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Value of a secretomic approach for distinguishing patients with COVID-19 viral pneumonia among patients with respiratory distress admitted to intensive care unit.

In intensive care units, COVID-19 viral pneumonia patients (VPP) present symptoms similar to those of other patients with Nonviral infection (NV-ICU). To better manage VPP, it is therefore interesting to better understand the molecular pathophysiology of viral pneumonia and to search for biomarkers that may clarify the diagnosis. The secretome being a set of proteins secreted by cells in response to stimuli represents an opportunity to discover new biomarkers. The objective of this study is to identify the secretomic signatures of VPP with those of NV-ICU. Plasma samples and clinical data from NV-ICU (n = 104), VPP (n = 30) or healthy donors (HD, n = 20) were collected at Nantes Hospital (France) upon admission. Samples were enriched for the low-abundant proteins and analyzed using nontarget mass spectrometry. Specifically deregulated proteins (DEP) in VPP versus NV-ICU were selected. Combinations of 2 to 4 DEPs were established. The differences in secretome profiles of the VPP and NV-ICU groups were highlighted. Forty-one DEPs were specifically identified in VPP compared to NV-ICU. We describe five of the best combinations of 3 proteins (complement component C9, Ficolin-3, Galectin-3-binding protein, Fibrinogen alpha, gamma and beta chain, Proteoglycan 4, Coagulation factor IX and Cdc42 effector protein 4) that show a characteristic receptor function curve with an area under the curve of 95.0%. This study identifies five combinations of candidate biomarkers in VPP compared to NV-ICU that may help distinguish the underlying causal molecular alterations.

Humans

Measuring economic efficiency in adult intensive care units: A systematic review of methods, metrics, and evidence.

OBJECTIVES: Intensive care units (ICUs) consume substantial hospital resources, yet "efficiency" is inconsistently defined and measured. This study systematically reviewed how economic efficiency has been conceptualised and quantified in adult ICUs and appraised the quality of evidence. METHODS: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD420251107866), we searched MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science (2000-August 2025), plus global grey sources. Eligible studies explicitly defined efficiency and reported an efficiency metric/model linking ICU inputs (e.g., staff, beds/capacity, time, consumables, or costs) to outputs/outcomes (e.g., throughput/discharges, length of stay/resource use, risk-adjusted mortality). Dual independent screening and extraction were performed. Study quality was appraised using MMAT, and findings were synthesised narratively (SWiM), given heterogeneity. RESULTS: 39 studies (2001-2025) from 17 countries were included, all from high-income or upper-middle-income settings. Four methodological families were identified: (1) frontier modelling (predominantly DEA; occasional SFA/RFDH), (2) benchmarking indicators (risk-adjusted mortality and LOS/resource-use ratios; "efficiency matrix" quadrant classification), (3) cost-outcome evaluations, and (4) operational/process metrics. Across families, variation in decision-making units, input/output selection, and risk adjustment limited comparability; long-term and patient-reported outcomes were absent, and equity considerations were uncommon. CONCLUSIONS: ICU efficiency research is feasible but fragmented and often methodologically limited. Standardised definitions, validated risk adjustment, uncertainty quantification, and inclusion of patient-centred and equity-relevant outcomes are needed before efficiency metrics can reliably inform value-based decision making.

Intensive Care Units

Gut Colonization With Vancomycin-Resistant Enterococcus Shapes the Gut Microbiome in the Intensive Care Unit.

BACKGROUND: Gut pathogen colonization with vancomycin-resistant Enterococcus (VRE) is common in the intensive care unit (ICU) and is associated with worse clinical outcomes; however, the timing of VRE colonization and its collateral effects on the gut microbiome are incompletely understood. METHODS: Medical ICU patients admitted with sepsis and receiving broad-spectrum antibiotics were sampled via deep rectal swabs at ICU admission and on ICU day 3, 7, 14, and 30. Rectal swabs were cultured for VRE on selective media and analyzed via 16S ribosomal RNA gene sequencing. RESULTS: Ninety patients were sampled (340 longitudinal swabs). VRE positivity rose from 20% at ICU admission to a peak of 33% by ICU day 14 and then modestly declined to 31% by ICU day 30. Paralleling this, alpha diversity fell while Enterococcus relative abundance rose through ICU day 14 with both returning to baseline by ICU day 30. The median relative abundance of Enterococcus was 38% (interquartile range [IQR], 7.4%-75%) for VRE-positive samples compared to 0.01% (IQR, 0%-19%) for VRE-negative samples (rank-sum P < .01); 38 samples had &#x2265;90% Enterococcus and 8 samples were 100% Enterococcus by sequencing. VRE was associated with lower alpha diversity (median Shannon index 1.90 [IQR, 0.89-2.66] if VRE positive versus 2.64 [IQR, 1.58-3.22] if VRE negative; P < .01). CONCLUSIONS: VRE gut colonization peaked at ICU day 14 followed by a modest decline and was associated with low alpha diversity. Improved understanding of dynamic changes in the gut microbiome may facilitate successful future ICU interventions. CLINICAL TRIALS REGISTRATION: NCT03865706.

