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Assessing the threat of Bacillus cereus: From toxin characterization to modern detection strategies.

Bacillus cereus is a spore-forming pathogen responsible for both diarrheal and emetic foodborne illnesses worldwide. Its significance in food safety has received growing attention. Recent advances, including the discovery of novel virulence factors and the development of emerging detection technologies, have provided new insights into its pathogenic mechanisms and surveillance strategies. This review critically examines the global burden of B. cereus infections, and molecular mechanisms of its major virulence factors, and the performance characteristics of current detection knowledge gaps such as the viable-but-non-culturable state and regulatory blind spots for emetic toxins, and discuss unresolved challenges in clinical management. By integrating epidemiological, microbiological, and technological perspectives with critical lens, this review aims to provide a valuable reference for future research and food safety practices.

Bacillus cereus

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans

Comparative genomic epidemiology of food- and patient-derived diarrheagenic Escherichia coli from sentinel surveillance in Southeast China.

Diarrheagenic Escherichia coli (DEC) remains an important foodborne pathogen, yet long-term comparative genomic surveillance data jointly characterizing food-derived and patient-derived isolates remain limited. This surveillance-based comparative study integrated antimicrobial susceptibility testing and whole-genome sequencing to characterize diarrheagenic Escherichia coli isolates recovered from food and patient sources in Lishui, Southeast China, during 2018-2025, with emphasis on occurrence, resistance profiles, genomic backgrounds, and plasmid replicon-associated features. Antimicrobial susceptibility testing was performed for 258 selected isolates, and whole-genome sequencing was conducted for a curated analytical subset of 204 isolates. The sequenced subset was used for diversity-oriented comparative genomic analysis rather than for unbiased prevalence estimation of the entire DEC collection. EAEC predominated in both sources, although food-associated occurrence was heterogeneous across categories, with the highest recovery rate observed in raw meat. Patient-derived isolates showed a broader overall resistance burden, whereas food-derived isolates retained substantial resistance to tetracycline, chloramphenicol, and florfenicol. Phylogenetic analysis showed partial overlap in genomic backgrounds between food-derived and patient-derived isolates, while representative resistance determinants displayed both broadly distributed and lineage-enriched patterns. Replicon-based plasmid profiling identified 42 plasmid types, including 12 detected in both sources, with IncF-related replicons predominating among these shared profiles. Several food-derived isolates carried multiple plasmid replicon types that were also observed in patient-derived isolates. Overall, food-derived and patient-derived DEC showed partial overlap in genomic backgrounds, resistance determinants, and replicon-defined plasmid profiles within this surveillance setting, while retaining source-associated heterogeneity. These findings should be interpreted as surveillance-based comparative evidence rather than as evidence of direct source attribution or transmission.

Humans

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans

Efficacy of a self-guided online resilience intervention for improving mental health among university students: A randomized controlled trial.

Epidemiological data indicates that university students are an at-risk population for the development of mental disorders. Online interventions have been proposed as promising tools for reducing barriers to treatment and establishing easily accessible health-care services promoting mental health and resilience. This study investigated the efficacy of a Learning Management System (LMS)-based self-guided online resilience intervention. 216 university students took part in a randomized controlled trial with an intervention and a waitlist control group and three measurement points (pre, post and follow-up). We conducted per-protocol (PP) and intention-to-treat (ITT) analyses with mental distress as primary outcome, and self-reported resilience and resilience factors as secondary outcomes. Further, attitudes towards online interventions, adherence, satisfaction and possible negative effects were explored. Satisfaction with the intervention was high and PP analyses (n = 150) revealed significant improvements in mental distress and self-compassion at post-test and acceptance at follow-up. No favourable effects were found for self-reported resilience and resilience factors. Adherence was low and ITT analyses revealed no significant effects. Overall, the study provides preliminary evidence for the LMS-based self-guided online intervention as a potentially valuable tool for university mental health services under optimal adherence conditions. Further research into determinants of adherence is needed to improve intervention reach.

Humans

The return of measles: a dangerous comeback.

