Nevin Manimala

Rheumatology (Oxford). 2025 May 21:keaf265. doi: 10.1093/rheumatology/keaf265. Online ahead of print.

ABSTRACT

OBJECTIVES: ANCA-associated vasculitis (AAV) is a group of systemic autoimmune diseases affecting small blood-vessels. Class-II HLA genes often reported as major genetic determinants. We conducted a systematic review and meta-analysis to evaluate the susceptibility conferred by HLA genes in AAV and five sub-types i.e. PR3+AAV, MPO+AAV, Granulomatosis with polyangiitis (GPA), Microscopic polyangiitis (MPA) and Eosinophilic granulomatosis with polyangiitis (EGPA).

METHODS: Relevant articles were retrieved until March 2024, from electronic databases using appropriate keywords. Eligible studies were included following inclusion-exclusion criteria. Funnel plots, Newcastle-Ottawa Scale and GRADE tools were used to evaluate the quality of evidence and research findings. Statistical analyses were performed by RevMan 5.4.1. The meta-odds ratio and Z test p-value were considered to check the HLA associations.

RESULTS: Meta-analysis of HLA-alleles identified 30 significant associations with AAV and its sub-types of which 17 withstood Bonferroni corrections. rs9277554-C from HLA-DPB1 (Meta-OR = 3.92(3.27-4.69)), rs1049072-A from HLA-DQB1 (Meta-OR = 1.39(1.27-1.52)) and rs9277341-C from HLA-DPA1 (Meta-OR = 0.41(0.03-0.57)) were significantly associated (p < 0.00001) with AAV and GPA respectively. DRB1*09:01 was significantly (p < 0.00001) predisposing allele in AAV (Meta-OR = 1.72(1.46-2.03)) and MPO+AAV (Meta-OR = 1.65(1.41-1.93)) and MPA (Meta-OR = 1.75(1.41-2.19)). Significant association (p ≤ 0.0005) was also observed for DPB1*01:01 (Meta-OR = 0.38(0.24-0.62)) and DRB1*11:01 (Meta-OR = 2.11(1.39-3.20)) for AAV and MPA respectively. Sensitivity analysis identified additional significant (p ≤ 0.001) predisposing alleles DPB1*04:01 and DPB1*02:01 in AAV and more than one sub-types.

CONCLUSION: Multiple alleles from HLA-DRB1 and DPB1 were found to provide predisposition to AAV and sub-types. Predisposition by DPB1*04:01 and protection by DPB1*02:01 were specific for AAV, PR3+AAV and GPA. Predisposition by DRB1*09:01 was observed among AAV, MPO+AAV and MPA.

PMID:40397991 | DOI:10.1093/rheumatology/keaf265

Rheumatology (Oxford). 2025 May 21:keaf272. doi: 10.1093/rheumatology/keaf272. Online ahead of print.

ABSTRACT

OBJECTIVES: The role of neutrophil extracellular traps (NETs) in immunoglobulin A vasculitis (IgAV) pathogenesis is emerging, with NETosis-associated markers potentially linked to disease activity. This study aimed to explore the relationship between NETosis biomarkers and IgAV disease phases.

METHODS: A longitudinal study involving 33 pediatric IgAV patients and 26 healthy controls was conducted. Blood and urine samples were collected from healthy controls and patients during active and inactive disease phases. NETosis markers, including cell-free DNA (cf-DNA), neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated histone H3 (cit-H3) were measured using ELISA kits. Statistical analyses were conducted to compare differences for NETosis markers between groups and to evaluate correlations among variables using appropriate statistical tests.

RESULTS: There was no significant difference in gender and age between the patient and control groups. The serum cf-DNA level was significantly higher in the active patient group compared with the control and inactive patient groups (p= 0.04; p= 0.04, respectively). In urine, MPO levels were significantly lower in the active phase of patients than controls (p= 0.009), while cit-H3 levels were higher in both active and inactive phases compared with controls (p= 0.01 and p= 0.03, respectively). A cf-DNA threshold of 935 ng/ml was identified, which achieved a sensitivity of 93% (correctly identifying 93% of active patients) and a specificity of 72% (correctly identifying 72% of healthy controls).

CONCLUSION: Elevated serum cf-DNA and urine cit-H3 suggest a potential role for NETosis in IgAV activity, highlighting these markers as potential indicators for disease monitoring. Further studies are warranted to establish standardized protocols for NETosis marker assessment in IgAV.

PMID:40397989 | DOI:10.1093/rheumatology/keaf272

J Clin Ethics. 2025 Summer;36(2):121-131. doi: 10.1086/734771.

