Predictors of Potentially Inappropriate Stimulant Prescribing Among Adults.

Purpose: Increases in adult stimulant prescribing pose a potential risk due to the higher prevalence of contraindicated conditions among this population. We sought to identify patient, provider, and visit characteristics predictive of potentially inappropriate adult stimulant prescriptions.

Methods: We conducted a repeated cross-sectional study using the National Ambulatory Medical Care Survey, a nationally representative weighted sample of 5 453 702 723 ambulatory care visits from 2012 to 2019.

Frontiers in laccase nanozymes-enabled colorimetric sensing: A review.

In recent years, nanozyme-based analytics have become popular. Among these, laccase nanozyme-based colorimetric sensors have emerged as simple and rapid colorimetric detection methods for various analytes, effectively addressing natural enzymes' stability and high-cost limitations. Laccase nanozymes are nanomaterials that exhibit inherent laccase enzyme-like activity.

Highly parallel simulation tool for the design of isotachophoresis experiments.

Background: Isotachophoresis (ITP) is a well-established electrokinetic method for separation and preconcentration of analytes. Several simulation tools for ITP have been published, but their use for experimental design is limited by the computational time for a single run and/or by the number of conditions that can be investigated per simulation run. A large fraction of the existing solvers also do not account for ionic strength effects, which can influence whether an analyte focuses in ITP.

Digital recombinase polymerase amplification chip based on asymmetric contact angle composite interface.

Background: Digital recombinase polymerase amplification (dRPA) is an effective tool for the absolute quantification of nucleic acids and the detection of rare mutations. Due to the high viscosity or other physical properties of the reagent, this can compromise the accuracy and reproducibility of detection results, which limits the broader adoption and practical application of this technology. In this study, we developed an asymmetric contact angle digital isothermal detection (ACA-DID) chip and optimized the ACA-DID chip structure to achieve rapid digital recombinase polymerase amplification.

Spontaneous conversion of fetal heart block to sinus rhythm post externalized pacemaker placement in an undiagnosed mother with lupus antibodies.

The incidence for congenital heart block is estimated as high as 1 in 15,000 live births. Up to 90% of cases of congenital heart block, in which there is no anatomical abnormalities, are attributed to maternal systemic lupus erythematous or Sjögren's disease. 50% of these mothers are asymptomatic at time of diagnosis.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Informing etiological heterogeneity of mild cognitive impairment and risk for progression to dementia with plasma p-tau217.

Background: Mild cognitive impairment (MCI) is a clinical diagnosis representing early symptom changes with preserved functional independence. There are multiple potential etiologies of MCI. While often presumed to be related to Alzheimer's disease (AD), other neurodegenerative and non-neurodegenerative causes are common.

Expert opinion on Centiloid thresholds suitable for initiating anti-amyloid therapy. Summary of discussion at the 2024 spring Alzheimer's Association Research Roundtable.

A 24-30 Centiloid (CL) threshold was collectively considered by a group of global dementia experts as a practical and implementable cut-off for anti-amyloid therapy intervention, in Alzheimer's disease patients who have been diagnosed at the mild cognitive impairment or mild dementia stage of their disease. Though additional validation is needed, knowledge of this threshold would be valuable to those involved in diagnosing and treating patients in the new AD care pathways, as well as entry into clinical trials. Therapy monitoring to determine future treatment response and assess amyloid clearance can be accomplished with amyloid PET with some technical details still to be elucidated.

INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease.

Background: Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.

Objectives: To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

Motor abilities and cognitive performance in Latinos with autosomal dominant Alzheimer's disease.

Background: Declining motor abilities might be a noninvasive biomarker for Alzheimer's disease (AD). Studying motor ability and AD progression in younger Latinos with autosomal dominant Alzheimer's disease (ADAD) can provide insights into the interplay between motor ability and cognition in individuals with minimal confounding from age-normative changes and comorbid medical conditions.

Objectives: This study aimed to (1) examine motor abilities as a function of years to dementia diagnosis and (2) examine associations between motor ability and cognitive performance.

Cardiovascular health, genetic predisposition, and dementia risk among atherosclerotic cardiovascular disease patients.

Background: While optimal cardiovascular health (CVH) has been linked to a lower risk of dementia, few studies considered individuals' genetic background. We aimed to examine the interaction between CVH and genetic predisposition on dementia risk among individuals with atherosclerotic cardiovascular disease (ASCVD).

Methods: We included 30,818 ASCVD patients from the UK Biobank.

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.

Background: There are no approved oral disease-modifying treatments for Alzheimer's disease (AD).

Objectives: The objective of this study was to assess efficacy and safety of blarcamesine (ANAVEX®2-73), an orally available small-molecule activator of the sigma-1 receptor (SIGMAR1) in early AD through restoration of cellular homeostasis including autophagy enhancement.

