Gender and age disparities in cardiac immune-related adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FAERS database

Objectives
The cardiotoxicity of immune checkpoint inhibitors (ICIs) has garnered significant clinical attention due to its high mortality rate. However, limited clinical research and inconsistent results have hindered a comprehensive understanding of this issue. This study seeks to elucidate gender and age differences in cardiac-related adverse reactions, aiming to offer scientific evidence to inform clinical practice.

Design
A retrospective pharmacovigilance study.

Setting
Based on the reports of ICIs in the FDA Adverse Event Reporting System database from 2003–2023, we conducted a disproportionality analysis to identify cardiac immune-related adverse events (irAEs) and explored the correlation of age and gender with these adverse events.

Main outcome measures
The main cardiac irAEs were defined by four preferred terms: myocarditis, atrial fibrillation, cardiac failure and pericardial effusion. Both the proportional reporting ratio (PRR) and reporting odds ratio (ROR) are frequency methods. Data mining was performed using the PRR method, which assesses the relative risk of adverse drug reactions by comparing the frequency of reports associating a specific drug with a particular adverse reaction to the frequency of reports linking any drug to the same reaction. A higher PRR indicates a more robust adverse event signal, suggesting a stronger statistical association between the drug of interest and the target adverse event. In the research process, we primarily used the ROR and PRR from disproportionality analysis to screen for cardiac irAEs, while also elucidating the correlation between these reactions and factors such as age and gender.

Results
A total of 2033 adverse events were retrieved, and myocarditis was the most common cardiac irAEs. Gender disparities exist in the incidence of various adverse reactions to the same medication. Female patients need to be particularly vigilant for cardiac adverse events when taking atezolizumab, and male patients should be especially cautious for cardiac adverse events when using ipilimumab. Furthermore, ipilimumab produced a positive signal for pericardial effusion in the elderly group but not in the younger group, suggesting that elderly patients may be more susceptible to adverse reactions. Therefore, increased vigilance and careful monitoring are warranted during clinical administration of this medication to elderly patients.

Conclusion
Our study highlights the gender and age differences in cardiac adverse events with ICIs, providing valuable insights for clinical application.

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[Articles] Long-term outcome in Wiskott-Aldrich syndrome and X-linked thrombocytopenia patients: an observational -prospective multi-center study of the Italian Primary Immune Deficiency Network (IPINET)

The evidence of the heterogeneity of WAS and XLT outcomes could be instrumental to draw updated recommendations for the management of the patients affected by these rare conditions. It would be desirable to expand the tools to estimate the risk of infectious and autoimmune events in patients with XLT and the impact of their treatment, including HSCT over time.

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Access to mental healthcare for refugees, asylum seekers and migrants: an umbrella review of barriers

Objective
To identify the factors that prevent or hinder access to mental healthcare services for refugees, asylum seekers and migrants.

Design
An umbrella review was conducted on scoping reviews, systematic reviews, meta-analyses and meta-syntheses published between January 2013 and December 2023.

Data sources
The databases searched (on 11 December 2023) included PubMed (via NCBI, including MEDLINE), Embase (via Embase.com), Web of Science Core Collection, Scopus and the Cochrane Database of Systematic Reviews (via Cochrane Library). Search strings were categorised as concepts, wherein concept one was population (refugees, asylum seekers and migrants), concept two was mental health services and concept three was the type of review (systematic review, meta-analysis, scoping review or literature review).

Eligibility criteria for selecting studies
Reviews were included if study participants were refugees, asylum seekers and migrants. Additionally, mental health-providing services or organisations and mental health providers were included. Excluded study participants were people with a migration background and second- or third-generation migrants.

Data extraction and synthesis
Two independent reviewers screened the identified articles on title and abstract. The 48 full-text articles were assessed in detail against inclusion and exclusion criteria by the two researchers and one person from the Belgian Superior Health Council.

Results
18 reviews were included. The extensive literature review identified various factors that prevent and restrict access to mental healthcare services for individuals with a recent migration background. Among the eight concepts of barriers, the most frequently mentioned were stigma and stigmatisation, language and communication challenges, financial obstacles, cultural barriers (including religious beliefs and faith) and issues with service delivery. Additionally, differences in culture, education and gender were recognised as factors limiting access to mental health services. Recommendations for policy and practice included implementing a multidisciplinary and multi-agency approach to facilitate access for newly arriving migrants and refugees, increasing financial allocations for translation and interpretation services, enabling policies to promote mental health utilisation and introducing educational programmes at the grassroot level among migrants and refugees.

