Tag: pubmed

Health Technol Assess. 2026 Jan;30(2):1-28. doi: 10.3310/AAVV3131.

ABSTRACT

BACKGROUND: For women with chronic or gestational hypertension who remain well, early term birth (at 37-38 weeks’ gestation) may reduce maternal complications, caesareans and stillbirths, but it may increase neonatal morbidity compared with expectant care. Expectant care may increase costs. There are no high-quality data to guide care, which currently involves maternal-fetal surveillance and intervention for maternal or fetal compromise, which may be rapid or unexpected.

OBJECTIVE: To investigate optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well.

DESIGN: Pragmatic, unmasked, multicentre randomised trial with a health economic analysis.

SETTING: Fifty United Kingdom hospitals.

PARTICIPANTS: Inclusion: maternal age ≥ 16 years, chronic or gestational hypertension, singleton pregnancy, live fetus, 36⁺⁰-37⁺⁶ weeks’ gestation and able to give documented informed consent. Exclusion: contraindication to either trial arm (e.g. pre-eclampsia), blood pressure ≥ 160/110 mmHg until controlled, major fetal anomaly anticipated to require neonatal care unit admission or participation in another timed birth trial.

INTERVENTIONS: Planned early term birth at 38^+0-3 weeks’ (intervention) or ‘usual care at term’ (control, revised from ‘expectant care until at least 40⁺⁰ weeks’, August 2022).

MAIN OUTCOME MEASURES: Maternal coprimary: composite of ‘poor maternal outcome’ (severe hypertension, maternal death or maternal morbidity and superiority hypothesis). Neonatal coprimary: neonatal care unit admission ≥ 4 hours (non-inferiority hypothesis). Each coprimary is measured until primary hospital discharge or 28 days post birth (whichever is earlier). Key secondary: caesarean birth.

RANDOMISATION: 1 : 1 ratio, minimised for key prognostic variables: site, hypertension type and prior caesarean.

BLINDING: It was not possible to mask care providers or participants to the intervention. For the coprimary maternal outcome, there was local site principal investigator/delegate sign-off based on review, masked to allocated group, of primary case notes.

RESULTS: From 2019 to 2022, 403 participants were randomised (37% of target 1080) to intervention (n = 201) or control (n = 202). The funder stopped the trial during the coronavirus disease discovered in 2019 pandemic for delayed recruitment. In the intervention (vs. control) group, birth was a median of 0.9 weeks earlier (38.4, interquartile range 38.3-38.6 vs. 39.3, interquartile range 38.7-39.9 weeks). There was no evidence of a difference in ‘poor maternal outcome’ (13% vs. 12%, respectively; adjusted risk ratio 1.16, 95% confidence interval 0.72 to 1.87). For ‘neonatal care unit admission ≥ 4 hours’, the intervention was considered to be non-inferior to control, as the adjusted risk difference, 95% confidence interval upper bound did not cross the 8% pre-specified non-inferiority margin (7% vs. 7%, respectively; adjusted risk difference 0.003, 95% confidence interval -0.05 to +0.06), although event rates were lower than estimated. There was no evidence of a difference in caesarean (29% vs. 36%, respectively; adjusted risk ratio 0.81, 95% confidence interval 0.61 to 1.08).

LIMITATIONS: Recruitment was 37% of the anticipated sample size (as above).

CONCLUSIONS: Despite being unable to recruit to target in this study, we observed that most women with chronic or gestational hypertension required labour induction and planned birth at 38^0-3 weeks (vs. usual care), which resulted in birth an average of 6 days earlier and there were no differences in poor maternal outcome or neonatal morbidity. Our findings provide reassurance about planned birth at 38^0-3 weeks as a clinical option for these women.

FUTURE WORK: An individual participant data meta-analysis is planned to address whether the intervention (vs. control) reduces caesarean; low adverse event rates would make unfeasible mounting another randomised trial.

FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/167/123.

PMID:41556143 | DOI:10.3310/AAVV3131

Am J Med Genet A. 2026 Jan 20. doi: 10.1002/ajmga.70041. Online ahead of print.