PURPOSE OF REVIEW: Measles has reemerged as a significant global public health threat, with increasing morbidity and mortality associated with declining vaccination rates. This review summarizes current global outbreaks, history of measles, vaccination and elimination status, vaccine hesitancy, and outbreak response and lessons learned highlighting different novel digital epidemiological tools. RECENT FINDINGS: Measles continues to surge worldwide with an estimated 11 million infections in 2024, which is more than prepandemic levels. Developing and developed countries are both facing measles outbreaks, with the United States at risk of losing measles elimination status. Recent studies have showed that worldwide percentages of two-dose measles vaccination were lower than 95% that is required to interrupt measles transmission in all WHO regions. Novel epidemiological tools such as interactive simulators, real-time use of dynamic models, serosurveillance, and others are transforming measles outbreak response and enable earlier outbreak detection, tracking, and targeted public health interventions. SUMMARY: Vaccine hesitancy is one of the top global health threats and developing a tailored evidence-based approach is necessary to establish and maintain measles elimination.

Humans

Co-occurrence of rheumatoid arthritis and calcium pyrophosphate deposition disease: A systematic literature review.

BACKGROUND: Rheumatoid arthritis (RA) and calcium pyrophosphate deposition (CPPD) disease are forms of inflammatory arthritis which may have similar presentations. There is growing recognition that these conditions can coexist, especially in elderly patients. This systematic literature review aims to examine the epidemiology and clinical characteristics of patients with both RA and CPPD disease. METHODS: A systematic literature search was performed from database inception to 31st January 2026 using the databases EMBASE, MEDLINE, Scopus, PubMed, CINAHL, and Cochrane. Keywords relating to RA, CPPD and chondrocalcinosis were used. Inclusion criteria were studies published in English and those that addressed the co-occurrence of RA and CPPD. RESULTS: The search yielded 24 studies comprising 12 cross-sectional studies, 2 case series, and 10 case reports published between 1965 and 2026. A total of 404 patients had both RA and CPPD, with 397/404 (98.3%) aged over 60 years old. Of 365 patients with serostatus data, 204/339 (60.2%) were seronegative for both rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA). Radiographic chondrocalcinosis was evident in 271/287 (94.4%). Of 271 patients with chondrocalcinosis, 162 (59.8%) were seronegative for both RF and ACPA. The most prescribed medications were methotrexate and prednisolone, in 75/205 (36.6%) and 64/205 (31.2%) patients, respectively. Colchicine was prescribed for 24/205 (11.7%). CONCLUSION: While the studies were small, RA, which is commonly seronegative, and CPPD can co-exist in the elderly. Higher-quality studies are required to determine the prevalence of co-existent RA and CPPD, thereby improving insight into the epidemiology and potentially enhancing outcomes of these patients.

Humans

Putting Globus Into Context: Prevalence, Characteristics, and Overlap With Other Disorders of Gut-Brain Interaction.

OBJECTIVE: Globus is characterized by the sensation of a lump in the throat without dysphagia or underlying structural abnormality or major motility disorder. Reported prevalences vary considerably across studies. Globus has been linked to both heartburn and affective disorders. This study aims to determine the global prevalence of globus, its association with heartburn, overlap with disorders of gut-brain interaction (DGBI) and psychosocial disorders, and its impact on health-related quality of life (HRQOL). METHODS: Internet surveys from the Rome Foundation Global Epidemiology study were used (N = 54,127). Rome IV criteria were used to identify globus and concurrent DGBI. Heartburn was defined as symptoms ≥ 2-3 days/week. Psychosocial co-morbidity and somatic symptom severity were assessed with PHQ-4 and PHQ-15, and HRQOL by PROMIS-10. RESULTS: The global prevalence of globus according to Rome IV criteria was 0.75%, representing 12.8% of esophageal DGBI and 1.86% of all DGBI. Prevalence was highest in Western Europe (0.94%) and Asia (0.90%), and lowest in the Middle East (0.31%). Globus was slightly more common in females (55.4%), and most affected individuals were aged between 40 and 64 years (46.6%). Coexisting heartburn was reported in 17.4% of cases, esophageal DGBI in 9.1%, and non-esophageal DGBI in 49.0%. Anxiety and/or depression was present in 60.5%. CONCLUSION: Global prevalence of globus is 0.75%, with a slight female predominance, and is most prevalent below 65 years. Overlap with non-esophageal DGBI was greater than with heartburn symptoms or esophageal DGBI, and most patients had anxiety and/or depressive symptoms.

Humans

Mining Stored-Specimen Studies for Information about Cancer Natural History.

