Operation Metro Surge, a joint initiative by the Department of Homeland Security and the United States Immigration and Customs Enforcement (ICE), significantly disrupted daily life in Minnesota. Despite numerous anecdotal reports, the impact and scale of this disruption to local health care systems had not been quantified. An interrupted-time series analysis was used to assess the impact of ICE Metro Surge on missed appointments and reschedule requests in 2 hospital-based general pediatrics practices located on the Minneapolis and St Paul campuses of Minnesota's flagship pediatric hospital. We identified a total of 15 611 eligible appointments in the post-Metro Surge period and 113 934 in the pre-Metro Surge period. The rate of missed appointments among Hispanic/Latiné patients increased by 51.2% during Metro Surge compared to the same time period (the first week of December to second week of February) in the prior 2 years (31.3% vs 20.7%; P < .001). Missed appointment rates increased by 80.4% among Spanish-speaking families (34.1% vs 18.9%, P < .001) and 53.1% among families with a need for interpretation (28.1% vs 18.4%, P < .001). During the Metro Surge period, reschedule requests for well-child visits increased 51% compared to previous years (P < .001). Our findings demonstrate that Metro Surge decreased pediatric outpatient use in Minneapolis and St Paul, Minnesota. The observed decrease in outpatient care exceeded predicted outpatient care based on preexisting and seasonal trends in missed appointments and reschedule requests. The cumulative effect of this period of exacerbated health care disparities and delayed care may have long-term impacts on child health.
Exposure to anthropogenic volatile organic compounds (VOCs) has been associated with preterm birth, yet the spatial distribution of VOC exposures within urban environments remains poorly characterized, particularly for vapor intrusion pathways. Plants have recently been used as a cost-effective, non-invasive tool to "phytoscreen" for belowground contaminants. Here, we evaluated the use of phytoscreening within a birth cohort in metro Detroit, Michigan, USA by (a) assessing participant willingness to allow sampling in residential front yards, (b) quantifying VOC concentrations across plant tissue types (leaves and twigs), and (c) testing whether VOC detections in plants are associated with proximity to brownfield sites. Of 20 pregnant participants, 18 agreed to phytoscreening and sampling was completed at 13 residences, indicating high feasibility. Across 15 plant species, five of six target VOCs (benzene, toluene, ethylbenzene, xylene, trichloroethylene, tetrachloroethylene) were detected. Specifically, toluene was detected at all 13 homes and in 68% of samples. While less common, ethylbenzene was detected in 12 samples across 3 homes and trichloroethylene was detected in one sample that exceeded Michigan's risk-based screening level for soil vapor intrusion. Additionally, VOCs were detected more frequently and at higher concentrations in leaves compared to twigs. However, VOC concentrations in plants were not associated with proximity to known or suspected brownfield sites in this small sample size. Overall, these findings demonstrate the feasibility of phytoscreening in epidemiological studies and highlight its utility for characterizing spatial patterns of VOC exposure. Incorporating plant-based sampling approaches may help identify localized hotspots of human exposure and inform targeted environmental remediation efforts.
Cardiovascular diseases remain a major cause of morbidity and mortality in Ghana. This study aimed to determine the association between anthropometric indices and elevated estimated 10-year cardiovascular disease (CVD) risk among adults in the Kumasi Metropolis. This cross-sectional study involved 480 adults aged 40-79 years. Anthropometric indices and lipid profile were determined using standard methods. Blood pressure was measured using an automated sphygmomanometer. The World Health Organization/International Society of Hypertension laboratory-based risk assessment charts were used to estimate 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk. Estimated CVD risk ≥ 10% was considered elevated. Anthropometric indices were examined for association with elevated risk using chi-square, Fisher's exact and Wilcoxon rank-sum tests. Multivariable modified Poisson regression analysis was used to determine factors associated with elevated estimated CVD risk. An elevated estimated10-year ASCVD risk was observed in 56.9% (103/181) of males and 38.8% (116/299) of females. Lower education level was associated with elevated CVD risk. Waist-to-hip ratio (WHR) (aPR = 1.36, 95% CI: 1.11-1.68), body shape index (ABSI) (aPR = 1.35, 95% CI: 1.08-1.69), hip circumference (HC) (aPR = 0.98, 95% CI: 0.97-0.99), and mid-arm circumference (MAC) (aPR = 0.95, 95% CI: 0.92-0.98) were associated with elevated estimated CVD risk. After stratifying by sex, WHR remained independently associated with elevated estimated CVD risk in females (aPR = 1.36, 95% CI: 1.01-1.84); as did ABSI (aPR = 1.45, 95% CI: 1.05-2.01) and MAC (aPR = 0.93, 95% CI: 0.88-0.99) in males. WHR, ABSI and MAC assessments should be integrated into CVD risk evaluation in Ghana, especially in deprived areas where lipid profile is not routinely assessed.
