Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials.

In the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1 (NCT03697252), EMERGENT-2 (NCT04659161), and EMERGENT-3 (NCT04738123) trials, xanomeline and trospium chloride (formerly known as KarXT) significantly improved symptoms of schizophrenia and was generally well tolerated. We pooled data from the EMERGENT trials to further characterize the efficacy of xanomeline/trospium and provide sufficient statistical power to analyze responses in participant subgroups. In pooled analyses, xanomeline/trospium significantly improved Positive and Negative Syndrome Scale (PANSS) total score at week 5 versus placebo (least squares mean difference, -9.

Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials.

Background: Currently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M /M preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms.

Examining the impact and response to an outbreak of carbapenemase-producing in a neonatal unit in the United Kingdom: An outbreak report.

Background: Carbapenemase-producing (CPE) are a group of Gram-negative bacteria causing global concern due to their resistance to carbapenems. In this report, we detail the learning points from a CPE outbreak in a tertiary neonatal unit (NU) in the UK.

Methods: Routine surveillance screening (rectal swabs) of babies on the NU identified a potential cluster of CPE carriage.

Patient preferences for treatment attributes in moderate-to-severe atopic dermatitis: a discrete choice experiment.

Evidence on treatment preferences of patients with moderate-to-severe atopic dermatitis (AD) in the United States (US) is limited and an assessment of treatment preferences in this group is warranted. An online discrete choice experiment survey was conducted (June 2023) among US adults with self-reported moderate-to-severe AD or experience with systemic therapy who had inadequate response to topical treatments. Preference weights estimated from conditional logistic regression models were used to calculate willingness to trade off and attributes' relative importance (RI).

Functioning and Cognition in Patients with Schizophrenia After Initiating Treatment with Aripiprazole Lauroxil: Secondary Outcomes and Post Hoc Analysis.

Background: Clinical practice guidelines support efforts to improve functioning in patients with schizophrenia. Discrepancies in the perception of cognitive status between clinicians, patients with schizophrenia, and their caregivers have been associated with impaired functional abilities in patients; medication side effects might worsen both cognition and daily functioning. We assessed daily/social functioning and cognition in stable patients with schizophrenia who switched to the long-acting injectable (LAI) antipsychotic aripiprazole lauroxil (AL).

A Potential Prognostic Gene Signature Associated with p53-Dependent NTRK1 Activation and Increased Survival of Neuroblastoma Patients.

Neuroblastoma is the most common extracranial solid tumour in children, comprising close to 10% of childhood cancer-related deaths. We have demonstrated that activation of NTRK1 by TP53 repression of PTPN6 expression is significantly associated with favourable survival in neuroblastoma. The molecular mechanisms by which this activation elicits cell molecular changes need to be determined.

A diminutive new basilosaurid whale reveals the trajectory of the cetacean life histories during the Eocene.

Soon after whales originated from small terrestrial artiodactyl ancestors, basal stem forms (archaeocetes) came to inhabit more specialized aquatic ecologies and underwent a tremendous adaptive radiation that culminated in the adoption of a fully aquatic lifestyle. This adaptive strategy is first documented by the geographically widespread extinct family Basilosauridae. Here we report a new basilosaurid genus and species, Tutcetus rayanensis, from the middle Eocene of Fayum, Egypt.

Characterising the chemical and physical properties of phase-change nanodroplets.

Phase-change nanodroplets have attracted increasing interest in recent years as ultrasound theranostic nanoparticles. They are smaller compared to microbubbles and they may distribute better in tissues (e.g.

Do plasmids containing heavy metal resistance genes play a role in neonatal sepsis and invasive disease caused by and ?

species are some of those most implicated in neonatal sepsis. However, many isolates from infections appear unremarkable; they are generally susceptible to antibiotics and often of sporadic types not associated with virulence. Investigation is needed to identify if such isolates have virulence characteristics.

Possible In Utero Transmission of SARS-CoV-2 and Severe Respiratory Disease in a Preterm Infant.

Severe acute respiratory syndrome coronavirus 2 infections are uncommon in newborn infants. This report describes possible in utero transmission of the B.1.

Handwriting Kinematics in Patients with Schizophrenia Treated with Long-Acting Injectable Atypical Antipsychotics: Results From the ALPINE Study.

Handwriting kinematics (HWKs) were assessed in the randomized controlled ALPINE study of 2 long-acting injectable antipsychotics started during an acute exacerbation of schizophrenia. This exploratory analysis examined the relationship between baseline HWKs and response to acute antipsychotic treatment. Adults with acute schizophrenia were assigned to aripiprazole lauroxil or paliperidone palmitate (groups combined for this analysis).

Development and psychometric properties of the tool for assessing LGBTQI+ health training (TALHT) in pre-licensure nursing curricula.

Background: There is a lack of comprehensive lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) content in pre-licensure nursing curricula. LGBTQI+ people commonly experience mistreatment from nurses and healthcare providers due to a lack of knowledge or personal biases. To date, few instruments exist to guide LGBTQI+-specific curricular improvement.

Aripiprazole lauroxil 2-month formulation with 1-day initiation in patients hospitalized for an acute exacerbation of schizophrenia: exploratory efficacy and patient-reported outcomes in the randomized controlled ALPINE study.