ABSTRACT

AbstractContext: As advance directives (ADs) become more frequently utilized, opportunities increase for conflict between a patient’s designated healthcare power of attorney (POA) and the treatment preferences outlined in their living will (LW). Little is known about patient preferences regarding how to resolve these conflicts.

OBJECTIVES: To assess patient preferences regarding whether their POA or LW should have authority in times of conflict.

METHODS: In this mixed methods study, we completed a retrospective chart review to analyze patient selections in their AD, including selections in a novel section of the AD called the “Binding Guidance” section that gives patients the ability to designate whether their POA or LW should have authority when there is conflict between the two. Additionally, willing patient participants were asked two interview questions about their selections to further elucidate their perspectives.

RESULTS: Out of 143 patients, 48.3 percent (n = 69) chose to have their LW followed over their POA and 51.7 percent (n = 74) chose to have their POA followed over their LW. Several statistically significant associations were identified regarding binding guidance selections. Seventy-four (51.75%) of these patients also answered the additional interview questions, with the participants evenly distributed (n = 37 each) in their binding guidance selections.

CONCLUSION: Patients have varying preferences regarding whether their POA or LW should have authority in times of conflict. ADs should reflect this variation in preferences and allow patients the ability to designate whether they prefer their POA or LW to have ultimate authority when in conflict.

PMID:40397975 | DOI:10.1086/734771

PLoS One. 2025 May 21;20(5):e0324231. doi: 10.1371/journal.pone.0324231. eCollection 2025.

ABSTRACT

Rising global food insecurity driven by population growth needs urgent measure for universal access to food. This research employs Comparative Performance Analysis (CPA) to evaluate the Global Food Security Index (GFSI), its components [Affordability (AF), Availability (AV), Quality & Safety (Q&S) and Sustainability & Adaptation (S&A)] in tandem with Annual Population Change (APC) for world’s five most populous countries (India, China, USA, Indonesia and Pakistan) using dataset spanning from 2012 to 2022. CPA is applied using descriptive analysis, correlation analysis, Rule of Thumb (RoT) and testing of hypothesis etc. RoT is used with a new analytical approach by applying the significance measures for correlation coefficients. The study suggests that India should enhance its GFSI rank by addressing AF and mitigating the adverse effects of APC on GFSI with a particular focus on Q&S and S&A. China needs to reduce the impact of APC on GFSI by prioritizing AV and S&A. The USA is managing its GFSI well, but focused efforts are still required to reduce APC’s impact on Q&S and S&A. Indonesia should improve across all sectors with a particular focus on APC reduction and mitigating its adverse effects on AF, AV, and S&A. Pakistan should intensify efforts to boost its rank and enhance all sectors with reducing APC. There is statistically significant and negative relation between GFSI and APC for China, Indonesia and found insignificant for others countries. This study holds promise for providing crucial policy recommendations to enhance food security by tackling its underlying factors.

PMID:40397971 | DOI:10.1371/journal.pone.0324231

Chem Biodivers. 2025 May 21:e00561. doi: 10.1002/cbdv.202500561. Online ahead of print.

ABSTRACT

Teucrium montanum is an evergreen shrub that is widespread in Europe. The aim of this study was to determine the composition of the essential oils of T. montanum and their relationship to ecology, morphology and genetics. The essential oils were analysed by gas chromatography-mass spectrometry and the data were evaluated by multivariate statistics and multiple regression. This species showed a remarkable variability of essential oils in the Balkan Peninsula. All registered compounds were used to define four chemotypes that showed no spatial regularity and did not correlate with most bioclimatic parameters. The classification of samples into chemotypes and different categorical variables proved to be completely independent. Moreover, the identified compounds showed no correlation with the bioclimatic parameters, including other categorical variables. To study such a complex phenomenon as the variation of essential oils of T. montanum, a different sampling approach must be adopted (e.g., ‘one individual, one sample’), but this could affect the viability of the population of this species.

PMID:40397960 | DOI:10.1002/cbdv.202500561

PLoS One. 2025 May 21;20(5):e0324497. doi: 10.1371/journal.pone.0324497. eCollection 2025.

ABSTRACT

This paper presents a novel longitudinal study examining interactions in healthcare expenditure (HCE). Utilizing fuzzy-set qualitative comparative analysis (fsQCA), the study constructs a consumption-provision-finance model to investigate factors influencing HCE. Data from the Organization for Economic Cooperation and Development (OECD) database for the years 2010-2022 are analyzed, covering 37 OECD countries (excluding Luxembourg due to insufficient data). By treating each country-year OECD observation as a case, causal recipes are identified and interpreted. The characteristics of the panel data set are examined by assessing the stability of causal patterns over multiple years and exploring the consistency of these patterns within individual countries across various years. The findings of this study offer significant insights for policy management and future research, particularly in relation to the diverse annual relationships observed between factors and HCE in different countries. Additionally, comparisons are drawn between panel fsQCA and cross-sectional fsQCA conducted for specific years.