Superficial vein thrombosis (SVT) of the legs is a common disease linked with venous thromboembolism (VTE), with an uncertain recurrence risk. Data on secondary prevention of recurrent or extending SVT and on its natural history are lacking. Mesoglycan (MGY) shows a mild antithrombotic effect and the capacity to repair the endothelial layer, by restoring the integrity of the glycocalyx. This study aimed to evaluate the efficacy and safety of MGY for secondary prevention of VTE after an episode of lower-limb SVT. This was a multicentre, randomised, double-blind, placebo-controlled, superiority, phase II study conducted at 16 sites in Italy. Patients (aged > 18 years) with lower-limb SVT, who completed a 45-day treatment course of fondaparinux were randomised (1:1) to receive either oral MGY 50 mg or matching placebo twice-daily for 12 months, and were subsequently followed-up for another 12 months. The efficacy outcome was a composite of symptomatic recurrence or extension of SVT; new symptomatic or asymptomatic proximal deep-vein thrombosis, or new symptomatic distal deep-vein thrombosis, or new symptomatic non-fatal pulmonary embolism, or fatal pulmonary embolism at 12 months (primary outcome) and 24 months (secondary outcome) post-enrolment. The primary safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding at 12 months. This trial was registered with EudraCT (2016-005184-13) and ClinicalTrials.gov (NCT03428711). Between March 26, 2018, and Dec 31, 2024, 553 patients were randomly allocated to treatment (272 to MGY and 281 to placebo), below the planned sample size due to slow recruitment because of SARS-CoV2 pandemic. At 12 months, the cumulative rate of efficacy events was 21.8% (54 patients) in the MGY group and 24.5% (63 patients) in the placebo group, respectively, showing no difference between these two groups (HR 0.89, 95% C.I. 0.62-1.29; p = 0.56). At 24 months, the cumulative rate of efficacy events was 30.6% (74 patients) in the MGY group and 42.5% (105 patients) in the placebo group, respectively (p = 0.043). This difference was entirely accounted for by a lower rate of recurrent SVT in the MGY group. The 24-month recurrence rate of SVT was 39% in the placebo group. No bleeding events were observed in either group. No significant differences were observed between MGY and placebo in terms of recurrent or extending SVT, at the end of the 12-month treatment course. However, we recorded a significant difference in favour of MGY at 24 months. These findings should be interpreted cautiously, given that the incidence of recurrent or extending SVT in the placebo group was higher than previously reported and the planned sample size was not reached due to slow recruitment. Our findings need to be confirmed in future, larger studies. Neopharmed Gentili S.p.A.
Outcomes in status epilepticus (SE) depend on rapid seizure control, yet transport times/resources differ by hospital type. We hypothesized that hospital outcomes vary across hospital types: metro-academic (MA), metro-nonacademic (MNA), and non-metro hospitals (NM). Outcomes of interest included in-hospital mortality, length of stay (LOS), 30-/90-day readmission, discharge disposition, and costs, METHODS: Retrospective cohort of adults with SE from the 2016-2022 NRD. Survey-weighted multivariable logistic regression evaluated in-hospital mortality and 30-/90-day readmission. Linear regression evaluated LOS and cost. Models adjusted for age, Charlson Comorbidity Index, ZIP income quartile, and in-hospital severity markers, reporting adjusted OR/coefficients with 95% confidence intervals/ p-values. SE hospitalizations occurred predominantly at MA hospitals, whereas NM hospitals disproportionately served patients in the lowest income quartile (64%). MA hospitalizations had higher illness severity, characterized by coma (7.4%), use of mechanical ventilators (<24 h: 15.1%, 24-96 h: 20.8%, >96 h: 10.1%), cardiac arrest (1.6%), sepsis (5.5%), vasopressor infusion (2.3%), and tracheostomy placement (2.1%). MA hospitalizations had greater association with in-hospital complications, including respiratory failure (40.1%), pneumonia (8.1%), acute kidney failure (18.5%), venous thromboembolism (2.1%), pressure ulcers (3.4%), and delirium (2.9%). Mortality (3%) and discharge disposition were similar across hospital types. However, MA hospitalizations had higher 30-/90-day readmissions, longer LOS (t = 12.14, p < 0.0001), and higher costs (t = 13.27, p < 0.0001). Despite higher illness severity at MA hospitals, in-hospital mortality and discharge disposition were similar across hospital types. Increased readmissions, LOS, and costs at MA centers likely reflect greater case complexity and may inform resource allocation and interhospital transfer practices.