The advent of new multicancer early detection tests and publication of early diagnostic results have generated expectations of clinical benefit from multicancer screening. The clinical benefit of a cancer screening test depends critically on disease natural history, which is typically learned from prospective screening studies. Retrospective studies of stored blood specimens are important in learning about a test's preclinical diagnostic performance but have rarely been used to infer natural history. The extent to which these studies might be harnessed to also learn natural history is discussed in the context of an article in this issue that infers the combined natural history of a range of cancers targeted by a multicancer early detection test using a case-control subsample of specimens from a large cohort study. The critical question concerns the identifiability of key transition rates in multistate models of natural history alongside state-specific sensitivities. The article suggests that these parameters are estimable within a Bayesian framework that leverages prior information about test sensitivity from diagnostic studies. We offer a heuristic discussion of identifiability in this setting and encourage formal study to determine the extent to which models with varying degrees of complexity may be learned from stored-specimen studies. See related article by Dai et al., p. 1535.

Humans

Understanding Suicide through Coroners' Narratives: implications for primary care from a mixed‑methods study of 157 Coroners' reports.

Suicide is a major public health concern, and general practice is often a recent point of contact before death. While mental illness is well recognised, the broader social and contextual factors influencing suicide risk remain under-reported in primary care and epidemiological research Aim To describe the demographic, clinical, and psychosocial characteristics of individuals who died by suicide, integrating coronial quantitative data with qualitative narrative accounts to identify implications for primary/ secondary care and public health. Design and setting Explanatory sequential mixed‑methods study of 157 consecutive deaths by suicide recorded by coroners (2018-19) across five English local authorities. Method Demographic, clinical, and social data were extracted from coroners' records and summarised descriptively. Narrative case summaries were coded and analysed thematically to identify contextual, relational, and service factors preceding death. Results Of 157 individuals: 79% were male; 65% lived in the most deprived IMD quintile; 85% had a diagnosed mental health condition; 62% had a long‑term physical illness; 41% had a previous suicide attempt. About half consulted a GP in the preceding three months; mental health featured in about half of those consultations. Common stressors were relationship breakdown (37.2%), housing instability (22.1%), and work pressures (18.2%). Seven interlinked themes were identified: Mental health; Alcohol/Substance use, Physical health; Social connectedness; Life course trauma, Socioeconomic and Structural Vulnerability; Healthcare access. Service transitions were key vulnerability points Conclusion Coroners' records offer important insights into the complex circumstances preceding suicide and highlight opportunities for GPs to recognise intersectional complexity and support integrated, cross-sector suicide prevention approaches.

General Practice

Influenza A virus in Swiss pig herds with respiratory disease: Seasonality and age dependence.

Influenza A virus (IAV) is an important respiratory pathogen in pigs and poses a zoonotic risk to humans in close contact. While IAV epidemiology has been extensively studied in large-scale production systems, data from Switzerland - characterized by small herds and limited live pig imports - remain scarce. This exploratory nationwide cross-sectional study aimed to assess the association between herd-level IAV detection and reported respiratory disease in pig herds, and to explore associations with husbandry-, animal-, and human health-related factors. Between November 2023 and April 2025, 25 Swiss pig herds with caretaker-suspected respiratory symptoms were investigated. In each herd, five nasal swabs were collected and analyzed by quantitative PCR. Herd managers completed an interview, and clinical examinations were performed. Overall, 56 % (95 % CI: 37,1 - 73,3) of herds tested positive for IAV, comparable to reports from other European countries. The estimated intra-herd detection rate was 49,6 % (95 % CI: 31,2 - 68,0). Respiratory disease outbreaks associated with IAV detection showed indications of seasonal variation, with no positive herds identified during summer. Across age groups, pigs aged 11-14 weeks had a higher likelihood of IAV detection, with 15,79-fold increased odds (95 % CI: 1,50 - 860,4), although with considerable uncertainty. The interpretation is limited by the small sample size, heterogeneous data, and reliance on single time-point qPCR detection. The results suggest that IAV detection in clinically apparent respiratory outbreaks may follow seasonal patterns in Swiss pig herds. Weaners and newly introduced fattening pigs may play a role in such respiratory outbreaks and could represent relevant targets for IAV surveillance in Switzerland. Continued monitoring and the implemen tation of appropriate control measures remain important given the virus's zoonotic potential and impact on pig health.