Aged

Implementing customized genomic sequencing reports to empower providers in safety-net neonatal intensive care units.

PURPOSE: Through our implementation study providing rapid genomic sequencing (rGS) in safety-net neonatal intensive care units (NICUs), we investigated the feasibility and perceived usefulness of customized "clinical interpretive reports" (CIRs) to help neonatal providers with interpreting, disclosing, and managing care based on rGS results. METHODS: Enrolled infants received rGS through a clinically accredited vendor. We developed 5 CIR types to provide customized interpretation of rGS results and link results to clinical management considerations, research opportunities, and resources. We developed workflows to triage, create, and deliver CIRs within 3 business days. Providers received the vendor reports and CIRs, disclosed results, and completed post-disclosure surveys. We analyzed summary statistics for the first 100 cases. RESULTS: We delivered 97 of 100 CIRs (97%) within our goal time frame (average 1.3 days) and provided clinical management recommendations in 40 of 100 (40%). Neonatal providers completed the post-disclosure surveys for 86 of 100 disclosures (86%). Most reported using the CIR before disclosure (80/86, 93%) and found it helpful at providing useful information beyond the vendor report (79/80, 99%). CONCLUSION: It is feasible and useful to develop customized rGS reports to assist non-genetics providers in safety-net NICU settings. Similar approaches may hold promise for equitably advancing genomic care in non-NICU settings.

Humans

Clinical impact of metagenomic next-generation sequencing for pathogen identification and guided therapy in pediatric intensive care unit patients with severe pulmonary infections.

UNLABELLED: To explore the diagnostic efficiency, clinical concordance, and precision treatment value of metagenomic next-generation sequencing (mNGS) for severe pulmonary infections in children in the pediatric intensive care unit (PICU), and to provide evidence for improving microbiological diagnosis and optimizing anti-infective strategies. A retrospective cohort study included 89 children with severe pneumonia in the PICU in 2024. All underwent routine microbiological testing and mNGS of bronchoalveolar lavage fluid (BALF). Detection rates, pathogen composition, co-infection identification, diagnostic concordance, and treatment impact were analyzed. Metagenomic next-generation sequencing demonstrated high diagnostic sensitivity in the PICU setting, achieving a positive detection rate of 90.0% (80/89) and identifying a diverse spectrum of 103 pathogens, including 50.5% viruses, 43.7% bacteria, 38.8% co-infections (vs 11.6%), and 86.3% diagnostic concordance (vs 55.8%, P < 0.01). Among 46 patients included in the therapeutic outcome analysis (22 in the mNGS-guided group), 21 patients in the mNGS-guided group improved. Multivariate logistic regression analysis, adjusting for confounding factors (age, underlying diseases, PaO2/FiO2 ratio, PRISM III score, and preoperative antibiotic use duration), confirmed that mNGS-guided therapy was an independent protective factor for achieving the primary outcome (OR = 5.23, 95% CI: 1.87-14.61, P = 0.002) and secondary outcomes (C-reactive protein reduction &#x2265;50%: OR = 4.89, 95% CI: 1.72-13.93, P = 0.003; oxygenation improvement: OR = 5.67, 95% CI: 1.98-16.21, P = 0.001). Metagenomic next-generation sequencing demonstrated high diagnostic sensitivity in the PICU setting, guiding precision therapy, and improving prognosis. IMPORTANCE: It supports metagenomic next-generation sequencing (mNGS) as a supplementary tool for pediatric intensive care unit (PICU) refractory infections, guides anti-infective adjustments, and informs tiered diagnostic pathways for resource-limited settings to optimize cost-effectiveness.