Local socioeconomic status may influence psychiatrist distribution, yet this remains systematically unexamined in Australia. We aimed to assess how psychiatrist availability varies across regions with differing socioeconomic advantage. Psychiatrist workforce data from the Health Workforce Data Tool (2013-2023) were linked to local government areas-level quintiles of the Index of Relative Socioeconomic Advantage and Disadvantage. We calculated and compared the proportion of local government areas with psychiatrists, psychiatrist counts per local government area, and psychiatrists per 10,000 population by Socio-Economic Indexes for Areas quintile. Panel regression analyses examined per capita variations, adjusting for state/territory and year effects in the same analyses. Outer regional/remote/very remote areas had relatively low access to psychiatrists compared to metropolitan/inner regional areas. Disparities widened over time between the highest socioeconomic status quintile and all others. The average psychiatrist count per 10,000 population for top-quintile local government areas was 2.8 (standard deviation: ±4.8; from 0.6 (standard deviation: ±1.0, Northern Territory) to 5.5 (standard deviation: ±7.0, South Australia)), compared with 0.2-0.5 per 10,000 population for all lower socioeconomic status quintiles. In panel regression with interaction between Socio-Economic Indexes for Areas and remoteness, psychiatrist counts (adjusted for state/territory and year) in non-top-quintile local government areas were 2.6 (95% confidence interval: -4.1 to -1.1) to 3.0 (95% confidence interval: -4.4- to -1.7) per 10,000 population lower than top-quintile metropolitan and inner regional local government areas. Psychiatrists are densely concentrated in high socioeconomic status and metropolitan/inner regional areas. Lower socioeconomic status local government areas shared similar, limited psychiatrist distributions. Targeted strategies are required to improve the equitable distribution of mental health resources across socioeconomic gradients.
Fixed-dose combinations (FDCs), particularly sulfonylurea-based triple therapies, play a central role in managing type 2 diabetes in India. With growing focus on safety and personalization, lower-dose alternatives are gaining attention, especially for early-stage and vulnerable patients. To obtain expert consensus from Indian physicians on the clinical relevance, preferred patient profiles, and prescribing intent for a low-dose triple FDC comprising glimepiride 0.5 mg, metformin 500 mg sustained-release (SR), and voglibose 0.2 mg. A structured cross-sectional survey was conducted among 112 physicians from metro and nonmetro regions of India. The survey used close- and open-ended questions to explore the need, clinical positioning, and use scenarios for this low-dose triple combination. Responses were analyzed and synthesized into expert consensus per the Oxford Centre for Evidence-Based Medicine (OCEBM) framework (Level V evidence). Most physicians (86.6%) supported the need for this combination. Common use cases included early-stage diabetes, elderly patients, and those with postprandial hyperglycemia or hypoglycemia risk. It was also preferred for step-up therapy and deintensification with agents, such as SGLT2 inhibitors or insulin (77.7%). Advantages cited included improved safety, simplified dosing, and affordability. Expert consensus affirms this FDC's clinical relevance across multiple diabetes stages. Further real-world evidence and outcome-driven studies are warranted to support broader clinical integration and guideline inclusion.