ABSTRACT

Genetic conditions suspected in children often require genetic testing for accurate diagnoses, but testing remains costly. Case management teams review genetic test requests to improve access for patients while reducing the financial burden for medical institutions. Limited data exist on the diagnostic yields of genetic testing in the inpatient versus outpatient setting and the impact to care denial of inpatient genetic testing may pose. This study investigates diagnostic yields between patients approved for versus denied inpatient genetic testing and its impact to care. One thousand and fifty-two charts of children admitted inpatient who received a genetic consult between July 2018 and June 2023 were reviewed; charts of children that followed up at the outpatient genetics clinic after inpatient discharge were additionally reviewed. Collected data included recommendations, completion, and results of genetic testing, and management recommendations based on a diagnosis. Statistical analysis assessed differences between the groups. Private insurance holders and patients with no prematurity history were less likely to be approved for inpatient genetic testing. The outpatient group had nearly twice the diagnostic yield and management recommendations did not differ between the groups. Inclusion of genetic providers in the review of inpatient genetic testing requests should be considered to improve outcomes.

PMID:41556137 | DOI:10.1002/ajmga.70041

J Antimicrob Chemother. 2026 Jan 19;81(2):dkag002. doi: 10.1093/jac/dkag002.

ABSTRACT

BACKGROUND: Gender shapes health behaviours, access, and outcomes, thereby influencing antibiotic use. Intersecting socio-economic factors, such as education, labour force participation, and political representation, further mediate gender differences in the risk of antimicrobial resistance (AMR). However, evidence linking gender inequalities to antibiotic consumption remains limited.

METHODS: This study is an observational, country-level analysis using IQVIA MIDAS® data on yearly antibiotic consumption (defined daily doses/DDDs) from 70 countries (2000-22). We used four gender equality indicators: proportion of females with secondary or higher education, female-to-male labour force participation (FMLFP) ratio, proportion of women in parliament, and share of female population. Using country and year fixed-effects regression models, the study estimated within-country associations between these indicators and overall antibiotic consumption, as well as by antibiotic class, controlling for income, education, healthcare access, and health spending, and demographics. Sensitivity was assessed through an alternative model specification, stratified analyses by income groups and by time periods.

RESULTS: Antibiotic consumption varied widely across countries with an average of 19.13 DDDs per day per 1000 population. Our main findings are that higher female education (P < 0.05) and FMLFP ratio (P < 0.01) were significantly associated with lower antibiotic consumption, while a higher share of females in the population was significantly associated with slightly higher consumption (P < 0.01). Women’s parliamentary representation showed no significant association. These associations remained directionally consistent across alternative model specifications and income groups.

CONCLUSIONS: Gender inequalities influence antibiotic consumption patterns. The study underscores the need for a community-based approach in tackling AMR, specifically, investments in gender-responsive AMR strategies.

PMID:41556127 | DOI:10.1093/jac/dkag002

Eur J Anaesthesiol. 2026 Jan 20. doi: 10.1097/EJA.0000000000002355. Online ahead of print.

ABSTRACT

Research that assesses causal relations based on observational data remains challenging because of the well known tension between natural causal thinking and classic statistical association methods. This tension, over a period of decades, has generated the development of a statistical framework, with specific methods and reasoning, to allow the drawing of causal inference. A part of this framework is the directed acyclic graph (DAG), a specific type of causal diagram that is based on graph theory. This intuitive representation of the mechanistic processes of a specific problem, and the logical consequences that come with it, closes the gap between observed associations and causality. The advantage of integrating DAGs into observational research has been emphasised in several reviews. This review is an anaesthetist-friendly (re-)introduction to this graphical reasoning. We provide some examples of how this framework can be used beyond observational data and studies. We explain how important aspects of randomised controlled trials like covariate adjustments, handling of missing data and protocol violations can be both understood and taught by drawing and interpreting a DAG. We consider the case of the titration paradox and show how combining knowledge of how a specific dataset was built, with pharmacology, into a more advanced DAG, can help solve and understand these seemingly paradoxical findings. In all of this, we use anaesthesia-oriented examples to illustrate how DAGs can be a valuable scientific language that helps us to understand, organise and communicate study results and research questions.