Humans

Rapid genome sequencing identifies treatable conditions in non-intensive care unit hospitalized children.

PURPOSE: The utility of rapid genome sequencing (RGS) has been evaluated in pediatric intensive care unit (ICU) settings, but few studies have investigated its use in non-critically ill hospitalized children. Our study assesses the impact of RGS use in the non-ICU setting. METHODS: We analyzed RGS results obtained for hospitalized children from 2019 to 2023 and evaluated the impact on non-ICU patient care. Changes in management were determined via chart review of the first 30 days after testing. RESULTS: RGS was performed on 422 individuals: 339 ICU and 83 non-ICU. The diagnostic rate was 39% (32 of 83) in non-ICU and 35% (120 of 339) in ICU patients. Eighty-one percent of diagnostic RGS results in non-ICU patients had a management change within 30 days, and 56% (18 of 32) received a disease-targeted intervention, including medication or diet change, listing for transplant, or connection with a clinical trial. Of the children who received these intervention changes, the most common disease categories were metabolic (61%, 11 of 18) and epilepsy (22%, 4 of 18). CONCLUSION: RGS is effective at identifying treatable diagnoses in the non-ICU setting, with most patients experiencing a change in their care, and over half receiving disease-focused interventions. Our results support the utility of RGS in non-ICU hospitalized children and can impact providers' decision-making and payer coverage.

Genome sequencing

Candida auris outbreak in a cardiothoracic transplant intensive care unit: implications for infection prevention practices and keeping pace with an evolving landscape.

OBJECTIVE: To describe the mitigation strategies for a Candida auris outbreak in a cardiothoracic transplant intensive care unit (CTICU) and its implications for infection prevention practices. DESIGN: Retrospective cohort study from July 2023 to February 2024. SETTING: A large academic medical center. METHODS: A multidisciplinary team convened to conduct the outbreak investigation and develop mitigation strategies in the CTICU. RESULTS: From July 2023 to February 2024, 34 possible hospital-onset cases of C. auris were identified in our CTICU. Whole-genome sequencing and phylogenetic analysis based on pairwise single nucleotide polymorphism (WG-SNP) distance revealed two distinct outbreak clusters. Of the 34 patients, 11 (32.3%) were solid organ transplant recipients and 12 (35.3%) had a mechanical circulatory support device. Of the cohort, only 11/34 (32.3%) had prior exposure to high-risk healthcare facilities within six months prior to admission, as follows: acute inpatient rehabilitation facilities (AIRs) (n = 5, 14.7%), skilled nursing facilities (SNFs) (n = 3, 8.8%), and long-term acute care hospitals (LTACHs) (n = 3, 8.8%). The cohort had a median of 22.0 antibiotic-days prior to their positive results. Five (14.7%) patients had C. auris candidemia, three of whom expired likely due to infection. Infection Prevention (IP) interventions addressed several modes of transmission, including healthcare personnel hands, shared patient equipment, and the environment. CONCLUSION: Our experience suggests that the epidemiology of C. auris may be changing, pointing towards a rising prevalence in acute care settings. IP interventions targeting hand hygiene behavior and promoting centralizing cleaning and disinfection of shared patient equipment may have contributed to outbreak resolution.

Humans

Impact of early nurse-led implementation of an intensive care unit diary following major trauma on quality of life: The QUALITRAU randomized controlled trial.