. More than two million older adults are homebound and five million need help leaving their homes. They often experience social isolation, food insecurity, and lack of connection to community resources. Affordable, adaptable, comprehensive home-based services for those aging in place are lacking. This study examined the benefits of an intergenerational home-based service-learning program on goal attainment in 1) social support, 2) home safety and cleanliness, 3) access to community resources, 4) food access, and 5) improving physical health. . 201 homebound and near-homebound older adults enrolled in Lori's Hands in Newark, DE; Baltimore, MD; and Metro Detroit, MI were surveyed between December 2021 and May 2026. Descriptive and chi-square analyses were conducted to examine changes in domain-specific subjective assessment of goal attainment over time. Findings indicated that 83% of clients reported positive changes in at least one of the five target service areas over six or more months of participation in the program. The majority of participants reported 1) home safety and cleanliness and 2) social support as their most important goals. Results from the chi-square test indicated statistically significant differences in goal attainment for all five service areas. Results from this study suggest that intergenerational in-home support services can improve social support, home safety and cleanliness, physical activity, food access and nutrition, and access to community resources for homebound older adults, thereby supporting aging in place and reducing the load on informal caregivers. . Policies and practice can support a pipeline of health professionals through innovative service-learning models to benefit older adults, caregivers, students, and the broader community.
Consumer and community involvement (CCI) can enhance research and healthcare outcomes. However, orientation processes, including mandatory training, can pose barriers when not designed for consumers, particularly those with diverse communication, language, and literacy needs. To (1) explore consumer and staff experiences of hospital-based orientation, including existing infection control training materials; and (2) co-design an accessible infection control mandatory training resource for consumers who partner with the hospital. Qualitative study using semi-structured interviews (consumers and staff) and a series of three co-design workshops (consumers, staff, researchers). The study was conducted at a metropolitan rehabilitation hospital in Australia in 2025. Participants included consumers, staff and researchers with knowledge in consumer partnering, infection control and orientation. Experiences of consumer orientation, including infection-control training and priorities for the design, content, accessibility and acceptability of a co-designed infection-control training for consumers. Qualitative themes relating to barriers and enablers in consumer orientation and characteristics of the co-designed training resource. Nine participants completed an interview, and 14 contributed to co-design workshops. Consumers described orientation as inflexible, insufficiently tailored and sometimes inaccessible, particularly for people with diverse needs. They valued orientation as an opportunity to build relationships, ask questions and understand their role. Staff highlighted that processes lacked the flexibility needed for person-centred partnering and described challenges in tailoring information for consumer audiences. Interview findings informed co-design workshops in which consumers, staff and researchers developed and refined an infection control training resource for consumers in a hospital setting. Key design features included plain language, visual supports, concise content, opportunities for questions and accessible formatting. Consumer orientation is an important but underexamined stage of healthcare partnering. Accessible, flexible and consumer-centred processes may support inclusive and meaningful involvement. Contributions from staff and consumers were valuable in ensuring that the end product was fit for purpose from organisational and end-user perspectives. Orientation and mandatory training may create barriers when not tailored to consumers' needs. Co-designing accessible training resources offers a practical approach to improving consumer orientation and understanding of infection control principles, supporting more inclusive partnerships with health services. This study was initiated in response to feedback from a consumer network at a metropolitan hospital in Queensland, Australia. Consumers contributed as interview participants and co-designers in developing the training resource.
Due to only 25% of U.S. children meeting the physical activity guidelines, we aimed to determine feasibility of team sports to engage children in at least 60 min of moderate-to-vigorous physical activity daily and increase health knowledge. This 11-week quasi-experimental pre/post intervention study was conducted in two after-school programs around metro Atlanta, GA, USA (C1, n = 18; C2, n = 22). The 11 for Health program is an 11-week active learning model that involves 2 × 45 min per week soccer drills, small-sided games, and health education modules. Assessments included health knowledge and physical fitness metrics such as estimated VO2, standing long jump, balance, agility, and handgrip strength. Non-participants were defined as missing 3 or more sessions and/or not participating in the activities. Descriptive statistics and t-tests were used to compare pre- and post-intervention assessments, stratified by participation level. C1 were on average 9.2 years old, 31% female, and 100% White. C2 were on average 9.8 years, 48% female, and 67% Hispanic and 33% Black. Attendance was 69% (SD 0.26) in average over the 11 weeks for both cohorts, with no difference in attendance between groups. Agility improved significantly [2.7 s(1.5); 95% CI: -3.2,-2.2] overall but no between-group difference was found. C2 participants improved significantly compared to C1 participants (p = 0.006) in left handgrip. C1 performed significantly better on the health knowledge test (p = 0.023; 95% CI: 0.018, 0.225) but neither cohort improved over time. The program is feasible for American children; however, careful consideration of setting and coaching staff is necessary.