Conclusion
Policy implementation should address the identified barriers and be routinely assessed for efficacy in service delivery and uptake. Future research should focus on enabling the utilisation of mental healthcare services among migrants, asylum seekers, and refugees.

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Unleashing the potential of exosome ncRNAs for early gastric cancer detection–a critical appraisal of machine learning approaches

We read with great interest the article by Cai et al,1 titled ‘Construction of exosome non-coding RNA feature for non-invasive, early detection of gastric cancer patients by machine learning: a multi-cohort study’, published in Gut. The study presents a novel approach for the early detection of gastric cancer (GC) using serum exosome non-coding RNAs (ncRNAs) and machine learning, which is a significant step forward in the field of liquid biopsy for cancer diagnostics. The study by Cai et al has several notable strengths. First, the comprehensive multi-cohort design, including both training and external validation cohorts, provides robust evidence for the diagnostic potential of the identified exosome ncRNA feature. The use of machine learning algorithms, particularly LASSO-logistic regression, to develop the combined diagnostic model (cd-score) is innovative and demonstrates high diagnostic accuracy with an area under the curve of 0.959 in the training cohort and 0.949 in the…

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Prevalence and factors influencing fear of disease progression in stroke patients: a systematic review and meta-analysis with a focus on China

Objectives
To systematically estimate the prevalence and influencing factors of fear of disease progression (FoP) in patients who had a stroke, with a focus on China.

Design
Systematic review and meta-analysis of observational clinical studies.

Data sources
Eight databases (China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database (VIP), CBM, Web of Science, PubMed, Cochrane Library, Embase) were searched from inception to March 2024, supplemented by manual reference screening.

Eligibility criteria
Cross-sectional studies reporting FoP incidence or influencing factors in Chinese stroke patients using the Fear of Progression Questionnaire-Short Form scale were included.

Data extraction and synthesis
Two reviewers independently screened studies, extracted data and assessed study quality using the Agency for Healthcare Research and Quality tool (score range: 0–11 points). Random-effects models were applied to address substantial heterogeneity. Stata 17.0 software was used for meta-analysis.

Results
A total of 20 studies (15 medium-quality, 5 high-quality) involving 7156 patients were included. The pooled incidence of FoP in Chinese stroke patients was 56% (95% CI=45% to 66%), derived from a random-effects model despite significant between-study heterogeneity (I²= 98.7%), with subgroup analyses and leave-one-out sensitivity analysis confirming result robustness. Subgroup analysis revealed that the incidence was highest in East China (70%, 95% CI=56% to 83%), followed by Central China (55%, 95% CI=36% to 73%) and North China (43%, 95% CI=38% to 47%). The incidence of FoP in haemorrhagic stroke (72%, 95% CI=49% to 95%) was higher than that in ischaemic stroke (45%, 95% CI=27% to 64%). The incidence of FoP after 2020 (59%, 95% CI=48% to 70%) was higher than that before 2020 (40%, 95% CI=32% to 47%). Meta-regression identified publication year (p=0.004) and research region (p=0.001) as key heterogeneity sources. The main influencing factors of FoP in Chinese stroke patients included age (OR=0.94, 95% CI=0.92 to 0.97, p

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Global, regional and national burden of infections among pregnant women, 1990-2021: a prospective cohort study

Objectives
We aimed to analyse the trends, age distribution and disease burden of maternal sepsis and other maternal infections (MSMI) to improve management strategies.

Design
We extracted data from the global burden of disease (GBD) 2021 database to evaluate MSMI burden with different measures for the whole world, 21 GBD regions and 204 countries from 1990 to 2021.

Setting
Studies from the GBD 2021 database generated by population-representative data sources identified through a literature review and research collaborations were included.

Participants
Patients with an MSMI diagnosis.

Outcomes
Total numbers, age-standardised rates (ASRs) of incidence, prevalence, mortality and disability-adjusted life years (DALYs) on MSMI from the GBD 2021 study and their estimated annual percentage changes (EAPCs) were the primary outcomes.