BACKGROUND: Survivors of major trauma often experience long-term impairments in health-related quality of life (HRQoL) and post-traumatic stress disorder (PTSD). Intensive care unit (ICU) diaries have been proposed to reduce psychological sequelae, but evidence remains conflicting and not specific to trauma patients. OBJECTIVE: To assess whether, in patients with major trauma, a nurse-led ICU diary implemented within the first 48&#xa0;h after trauma improves HRQoL at 1&#xa0;year vs. usual care. METHODS: The QUALITRAU randomized controlled trial was conducted in three ICUs of a French tertiary hospital. Adult patients with major trauma (Injury Severity Score&#xa0;>&#xa0;15) were randomized within 48&#xa0;h of admission to receive either an ICU diary combined with usual care or usual care alone. The primary outcome was HRQoL at 12&#xa0;months, assessed with the 4 domains of the WHOQOL-BREF questionnaire. Secondary outcomes included PTSD severity measured with the Impact of Event Scale (IES). Analyses were performed on an intention-to-treat basis. RESULTS: Between November 2014 and November 2016, 208 patients were randomized (101 intervention, 107 control), with primary outcome available for 121 (53 intervention, 68 control). Median age was 35&#xa0;years [IQR 25-51], 81% were men, and 63% had severe traumatic brain injury. At 12&#xa0;months, there were no differences between intervention and control groups in the WHOQOL-BREF domains (physical: 5.7 [IQR 4.6-11.4] vs 9.1 [IQR 4.6-13.1],P&#xa0;=&#xa0;0.16; psychological: 8.0 [IQR 6.7-13.3] vs 11.3 [IQR 6.7-13.3],P&#xa0;=&#xa0;0.08; social: 5.3 [IQR 4.0-14.7] vs 12.0 [IQR 4.0-14.7],P&#xa0;=&#xa0;0.10; environment: 8.0 [IQR 5.5-14.5] vs 12.0 [IQR 5.5-15.5], P&#xa0;=&#xa0;0.05). IES scores were also not different. CONCLUSIONS: Early implementation of nurse-led ICU diaries was not associated with improved long-term HRQoL or reduced PTSD symptoms in patients with major trauma. IMPLICATION FOR CLINICAL PRACTICE: These findings suggest that ICU diaries may need to be integrated into broader, multimodal rehabilitation strategies and may depend on factors such as timing, content, or patient characteristics.

Humans

Teaching Engagement and Caregiving Help in the Intensive Care Unit (TEACH-ICU) Scale: Content Validity.

BACKGROUND: Having family members provide care to their loved ones in the intensive care unit (ICU) is a beneficial yet seldom implemented approach. For family members to perform caregiving, nurses must be willing to teach, and such willingness is a developing area of research. OBJECTIVES: To adapt an instrument validated in family members, the Family Willingness for Caregiving Scale, to address nurses' willingness to teach family members caregiving skills. METHODS: Purposive and snowball sampling were used to recruit 10 expert ICU nurses through the American Association of Critical-Care Nurses' research website and social media platforms. The researchers conducted cognitive interviews with the nurses to address the instrument's content validity. RESULTS: The scale was refined based on the participants' feedback. Items were deleted, added, and revised. Furthermore, scale instructions were adjusted to emphasize the willingness to teach families of patients receiving mechanical ventilation. Qualitative themes emerged related to barriers to family engagement, including time constraints, patient acuity, and nurse and family characteristics. CONCLUSIONS: Content validity of the scale was assessed, with future research aimed at pilot testing and evaluating construct validity before using the scale as a research instrument. Practical implications include using the scale as an evaluation tool to determine nurses' willingness to teach family members about caregiving. After evaluation, various strategies could be incorporated to enhance family engagement in adult ICUs.

Humans

Rapid pan-microbial metagenomics for pathogen detection and personalised therapy in the intensive care unit: a single-centre prospective observational study.

BACKGROUND: Most clinical metagenomic studies do not provide rapid results, detect pathogens from all microbial kingdoms, or measure clinical impacts. We aimed to evaluate the feasibility, performance, and clinical impacts of a rapid pan-microbial respiratory metagenomic service for patients admitted to intensive care units (ICUs). METHODS: This was a single-centre observational study of a rapid metagenomics service that tests respiratory samples from ICU patients at Guy's and St Thomas' hospitals, London, UK, between Dec 5, 2023, and April 12, 2024. Testing used a previously published pan-microbial metagenomics workflow, which simultaneously detects bacteria, fungi, and DNA and RNA viruses; provides same-day preliminary results after 2 h; and provides final results after 24 h. Patients were included if they were aged 18 years or older, admitted to the ICU, had confirmed respiratory failure requiring supplemental oxygen or advanced airway support, and had at least one of the following: (1) clinical suspicion of lower respiratory tract infection based on clinical, biochemical, or radiological findings, (2) sepsis of unknown origin, and (3) concern from an intensive care physician regarding inflammatory pathology. Patients with a suspected or confirmed containment level three organism were excluded. The outcome was performance characteristics of the metagenomic test compared with routine diagnostic testing, detection of additional pathogens by metagenomics, change in antimicrobial prescribing within 24 h of testing, and initiation of immunomodulation. FINDINGS: We processed 114 samples (1-5 per day) from 74 patients (39 [53%] female and 35 [47%] male). 107 (94%) of 114 samples passed quality control, of which 101 (94%) provided same-day preliminary results. Bacteria were detected in 45 (43%) of 104 tested specimens, fungal organisms in 17 (16%) of 104 tested specimens, and viruses in 28 (34%) of 83 tested specimens. Sensitivity in lower respiratory tract samples after 24 h was 97% (95% CI 87-100) for bacteria, 89% (65-99) for fungi, and 89% (71-98) for viruses, with only one false positive for bacteria. Metagenomics identified 42 pathogens not detected by other tests in 32 (30%) of 107 samples. Antimicrobial therapy was changed after metagenomic results from 30 (28%) of 107 samples: 22 (21%) were de-escalated and eight (7%) were escalated. Metagenomics contributed to the initiation of immunomodulation in 15 (20%) of 74 patients for a range of inflammatory conditions. Pathogens with clinical significance to local infection control or national public health were found in ten (14%) of 74 patients, including three invasive Group A streptococci, two parvovirus B19, and one each of HIV-1, measles virus, Mycobacterium tuberculosis, Neisseria meningitidis, and Mycoplasma pneumoniae. INTERPRETATION: Respiratory metagenomics for ICU patients showed good performance and turnaround time, and diverse clinical and public health benefits. This ability to inform both personalised patient therapy and infectious disease surveillance needs evaluation in multicentre studies. FUNDING: None.