PMID:40397958 | DOI:10.1371/journal.pone.0324497

PLoS One. 2025 May 21;20(5):e0323815. doi: 10.1371/journal.pone.0323815. eCollection 2025.

ABSTRACT

The COVID-19 pandemic highlighted the crucial role of vaccines in controlling the virus. Despite their effectiveness, however, vaccine hesitancy remained a challenge, particularly within certain population groups. This multi-disciplinary study investigates the diverse socio-demographic factors influencing COVID-19 vaccination decisions in the United States. Through a nationally representative survey of 5,240 people, the research explores the interplay of information sources, religious beliefs, political party, and demographic characteristics of the respondents. Our findings reveal associations of main sources of information with vaccination likelihood, with the Centers for Disease Control and Prevention demonstrating the highest association with full vaccination. Religious beliefs are significant determinants, with Evangelical Protestants exhibiting the lowest vaccination rates. We also highlight the intricate relationship between political leanings and vaccination behavior, emphasizing higher levels of vaccination among Democrats. Demographic variables, including age, education, gender, and race/ethnicity, also play pivotal roles, exposing disparities in vaccination access and decisions. In particular, older individuals and those with higher levels of education show a greater inclination to achieve full vaccination, while women and African Americans are less likely to attain complete vaccination. Lastly, while major ethnoracial groups seem to respond to different sources of information similarly, there are also nuanced differences, such as Asians being especially likely to be fully vaccinated if they depend on the CDC or other health sources while more disadvantaged groups seem less responsive to these sources. Overall, this research provides a comprehensive analysis of the nuanced factors shaping vaccination behavior. It contributes valuable knowledge to public health strategies, emphasizing the need for targeted communication campaigns tailored to diverse communities.

PMID:40397952 | DOI:10.1371/journal.pone.0323815

JMIR Res Protoc. 2025 May 21;14:e63627. doi: 10.2196/63627.

ABSTRACT

BACKGROUND: Hearing loss is a common late effect in childhood cancer survivors, caused by ototoxic cancer treatments, such as platinum chemotherapy, cranial radiation with doses of ≥30 Gray, and surgery involving the auditory system. Early recognition of hearing loss as part of follow-up care allows for therapeutic support to mitigate consequences. However, hearing tests are usually only repeated in childhood cancer survivors with abnormal hearing during or right after treatment ends, leaving hearing loss undetected in childhood cancer survivors with late onset or when missed during cancer treatment. Further, general follow-up care attendance may be low after childhood cancer survivors transition to adult care, contributing to missing hearing screening posttherapy. Low attendance may be attributed to childhood cancer survivors finding follow-up care burdensome and time-consuming, lacking awareness of their risk for certain late effects, or the absence of suitable interdisciplinary follow-up clinics. A low-threshold, easily accessible screening program requiring minimal participant effort may address these barriers and improve access to hearing loss screening for childhood cancer survivors.

OBJECTIVE: The HEAR study aims to develop, conduct, and evaluate the feasibility of a low-threshold, community-based screening program for hearing loss in childhood cancer survivors, using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, a tool to plan and evaluate health interventions. Within the screening program, participating childhood cancer survivors completed a standardized hearing assessment at a local Swiss hearing aid provider’s shop. This approach provides low-threshold access to detect hearing loss as it is easily and conveniently accessible for everyone.

METHODS: Eligible childhood cancer survivors were identified through the Childhood Cancer Registry Switzerland and included those diagnosed with cancer between 1976 and 2019 before 21 years and who were ≥2 years post diagnosis. We invited eligible childhood cancer survivors by post. Participants scheduled a hearing test appointment at a hearing aid shop. They completed a baseline questionnaire before the hearing test, and 2 follow-up questionnaires afterward to assess program feasibility and participant experiences. Semistructured interviews with participants, hearing aid shop staff, and group discussions with health care professionals will provide qualitative insights. The RE-AIM framework will guide the program evaluation using the quantitative and qualitative data collected.

RESULTS: As of February 2025, all participants have been recruited, and all steps of the study up to the group discussions and the RE-AIM evaluation have been completed.

CONCLUSIONS: The HEAR study introduces a novel, simple, and low-threshold approach to screening for hearing loss after cancer treatment through hearing aid shops located in the community and close to participants’ homes. This approach has the potential to supplement existing follow-up care programs by reducing the burden of hearing screening for adult childhood cancer survivors and reaching those who might otherwise be lost to follow-up.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06036407; https://clinicaltrials.gov/study/NCT06036407.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63627.