Animals

Prevalence of psychosis in South Asia: A systematic review and meta-analysis.

BACKGROUND: Psychotic disorders are a major contributor to global disability, yet prevalence data from South Asia which inhabits a quarter of the world's population, remain limited. Reliable estimates are essential for health service planning, policy, and closing the substantial treatment gap. This review provides the first comprehensive synthesis of psychosis prevalence across South Asia. METHODS: We searched PubMed, Embase, Web of Science, Global Health, and Medline to 18 December 2024 for DSM- or ICD-based prevalence studies in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. Cross-sectional and longitudinal studies in community or clinical populations were included. Study quality was assessed using the Joanna Briggs Institute checklist. Random-effects meta-analyses estimated pooled prevalence using the logit transformation. Heterogeneity was explored with meta-regression of key methodological variables (publication year, diagnostic system, residential setting). FINDINGS: Thirty-one studies from five countries were included. Among community-dwelling adults, pooled point prevalence was 0.85% and lifetime prevalence was 1.40%, with inter-country differences (India 1.18%, Pakistan 2.13%, Nepal 2.90%). Clinical samples showed substantially higher proportions of individuals with psychosis in service settings (11.44%), reflecting concentration of cases in treatment-seeking samples. Data for children and adolescents were limited and summarised narratively. Heterogeneity was high across meta-analyses, and exploratory meta-regression did not identify any significant moderators. INTERPRETATION: Psychosis prevalence estimates in South Asia appear higher than global averages but should be interpreted cautiously due to substantial heterogeneity and methodological variation; nevertheless, they highlight the need for culturally sensitive screening, improved detection, and strengthened mental health services.

Humans

Waterborne norovirus outbreaks in China, 2000-2022: a systematic review.

In China, waterborne transmission is a relatively rare route for norovirus outbreaks; however, once it occurs, the outbreaks tend to be large in scale, prolonged in duration, and difficult to control. This systematic review characterizes the epidemiological features of such outbreaks in China. We searched the WANFANG, CNKI, PubMed, and Web of Science databases for literature on waterborne norovirus outbreaks published up to November 2023. From 2000 to 2022, a total of 112 outbreaks were reported in China among the 97 articles included. These outbreaks involved approximately 19,796 cases and 565,485 exposures, median of 98 cases per outbreak, with a median attack rate of 6.09 %. Most outbreaks occurred in southern regions, particularly in coastal provinces, with schools (59, 52.68 %) and towns or villages (25, 22.52 %) being the most common settings. The highest number of outbreaks was reported in February and the lowest in July, with an average of 8.25 outbreaks per month. Higher attack rates were associated with outbreaks occurring in winter, in primary schools, and in southern regions of the Qinling-Huaihe line. Contamination of barreled water and self-provided wells was the primary risk factor for waterborne norovirus outbreaks. Although waterborne transmission is a relatively rare route for norovirus outbreaks in China, it can cause large-scale outbreaks in a short period. Consequently, it is still necessary to enhance protection of water sources, rigorous water quality monitoring, and public health education on water sanitation.

Humans

Non-motor symptoms and healthcare utilization before diagnosis of myasthenia gravis: a nationwide cohort study.

BACKGROUND: Non-motor symptoms have been reported prior to myasthenia gravis (MG) diagnosis. However, the temporal patterns of non-motor symptoms and healthcare utilization before MG diagnosis remain unclear. METHODS: We conducted a retrospective, population-based cohort study using the Korean National Health Insurance Service (KNHIS) database from 2011 to 2021. Incident MG cases were identified using the International Classification of Diseases, Tenth and Rare Intractable Disease codes. Individuals younger than 20  years or with missing health screening data were excluded. Each MG case was matched 1:10 by age, sex, and index date to controls. Non-motor symptoms and healthcare utilization were defined using operational criteria derived from KNHIS claims data. Rate ratios (RRs) and 95 % confidence intervals (CIs) were estimated across four prespecified intervals (0-1, 1-2, 2-5, and 5-10  years) before MG diagnosis. RESULTS: We included 8,355 MG patients and 83,550 controls (mean age, 53.7  years; male, 44 %). MG patients had higher rates of any non-motor symptoms over 10  years(RR 1.34; 95 % CI 1.30-1.39), with the sharpest increase in the year before diagnosis. Depression, anxiety, migraine, constipation, and insomnia consistently showed higher RRs across all intervals. Hospitalizations (RR 1.66; 95 % CI 1.61-1.71) and outpatient clinic visits (RR 1.10; 95 % CI 1.04-1.17) were consistently higher across 10  years, peaking during the 0-1 year before MG diagnosis. CONCLUSION: Non-motor symptoms and healthcare utilization increased years before MG diagnosis. Earlier recognition of these symptom patterns may facilitate timelier evaluation for MG and improve diagnostic pathways.