Humans

Difficult-to-treat resistant Gram-negative bacteria and genomic resemblances between colonization and infection among patients in an intensive care unit of a tertiary care hospital in Bangladesh.

Colonization with difficult-to-treat-resistant Gram-negative bacteria (DTR-GNB) increases the risk of subsequent infections with limited treatment options. This study aimed to assess the burden of DTR-GNB colonization in ICU patients, explore its association with clinical outcomes, and examine genomic similarities. This secondary analysis included patients enrolled within 24 h of ICU admission between July 2023 and January 2024. Rectal swabs were collected at enrollment, on days 3, 7, and weekly during ICU stay to detect colonization. Bacterial isolates grown on selective chromogenic agar media were identified and tested for antimicrobial susceptibility using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and automated broth microdilution, respectively. Blood, urine, and/or tracheal aspirate cultures were performed if clinically suspected sepsis. Whole-genome sequencing (WGS) was performed on paired colonization and infection isolates, and genomic relatedness was assessed using FastANI, core-genome single-nucleotide polymorphism (SNP) analysis, and phylogenetic reconstruction. Among 373 patients, 181 (48.5%) were colonized with DTR-GNB; 76 (20.4%) at enrollment, and 105 (53.0%) acquired during hospital stay. Among 52 (13.9%) patients evaluated for suspected infection, 30 (57.7%) had positive cultures, predominantly Acinetobacter baumannii (n = 15) and Klebsiella pneumoniae (n = 11) of DTR-phenotypes. Compared to non-colonized patients, patients colonized with DTR-GNB had higher risks of infections (risk ratio [RR]: 2.18, 95% CI: 1.27-3.76) and longer ICU stays (median 7 vs 2 days, P < 0.001). DTR-GNB-infected patients had a higher risk of death (RR: 1.57, 95% CI: 1.34-1.84) compared to patients without DTR-GNB infection. WGS revealed that 13 of 14 paired colonization-infection isolates were conspecific, with three pairs being highly clonal; whereas the remaining pairs showed greater genomic divergence, consistent with the SNP and phylogenetic analyses. While common, more than half acquired DTR-GNB colonization from the ICU. Its association with subsequent infection and prolonged ICU stays underscores the need for enhanced infection prevention and control measures to mitigate nosocomial transmission and improve patient outcomes.IMPORTANCEThis study underscores the growing threat posed by difficult-to-treat resistant Gram-negative bacteria (DTR-GNB) in intensive care units. Nearly half of critically ill patients were colonized, with a considerable proportion acquiring these multidrug-resistant organisms during their ICU stay. Colonization with these pathogens substantially increased the risk of subsequent infections, even by the same colonizing strain, prolonged ICU stays, and likely worsened clinical outcomes due to the unavailability of susceptible antibiotics. Alarmingly, more than 90% of patients infected with DTR-GNB expired in the hospital. These findings highlight the urgent need for robust infection prevention and control strategies to curb nosocomial transmission and mitigate the impact of DTR-GNB on vulnerable patient populations. Addressing this emerging resistance phenotype is critical to improving patient safety and reducing the burden on healthcare systems.