PMID:40397950 | DOI:10.2196/63627

JMIR Aging. 2025 May 21;8:e70302. doi: 10.2196/70302.

ABSTRACT

BACKGROUND: Cyberchondria is the compulsive searching for health information online that continues despite harmful effects. It leads to increased health anxiety and lower health-related quality of life (HRQOL). Older adults face higher risks of cyberchondria due to their limited digital literacy skills and more frequent health concerns. However, researchers have not thoroughly studied how cyberchondria affects this age group.

OBJECTIVE: This study aimed to explore cyberchondria in the older population and investigate its relationship with cognitive fusion (ie, the tendency to become entangled with thoughts and perceive them as literal truths that dictate behavior), HRQOL, and mental well-being.

METHODS: A web-based, cross-sectional survey was conducted in May 2024 with a sample of 638 participants from China aged ≥60 years recruited through the online panel of a survey company. The participants completed questionnaires assessing cyberchondria (using the Cyberchondria Severity Scale-12 [CSS-12]), cognitive fusion, HRQOL, and mental well-being. Structural equation modeling (SEM) was used to assess the hypothesized mediation model, and standardized estimates and their 95% CIs were calculated for all structural paths.

RESULTS: Participants had a mean CSS-12 score of 40 (SD 8.5), suggesting a fairly high level of cyberchondria in this sample. Participants with a higher socioeconomic status tended to report lower levels of cyberchondria. The SEM showed that cyberchondria was positively associated with cognitive fusion (β=0.505, P<.001 for both models) and negatively associated with HRQOL (β=-0.221, P<.001) and mental well-being (β=-0.212, P<.001). The mediation model showed a good fit and demonstrated that cognitive fusion fully mediated the total effect of cyberchondria on HRQOL and mental well-being.

CONCLUSIONS: Cyberchondria may be more prominent in older Chinese adults, especially those residing in rural areas and with a lower socioeconomic status. Additionally, cyberchondria can enhance cognitive fusion, contributing to poor HRQOL and mental well-being. Interventions focused on “defusing” cyberchondria-relevant thoughts may help reduce maladaptive behaviors associated with cyberchondria and improve the overall well-being of older populations.

PMID:40397949 | DOI:10.2196/70302

JMIR Serious Games. 2025 May 21;13:e65878. doi: 10.2196/65878.

ABSTRACT

BACKGROUND: Exergame-based training enhances physical and cognitive performance in older adults, including those with mild neurocognitive disorder (mNCD). In-game metrics generated from user interactions with exergames enable individualized adjustments. However, there is a need to systematically investigate how well such game metrics capture true cognitive and motor-cognitive performance to provide a more robust basis for personalized training.

OBJECTIVE: The primary objective was to identify valid game metrics as indicators for in-game domain-specific cognitive performance during exergaming in individuals with mNCD. We also aimed to explore game metric performance changes over time during exergame-based training.

METHODS: Data were analyzed from individuals with mNCD who completed a 12-week home-based, exergame-based intervention following the Brain-IT training concept. A cross-sectional analysis was conducted by correlating game metrics with standardized neurocognitive reference assessments. To confirm the alternative hypothesis, we predetermined the following criteria: (1) statistically significant correlation (P≤.05; uncorrected; 1-sided) with (2) a correlation coefficient (Pearson r or Spearman ρ) of ≥0.4. Visual and curve-fitting longitudinal analyses were conducted to explore game performance changes over time.

RESULTS: Data were available from 31 participants (mean age 76.4, SD 7.5 y; n=9, 29% female). In total, 33% (6/18) of the game metrics were identified as valid indicators for in-game cognitive performance during exergaming. In the neurocognitive domain of learning and memory, these metrics included the mean reaction time (ρ=-0.747), the number of collected items (ρ=0.691), and the precision score (r=-0.607) for the game Shopping Tour (P<.001 in all cases), as well as the point rate (P=.008; r=0.471) for the game Simon. In addition, point rate was a valid indicator for executive function (P=.006; r=0.455) and visuospatial skills (P=.02; r=0.474) for the games Targets and Gears, respectively. The exploratory longitudinal analysis revealed high interindividual variability, with a general trend of the expected typical curvilinear curves of rapid initial improvements followed by a plateau in performance.

CONCLUSIONS: This study demonstrated that metrics reflecting the precision of responses generally performed better than metrics reflecting the speed of responses. These observations highlight the importance of selecting valid game metrics for implementation in exergame designs. Further research is needed to explore the potential of game metrics and identify factors contributing to individual variability in in-game performance and performance progression, as well as identifying and adopting strategies that facilitate individual learning success and thus promote effectiveness in improving health outcomes.

PMID:40397948 | DOI:10.2196/65878