Peritoneal dialysis is a widely used treatment for kidney failure; however, peritoneal dialysis-related infections (exit-site, tunnel infection, peritonitis) occur frequently. The effect of standardised nurse and patient training on peritoneal dialysis infections is uncertain. The aim of this study was to determine whether implementing an international guideline-based standardised training curriculum for nurse trainers and new peritoneal dialysis patients reduces the risk of peritoneal dialysis-related infections compared with existing local training practices. Targeted Education ApproaCH to improve Peritoneal Dialysis (TEACH-PD) was a pragmatic, investigator-initiated, cluster-randomised controlled trial conducted in Australia and New Zealand. Adult patients 18 years of age or older with kidney failure who required training for incident peritoneal dialysis treatment and who were able to provide written informed consent were eligible. Clusters were randomised 1:1 to either the standardised training curriculum or usual care. Participant data and infection outcomes were routinely collected in national patient registries. The primary outcome was time to first peritoneal dialysis-related infection (exit site infection, tunnel infection, or peritonitis). Secondary outcomes were the first of each individual infection type in the primary composite outcome, catheter removal, haemodialysis transfer, all-cause death and quality of life. This trial was registered with ClinicalTrials.gov, number NCT03816111. Between 22 July 2019 and 29 September 2023, 42 clusters were randomised: 21 to the standardised training group and 21 to the usual care group. Overall, 1462 incident peritoneal dialysis patients were included; 667 were assigned to the standardised training group and 795 to the usual care group. A peritoneal dialysis-related infection occurred in 296 of 667 patients in the standardised training group and 297 of 795 patients in the usual care group (sub-hazard ratio 1.230, 95% confidence interval [CI] 1.004-1.507, p = 0.0457). Secondary outcomes were similar in the two groups. Among patients commencing peritoneal dialysis, the use of a standardised training curriculum for nurses and patients based on the International Society for Peritoneal Dialysis guidelines increased peritoneal dialysis-related infection. Implementation-focused research is needed to identify which elements of training require standardisation and where individualisation is most beneficial to support safe, sustainable and patient-centred peritoneal dialysis care. The TEACH-PD trial is funded by MRFF Clinical Trials Activity: Rare Cancers, Rare Diseases and Unmet Need Grant Opportunity; National Health & Medical Research Council BEAT-CKD Program Grant; Health Research Council of New Zealand grant; Metro South Health Research Support Scheme Research Fund-Health System and Health Economics Project Grant; Queensland Health; South Western Sydney Research Small Grant Scheme; International Society for Peritoneal Dialysis; Translational Research Institute Australia; Amgen and Baxter Healthcare (Vantive).
Co-design in health services is increasingly recognised as essential for creating services and policies that address patient and community needs. However, genuine co-design can be challenging, with existing toolkits often catering to professionals, reinforcing power imbalances and limiting community leadership. This paper aims to present a novel co-design framework for health services and describe the co-design process taken in its development. The co-design process involved a series of engagement activities (online forums, focus groups, discussions and workshops) with health consumers, health professionals and researchers within a metropolitan health service in Queensland, Australia. This process, co-led by a clinician researcher and health consumer, explored the implicit meaning of co-design and the barriers and enablers to co-design within the local setting, and the strategies required to support operationalisation of co-design. These data were combined with research literature, existing frameworks and lived experience to iteratively co-design the online framework. Eight focus groups, forums and workshops across five hospitals and multiple community health services involved 128 individuals who contributed their professional and lived experience with co-design to inform the development of the co-design framework. The resultant 'Better Healthcare Together' framework includes three main components: (1) before you start co-design, (2) the co-design team and (3) the co-design process. A key feature of the framework is its deliberate focus on power, inclusion, equity, and bringing together diverse lived and professional experience to solve healthcare problems. This co-design framework provides a flexible approach to consumer partnerships, with reflections on the process highlighting the relational nature, the need to avoid expert mindset and the evolving landscape of consumer engagement. While widely used, the framework alone may not build true health system co-design capability due to the need to address systemic and organisational barriers to co-design. Members of the public contributed to this work across all stages of this project, including as project co-leads and co-researchers, members of the steering committee, workshop co-facilitators, and co-design participants. They are also co-authors on this paper.