Humans

Direct Oral Anticoagulant Transition Strategies Using Anti-Xa Concentrations Upon Intensive Care Unit Admission.

Background: The increased utilization of oral factor Xa inhibitors (FXaI) has led to a growing interest in the clinical utility of FXaI-specific anti-Xa concentrations. Critically ill populations are at risk of bleeding secondary to FXaI accumulation in the setting of end-organ dysfunction. To mitigate this risk, an FXaI anti-Xa concentration-guided approach to transitioning between oral and parenteral anticoagulation has been explored. Objective: To compare the incidence of bleeding upon intensive care unit (ICU) admission between 2 different FXaI transition strategies: concentration versus non-concentration-guided. Methods: We performed a retrospective chart review of patients admitted between January 2019 and May 2022 with objective evidence of FXaI exposure within 48 hours preceding ICU admission. Patients were excluded if they were admitted to the ICU with a primary diagnosis related to a bleeding event, received a non-FXaI anticoagulant 48 hours preceding ICU admission, remained off anticoagulation during their ICU admission, or underwent surgical procedures. The primary outcome was the incidence of major bleeding within 5 days of ICU admission. Thromboembolic events were evaluated as a secondary endpoint. Results: A total of 433 patients (184 concentration-guided vs 249 non-concentration-guided) were included. There was no difference in major bleeding between groups (2.7% in concentration-guided vs 3.6% in non-concentration-guided; P = 0.79). Thromboembolic complications were similar between groups (1.6% in concentration-guided vs 2.0% in non-concentration-guided; P = 1.00) despite a longer time from last FXaI dose to anticoagulant transition in the concentration-guided group (29.9 hours vs 19.4 hours; P < 0.01). Conclusion and relevance: Use of FXaI concentrations to guide anticoagulation transition in the ICU had no impact on major bleeding events or thromboembolic complications. Further analyses are needed to validate FXaI concentration-guided strategies and solidify anti-Xa cutoffs to create a standardized approach to FXaI transitions in the critically ill patient population.

DOAC

Effectiveness of chlorhexidine gluconate-impregnated dressings in preventing central line-associated bloodstream infection in a paediatric intensive care unit: A randomised controlled trial.

OBJECTIVES: To compare the effectiveness and dermatological safety of chlorhexidine gluconate (CHG)-impregnated dressings versus conventional transparent dressings in preventing central line-associated bloodstream infection (CLABSI) in paediatric patients admitted to a PICU. METHODS: A single-blind, randomised controlled trial with a 1:1 allocation ratio was conducted in a tertiary PICU. A total of 250 paediatric patients with a central venous catheter were included (125 per group). Patient characteristics, catheter-related variables, catheter dwell time and skin alterations were recorded. The primary outcome was CLABSI, defined according to CDC/NHSN criteria. Bivariate analyses and multivariable logistic regression were performed, including clinically relevant covariates related to catheter exposure, dressing type, and vaccination status. The trial was registered at ClinicalTrials.gov (NCT07175116). RESULTS: CLABSI incidence was significantly lower in the CHG group compared with the conventional dressing group (2.4% vs. 18.4%; p&#xa0;<&#xa0;0.001). In multivariable analysis, CHG-impregnated dressings were independently associated with reduced CLABSI risk (OR = 0.15; 95% CI: 0.04-0.58). Longer catheter dwell time (OR = 1.13 per day; 95% CI: 1.04-1.22) and absence of complete vaccination (OR = 8.68; 95% CI: 2.48-30.47) were also associated with increased infection risk. Incomplete vaccination showed a similar trend without reaching statistical significance (OR = 6.48; 95% CI: 0.95-44.20). Skin alterations were more frequent in the CHG group (16.8% vs. 11.2%), predominantly in younger infants. CONCLUSIONS: CHG-impregnated dressings were associated with a significant reduction in CLABSI incidence in critically ill paediatric patients, although their use was linked to a modest increase in mild skin reactions. IMPLICATIONS FOR CLINICAL PRACTICE: CHG-impregnated dressings may be considered as part of a multifaceted infection prevention strategy, alongside appropriate catheter management, minimisation of catheter manipulation and proactive skin monitoring, with cautious and individualised use in infants.

Humans

Advancing the science of Staphylococcus aureus infection prevention in the neonatal intensive care unit.