PMID:41556118 | DOI:10.1097/EJA.0000000000002355

Psychol Med. 2026 Jan 20;56:e26. doi: 10.1017/S0033291725103139.

ABSTRACT

BACKGROUND: Parental prenatal mood and anxiety disorders (PMADs) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors.

METHODS: A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to September 2025. Of 2,420 articles screened, 74 met the inclusion criteria. Meta-analyses were conducted on 21 studies, and 53 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I²) and publication bias (Egger’s test). The review followed PRISMA and MOOSE guidelines.

RESULTS: Maternal PMADs were associated with a significantly increased risk of attention-deficit/hyperactivity disorder (ADHD; odds ratio [OR] 1.91, 95% confidence interval [CI] 1.45-2.52) and autism spectrum disorder (ASD; OR 1.75, 95% CI 1.43-2.14) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR = 1.23, 95% CI 1.14-1.33). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior.

CONCLUSIONS: Parental PMADs are associated with increased risk of NDDs in children. These findings likely reflect a combination of inherited liability and environmental processes; clarifying mechanisms will require genetically informed designs. Regardless of mechanism, offering optional, family-centered developmental support may help promote child well-being in families where a parent is experiencing PMADs.

PMID:41556101 | DOI:10.1017/S0033291725103139

Biomed Khim. 2025 Dec;71(6):441-453. doi: 10.18097/PBMCR1599.

ABSTRACT

Sepsis-associated encephalopathy (SAE) is a condition characterized by acute brain dysfunction developed in the absence of a primary infection in the central nervous system. The aim of this study was to perform a pilot, untargeted metabolomic profiling of the blood plasma of SAE patients to identify metabolic changes potentially associated with the pathological condition and to generate hypotheses for further studies of its pathogenesis, as well as to the search for promising biomarkers, and the assessment of the severity of the patient’s condition. Metabolomic profiling was performed using HPLC-HR-MS, followed by statistical analysis of the obtained data. This blinded, randomized, controlled clinical trial revealed significant differences in the metabolic profiles of the study and control groups. Functional analysis showed the metabolic pathways most affected by pathological processes in SAE patients. These included metabolism of acylcarnitines, lysophosphatidylcholines, and taurine, folate biosynthesis, and the drug metabolism involving the cytochrome P450 pathway. In SAE patients with impaired consciousness, including delirium and coma, decreased levels of long-chain acylcarnitines and lysophosphatidylcholines were observed. The metabolomic profiles of SAE patients differed significantly between the groups of deceased and surviving patients: concentrations of sulfur-containing amino acids were significantly lower in the group of deceased than in the group of survivors. Our study identified 64 candidate biomarkers that could potentially be used to predict sepsis outcomes. However, further study is needed using an expanded and independent cohort of patients.

PMID:41556075 | DOI:10.18097/PBMCR1599

Biomed Eng Comput Biol. 2026 Jan 17;17:11795972251407864. doi: 10.1177/11795972251407864. eCollection 2026.

ABSTRACT

BACKGROUND: Explainability (xAI) is critical for fostering trust, ensuring safety, and supporting regulatory compliance in healthcare AI systems. Large Language Models (LLMs), with impressive capabilities, operate as “black boxes” with prohibitive computational demands and regulatory challenges. Small Language Models (SLMs) with open-source architectures present a pragmatic alternative, offering efficiency, potential interpretability, and alignment with data privacy frameworks. This study evaluates whether token-level attribution (TLA) methods can provide technical traceability in SLMs for clinical decision support.

METHODS: The Captum 0.7 attribution library was applied to a Qwen-2.5-1.5B model on 20 breast cancer cases from a publicly available dataset. Hardware requirements were profiled on consumer-grade GPU. Using perturbation-based integrated gradients, we analyzed how clinical input features statistically influenced token generation probabilities.

