Burkholderia cenocepacia outbreak linked to taps in a neonatal intensive care unit.

Background: Burkholderia cenocepacia complex is an important cause of hospital acquired infections. We describe the management of an outbreak in a neonatal intensive care unit (NICU) due to tap colonisation.

Methods: Microbiological testing of touch (n = 26) and non-touch taps (n = 28), sinks and drains, including genomic sequencing of selected isolates.

Justification, margin values, and analysis populations for oncologic noninferiority and equivalence trials: a meta-epidemiological study.

Background: Noninferiority (NI) and equivalence trials evaluate whether an experimental therapy's effect on the primary endpoint (PEP) is contained within an acceptable margin compared to standard-of-care. The reliability and impact of this conclusion, however, is largely dependent on the justification for this design, the choice of margin, and the analysis population used.

Methods: A meta-epidemiological study was performed of phase 3 randomized NI and equivalence oncologic trials registered at ClinicalTrials.

Buruli ulcer in Australia: Evidence for a new endemic focus at Batemans Bay, New South Wales.

We describe two locally acquired cases of Mycobacterium ulcerans infection (Buruli ulcer) in the town of Batemans Bay on the east coast of New South Wales (NSW), Australia, 150 km north of Eden, the only other place in NSW where Buruli ulcer has likely been locally acquired. Genomic analysis showed that the bacterial isolates from the cases were identical but belonged to a phylogenetically distinct M. ulcerans clade that was most closely related to the isolate from the earlier case in Eden to the south.

Successful management of a multi-species outbreak of carbapenem-resistant organisms in Fiji: a prospective genomics-enhanced investigation and response.

Background: Fiji is a Pacific Island nation grappling with the increasing threat of antimicrobial resistance (AMR). While genomic technologies are increasingly utilised to understand the emergence and spread of AMR globally, its application to inform outbreak responses in low- and middle-income settings has not been reported.

Methods: Through an established capacity building program, suspected carbapenem-resistant organisms (CRO) identified at Colonial War Memorial Hospital in Fiji (Jan 2022-Oct 2023) underwent whole genome sequencing and analysis.

Spontaneous mutation in 2310061I04Rik results in reduced expression of mitochondrial genes and impaired brain myelination.

Here, we describe a spontaneous mouse mutant with a deletion in a predicted gene 2310061I04Rik (Rik) of unknown function located on chromosome 17. A 59 base pair long deletion occurred in the first intron of the Rik gene and disrupted its expression. Riknull mice were born healthy and appeared anatomically normal up to two weeks of age.

Fluorescence Lifetime Imaging for Quantification of Targeted Drug Delivery in Varying Tumor Microenvironments.

Trastuzumab (TZM) is a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) and is clinically used for the treatment of HER2-positive breast tumors. However, the tumor microenvironment can limit the access of TZM to the HER2 targets across the whole tumor and thereby compromising TZM's therapeutic efficacy. An imaging methodology that can non-invasively quantify the binding of TZM-HER2, which is required for therapeutic action, and distribution within tumors with varying tumor microenvironments is much needed.

Diabetes prevention after gestational diabetes: challenges and opportunities.

Gestational diabetes mellitus (GDM) poses significant health concerns for women and their offspring, with implications that extend beyond pregnancy. While GDM often resolves postpartum, a diagnosis of GDM confers a greater risk of future type 2 diabetes (T2D) and other chronic illnesses. Furthermore, the intergenerational impact of GDM predisposes offspring to increased chronic disease risk.

High incidence of multidrug-resistant tuberculosis in Bhutan: A cohort study based on national TB surveillance data.

Objectives: The emergence of multidrug-resistant tuberculosis (MDR-TB) has made the elimination of TB difficult. Currently, there are limited data on MDR-TB and other drug-resistant TB in Bhutan. We aimed to estimate the incidence and explore the potential risk factors associated with MDR/pre-extensively drug-resistant (pre-XDR)-TB using comprehensive national TB data.

Single cell RNA-seq reveals cellular and transcriptional heterogeneity in the splenic CD11bLy6C monocyte population expanded in sepsis-surviving mice.

Background: Sepsis survivors exhibit immune dysregulation that contributes to poor long-term outcomes. Phenotypic and functional alterations within the myeloid compartment are believed to be a contributing factor. Here we dissect the cellular and transcriptional heterogeneity of splenic CD11bLy6C myeloid cells that are expanded in mice that survive the cecal ligation and puncture (CLP) murine model of polymicrobial sepsis to better understand the basis of immune dysregulation in sepsis survivors.