Despite advances in infection prevention, infections due to Staphylococcus aureus continue to be an important cause of morbidity and mortality in NICUs. Whole genome sequencing (WGS) using advanced analytic approaches for defining transmission have shed new insights into transmission and persistence patterns in the NICU. WGS has also helped uncover important associations between transmission, persistence, and the risk of invasive infections. Current infection prevention strategies rely on hand hygiene compliance and surveillance and decolonization of patients positive for S. aureus. Parent decolonization may also play a role in decreasing parent-child transmission. In the future, precision surveillance of high-risk strains and targeted infection prevention efforts to decrease bacterial burden of those specific strains may provide a more effective and efficient approach to decreasing risk of invasive infections.

Humans

Acceptability and Feasibility of an Educational Intervention to Improve Researcher-Participant Interactions in a Neonatal Intensive Care Unit Clinical Trial: Research Team Feedback on the BRIEF Intervention.

OBJECTIVE: Interactions with families are essential to successful recruitment conversations that promote informed decision-making about clinical research enrollment. However, there is little evidence about how to implement communication-oriented recruitment training among pediatric clinical research teams. Our objective was to evaluate the feasibility and acceptability of Better Research Interactions for Every Family (BRIEF), a multipart educational intervention to improve relationship-based conversations about clinical trial enrollment with families in the neonatal setting. STUDY DESIGN: We piloted BRIEF in partnership with a neonatal clinical research team. Research team members completed surveys following the BRIEF intervention's online module and the BRIEF group training session. They completed self-assessments after consent discussions before and after the BRIEF intervention, in which they rated their achievement of recruitment skills taught in BRIEF. Research team members also completed a final study interview to provide feedback on the intervention components, training content, and use of skills in practice. RESULTS: All nine research team members completed all components of BRIEF. Survey responses showed moderate to low satisfaction with previous recruitment training before BRIEF and high satisfaction with the BRIEF training. Self-assessments showed significant increases in reported partnership with bedside nursing (p&#x2009;=&#x2009;0.02) and confirmation of family names (p&#x2009;=&#x2009;0.05) after BRIEF training. Interviews provided further evidence of overall satisfaction with the BRIEF training, its content, and the skills learned, as well as opportunities for improvement, particularly in supporting challenging conversations. CONCLUSION: This pilot study demonstrated the feasibility and acceptability of the BRIEF intervention, as well as opportunities for improvement in future training. KEY POINTS: &#xb7; It was feasible to implement the BRIEF researcher training in a single-site NICU trial.. &#xb7; BRIEF training was acceptable to research team members.. &#xb7; BRIEF training shows potential to improve relationship-based research communication..

Humans

Applicability of Nanopore-only whole-genome sequencing for Pseudomonas aeruginosa outbreak investigation in the ICU setting: a multicentric study.

UNLABELLED: Pseudomonas aeruginosa outbreaks frequently occur in intensive care units (ICUs). In particular, ICU patients requiring mechanical ventilation are vulnerable to P. aeruginosa ventilator-associated pneumonia, which is associated with high morbidity and mortality. Fast and accurate genotyping during the early stage is crucial to document and manage P. aeruginosa outbreaks at the ICU. In this study, we have evaluated the applicability of Oxford Nanopore whole-genome sequencing (WGS) for outbreak investigation and antimicrobial resistance (AMR) prediction. To evaluate whether a Nanopore-only WGS workflow was able to reproduce Illumina-confirmed transmission clusters, 19 P. aeruginosa isolates from ICUs at UZ Brussels (Belgium) that were previously sequenced with Illumina were sequenced using a Nanopore-only workflow based on the latest V14 chemistry, followed by bioinformatic analysis via BugSeq and MBioSEQ Ridom Typer. Although both bioinformatic platforms showed high concordance between Illumina and Nanopore data, MBioSEQ Ridom Typer yielded the lowest allelic distance (maximum one cgMLST allele), confirming all outbreak clusters. When applying the Nanopore-only workflow to longitudinally collected isolates, low genetic heterogeneity (maximum three cgMLST alleles) was observed between isolates from the same patient. WGS and subsequent outbreak analysis of 65 respiratory P. aeruginosa isolates collected from 38 different ICU patients across six Belgian hospitals during a 9-month period showed no intra- or inter-hospital transmission. When the Nanopore-only WGS data were used to predict AMR, there was high categorical agreement (95%) between AMR genotype and phenotype. These findings highlight the potential of Nanopore WGS as a rapid and accurate tool for outbreak investigation of P. aeruginosa. IMPORTANCE: In recent years, Nanopore sequencing has found its way to clinical laboratories because of its affordability, scalability, and, most importantly, its ability to obtain sequencing results in near-real time. However, despite improved raw read accuracies with the latest generation R10.4.1 flow cells, the question remains whether the achieved accuracy is sufficient for accurate bacterial outbreak investigation, particularly in high-risk settings such as intensive care units (ICUs). In this study, we show that Nanopore-only whole-genome sequencing (WGS) is able to match Illumina-only WGS in terms of accuracy for Pseudomonas aeruginosa outbreak investigation in the ICU setting, although important sequence type-dependent and even strain-specific methylation issues need to be resolved in order to guarantee this accuracy. By providing a fast and accurate workflow for reliable P. aeruginosa outbreak investigation, this study could pave the way for large-scale implementation of Nanopore-only WGS, leading to faster outbreak response times.