RESULTS: Attribution heatmaps successfully identified clinically relevant input features, with high-attribution tokens corresponding to expected clinical factors. The model occupied minimal storage, enabling local deployment without cloud infrastructure. This validates that SLMs can provide algorithmic traceability required for regulatory frameworks.

CONCLUSIONS: This proof-of-concept demonstrates the technical feasibility of combining SLMs with perturbation-based xAI methods to achieve auditable clinical AI within practical hardware constraints. While TLA provides statistical associations, bridging toward causal clinical reasoning requires further research.

PMID:41556064 | PMC:PMC12812195 | DOI:10.1177/11795972251407864

PeerJ. 2026 Jan 15;14:e20622. doi: 10.7717/peerj.20622. eCollection 2026.

ABSTRACT

BACKGROUND: This study aimed to validate the Chinese version of the perceptions of palliative care instrument (C-PPCI) for assessing the perceptions and needs of advanced cancer (AC) patients regarding palliative care in China.

METHODS: The C-PPCI was translated following Brislin’s guidelines and tested for psychometric properties through a cross-sectional survey of 537 AC patients. Internal consistency was evaluated using Cronbach’s alpha, and test-retest reliability was assessed with the intra-class correlation coefficient (ICC). Content validity was examined with the content validity index (CVI), and construct validity was explored using exploratory factor analysis (EFA) and confirmed with confirmatory factor analysis (CFA). Concurrent validity was assessed by correlating the C-PPCI with the Edmonton symptom assessment scale (ESAS) and distress thermometer (DT).

RESULTS: Of 537 recruited participants, 444 completed the questionnaire (response rate: 82.6%). The scale-level content validity index (S-CVI) was 0.99. The C-PPCI demonstrated strong internal consistency, with a Cronbach’s alpha of 0.852 for the total scale (subscale range: 0.820-0.872). Test-retest reliability was good, with an ICC of 0.855 for the total scale (subscale range: 0.751-0.815). EFA yielded a four-domain, nine-factor structure explaining 64% to 75% of the total variance. CFA supported this model with good fit indices (comparative fit index (CFI) = 0.917, Tucker-Lewis index (TLI) = 0.904, root mean square error of approximation (RMSEA) = 0.051, standardized root mean square residual (SRMR) = 0.072). Concurrent validity was supported by significant correlations with the ESAS and DT for most subscales.

CONCLUSIONS: The 35-item C-PPCI is a valid and reliable instrument for measuring Chinese AC patients’ perceptions and needs regarding palliative care, providing a valuable tool for clinicians to enhance palliative care (PC) utilization in this context.

PMID:41556055 | PMC:PMC12812269 | DOI:10.7717/peerj.20622

PeerJ. 2026 Jan 15;14:e20617. doi: 10.7717/peerj.20617. eCollection 2026.

ABSTRACT

BACKGROUND: To investigate the molecular genetic features of multiple primary lung cancer (MPLC) to provide a basis and new methods for its identification, diagnosis, and treatment.

METHODS: Transcriptome sequencing (RNA-seq) was performed on 16 tissue samples from eight patients with synchronous multiple primary lung adenocarcinoma (sMP-LUAD) and eight tissue samples from eight patients with single primary lung adenocarcinoma (SP-LUAD). Differentially expressed genes selected by bioinformatic methods were validated in 24 sets of sMP-LUAD and SP-LUAD samples using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Based on The Cancer Genome Atlas (TCGA) database, the differentially expressed genes responsible for the biological behavior of lung adenocarcinoma and their clinical significance were analyzed.