The functional and molecular definition of progenitors giving rise to blood vessel endothelium in vivo remains disputed. Upon investigating the overlap of seemingly divergent reports currently defining putative endothelial progenitor cells (EPCs) using single-cell RNA-sequencing and flow cytometry, Protein C Receptor (PROCR) and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) largely overlapped with previously characterized murine aorta's CD34+CD31low endovascular progenitors (EVPs). Functional assays and lineage tracing in homeostatic aorta and excisional wounds demonstrated increased clonogenic capacity, engraftment potential, and ability to form differentiated endothelial (D) cells of PROCR+ PDGFRA+ EPCs, termed as refined endothelial progenitor cell (rEPC), as compared to PROCRnegPDGFRAneg EVPs. Similar PROCR and PDGFRA expression in normal human aorta, and increased clonogenic capacity of CD34+CD31lowPROCR+ endothelial cells from freshly isolated human term placenta were observed as compared to controls. Functional validation of human rEPCs is supported by PROCR enrichment, while PDGFRA co‑expression in human endothelial progenitor-like cells is supported at the transcriptomic level only. Thus, overlapping PROCR and PDGFRA expression in EVPs narrows the population with true functional progenitor capacity.
Hepatitis A virus (HAV) causes acute hepatitis through ingestion of contaminated food and water, with bivalve molluscs as common vehicles of transmission. As filter feeders, HAV concentrates in their digestive tissues when grown in contaminated waters. In 2020, the Philippines produced nearly 75 MT of shellfish. However, maintaining proper sanitation in growing areas remains challenging, and data on the occurrence of HAV in these commercially significant shellfish is lacking. This study aimed to detect HAV in Philippine cupped oysters (Magallana bilineata), green mussels (Perna viridis), and seawater from their growing areas. Samples were collected in Pangasinan (August 2022), Cavite (April 2023), and Capiz (June 2023), and HAV detection was conducted using quantitative reverse transcription polymerase chain reaction (RT-qPCR). HAV RNA was not detected in the shellfish and seawater samples, consistent with zero reported cases of Hepatitis A during the collection periods. However, a disparity was noted between these findings and potential sewage run-off linked to net positive rainfall. The Department of Health reported 111 and 127 Hepatitis A cases nationwide in 2022 and 2023, respectively, indicating that HAV remains endemic. Identifying sources, transmission modes, and environmental factors is crucial for integrating HAV risks into the food safety risk assessment framework.
Recurrent/Metastatic (R/M) ACC is aggressive with few effective treatment options. The role of surgery after chemotherapy remains unclear. Moreover, prognostic factors in R/M ACC are not well defined. R/M ACC patients treated at Princess Margaret Cancer Centre (2002-2019) were retrospectively reviewed. Descriptive statistics were used to summarize clinical characteristics. OS was estimated by Kaplan-Meier method. Cox regression analysis was used to compute prognostic variables. Among 83 patients with metastatic ACC [36.2% de novo and 63.8% recurrent], 49 (59.0%) received systemic therapy (ST) with which 15 (30.6%) had a partial response (PR) and 8 (16.3%) had stable disease (SD). 9 (18.4%) had surgery after ST (combined therapy group); 6 (66.6%) were rendered disease free with surgery. The median OS was 26 months (20.4-40.5) for entire cohort (f/up 18 months). OS for patients having combined therapy was 31.2 months (21.4-63.3) vs 24.7 months (17.7-35.2), p = 0.48 for patients receiving systemic therapy alone. Being disease free after surgery was associated with better OS [39.6 (24.8-not reached), vs 23.5 months (21.4-not reached), p = 0.02]. Selected patients with R/M ACC may achieve long term survival with surgery after chemotherapy. These data highlight the potential role for multimodal therapy in managing such patients.