Perceived Cognitive Function in Neurosurgical Patients.

Background And Objectives: This study explores perceived cognitive function in preoperative cranial neurosurgical patients and its association with neuropsychological testing (NPT).

Methods: A total of 96 patients were referred for NPT by neurosurgical service. Patients completed the Neuro-QoL Item Bank v2.

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin.

Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease, causes cross-resistance to daptomycin in VREfm.

Diversity, functional classification and genotyping of SHV β-lactamases in .

Interpreting the phenotypes of alleles in genomes is complex. Whilst all strains are expected to carry a chromosomal copy conferring resistance to ampicillin, they may also carry mutations in chromosomal alleles or additional plasmid-borne alleles that have extended-spectrum β-lactamase (ESBL) activity and/or β-lactamase inhibitor (BLI) resistance activity. In addition, the role of individual mutations/a changes is not completely documented or understood.

Off-Protocol Radiation Therapy in Phase 3 Metastatic Solid Tumor Trials.

Purpose: Increasing data suggest that radiation therapy, particularly ablative radiation therapy, alters the natural history of metastatic disease. For patients with metastatic disease enrolled in prospective trials testing systemic therapy, the use of off-protocol radiation therapy to improve clinical symptoms or extend the duration of study systemic therapy may influence study endpoints. We sought to evaluate how often off-protocol radiation therapy was permitted among systemic therapy phase 3 trials, how often off-protocol radiation therapy is used, and whether off-protocol radiation therapy correlated with study outcomes.

Evidenced-Based Prior for Estimating the Treatment Effect of Phase III Randomized Trials in Oncology.

Purpose: The primary results of phase III oncology trials may be challenging to interpret, given that results are generally based on value thresholds. The probability of whether a treatment is beneficial, although more intuitive, is not usually provided. Here, we developed and released a user-friendly tool that calculates the probability of treatment benefit using trial summary statistics.

Buprenorphine for the Treatment of Pain in Cancer Patients.

Background: Opioids remain the cornerstone for the treatment of moderate to severe cancer pain. Due to benefits over full agonist opioids (FAO), buprenorphine has emerged as an alternative treatment.

Purpose/hypothesis: Buprenorphine is only approved for the treatment of pain that is chronic non-cancer.

A meta-epidemiological analysis of post-hoc comparisons and primary endpoint interpretability among randomized noncomparative trials in clinical medicine.

Objectives: Randomized noncomparative trials (RNCTs) promise reduced accrual requirements vs randomized controlled comparative trials because RNCTs do not enroll a control group and instead compare outcomes to historical controls or prespecified estimates. We hypothesized that RNCTs often suffer from two methodological concerns: (1) lack of interpretability due to group-specific inferences in nonrandomly selected samples and (2) misinterpretation due to unlicensed between-group comparisons lacking prespecification. The purpose of this study was to characterize RNCTs and the incidence of these two methodological concerns.

Effect of hearing intervention on communicative function: A secondary analysis of the ACHIEVE randomized controlled trial.

Background: The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) Study was designed to determine the effects of a best-practice hearing intervention on cognitive decline among community-dwelling older adults. Here, we conducted a secondary analysis of the ACHIEVE Study to investigate the effect of hearing intervention on self-reported communicative function.

Methods: The ACHIEVE Study is a parallel-group, unmasked, randomized controlled trial of adults aged 70-84 years with untreated mild-to-moderate hearing loss and without substantial cognitive impairment.

Contrasting the effect of hinge region insertions and non-active site mutations on HIV protease-inhibitor interactions: Insights from altered flap dynamics.

HIV-1 protease (PR) enzyme is a viable antiretroviral drug target due to its crucial role in HIV maturation. Over many decades, the HIV-1 PR enzyme has exhibited mutations brought on by drug pressure and error-prone nature of HIV-1 reverse transcriptase. Non-active site mutations have played a pivotal role in drug resistance; however, their mechanism of action has not been fully elucidated.

Increasing Power in Phase III Oncology Trials With Multivariable Regression: An Empirical Assessment of 535 Primary End Point Analyses.

Purpose: A previous study demonstrated that power against the (unobserved) true effect for the primary end point (PEP) of most phase III oncology trials is low, suggesting an increased risk of false-negative findings in the field of late-phase oncology. Fitting models with prognostic covariates is a potential solution to improve power; however, the extent to which trials leverage this approach, and its impact on trial interpretation at scale, is unknown. To that end, we hypothesized that phase III trials using multivariable PEP analyses are more likely to demonstrate superiority versus trials with univariable analyses.