Humans

What's the meta now? More updates on the problems with systematic reviews.

BACKGROUND: Systematic reviews are intended to provide trustworthy evidence synthesis, yet previous iterations of this living review have identified numerous recurring problems in their conduct and reporting. This article presents the third version and second update of the living systematic review examining issues raised across the academic literature. METHODS: Using consistent eligibility criteria and methods from earlier versions, literature searches were updated to May 2025. Eligible meta-research and editorial articles describing problems with systematic reviews were analyzed to identify emerging themes. Additionally, four basic indicators of methodological quality of the included meta-research were presented across review versions. RESULTS: The update included 209 additional articles. Critically low methodological quality and absence of protocols remained among the most frequently reported issues in systematic reviews across disciplines and journals but notably in evidence underpinning clinical practice guidelines. Spin in abstracts and conflicts of interest continued to be common. Apparent improvements in reporting quality were inconsistent, with modest gains in some full-text reporting but persistent deficiencies in abstracts. Authorship diversity of systematic reviews improved in gender representation but remained geographically concentrated in high-income countries, and primary research included in reviews similarly lacked global representativeness. The issue of misalignment between systematic review evidence bases and global burden of disease bring the total number of problems with systematic reviews to 69. Emerging use of automation and artificial intelligence was variably reported. Descriptive comparison of meta-research articles over the three versions of this living review suggests a greater proportion meeting basic quality indicators in more recent updates. CONCLUSION: Across successive updates, problems with systematic reviews remain widespread and consistent rather than isolated. Incremental reporting improvements coexist with persistent concerns about transparency, bias, and representativeness. Future efforts should prioritize evaluating interventions and aligning research incentives to support genuinely trustworthy evidence synthesis.

Humans

Stage shift, histological differentiation, and survival patterns of lung squamous cell carcinoma versus adenocarcinoma in low-dose CT screening.

BACKGROUND: Whether LDCT-associated stage shift translates into similar survival patterns across lung cancer histologies remains uncertain. We compared stage shift, histological differentiation, tumor characteristics, and survival between lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) in the National Lung Screening Trial. METHODS: Among participants diagnosed with LUSC or LUAD, stage distribution and histological differentiation were compared between LDCT and chest X-ray (CXR) arms. Survival among diagnosed cases was measured from randomization. Multivariable models tested screening arm-by-histology interactions. Screen-detected LDCT tumors were compared by histology. RESULTS: During 6.5 years of median follow-up, 498 LUAD and 249 LUSC cases were diagnosed in the LDCT arm, and 374 and 212, respectively, were diagnosed in the CXR arm. LDCT was associated with higher odds of stage I disease for LUAD (adjusted odds ratio [aOR], 2.48; 95% CI 1.88-3.28) and LUSC (aOR, 1.71; 95% CI 1.17-2.48), without significant interaction (P&#x202f;=&#x202f;0.116). LDCT was associated with lower hazard of lung cancer-specific death among diagnosed LUAD cases (adjusted hazard ratio [aHR], 0.54; 95% CI 0.43-0.66), but not among diagnosed LUSC cases (aHR, 1.04; 95% CI 0.78-1.39; P for interaction<0.001). LUSC had lower screening sensitivity, more frequent detection in annual screening rounds, greater prediagnostic tumor size increase, and fewer well-differentiated stage I tumors than LUAD. CONCLUSION: LDCT was associated with stage shift for both subtypes, but favorable survival patterns among diagnosed cases were mainly observed for LUAD. Lower screening sensitivity, greater prediagnostic tumor size increase, and poorer histological differentiation may help explain why stage shift did not translate into similar survival patterns for LUSC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00047385.

Humans

Cefiderocol susceptibility rates in carbapenem-resistant Gram-negative bacteria in a comparative, multicenter surveillance study in China.