Background: A randomized, controlled, phase 3b study (ALPINE) evaluated efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) using a 1-day initiation regimen in patients hospitalized for an acute exacerbation of schizophrenia. Paliperidone palmitate (PP) was used as an active control. Exploratory endpoint assessments included severity of illness, positive and negative symptoms, quality of life, caregiver burden, and satisfaction with medication.

Analysis of prolactin and sexual side effects in patients with schizophrenia who switched from paliperidone palmitate to aripiprazole lauroxil.

One strategy to address hyperprolactinemia and associated sexual side effects in patients receiving antipsychotics is switching to an antipsychotic not associated with prolactin elevation (eg, aripiprazole). This post hoc analysis assessed prolactin concentrations and sexual side effects in an open-label prospective study of switching long-acting injectable antipsychotics from paliperidone palmitate (PP) to aripiprazole lauroxil (AL). Serum prolactin was measured throughout the study.

Nanotools for Sepsis Diagnosis and Treatment.

Sepsis is one of the leading causes of death worldwide with high mortality rates and a pathological complexity hindering early and accurate diagnosis. Today, laboratory culture tests are the epitome of pathogen recognition in sepsis. However, their consistency remains an issue of controversy with false negative results often observed.

A Comparison of Volatile Anesthesia and Total Intravenous Anesthesia (TIVA) Effects on Outcome From Cardiac Surgery: A Systematic Review and Meta-Analysis.

Objective: The primary objective of this study was to compare one-year mortality in patients undergoing cardiac surgery with volatile anesthesia or total intravenous anesthesia (TIVA). Secondary objectives were to compare in-hospital and 30-day mortality, postoperative levels of creatine kinase (CK-MB) and cardiac troponin, and durations of tracheal intubation, intensive care unit (ICU) and hospital stays.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.

Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.

Design, Setting, And Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin.

Beyond 52-Week Long-Term Safety: Long-Term Outcomes of Aripiprazole Lauroxil for Patients With Schizophrenia Continuing in an Extension Study.

Objective: To describe the long-term safety, tolerability, and symptom trajectory with the long-acting injectable antipsychotic aripiprazole lauroxil (AL) in patients with DSM-5-diagnosed schizophrenia followed for up to 180 weeks (3.5 years).

Methods: Long-term safety of 2 fixed doses of AL (441 or 882 mg every 4 weeks) was assessed during up to 180 weeks (3.

The challenge of recognising sepsis: Future nanotechnology solutions.

The urgent need to start anti-infective therapeutic interventions in suspected sepsis, and the lack of specific time-critical diagnostic information often lead to the widespread administration of broad-spectrum antimicrobial therapies, increasing the risk of unwanted patient harms and contributing to rising pathogen antimicrobial resistance. Nanotechnology, which involves engineering at the nanoscale, allows for the bespoke development of diagnostic solutions with multi-functionality and high sensitivity that has the potential to help provide time-critical information to make more accurate diagnoses and treatment decisions for sepsis. Nanotechnologies also have the potential to improve upon the current strategies used for novel biomarker discovery.

Efficacy and Safety of a 2-Month Formulation of Aripiprazole Lauroxil With 1-Day Initiation in Patients Hospitalized for Acute Schizophrenia Transitioned to Outpatient Care: Phase 3, Randomized, Double-Blind, Active-Control ALPINE Study.

Objective: Evaluate efficacy and safety of a 2-month formulation of aripiprazole lauroxil (AL) with 1-day initiation during hospitalization for acute exacerbation of schizophrenia followed by transition to outpatient care.

Methods: The phase 3b double-blind Aripiprazole Lauroxil and Paliperidone palmitate: INitiation Effectiveness (ALPINE) study was conducted from November 2017 to March 2019. Adults with acute schizophrenia according to DSM-5 criteria were randomized (1:1) to AL (AL NanoCrystal Dispersion + oral aripiprazole 30 mg, day 1; AL 1,064 mg, day 8 and every 8 weeks [q8wk]) or paliperidone palmitate (PP 234 mg, day 1; PP 156 mg, day 8 and then q4wk) for 25 weeks.

Protein corona fingerprinting to differentiate sepsis from non-infectious systemic inflammation.

Rapid and accurate diagnosis of sepsis remains clinically challenging. The lack of specific biomarkers that can differentiate sepsis from non-infectious systemic inflammatory diseases often leads to excessive antibiotic treatment. Novel diagnostic tests are urgently needed to rapidly and accurately diagnose sepsis and enable effective treatment.

Femoral neck and shaft structure in Homo naledi from the Dinaledi Chamber (Rising Star System, South Africa).

The abundant femoral assemblage of Homo naledi found in the Dinaledi Chamber provides a unique opportunity to test hypotheses regarding the taxonomy, locomotion, and loading patterns of this species. Here we describe neck and shaft cross-sectional structure of all the femoral fossils recovered in the Dinaledi Chamber and compare them to a broad sample of fossil hominins, recent humans, and extant apes. Cross-sectional geometric (CSG) properties from the femoral neck (base of neck and midneck) and diaphysis (subtrochanteric region and midshaft) were obtained through CT scans for H.