Design: ANAVEX2-73-AD-004 was a randomized, double-blind, placebo-controlled, 48-week Phase IIb/III trial.

Diagnostic accuracy in coronary CT angiography analysis: artificial intelligence versus human assessment.

Background: Visual assessment of coronary CT angiography (CCTA) is time-consuming, influenced by reader experience and prone to interobserver variability. This study evaluated a novel algorithm for coronary stenosis quantification (atherosclerosis imaging quantitative CT, AI-QCT).

Methods: The study included 208 patients with suspected coronary artery disease (CAD) undergoing CCTA in Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography-1.

End-to-end deep-learning model for the detection of coronary artery stenosis on coronary CT images.

Purpose: We examined whether end-to-end deep-learning models could detect moderate (≥50%) or severe (≥70%) stenosis in the left anterior descending artery (LAD), right coronary artery (RCA) or left circumflex artery (LCX) in iodine contrast-enhanced ECG-gated coronary CT angiography (CCTA) scans.

Methods: From a database of 6293 CCTA scans, we used pre-existing curved multiplanar reformations (CMR) images of the LAD, RCA and LCX arteries to create end-to-end deep-learning models for the detection of moderate or severe stenoses. We preprocessed the images by exploiting domain knowledge and employed a transfer learning approach using EfficientNet, ResNet, DenseNet and Inception-ResNet, with a class-weighted strategy optimised through cross-validation.

Diabetes is associated with a higher incidence of short-term mortality risk and readmission in patients who undergo surgical but not transcatheter aortic valve replacement.

Background: Transcatheter aortic valve replacement (TAVR) is increasingly used for aortic valve replacement instead of surgical aortic valve replacement (sAVR). We aimed to examine the impact of diabetes on 30-day mortality, 30-day readmission and compare outcomes between TAVR and sAVR.

Methods: Data were extracted from the Nationwide Readmissions Database from 2012 to 2017.

What is the risk of transfusing group O RhD-positive red blood cells to female service personnel of childbearing potential?

The traditional approach to resuscitating injured women of childbearing potential (WCBP) with an unknown RhD type is to transfuse RhD-negative blood products. This is to prevent alloimmunisation to the RhD antigen and ultimately prevent haemolytic disease of the fetus and newborn (HDFN) in future pregnancies should she survive. RhD-negative blood products are scarce in both military and civilian blood stocks.

Systematic review of health and social outcomes among Indigenous People exposed to the child welfare system: a protocol.

Introduction: The link between parent-child separation through child welfare systems and negative health and social outcomes is well documented. In contrast, despite the over-representation of Indigenous children and youth in child welfare systems, the relationship between child welfare system involvement and health and social outcomes among Indigenous populations has not been systematically reviewed. Our objective is to assess whether Indigenous People who have been exposed to a child welfare system personally or intergenerationally (ie, parents and/or grandparents) within Canada, Australia, New Zealand and the USA (CANZUS countries) and the circumpolar region are at an increased risk for negative health and social outcomes compared with other exposed and non-exposed groups.

Patient and provider factors associated with follow-up for positive depression screens in adults: a retrospective review of University of Utah primary and specialty care clinics.

Objective: To identify patient and provider factors associated with lower rates of follow-up for positive depression screens in outpatient settings.

Design: Retrospective cohort study with electronic health record analysis investigating factors associated with follow-up care for patients with moderate-to-severe depressive symptoms. Patient and provider variables were associated with rates of follow-up for positive depression screens.

Examining the effect of direct-from-blood bacterial testing on antibiotic administration and clinical outcomes: a protocol and statistical analysis plan for a pragmatic randomised trial.

Introduction: Patients with suspected bacterial infection frequently receive empiric, broad-spectrum antibiotics prior to pathogen identification due to the time required for bacteria to grow in culture. Direct-from-blood diagnostics identifying the presence or absence of bacteria and/or resistance genes from whole blood samples within hours of collection could enable earlier antibiotic optimisation for patients suspected to have bacterial infections. However, few randomised trials have evaluated the effect of using direct-from-blood bacterial testing on antibiotic administration and clinical outcomes.

Improving 1-year liver allograft survival hazard ratios.

Background: The Scientific Registry for Transplant Recipients (SRTR) publishes outcomes of all transplant centres in the USA two times a year. The outcomes are publicly available and used by insurance payers and patients to assess the performance of a programme. Poor performance can result in temporary suspension or termination of a transplant programme.

Implementation of patient-reported outcome dashboards within the electronic health record to support shared decision-making in serious chronic illness.

Background: Attending to patient-reported outcomes (PROs) using data visualisation dashboards could enhance shared decision-making (SDM) and care delivery for serious chronic illnesses. However, few studies have evaluated real-world strategies and resulting implementation outcomes of PRO dashboards.

Method: From June 2020 to January 2022, we implemented an electronic health record (EHR)-integrated PRO dashboard for advanced cancer and chronic kidney disease.