BACKGROUND: Cefiderocol is a siderophore cephalosporin with potent, broad spectrum of activity against carbapenem-resistant (CR) Gram-negative bacteria. The objective of this surveillance study was to assess cefiderocol susceptibility in molecularly characterized CR Gram-negative pathogens collected from hospitalized patients across China. METHODS: Susceptibility testing was performed by the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines, using pre-prepared frozen 96-well microtiter Thermo Fisher plates. Susceptibilities to cefiderocol and most comparators were determined by Clinical and Laboratory Standards Institute breakpoints, to tigecycline by US Food and Drug Administration breakpoints, and to colistin by European Committee on Antimicrobial Susceptibility Testing criteria. Carbapenemases were identified by whole-genome sequencing and polymerase chain reaction. RESULTS: Of 149 CR Klebsiella pneumoniae, 95.3% were susceptible to cefiderocol (OXA-48-positive 100% [n = 15]; IMP-positive 100% [n = 9]; KPC-positive 95.4% [n = 108]; NDM-positive 88.2% [n = 17]) and against 103 NDM-positive CR Escherichia coli, cefiderocol susceptibility was 45.6%. Among comparator antibiotics, ceftazidime-avibactam was only active against K. pneumoniae carbapenemase-positive and OXA-48-positive K. pneumoniae isolates. Susceptibilities to tigecycline and colistin were between 22.2% and 97.1% and between 88.2% and 100% across CR Enterobacterales with different carbapenemases, respectively. High cefiderocol susceptibility rates were found for CR Pseudomonas aeruginosa (98.4%), CR Acinetobacter baumannii (99.6%), and Stenotrophomonas maltophilia (99.6%). Among comparator antibiotics, only colistin showed high activity against CR P. aeruginosa (99.2%) and CR A. baumannii (99.2%). CONCLUSIONS: Cefiderocol susceptibility rates were &#x2265;88% against a collection of carbapenemase-positive CR Gram-negative isolates, except for lower susceptibility in NDM-positive CR E. coli isolates. Continuous monitoring of cefiderocol susceptibility is warranted.

Cefiderocol

Mechanisms of impact of mental health peer support in high-, middle- and low-income settings: mediation analysis of the UPSIDES randomised controlled trial.

AIMS: While there is growing evidence for the effectiveness of peer support (PS) in improving psychosocial outcomes among individuals with severe mental health conditions, the mechanisms through which these effects occur remain insufficiently understood. This study examines whether social inclusion, hope and empowerment mediate the relationship between PS, personal recovery and health and social functioning. METHODS: Data were collected from 565 adults with severe mental health conditions who participated in the multicentre UPSIDES randomised controlled trial across six sites in Germany, Uganda, Tanzania, India and Israel. Participants in the intervention group received structured PS from trained peer workers over a 6- to 8-month period. Standardised, self-report measures of social inclusion, hope, empowerment and personal recovery, as well as clinician-rated health and social functioning, were administered at baseline, 4&#xa0;months, end of intervention (8&#xa0;months) and 12-month follow-up. Cross-lagged panel modelling was used to explore longitudinal associations and mediating pathways. RESULTS: The cross-lagged models showed strong autoregressive effects across all variables, indicating high temporal stability. There were no significant direct effects of PS on recovery or health and social functioning. However, mediation analysis identified significant indirect effects of PS on personal recovery via social inclusion (&#x3b2;&#xa0;=&#xa0;0.114, 95% confidence interval [CI] [0.049, 0.194], P&#xa0;<&#xa0;0.05) and hope (&#x3b2;&#xa0;=&#xa0;0.037, 95% CI [0.001, 0.086], P&#xa0;<&#xa0;0.05). Similar indirect effects were observed for health and social functioning (via social inclusion: &#x3b2;&#xa0;=&#xa0;-0.035, 95% CI [-0.064,&#xa0;-0.013]; via hope: &#x3b2;&#xa0;=&#xa0;-0.026, 95% CI [-0.052, -0.006]; both P&#xa0;<&#xa0;0.05). CONCLUSIONS: Findings suggest that PS affects recovery-related outcomes primarily through intermediate mechanisms of enhanced hope and social inclusion. These results support theoretical models positing indirect pathways of change in PS interventions and highlight the value of targeting social and psychological domains when designing and implementing PS in mental health services. Individuals with lower baseline levels of hope and social inclusion may particularly benefit from PS.

Humans