Results
There were 19 047 404 (95% uncertainty interval (UI) 14 608 563 to 24 086 486) annual incident cases, 2 376 876 (95% UI 1 678 868 to 3 421 377) prevalent cases at a single time point, 17 665 (95% UI 14 628 to 21 191) death cases and 1 144 233 (95% UI 956 988 to 1 352 034) DALYs of total MSMI in 2021. From 1990, the case number and ASRs of incidences and prevalence showed decreasing trends, while the case number and ASRs of mortality and DALYs gradually increased with time, reaching the peak in 2001, and then declined. In 2021, the ASRs of incidence, prevalence, mortality and DALYs sharply increased with age, which reached the peak in the 20–24 age group. The ASRs were decreased with increasing sociodemographic index (SDI). In 2021, it showed a positive correlation between EAPC and ASR of DALYs (r=0.3398, p

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Experiences of stigma and access to care among long COVID patients: a qualitative study in a multi-ethnic population in the Netherlands

Objective
This study explored the experience of stigma and access to healthcare by persons with long COVID from the majority Dutch and two ethnic minority populations (Turkish and Moroccan) living in the Netherlands.

Design
This was a cross-sectional qualitative study that employed inductive and deductive thematic approaches to data analysis using MAXQDA.

Setting and participants
Between October 2022 and January 2023, 23 semi-structured interviews were conducted with participants of Dutch, Moroccan and Turkish ethnic origins with long COVID living in the Netherlands. Participants were men and women aged 30 years and above.

Results
Guided by the concepts of stigma and candidacy, the findings are structured according to the broader themes of stigma and access to care. The findings show that people with long COVID suffer self and public stigma resulting from the debilitating illness and symptoms. Especially among Turkish and Moroccan ethnic minority participants, strong filial obligations and gendered expectations of responsibility and support within their communities further worsen self-stigma. This experience of stigma persisted within healthcare where lack of information and appropriate care pathways led to feelings of frustration and abandonment, especially for participants with pre-existing health conditions which further complicate candidacy. Under the access to healthcare theme, the findings show multiple challenges in accessing healthcare for long COVID due to several multifaceted factors related to the various stages of candidacy which impacted access to care. Particularly for Turkish and Moroccan ethnic minority participants, additional challenges resulting from limited access to information, pre-existing structural challenges and experience of stereotyping based on ethnicity or assumed migrant identity by health professionals further complicate access to health information and long COVID care.

Conclusions
The findings call for urgent attention and research to identify and coordinate healthcare for long COVID. There is also a need for accessible, informative and tailored support systems to facilitate patients’ access to information and care pathways for long COVID. Providing tailored information and support, addressing the various barriers that hinder optimal operating conditions in healthcare and leveraging on social networks is crucial for addressing stigma and facilitating candidacy for persons with long COVID towards improving access to care.

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Association between medical comorbidities at diagnosis and paediatric acute lymphoblastic leukaemia and lymphoblastic lymphoma outcomes: protocol for a systematic review

Introduction
Medical comorbidity at diagnosis is associated with treatment outcome in cancer. The aim of this project is to synthesise the evidence on the association between medical comorbidities and paediatric acute lymphoblastic leukaemia and lymphoblastic lymphoma outcomes.

Methods and analysis
A systematic review of the literature will be conducted by developing a search strategy that will combine medical subject headings and natural language key words related to acute lymphoblastic leukaemia or lymphoma, medical comorbidities and treatment-related outcomes. We will search MEDLINE and EMBASE to identify studies in human subjects and written in English from the inception of each database to 30 September 2022. Two authors will independently screen the titles and abstracts of retrieved studies based on the inclusion and exclusion criteria to identify potentially eligible studies. Full-text articles of eligible studies and final included articles will be retrieved and reviewed in a similar manner by two independent reviewers. Data extraction from included articles will be conducted independently by two authors using a standardised data extraction form. Risk of bias in the included studies will be assessed using existing relevant tools. A narrative and tabular summary of the data, including outcomes, will be provided if the data do not warrant a meta-analysis. If a meta-analysis is feasible, we will pool all the effect estimates. Heterogeneity among study effect sizes will be tested with Cochran’s Q test and quantified by the I2 statistic.

Ethics and dissemination
This study will not include the collection of original data, but it will be a summary of aggregate existing data. Thus, ethics approval is not applicable. The findings of the study will be disseminated through peer-reviewed publications.

PROSPERO registration number
CRD42022366669.

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