Humans

Evaluating pregnancy and neonatal outcomes in mothers with genetic disease using electronic health care records.

PURPOSE: The effect of Mendelian disorders on pregnancy and neonatal outcomes is poorly understood because of their rarity and the challenge of compiling complete prenatal and postnatal records. METHODS: Using electronic health records from a single academic center, we developed a retrospective cohort of maternal-infant dyads. Cases were mothers with molecularly confirmed Mendelian disorders paired with live-born infants; controls had no documented genetic disease. Outcomes were evaluated overall, by organ system, and by individual disorder. RESULTS: The cohort included 58,912 dyads, 241 with genetic diagnoses and 58,671 controls. Although overall outcomes were generally favorable, mothers with genetic disorders had higher rates of cesarean delivery and neonatal intensive care unit admission, earlier gestational age, and lower Apgar scores. Neonatal risks were greatest among neurological and cardiovascular disorders. Known associations were replicated, including increased neonatal intensive care unit admission in 22q11.2 deletion syndrome, cesarean delivery in Turner syndrome, and gestational diabetes in cystic fibrosis. We also provided descriptive electronic-health-record-based case reports and case series for 35 disorders previously lacking published pregnancy outcome data. CONCLUSION: This study identifies elevated perinatal risks in specific Mendelian disease groups and demonstrates how electronic-health-record-linked data can support prenatal counseling, risk stratification, and individualized care for individuals with genetic disorders.

Humans

Treatment response variations to a single large bolus of enteral cholecalciferol in vitamin D deficient critically Ill children: Metabolomic insights for precision nutrition.

Vitamin D deficiency (VDD) is prevalent globally and in pediatric intensive care units, where it represents a modifiable risk factor that may impact patient recovery during hospitalization. Herein, we performed a retrospective analysis of serum samples from a phase-II randomized placebo-controlled trial involving a single large bolus of 10,000 IU/kg vitamin D3 ingested by critically ill children with VDD (25-OH-D < 50 nmol/L). Targeted and untargeted methods were used to comprehensively measure 6 vitamin D metabolites, 239 lipids, 68 polar metabolites, and 4 electrolytes using a multi-step data workflow for compound authentication. Complementary statistical methods classified circulating metabolites/lipids associated with vitamin D repletion following high-dose vitamin D3 intake (n&#x202f;=&#x202f;20) versus placebo (n&#x202f;=&#x202f;11) comprising an optional standard of care maintenance dose (< 1000 IU/day). There was a striking increase in median serum concentrations of 25-OH-D3 (4.7-fold), 3-epi-25-OH-D3 (24-fold) and their C3-epimer ratio (6.7-fold) in treated patients on day 3, whereas serum vitamin D3 peaked on day 1 (128-fold) unlike placebo. Treatment response differences were attributed to D3 bioavailability and C3-epimerase activity without evidence of hypercalcemia. For the first time, we report the detection of circulating 3-epi-D3 that was strongly correlated with vitamin D3 uptake (r&#x202f;=&#x202f;0.898). Metabolomic studies revealed that vitamin D sufficiency (serum 25-OH-D >75 nmol/L) coincided with lower circulating levels of 3-methylhistidine, cystine, S-methylcysteine, uric acid, and two lysophosphatidylcholines 7 days after treatment. Rapid correction of VDD was associated with indicators of lower oxidative stress, inflammation, and muscle protein turn-over that may contribute clinical benefits in high-risk critically ill children.

Humans