Effective surgical antimicrobial prophylaxis requires activity against likely pathogens and antibiotic concentrations above the minimum inhibitory concentration (MIC) throughout surgery. We compared microbiological coverage and PK/PD target attainment of cefazolin, cefuroxime or vancomycin, alone or with gentamicin, for primary total knee or hip arthroplasty. We linked two datasets: archived prosthetic joint infection (PJI) isolates after primary total knee or hip arthroplasty, used for susceptibility testing and MIC determination; and plasma antibiotic concentrations at closure from a 135-patient prospective cohort receiving a study regimen. We assessed microbiological coverage (percentage of isolates susceptible to ≥1 antibiotic) and PK/PD target attainment (percentage with isolate-specific MICs below the free plasma concentration at closure of ≥1 antibiotic, irrespective of categorical susceptibility). Among 75 isolates, coagulase-negative staphylococci (CoNS) (27; 36%) and Staphylococcus aureus (26; 35%) predominated. Single-agent coverage and PK/PD attainment were 49.3% and 72.0% for cefazolin, 52.0% and 64.0% for cefuroxime, and 81.3% and 81.3% for vancomycin. Only cefazolin showed a significant discrepancy between microbiological coverage and PK/PD attainment (p=0.004), mainly due to methicillin-resistant CoNS: 13/19 (68.4%) had MICs below the free concentration at closure despite categorical non-susceptibility. Gentamicin increased coverage (to 80.0%, 81.3% and 96.0%) and PK/PD attainment (to 89.3%, 82.7% and 96.0%), mainly through improved Gram-negative activity. Vancomycin-containing regimens outperformed cefuroxime-containing, but not cefazolin-containing, regimens in PK/PD attainment. Cefazolin may retain prophylactic activity against methicillin-resistant CoNS despite categorical non-susceptibility. Vancomycin-containing regimens had the highest PK/PD performance but were not significantly superior to cefazolin-based regimens. Gentamicin improved Gram-negative activity.
Maternal mental health has been linked to a range of offspring outcomes; however, population-based evidence examining intergenerational associations across multiple health-related quality of life (HRQoL) domains over the life course remains limited. This study examines associations between maternal mental health and offspring HRQoL using nationally representative longitudinal data from Australia. We used data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. The analytic sample comprised 8,737 offspring linked to 4,966 mothers. Three offspring's HRQoL outcomes were examined: mental health and general health domain of the SF-36 instrument and the Kessler Psychological Distress Scale. Maternal mental health was measured using the SF-36 mental health domain. Associations were estimated using weighted linear regression models with standard errors clustered at the maternal level, adjusting for socioeconomic and demographic characteristics. Gender differences were examined using interaction terms. Higher maternal mental health was significantly associated with better offspring mental health in fully adjusted models (β = 0.485 SD, p < 0.001). Higher maternal mental health was also associated with better offspring general health (β = 0.458 SD, p < 0.001). For psychological distress, higher maternal psychological distress was associated with higher offspring psychological distress (β = 0.419 SD, p < 0.001). Higher maternal mental health was also positively associated with offspring psychological distress (β = 0.216 SD, p < 0.001); however, this reflects differences in measurement constructs (higher distress scores indicate worse outcomes) and should be interpreted cautiously. Associations remained statistically significant after covariate adjustment and did not differ by offspring gender. Maternal mental health is associated with multiple dimensions of offspring HRQoL across the life course. These findings highlight maternal mental health as an important correlate of offspring health and underscore the relevance of family-centred, preventive strategies aimed at reducing intergenerational inequalities in mental health.
