vulnerabilities, across diverse geographic and socioeconomic contexts. Both peer-reviewed articles and grey literature (eg, reports, guidelines, theses) will be considered. Studies focusing solely on clinical or institutional rehabilitation without community components will be excluded. The study selection process will occur in two stages, involving the participation of three reviewers. A data extraction form will be used to systematically extract data from all included studies.

Ethics and dissemination
This scoping review was approved by the Ethics Committee of the University of Social Welfare and Rehabilitation Sciences (Code:IR.USWR.REC.1404.034), and the results will be published in a peer-reviewed scientific journal.

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Development and preliminary evaluation in community mental health teams of a cervical screening informed-choice tool for women with severe mental illness in England: a mixed-method study

Objectives
Women with severe mental illness (SMI) face barriers to cervical cancer screening, leading to lower participation and poorer outcomes. This research aimed to develop and test an informed-choice tool to help women with SMI make informed decisions about screening attendance.

Design
The tool was developed using a realist review of physical health interventions and a systematic review of informed-choice tools for people with SMI. A mixed-methods approach informed its development. Usability and acceptability were assessed through semistructured interviews and the think-aloud method with service users (n=18), clinicians (n=16) and key informants. A preliminary proof-of-concept (n=25) evaluated the impact on decisional conflict—the uncertainty around making value-sensitive choices.

Setting and participants
Conducted in two National Health Service (NHS) Mental Health Trusts (urban and rural). Participants included women with SMI accessing secondary mental healthcare, clinicians and service user groups. A key informants’ group guided clinical content.

Intervention
A cervical screening informed-choice leaflet and an accompanying video.

Results
The tool was usable and acceptable, especially for women overdue or never screened. It may reduce decisional conflict and increase screening uptake, potentially improving survival. An National Institute for Health and Care Research (NIHR)-funded feasibility trial (Improving uptake of cervical screening in people with severe mental illness (OPTMISE)) is underway. The current UK government guidance on Support for people who find it hard to attend cervical screening due to having a mental health condition or having experienced trauma or abuse is based on this research.

Conclusions
Future research may involve further assessments of the real-world impact of the tool and its adaptation to other health-related decisions.

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[Articles] Treatment outcomes for patients with newly diagnosed or relapsed/refractory TP53-mutated mantle cell lymphoma: a systematic review and meta-analysis

Our findings indicate that TT may benefit patients with newly diagnosed TP53m MCL, and Allo-HSCT, CAR-T cell therapy, or TT could be considered for relapsed/refractory cases. However, -suboptimal long-term survival highlights the urgent need for innovative therapies. Key limitations, including small sample sizes and few randomised controlled trials (RCTs), emphasize the need for well-designed RCTs with adequate sample size in this field.

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