RESULTS: Overall, 194 differentially expressed genes were identified (P < 0.05), including 22 up-regulated and 172 down-regulated genes. Two up-regulated (DUOX1 and CACNA2D2) and three down-regulated (GPX8, COL1A2, and COL1A1) genes were selected for validation by qRT-PCR analysis. The qRT-PCR results showed that the expression of DUOX1 mRNA in the sMP-LUAD group was significantly higher (P < 0.05) than that in the SP-LUAD group; mRNA CACNA2D2, GPX8, COL1A2, and COL1A1 expression in the sMP-LUAD group was not statistically different from that in the SP-LUAD group (P > 0.05). Gene ontology (GO) enrichment analysis showed that DUOX1 mRNA was mainly enriched in the entries of positive regulation of wound healing and oxidation-reduction processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DUOX1 can promote reactive oxygen species (ROS) production and be related to thyroid hormone production. Furthermore, based on the TCGA database, we analyzed the biological behavior and clinical significance of DUOX1 in lung adenocarcinoma using bioinformatics technology. DUOX1 mRNA expression was decreased in all stages and pathological subtypes of lung adenocarcinoma (P < 0.05). Immune infiltration analysis showed that DUOX1 with mast cells and eosinophils was positively correlated (P < 0.05), and Th2 cells were negatively correlated (P < 0.05). Logistic regression analysis showed that the expression of DUOX1 mRNA was significantly correlated with the patient’s age, lymph node metastasis, and pathologic stage (P < 0.05). Kaplan-Meier survival plots showed that low DUOX1 expression was not significantly correlated with OS, DSS, and PFI (P > 0.05). Univariate and multivariate COX regression analysis revealed that DUOX1 mRNA could not be used as an independent factor for predicting prognosis (P > 0.05). Therefore, we developed a predictive nomogram model combining clinicopathological variables and DUOX1 mRNA to predict the survival of patients with lung adenocarcinoma.

PMID:41556052 | PMC:PMC12812280 | DOI:10.7717/peerj.20617

PeerJ. 2026 Jan 15;14:e20604. doi: 10.7717/peerj.20604. eCollection 2026.

ABSTRACT

BACKGROUND: Obesity is accompanied by chronic low-grade inflammation, largely driven by imbalances in macrophage polarization. While pro-inflammatory M1 macrophages accumulate in adipose tissue and circulation, contributing to insulin resistance and metabolic disruption, alternatively activated M2 macrophages exert anti-inflammatory and tissue-protective effects. Exercise is widely recognized as a non-pharmacological strategy to improve metabolic health; however, the extent to which short-term aerobic training influences systemic macrophage polarization in obesity is not fully understood. This study examined whether a 4-week aerobic exercise intervention alters systemic macrophage polarization in diet-induced obese mice and explored its role in attenuating obesity-related inflammation.

METHODS: Male C57BL/6J mice (8 weeks old) were fed either a standard chow diet (Ch) or a high-fat diet (HF; 60% kcal from fat) for 12 weeks. Following obesity induction, HF-fed mice were assigned to either a sedentary (HF-Sed) or exercise-trained (HF-Exe) group. The training protocol involved treadmill running at moderate intensity, performed twice daily, 5 days per week, for 4 weeks. Plasma concentrations of M1-associated markers (TNF-α, IFN-γ , IL-1β, IL-6) and M2-associated markers (IL-10, Arg1, CD163) were measured by an enzyme-linked immunosorbent assay (ELISA). Statistical differences were analyzed using analysis of variance (ANOVA) with post hoc testing.

RESULTS: After 12 weeks of high-fat feeding, mice exhibited approximately 20% higher body weight than chow controls, confirming obesity induction. Four weeks of exercise training did not significantly reduce body weight but improved metabolic indices, including plasma glucose and insulin sensitivity. HF-Sed mice displayed elevated circulating M1 cytokines, whereas HF-Exe mice had significantly lower levels of IL-6, and TNF-α. Conversely, exercise enhanced M2-associated markers, including IL-10, Arg1, and CD163. Thus, aerobic training shifted systemic macrophage polarization away from a pro-inflammatory toward an anti-inflammatory profile, independent of substantial weight loss.

CONCLUSION: Short-term aerobic exercise is sufficient to promote M2 macrophage polarization and dampen systemic inflammation in obese mice. These findings underline the rapid immunomodulatory potential of exercise and support its role as an effective non-pharmacological approach to counteract obesity-related inflammation and metabolic dysfunction.

PMID:41556049 | PMC:PMC12812270 | DOI:10.7717/peerj.20604