Linezolid is a critical last-resort antimicrobial for multidrug-resistant Enterococcus faecium, particularly against vancomycin-resistant lineages where therapeutic options are severely limited. While resistance has historically arisen through de novo chromosomal mutations, the global emergence of transferable resistance mechanisms threatens to render more infections untreatable. Here, we characterize a recent (2023-2024) hospital-associated outbreak of linezolid-resistant E. faecium in Queensland, Australia. Although the cohort comprised a variety of sequence types, the outbreak was primarily driven by the clonal expansion of an ST80 lineage carrying the plasmid-borne poxtA gene. Standard short-read genomic surveillance failed to resolve the genetic context of the resistance determinant. However, long-read sequencing revealed that poxtA was carried within a novel transposon, Tn8026, situated on a linear plasmid. Structural analysis defined Tn8026 as a unique element flanked by IS1678 and the novel insertion sequence ISEfa26. Furthermore, we identified an instance of Tn8026 integration into the chromosome, providing functional evidence of its mobility and capacity for stabilization within the genome. Global genomic screening demonstrated that Tn8026 significantly predates the local outbreak, identified in a historical Norwegian isolate from 2012, indicating a long-standing yet unrecognized global reservoir. Phylogenomic analysis provided strong evidence that the linear plasmid was imported from the Indian subcontinent, initiating a chain of silent dissemination in eastern Australia where the lineage circulated undetected prior to clinical recognition. Crucially, we also confirmed the presence of the linear plasmid in Enterococcus gallinarum, demonstrating its capacity to mobilize transmissible linezolid resistance across enterococcal species boundaries. These findings emphasize the need for detailed long-read-based surveillance of mobile genetic elements, with a particular focus on identifying linear plasmids that are often overlooked.
Peer-supported self-management at discharge from early intervention in psychosis services (EIPS) has received limited attention. The MyPREPED (My Personal Recovery Plan for Early Discharge) trial will evaluate a co-designed, digital and paper-based, peer-delivered recovery and self-management focused intervention, tailored for young people exiting EIPS. This protocol describes a hybrid type 2 effectiveness-implementation trial designed to assess MyPREPED's impact, feasibility, real-world implementation and cost-utility. This multi-site, mixed-method, two-arm (1:1), parallel-group, randomised controlled trial (MyPREPED versus treatment as usual) trial will be delivered across eight Australian EIPS that deliver ultra-high risk and/or first-episode psychosis streams, using a hybrid type 2 implementation-effectiveness design. Eligible participants are young people aged 16 years and over within 6 months of planned discharge from EIPS. Peer coaches will deliver up to ten sessions of using a self-management plan (modules: discharge, recovery, well-being, relapse prevention, goal-setting, service navigation). Co-primary outcomes include (a) mental health recovery (Recovery Assessment Scale - Domains and Stages; effectiveness outcome) and (b) feasibility (Feasibility of Implementation Measure; implementation outcome). Secondary outcomes assess broader effectiveness domains (mental health quality of life, clinical and functional outcomes) and other implementation outcomes. A cost-utility analysis will estimate incremental costs and quality-adjusted life-years associated with MyPREPED, alongside a secondary cost-effectiveness analysis. Analyses will follow intention-to-treat principles, using mixed-effects models. This study will provide the first rigorous test of a co-designed, peer-delivered recovery and self-management focused intervention specifically targeting EIPS discharge.
Although rebiopsy at progression on osimertinib is recommended for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), its real-world impact on clinical outcomes remains unclear. Rebiopsy on Osi is a multicenter, retrospective study assessing rebiopsy patterns, resistance mechanisms, and their impact on second-line treatment choices and outcomes in routine clinical practice. A total of 457 patients with advanced NSCLC harboring a common EGFR mutation (exon 19 deletion or L858R) who progressed on first-line osimertinib were identified from the Italian ATLAS registry. Patients were stratified according to rebiopsy status (tissue and/or plasma-based next generation sequencing) and receipt of biomarker-driven adaptive second-line therapy. Rebiopsy was performed in 206 patients (45.1%), predominantly via tissue sampling (66.2%). A resistance mechanism was identified in 80 cases (38.8%), with higher detection rates by tissue rebiopsy (46.6%) versus liquid (13.5%). MET amplification/overexpression emerged as the most frequent actionable resistance mechanism. Among 239 patients treated with second-line therapy, 39 (16.3%) received adaptive treatment, including 29 out of 39 patients (74.3%) with MET amplification/overexpression treated with a MET-TKI-based regimen. Median progression-free (PFS) and overall (OS) survival were longer with adaptive therapy (7.3 and 14.1 months) than with rebiopsy without treatment adaptation (6.5 and 12.2 months) or no rebiopsy (5.1 and 8.2 months). In real-world practice, rebiopsy identifies a resistance mechanism in slightly more than one third of patients, with actionable MET amplification/overexpression accounting for approximately one fifth of cases. Biomarker-driven adaptive therapy may improve clinical outcomes, supporting implementation of rebiopsy in routine practice.